US20040101822A1 - Fluorescent silica-based nanoparticles - Google Patents
Fluorescent silica-based nanoparticles Download PDFInfo
- Publication number
- US20040101822A1 US20040101822A1 US10/306,614 US30661402A US2004101822A1 US 20040101822 A1 US20040101822 A1 US 20040101822A1 US 30661402 A US30661402 A US 30661402A US 2004101822 A1 US2004101822 A1 US 2004101822A1
- Authority
- US
- United States
- Prior art keywords
- nanoparticle
- fluorescent
- ligated
- cell
- therapeutic agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82B—NANOSTRUCTURES FORMED BY MANIPULATION OF INDIVIDUAL ATOMS, MOLECULES, OR LIMITED COLLECTIONS OF ATOMS OR MOLECULES AS DISCRETE UNITS; MANUFACTURE OR TREATMENT THEREOF
- B82B1/00—Nanostructures formed by manipulation of individual atoms or molecules, or limited collections of atoms or molecules as discrete units
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/02—Use of particular materials as binders, particle coatings or suspension media therefor
- C09K11/025—Use of particular materials as binders, particle coatings or suspension media therefor non-luminescent particle coatings or suspension media
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82B—NANOSTRUCTURES FORMED BY MANIPULATION OF INDIVIDUAL ATOMS, MOLECULES, OR LIMITED COLLECTIONS OF ATOMS OR MOLECULES AS DISCRETE UNITS; MANUFACTURE OR TREATMENT THEREOF
- B82B3/00—Manufacture or treatment of nanostructures by manipulation of individual atoms or molecules, or limited collections of atoms or molecules as discrete units
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B33/00—Silicon; Compounds thereof
- C01B33/113—Silicon oxides; Hydrates thereof
- C01B33/12—Silica; Hydrates thereof, e.g. lepidoic silicic acid
- C01B33/18—Preparation of finely divided silica neither in sol nor in gel form; After-treatment thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
- G01N33/54346—Nanoparticles
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
- G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
- G01N33/585—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with a particulate label, e.g. coloured latex
- G01N33/587—Nanoparticles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y20/00—Nanooptics, e.g. quantum optics or photonic crystals
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2002/00—Crystal-structural characteristics
- C01P2002/80—Crystal-structural characteristics defined by measured data other than those specified in group C01P2002/70
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/01—Particle morphology depicted by an image
- C01P2004/03—Particle morphology depicted by an image obtained by SEM
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/60—Particles characterised by their size
- C01P2004/64—Nanometer sized, i.e. from 1-100 nanometer
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/24—Structurally defined web or sheet [e.g., overall dimension, etc.]
- Y10T428/24355—Continuous and nonuniform or irregular surface on layer or component [e.g., roofing, etc.]
- Y10T428/24372—Particulate matter
- Y10T428/2438—Coated
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/31504—Composite [nonstructural laminate]
- Y10T428/31652—Of asbestos
- Y10T428/31663—As siloxane, silicone or silane
Definitions
- the invention generally relates to nanoparticles, and more specifically to ligated-fluorescent nanoparticles, methods of making ligated-fluorescent nanoparticles, and methods of using the ligated-fluorescent nanoparticles as biomarkers to, for example, monitor the motion or movement of cellular components on or within cell systems, and for the detection, diagnosis, or treatment of diseases or conditions, for example in intact or living cells.
- Fluorescent and magnetic polymeric particles have known utility as markers and indicators in various biomedical assays.
- markers for sorting cells are immunoconjugates or immunological labels which include, for example, immuno-fluorescent and immuno-magnetic labels.
- Immunofluorescent labels typically include, for example, a fluorescent molecule joined to an antibody.
- Immuno-magnetic labels typically include, for example, a superparamagnetic particle joined to either a primary or secondary antibody.
- Cell labeling can be performed by, for example, attaching the antibody to a marker of interest (e.g., receptor site) on the surface of the cell, that is, a cell surface marker.
- a marker of interest e.g., receptor site
- the chemical and physical structure of cell surface marker and density of immunological labels attached to the cell surface have generally been difficult to accurately determine.
- Fluorescent labels have been prepared, for example, by embedding or covalently coupling a fluorescent dye onto a polymeric particle.
- the resulting fluorescent microparticles can be analyzed manually or by other methods known in the art but preferably using an automated technique, e.g., flow cytometry, such as disclosed in U.S. Pat. No. 4,665,024, to Mansour, et al.
- the versatility of the fluorescent particles can be further enhanced by the incorporation of multiple fluorescent materials in a single particle.
- Magnetic particles such as known magnetically active materials, can be bonded or attached to, for example, antibodies, such as, monoclonal antibodies that are specific to a particular cell type, antigen, or other targets.
- the resulting magnetic-antibodies can then be mixed with a large population of many different cell types, for example, crude tissue samples, cells grown in a reactor, and the like.
- the magnetic-antibodies therefore attach only to their pre-selected target cell type, forming a magnetic-antibody-cell conjugate.
- the conjugate can then be separated from the rest of the cell population using a magnetic field.
- a shortcoming of magnetic particles is the lack of specificity in magnetic labeling in that a cell or other biological target analyte may be rendered paramagnetic by a number of different routes which can confound the analysis and diagnostic information afforded by the method, for example, by binding a specific paramagnetic compound to a specific hapten on a cell or by specific or non-specific binding of a paramagnetic metal or metal complex directly to a cell, such as, a metal binding microorganism or by phagocytosis.
- Other problems encountered with magnetic particles used in detection and diagnostics include, for example, difficulty in obtaining highly accurate quantification of a cell population's magnetic susceptibility. In addition to their magnetic properties (i.e.
- magnetic, paramagnetic, and superparamagnetic magnetic-antibodies can be classified, for example, into three broad categories based on their relative descending particle size: magnetic particulate labels, colloidal magnetic labels, and molecular magnetic labels, see for example U.S. Pat. No. 6,412,359.
- Latex nanoparticles having a polymeric core and a surface decorated with, for example, a ligand molecule capable of specific binding with a cell surface and optionally decorated with genetic material, such as a mutant gene, are known and may have utility in, for example, gene delivery to a cell and expression therein, for disrupting tumors, and related treatment applications, see for example, Science, 296, 2404 (2002).
- Optically active nanoparticles such as fluorescent nanoparticles, having an electrically conducting shell and a silica core are known and have utility in, for example, modulated delivery of a chemical and treatment applications, see for example, U.S. Pat. No. 6,344,272, and 6,428,811.
- a shortcoming of existing fluorescent probe nanoparticles is their limited brightness and their attenuated detectability as fluorescent probes in dispersed systems, particularly with single fluorescent nanoparticles.
- the invention provides a fluorescent nanoparticle comprising: a core comprising a fluorescent silane compound; and a silica shell on the core.
- the invention also provides a fluorescent nanoparticle comprising:
- a core comprising a fluorescent silane compound; and a porous silica shell on the core.
- the invention also provides a fluorescent nanoparticle which can further include a ligand, such as a antibody, conjugated with or coated on the surface of the fluorescent nanoparticle to form a ligated-fluorescent nanoparticle.
- a ligand such as a antibody
- the ligated- or ligand bearing-fluorescent nanoparticles of the present invention can be used, for example, as highly target specific diagnostic agents, and motion monitoring agents when combined with cells or cell components.
- the invention also provides a pharmaceutical carrier or drug delivery vehicle comprising the fluorescent nanoparticles or the ligated-fluorescent nanoparticles of the present invention.
- the invention also provides a fluorescent imaging agent comprising the ligated-fluorescent nanoparticles of the present invention.
- the invention also provides ligated-fluorescent nanoparticles as pharmaceutical carrier particles.
- the ligated-fluorescent nanoparticles can further include a therapeutic agent, which therapeutic agent is on the surface or is conjugated with the surface of the fluorescent nanoparticle to form a pharmaceutical composition.
- the invention also provides a method of making a fluorescent nanoparticle comprising:
- a fluorescent compound such as a reactive fluorescent dye
- an organo-silane compound such as a co-reactive organo-silane compound
- the invention also provides a method for monitoring movement of a cellular component of a cell comprising:
- the invention also provides a method for treating disease comprising:
- a ligated-fluorescent nanoparticle which nanoparticle optionally includes a therapeutic agent, the nanoparticle being adapted to selectively associate with a disease producing component of the cell, to form a selectively decorated cell with the ligated-fluorescent nanoparticle;
- the invention also provides a method for treatment comprising:
- the invention also provides a kit for use in the detection of an analyte, the kit comprising a ligated-fluorescent nanoparticle, as illustrated herein.
- the invention also provides a kit for detecting and monitoring a cell surface component comprising a ligated-fluorescent nanoparticle for detecting the cell surface component, and optionally a recorder for monitoring the cell surface component.
- the invention also provides an assay method for detecting motion or a change in the location of a cellular component in, or on the surface of, a cell when the cell is treated with a therapeutic agent comprising:
- FIG. 1A illustrates an example of the fluorescent brightness of the fluorescent nanoparticles of the present invention compared to latex particles.
- FIG. 2A illustrates an example of bio-molecule binding specificity of the fluorescent nanoparticles of the present invention.
- FIG. 2B illustrates an example of bio-molecule binding specificity of comparative latex particles.
- Applicants have discovered fluorescent nanoparticles, and linked- or ligated-fluorescent nanoparticles of the invention that are useful for labeling, detection, identification, motion monitoring, and like applications, of various biological and non-biological analytes.
- the linked- or ligated-fluorescent nanoparticles of the invention can also be useful in therapeutic treatment, when used as a pharmaceutical carriers, for example, in combination with a suitable therapeutic agent.
- the present invention provides nanoparticles which can have useful multifunctional architectures, for example, a fluorescent nano-sized core which can optionally contain other functionality such as a magnetic component, a silica shell which can be made to have a range of useful thicknesses and surface properties, such as a smooth monolithic surface or a highly porous surface, and which silica surface can be further physically or chemically modified with, for example, a ligand or a therapeutic agent.
- useful multifunctional architectures for example, a fluorescent nano-sized core which can optionally contain other functionality such as a magnetic component, a silica shell which can be made to have a range of useful thicknesses and surface properties, such as a smooth monolithic surface or a highly porous surface, and which silica surface can be further physically or chemically modified with, for example, a ligand or a therapeutic agent.
- the present invention provides for the preparation and characterizations of fluorescent nanoparticles in various sizes suitable for single particle tracking (SPT) applications. Nanoparticles of various diameters can be prepared having narrow size distributions.
- the versatility of the preparative route allows for the incorporation of different fluorescent materials, such as dyes, depending on the intended nanoparticle application.
- Methods for surface functionalization are also provided which enable the conjugation of specific ligands, such as antibodies or proteins, onto the fluorescent nanoparticles to form probes useful for specific SPT experiments.
- the nanoparticle preparative procedure enables the preparation, by in situ systematic nanoparticle size-growth, of fluorescent nanoparticles in the range of, for example, from about 10 to about 500 nm, and from about 25 to about 100 nm, and narrower ranges therein as illustrated herein.
- the fluorescent nanoparticles can be conjugated with a molecule or entity, such as an antibody ligand or linker, to provide a linked- or ligated-fluorescent nanoparticle which can be used to identify, detect, target (i.e. pinpoint or specify with a high level of certainty), monitor, or modify a disease state or condition, such as the presence or absence of particular receptors, metabolic levels of particular receptors, and like components.
- a molecule or entity such as an antibody ligand or linker
- the linked- or ligated-fluorescent nanoparticle can be still further conjugated or associated with, for example, a therapeutic agent and used to, for example, treat a disease state or condition, such as by delivering the therapeutic agent to a diseased site in a highly specific or localized manner and in a relatively high concentration with release of the therapeutic agent in a relatively controlled manner.
- the ligated-fluorescent nanoparticles can be used for directed delivery of a therapeutic agent to a desired location in a variety of systems, such as on, or within, a cell or cell component, or within the body of an organism, such as a human, e.g. across the blood-brain barrier.
- the therapeutic agent can be either or both absorbed into, such as the interstices or pores of the silica shell, or coated onto the silica shell of the fluorescent nanoparticle.
- the therapeutic agent can be associated with the fluorescent core, such as by physical absorption or by bonding interaction.
- the therapeutic agent can also be associated with the ligand of a ligated-fluorescent nanoparticle if desired.
- the ligated-fluorescent nanoparticles of the present invention can be used in a variety of diagnostic and treatment applications, for example, as a pharmaceutical carrier for therapeutic agents, and as a fluorescent marker in, for example, single nucleotide polymorphorism (SNPs) experiments, such as where a DNA sample is stained with a fluorescent marker and gene activity can be detected as a colored glow of the marker when illuminated with a laser.
- SNPs single nucleotide polymorphorism
- the nanoparticles of the invention can be used for passive or covalent coupling of biological material, i.e. an analyte, such as haptens, antigens, antibodies, enzymes or nucleic acids, and used for various types of analyte assays such as immunoassays, nucleic acid (DNA or RNA) assays, affinity purification, cell separation, and other medical, diagnostic, environmental, and industrial applications.
- analyte such as haptens, antigens, antibodies, enzymes or nucleic acids
- analyte assays such as immunoassays, nucleic acid (DNA or RNA) assays, affinity purification, cell separation, and other medical, diagnostic, environmental, and industrial applications.
- the nanoparticles incorporate known fluorescently responsive materials, such as, dyes, pigments, or combinations thereof.
- a typical fluorophore is, for example, a fluorescent aromatic or heteroaromatic compound such as is a pyrene, an anthracene, a naphthalene, an acridine, a stilbene, an indole or benzindole, an oxazole or benzoxazole, a thiazole or benzothiazole, a 4-amino-7-nitrobenz-2-oxa-1,3-diazole (NBD), a cyanine, a carbocyanine, a carbostyryl, a porphyrin, a salicylate, an anthranilate, an azulene, a perylene, a pyridine, a quinoline, a coumarin (including hydroxycoumarins and aminocoumarins and fluorinated derivatives thereof), and like compounds, see for example U.S. Pat. Nos. 5,830,912; 4,774,339; 5,187,288; 5,248,
- the co-reactive organosilane used for forming the fluorescent core has the general formula R (4-n) SiX n , where X can be a hydrolyzable group such as ethoxy, methoxy, or 2-methoxy-ethoxy; R can be a monovalent organic radical of from 1 to 12 carbon atoms which can optionally contains a functional organic group such as mercapto, epoxy, acrylyl, methacrylyl, or amino; and n is an integer of from 0 to 4.
- the co-reactive organosilane used for forming the fluorescent core preferably has n equal to 3.
- a organosilane used for forming the silica shell has n equal to 4.
- the above mentioned organo-silane compounds and like coupling agents can be used: to make the core; to make the silica shell, to modify the surface of the resulting silica shell coated fluorescent core nanoparticles; to attach or couple a ligand to the fluorescent nanoparticles; or to modify the properties of ligand before or after attachment to fluorescent nanoparticle.
- the organo-silane can cause gels, so it may be desirable to employ an alcohol or other known stabilizers.
- a stabilizer can be selected that does not interfere with the polymerization.
- An alcohol, such as methanol, is especially useful and can be employed in amounts, for example, from about twice to about ten times the amount of the organo-silane.
- the nanoparticles can optionally incorporate known magnet or magnetically responsive materials, such as, superparamagnetic, paramagnetic, ferromagnetic metal oxide, and combinations thereof.
- the fluorescent nanoparticles of the present invention comprise a core comprising a fluorescent silane compound; and a silica shell on the core.
- the core of the nanoparticle can comprise, for example, the reaction product of a reactive fluorescent compound and an co-reactive organo-silane compound
- the shell can comprise, for example, the reaction product of a silica forming compound.
- the silica forming compound can produce, for example, one or more layers of silica, such as from 1 to about 20 layers, and depending upon the shell characteristics desired, such as shell layer thickness, the ratio of the shell thickness to the core thickness or diameter, silica shell surface coverage of the core, porosity and carrying capacity of the silica shell, and like considerations.
- the silica shell coating on the core can cover, for example, from about 10 to about 100 percent of the surface area of the core.
- the ligand when ligated on the surface of the fluorescent nanoparticle can cover, for example, from about 0.1 to about 100 percent of the surface area of the core.
- the thickness or diameter of the core to the thickness of the silica shell can be in a ratio of, for example, from about 1:1 to about 1:100.
- the diameter of the fluorescent nanoparticle can be, for example, from about 1 to about 1,000 nanometers.
- the diameter of a ligated-fluorescent nanoparticle can be comparable to or larger than the diameter of the fluorescent nanoparticle depending upon, for example, the size and the amount of the ligand selected.
- the diameter of the core can be, for example, from about 10 to about 300 nanometers, and preferably from about 25 to about 200 nanometers
- the thickness of the silica shell can be, for example, from about 25 to about 800 nanometers, and preferably from about 25 to about 500 nanometers.
- the silica shell is made porous to accommodate for example a therapeutic agent, and as illustrated herein. More preferably the nanoparticles
- the preparative methods for fluorescent nanoparticles of the present invention can yield nanoparticles, for example, of about an order of magnitude smaller in size than those reported by van Blaaderen and Vri, Langmuir, 8, 2921-2925 (1992) (monodisperse silica sphere core particles coated with dyes and further encapsulated with silica).
- the silica shell can be either solid, that is relatively non-porous, or meso-porous, such as semi-porous.
- the silica shell of the fluorescent nanoparticles is preferably dielectric.
- the silica shell of the fluorescent nanoparticles can be adapted to function as a pharmaceutical carrier nanoparticle, that is made to contain, for example, therapeutic agents, such as drugs or proteins for transport and delivery of in vivo or in vitro.
- therapeutic agents such as drugs or proteins for transport and delivery of in vivo or in vitro.
- the fluorescent nanoparticles of the present invention can provide a pharmaceutical carrier system which can be adapted for controlled delivery or release of therapeutic agents.
- a ligand placed on the surface of the fluorescent nanoparticle forms a ligated-fluorescent nanoparticle.
- the placement of the ligand can be accomplished, for example, by attachment with a covalent bond or by physical absorption.
- the ligand on the surface of the fluorescent nanoparticle can be, for example, a biopolymer, a synthetic polymer, an antigen, an antibody, a virus or viral component, a receptor, a hapten, an enzyme, a hormone, a chemical compound, a pathogen, a microorganism or a component thereof, a toxin, a surface modifier, such as a surfactant to alter the surface properties or histocompatability of the nanoparticle or of an analyte when a nanoparticle associates therewith, and combinations thereof.
- Preferred ligands are for example, antibodies, such as monoclonal or polyclonal.
- the present invention also provides a method of preparing analytes which are selectively labeled with ligated-fluorescent nanoparticles by, for example, coupling (e.g. covalently) or any other known method(s) of associating the ligated-fluorescent nanoparticles directly to the analyte (e.g., through ionic bonds, hydrogen bonds, by simple adsorption).
- the resulting selectively labeled analytes having a coupled or associated ligated-fluorescent nanoparticle i.e. ligated-fluorescent nanoparticle-analyte complex
- can be useful as an authentic or reference sample for example, in a treatment method or diagnostic kit.
- An “analyte” of the present invention is the object or the target of the ligated-fluorescent nanoparticle for attachment or association therewith.
- the analyte can be, for example, a microorganism or a component thereof, a virus or viral component, a cell or a component thereof, a biopolymer, a synthetic polymer, a synthetic material, such as a carbon nanotube, an antigen, an antibody, a receptor, a hapten, an enzyme, a hormone, a chemical compound, a pathogen, a toxin, combinations thereof, and like substances.
- Analytes of particular interest are microorganisms and cells, including viruses, prokaryotic and eukaryotic cells, unicellular and multi-cellular organism, e.g., fungi, bacterial, mammalian, etc., and fragments or components thereof.
- Other analytes of particular interest are pathogens.
- Monoclonal or polyclonal antibodies or other selective ligands which are part of the ligated-fluorescent nanoparticle can be linked to the surface of, for example, a pathogen.
- a fluorescent nanoparticle for example, comprising:
- a fluorescent compound such as a reactive fluorescent dye
- an organo-silane compound such as a co-reactive organo-silane compound
- the methods of making the nanoparticles of the present invention can further comprise combining the resulting fluorescent nanoparticle with a ligand such as a biopolymer, a synthetic polymer, an antigen, an antibody, a microorganism, a virus, a receptor, a hapten, an enzyme, a hormone, a chemical compound, a pathogen, a toxin, a surface modifier, for example, to alter the surface or compatibility properties of the nanoparticle, combinations thereof, and like materials.
- a ligand such as a biopolymer, a synthetic polymer, an antigen, an antibody, a microorganism, a virus, a receptor, a hapten, an enzyme, a hormone, a chemical compound, a pathogen, a toxin, a surface modifier, for example, to alter the surface or compatibility properties of the nanoparticle, combinations thereof, and like materials.
- the methods of making the nanoparticles can also further comprise combining the resulting nanoparticle with a therapeutic agent, with or without a ligand attached to the nanoparticle.
- Combining the nanoparticles with a ligand or a therapeutic agent can be accomplished by, for example, coating the ligand or therapeutic agent onto the surface of the nanoparticle.
- combining a nanoparticle with a ligand or a therapeutic agent can be accomplished by, for example, imbibing the ligand or therapeutic agent into the surface of the nanoparticle. Imbibing means to assimilate or to take in or up, for example, where a porous nanoparticle surface is imbibed with a ligand, a therapeutic agent, or both.
- combining a nanoparticle with a ligand or a therapeutic agent can be accomplished by, for example, bonding the ligand or therapeutic agent to the surface of the resulting nanoparticle.
- Bonding includes, for example, known covalent, ionic, hydrogen, hydrophobic, coordination, adhesive, combinations thereof, and like bonding associative methods.
- the nanoparticles of the present invention can provide “molecular labels” which can readily associate with or be bonded to another entity, such as a ligand or a therapeutic agent, and thereafter be readily transported to and selectively attached to a target analyte.
- the selective attachment enables useful analytical detection, diagnostic, or differentiation schemes.
- the size of the ligated-fluorescent nanoparticles for use in embodiments of the present invention can be selected based on the number of nanoparticles to be attached to the analyte and the sensitivity of the optical or spectroscopic schemes selected.
- the present invention provides a method for monitoring movement of a cellular component of a cell comprising:
- the fluorescent loci can correspond to a single ligated-fluorescent nanoparticle bound to a component of the cell.
- the fluorescent loci can correspond to two or more ligated-fluorescent nanoparticles bound to a component of the cell.
- the monitoring method enables an operator to, for example, track the diffusion of one or more fluorescent loci, such as a receptor to which a single ligated-fluorescent nanoparticle is bound, such as, in real-time or with time-lapse techniques.
- the ligated-fluorescent nanoparticle is preferably adapted to selectively associate with a targeted cellular component of the cell, for example, by appropriate selection of the ligand.
- the cellular component can be, for example, a receptor, an antibody, a hapten, an enzyme, a hormone, a biopolymer, an antigen, a microorganism, a virus, a pathogen, a toxin, combinations thereof, and like components.
- the ligated-fluorescent nanoparticle can be a fluorescent nanoparticle conjugated with an antibody.
- the conjugated antibody can be an immunoglobin, such as IgE.
- Suitable means for detecting, recording, measuring, or imaging in embodiments of the present invention include, for example, a flow cytometer, a laser scanning cytometer, a fluorescence micro-plate reader, a fluorescence microscope, a confocal microscope, a bright-field microscope, a high content scanning system, and like devices.
- the recording can be accomplished, for example, with a microscopically adapted camera, such as a video-microscopy camera, a digital camera, a silver halide single exposure camera, and like devices.
- the recording time can be any convenient and useful time period to observe notable events or phenomena, for example, intervals from about 1 microsecond to about 30 days.
- recording for a time period can be, for example, from about 1 second to about 60 minutes, more preferably from about 1 second to about 40 minutes, and even more preferably, from about 1 minute to about 30 minutes.
- the recording time period can often be conveniently shortened or lengthened as desired by changing the ambient temperature of the sample or system.
- the contacting and the recording can be accomplished in vitro using conventional microscopic photography techniques.
- the contacting and the recording can also be accomplished in vivo using, for example, a catheter adapted with a microscopic camera or fiber optic camera.
- “recording” can be synonymous with “detecting,” since for example making a photographic recording of an illuminated specimen can also simultaneously afford detection of fluorescent loci, such as a cell or cell component selectively decorated with a ligated-fluorescent nanoparticle.
- a pharmaceutical carrier comprising the fluorescent nanoparticle of the present invention, and optionally a ligand associated with the fluorescent nanoparticle.
- a pharmaceutical composition comprising a ligated-fluorescent nanoparticle, and a therapeutic agent associated with the fluorescent nanoparticle.
- an imaging agent comprising the ligated-fluorescent nanoparticle, for example, where the ligand of the ligated-fluorescent nanoparticle is on the surface of the nanoparticle.
- the imaging agent can be used in conventional imaging processes, and preferably where, for example, a high fluorescent yield or fluorescent brightness is desired.
- the ligated-fluorescent nanoparticles of the present invention can provide enhanced fluorescent brightness which is, for example, from about 2 to about 10 times greater compared to conventional surface decorated fluorescent particles, such as fluorescent latex particles.
- a method for treating a disease or disorder comprising:
- a ligated-fluorescent nanoparticle which nanoparticle optionally includes a therapeutic agent, wherein the nanoparticle is adapted to selectively associate with a disease producing component of the cell, to form a selectively decorated cell with the ligated-fluorescent nanoparticle;
- the ligated-fluorescent nanoparticle by itself or as part of a decorated cell, when illuminated can fluoresce, heat-up, or both.
- the selection of the reactive fluorescent compound in preparing the fluorescent nanoparticle, and the selection of the ligand can be made empirically depending upon the balance of fluorescent and non-fluorescent (heat dissipation) properties desired. Higher fluorescent properties may be desired where detection is paramount or difficult, for example in dilute systems. Higher non-fluorescent properties may be desired where high heating is needed to, for example, promote liberation of a therapeutic agent or to accomplish selective microscopic-cauterization or microscopic-heat therapy.
- the ligated-fluorescent nanoparticles of the present invention can be used to treat a light- or heat-sensitive diseases or disorders.
- Light therapy is known for activation of medicaments at one or more treatment sites within a living body.
- a particular embodiment of light therapy for example, is photodynamic therapy (PDT) which is a two-step treatment process which has been found to be effective in destroying a wide variety of cancers.
- PDT is performed by first systemically or topically administering a photosensitizer compound or like compounds, and subsequently illuminating a treatment site with light in a waveband, which corresponds to an absorption waveband of the photosensitizer.
- the light energy activates the photosensitizer compound, causing it to destroy the diseased tissue, see for example, U.S. Pat. No. 6,454,789. It is readily evident to one skilled in the art that a fluorescent material, such as the ligated-fluorescent nanoparticles of the present invention, can be used in place of a photosensitizer compound.
- Heat therapy methods are also known, for example, to shrink desired tissues, see U.S. Pat. No. 6,480,746, and for localized treatment of cutaneous warts, see Arch. Dermatol , (July 1992), vol. 128, p. 945-948, and to induce macrophage apoptosis, see U.S. Pat. No. 6,451,044.
- heat therapy can be accomplished within a body or across the skin by means of, for example, irradiation or illumination, such as ultraviolet radiation, infrared radiation, microwave radiation, etc.
- irradiation or illumination such as ultraviolet radiation, infrared radiation, microwave radiation, etc.
- the present invention also provides a method of treatment comprising:
- the amount and the duration of the contacting as well as the amount and the duration of irradiating can depend on, for example, the diagnostic or therapeutic objectives of the treatment method, such as fluorescent detection of a diseased state or condition, the delivery of an effect therapeutic agent, or both.
- the amount and the duration of the contacting and irradiating can also depend on, for example, the relative concentration ligated-fluorescent nanoparticle to the target analyte, and the state of the cell for treatment, such as in vivo or in vitro whole cells, permeabilized cells, homogenized cells, sensitized cells, and like cell preparations.
- the ligated-fluorescent nanoparticles of the present invention also have application in diagnostic kits or assays, such as immunoassays, in improved imaging agents, in purification processes, in drugs, for example, treatment regimes and therapies, such as drug delivery to specifically target and shrink tumors or to identify and separate infectious agents, and like applications.
- the invention provides a kit for use in the detection of an analyte, the kit comprising a ligated-fluorescent nanoparticle, as illustrated herein.
- the invention also provides a kit for detecting and monitoring a cell surface component comprising a ligated-fluorescent nanoparticle for detecting the cell surface component, and optionally a recorder for monitoring the cell surface component.
- kits include packaging of the kit component(s) and instructions for use of the kit.
- the invention also provides an assay method for detecting motion or a change in the location of a cellular component in, or on the surface of, a cell when the cell is treated with a therapeutic agent comprising:
- the motion or movement of the fluorescent loci that is an analyte bound by a ligated-fluorescent nanoparticle, is representative of and can be correlated to the motion or movement of the bound analyte, such as a cellular component.
- the assay method for detecting motion or a change in the location of a cellular component can include, for example, optionally mapping or plotting the recorded positions of ligated-fluorescent nanoparticle.
- the assay method can further comprise determining the difference between the motion or movement of the analyte bound ligated-fluorescent nanoparticle in the presence and absence of the therapeutic agent, for example, in a tandem or control experimental design.
- the nanoparticles materials such as the ligated-fluorescent nanoparticles, and methods of use of the present invention can be used as, for example, labeled assay reagents or reagent products made therefrom, for assaying the presence of a cell component, for example, an enzyme, a receptor, and like cell components.
- a cell component for example, an enzyme, a receptor, and like cell components.
- the location of the cell component can be detected and determined, for example, inside a metabolically active whole cell, in a whole cell lysate, in a permeabilized cell, in a fixed cell, or with a partially purified cell component in a cell-free environment.
- the ligated-fluorescent nanoparticle contains an associated ligand or ligator, such as an antibody, which nanoparticle targets or associates with a specific cell component of interest.
- the ligated-fluorescent nanoparticle also contains a fluorescent label or fluorescent component in the nanoparticle core, which fluorescent component marks or reports on the presence of the target cell component when the nanoparticle and the target cell component are associated and appropriately illuminated or irradiated.
- the invention also provides methods for treating a disease by administration of an effective amount of a linked fluorescent nanoparticles.
- the methods may involve administration of a linked fluorescent nanoparticles as described herein, alone, in a pharmaceutical composition, or in combination with other therapeutic agents or pharmaceutical compositions.
- the invention also provides methods to increase the effectiveness of a therapeutic agent by linking the therapeutic agent to a fluorescent nanoparticle.
- the fluorescent nanoparticles and pharmaceutical compositions thereof may also be used to associate therapeutic agents to increase the therapeutic efficiency of the therapeutic agent.
- Conjugation of a fluorescent nanoparticle with a ligand to form a linked- or ligated-fluorescent nanoparticle is preferably accomplished in vitro where, for example, ligand amounts and conditions can be carefully controlled to produce a product of high purity and high quality.
- modifying the linked fluorescent nanoparticle with a therapeutic agent is preferably accomplished in vitro.
- the present invention provides fluorescent nanoparticles and ligated-fluorescent nanoparticle thereof, and methods for their use in, for example, immunolabeling, sub-cellular recognition procedures, diagnostics, or cell sorting.
- the methods of the present invention provide advantages which overcome shortcomings of known methodologies and as illustrated herein.
- the present invention provides ligated-fluorescent nanoparticles which are highly dispersible, and are useful, for example, in improved methods for chemical and biochemical analysis, such as, the detection of biological analytes including micro-organisms or sub-cellular components.
- the ligated-fluorescent nanoparticle can provide high local concentrations of fluorescent material because of their high target selectively or affinity, and because of their enhanced brightness compared to known fluorescent particles.
- the fluorescent material is present throughout the nanoparticle core and not simply as a surface coating material as in many conventional materials.
- a “therapeutic agent” is a substance that may be used in the diagnosis, cure, mitigation, treatment, or prevention of disease in a human or another animal.
- Such therapeutic agents include substances recognized in the official United States Pharmacopeia, official Homeopathic Pharmacopeia of the United States, official National Formulary, or any supplement thereof.
- Therapeutic agents that can be incorporated with the fluorescent nanoparticles or the ligated-fluorescent nanoparticles of the invention include nucleosides, nucleoside analogs, oligopeptides, polypeptides, COX-2 inhibitors, apoptosis promoters, urinary tract agents, vaginal agents, vasodilators neurodegenerative agents (e.g., Parkinson's disease), obesity agents, ophthalmic agents, osteoporosis agents, para-sympatholytics, para-sympathometics, antianesthetics, prostaglandins, psychotherapeutic agents, respiratory agents, sedatives, hypnotics, skin and mucous membrane agents, anti-bacterials, anti-fungals, antineoplastics, cardioprotective agents, cardiovascular agents, anti-thrombotics, central nervous system stimulants, cholinesterase inhibitors, contraceptives, dopamine receptor agonists, erectile dysfunction agents, fertility agents, gastrointestinal agents, gout agents
- Examples of specific therapeutic agents that can be linked, ligated, or associated with the fluorescent nanoparticles of the invention are flomoxef; fortimicin(s); gentamicin(s); glucosulfone solasulfone; gramicidin S; gramicidin(s); grepafloxacin; guamecycline; hetacillin; isepamicin; josamycin; kanamycin(s); flomoxef; fortimicin(s); gentamicin(s); glucosulfone solasulfone; gramicidin S; gramicidin(s); grepafloxacin; guamecycline; hetacillin; isepamicin; josamycin; kanamycin(s); bacitracin; bambermycin(s); biapenem; brodimoprim; butirosin; capreomycin; carbenicillin; carbomycin; carum
- streptozocin doxorubicin; daunorubicin; plicamycin; idarubicin; mitomycin C; pentostatin; mitoxantrone; cytarabine; fludarabine phosphate; butorphanol; nalbuphine.
- a “pharmaceutical composition” includes a therapeutic agent as exemplified herein in combination with a fluorescent nanoparticle of the invention, for example, where the fluorescent nanoparticle can act as the pharmaceutically acceptable carrier.
- a pharmaceutical composition of the present invention in addition to a therapeutic agent combination with a fluorescent nanoparticle, can be formulated into or with other acceptable carriers or dosage forms, such as, a solid, gelled or liquid diluent or an ingestible capsule.
- the pharmaceutical compositions of the invention, the salts thereof, or a mixture thereof may be administered orally in the form of a suitable pharmaceutical unit dosage form.
- the pharmaceutical compositions of the invention may be prepared in many forms that include tablets, hard or soft gelatin capsules, aqueous solutions, suspensions, and liposomes and other slow-release formulations, such as shaped polymeric gels.
- Oral liquid pharmaceutical compositions may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, or may be presented as a dry product for constitution with water or other suitable vehicle before use.
- Such liquid pharmaceutical compositions may contain conventional additives such as suspending agents, emulsifying agents, non-aqueous vehicles (which may include edible oils), or preservatives.
- the nanoparticle pharmaceutical compositions of the invention may also be formulated for parenteral administration (e.g., by injection, for example, bolus injection or continuous infusion) and may be presented in unit dosage form in ampules, pre-filled syringes, small volume infusion containers or multi-dose containers with an added preservative.
- the pharmaceutical compositions may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents.
- the pharmaceutical compositions of the invention may be in powder form, obtained by aseptic isolation of sterile solid or by lyophilization from solution, for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water, before use.
- the pharmaceutical compositions may be formulated as ointments, creams or lotions, or as the active ingredient of a transdermal patch.
- Suitable transdermal delivery systems are disclosed, for example, in A. Fisher et al. (U.S. Pat. No. 4,788,603), or R. Bawa et al. (U.S. Pat. Nos. 4,931,279; 4,668,506; and 4,713,224).
- Ointments and creams may, for example, be formulated with an aqueous or oily base with the addition of suitable thickening and/or gelling agents.
- Lotions may be formulated with an aqueous or oily base and will in general also contain one or more emulsifying agents, stabilizing agents, dispersing agents, suspending agents, thickening agents, or coloring agents.
- the pharmaceutical compositions can also be delivered via ionophoresis, e.g., as disclosed in U.S. Pat. Nos. 4,140,122; 4,383,529; or 4,051,842.
- compositions suitable for topical administration in the mouth include unit dosage forms such as lozenges comprising a pharmaceutical composition of the invention in a flavored base, usually sucrose and acadia or tragacanth; pastilles comprising the pharmaceutical composition in an inert base such as gelatin and glycerin or sucrose and acacia; mucoadherent gels, and mouthwashes comprising the pharmaceutical composition in a suitable liquid carrier.
- unit dosage forms such as lozenges comprising a pharmaceutical composition of the invention in a flavored base, usually sucrose and acadia or tragacanth
- pastilles comprising the pharmaceutical composition in an inert base such as gelatin and glycerin or sucrose and acacia
- mucoadherent gels such as mucoadherent gels
- mouthwashes comprising the pharmaceutical composition in a suitable liquid carrier.
- the pharmaceutical compositions can be administered as drops, gels (S. Chrai et al., U.S. Pat. No. 4,255,415), gums (S. L. Lin et al., U.S. Pat. No. 4,136,177) or via a prolonged-release ocular insert (A. S. Michaels, U.S. Pat. No. 3,867,519 and H. M. Haddad et al., U.S. Pat. No. 3,870,791).
- compositions can be adapted to give sustained release of a therapeutic compound employed, e.g., by combination with certain hydrophilic polymer matrices, e.g., comprising natural gels, synthetic polymer gels or mixtures thereof.
- compositions suitable for rectal administration wherein the carrier is a solid are most preferably presented as unit dose suppositories.
- Suitable carriers include cocoa butter and other materials commonly used in the art, and the suppositories may be conveniently formed by admixture of the pharmaceutical composition with the softened or melted carrier(s) followed by chilling and shaping in molds.
- compositions suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or sprays containing, in addition to the nanoparticles and the therapeutic agent, such carriers are well known in the art.
- the pharmaceutical compositions according to the invention are conveniently delivered from an insufflator, nebulizer or a pressurized pack or other convenient means of delivering an aerosol spray.
- Pressurized packs may comprise a suitable propellant such as dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas.
- the dosage unit may be determined by providing a valve to deliver a metered amount.
- the pharmaceutical compositions of the invention may take the form of a dry powder composition, for example, a powder mix of the pharmaceutical composition and a suitable powder base such as lactose or starch.
- the powder composition may be presented in unit dosage form in, for example, capsules or cartridges or, e.g., gelatin or blister packs from which the powder may be administered with the aid of an inhalator or insufflator.
- the pharmaceutical compositions of the invention may be administered via a liquid spray, such as via a plastic bottle atomizer.
- a liquid spray such as via a plastic bottle atomizer.
- mistometer® isoproterenol inhaler-Wintrop
- Medihaler® isoproterenol inhaler—Riker.
- compositions of the invention may also contain other adjuvants such as flavorings, colorings, anti-microbial agents, or preservatives.
- the amount of the pharmaceutical compositions required for use in treatment will vary not only with the particular salt selected but also with the route of administration, the nature of the condition being treated and the age and condition of the patient and will be ultimately at the discretion of the attendant physician or clinician.
- the amount of a therapeutic agent in combination with ligated-fluorescent nanoparticles of the invention which can be administered and the frequency of administration to a given human patient will depend upon a variety of variables related to the patient's psychological profile and physical condition. For evaluations of these factors, see J. F. Brien et al., Europ. J. Clin. Pharmacol., 14, 133 (1978); and Physicians' Desk Reference, Charles E. Baker, Jr., Pub., Medical Economics Co ., Oradell, N.J. (41st ed., 1987). Generally, the dosages of the therapeutic agent when used in combination with the ligated-fluorescent nanoparticles of the present can be lower than when the therapeutic agent is administered alone or in conventional pharmaceutical dosage forms.
- the high specificity of the ligated-fluorescent nanoparticle for a target site can provide relatively high localized concentrations of a therapeutic agent, or alternatively, a sustained release of a therapeutic agent over an extended time period.
- “Pharmaceutically acceptable salts” of the ligated-fluorescent nanoparticles and the therapeutic agents of the invention can include, but are not limited to, the nontoxic addition salts with organic and inorganic acids, such as the citrates, bicarbonates, malonates, tartrates, gluconates, hydrochlorides, sulfates, phosphates, and like salts. Additionally, in cases where the nanoparticles are sufficiently basic or acidic to form stable acid or base salts, preparation of the nanoparticles as salts may be appropriate.
- acceptable salts are organic acid addition salts formed with acids which form a acceptable anion, for example, tosylate, methanesulfonate, acetate, citrate, malonate, tartarate, succinate, benzoate, ascorbate, ⁇ -ketoglutarate, and ⁇ -glycerophosphate.
- Suitable inorganic salts may also be formed, including hydrochloride, sulfate, nitrate, bicarbonate, and carbonate salts.
- Acceptable salts may be obtained using standard procedures known in the art, for example by reacting a sufficiently basic compound such as an amine with a suitable acid affording a diagnostically acceptable anion.
- Alkali metal e.g., sodium, potassium or lithium
- alkaline earth metal e.g. calcium
- Receptor is any macromolecular compound or composition capable of recognizing (e.g. such as having an enhanced binding affinity to) a particular spatial and polar organization of a molecule, i.e., epitopic or determinant site.
- Illustrative receptors include naturally occurring receptors, e.g., thyroxine binding globulin, antibodies, enzymes, immunoglobulin (Fab) fragments, lectins, various proteins found on the surface of cells (cluster of differentiation or CD molecules), and the like.
- CD molecules denote known and unknown proteins on the surface of eukaryotic cells, for example, CD4 is the molecule that primarily defines helper T lymphocytes.
- “Haptens” can include naturally occurring hormones, naturally occurring drugs, synthetic drugs, pollutants, allergens, affector molecules, growth factors, chemokines, cytokines, lymphokines, amino acids, oligopeptides, chemical intermediates, nucleotides, oligonucleotides, and the like.
- the use for such compounds may be in the detection of drugs of abuse, therapeutic dosage monitoring, health status, donor matching for transplantation purposes, pregnancy (e.g., hCG or alpha-fetoprotein), detection of disease, e.g. endotoxins, cancer antigens, pathogens, and the like.
- Immunoconjugate is a molecule formed by attachment of two different molecules or entities, such as an antibody ligated to a fluorescent nanoparticle, and a second usually biologically active molecular entity (analyte) such as an organic drug molecule, a radionuclide, an enzyme, a toxin, a protein, and like materials that can be conjugated to the antibody to form the conjugate.
- analyte such as an organic drug molecule, a radionuclide, an enzyme, a toxin, a protein, and like materials that can be conjugated to the antibody to form the conjugate.
- the antibody portion directs or guides the attached fluorescent nanoparticle to the target analyte enabling the fluorescent nanoparticle to efficiently produce a biological or marking effect.
- Pathogens of interest can be, for example, viruses such as Herpesviruses, Poxviruses, Togaviruses, Orthomyxoviruses, Paramyxoviruses, Rhabdoviruses, Coronaviruses, Arenaviruses, and Retroviruses.
- viruses such as Herpesviruses, Poxviruses, Togaviruses, Orthomyxoviruses, Paramyxoviruses, Rhabdoviruses, Coronaviruses, Arenaviruses, and Retroviruses.
- Pathogens also include prions and bacteria including but not limited to Escherichia coli, Pseudomonas aeruginosa, Enterobacter cloacae, Staphylococcus aureus, Enterococcus faecalis, Klebsiella pneumoniae, Salmonella typhimurium, Staphylococcus epidermidis, Serratia marcescens, Mycobacterium bovis , methicillin resistant Staphylococcus aureus and Proteus vulgaris .
- a non-exhaustive list of these organisms and associated diseases can be found, for example, in U.S. Pat. No. 5,795,158.
- Assays using nanoparticles of the invention can be carried out in a biological fluid, including separated or unfiltered biological fluids such as urine, cerebrospinal fluid, pleural fluid, synovial fluid, peritoneal fluid, amniotic fluid, gastric fluid, blood, serum, plasma, lymph fluid, interstitial fluid, tissue homogenate, cell extracts, saliva, sputum, stool, physiological secretions, tears, mucus, sweat, milk, semen, vaginal secretions, fluid from ulcers and other surface eruptions, blisters, abscesses, and extracts of tissues including biopsies of normal, malignant, and suspect tissues or any other constituents of the body which may contain the analyte of interest.
- biological fluids such as urine, cerebrospinal fluid, pleural fluid, synovial fluid, peritoneal fluid, amniotic fluid, gastric fluid, blood, serum, plasma, lymph fluid, interstitial fluid, tissue homogenate, cell extracts, saliva, sputum, stool, physiological secret
- test sample can be obtained from an environmental source, such as soil, water, or air; or from an industrial source such as taken from a waste stream, a water source, a supply line, or a production lot.
- Industrial sources also include fermentation media, such as from a biological reactor or food fermentation process such as brewing; or foodstuff, such as meat, game, produce, or dairy products.
- the test sample can be pre-treated prior to use, such as preparing plasma from blood, diluting viscous fluids, and the like; methods of pretreatment can involve filtration, fractionation, distillation, concentration, inactivation of interfering compounds, and addition of reagents, and like steps, or combinations thereof.
- Methods for detecting multiple subpopulations of analytes are known, see for example, U.S. Pat. No. 5,567,627, to Lehnen, and can be adapted to the present invention.
- Methods for detecting a nucleic acid with one or more nanoparticle having oligonucleotides attached thereto including an electrochemical assay with a probe oligonucleotide having attached a redox-active molecule, for example as in U.S. Pat. No. 6,417,340, to Mirkin, et al, can be adapted to the present invention.
- the nanoparticle's fluorescent component should provide a signal related to the presence of analyte in the sample.
- a ligand which includes a fluorescent nanoparticle, it should provide a fluorescent signal related to the presence of analyte in the sample and which signal can be detected as electromagnetic radiation, particularly as radiation in the ultra-violet, visible or infrared range.
- “Optional” or “optionally” mean that the subsequently described event or condition may but need not occur, and that the description includes instances where the event or condition occurs and instances in which it does not.
- “optionally including” means that the named component may be present but need not be present, and the description includes situations where the named component is included and situations where the named component is not included.
- a fluorescent nanoparticle of the invention can be prepared, for example, mixing a reactive fluorescent compound, such as, a reactive fluorescent material, such as a dye (D) and a co-reactive organo-silane compound such as, a known organo-functional silane compound (OS) to form a fluorescent core particle (D-OS); and mixing the resulting core particle (D-OS) with a silica forming compound, such as a (Si(OR) 4 ), to form a silica shell on the core which product is a fluorescent nanoparticle (D-OS)(SiO 2 ).
- a reactive fluorescent compound such as, a reactive fluorescent material, such as a dye (D) and a co-reactive organo-silane compound such as, a known organo-functional silane compound (OS)
- OS organo-functional silane compound
- the molar equivalent ratio of the reactive fluorescent material (D) and the co-reactive organo-silane compound (OS) can be, for example, from about 1:1 to about 1:100.
- the molar equivalent ratio of the fluorescent core particle (D-OS) to the silica forming compound (Si(OR) 4 ) can be, for example, from about 1:1 to about 1:100.
- the nanoparticles of the present invention can be selectively linked to either or both a ligand and analyte by, for example, any known chemical coupling reactions such as carbodiimide coupling.
- Other coupling methods include use of carboxylates, esters, alcohols, carbamides, aldehydes, amines, sulfur oxides, nitrogen oxides, or halides, and other methods known in the art can be used.
- Coupling a fluorescent nanoparticle to a ligand, or a ligated-fluorescent nanoparticle to an analyte, and like combinations can generally be accomplished by applying the procedures and principles disclosed in U.S. Pat. No. 6,268,222, or other procedures known in the art as applied to the present invention.
- linked-fluorescent nanoparticle such as a surface modified fluorescent nanoparticle of the invention
- a surface modified fluorescent nanoparticle of the invention can be prepared, for example, from a preformed fluorescent nanoparticle fluorescent nanoparticle (D-OS)(SiO 2 ) and a ligand, such as a biologically active compound (of formula X 1 -R 1 -X 2 ), and optionally a linker precursor (of formula Z 1 -L-Z 2 ), wherein X 1 , X 2 , Z 1 , and Z 2 can be selected from the values in the table below.
- a linker precursor of formula Z 1 -L-Z 2
- the ligand and the linker precursor can be reacted or polymerized using well known synthetic techniques (e.g. by condensation) to provide a ligated-fluorescent nanoparticle or linked product of the invention.
- a corresponding functional group (Z 1 or Z 2 ) can be selected from the following table, to provide an ester linkage, thioester linkage, or amide linkage in the ligated-fluorescent nanoparticle or linked product.
- suitable protecting groups can be used during the ligation reaction.
- other functional groups present in the biologically active compound, on the nanoparticle surface, or the linker precursor can be partially or completely protected during ligation, and the protecting groups can subsequently be removed to provide the ligated-fluorescent nanoparticles of the invention.
- Suitable protecting groups and methods for their incorporation and removal are well known in the art (see for example Greene, T. W.; Wutz, P. G. M. “Protecting Groups In Organic Synthesis” second edition, 1991, New York, John Wiley & sons, Inc.).
- carboxylic acid when a carboxylic acid is reacted with a hydroxy group, a mercapto group, or an amine group to provide an ester linkage, thioester linkage, or an amide linkage, the carboxylic acid can be activated prior to the reaction, for example, by formation of the corresponding acid chloride.
- Numerous methods for activating carboxylic acids, and for preparing ester linkages, thioester linkages, and amide linkages, are known in the art (see for example, Advanced Organic Chemistry: Reaction Mechanisms and Structure, 4th ed., Jerry March, John Wiley & Sons, pages 419-437 and 1281).
- the silica shell surface of the nanoparticles can be further modified if desired by, for example, surface functionalization reactions using known cross-linking agents to afford surface functional groups and as illustrated herein.
- Crosslinking agents are, for example, divinyl benzene, ethylene glycol dimethacrylate, trimethylol propane trimethacrylate, N,N′-methylene-bis-acrylamide, alkyl ethers, sugars, peptides, DNA fragments, or other known functionally equivalent agents. It is readily evident to one skilled in the art that many cross-linking agents can be used in combination with, or suitable for use as the ligand in forming ligated-fluorescent nanoparticles of present invention. It is readily evident to one skilled in the art in possession of the present invention that cross-linking agents can be used in surface modifying reactions to modify the surface properties of fluorescent nanoparticles, or ligated-fluorescent nanoparticles, and as illustrated herein.
- Amounts of water, ammonia and solvent were measured in graduated cylinders. Fluorescent seed particle synthesis was carried out in 1 L Erlenmeyer flasks and stirred with magnetic TEFLON® coated stir bars at about 600 rpm. De-ionized water and ammonia solution were added to ethanol and stirred. About 2 mL of the reactive dye precursor in either ethanol or THF containing about 425 micromolar APTS, was added to the reaction vessel. The resulting mixture was stirred for about 1 to about 3 hours at room temperature with the reaction vessel covered with aluminum foil to minimize exposure to light to afford a fluorescent seed particle mixture. Tetrahydrofuran (THF) and absolute ethanol (EtOH) were distilled under nitrogen. Organic dyes were brought to room temperature from storage temperatures of about ⁇ 20° C., then placed in a glove box.
- the silica shell coating and growth step was performed in the above mentioned fluorescent seed particle reaction mixture with regular addition of solvent, such as ethanol, methanol, or isopropanol, to prevent drastic changes in solution ionic strength while the silica forming monomer tetraethoxysilane (TEOS) was added. This prevents particle aggregation during synthesis, which can broaden the particle size distribution.
- solvent such as ethanol, methanol, or isopropanol
- FIG. 1A there is illustrated an example of fluorescent brightness properties of the fluorescent nanoparticles (10) of the present invention compared to polystyrene latex beads (20).
- Fluorescence correlation spectroscopy FCS was used to obtain the count rates for the nanoparticles and beads as follows: 100 or 300 nanometer fluorescent nanoparticles had 299.1 kHz per particle; and 300 nanometer polystyrene latex beads had 69.84 kHz per bead. Fluorescence count rates indicated that the fluorescent nanoparticles (10) were about four times brighter than the polystyrene latex beads.
- Photo-physical characterizations were performed to determine: dye content per particle content, fluorescence lifetimes, and action cross-sections.
- the action cross-section metric is essentially the product of quantum yield and absorbance profile. Time resolved fluorescence measurements of fluorescence versus time in nanoseconds (ns) showed that a dye incorporated in a nanoparticle exhibited a longer lifetime than free dyes in solution, indicating that each dye molecule could be about 46% brighter when contained inside the core of the nanoparticles than when free in solution.
- TRITC dyes contained within the core of the nanoparticle had a fluorescence lifetime of about 3.33 ns, compared to TRITC dyes free in solution which had a fluorescence lifetime of about 2.28 ns.
- Alexa Fluor® 488 carboxylic acid 5 mg was dissolved in THF.
- the molar ratio of 3-Aminopropyltriethoxysilane (APTS) to Alexa Flour® 488 carboxylic acid, succinimidyl ester was 100 to 1, with 2 ml of THF per mg of APTS.
- APTS 3-Aminopropyltriethoxysilane
- APTS was added to the reaction vessel and stirred for 12 hours in darkness at room temperature. Due to the minute quantities, the fluorescent dye-core adducts were not isolated from the reaction medium before the silica shell was deposited.
- TEOS was added in small aliquots intermittently, such as 300 microliters in about 10 to 15 minute intervals, and stirred overnight at room temperature in darkness. Molar ratio of de-ionized water to monomer was kept maintained at about at least 6-fold but not more. To better monitor water content in the reaction mixture, 2.0 M ammonia was used as the catalyst source, dissolved in ethanol, methanol or isopropanol, depending on the primary solvent of the synthesis, such as 2.0 M ammonia in ethanol.
- tetraethyl orthosilicate monomer was added intermittently, such as 300 microliters every 10 minutes to grow the siliceous shell.
- the smaller particle size procedure for particles below about 70 nm
- the TEOS monomer was added intermittently.
- the alternative procedure for preparing silica shell coated fluorescent nanoparticles was devised because the size distribution of silica nanoparticles prepared by the known Stöber procedure (J. Colloid and Interface Sci., 26 62-69 (1968)) has a self-sharpening characteristic as particle size increases beyond 70 nm as more monomer is added to the reaction mixture.
- silica nanoparticles smaller than 70 nm generally have a much broader size distribution. Therefore, the first mentioned procedure of Example 3, was modified as described thereafter to obtain nanoparticles with a narrower size distribution than what might be expected for particle sizes in the range of about 10 to about 70 nm.
- Nanoparticle Ligation (coupling) with IgE by Adsorption Silica coated fluorescent nanoparticles of Example 3 were diluted (1: 10-1:20) with phosphate buffered saline (PBS) or Tyrodes buffer at pH 7.
- Immunoglobulin E (IgE) (0.85 mg/mL stock concentration) was adsorbed onto the fluorescent nanoparticles by incubating with IgE for about 3 hours at room temperature to provide, for example, nanoparticle-IgE ratios of from about 1:1 to about 1:4. For nanoparticles greater than about 50 nm, unbound IgE was removed by centrifugation.
- the unbound IgE was removed by adding 100 microliters (in a total volume of 500 microliters nanoparticles-IgE) of 0.25 wt % latex particles of size 1:2 microns. Unbound IgE stuck to the large latex particles which then settled out of suspension if undisturbed in several hours, for example, with overnight incubation at 4° C. The residual pellet mass was confirmed to be primarily latex particles bound with IgE and discarded. The resulting supernatant containing the IgE coupled-nanoparticle (IgE ligated-fluorescent nanoparticle) was carefully separated and placed in a vial.
- the resulting IgE coupled-nanoparticle samples (i.e. IgE adsorbed onto nanoparticles) were stored at 4° C. for cell binding experiments.
- the IgE coupled nanoparticles were diluted in Tyrodes-BSA before cell binding. The dilution was according to the IgE coupled-nanoparticle number density desired per cell.
- Nanoparticle Surface Functionalization The surface of the nanoparticles can be further chemically modified to improve the versatility and stability of the nanoparticles, for example, introducing carboxylic acid groups or like chemical functional groups.
- Introducing functional groups, such as carboxylic acid groups, to the surface of silica coated nanoparticles can provide attachment points to enable covalent attachment of bio-molecules, for example, proteins and antibodies, to the surface of the nanoparticles.
- Surface functional groups, especially ionizable groups provide other desirable properties to the nanoparticles, such as charge stabilization in buffered media. Charged carboxylate surface groups can maintain the nanoparticles as single particle colloidal dispersions which avoid or minimize nanoparticle agglomeration.
- Nanoparticle surface functionalization procedures are known and include, for example, carbodiimide modification and as illustrated herein.
- APDMES 3-aminopropyldimethylethoxysilane
- MSA Methyl N-succinimidyl adipate
- Nanoparticle surface functionalization was accomplished as follows. A 20 mL suspension of nanoparticles with a diameter of 25 nm, as described in Table I, was used. The nanoparticle concentration was 4.33 mg/mL as determined by fluorescence correlation spectroscopy, and by drying and weighing known volumes of the suspension. Other nanoparticle sizes and concentrations can be surface modified according to this procedure when appropriately adapted in view of differences in particle size, surface area, concentration, and like considerations.
- Fluorescent nanoparticles having a silica shell were cleaned by dialysis after their initial preparation described above.
- concentration of the silica shelled nanoparticle suspension was determined by drying aliquots of the nanoparticle suspension in a vacuum oven and weighing, or by fluorescence correlation spectroscopy. Assuming a density of 2 g/mL and knowing the size of the nanoparticles, the number of particles per mL of suspension was calculated to be about 1.78 ⁇ 10 16 .
- the density of silanol groups can be estimated as about 1.4 —OH groups per square nanometer according to literature values (e.g. R.
- APDMES The Chemistry of Silica ), and hence there is about 7.78 ⁇ 10 ⁇ 5 moles of —OH groups available for reaction with APDMES for 100% amine coverage.
- APDMES was added in a 2 molar excess with about 5 mg of ammonium fluoride as a catalyst, and allowed to react for about 12 hours at ambient temperature and shielded from ambient light. Excess unreacted APDMES was dialyzed away in phosphate buffer at pH 7 over 12 hours. The resulting aminated nanoparticles suspended in phosphate buffer pH 7 were then reacted with 2-molar excess of MSA dissolved in dimethyl sulfoxide at ambient temperature for about 2 to 6 hours.
- the nanoparticle products at each functionalization step described above were characterized by Fourier Transform Infra-Red (FTIR) spectroscopy.
- FTIR Fourier Transform Infra-Red
- the vibration bands of the mono-substituted amide groups at 1500-1600 cm ⁇ 1 indicated the linkage between amine groups of the silane compound APDMES and the succinimidyl ester groups of the MSA compound, as well as the carboxylic acid signature at 1700 cm ⁇ 1 .
- the observed spectroscopic changes compared to the starting nanoparticles were indicative of successful surface functionalization reactions.
- Nanoparticle Ligation (coupling) by Covalent Conjugation Other surface functionalization examples can be accomplished by covalent conjugation of fluorescent nanoparticles with various biomolecules as described above.
- Confocal microscope images showed, for example, the top surface of the cells decorated with the red nanoparticles, and the antibody IgE is labeled with a green fluorophore to show co-localization of the antibody with the nanoparticles.
- Another set of images, taken from the equitorial view of the cells showed an alternative confocal view where diffusive motions of the antibody receptors marked by the fluorescent nanoparticles can be monitored via SPT. Appropriate controls were performed to check for non-specific binding as follows. Control cells were pre-sensitized overnight using IgE, so that all the receptor sites were blocked.
- FIGS. 2A and 2B there is illustrated an example of high biomolecular binding specificity of, for example, 100 or 300 nanometer diameter fluorescent nanoparticles of the present invention (FIG. 2A) compared to polystyrene latex beads (FIG. 2B) as measured by cell counting statistics.
- rat basophilic leukemia (RBL) mast cells coupled with IgE coupled-nanoparticles and cells coupled with polystyrene latex beads are comparable whereas less desirable or undesired non-specific interactions (represented by the right-side of the bar pairs), such as “sticking” interactions, were greater for polystyrene latex beads and cells compared to IgE coupled-nanoparticles and cells.
- RBL basophilic leukemia
- IgE M refers to mouse IgE which will bind specifically to IgE receptors of rat basophilic leukemia (RBL) mast cells;
- control: IgE H refers to human IgE which will not bind to IgE receptors of the aforementioned rat cells
- control: particles alone refers to the respective binding of IgE coupled-fluorescent nanoparticles with cells, and binding of polystyrene latex beads with cells.
- SPT Single fluorescent nanoparticle Tracking
- Single particle tracking evaluates lateral diffusion of individual components on cell surfaces. This method is based on direct observation of bright fluorescent probes that are specifically conjugated to macromolecules of interest. Tracking of individual components reveals a variety of interesting and useful behaviors including confinement to a small region or movement along a track. This information enables an understanding of how components interact within cells, on cell membranes and like structures or components. However, the method is highly dependent on the quality of the probes. A significant shortcoming of the method has been nonspecific binding of the particles to cells.
- the fluorescent nanoparticles and the ligated-fluorescent nanoparticles of the present invention provide enhanced brightness and high conjugation specificity to a component of interest. The ligated-fluorescent nanoparticles were demonstrated to be biocompatible and minimize non-specific binding interactions.
- the HDTB serves as a templating agent around which the silica shell's formation is ordered and perturbed to enable pore formation by subsequent removal of the HDTB associated with the surface. Subsequent cleaning or removal of the HDTB from the nanoparticle provides fluorescent nanoparticles having a mesoporous silica shell.
- a vacuum distillation was carried out to exchange ethanol solvent with dimethyl sulfoxide (DMSO). Final concentrations were determined by drying an aliquot of the suspension and weighing the solid mass. The resulting meso-porous nanoparticles in DMSO were suitable for loading therapeutic agent as illustrated below.
- DMSO dimethyl sulfoxide
- Sonication was done at 15% power with a pulse rate of 1.0 second on and 1.0 second off for 30 seconds of pulsing or until the solution appeared homogenous. The centrifugation was done at 25° C. at 3,000 rpm for 5 minutes. Therapeutic agent loaded particles were stored at room temperature.
Abstract
The present invention provides nanoparticle compositions comprising, for example, a core comprising a fluorescent silane compound; and a silica shell on the core. Also provided are methods for the preparation of nanoparticle compositions including fluorescent nanoparticles, ligated-fluorescent nanoparticles, ligated-fluorescent nanoparticles having therapeutic agents, and ligated-fluorescent nanoparticles coupled or associated with an analyte. Also provided are methods: for the detection of the ligated-fluorescent nanoparticles; for associating the linked-fluorescent nanoparticles with a cellular component of interest and recording or monitoring the movement of the cellular component; for improving the therapeutic properties of the therapeutic agent by combining the therapeutic agent with linked-fluorescent nanoparticles and contacting or administering the combination to a cell or organism; for making and using the fluorescent nanoparticles in, for example, diagnostic agents for the detection of various analytes, and like applications.
Description
- The invention generally relates to nanoparticles, and more specifically to ligated-fluorescent nanoparticles, methods of making ligated-fluorescent nanoparticles, and methods of using the ligated-fluorescent nanoparticles as biomarkers to, for example, monitor the motion or movement of cellular components on or within cell systems, and for the detection, diagnosis, or treatment of diseases or conditions, for example in intact or living cells.
- Fluorescent and magnetic polymeric particles have known utility as markers and indicators in various biomedical assays. Among the most commonly used markers for sorting cells are immunoconjugates or immunological labels which include, for example, immuno-fluorescent and immuno-magnetic labels. Immunofluorescent labels typically include, for example, a fluorescent molecule joined to an antibody. Immuno-magnetic labels typically include, for example, a superparamagnetic particle joined to either a primary or secondary antibody. Cell labeling can be performed by, for example, attaching the antibody to a marker of interest (e.g., receptor site) on the surface of the cell, that is, a cell surface marker. However, the chemical and physical structure of cell surface marker and density of immunological labels attached to the cell surface have generally been difficult to accurately determine.
- Fluorescent labels have been prepared, for example, by embedding or covalently coupling a fluorescent dye onto a polymeric particle. The resulting fluorescent microparticles can be analyzed manually or by other methods known in the art but preferably using an automated technique, e.g., flow cytometry, such as disclosed in U.S. Pat. No. 4,665,024, to Mansour, et al. The versatility of the fluorescent particles can be further enhanced by the incorporation of multiple fluorescent materials in a single particle. However, while simple absorption of a single dye into a particle can be adequate for most purposes, problems can arise when more than one dye is absorbed into a particle, including: inconsistent emissions attributable to, for example, intermolecular fluorescent energy transfer; differential fluorophore uptake ratios attributable to different dye solubilities within the polymeric matrix; and substrate induced changes in either or both the absorption and emission spectrum of the intercalated fluorophore.
- Magnetic particles, such as known magnetically active materials, can be bonded or attached to, for example, antibodies, such as, monoclonal antibodies that are specific to a particular cell type, antigen, or other targets. The resulting magnetic-antibodies can then be mixed with a large population of many different cell types, for example, crude tissue samples, cells grown in a reactor, and the like. The magnetic-antibodies therefore attach only to their pre-selected target cell type, forming a magnetic-antibody-cell conjugate. The conjugate can then be separated from the rest of the cell population using a magnetic field. A shortcoming of magnetic particles is the lack of specificity in magnetic labeling in that a cell or other biological target analyte may be rendered paramagnetic by a number of different routes which can confound the analysis and diagnostic information afforded by the method, for example, by binding a specific paramagnetic compound to a specific hapten on a cell or by specific or non-specific binding of a paramagnetic metal or metal complex directly to a cell, such as, a metal binding microorganism or by phagocytosis. Other problems encountered with magnetic particles used in detection and diagnostics include, for example, difficulty in obtaining highly accurate quantification of a cell population's magnetic susceptibility. In addition to their magnetic properties (i.e. magnetic, paramagnetic, and superparamagnetic) magnetic-antibodies can be classified, for example, into three broad categories based on their relative descending particle size: magnetic particulate labels, colloidal magnetic labels, and molecular magnetic labels, see for example U.S. Pat. No. 6,412,359.
- Latex nanoparticles having a polymeric core and a surface decorated with, for example, a ligand molecule capable of specific binding with a cell surface and optionally decorated with genetic material, such as a mutant gene, are known and may have utility in, for example, gene delivery to a cell and expression therein, for disrupting tumors, and related treatment applications, see for example,Science, 296, 2404 (2002).
- Optically active nanoparticles, such as fluorescent nanoparticles, having an electrically conducting shell and a silica core are known and have utility in, for example, modulated delivery of a chemical and treatment applications, see for example, U.S. Pat. No. 6,344,272, and 6,428,811.
- A shortcoming of existing fluorescent probe nanoparticles is their limited brightness and their attenuated detectability as fluorescent probes in dispersed systems, particularly with single fluorescent nanoparticles.
- There is currently a need for improved fluorescent nanoparticles and methods for detection and analysis therewith, including their use as fluorescent markers or probes in dispersed biological media.
- The invention provides a fluorescent nanoparticle comprising: a core comprising a fluorescent silane compound; and a silica shell on the core.
- The invention also provides a fluorescent nanoparticle comprising:
- a core comprising a fluorescent silane compound; and a porous silica shell on the core.
- The invention also provides a fluorescent nanoparticle which can further include a ligand, such as a antibody, conjugated with or coated on the surface of the fluorescent nanoparticle to form a ligated-fluorescent nanoparticle. The ligated- or ligand bearing-fluorescent nanoparticles of the present invention can be used, for example, as highly target specific diagnostic agents, and motion monitoring agents when combined with cells or cell components.
- The invention also provides a pharmaceutical carrier or drug delivery vehicle comprising the fluorescent nanoparticles or the ligated-fluorescent nanoparticles of the present invention.
- The invention also provides a fluorescent imaging agent comprising the ligated-fluorescent nanoparticles of the present invention.
- The invention also provides ligated-fluorescent nanoparticles as pharmaceutical carrier particles. Thus, the ligated-fluorescent nanoparticles can further include a therapeutic agent, which therapeutic agent is on the surface or is conjugated with the surface of the fluorescent nanoparticle to form a pharmaceutical composition.
- The invention also provides a method of making a fluorescent nanoparticle comprising:
- mixing a fluorescent compound, such as a reactive fluorescent dye, and an organo-silane compound, such as a co-reactive organo-silane compound, to form a fluorescent core; and
- mixing the resulting core with a silica forming compound, such as a tetraalkoxysilane, to form a silica shell on the core.
- The invention also provides a method for monitoring movement of a cellular component of a cell comprising:
- contacting the cell with a ligated-fluorescent nanoparticle to form a cell selectively decorated with the ligated-fluorescent nanoparticle; and
- recording the motion of a fluorescent loci for a time.
- The invention also provides a method for treating disease comprising:
- administering to a patient in need of treatment with an effective amount of a ligated-fluorescent nanoparticle, which nanoparticle optionally includes a therapeutic agent, the nanoparticle being adapted to selectively associate with a disease producing component of the cell, to form a selectively decorated cell with the ligated-fluorescent nanoparticle; and
- illuminating the decorated cell.
- The invention also provides a method for treatment comprising:
- contacting a cell with a ligated-fluorescent nanoparticle, which nanoparticle optionally includes a therapeutic agent, to form a cell selectively decorated with the ligated-fluorescent nanoparticle; and irradiating the resulting decorated cell for a time.
- The invention also provides a kit for use in the detection of an analyte, the kit comprising a ligated-fluorescent nanoparticle, as illustrated herein.
- The invention also provides a kit for detecting and monitoring a cell surface component comprising a ligated-fluorescent nanoparticle for detecting the cell surface component, and optionally a recorder for monitoring the cell surface component.
- The invention also provides an assay method for detecting motion or a change in the location of a cellular component in, or on the surface of, a cell when the cell is treated with a therapeutic agent comprising:
- contacting a cell with a ligated-fluorescent nanoparticle, wherein the nanoparticle includes a therapeutic agent, to bind the ligated-fluorescent nanoparticle to a cellular component; and
- recording the fluorescent signal.
- FIG. 1A illustrates an example of the fluorescent brightness of the fluorescent nanoparticles of the present invention compared to latex particles.
- FIG. 2A illustrates an example of bio-molecule binding specificity of the fluorescent nanoparticles of the present invention.
- FIG. 2B illustrates an example of bio-molecule binding specificity of comparative latex particles.
- Applicants have discovered fluorescent nanoparticles, and linked- or ligated-fluorescent nanoparticles of the invention that are useful for labeling, detection, identification, motion monitoring, and like applications, of various biological and non-biological analytes. The linked- or ligated-fluorescent nanoparticles of the invention can also be useful in therapeutic treatment, when used as a pharmaceutical carriers, for example, in combination with a suitable therapeutic agent.
- The present invention provides nanoparticles which can have useful multifunctional architectures, for example, a fluorescent nano-sized core which can optionally contain other functionality such as a magnetic component, a silica shell which can be made to have a range of useful thicknesses and surface properties, such as a smooth monolithic surface or a highly porous surface, and which silica surface can be further physically or chemically modified with, for example, a ligand or a therapeutic agent.
- The present invention provides for the preparation and characterizations of fluorescent nanoparticles in various sizes suitable for single particle tracking (SPT) applications. Nanoparticles of various diameters can be prepared having narrow size distributions. The versatility of the preparative route allows for the incorporation of different fluorescent materials, such as dyes, depending on the intended nanoparticle application. Methods for surface functionalization are also provided which enable the conjugation of specific ligands, such as antibodies or proteins, onto the fluorescent nanoparticles to form probes useful for specific SPT experiments. The nanoparticle preparative procedure enables the preparation, by in situ systematic nanoparticle size-growth, of fluorescent nanoparticles in the range of, for example, from about 10 to about 500 nm, and from about 25 to about 100 nm, and narrower ranges therein as illustrated herein.
- The fluorescent nanoparticles can be conjugated with a molecule or entity, such as an antibody ligand or linker, to provide a linked- or ligated-fluorescent nanoparticle which can be used to identify, detect, target (i.e. pinpoint or specify with a high level of certainty), monitor, or modify a disease state or condition, such as the presence or absence of particular receptors, metabolic levels of particular receptors, and like components. The linked- or ligated-fluorescent nanoparticle can be still further conjugated or associated with, for example, a therapeutic agent and used to, for example, treat a disease state or condition, such as by delivering the therapeutic agent to a diseased site in a highly specific or localized manner and in a relatively high concentration with release of the therapeutic agent in a relatively controlled manner. The ligated-fluorescent nanoparticles can be used for directed delivery of a therapeutic agent to a desired location in a variety of systems, such as on, or within, a cell or cell component, or within the body of an organism, such as a human, e.g. across the blood-brain barrier.
- In embodiments the therapeutic agent can be either or both absorbed into, such as the interstices or pores of the silica shell, or coated onto the silica shell of the fluorescent nanoparticle. In other embodiments where the silica shell is incomplete, the therapeutic agent can be associated with the fluorescent core, such as by physical absorption or by bonding interaction. The therapeutic agent can also be associated with the ligand of a ligated-fluorescent nanoparticle if desired.
- The ligated-fluorescent nanoparticles of the present invention can be used in a variety of diagnostic and treatment applications, for example, as a pharmaceutical carrier for therapeutic agents, and as a fluorescent marker in, for example, single nucleotide polymorphorism (SNPs) experiments, such as where a DNA sample is stained with a fluorescent marker and gene activity can be detected as a colored glow of the marker when illuminated with a laser.
- The nanoparticles of the invention, alone or in combination with a ligand, can be used for passive or covalent coupling of biological material, i.e. an analyte, such as haptens, antigens, antibodies, enzymes or nucleic acids, and used for various types of analyte assays such as immunoassays, nucleic acid (DNA or RNA) assays, affinity purification, cell separation, and other medical, diagnostic, environmental, and industrial applications. The nanoparticles incorporate known fluorescently responsive materials, such as, dyes, pigments, or combinations thereof. A wide variety of suitable chemically reactive fluorescent dyes are known, see for example MOLECULAR PROBES HANDBOOK OF FLUORESCENT PROBES AND RESEARCH CHEMICALS, 6th ed., R. P. Haugland, ed. (1996). A typical fluorophore is, for example, a fluorescent aromatic or heteroaromatic compound such as is a pyrene, an anthracene, a naphthalene, an acridine, a stilbene, an indole or benzindole, an oxazole or benzoxazole, a thiazole or benzothiazole, a 4-amino-7-nitrobenz-2-oxa-1,3-diazole (NBD), a cyanine, a carbocyanine, a carbostyryl, a porphyrin, a salicylate, an anthranilate, an azulene, a perylene, a pyridine, a quinoline, a coumarin (including hydroxycoumarins and aminocoumarins and fluorinated derivatives thereof), and like compounds, see for example U.S. Pat. Nos. 5,830,912; 4,774,339; 5,187,288; 5,248,782; 5,274,113; 5,433,896; 4,810,636; and 4,812,409.
- The co-reactive organosilane used for forming the fluorescent core has the general formula R(4-n)SiXn, where X can be a hydrolyzable group such as ethoxy, methoxy, or 2-methoxy-ethoxy; R can be a monovalent organic radical of from 1 to 12 carbon atoms which can optionally contains a functional organic group such as mercapto, epoxy, acrylyl, methacrylyl, or amino; and n is an integer of from 0 to 4. The co-reactive organosilane used for forming the fluorescent core preferably has n equal to 3. A organosilane used for forming the silica shell has n equal to 4. The use of functional mono-, bis- and tris-alkoxysilanes for coupling and modification of co-reactive functional groups or hydroxy-functional surfaces, including glass surfaces, is also known, see Kirk-Othmer, Encyclopedia of Chemical Technology, Vol. 20, 3rd Ed., J. Wiley, N.Y. Although not desired to be limited by theory, the coupling arises as a result of hydrolysis of the alkoxysilane groups to silanol groups and as a result of condensation with hydroxyl groups of the surface, see E. Pluedemann, Silane Coupling Agents, Plenum Press, N.Y. 1982. Thus, the above mentioned organo-silane compounds and like coupling agents can be used: to make the core; to make the silica shell, to modify the surface of the resulting silica shell coated fluorescent core nanoparticles; to attach or couple a ligand to the fluorescent nanoparticles; or to modify the properties of ligand before or after attachment to fluorescent nanoparticle. The organo-silane can cause gels, so it may be desirable to employ an alcohol or other known stabilizers. When the organo-silane is to be copolymerized with another monomer such as a reactive fluorescent compound, a stabilizer can be selected that does not interfere with the polymerization. An alcohol, such as methanol, is especially useful and can be employed in amounts, for example, from about twice to about ten times the amount of the organo-silane.
- The nanoparticles can optionally incorporate known magnet or magnetically responsive materials, such as, superparamagnetic, paramagnetic, ferromagnetic metal oxide, and combinations thereof.
- The fluorescent nanoparticles of the present invention comprise a core comprising a fluorescent silane compound; and a silica shell on the core. The core of the nanoparticle can comprise, for example, the reaction product of a reactive fluorescent compound and an co-reactive organo-silane compound, and the shell can comprise, for example, the reaction product of a silica forming compound. The silica forming compound can produce, for example, one or more layers of silica, such as from 1 to about 20 layers, and depending upon the shell characteristics desired, such as shell layer thickness, the ratio of the shell thickness to the core thickness or diameter, silica shell surface coverage of the core, porosity and carrying capacity of the silica shell, and like considerations.
- The silica shell coating on the core can cover, for example, from about 10 to about 100 percent of the surface area of the core. The ligand when ligated on the surface of the fluorescent nanoparticle can cover, for example, from about 0.1 to about 100 percent of the surface area of the core. The thickness or diameter of the core to the thickness of the silica shell can be in a ratio of, for example, from about 1:1 to about 1:100. The diameter of the fluorescent nanoparticle can be, for example, from about 1 to about 1,000 nanometers. The diameter of a ligated-fluorescent nanoparticle can be comparable to or larger than the diameter of the fluorescent nanoparticle depending upon, for example, the size and the amount of the ligand selected. In embodiments the diameter of the core can be, for example, from about 10 to about 300 nanometers, and preferably from about 25 to about 200 nanometers, and the thickness of the silica shell can be, for example, from about 25 to about 800 nanometers, and preferably from about 25 to about 500 nanometers. In preferred embodiments, such as when the nanoparticles are selected as a carriers, the silica shell is made porous to accommodate for example a therapeutic agent, and as illustrated herein. More preferably the nanoparticles
- The preparative methods for fluorescent nanoparticles of the present invention can yield nanoparticles, for example, of about an order of magnitude smaller in size than those reported by van Blaaderen and Vri,Langmuir, 8, 2921-2925 (1992) (monodisperse silica sphere core particles coated with dyes and further encapsulated with silica). The silica shell can be either solid, that is relatively non-porous, or meso-porous, such as semi-porous. The silica shell of the fluorescent nanoparticles is preferably dielectric. The silica shell of the fluorescent nanoparticles can be adapted to function as a pharmaceutical carrier nanoparticle, that is made to contain, for example, therapeutic agents, such as drugs or proteins for transport and delivery of in vivo or in vitro. Thus, the fluorescent nanoparticles of the present invention can provide a pharmaceutical carrier system which can be adapted for controlled delivery or release of therapeutic agents.
- In embodiments, a ligand placed on the surface of the fluorescent nanoparticle forms a ligated-fluorescent nanoparticle. The placement of the ligand can be accomplished, for example, by attachment with a covalent bond or by physical absorption. The ligand on the surface of the fluorescent nanoparticle can be, for example, a biopolymer, a synthetic polymer, an antigen, an antibody, a virus or viral component, a receptor, a hapten, an enzyme, a hormone, a chemical compound, a pathogen, a microorganism or a component thereof, a toxin, a surface modifier, such as a surfactant to alter the surface properties or histocompatability of the nanoparticle or of an analyte when a nanoparticle associates therewith, and combinations thereof. Preferred ligands are for example, antibodies, such as monoclonal or polyclonal.
- The present invention also provides a method of preparing analytes which are selectively labeled with ligated-fluorescent nanoparticles by, for example, coupling (e.g. covalently) or any other known method(s) of associating the ligated-fluorescent nanoparticles directly to the analyte (e.g., through ionic bonds, hydrogen bonds, by simple adsorption). The resulting selectively labeled analytes having a coupled or associated ligated-fluorescent nanoparticle (i.e. ligated-fluorescent nanoparticle-analyte complex) can be useful as an authentic or reference sample, for example, in a treatment method or diagnostic kit.
- An “analyte” of the present invention is the object or the target of the ligated-fluorescent nanoparticle for attachment or association therewith. The analyte can be, for example, a microorganism or a component thereof, a virus or viral component, a cell or a component thereof, a biopolymer, a synthetic polymer, a synthetic material, such as a carbon nanotube, an antigen, an antibody, a receptor, a hapten, an enzyme, a hormone, a chemical compound, a pathogen, a toxin, combinations thereof, and like substances. Analytes of particular interest are microorganisms and cells, including viruses, prokaryotic and eukaryotic cells, unicellular and multi-cellular organism, e.g., fungi, bacterial, mammalian, etc., and fragments or components thereof. Other analytes of particular interest are pathogens. Monoclonal or polyclonal antibodies or other selective ligands which are part of the ligated-fluorescent nanoparticle can be linked to the surface of, for example, a pathogen.
- In embodiments of the present invention there are provided methods of making a fluorescent nanoparticle, for example, comprising:
- mixing a fluorescent compound, such as a reactive fluorescent dye, and an organo-silane compound, such as a co-reactive organo-silane compound, to form a fluorescent core; and
- mixing the resulting core with a silica forming compound, such as a tetraalkoxysilane, to form a silica shell on the core, to provide the fluorescent nanoparticle.
- The methods of making the nanoparticles of the present invention can further comprise combining the resulting fluorescent nanoparticle with a ligand such as a biopolymer, a synthetic polymer, an antigen, an antibody, a microorganism, a virus, a receptor, a hapten, an enzyme, a hormone, a chemical compound, a pathogen, a toxin, a surface modifier, for example, to alter the surface or compatibility properties of the nanoparticle, combinations thereof, and like materials. The resulting combination of the fluorescent nanoparticle and a ligand provides a ligated-fluorescent nanoparticle. The methods of making the nanoparticles can also further comprise combining the resulting nanoparticle with a therapeutic agent, with or without a ligand attached to the nanoparticle. Combining the nanoparticles with a ligand or a therapeutic agent can be accomplished by, for example, coating the ligand or therapeutic agent onto the surface of the nanoparticle. Alternatively or additionally, combining a nanoparticle with a ligand or a therapeutic agent can be accomplished by, for example, imbibing the ligand or therapeutic agent into the surface of the nanoparticle. Imbibing means to assimilate or to take in or up, for example, where a porous nanoparticle surface is imbibed with a ligand, a therapeutic agent, or both. Alternatively or additionally, combining a nanoparticle with a ligand or a therapeutic agent can be accomplished by, for example, bonding the ligand or therapeutic agent to the surface of the resulting nanoparticle. Bonding includes, for example, known covalent, ionic, hydrogen, hydrophobic, coordination, adhesive, combinations thereof, and like bonding associative methods.
- Because of the small size and uniformity of the nanoparticles of the present invention and their apparent solubility or high dispersibility properties, the nanoparticles can provide “molecular labels” which can readily associate with or be bonded to another entity, such as a ligand or a therapeutic agent, and thereafter be readily transported to and selectively attached to a target analyte. The selective attachment enables useful analytical detection, diagnostic, or differentiation schemes. The size of the ligated-fluorescent nanoparticles for use in embodiments of the present invention can be selected based on the number of nanoparticles to be attached to the analyte and the sensitivity of the optical or spectroscopic schemes selected.
- In embodiments the present invention provides a method for monitoring movement of a cellular component of a cell comprising:
- contacting the cell with a ligated-fluorescent nanoparticle to form a cell selectively decorated with the ligated-fluorescent nanoparticle; and
- recording the motion of a fluorescent loci for a time.
- The fluorescent loci can correspond to a single ligated-fluorescent nanoparticle bound to a component of the cell. The fluorescent loci can correspond to two or more ligated-fluorescent nanoparticles bound to a component of the cell. The monitoring method enables an operator to, for example, track the diffusion of one or more fluorescent loci, such as a receptor to which a single ligated-fluorescent nanoparticle is bound, such as, in real-time or with time-lapse techniques. The ligated-fluorescent nanoparticle is preferably adapted to selectively associate with a targeted cellular component of the cell, for example, by appropriate selection of the ligand.
- The cellular component can be, for example, a receptor, an antibody, a hapten, an enzyme, a hormone, a biopolymer, an antigen, a microorganism, a virus, a pathogen, a toxin, combinations thereof, and like components. In embodiments, the ligated-fluorescent nanoparticle can be a fluorescent nanoparticle conjugated with an antibody. In embodiments, the conjugated antibody can be an immunoglobin, such as IgE.
- Suitable means for detecting, recording, measuring, or imaging in embodiments of the present invention are known in the art and include, for example, a flow cytometer, a laser scanning cytometer, a fluorescence micro-plate reader, a fluorescence microscope, a confocal microscope, a bright-field microscope, a high content scanning system, and like devices.
- The recording can be accomplished, for example, with a microscopically adapted camera, such as a video-microscopy camera, a digital camera, a silver halide single exposure camera, and like devices. The recording time can be any convenient and useful time period to observe notable events or phenomena, for example, intervals from about 1 microsecond to about 30 days. In typical extracellular, surface-cellular, or intra-cellular events, recording for a time period can be, for example, from about 1 second to about 60 minutes, more preferably from about 1 second to about 40 minutes, and even more preferably, from about 1 minute to about 30 minutes. The recording time period can often be conveniently shortened or lengthened as desired by changing the ambient temperature of the sample or system. The contacting and the recording can be accomplished in vitro using conventional microscopic photography techniques. The contacting and the recording can also be accomplished in vivo using, for example, a catheter adapted with a microscopic camera or fiber optic camera. It will be readily evident to one of ordinary skill in the art in embodiments of the present invention that “recording” can be synonymous with “detecting,” since for example making a photographic recording of an illuminated specimen can also simultaneously afford detection of fluorescent loci, such as a cell or cell component selectively decorated with a ligated-fluorescent nanoparticle.
- In embodiments there is provided a pharmaceutical carrier comprising the fluorescent nanoparticle of the present invention, and optionally a ligand associated with the fluorescent nanoparticle.
- In embodiments there is also provided a pharmaceutical composition comprising a ligated-fluorescent nanoparticle, and a therapeutic agent associated with the fluorescent nanoparticle.
- In embodiments there is provided an imaging agent comprising the ligated-fluorescent nanoparticle, for example, where the ligand of the ligated-fluorescent nanoparticle is on the surface of the nanoparticle. The imaging agent can be used in conventional imaging processes, and preferably where, for example, a high fluorescent yield or fluorescent brightness is desired. In embodiments, the ligated-fluorescent nanoparticles of the present invention can provide enhanced fluorescent brightness which is, for example, from about 2 to about 10 times greater compared to conventional surface decorated fluorescent particles, such as fluorescent latex particles.
- In embodiments there is provided a method for treating a disease or disorder comprising:
- administering to a patient in need of treatment an effective amount of a ligated-fluorescent nanoparticle which nanoparticle optionally includes a therapeutic agent, wherein the nanoparticle is adapted to selectively associate with a disease producing component of the cell, to form a selectively decorated cell with the ligated-fluorescent nanoparticle; and
- illuminating the decorated cell.
- The ligated-fluorescent nanoparticle, by itself or as part of a decorated cell, when illuminated can fluoresce, heat-up, or both. Thus, the selection of the reactive fluorescent compound in preparing the fluorescent nanoparticle, and the selection of the ligand, can be made empirically depending upon the balance of fluorescent and non-fluorescent (heat dissipation) properties desired. Higher fluorescent properties may be desired where detection is paramount or difficult, for example in dilute systems. Higher non-fluorescent properties may be desired where high heating is needed to, for example, promote liberation of a therapeutic agent or to accomplish selective microscopic-cauterization or microscopic-heat therapy. In embodiments it may be desirable to use a mixture of two or more ligated-fluorescent nanoparticles having different fluorescent and non-fluorescent properties to exploit the benefits of the different properties, for example, simultaneously or sequentially, such as in the detection and treatment of a cancerous tumor.
- Thus, the ligated-fluorescent nanoparticles of the present invention can be used to treat a light- or heat-sensitive diseases or disorders. Light therapy is known for activation of medicaments at one or more treatment sites within a living body. A particular embodiment of light therapy, for example, is photodynamic therapy (PDT) which is a two-step treatment process which has been found to be effective in destroying a wide variety of cancers. PDT is performed by first systemically or topically administering a photosensitizer compound or like compounds, and subsequently illuminating a treatment site with light in a waveband, which corresponds to an absorption waveband of the photosensitizer. The light energy activates the photosensitizer compound, causing it to destroy the diseased tissue, see for example, U.S. Pat. No. 6,454,789. It is readily evident to one skilled in the art that a fluorescent material, such as the ligated-fluorescent nanoparticles of the present invention, can be used in place of a photosensitizer compound.
- Heat therapy methods are also known, for example, to shrink desired tissues, see U.S. Pat. No. 6,480,746, and for localized treatment of cutaneous warts, seeArch. Dermatol, (July 1992), vol. 128, p. 945-948, and to induce macrophage apoptosis, see U.S. Pat. No. 6,451,044. In these and related applications heat therapy can be accomplished within a body or across the skin by means of, for example, irradiation or illumination, such as ultraviolet radiation, infrared radiation, microwave radiation, etc. One of ordinary skill in the art once in possession of the present invention would readily recognize how to adapt its materials and methods to accomplish light therapy or heat therapy.
- The present invention also provides a method of treatment comprising:
- contacting a cell with a ligated-fluorescent nanoparticle, optionally having a therapeutic agent associated with the nanoparticle, to form a cell selectively decorated with the ligated-fluorescent nanoparticle; and
- irradiating the resulting decorated cell for a time.
- The amount and the duration of the contacting as well as the amount and the duration of irradiating can depend on, for example, the diagnostic or therapeutic objectives of the treatment method, such as fluorescent detection of a diseased state or condition, the delivery of an effect therapeutic agent, or both. The amount and the duration of the contacting and irradiating can also depend on, for example, the relative concentration ligated-fluorescent nanoparticle to the target analyte, and the state of the cell for treatment, such as in vivo or in vitro whole cells, permeabilized cells, homogenized cells, sensitized cells, and like cell preparations.
- The ligated-fluorescent nanoparticles of the present invention also have application in diagnostic kits or assays, such as immunoassays, in improved imaging agents, in purification processes, in drugs, for example, treatment regimes and therapies, such as drug delivery to specifically target and shrink tumors or to identify and separate infectious agents, and like applications.
- The invention provides a kit for use in the detection of an analyte, the kit comprising a ligated-fluorescent nanoparticle, as illustrated herein.
- The invention also provides a kit for detecting and monitoring a cell surface component comprising a ligated-fluorescent nanoparticle for detecting the cell surface component, and optionally a recorder for monitoring the cell surface component.
- The aforementioned kits include packaging of the kit component(s) and instructions for use of the kit.
- The invention also provides an assay method for detecting motion or a change in the location of a cellular component in, or on the surface of, a cell when the cell is treated with a therapeutic agent comprising:
- contacting a cell with a ligated-fluorescent nanoparticle, wherein the nanoparticle includes a therapeutic agent, to bind the ligated-fluorescent nanoparticle to a cellular component; and
- recording the fluorescent signal, such as from one or more fluorescent loci, and determining the relative motion or a change in the location of a targeted cellular component.
- The motion or movement of the fluorescent loci, that is an analyte bound by a ligated-fluorescent nanoparticle, is representative of and can be correlated to the motion or movement of the bound analyte, such as a cellular component.
- The assay method for detecting motion or a change in the location of a cellular component can include, for example, optionally mapping or plotting the recorded positions of ligated-fluorescent nanoparticle. The assay method can further comprise determining the difference between the motion or movement of the analyte bound ligated-fluorescent nanoparticle in the presence and absence of the therapeutic agent, for example, in a tandem or control experimental design.
- The nanoparticles materials, such as the ligated-fluorescent nanoparticles, and methods of use of the present invention can be used as, for example, labeled assay reagents or reagent products made therefrom, for assaying the presence of a cell component, for example, an enzyme, a receptor, and like cell components. The location of the cell component can be detected and determined, for example, inside a metabolically active whole cell, in a whole cell lysate, in a permeabilized cell, in a fixed cell, or with a partially purified cell component in a cell-free environment. The ligated-fluorescent nanoparticle contains an associated ligand or ligator, such as an antibody, which nanoparticle targets or associates with a specific cell component of interest. The ligated-fluorescent nanoparticle also contains a fluorescent label or fluorescent component in the nanoparticle core, which fluorescent component marks or reports on the presence of the target cell component when the nanoparticle and the target cell component are associated and appropriately illuminated or irradiated.
- The invention also provides methods for treating a disease by administration of an effective amount of a linked fluorescent nanoparticles. The methods may involve administration of a linked fluorescent nanoparticles as described herein, alone, in a pharmaceutical composition, or in combination with other therapeutic agents or pharmaceutical compositions.
- The invention also provides methods to increase the effectiveness of a therapeutic agent by linking the therapeutic agent to a fluorescent nanoparticle. The fluorescent nanoparticles and pharmaceutical compositions thereof may also be used to associate therapeutic agents to increase the therapeutic efficiency of the therapeutic agent. Conjugation of a fluorescent nanoparticle with a ligand to form a linked- or ligated-fluorescent nanoparticle is preferably accomplished in vitro where, for example, ligand amounts and conditions can be carefully controlled to produce a product of high purity and high quality. Similarly, modifying the linked fluorescent nanoparticle with a therapeutic agent is preferably accomplished in vitro.
- The present invention provides fluorescent nanoparticles and ligated-fluorescent nanoparticle thereof, and methods for their use in, for example, immunolabeling, sub-cellular recognition procedures, diagnostics, or cell sorting. The methods of the present invention provide advantages which overcome shortcomings of known methodologies and as illustrated herein.
- The present invention provides ligated-fluorescent nanoparticles which are highly dispersible, and are useful, for example, in improved methods for chemical and biochemical analysis, such as, the detection of biological analytes including micro-organisms or sub-cellular components. The ligated-fluorescent nanoparticle can provide high local concentrations of fluorescent material because of their high target selectively or affinity, and because of their enhanced brightness compared to known fluorescent particles. The fluorescent material is present throughout the nanoparticle core and not simply as a surface coating material as in many conventional materials.
- A “therapeutic agent” is a substance that may be used in the diagnosis, cure, mitigation, treatment, or prevention of disease in a human or another animal. Such therapeutic agents include substances recognized in the official United States Pharmacopeia, official Homeopathic Pharmacopeia of the United States, official National Formulary, or any supplement thereof.
- Therapeutic agents that can be incorporated with the fluorescent nanoparticles or the ligated-fluorescent nanoparticles of the invention include nucleosides, nucleoside analogs, oligopeptides, polypeptides, COX-2 inhibitors, apoptosis promoters, urinary tract agents, vaginal agents, vasodilators neurodegenerative agents (e.g., Parkinson's disease), obesity agents, ophthalmic agents, osteoporosis agents, para-sympatholytics, para-sympathometics, antianesthetics, prostaglandins, psychotherapeutic agents, respiratory agents, sedatives, hypnotics, skin and mucous membrane agents, anti-bacterials, anti-fungals, antineoplastics, cardioprotective agents, cardiovascular agents, anti-thrombotics, central nervous system stimulants, cholinesterase inhibitors, contraceptives, dopamine receptor agonists, erectile dysfunction agents, fertility agents, gastrointestinal agents, gout agents, hormones, immunomodulators, suitably functionalized analgesics or general or local anesthetics, anti-convulsants, anti-diabetic agents, anti-fibrotic agents, anti-infectives, motion sickness agents, muscle relaxants, immuno-suppresives, migraine agents, non-steroidal anti-inflammatory drugs (NSAIDs), smoking cessation agents, or sympatholytics (see Physicians' Desk Reference, 55th ed., 2001, Medical Economics Company, Inc., Montvale, N.J., pages 201-202).
- Examples of specific therapeutic agents that can be linked, ligated, or associated with the fluorescent nanoparticles of the invention are flomoxef; fortimicin(s); gentamicin(s); glucosulfone solasulfone; gramicidin S; gramicidin(s); grepafloxacin; guamecycline; hetacillin; isepamicin; josamycin; kanamycin(s); flomoxef; fortimicin(s); gentamicin(s); glucosulfone solasulfone; gramicidin S; gramicidin(s); grepafloxacin; guamecycline; hetacillin; isepamicin; josamycin; kanamycin(s); bacitracin; bambermycin(s); biapenem; brodimoprim; butirosin; capreomycin; carbenicillin; carbomycin; carumonam; cefadroxil; cefamandole; cefatrizine; cefbuperazone; cefclidin; cefdinir; cefditoren; cefepime; cefetamet; cefixime; cefinenoxime; cefininox; cladribine; apalcillin; apicycline; apramycin; arbekacin; aspoxicillin; azidamfenicol; aztreonam; cefodizime; cefonicid; cefoperazone; ceforamide; cefotaxime; cefotetan; cefotiam; cefozopran; cefpimizole; cefpiramide; cefpirome; cefprozil; cefroxadine; cefteram; ceftibuten; cefuzonam; cephalexin; cephaloglycin; cephalosporin C; cephradine; chloramphenicol; chlortetracycline; clinafloxacin; clindamycin; clomocycline; colistin; cyclacillin; dapsone; demeclocycline; diathymosulfone; dibekacin; dihydrostreptomycin; 6-mercaptopurine; thioguanine; capecitabine; docetaxel; etoposide; gemcitabine; topotecan; vinorelbine; vincristine; vinblastine; teniposide; melphalan; methotrexate; 2-p-sulfanilyanilinoethanol; 4,4′-sulfinyldianiline; 4-sulfanilamidosalicylic acid; butorphanol; nalbuphine. streptozocin; doxorubicin; daunorubicin; plicamycin; idarubicin; mitomycin C; pentostatin; mitoxantrone; cytarabine; fludarabine phosphate; butorphanol; nalbuphine. streptozocin; doxorubicin; daunorubicin; plicamycin; idarubicin; mitomycin C; pentostatin; mitoxantrone; cytarabine; fludarabine phosphate; acediasulfone; acetosulfone; amikacin; amphotericin B; ampicillin; atorvastatin; enalapril; ranitidine; ciprofloxacin; pravastatin; clarithromycin; cyclosporin; famotidine; leuprolide; acyclovir; paclitaxel; azithromycin; lamivudine; budesonide; albuterol; indinavir; metformin; alendronate; nizatidine; zidovudine; carboplatin; metoprolol; amoxicillin; diclofenac; lisinopril; ceftriaxone; captopril; salmeterol; xinafoate; imipenem; cilastatin; benazepril; cefaclor; ceftazidime; morphine; dopamine; bialamicol; fluvastatin; phenamidine; podophyllinic acid 2-ethylhydrazine; acriflavine; chloroazodin; arsphenamine; amicarbilide; aminoquinuride; quinapril; oxymorphone; buprenorphine; floxuridine; dirithromycin; doxycycline; enoxacin; enviomycin; epicillin; erythromycin; leucomycin(s); lincomycin; lomefloxacin; lucensomycin; lymecycline; meclocycline; meropenem; methacycline; micronomicin; midecamycin(s); minocycline; moxalactam; mupirocin; nadifloxacin; natamycin; neomycin; netilmicin; norfloxacin; oleandomycin; oxytetracycline; p-sulfanilylbenzylamine; panipenem; paromomycin; pazufloxacin; penicillin N; pipacycline; pipemidic acid; polymyxin; primycin; quinacillin; ribostamycin; rifamide; rifampin; rifamycin SV; rifapentine; rifaximin; ristocetin; ritipenem; rokitamycin; rolitetracycline; rosaramycin; roxithromycin; salazosulfadimidine; sancycline; sisomicin; sparfloxacin; spectinomycin; spiramycin; streptomycin; succisulfone; sulfachrysoidine; sulfaloxic acid; sulfamidochrysoidine; sulfanilic acid; sulfoxone; teicoplanin; temafloxacin; temocillin; tetroxoprim; thiamphenicol; thiazolsulfone; thiostrepton; ticarcillin; tigemonam; tobramycin; tosufloxacin; trimethoprim; trospectomycin; trovafloxacin; tuberactinomycin; vancomycin; azaserine; candicidin(s); chlorphenesin; dermostatin(s); filipin; fungichromin; mepartricin; nystatin; oligomycin(s); perimycin A; tubercidin; 6-azauridine; 6-diazo-5-oxo-L-norleucine; aclacinomycin(s); ancitabine; anthramycin; azacitadine; azaserine; bleomycin(s); ethyl biscoumacetate; ethylidene dicoumarol; iloprost; lamifiban; taprostene; tioclomarol; tirofiban; amiprilose; bucillamine; gusperimus; gentisic acid; glucamethacin; glycol salicylate; meclofenamic acid; mefenamic acid; mesalamine; niflumic acid; olsalazine; oxaceprol; S-enosylmethionine; salicylic acid; salsalate; sulfasalazine; tolfenamic acid; carubicin; carzinophillin A; chlorozotocin; chromomycin(s); denopterin; doxifluridine; edatrexate; eflornithine; elliptinium; enocitabine; epirubicin; mannomustine; menogaril; mitobronitol; mitolactol; mopidamol; mycophenolic acid; nogalamycin; olivomycin(s); peplomycin; pirarubicin; piritrexim; prednimustine; procarbazine; pteropterin; puromycin; ranimustine; streptonigrin; thiamiprine; mycophenolic acid; procodazole; romurtide; sirolimus (rapamycin); tacrolimus; butethamine; fenalcomine; hydroxytetracaine; naepaine; orthocaine; piridocaine; salicyl alcohol; 3-amino-4-hydroxybutyric acid; aceclofenac; alminoprofen; amfenac; bromfenac; bromosaligenin; bumadizon; carprofen; diclofenac; diflunisal; ditazol; enfenamic acid; etodolac; etofenamate; fendosal; fepradinol; flufenamic acid; Tomudex® (N-[[5-[[(1,4-Dihydro-2-methyl-4-oxo-6-quinazolinyl)methyl]methylamino]-2-thienyl]carbonyl]-L-glutamic acid), trimetrexate, tubercidin, ubenimex, vindesine, zorubicin; argatroban; coumetarol or dicoumarol.
- Lists of additional therapeutic agents can be found, for example, in: Physicians' Desk Reference, 55th ed., 2001, Medical Economics Company, Inc., Montvale, N.J.; USPN Dictionary of USAN and International Drug Names, 2000, The United States Pharmacopeial Convention, Inc., Rockville, Md.; and The Merck Index, 12th ed., 1996, Merck & Co., Inc., Whitehouse Station, N.J.
- It will be readily appreciated by those skilled in the art how to determine, for example, therapeutic activity using standard tests or other similar tests which are known in the art.
- A “pharmaceutical composition” includes a therapeutic agent as exemplified herein in combination with a fluorescent nanoparticle of the invention, for example, where the fluorescent nanoparticle can act as the pharmaceutically acceptable carrier. A pharmaceutical composition of the present invention, in addition to a therapeutic agent combination with a fluorescent nanoparticle, can be formulated into or with other acceptable carriers or dosage forms, such as, a solid, gelled or liquid diluent or an ingestible capsule. The pharmaceutical compositions of the invention, the salts thereof, or a mixture thereof, may be administered orally in the form of a suitable pharmaceutical unit dosage form. The pharmaceutical compositions of the invention may be prepared in many forms that include tablets, hard or soft gelatin capsules, aqueous solutions, suspensions, and liposomes and other slow-release formulations, such as shaped polymeric gels.
- Oral liquid pharmaceutical compositions may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, or may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid pharmaceutical compositions may contain conventional additives such as suspending agents, emulsifying agents, non-aqueous vehicles (which may include edible oils), or preservatives.
- The nanoparticle pharmaceutical compositions of the invention may also be formulated for parenteral administration (e.g., by injection, for example, bolus injection or continuous infusion) and may be presented in unit dosage form in ampules, pre-filled syringes, small volume infusion containers or multi-dose containers with an added preservative. The pharmaceutical compositions may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Alternatively, the pharmaceutical compositions of the invention may be in powder form, obtained by aseptic isolation of sterile solid or by lyophilization from solution, for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water, before use.
- For topical administration to the epidermis, the pharmaceutical compositions may be formulated as ointments, creams or lotions, or as the active ingredient of a transdermal patch. Suitable transdermal delivery systems are disclosed, for example, in A. Fisher et al. (U.S. Pat. No. 4,788,603), or R. Bawa et al. (U.S. Pat. Nos. 4,931,279; 4,668,506; and 4,713,224). Ointments and creams may, for example, be formulated with an aqueous or oily base with the addition of suitable thickening and/or gelling agents. Lotions may be formulated with an aqueous or oily base and will in general also contain one or more emulsifying agents, stabilizing agents, dispersing agents, suspending agents, thickening agents, or coloring agents. The pharmaceutical compositions can also be delivered via ionophoresis, e.g., as disclosed in U.S. Pat. Nos. 4,140,122; 4,383,529; or 4,051,842.
- Pharmaceutical compositions suitable for topical administration in the mouth include unit dosage forms such as lozenges comprising a pharmaceutical composition of the invention in a flavored base, usually sucrose and acadia or tragacanth; pastilles comprising the pharmaceutical composition in an inert base such as gelatin and glycerin or sucrose and acacia; mucoadherent gels, and mouthwashes comprising the pharmaceutical composition in a suitable liquid carrier.
- For topical administration to the eye, the pharmaceutical compositions can be administered as drops, gels (S. Chrai et al., U.S. Pat. No. 4,255,415), gums (S. L. Lin et al., U.S. Pat. No. 4,136,177) or via a prolonged-release ocular insert (A. S. Michaels, U.S. Pat. No. 3,867,519 and H. M. Haddad et al., U.S. Pat. No. 3,870,791).
- When desired, the above-described pharmaceutical compositions can be adapted to give sustained release of a therapeutic compound employed, e.g., by combination with certain hydrophilic polymer matrices, e.g., comprising natural gels, synthetic polymer gels or mixtures thereof.
- Pharmaceutical compositions suitable for rectal administration wherein the carrier is a solid are most preferably presented as unit dose suppositories. Suitable carriers include cocoa butter and other materials commonly used in the art, and the suppositories may be conveniently formed by admixture of the pharmaceutical composition with the softened or melted carrier(s) followed by chilling and shaping in molds.
- Pharmaceutical compositions suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or sprays containing, in addition to the nanoparticles and the therapeutic agent, such carriers are well known in the art.
- For administration by inhalation, the pharmaceutical compositions according to the invention are conveniently delivered from an insufflator, nebulizer or a pressurized pack or other convenient means of delivering an aerosol spray. Pressurized packs may comprise a suitable propellant such as dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol, the dosage unit may be determined by providing a valve to deliver a metered amount.
- Alternatively, for administration by inhalation or insufflation, the pharmaceutical compositions of the invention may take the form of a dry powder composition, for example, a powder mix of the pharmaceutical composition and a suitable powder base such as lactose or starch. The powder composition may be presented in unit dosage form in, for example, capsules or cartridges or, e.g., gelatin or blister packs from which the powder may be administered with the aid of an inhalator or insufflator.
- For intra-nasal administration, the pharmaceutical compositions of the invention may be administered via a liquid spray, such as via a plastic bottle atomizer. Typical of these are the Mistometer® (isoproterenol inhaler-Wintrop) and the Medihaler® (isoproterenol inhaler—Riker).
- Pharmaceutical compositions of the invention may also contain other adjuvants such as flavorings, colorings, anti-microbial agents, or preservatives.
- It will be further appreciated that the amount of the pharmaceutical compositions required for use in treatment will vary not only with the particular salt selected but also with the route of administration, the nature of the condition being treated and the age and condition of the patient and will be ultimately at the discretion of the attendant physician or clinician.
- The amount of a therapeutic agent in combination with ligated-fluorescent nanoparticles of the invention which can be administered and the frequency of administration to a given human patient will depend upon a variety of variables related to the patient's psychological profile and physical condition. For evaluations of these factors, see J. F. Brien et al.,Europ. J. Clin. Pharmacol., 14, 133 (1978); and Physicians' Desk Reference, Charles E. Baker, Jr., Pub., Medical Economics Co., Oradell, N.J. (41st ed., 1987). Generally, the dosages of the therapeutic agent when used in combination with the ligated-fluorescent nanoparticles of the present can be lower than when the therapeutic agent is administered alone or in conventional pharmaceutical dosage forms. The high specificity of the ligated-fluorescent nanoparticle for a target site, such as a receptor situated on a cell's surface, can provide relatively high localized concentrations of a therapeutic agent, or alternatively, a sustained release of a therapeutic agent over an extended time period.
- “Pharmaceutically acceptable salts” of the ligated-fluorescent nanoparticles and the therapeutic agents of the invention can include, but are not limited to, the nontoxic addition salts with organic and inorganic acids, such as the citrates, bicarbonates, malonates, tartrates, gluconates, hydrochlorides, sulfates, phosphates, and like salts. Additionally, in cases where the nanoparticles are sufficiently basic or acidic to form stable acid or base salts, preparation of the nanoparticles as salts may be appropriate. Examples of acceptable salts are organic acid addition salts formed with acids which form a acceptable anion, for example, tosylate, methanesulfonate, acetate, citrate, malonate, tartarate, succinate, benzoate, ascorbate, α-ketoglutarate, and α-glycerophosphate. Suitable inorganic salts may also be formed, including hydrochloride, sulfate, nitrate, bicarbonate, and carbonate salts. Acceptable salts may be obtained using standard procedures known in the art, for example by reacting a sufficiently basic compound such as an amine with a suitable acid affording a diagnostically acceptable anion. Alkali metal (e.g., sodium, potassium or lithium) or alkaline earth metal (e.g. calcium) salts of carboxylic acids can also be made.
- “Receptor” is any macromolecular compound or composition capable of recognizing (e.g. such as having an enhanced binding affinity to) a particular spatial and polar organization of a molecule, i.e., epitopic or determinant site. Illustrative receptors include naturally occurring receptors, e.g., thyroxine binding globulin, antibodies, enzymes, immunoglobulin (Fab) fragments, lectins, various proteins found on the surface of cells (cluster of differentiation or CD molecules), and the like. CD molecules denote known and unknown proteins on the surface of eukaryotic cells, for example, CD4 is the molecule that primarily defines helper T lymphocytes.
- “Haptens” can include naturally occurring hormones, naturally occurring drugs, synthetic drugs, pollutants, allergens, affector molecules, growth factors, chemokines, cytokines, lymphokines, amino acids, oligopeptides, chemical intermediates, nucleotides, oligonucleotides, and the like. The use for such compounds may be in the detection of drugs of abuse, therapeutic dosage monitoring, health status, donor matching for transplantation purposes, pregnancy (e.g., hCG or alpha-fetoprotein), detection of disease, e.g. endotoxins, cancer antigens, pathogens, and the like.
- “Immunoconjugate” is a molecule formed by attachment of two different molecules or entities, such as an antibody ligated to a fluorescent nanoparticle, and a second usually biologically active molecular entity (analyte) such as an organic drug molecule, a radionuclide, an enzyme, a toxin, a protein, and like materials that can be conjugated to the antibody to form the conjugate. The antibody portion directs or guides the attached fluorescent nanoparticle to the target analyte enabling the fluorescent nanoparticle to efficiently produce a biological or marking effect.
- Pathogens of interest can be, for example, viruses such as Herpesviruses, Poxviruses, Togaviruses, Orthomyxoviruses, Paramyxoviruses, Rhabdoviruses, Coronaviruses, Arenaviruses, and Retroviruses. Pathogens also include prions and bacteria including but not limited toEscherichia coli, Pseudomonas aeruginosa, Enterobacter cloacae, Staphylococcus aureus, Enterococcus faecalis, Klebsiella pneumoniae, Salmonella typhimurium, Staphylococcus epidermidis, Serratia marcescens, Mycobacterium bovis, methicillin resistant Staphylococcus aureus and Proteus vulgaris. A non-exhaustive list of these organisms and associated diseases can be found, for example, in U.S. Pat. No. 5,795,158.
- Assays using nanoparticles of the invention can be carried out in a biological fluid, including separated or unfiltered biological fluids such as urine, cerebrospinal fluid, pleural fluid, synovial fluid, peritoneal fluid, amniotic fluid, gastric fluid, blood, serum, plasma, lymph fluid, interstitial fluid, tissue homogenate, cell extracts, saliva, sputum, stool, physiological secretions, tears, mucus, sweat, milk, semen, vaginal secretions, fluid from ulcers and other surface eruptions, blisters, abscesses, and extracts of tissues including biopsies of normal, malignant, and suspect tissues or any other constituents of the body which may contain the analyte of interest. Other similar specimens such as cell or tissue culture or culture broth are also of interest. Alternatively, the sample can be obtained from an environmental source, such as soil, water, or air; or from an industrial source such as taken from a waste stream, a water source, a supply line, or a production lot. Industrial sources also include fermentation media, such as from a biological reactor or food fermentation process such as brewing; or foodstuff, such as meat, game, produce, or dairy products. The test sample can be pre-treated prior to use, such as preparing plasma from blood, diluting viscous fluids, and the like; methods of pretreatment can involve filtration, fractionation, distillation, concentration, inactivation of interfering compounds, and addition of reagents, and like steps, or combinations thereof.
- Methods for detecting multiple subpopulations of analytes are known, see for example, U.S. Pat. No. 5,567,627, to Lehnen, and can be adapted to the present invention. Methods for detecting a nucleic acid with one or more nanoparticle having oligonucleotides attached thereto, including an electrochemical assay with a probe oligonucleotide having attached a redox-active molecule, for example as in U.S. Pat. No. 6,417,340, to Mirkin, et al, can be adapted to the present invention. Methods for electrochemical detection and localization of genetic point mutations and other base-stacking perturbations within oligonucleotide duplexes adsorbed onto electrodes, such as U.S. Pat. No. 6,221,586, to Barton, et al., can be adapted to the present invention. Methods for multiplexed fluorescent analysis of a plurality of analytes in a sample, such as U.S. Pat. No. 6,268,222, to Chandler, et al., can be adapted to the present invention. Other detection methods include using ultraviolet and visible spectroscopy, see for example X. Gong and E. S. Yeung,Anal. Chem., 71, 4989 (1999), “An Absorption Detection Approach for Multiplexed Capillary Electrophoresis Using a Linear Photodiode Array”. Methods for separating cells using a flow through fractional cell sorting process based on the application of a magnetic force to cells having a range of magnetic labeling densities, such as U.S. Pat. No. 5,968,820, to Zborowski, et al., can be adapted to the present invention. Methods for separating particles bound to each other via non-covalent binding and agglomeration, such as U.S. Pat. No. 4,279,617, to Masson et al., can be adapted to the present invention.
- For the purposes of the present invention the nanoparticle's fluorescent component should provide a signal related to the presence of analyte in the sample. Similarly, when a ligand is selected, which includes a fluorescent nanoparticle, it should provide a fluorescent signal related to the presence of analyte in the sample and which signal can be detected as electromagnetic radiation, particularly as radiation in the ultra-violet, visible or infrared range.
- “Optional” or “optionally” mean that the subsequently described event or condition may but need not occur, and that the description includes instances where the event or condition occurs and instances in which it does not. For example, “optionally including” means that the named component may be present but need not be present, and the description includes situations where the named component is included and situations where the named component is not included.
- The terms “include”, “for example”, “such as”, and the like are used illustratively and are not intended to limit the present invention.
- The indefinite articles “a” and “an” mean “at least one” or “one or more” when used in this application, including the claims, unless specifically indicated otherwise.
- The following general methods were employed in preparing and evaluating nanoparticles, and conjugates or adducts, of the present invention.
- Preparation of Fluorescent Nanoparticles
- Processes and intermediates for preparing fluorescent nanoparticles of the invention are provided as further embodiments of the invention and are illustrated by the following procedures in which the meanings of the generic radicals are as given unless otherwise specified.
- In embodiments, a fluorescent nanoparticle of the invention can be prepared, for example, mixing a reactive fluorescent compound, such as, a reactive fluorescent material, such as a dye (D) and a co-reactive organo-silane compound such as, a known organo-functional silane compound (OS) to form a fluorescent core particle (D-OS); and mixing the resulting core particle (D-OS) with a silica forming compound, such as a (Si(OR)4), to form a silica shell on the core which product is a fluorescent nanoparticle (D-OS)(SiO2).
- The molar equivalent ratio of the reactive fluorescent material (D) and the co-reactive organo-silane compound (OS) can be, for example, from about 1:1 to about 1:100. The molar equivalent ratio of the fluorescent core particle (D-OS) to the silica forming compound (Si(OR)4) can be, for example, from about 1:1 to about 1:100.
- The nanoparticles of the present invention can be selectively linked to either or both a ligand and analyte by, for example, any known chemical coupling reactions such as carbodiimide coupling. Other coupling methods include use of carboxylates, esters, alcohols, carbamides, aldehydes, amines, sulfur oxides, nitrogen oxides, or halides, and other methods known in the art can be used. Coupling a fluorescent nanoparticle to a ligand, or a ligated-fluorescent nanoparticle to an analyte, and like combinations, can generally be accomplished by applying the procedures and principles disclosed in U.S. Pat. No. 6,268,222, or other procedures known in the art as applied to the present invention.
- In embodiments, linked-fluorescent nanoparticle, such as a surface modified fluorescent nanoparticle of the invention can be prepared, for example, from a preformed fluorescent nanoparticle fluorescent nanoparticle (D-OS)(SiO2) and a ligand, such as a biologically active compound (of formula X1-R1-X2), and optionally a linker precursor (of formula Z1-L-Z2), wherein X1, X2, Z1, and Z2 can be selected from the values in the table below. In the absence of an optional linker precursor the surface silanol (Si—OH) groups of the silica shell can be used to link or associate with the ligand. The ligand and the linker precursor can be reacted or polymerized using well known synthetic techniques (e.g. by condensation) to provide a ligated-fluorescent nanoparticle or linked product of the invention. Depending on the reactive functional group (X1 or X2) of the ligand, a corresponding functional group (Z1 or Z2) can be selected from the following table, to provide an ester linkage, thioester linkage, or amide linkage in the ligated-fluorescent nanoparticle or linked product.
Resulting Linkage Functional Group On in the Ligated- Functional Group On Linker Precursor Fluorescent ligand (X1 or X2) (Z1 or Z2) Nanoparticle —COOH —OH Ester —COOH —NHR Amide —COOH —SH Thioester —OH —COOH Ester —SH —COOH Thioester —NHR —COOH Amide —SO3H —OH Sulfate Ester —OH —SO3H Sulfate Ester - As will be clear to one skilled in the art, suitable protecting groups can be used during the ligation reaction. For example, other functional groups present in the biologically active compound, on the nanoparticle surface, or the linker precursor can be partially or completely protected during ligation, and the protecting groups can subsequently be removed to provide the ligated-fluorescent nanoparticles of the invention. Suitable protecting groups and methods for their incorporation and removal are well known in the art (see for example Greene, T. W.; Wutz, P. G. M. “Protecting Groups In Organic Synthesis” second edition, 1991, New York, John Wiley & sons, Inc.).
- Additionally, when a carboxylic acid is reacted with a hydroxy group, a mercapto group, or an amine group to provide an ester linkage, thioester linkage, or an amide linkage, the carboxylic acid can be activated prior to the reaction, for example, by formation of the corresponding acid chloride. Numerous methods for activating carboxylic acids, and for preparing ester linkages, thioester linkages, and amide linkages, are known in the art (see for example,Advanced Organic Chemistry: Reaction Mechanisms and Structure, 4th ed., Jerry March, John Wiley & Sons, pages 419-437 and 1281).
- The silica shell surface of the nanoparticles can be further modified if desired by, for example, surface functionalization reactions using known cross-linking agents to afford surface functional groups and as illustrated herein. Crosslinking agents are, for example, divinyl benzene, ethylene glycol dimethacrylate, trimethylol propane trimethacrylate, N,N′-methylene-bis-acrylamide, alkyl ethers, sugars, peptides, DNA fragments, or other known functionally equivalent agents. It is readily evident to one skilled in the art that many cross-linking agents can be used in combination with, or suitable for use as the ligand in forming ligated-fluorescent nanoparticles of present invention. It is readily evident to one skilled in the art in possession of the present invention that cross-linking agents can be used in surface modifying reactions to modify the surface properties of fluorescent nanoparticles, or ligated-fluorescent nanoparticles, and as illustrated herein.
- Materials and Methods
- All reagents were used as received without further purification and distillation. The ammonia molarity was determined by titration with methyl blue indicator before each synthesis. Glassware was cleaned by methods described in literature and dried using a heat gun before the synthetic procedure. The volume after mixing was ignored in the molarity calculations. The amount of 3-aminopropyltriethoxysilane (APTS) in the synthesis of the fluorescent core was not taken into account in the calculations of monomer molarity in Table I.
- Nanoparticle Synthesis Materials
- Absolute ethanol (Aldrich), Tetrahydrofuran (Aldrich), Ammonium hydroxide (Fluka, 28%), Tetraethoxysilane (Aldrich, 98%), 3-Aminopropyltriethoxysilane (Aldrich, 99%), 3-Mercaptopropyltriethoxysilane (Gelest, 99%), Tetramethylrhodamine-5-(and -6-)-isothiocyanate *mixed isomers* (TRITC) (Molecular Probes, 88%), Alexa Fluor® 488 C5 Meleimide (Molecular Probes, 97%), Alexa Flour® 488 carboxylic acid, and succinimidyl ester (Molecular Probes, ≧50%).
- Preparation of Core (Fluorescent Seed) Nanoparticles Generally
- Amounts of water, ammonia and solvent were measured in graduated cylinders. Fluorescent seed particle synthesis was carried out in 1 L Erlenmeyer flasks and stirred with magnetic TEFLON® coated stir bars at about 600 rpm. De-ionized water and ammonia solution were added to ethanol and stirred. About 2 mL of the reactive dye precursor in either ethanol or THF containing about 425 micromolar APTS, was added to the reaction vessel. The resulting mixture was stirred for about 1 to about 3 hours at room temperature with the reaction vessel covered with aluminum foil to minimize exposure to light to afford a fluorescent seed particle mixture. Tetrahydrofuran (THF) and absolute ethanol (EtOH) were distilled under nitrogen. Organic dyes were brought to room temperature from storage temperatures of about −20° C., then placed in a glove box.
- Preparation of the Silica Shell on the Core (Fluorescent Seed) Particles Generally
- The silica shell coating and growth step was performed in the above mentioned fluorescent seed particle reaction mixture with regular addition of solvent, such as ethanol, methanol, or isopropanol, to prevent drastic changes in solution ionic strength while the silica forming monomer tetraethoxysilane (TEOS) was added. This prevents particle aggregation during synthesis, which can broaden the particle size distribution.
- Characterization of Fluorescence Nanoparticles
- The particle size and particle size distribution of the resulting fluorescent nanoparticles were characterized by electron microscopy (SEM) and fluorescence correlation spectroscopy (FCS).
- Referring to FIG. 1A, there is illustrated an example of fluorescent brightness properties of the fluorescent nanoparticles (10) of the present invention compared to polystyrene latex beads (20). Fluorescence correlation spectroscopy (FCS) was used to obtain the count rates for the nanoparticles and beads as follows: 100 or 300 nanometer fluorescent nanoparticles had 299.1 kHz per particle; and 300 nanometer polystyrene latex beads had 69.84 kHz per bead. Fluorescence count rates indicated that the fluorescent nanoparticles (10) were about four times brighter than the polystyrene latex beads.
- Photo-physical characterizations were performed to determine: dye content per particle content, fluorescence lifetimes, and action cross-sections. The action cross-section metric is essentially the product of quantum yield and absorbance profile. Time resolved fluorescence measurements of fluorescence versus time in nanoseconds (ns) showed that a dye incorporated in a nanoparticle exhibited a longer lifetime than free dyes in solution, indicating that each dye molecule could be about 46% brighter when contained inside the core of the nanoparticles than when free in solution. For example, TRITC dyes contained within the core of the nanoparticle (with a diameter of about 25 nanometers), had a fluorescence lifetime of about 3.33 ns, compared to TRITC dyes free in solution which had a fluorescence lifetime of about 2.28 ns.
- From absorbance measurements over the range of 250 to 650 nanometers it was established that there are, for example, about 20 dye molecules per nanoparticle. For example, sample R30 had about 23 TRITC dye molecules per nanoparticle; and sample R29 had about 21 TRITC dye molecules per nanoparticle. However, action cross section measurements, σ2p (GM) over the range of 700 to about 1,000 nm for two separate preparations of 25 nm particles (samples R29 and R30) demonstrated that R30 was almost twice as bright as R29 over the range and particularly at absorbance maxima at about 700 and about 840 nanometers, even though the dye content is almost identical. This observation suggested great complexity associated with interaction effects between the core and the shell and they may be responsible for the enhanced quantum efficiency observed. Thus, it is possible to further optimize the fluorescence properties of the nanoparticles of the present invention, for example, for use as biomarkers, by straight-forward procedures such as changing the thickness of the core or shell as disclosed herein. The invention will now be illustrated by the following non-limiting examples:
- Preparation of Red Core Nanoparticles. 10 mg of tetramethylrhodamine-5-(and 6-)isothiocyanate (TRITC) were dissolved in ethanol. The molar ratio of 3-aminopropyltriethoxysilane (APTS) to TRITC was 50 to 1, with 2 mL of ethanol, per mg of APTS. Following complete dissolution of TRITC in ethanol, APTS was added to the reaction vessel. The reaction was stirred in the dark in the glove box for about 12 hours at room temperature.
- Preparation of Green Core Nanoparticles.
- 5 mg of Alexa Fluor® 488 C5 Meleimide was dissolved in ethanol. The molar ratio of 3-mercaptopropyltriethoxysilane (MPTS) was 100 to 1, with 2 mL of ethanol per mg of MPTS. Following complete dissolution of TRITC in ethanol, MPTS was added to the reaction vessel and stirred for about 12 hours in darkness at room temperature.
- 5 mg of Alexa Fluor® 488 carboxylic acid, succinimidyl ester was dissolved in THF. The molar ratio of 3-Aminopropyltriethoxysilane (APTS) to Alexa Flour® 488 carboxylic acid, succinimidyl ester was 100 to 1, with 2 ml of THF per mg of APTS. Following complete dissolution of Alexa Fluor® 488 carboxylic acid, succinimidyl ester in THF, APTS was added to the reaction vessel and stirred for 12 hours in darkness at room temperature. Due to the minute quantities, the fluorescent dye-core adducts were not isolated from the reaction medium before the silica shell was deposited.
- Preparation of Sized Silica Coated Fluorescent Nanoparticles Preparation of silica coated fluorescent nanoparticles of different sizes was accomplished using different relative molar amounts of reagents as described above. The molar amounts of reagents for the synthesis of 20 nm to 200 nm particles are tabulated in Table I. All silica coating of fluorescent nanoparticle procedures were accomplished at ambient conditions, i.e. at room temperature with ethanol as the solvent. A representative procedure follows.
- To a mixture containing fluorescent core particles there was added continuously 2 mL of TEOS in 100 mL additional solvent, dropwise such as over about 20 minutes. The remaining larger quantity of the TEOS was added at a more rapid rate, such as over about a 45 minute period with simultaneous addition of 400 mL of additional solvent. Optionally, water was added at this stage to grow particles larger than about 100 nm and to maintain the molar ratio of water to TEOS as tabulated in Table I. The resulting suspension was stirred overnight at room temperature in darkness.
TABLE I Reactants (in molarity) for the Preparation and the Resulting Particle Size of Silica Shell Coated Fluorescent Nanoparticles Nominal particle Size by Size by size [NH3] [H2O] [TEOS] Solvent FCS SEM 500 nm 6.127 M 16.83 M 0.1923 M i-PrOH — 500 nm 300 nm 6.127 M 16.83 M 0.1923 M EtOH — 300 nm 200 nm 3.892 M 10.80 M 0.2443 M EtOH — 200 nm 100 nm 3.892 M 10.80 M 0.2443 M i-PrOH:MeOH — 125 nm (v:v = 3:1) 70 nm 0.0085 M 17.60 M 0.2003 M EtOH — 75 nm 50 nm 0.0096 M 26.68 M 0.1518 M MeOH 48.6 nm — 40 nm 0.318 M 1.153 M 0.155 M EtOH 37.6 nm — 30 nm 0.150 M 1.710 M 0.155 M EtOH 28.8 nm 30 nm 25 nm 0.200 M 1.494 M 0.155 M EtOH 24.4 nm — - Alternatively, to produce nanoparticles having a narrow particle size range below about 70 nm, TEOS was added in small aliquots intermittently, such as 300 microliters in about 10 to 15 minute intervals, and stirred overnight at room temperature in darkness. Molar ratio of de-ionized water to monomer was kept maintained at about at least 6-fold but not more. To better monitor water content in the reaction mixture, 2.0 M ammonia was used as the catalyst source, dissolved in ethanol, methanol or isopropanol, depending on the primary solvent of the synthesis, such as 2.0 M ammonia in ethanol. After the dye-rich core/seed particle was prepared, tetraethyl orthosilicate monomer was added intermittently, such as 300 microliters every 10 minutes to grow the siliceous shell. In contrast to the larger particle procedure where monomer was added continuously via a dropping funnel, the smaller particle size procedure (for particles below about 70 nm) the TEOS monomer was added intermittently. The alternative procedure for preparing silica shell coated fluorescent nanoparticles was devised because the size distribution of silica nanoparticles prepared by the known Stöber procedure (J. Colloid and Interface Sci., 26 62-69 (1968)) has a self-sharpening characteristic as particle size increases beyond 70 nm as more monomer is added to the reaction mixture. Thus, silica nanoparticles smaller than 70 nm generally have a much broader size distribution. Therefore, the first mentioned procedure of Example 3, was modified as described thereafter to obtain nanoparticles with a narrower size distribution than what might be expected for particle sizes in the range of about 10 to about 70 nm.
- Nanoparticle Ligation (coupling) with IgE by Adsorption Silica coated fluorescent nanoparticles of Example 3 were diluted (1: 10-1:20) with phosphate buffered saline (PBS) or Tyrodes buffer at
pH 7. Immunoglobulin E (IgE) (0.85 mg/mL stock concentration) was adsorbed onto the fluorescent nanoparticles by incubating with IgE for about 3 hours at room temperature to provide, for example, nanoparticle-IgE ratios of from about 1:1 to about 1:4. For nanoparticles greater than about 50 nm, unbound IgE was removed by centrifugation. For nanoparticles of size of 50 nm or smaller, the unbound IgE was removed by adding 100 microliters (in a total volume of 500 microliters nanoparticles-IgE) of 0.25 wt % latex particles of size 1:2 microns. Unbound IgE stuck to the large latex particles which then settled out of suspension if undisturbed in several hours, for example, with overnight incubation at 4° C. The residual pellet mass was confirmed to be primarily latex particles bound with IgE and discarded. The resulting supernatant containing the IgE coupled-nanoparticle (IgE ligated-fluorescent nanoparticle) was carefully separated and placed in a vial. The resulting IgE coupled-nanoparticle samples (i.e. IgE adsorbed onto nanoparticles) were stored at 4° C. for cell binding experiments. The IgE coupled nanoparticles were diluted in Tyrodes-BSA before cell binding. The dilution was according to the IgE coupled-nanoparticle number density desired per cell. - Nanoparticle Surface Functionalization The surface of the nanoparticles can be further chemically modified to improve the versatility and stability of the nanoparticles, for example, introducing carboxylic acid groups or like chemical functional groups. Introducing functional groups, such as carboxylic acid groups, to the surface of silica coated nanoparticles can provide attachment points to enable covalent attachment of bio-molecules, for example, proteins and antibodies, to the surface of the nanoparticles. Surface functional groups, especially ionizable groups, provide other desirable properties to the nanoparticles, such as charge stabilization in buffered media. Charged carboxylate surface groups can maintain the nanoparticles as single particle colloidal dispersions which avoid or minimize nanoparticle agglomeration. Nanoparticle surface functionalization procedures are known and include, for example, carbodiimide modification and as illustrated herein.
- Materials
- 3-aminopropyldimethylethoxysilane (APDMES) (Gelest Inc.); Bifunctional Crosslinking Reagent (Pierce Endogen Inc.): Methyl N-succinimidyl adipate (MSA).
- Nanoparticle surface functionalization was accomplished as follows. A 20 mL suspension of nanoparticles with a diameter of 25 nm, as described in Table I, was used. The nanoparticle concentration was 4.33 mg/mL as determined by fluorescence correlation spectroscopy, and by drying and weighing known volumes of the suspension. Other nanoparticle sizes and concentrations can be surface modified according to this procedure when appropriately adapted in view of differences in particle size, surface area, concentration, and like considerations.
- Fluorescent nanoparticles having a silica shell were cleaned by dialysis after their initial preparation described above. The concentration of the silica shelled nanoparticle suspension was determined by drying aliquots of the nanoparticle suspension in a vacuum oven and weighing, or by fluorescence correlation spectroscopy. Assuming a density of 2 g/mL and knowing the size of the nanoparticles, the number of particles per mL of suspension was calculated to be about 1.78·×1016. The total nanoparticle surface area, assuming solid particles, was for example, about 3.35·×1019 nm2. The density of silanol groups can be estimated as about 1.4 —OH groups per square nanometer according to literature values (e.g. R. Iler, The Chemistry of Silica), and hence there is about 7.78·10−5 moles of —OH groups available for reaction with APDMES for 100% amine coverage. APDMES was added in a 2 molar excess with about 5 mg of ammonium fluoride as a catalyst, and allowed to react for about 12 hours at ambient temperature and shielded from ambient light. Excess unreacted APDMES was dialyzed away in phosphate buffer at
pH 7 over 12 hours. The resulting aminated nanoparticles suspended inphosphate buffer pH 7 were then reacted with 2-molar excess of MSA dissolved in dimethyl sulfoxide at ambient temperature for about 2 to 6 hours. Excess unreacted MSA was dialyzed away in phosphate buffer at pH 9.5 for about 6 to 12 hours, which also hydrolyzes the ester group in the MSA, to afford carboxylic acid groups covalently attached to the surface of the nanoparticle. - Nanoparticle Characterization by FTIR
- The nanoparticle products at each functionalization step described above were characterized by Fourier Transform Infra-Red (FTIR) spectroscopy. The vibration bands of the mono-substituted amide groups at 1500-1600 cm−1 indicated the linkage between amine groups of the silane compound APDMES and the succinimidyl ester groups of the MSA compound, as well as the carboxylic acid signature at 1700 cm−1. The observed spectroscopic changes compared to the starting nanoparticles were indicative of successful surface functionalization reactions.
- Nanoparticle Ligation (coupling) by Covalent Conjugation Other surface functionalization examples can be accomplished by covalent conjugation of fluorescent nanoparticles with various biomolecules as described above.
- Cell Binding with IgE Coupled-Fluorescent Nanoparticles Specificity binding experiments using a rat basophilic leukemia (RBL) mast cell model system demonstrated specific binding characteristics of the fluorescent silica-based nanoparticles. Cells (e.g. rat basophilic leukemia (RBL) mast cells) were harvested using Trypsin-EDTA. The cells were then counted to determine the cell concentration (number of cells per mL). The appropriate number of cells was incubated with IgE coupled-nanoparticles, for example, around 2×105 IgE coupled-nanoparticles per cell, for about 1 hour on ice to avoid any internalization. The resulting nanoparticle-IgE bound cells, i.e. IgE coupled-nanoparticles bound to cells, were washed with Tyrodes-BSA, and the cells were viewed under a confocal microscope for specific binding.
- Confocal microscope images showed, for example, the top surface of the cells decorated with the red nanoparticles, and the antibody IgE is labeled with a green fluorophore to show co-localization of the antibody with the nanoparticles. Another set of images, taken from the equitorial view of the cells showed an alternative confocal view where diffusive motions of the antibody receptors marked by the fluorescent nanoparticles can be monitored via SPT. Appropriate controls were performed to check for non-specific binding as follows. Control cells were pre-sensitized overnight using IgE, so that all the receptor sites were blocked. These blocked cells were then harvested in the same manner as above using Trypsin-EDTA, labeled with same IgE coupled-nanoparticles per cell concentration. These cells were then viewed under the confocal microscope for any non-specific binding (or sticking).
- Referring to FIGS. 2A and 2B, there is illustrated an example of high biomolecular binding specificity of, for example, 100 or 300 nanometer diameter fluorescent nanoparticles of the present invention (FIG. 2A) compared to polystyrene latex beads (FIG. 2B) as measured by cell counting statistics. The result indicate that specific interactions (represented by the left-side of the bar pairs) of rat basophilic leukemia (RBL) mast cells coupled with IgE coupled-nanoparticles and cells coupled with polystyrene latex beads are comparable whereas less desirable or undesired non-specific interactions (represented by the right-side of the bar pairs), such as “sticking” interactions, were greater for polystyrene latex beads and cells compared to IgE coupled-nanoparticles and cells. A comparable result is expected for fluorescent nanoparticles of the present invention with diameters between 25 and 100 nanometers.
- In FIGS. 2A and 2B, the legends:
- “IgEM” refers to mouse IgE which will bind specifically to IgE receptors of rat basophilic leukemia (RBL) mast cells;
- “control: IgEH” refers to human IgE which will not bind to IgE receptors of the aforementioned rat cells; and
- “control: particles alone” refers to the respective binding of IgE coupled-fluorescent nanoparticles with cells, and binding of polystyrene latex beads with cells.
- Single Particle Tracking (SPT) Single fluorescent nanoparticle tracking experiments were performed by confocally following the motion of a selected single bright fluorescent spot (corresponding to a single receptor bound particle) for about 20-30 minutes to track the diffusion of the receptor to which the single particle was bound. Alternatively, a plurality of selected single bright fluorescent spots could be tracked.
- Single particle tracking evaluates lateral diffusion of individual components on cell surfaces. This method is based on direct observation of bright fluorescent probes that are specifically conjugated to macromolecules of interest. Tracking of individual components reveals a variety of interesting and useful behaviors including confinement to a small region or movement along a track. This information enables an understanding of how components interact within cells, on cell membranes and like structures or components. However, the method is highly dependent on the quality of the probes. A significant shortcoming of the method has been nonspecific binding of the particles to cells. The fluorescent nanoparticles and the ligated-fluorescent nanoparticles of the present invention provide enhanced brightness and high conjugation specificity to a component of interest. The ligated-fluorescent nanoparticles were demonstrated to be biocompatible and minimize non-specific binding interactions.
- Mesoporous Silica Nanoparticles for Targeted Delivery and Controlled Release of a Therapeutic Agent Fluorescent core nanoparticles were prepared according to, for example, Examples 1 and 2, and in accord with the general core preparative procedure above.
- Mesoporous Shell
- A surface substantive agent, N-hexadecyltrimethylammonium bromide (2.4 g, 6.6 mmol, HDTB), was dissolved in the reaction mixture containing fluorescent seed core nanoparticles. The mixture was stirred (450 rpm) until the HDTB was fully dissolved and then 3.4 g TEOS (16 mmol) was added all at once. The HDTB serves as a templating agent around which the silica shell's formation is ordered and perturbed to enable pore formation by subsequent removal of the HDTB associated with the surface. Subsequent cleaning or removal of the HDTB from the nanoparticle provides fluorescent nanoparticles having a mesoporous silica shell.
- Cleaning Procedure
- After about 5 hours of reaction with TEOS, a solid was recovered from three centrifugation washes at 6,000 rpm. At each centrifugation step the supernatant was refreshed with absolute ethanol. Two washes by filtration in de-ionized water followed the centrifugation procedure. The centrifugation and filtration steps removed approximately 90% of the HDTB surfactant. The recovered nanoparticles containing solid was finally suspended in absolute ethanol. The suspension was homogenized by ultrasonic agitation.
- A vacuum distillation was carried out to exchange ethanol solvent with dimethyl sulfoxide (DMSO). Final concentrations were determined by drying an aliquot of the suspension and weighing the solid mass. The resulting meso-porous nanoparticles in DMSO were suitable for loading therapeutic agent as illustrated below.
- Loading Mesoporous Nanoparticles with a Therapeutic Agent
- The above mesoporous nanoparticles suspended in DMSO were stirred and transferred to a 50 mL Falcon tube. The solution was centrifuged at 3,000 rpm for about 5 minutes and the volume of DMSO was reduced to 4 mL by pouring off 6 mL of the supernatant fluid. A 16 mg sample of a therapeutic agent, camptothecin (CPT), was added to the solution. After 5 hours, the solution was centrifuged, and two washes with phosphate buffer saline (PBS) were done. For each wash, 20 mL of PBS was added, and the particles were sonicated and centrifuged. Sonication was done at 15% power with a pulse rate of 1.0 second on and 1.0 second off for 30 seconds of pulsing or until the solution appeared homogenous. The centrifugation was done at 25° C. at 3,000 rpm for 5 minutes. Therapeutic agent loaded particles were stored at room temperature.
- All publications, patents, and patent documents are incorporated by reference herein, as though individually incorporated by reference. The invention has been described with reference to various specific and preferred embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the invention.
Claims (58)
1. A fluorescent nanoparticle comprising:
a core comprising a fluorescent silane compound; and
a silica shell on the core.
2. The nanoparticle of claim 1 wherein the core comprises the reaction product of a reactive fluorescent compound and an organo-silane, and the shell comprises the reaction product of a silica forming compound.
3. The nanoparticle of claim 1 further comprising a ligand on the surface of the fluorescent nanoparticle to form a ligated-fluorescent nanoparticle.
4. The nanoparticle of claim 3 wherein the ligand on the surface of the fluorescent nanoparticle is attached by a covalent bond or by physical absorption.
5. The nanoparticle of claim 3 wherein the ligand on the surface of the fluorescent nanoparticle is selected from the group consisting of a biopolymer, a synthetic polymer, an antigen, an antibody, a microorganism, a virus, a receptor, a hapten, an enzyme, a hormone, a chemical compound, a pathogen, a toxin, a surface modifier, and combinations thereof.
6. The nanoparticle of claim 1 wherein the silica shell coating on the core covers from about 10 to about 100 percent of the surface area of the core.
7. The nanoparticle of claim 3 wherein the ligand on the surface of the fluorescent nanoparticle covers from about 10 to about 100 percent of the surface area of the core.
8. The nanoparticle of claim 1 wherein the thickness of the core to the silica shell is in a ratio of from about 1:1 to about 1:100.
9. The nanoparticle of claim 1 wherein the diameter of the nanoparticle is from about 1 to about 1,000 nanometers.
10. The nanoparticle of claim 1 further comprising a therapeutic agent.
11. The nanoparticle of claim 3 further comprising a therapeutic agent.
12. The nanoparticle of claim 10 or 11 wherein the therapeutic agent is selected from the group consisting of a drug, a biomolecule, a surface modifier, and combinations thereof.
13. The nanoparticle of claim 10 or 11 wherein the therapeutic agent is absorbed into the silica shell of the nanoparticle.
14. The nanoparticle of claim 10 or 11 wherein the therapeutic agent is coated onto the silica shell of the nanoparticle.
15. The nanoparticle of claim 3 wherein the therapeutic agent is associated with the ligand of the nanoparticle.
16. A method of making a fluorescent nanoparticle comprising:
mixing a fluorescent compound and an organo-silane compound to form a fluorescent core; and
mixing the resulting core with a silica forming compound to form a silica shell on the core, to provide the fluorescent nanoparticle.
17. The method of claim 16 further comprising combining the resulting nanoparticle with a ligand selected from the group consisting of a biopolymer, a synthetic polymer, an antigen, an antibody, a microorganism, a virus, a receptor, a hapten, an enzyme, a hormone, a chemical compound, a pathogen, a toxin, a surface modifier, and combinations thereof.
18. The method of claim 16 further comprising combining the resulting fluorescent nanoparticle with a therapeutic agent selected from the group consisting of a drug, a biomolecule, a surface modifier, and combinations thereof.
19. The method of any one of claim 17 or 18 wherein combining comprises coating the ligand or therapeutic agent onto the surface of the nanoparticle.
20. The method of any one of claim 17 or 18 wherein combining comprises imbibing the ligand or therapeutic agent into the surface of the nanoparticle.
21. The method of any one of claim 17 or 18 wherein combining comprises bonding the ligand or therapeutic agent to the surface of the resulting nanoparticle.
22. A method for monitoring movement of a cellular component of a cell comprising:
contacting the cell with a ligated-fluorescent nanoparticle to form a cell selectively decorated with the ligated-fluorescent nanoparticle and to form a fluorescent loci; and
recording the motion of the fluorescent loci for a time, to monitor the movement of a cellular component.
23. The method of claim 22 wherein the fluorescent loci corresponds to one or more ligated-fluorescent nanoparticle bound to a component of the cell.
24. The method of claim 22 wherein the fluorescent loci corresponds to a single ligated-fluorescent nanoparticle bound to a component of the cell.
25. The method of claim 22 wherein the ligated-fluorescent nanoparticle is adapted to selectively associate with a cellular component of the cell.
26. The method of claim 22 wherein the cellular component is a receptor, an antibody, a hapten, an enzyme, a hormone, a biopolymer, an antigen, a microorganism, a virus, a pathogen, a toxin, and combinations thereof.
27. The method of claim 22 wherein the ligated-fluorescent nanoparticle is a fluorescent nanoparticle conjugated with an antibody.
28. The method of claim 27 wherein the antibody is an immunoglobin.
29. The method of claim 28 wherein the antibody is IgE.
30. The method of claim 22 wherein recording is accomplished with a microscopically adapted camera.
31. The method of claim 22 wherein recording for a time is from about 1 microsecond to about 30 days
32. The method of claim 22 wherein recording for a time is from about 1 second to about 60 minutes.
33. The method of claim 22 wherein the contacting and the recording are accomplished in vitro.
34. The method of claim 22 wherein the contacting and the recording are accomplished in vivo.
35. A pharmaceutical carrier comprising the fluorescent nanoparticle of claim 1 , and optionally a ligand.
36. A pharmaceutical composition comprising the ligated-fluorescent nanoparticle of claim 3 and optionally a therapeutic agent.
37. An imaging agent comprising the ligated-fluorescent nanoparticle of claim 3 .
38. A method for treating disease or disorder comprising:
administering to a patient in need of treatment an effective amount of a ligated-fluorescent nanoparticle optionally including a therapeutic agent, the nanoparticle being adapted to selectively associate with a disease producing component of the cell, to form a selectively decorated cell with the ligated-fluorescent nanoparticle; and
illuminating the decorated cell to treat disease or disorder.
39. The method of claim 38 wherein the ligated-fluorescent nanoparticle fluoresces and heats-up when illuminated.
40. The method of claim 38 wherein the ligated-fluorescent nanoparticle is an antibody ligated to a fluorescent nanoparticle.
41. The method of claim 38 wherein the disease is cancerous tumor.
42. The method of claim 38 wherein the disease in sensitive to fluorescence, heat, or both.
43. A method of treating a disease or disorder comprising:
contacting a cell with a ligated-fluorescent nanoparticle to form a cell selectively decorated with the ligated-fluorescent nanoparticle; and
irradiating the resulting decorated cell for a time to treat the disease or disorder.
44. A kit for use in the detection of an analyte, the kit comprising packaging material containing a ligated-fluorescent nanoparticle.
45. A kit for detecting and monitoring a cell surface component, the kit comprising packaging material containing a ligated-fluorescent nanoparticle for detecting the cell surface component, and optionally a recorder for monitoring the cell surface component.
46. An assay method for detecting motion or a change in the location of a cellular component of a cell when the cell is treated with a therapeutic agent comprising:
contacting a cell with a ligated-fluorescent nanoparticle, the nanoparticle having a therapeutic agent, to bind the ligated-fluorescent nanoparticle to a cellular component; and
recording the fluorescent signal, to detect the motion or location change of the component.
47. The method of claim 46 further comprising determining the difference between the motion or movement of the bound ligated-fluorescent nanoparticle in the presence and absence of the therapeutic agent.
48. A method for detecting the presence of an analyte comprising:
contacting a sample which may contain an analyte with a ligated-fluorescent nanoparticle adapted to associate with the analyte, if present, to form a ligated-fluorescent nanoparticle-analyte complex;
optionally separating uncomplexed ligated-fluorescent nanoparticle; and
detecting the fluorescent signal of ligated-fluorescent nanoparticle-analyte complex to establish the presence of the analyte.
49. The method of claim 48 wherein the ligated-fluorescent nanoparticle-analyte comprises:
a ligated-fluorescent nanoparticle where the ligand is selected from the group consisting of a cell component, a biopolymer, a synthetic polymer, an antigen, an antibody, a receptor, a hapten, an enzyme, a hormone, a chemical compound, a pathogen, a toxin, and combinations thereof; and
an analyte selected from the group consisting of a microorganism, a virus, a cell, a cell component, a biopolymer, a synthetic polymer, an antigen, an antibody, a receptor, a hapten, an enzyme, a hormone, a chemical compound, a pathogen, a toxin, and combinations thereof.
50. A fluorescent nanoparticle comprising:
a core comprising a fluorescent silane compound; and
a porous silica shell on the core.
51. The nanoparticle of claim 50 further comprising a therapeutic agent, a ligand, or mixtures thereof, on the surface of the fluorescent nanoparticle.
52. The nanoparticle of claim 51 further comprising a ligand on the surface of the fluorescent nanoparticle.
53. The nanoparticle of claim 51 further comprising a therapeutic agent on the surface of the fluorescent nanoparticle.
54. The nanoparticle of claim 51 further comprising a magnetic component in the core of the fluorescent nanoparticle.
55. The method of claim 16 further comprising treating the fluorescent core with a templating agent prior to forming a silica shell on the core.
56. The method of claim 55 wherein the templating agent is a quaternary ammonium salt.
57. The method of claim 55 further comprising removing the templating agent after forming a silica shell on the core to afford a porous silica shell.
58. The method of claim 57 further comprising treating the porous silica shell with a ligand, a therapeutic, or mixtures thereof.
Priority Applications (23)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/306,614 US20040101822A1 (en) | 2002-11-26 | 2002-11-26 | Fluorescent silica-based nanoparticles |
EP03815190.8A EP1604031B1 (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
KR1020057009511A KR20050103186A (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
JP2004566499A JP4965804B2 (en) | 2002-11-26 | 2003-11-26 | Silica-based fluorescent nanoparticles |
JP2004568576A JP2006514708A (en) | 2002-11-26 | 2003-11-26 | Silica-based fluorescent nanoparticles |
CNB2003801092528A CN100443295C (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
PCT/US2003/037963 WO2004074504A2 (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
ES11156074T ES2753144T3 (en) | 2002-11-26 | 2003-11-26 | Silica-based fluorescent nanoparticles |
KR1020057009530A KR20050109455A (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
PCT/US2003/037793 WO2004063387A2 (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
US10/536,569 US8298677B2 (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
EP11156074.4A EP2369342B1 (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
ES03815995T ES2709398T3 (en) | 2002-11-26 | 2003-11-26 | Fluorescent nanoparticles based on silica |
CNA200810170588XA CN101387639A (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
AU2003303290A AU2003303290A1 (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
EP20110162895 EP2364840A1 (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
AU2003303309A AU2003303309B2 (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
EP03815995.0A EP1572445B1 (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
CNA200380109241XA CN1742094A (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
US12/579,302 US8409876B2 (en) | 2002-11-26 | 2009-10-14 | Fluorescent silica-based nanoparticles |
JP2009285153A JP2010070768A (en) | 2002-11-26 | 2009-12-16 | Fluorescent silica-based nanoparticle |
JP2010262238A JP2011052228A (en) | 2002-11-26 | 2010-11-25 | Fluorescent silica-based nanoparticle |
JP2014023357A JP2014133893A (en) | 2002-11-26 | 2014-02-10 | Fluorescent silica-based nanoparticle |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/306,614 US20040101822A1 (en) | 2002-11-26 | 2002-11-26 | Fluorescent silica-based nanoparticles |
Related Child Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/536,569 Continuation US8298677B2 (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
US11/536,569 Continuation US20070026044A1 (en) | 2002-05-06 | 2006-09-28 | Use of VEGF For Treating Bone Defects |
US12/579,302 Continuation US8409876B2 (en) | 2002-11-26 | 2009-10-14 | Fluorescent silica-based nanoparticles |
Publications (1)
Publication Number | Publication Date |
---|---|
US20040101822A1 true US20040101822A1 (en) | 2004-05-27 |
Family
ID=32325737
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/306,614 Abandoned US20040101822A1 (en) | 2002-11-26 | 2002-11-26 | Fluorescent silica-based nanoparticles |
US10/536,569 Active 2026-11-07 US8298677B2 (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
US12/579,302 Expired - Fee Related US8409876B2 (en) | 2002-11-26 | 2009-10-14 | Fluorescent silica-based nanoparticles |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/536,569 Active 2026-11-07 US8298677B2 (en) | 2002-11-26 | 2003-11-26 | Fluorescent silica-based nanoparticles |
US12/579,302 Expired - Fee Related US8409876B2 (en) | 2002-11-26 | 2009-10-14 | Fluorescent silica-based nanoparticles |
Country Status (8)
Country | Link |
---|---|
US (3) | US20040101822A1 (en) |
EP (4) | EP2364840A1 (en) |
JP (5) | JP4965804B2 (en) |
KR (2) | KR20050103186A (en) |
CN (3) | CN1742094A (en) |
AU (2) | AU2003303309B2 (en) |
ES (2) | ES2753144T3 (en) |
WO (2) | WO2004063387A2 (en) |
Cited By (613)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050025820A1 (en) * | 2003-04-25 | 2005-02-03 | Mark Kester | Method and system for systemic delivery of growth arresting, lipid-derived bioactive compounds |
FR2873021A1 (en) * | 2004-07-16 | 2006-01-20 | Oreal | Cosmetic composition, used as a make-up and/or skin care (particularly face, lips and/or keratinous fibers) product, comprises a photo luminescent mineral nanoparticles in a medium |
WO2006011014A1 (en) * | 2004-07-16 | 2006-02-02 | L'oreal | Cosmetic composition containing photoluminescent particles |
US20060113557A1 (en) * | 2004-11-30 | 2006-06-01 | Spire Corporation | Nanophotovoltaic devices |
US20060115917A1 (en) * | 2004-11-30 | 2006-06-01 | Linden Kurt J | Precision synthesis of quantum dot nanostructures for fluorescent and optoelectronic devices |
US20060216239A1 (en) * | 2005-03-18 | 2006-09-28 | Washington, University Of | Magnetic nanoparticle compositions and methods |
US20060222286A1 (en) * | 2005-03-31 | 2006-10-05 | Eastman Kodak Company | Polarized light emitting source with an electro-optical addressing architecture |
US20060222292A1 (en) * | 2005-03-31 | 2006-10-05 | Eastman Kodak Company | Placement of lumiphores within a light emitting resonator in a visual display with electro-optical addressing architecture |
US20060227840A1 (en) * | 2005-03-31 | 2006-10-12 | Eastman Kodak Company | Visual display with electro-optical addressing architecture |
US20060245971A1 (en) * | 2005-05-02 | 2006-11-02 | Burns Andrew A | Photoluminescent silica-based sensors and methods of use |
US20060291769A1 (en) * | 2005-05-27 | 2006-12-28 | Eastman Kodak Company | Light emitting source incorporating vertical cavity lasers and other MEMS devices within an electro-optical addressing architecture |
US20060293396A1 (en) * | 2005-01-14 | 2006-12-28 | Eastman Kodak Company | Amine polymer-modified nanoparticulate carriers |
US20070051674A1 (en) * | 2000-02-04 | 2007-03-08 | Bratten Jack R | Lift station and method |
WO2007029980A1 (en) * | 2005-09-08 | 2007-03-15 | Biterials Co., Ltd. | Magnetic nanoparticle having fluorescent and preparation method thereof and use thereof |
US20070154965A1 (en) * | 2005-04-22 | 2007-07-05 | Miqin Zhang | Chlorotoxin-labeled nanoparticle compositions and methods for targeting primary brain tumors |
US20070203584A1 (en) * | 2006-02-14 | 2007-08-30 | Amit Bandyopadhyay | Bone replacement materials |
US20070262116A1 (en) * | 2005-08-31 | 2007-11-15 | Hueil Joseph C | Surgical stapling device with multiple stacked actuator wedge cams for driving staple drivers |
EP1862794A1 (en) * | 2006-05-31 | 2007-12-05 | Carl Zeiss MicroImaging GmbH | Method for high resolution spatial images |
EP1883676A1 (en) * | 2005-05-27 | 2008-02-06 | Ciba Specialty Chemicals Holding Inc. | Functionalized nanoparticles |
US20080073163A1 (en) * | 2006-09-22 | 2008-03-27 | Weir Michael P | Micro-electromechanical device |
US20080086051A1 (en) * | 2006-09-20 | 2008-04-10 | Ethicon Endo-Surgery, Inc. | System, storage medium for a computer program, and method for displaying medical images |
KR100821192B1 (en) * | 2005-09-08 | 2008-04-11 | 주식회사바이테리얼즈 | Magnetic nanoparticle having fluorescent and preparation method thereof |
WO2008071772A2 (en) * | 2006-12-13 | 2008-06-19 | L'oreal | Use of coloured or fluorescent hybrid particles for treating keratin fibres |
FR2909869A1 (en) * | 2006-12-13 | 2008-06-20 | Oreal | Use of hybrid particles for dyeing keratinous fibers, obtained from an organosilane compound carrying a colored species |
US20080167521A1 (en) * | 2007-01-09 | 2008-07-10 | Sheetz Jane A | Method of in vivo monitoring using an imaging system including scanned beam imaging unit |
US20080221434A1 (en) * | 2007-03-09 | 2008-09-11 | Voegele James W | Displaying an internal image of a body lumen of a patient |
US20080226034A1 (en) * | 2007-03-12 | 2008-09-18 | Weir Michael P | Power modulation of a scanning beam for imaging, therapy, and/or diagnosis |
US20080234544A1 (en) * | 2007-03-20 | 2008-09-25 | Ethicon Endo-Sugery, Inc. | Displaying images interior and exterior to a body lumen of a patient |
US20080234566A1 (en) * | 2007-03-21 | 2008-09-25 | Ethicon Endo-Surgery, Inc. | Recognizing a real world fiducial in a patient image data |
US20080232656A1 (en) * | 2007-03-22 | 2008-09-25 | Ethicon Endo-Surgery, Inc. | Recognizing a real world fiducial in image data of a patient |
US20080242967A1 (en) * | 2007-03-27 | 2008-10-02 | Ethicon Endo-Surgery, Inc. | Medical imaging and therapy utilizing a scanned beam system operating at multiple wavelengths |
US20080255425A1 (en) * | 2007-04-13 | 2008-10-16 | Ethicon Endo-Surgery, Inc. | Nanoparticle treated medical devices |
US20080255458A1 (en) * | 2007-04-13 | 2008-10-16 | Ethicon Endo-Surgery, Inc. | System and method using fluorescence to examine within a patient's anatomy |
US20080252778A1 (en) * | 2007-04-13 | 2008-10-16 | Ethicon Endo-Surgery, Inc. | Combined SBI and conventional image processor |
US20080275305A1 (en) * | 2007-05-01 | 2008-11-06 | Ethicon Endo-Surgery, Inc. | Medical scanned beam imager and components associated therewith |
US20080274463A1 (en) * | 2007-05-04 | 2008-11-06 | Ventana Medical Systems, Inc. | Method for quantifying biomolecules conjugated to a nanoparticle |
US20080286371A1 (en) * | 2005-09-12 | 2008-11-20 | Cristalia Produtos Quimicos Farmaceuticos Ltda | Immunogenical Complex Formed by Vaccinal Antigens Encapsulated by Nanostructured Mesoporous Silica |
US20080293584A1 (en) * | 2005-12-27 | 2008-11-27 | The Furukawa Electric Co., Ltd. | Fluorescent silica nano-particle, fluorescent nano-material, and biochip and assay using the same |
US20080312490A1 (en) * | 2007-06-18 | 2008-12-18 | Ethicon Endo-Surgery, Inc. | Methods and devices for repairing damaged or diseased tissue using a scanning beam assembly |
US20090001130A1 (en) * | 2007-03-15 | 2009-01-01 | Hess Christopher J | Surgical procedure using a cutting and stapling instrument having releasable staple-forming pockets |
WO2009017695A1 (en) * | 2007-07-26 | 2009-02-05 | The Regents Of The University Of California | A single cell surgery tool and a cell transfection device utilizing the photothermal properties of thin films and/or metal nanoparticles |
US20090035802A1 (en) * | 2007-07-31 | 2009-02-05 | Digital Bio Technology, Co., Ltd. | Method for detection and enumeration of cell surface markers |
US20090043109A1 (en) * | 2007-08-07 | 2009-02-12 | Spangler Brenda D | Asymmetric one- and two-photon fluorophores for simultaneous detection of multiple analytes using a common excitation source |
US20090054761A1 (en) * | 2007-08-22 | 2009-02-26 | Ethicon Endo-Surgery, Inc. | Medical system, method, and storage medium concerning a natural orifice transluminal medical procedure |
US20090062658A1 (en) * | 2007-08-27 | 2009-03-05 | Dunki-Jacobs Robert J | Position tracking and control for a scanning assembly |
US20090060381A1 (en) * | 2007-08-31 | 2009-03-05 | Ethicon Endo-Surgery, Inc. | Dynamic range and amplitude control for imaging |
US20090062659A1 (en) * | 2007-08-28 | 2009-03-05 | Weir Michael P | Medical device including scanned beam unit with operational control features |
US20090068272A1 (en) * | 2006-04-25 | 2009-03-12 | Washington State University | Mesoporous calcium silicate compositions and methods for synthesis of mesoporous calcium silicate for controlled release of bioactive agents |
WO2009059677A1 (en) * | 2007-11-08 | 2009-05-14 | Merck Patent Gmbh | Method for the production of coated luminescent substances |
US20090137060A1 (en) * | 2005-07-11 | 2009-05-28 | Rikshospitalet Hf | Multicolored particles |
WO2009073193A2 (en) * | 2007-12-03 | 2009-06-11 | The Johns Hopkins University | Methods of synthesis and use of chemospheres |
US7558455B2 (en) | 2007-06-29 | 2009-07-07 | Ethicon Endo-Surgery, Inc | Receiver aperture broadening for scanned beam imaging |
US20090202816A1 (en) * | 2006-06-06 | 2009-08-13 | Florida State University Research Foundation, Inc. | Stabilized silica colloid |
US20090217932A1 (en) * | 2008-03-03 | 2009-09-03 | Ethicon Endo-Surgery, Inc. | Intraluminal tissue markers |
US20090226371A1 (en) * | 2005-11-16 | 2009-09-10 | Signalomics Gmbh | Fluorescent nanoparticles |
US20090276056A1 (en) * | 2006-04-25 | 2009-11-05 | Washington State University | Resorbable ceramics with controlled strength loss rates |
US20090289225A1 (en) * | 2007-04-19 | 2009-11-26 | Naiyong Jing | Reducing fluorescent self-quenching with nanoparticles |
US20100040693A1 (en) * | 2006-08-09 | 2010-02-18 | Korea Research Institute Of Bioscience And Biotech | Silica capsules having nano-holes or nano-pores on their surfaces and method for preparing the same |
US7665647B2 (en) | 2006-09-29 | 2010-02-23 | Ethicon Endo-Surgery, Inc. | Surgical cutting and stapling device with closure apparatus for limiting maximum tissue compression force |
WO2010021512A2 (en) * | 2008-08-22 | 2010-02-25 | Snu R&Db Foundation | Silica-based fluorescent nanoparticles |
US7669746B2 (en) | 2005-08-31 | 2010-03-02 | Ethicon Endo-Surgery, Inc. | Staple cartridges for forming staples having differing formed staple heights |
US7673781B2 (en) | 2005-08-31 | 2010-03-09 | Ethicon Endo-Surgery, Inc. | Surgical stapling device with staple driver that supports multiple wire diameter staples |
US20100089970A1 (en) * | 2008-10-10 | 2010-04-15 | Ethicon Endo-Surgery, Inc. | Powered surgical cutting and stapling apparatus with manually retractable firing system |
US7713265B2 (en) | 2006-12-22 | 2010-05-11 | Ethicon Endo-Surgery, Inc. | Apparatus and method for medically treating a tattoo |
US20100119500A1 (en) * | 2007-02-28 | 2010-05-13 | Mika Jokinen | Method for preparing silica compositions, silica compositions and uses thereof |
US20100184087A1 (en) * | 2006-11-01 | 2010-07-22 | Ventana Medical Systems, Inc. | Haptens, hapten conjugates, compositions thereof and method for their preparation and use |
US20100260686A1 (en) * | 2009-04-09 | 2010-10-14 | Washington, University Of | Nanoparticles for brain tumor imaging |
US20100311871A1 (en) * | 2008-02-12 | 2010-12-09 | Nissan Chemical Industries, Ltd. | Colloidal silica particles, process for producing the same, and organic solvent-dispersed silica sol, polymerizable compound-dispersed silica sol, and dicarboxylic anhydride-dispersed silica sol each obtained from the same |
US20100310872A1 (en) * | 2007-12-06 | 2010-12-09 | The University Of Tokushima | Nanofunctional silica particles and manufacturing method thereof |
US20100317537A1 (en) * | 2008-02-15 | 2010-12-16 | University Of Florida Research Foundation, Inc. | Biophysical parameters for systems biology |
US20100327482A1 (en) * | 2005-12-20 | 2010-12-30 | University Of Hawaii | Polymer matrix composites with nano-scale reinforcements |
US20100330366A1 (en) * | 2009-06-30 | 2010-12-30 | Keiser Bruce A | Silica-based particle composition |
US20110028662A1 (en) * | 2007-08-31 | 2011-02-03 | Hybrid Silica Technologies, Inc. | Peg-coated core-shell silica nanoparticles and methods of manufacture and use |
US7934630B2 (en) | 2005-08-31 | 2011-05-03 | Ethicon Endo-Surgery, Inc. | Staple cartridges for forming staples having differing formed staple heights |
US20110110858A1 (en) * | 2009-11-11 | 2011-05-12 | Omer Aras | Gold nanoparticle imaging agents and uses thereof |
US20110111233A1 (en) * | 2008-07-07 | 2011-05-12 | Kazuya Tsukada | Inorganic nanoparticle labeling agent |
US7982776B2 (en) | 2007-07-13 | 2011-07-19 | Ethicon Endo-Surgery, Inc. | SBI motion artifact removal apparatus and method |
US20110174860A1 (en) * | 2006-01-31 | 2011-07-21 | Ethicon Endo-Surgery, Inc. | Surgical instrument with force-feedback capabilities |
US20110203023P1 (en) * | 2010-02-16 | 2011-08-18 | Menachem Bronstein | Gypsophila Plant Named 'Pearl Blossom'' |
US20110214488A1 (en) * | 2010-03-04 | 2011-09-08 | Rose Peter E | Colloidal-crystal quantum dots as tracers in underground formations |
US8050520B2 (en) | 2008-03-27 | 2011-11-01 | Ethicon Endo-Surgery, Inc. | Method for creating a pixel image from sampled data of a scanned beam imager |
US20110288234A1 (en) * | 2008-02-19 | 2011-11-24 | The Research Foundation on State University of NY | Silica nanoparticles postloaded with photosensitizers for drug delivery in photodynamic therapy |
US20110300222A1 (en) * | 2009-02-20 | 2011-12-08 | The Regents Of The University Of California | Luminescent porous silicon nanoparticles, methods of making and using same |
US8113410B2 (en) | 2008-02-14 | 2012-02-14 | Ethicon Endo-Surgery, Inc. | Surgical stapling apparatus with control features |
US8161977B2 (en) | 2006-01-31 | 2012-04-24 | Ethicon Endo-Surgery, Inc. | Accessing data stored in a memory of a surgical instrument |
US8186555B2 (en) | 2006-01-31 | 2012-05-29 | Ethicon Endo-Surgery, Inc. | Motor-driven surgical cutting and fastening instrument with mechanical closure system |
US8196795B2 (en) | 2008-02-14 | 2012-06-12 | Ethicon Endo-Surgery, Inc. | Disposable motor-driven loading unit for use with a surgical cutting and stapling apparatus |
US8196796B2 (en) | 2007-06-04 | 2012-06-12 | Ethicon Endo-Surgery, Inc. | Shaft based rotary drive system for surgical instruments |
CN101457139B (en) * | 2008-08-22 | 2012-06-13 | 吉林大学 | High quantum production rate luminescent silicon ball with controllable structure and preparation method thereof |
US8273015B2 (en) | 2007-01-09 | 2012-09-25 | Ethicon Endo-Surgery, Inc. | Methods for imaging the anatomy with an anatomically secured scanner assembly |
US20120252140A1 (en) * | 2009-12-25 | 2012-10-04 | Konica Minolta Medical & Graphic, Inc. | Fluorescent substance-containing silica nanoparticles and biosubstance labeling agent |
US8332014B2 (en) | 2008-04-25 | 2012-12-11 | Ethicon Endo-Surgery, Inc. | Scanned beam device and method using same which measures the reflectance of patient tissue |
CN102921014A (en) * | 2012-11-15 | 2013-02-13 | 中国科学院化学研究所 | Biocompatible nano composite drug carrier with synergistic anti-tumor effect, drug with synergistic anti-tumor effect and preparation methods of biocompatible nano composite drug carrier and drug |
US20130064776A1 (en) * | 2009-10-09 | 2013-03-14 | Universite De Strasbourg | Labelled silica-based nanomaterial with enhanced properties and uses thereof |
US8397971B2 (en) | 2009-02-05 | 2013-03-19 | Ethicon Endo-Surgery, Inc. | Sterilizable surgical instrument |
CN103013016A (en) * | 2011-09-28 | 2013-04-03 | 国家纳米科学中心 | Medical carrier and medical composition and preparation method thereof |
US20130084643A1 (en) * | 2009-12-24 | 2013-04-04 | Total Sa | Use of nanoparticles for labelling oil field injection waters |
US8414577B2 (en) | 2009-02-05 | 2013-04-09 | Ethicon Endo-Surgery, Inc. | Surgical instruments and components for use in sterile environments |
US8424740B2 (en) | 2007-06-04 | 2013-04-23 | Ethicon Endo-Surgery, Inc. | Surgical instrument having a directional switching mechanism |
US8445191B2 (en) | 2007-05-23 | 2013-05-21 | Ventana Medical Systems, Inc. | Polymeric carriers for immunohistochemistry and in situ hybridization |
US8459525B2 (en) | 2008-02-14 | 2013-06-11 | Ethicon Endo-Sugery, Inc. | Motorized surgical cutting and fastening instrument having a magnetic drive train torque limiting device |
US8459520B2 (en) | 2007-01-10 | 2013-06-11 | Ethicon Endo-Surgery, Inc. | Surgical instrument with wireless communication between control unit and remote sensor |
US8479969B2 (en) | 2007-01-10 | 2013-07-09 | Ethicon Endo-Surgery, Inc. | Drive interface for operably coupling a manipulatable surgical tool to a robot |
US8534528B2 (en) | 2007-06-04 | 2013-09-17 | Ethicon Endo-Surgery, Inc. | Surgical instrument having a multiple rate directional switching mechanism |
US8540128B2 (en) | 2007-01-11 | 2013-09-24 | Ethicon Endo-Surgery, Inc. | Surgical stapling device with a curved end effector |
US8573461B2 (en) | 2008-02-14 | 2013-11-05 | Ethicon Endo-Surgery, Inc. | Surgical stapling instruments with cam-driven staple deployment arrangements |
US8573465B2 (en) | 2008-02-14 | 2013-11-05 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical end effector system with rotary actuated closure systems |
US8584919B2 (en) | 2008-02-14 | 2013-11-19 | Ethicon Endo-Sugery, Inc. | Surgical stapling apparatus with load-sensitive firing mechanism |
US8602288B2 (en) | 2008-09-23 | 2013-12-10 | Ethicon Endo-Surgery. Inc. | Robotically-controlled motorized surgical end effector system with rotary actuated closure systems having variable actuation speeds |
US8602287B2 (en) | 2008-09-23 | 2013-12-10 | Ethicon Endo-Surgery, Inc. | Motor driven surgical cutting instrument |
US8616431B2 (en) | 2007-06-04 | 2013-12-31 | Ethicon Endo-Surgery, Inc. | Shiftable drive interface for robotically-controlled surgical tool |
US8622274B2 (en) | 2008-02-14 | 2014-01-07 | Ethicon Endo-Surgery, Inc. | Motorized cutting and fastening instrument having control circuit for optimizing battery usage |
US8636736B2 (en) | 2008-02-14 | 2014-01-28 | Ethicon Endo-Surgery, Inc. | Motorized surgical cutting and fastening instrument |
US8652120B2 (en) | 2007-01-10 | 2014-02-18 | Ethicon Endo-Surgery, Inc. | Surgical instrument with wireless communication between control unit and sensor transponders |
US8657174B2 (en) | 2008-02-14 | 2014-02-25 | Ethicon Endo-Surgery, Inc. | Motorized surgical cutting and fastening instrument having handle based power source |
WO2014052875A1 (en) | 2012-09-27 | 2014-04-03 | Cynvenio Biosystems, Inc. | Stimulus-sensitive microparticles and methods of use |
US8703490B2 (en) | 2008-06-05 | 2014-04-22 | Ventana Medical Systems, Inc. | Compositions comprising nanomaterials and method for using such compositions for histochemical processes |
US8747238B2 (en) | 2012-06-28 | 2014-06-10 | Ethicon Endo-Surgery, Inc. | Rotary drive shaft assemblies for surgical instruments with articulatable end effectors |
US8752749B2 (en) | 2008-02-14 | 2014-06-17 | Ethicon Endo-Surgery, Inc. | Robotically-controlled disposable motor-driven loading unit |
US8763879B2 (en) | 2006-01-31 | 2014-07-01 | Ethicon Endo-Surgery, Inc. | Accessing data stored in a memory of surgical instrument |
US8783541B2 (en) | 2003-05-20 | 2014-07-22 | Frederick E. Shelton, IV | Robotically-controlled surgical end effector system |
US8789741B2 (en) | 2010-09-24 | 2014-07-29 | Ethicon Endo-Surgery, Inc. | Surgical instrument with trigger assembly for generating multiple actuation motions |
US20140220598A1 (en) * | 2011-09-09 | 2014-08-07 | Tohoku University | Biological substance detection method |
US8800838B2 (en) | 2005-08-31 | 2014-08-12 | Ethicon Endo-Surgery, Inc. | Robotically-controlled cable-based surgical end effectors |
US8820603B2 (en) | 2006-01-31 | 2014-09-02 | Ethicon Endo-Surgery, Inc. | Accessing data stored in a memory of a surgical instrument |
WO2014153051A1 (en) | 2013-03-14 | 2014-09-25 | University Of Washington Through Its Center For Commercialization | Polymer dot compositions and related methods |
US8844789B2 (en) | 2006-01-31 | 2014-09-30 | Ethicon Endo-Surgery, Inc. | Automated end effector component reloading system for use with a robotic system |
US8873041B1 (en) | 2013-01-29 | 2014-10-28 | Bayspec, Inc. | Raman spectroscopy using multiple excitation wavelengths |
US8893949B2 (en) | 2010-09-30 | 2014-11-25 | Ethicon Endo-Surgery, Inc. | Surgical stapler with floating anvil |
US8911471B2 (en) | 2006-03-23 | 2014-12-16 | Ethicon Endo-Surgery, Inc. | Articulatable surgical device |
US8961825B2 (en) | 2009-04-15 | 2015-02-24 | Cornell University | Fluorescent silica nanoparticles through silica densification |
US8978954B2 (en) | 2010-09-30 | 2015-03-17 | Ethicon Endo-Surgery, Inc. | Staple cartridge comprising an adjustable distal portion |
US8992422B2 (en) | 2006-03-23 | 2015-03-31 | Ethicon Endo-Surgery, Inc. | Robotically-controlled endoscopic accessory channel |
US9005230B2 (en) | 2008-09-23 | 2015-04-14 | Ethicon Endo-Surgery, Inc. | Motorized surgical instrument |
US9018347B2 (en) | 2010-02-04 | 2015-04-28 | Morphotek, Inc. | Chlorotoxin polypeptides and conjugates and uses thereof |
US9023595B2 (en) | 2008-05-15 | 2015-05-05 | Morphotek, Inc. | Treatment of metastatic tumors |
US9028494B2 (en) | 2012-06-28 | 2015-05-12 | Ethicon Endo-Surgery, Inc. | Interchangeable end effector coupling arrangement |
US9028519B2 (en) | 2008-09-23 | 2015-05-12 | Ethicon Endo-Surgery, Inc. | Motorized surgical instrument |
US9042765B2 (en) | 2012-01-16 | 2015-05-26 | Samsung Electronics Co., Ltd. | Image forming apparatus with improved heat transmission |
US9044230B2 (en) | 2012-02-13 | 2015-06-02 | Ethicon Endo-Surgery, Inc. | Surgical cutting and fastening instrument with apparatus for determining cartridge and firing motion status |
US9050084B2 (en) | 2011-09-23 | 2015-06-09 | Ethicon Endo-Surgery, Inc. | Staple cartridge including collapsible deck arrangement |
US9055941B2 (en) | 2011-09-23 | 2015-06-16 | Ethicon Endo-Surgery, Inc. | Staple cartridge including collapsible deck |
US20150177153A1 (en) * | 2013-12-20 | 2015-06-25 | Sicpa Holding Sa | Thermoluminescent composite particle and marking comprising same |
US9068084B2 (en) | 2010-01-19 | 2015-06-30 | Wuxi Zodolabs Biotech Co., Ltd. | Silica nanoparticles doped with dye having negative charge and preparing method thereof |
US9072535B2 (en) | 2011-05-27 | 2015-07-07 | Ethicon Endo-Surgery, Inc. | Surgical stapling instruments with rotatable staple deployment arrangements |
US9072536B2 (en) | 2012-06-28 | 2015-07-07 | Ethicon Endo-Surgery, Inc. | Differential locking arrangements for rotary powered surgical instruments |
US20150202848A1 (en) * | 2014-01-22 | 2015-07-23 | Samsung Display Co., Ltd. | Display device |
US9101385B2 (en) | 2012-06-28 | 2015-08-11 | Ethicon Endo-Surgery, Inc. | Electrode connections for rotary driven surgical tools |
US9101358B2 (en) | 2012-06-15 | 2015-08-11 | Ethicon Endo-Surgery, Inc. | Articulatable surgical instrument comprising a firing drive |
EP2833144A4 (en) * | 2012-03-28 | 2015-08-26 | Konica Minolta Inc | Method for detection biological substance |
US9119657B2 (en) | 2012-06-28 | 2015-09-01 | Ethicon Endo-Surgery, Inc. | Rotary actuatable closure arrangement for surgical end effector |
US9125662B2 (en) | 2012-06-28 | 2015-09-08 | Ethicon Endo-Surgery, Inc. | Multi-axis articulating and rotating surgical tools |
US9125552B2 (en) | 2007-07-31 | 2015-09-08 | Ethicon Endo-Surgery, Inc. | Optical scanning module and means for attaching the module to medical instruments for introducing the module into the anatomy |
US9138225B2 (en) | 2007-06-22 | 2015-09-22 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument with an articulatable end effector |
US9198662B2 (en) | 2012-03-28 | 2015-12-01 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator having improved visibility |
US9204878B2 (en) | 2008-02-14 | 2015-12-08 | Ethicon Endo-Surgery, Inc. | Surgical stapling apparatus with interlockable firing system |
US9204880B2 (en) | 2012-03-28 | 2015-12-08 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator comprising capsules defining a low pressure environment |
US9204879B2 (en) | 2012-06-28 | 2015-12-08 | Ethicon Endo-Surgery, Inc. | Flexible drive member |
US9211120B2 (en) | 2011-04-29 | 2015-12-15 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator comprising a plurality of medicaments |
US9220500B2 (en) | 2010-09-30 | 2015-12-29 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator comprising structure to produce a resilient load |
US9220501B2 (en) | 2010-09-30 | 2015-12-29 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensators |
US9226751B2 (en) | 2012-06-28 | 2016-01-05 | Ethicon Endo-Surgery, Inc. | Surgical instrument system including replaceable end effectors |
US9232941B2 (en) | 2010-09-30 | 2016-01-12 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator comprising a reservoir |
JP2016501286A (en) * | 2012-11-16 | 2016-01-18 | エスエヌユー アールアンドディービー ファウンデーショ | Coded polymer particles |
US9237891B2 (en) | 2005-08-31 | 2016-01-19 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical stapling devices that produce formed staples having different lengths |
US9272406B2 (en) | 2010-09-30 | 2016-03-01 | Ethicon Endo-Surgery, Llc | Fastener cartridge comprising a cutting member for releasing a tissue thickness compensator |
US9282974B2 (en) | 2012-06-28 | 2016-03-15 | Ethicon Endo-Surgery, Llc | Empty clip cartridge lockout |
US9282966B2 (en) | 2004-07-28 | 2016-03-15 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument |
US9283054B2 (en) | 2013-08-23 | 2016-03-15 | Ethicon Endo-Surgery, Llc | Interactive displays |
US9289256B2 (en) | 2012-06-28 | 2016-03-22 | Ethicon Endo-Surgery, Llc | Surgical end effectors having angled tissue-contacting surfaces |
US9301752B2 (en) | 2010-09-30 | 2016-04-05 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator comprising a plurality of capsules |
US9307989B2 (en) | 2012-03-28 | 2016-04-12 | Ethicon Endo-Surgery, Llc | Tissue stapler having a thickness compensator incorportating a hydrophobic agent |
US9307986B2 (en) | 2013-03-01 | 2016-04-12 | Ethicon Endo-Surgery, Llc | Surgical instrument soft stop |
US9314246B2 (en) | 2010-09-30 | 2016-04-19 | Ethicon Endo-Surgery, Llc | Tissue stapler having a thickness compensator incorporating an anti-inflammatory agent |
US9320521B2 (en) | 2006-06-27 | 2016-04-26 | Ethicon Endo-Surgery, Llc | Surgical instrument |
US9320523B2 (en) | 2012-03-28 | 2016-04-26 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator comprising tissue ingrowth features |
US9332984B2 (en) | 2013-03-27 | 2016-05-10 | Ethicon Endo-Surgery, Llc | Fastener cartridge assemblies |
US9332987B2 (en) | 2013-03-14 | 2016-05-10 | Ethicon Endo-Surgery, Llc | Control arrangements for a drive member of a surgical instrument |
US9332974B2 (en) | 2010-09-30 | 2016-05-10 | Ethicon Endo-Surgery, Llc | Layered tissue thickness compensator |
US9345481B2 (en) | 2013-03-13 | 2016-05-24 | Ethicon Endo-Surgery, Llc | Staple cartridge tissue thickness sensor system |
US9358005B2 (en) | 2010-09-30 | 2016-06-07 | Ethicon Endo-Surgery, Llc | End effector layer including holding features |
US9364233B2 (en) | 2010-09-30 | 2016-06-14 | Ethicon Endo-Surgery, Llc | Tissue thickness compensators for circular surgical staplers |
US9386984B2 (en) | 2013-02-08 | 2016-07-12 | Ethicon Endo-Surgery, Llc | Staple cartridge comprising a releasable cover |
US9393015B2 (en) | 2009-02-06 | 2016-07-19 | Ethicon Endo-Surgery, Llc | Motor driven surgical fastener device with cutting member reversing mechanism |
US9486214B2 (en) | 2009-02-06 | 2016-11-08 | Ethicon Endo-Surgery, Llc | Motor driven surgical fastener device with switching system configured to prevent firing initiation until activated |
US9532949B2 (en) | 2011-07-19 | 2017-01-03 | Stc.Unm | Intraperitoneally-administered nanocarriers that release their therapeutic load based on the inflammatory environment of cancers |
US9561038B2 (en) | 2012-06-28 | 2017-02-07 | Ethicon Endo-Surgery, Llc | Interchangeable clip applier |
US9574644B2 (en) | 2013-05-30 | 2017-02-21 | Ethicon Endo-Surgery, Llc | Power module for use with a surgical instrument |
US9572577B2 (en) | 2013-03-27 | 2017-02-21 | Ethicon Endo-Surgery, Llc | Fastener cartridge comprising a tissue thickness compensator including openings therein |
US9579283B2 (en) | 2011-04-28 | 2017-02-28 | Stc.Unm | Porous nanoparticle-supported lipid bilayers (protocells) for targeted delivery and methods of using same |
US9585657B2 (en) | 2008-02-15 | 2017-03-07 | Ethicon Endo-Surgery, Llc | Actuator for releasing a layer of material from a surgical end effector |
US9625456B2 (en) | 2009-07-02 | 2017-04-18 | Sloan-Kettering Institute For Cancer Research | Fluorescent silica-based nanoparticles |
US9629814B2 (en) | 2010-09-30 | 2017-04-25 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator configured to redistribute compressive forces |
US9629629B2 (en) | 2013-03-14 | 2017-04-25 | Ethicon Endo-Surgey, LLC | Control systems for surgical instruments |
US9649110B2 (en) | 2013-04-16 | 2017-05-16 | Ethicon Llc | Surgical instrument comprising a closing drive and a firing drive operated from the same rotatable output |
US9690362B2 (en) | 2014-03-26 | 2017-06-27 | Ethicon Llc | Surgical instrument control circuit having a safety processor |
US9693777B2 (en) | 2014-02-24 | 2017-07-04 | Ethicon Llc | Implantable layers comprising a pressed region |
US9724098B2 (en) | 2012-03-28 | 2017-08-08 | Ethicon Endo-Surgery, Llc | Staple cartridge comprising an implantable layer |
US9724094B2 (en) | 2014-09-05 | 2017-08-08 | Ethicon Llc | Adjunct with integrated sensors to quantify tissue compression |
US9743928B2 (en) | 2006-01-31 | 2017-08-29 | Ethicon Endo-Surgery, Inc. | Surgical instrument having a feedback system |
US9743929B2 (en) | 2014-03-26 | 2017-08-29 | Ethicon Llc | Modular powered surgical instrument with detachable shaft assemblies |
US9784730B2 (en) | 2013-03-21 | 2017-10-10 | University Of Washington Through Its Center For Commercialization | Nanoparticle for targeting brain tumors and delivery of O6-benzylguanine |
US9795382B2 (en) | 2005-08-31 | 2017-10-24 | Ethicon Llc | Fastener cartridge assembly comprising a cam and driver arrangement |
US9795384B2 (en) | 2013-03-27 | 2017-10-24 | Ethicon Llc | Fastener cartridge comprising a tissue thickness compensator and a gap setting element |
US9801627B2 (en) | 2014-09-26 | 2017-10-31 | Ethicon Llc | Fastener cartridge for creating a flexible staple line |
US9808246B2 (en) | 2015-03-06 | 2017-11-07 | Ethicon Endo-Surgery, Llc | Method of operating a powered surgical instrument |
US9814462B2 (en) | 2010-09-30 | 2017-11-14 | Ethicon Llc | Assembly for fastening tissue comprising a compressible layer |
US9820738B2 (en) | 2014-03-26 | 2017-11-21 | Ethicon Llc | Surgical instrument comprising interactive systems |
US9826978B2 (en) | 2010-09-30 | 2017-11-28 | Ethicon Llc | End effectors with same side closure and firing motions |
US9833241B2 (en) | 2014-04-16 | 2017-12-05 | Ethicon Llc | Surgical fastener cartridges with driver stabilizing arrangements |
WO2017210754A1 (en) * | 2016-06-10 | 2017-12-14 | The University Of Queensland | Detecting an analyte |
US9844375B2 (en) | 2014-12-18 | 2017-12-19 | Ethicon Llc | Drive arrangements for articulatable surgical instruments |
US9844376B2 (en) | 2014-11-06 | 2017-12-19 | Ethicon Llc | Staple cartridge comprising a releasable adjunct material |
US9844374B2 (en) | 2014-12-18 | 2017-12-19 | Ethicon Llc | Surgical instrument systems comprising an articulatable end effector and means for adjusting the firing stroke of a firing member |
WO2018005595A1 (en) * | 2016-06-28 | 2018-01-04 | The Trustees Of The University Of Pennsylvania | Superoleophobic membranes for oil/water separation |
US9861359B2 (en) | 2006-01-31 | 2018-01-09 | Ethicon Llc | Powered surgical instruments with firing system lockout arrangements |
US9895148B2 (en) | 2015-03-06 | 2018-02-20 | Ethicon Endo-Surgery, Llc | Monitoring speed control and precision incrementing of motor for powered surgical instruments |
US9895147B2 (en) | 2005-11-09 | 2018-02-20 | Ethicon Llc | End effectors for surgical staplers |
US9901342B2 (en) | 2015-03-06 | 2018-02-27 | Ethicon Endo-Surgery, Llc | Signal and power communication system positioned on a rotatable shaft |
US9913642B2 (en) | 2014-03-26 | 2018-03-13 | Ethicon Llc | Surgical instrument comprising a sensor system |
US9924961B2 (en) | 2015-03-06 | 2018-03-27 | Ethicon Endo-Surgery, Llc | Interactive feedback system for powered surgical instruments |
US9924944B2 (en) | 2014-10-16 | 2018-03-27 | Ethicon Llc | Staple cartridge comprising an adjunct material |
US9931118B2 (en) | 2015-02-27 | 2018-04-03 | Ethicon Endo-Surgery, Llc | Reinforced battery for a surgical instrument |
WO2018060722A1 (en) * | 2016-09-30 | 2018-04-05 | Sumitomo Chemical Company Limited | Composite particle |
US9937129B2 (en) | 2007-04-16 | 2018-04-10 | The Regents Of The University Of California | Materials and methods for delivering compositions to selected tissues |
US9943309B2 (en) | 2014-12-18 | 2018-04-17 | Ethicon Llc | Surgical instruments with articulatable end effectors and movable firing beam support arrangements |
US9944683B2 (en) | 2010-05-11 | 2018-04-17 | Fred Hutchinson Cancer Research Center | Chlorotoxin variants, conjugates, and methods for their use |
US9962161B2 (en) | 2014-02-12 | 2018-05-08 | Ethicon Llc | Deliverable surgical instrument |
US9987000B2 (en) | 2014-12-18 | 2018-06-05 | Ethicon Llc | Surgical instrument assembly comprising a flexible articulation system |
US20180155564A1 (en) * | 2015-06-18 | 2018-06-07 | Sicpa Holding Sa | Thermoluminescent and superparamagnetic composite particle and marking comprising same |
US9993258B2 (en) | 2015-02-27 | 2018-06-12 | Ethicon Llc | Adaptable surgical instrument handle |
US9993248B2 (en) | 2015-03-06 | 2018-06-12 | Ethicon Endo-Surgery, Llc | Smart sensors with local signal processing |
US9999694B2 (en) | 2009-07-02 | 2018-06-19 | Sloan-Kettering Institute For Cancer Research | Multimodal silica-based nanoparticles |
US10004498B2 (en) | 2006-01-31 | 2018-06-26 | Ethicon Llc | Surgical instrument comprising a plurality of articulation joints |
US10045776B2 (en) | 2015-03-06 | 2018-08-14 | Ethicon Llc | Control techniques and sub-processor contained within modular shaft with select control processing from handle |
US10045781B2 (en) | 2014-06-13 | 2018-08-14 | Ethicon Llc | Closure lockout systems for surgical instruments |
US10052044B2 (en) | 2015-03-06 | 2018-08-21 | Ethicon Llc | Time dependent evaluation of sensor data to determine stability, creep, and viscoelastic elements of measures |
US10052102B2 (en) | 2015-06-18 | 2018-08-21 | Ethicon Llc | Surgical end effectors with dual cam actuated jaw closing features |
US10076326B2 (en) | 2015-09-23 | 2018-09-18 | Ethicon Llc | Surgical stapler having current mirror-based motor control |
US10076325B2 (en) | 2014-10-13 | 2018-09-18 | Ethicon Llc | Surgical stapling apparatus comprising a tissue stop |
US10085751B2 (en) | 2015-09-23 | 2018-10-02 | Ethicon Llc | Surgical stapler having temperature-based motor control |
US10085748B2 (en) | 2014-12-18 | 2018-10-02 | Ethicon Llc | Locking arrangements for detachable shaft assemblies with articulatable surgical end effectors |
US10092292B2 (en) | 2013-02-28 | 2018-10-09 | Ethicon Llc | Staple forming features for surgical stapling instrument |
US10098642B2 (en) | 2015-08-26 | 2018-10-16 | Ethicon Llc | Surgical staples comprising features for improved fastening of tissue |
US10105139B2 (en) | 2015-09-23 | 2018-10-23 | Ethicon Llc | Surgical stapler having downstream current-based motor control |
US10111963B2 (en) | 2014-05-29 | 2018-10-30 | Memorial Sloan Kettering Cancer Center | Nanoparticle drug conjugates |
US10117649B2 (en) | 2014-12-18 | 2018-11-06 | Ethicon Llc | Surgical instrument assembly comprising a lockable articulation system |
US10130359B2 (en) | 2006-09-29 | 2018-11-20 | Ethicon Llc | Method for forming a staple |
US10156559B2 (en) | 2012-12-10 | 2018-12-18 | Fred Hutchinson Cancer Research Center | Lipocalin fusion partners |
US10172620B2 (en) | 2015-09-30 | 2019-01-08 | Ethicon Llc | Compressible adjuncts with bonding nodes |
US10172619B2 (en) | 2015-09-02 | 2019-01-08 | Ethicon Llc | Surgical staple driver arrays |
US10180463B2 (en) | 2015-02-27 | 2019-01-15 | Ethicon Llc | Surgical apparatus configured to assess whether a performance parameter of the surgical apparatus is within an acceptable performance band |
US10188385B2 (en) | 2014-12-18 | 2019-01-29 | Ethicon Llc | Surgical instrument system comprising lockable systems |
US10191060B2 (en) | 2009-11-09 | 2019-01-29 | University Of Washington | Functionalized chromophoric polymer dots and bioconjugates thereof |
US10203326B2 (en) | 2003-10-02 | 2019-02-12 | Furukawa Electric Co., Ltd. | Method of detecting target substance |
US10206676B2 (en) | 2008-02-14 | 2019-02-19 | Ethicon Llc | Surgical cutting and fastening instrument |
US10211586B2 (en) | 2017-06-28 | 2019-02-19 | Ethicon Llc | Surgical shaft assemblies with watertight housings |
US10213201B2 (en) | 2015-03-31 | 2019-02-26 | Ethicon Llc | Stapling end effector configured to compensate for an uneven gap between a first jaw and a second jaw |
US10226249B2 (en) | 2013-03-01 | 2019-03-12 | Ethicon Llc | Articulatable surgical instruments with conductive pathways for signal communication |
US10238386B2 (en) | 2015-09-23 | 2019-03-26 | Ethicon Llc | Surgical stapler having motor control based on an electrical parameter related to a motor current |
US10245030B2 (en) | 2016-02-09 | 2019-04-02 | Ethicon Llc | Surgical instruments with tensioning arrangements for cable driven articulation systems |
US10245033B2 (en) | 2015-03-06 | 2019-04-02 | Ethicon Llc | Surgical instrument comprising a lockable battery housing |
US10258418B2 (en) | 2017-06-29 | 2019-04-16 | Ethicon Llc | System for controlling articulation forces |
US10258331B2 (en) | 2016-02-12 | 2019-04-16 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US10258336B2 (en) | 2008-09-19 | 2019-04-16 | Ethicon Llc | Stapling system configured to produce different formed staple heights |
US10265068B2 (en) | 2015-12-30 | 2019-04-23 | Ethicon Llc | Surgical instruments with separable motors and motor control circuits |
US10265065B2 (en) | 2013-12-23 | 2019-04-23 | Ethicon Llc | Surgical staples and staple cartridges |
US10271849B2 (en) | 2015-09-30 | 2019-04-30 | Ethicon Llc | Woven constructs with interlocked standing fibers |
USD847989S1 (en) | 2016-06-24 | 2019-05-07 | Ethicon Llc | Surgical fastener cartridge |
US10293100B2 (en) | 2004-07-28 | 2019-05-21 | Ethicon Llc | Surgical stapling instrument having a medical substance dispenser |
US10292704B2 (en) | 2015-12-30 | 2019-05-21 | Ethicon Llc | Mechanisms for compensating for battery pack failure in powered surgical instruments |
US10299878B2 (en) | 2015-09-25 | 2019-05-28 | Ethicon Llc | Implantable adjunct systems for determining adjunct skew |
US10307170B2 (en) | 2017-06-20 | 2019-06-04 | Ethicon Llc | Method for closed loop control of motor velocity of a surgical stapling and cutting instrument |
USD850617S1 (en) | 2016-06-24 | 2019-06-04 | Ethicon Llc | Surgical fastener cartridge |
USD851762S1 (en) | 2017-06-28 | 2019-06-18 | Ethicon Llc | Anvil |
US10327769B2 (en) | 2015-09-23 | 2019-06-25 | Ethicon Llc | Surgical stapler having motor control based on a drive system component |
US10327767B2 (en) | 2017-06-20 | 2019-06-25 | Ethicon Llc | Control of motor velocity of a surgical stapling and cutting instrument based on angle of articulation |
WO2019123156A1 (en) * | 2017-12-19 | 2019-06-27 | 3M Innovative Properties Company | Compositions and methods to detect microorganisms |
US10335145B2 (en) | 2016-04-15 | 2019-07-02 | Ethicon Llc | Modular surgical instrument with configurable operating mode |
USD854151S1 (en) | 2017-06-28 | 2019-07-16 | Ethicon Llc | Surgical instrument shaft |
US10357247B2 (en) | 2016-04-15 | 2019-07-23 | Ethicon Llc | Surgical instrument with multiple program responses during a firing motion |
US10363036B2 (en) | 2015-09-23 | 2019-07-30 | Ethicon Llc | Surgical stapler having force-based motor control |
US10363037B2 (en) | 2016-04-18 | 2019-07-30 | Ethicon Llc | Surgical instrument system comprising a magnetic lockout |
US10368865B2 (en) | 2015-12-30 | 2019-08-06 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US10368864B2 (en) | 2017-06-20 | 2019-08-06 | Ethicon Llc | Systems and methods for controlling displaying motor velocity for a surgical instrument |
US10376263B2 (en) | 2016-04-01 | 2019-08-13 | Ethicon Llc | Anvil modification members for surgical staplers |
US10390841B2 (en) | 2017-06-20 | 2019-08-27 | Ethicon Llc | Control of motor velocity of a surgical stapling and cutting instrument based on angle of articulation |
US10398433B2 (en) | 2007-03-28 | 2019-09-03 | Ethicon Llc | Laparoscopic clamp load measuring devices |
US10398434B2 (en) | 2017-06-29 | 2019-09-03 | Ethicon Llc | Closed loop velocity control of closure member for robotic surgical instrument |
JP2019525379A (en) * | 2016-06-06 | 2019-09-05 | ダウ グローバル テクノロジーズ エルエルシー | LIGHT EMITTING DEVICE AND ELECTRONIC DEVICE EQUIPPED WITH THE SAME |
US10405859B2 (en) | 2016-04-15 | 2019-09-10 | Ethicon Llc | Surgical instrument with adjustable stop/start control during a firing motion |
US10413294B2 (en) | 2012-06-28 | 2019-09-17 | Ethicon Llc | Shaft assembly arrangements for surgical instruments |
US10426481B2 (en) | 2014-02-24 | 2019-10-01 | Ethicon Llc | Implantable layer assemblies |
US10426467B2 (en) | 2016-04-15 | 2019-10-01 | Ethicon Llc | Surgical instrument with detection sensors |
US10426471B2 (en) | 2016-12-21 | 2019-10-01 | Ethicon Llc | Surgical instrument with multiple failure response modes |
US10435661B2 (en) | 2011-05-13 | 2019-10-08 | The Regents Of The University Of California | Photothermal substrates for selective transfection of cells |
US10448950B2 (en) | 2016-12-21 | 2019-10-22 | Ethicon Llc | Surgical staplers with independently actuatable closing and firing systems |
US10448948B2 (en) | 2016-02-12 | 2019-10-22 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US10456137B2 (en) | 2016-04-15 | 2019-10-29 | Ethicon Llc | Staple formation detection mechanisms |
US10472651B2 (en) | 2014-03-28 | 2019-11-12 | The Regents Of The University Of California | Efficient delivery of large cargos into cells on a porous substrate |
US10485543B2 (en) | 2016-12-21 | 2019-11-26 | Ethicon Llc | Anvil having a knife slot width |
US10492783B2 (en) | 2016-04-15 | 2019-12-03 | Ethicon, Llc | Surgical instrument with improved stop/start control during a firing motion |
US10492785B2 (en) | 2016-12-21 | 2019-12-03 | Ethicon Llc | Shaft assembly comprising a lockout |
USD869655S1 (en) | 2017-06-28 | 2019-12-10 | Ethicon Llc | Surgical fastener cartridge |
US10499890B2 (en) | 2006-01-31 | 2019-12-10 | Ethicon Llc | Endoscopic surgical instrument with a handle that can articulate with respect to the shaft |
US10499914B2 (en) | 2016-12-21 | 2019-12-10 | Ethicon Llc | Staple forming pocket arrangements |
US10517594B2 (en) | 2014-10-29 | 2019-12-31 | Ethicon Llc | Cartridge assemblies for surgical staplers |
US10517596B2 (en) | 2016-12-21 | 2019-12-31 | Ethicon Llc | Articulatable surgical instruments with articulation stroke amplification features |
US10537324B2 (en) | 2016-12-21 | 2020-01-21 | Ethicon Llc | Stepped staple cartridge with asymmetrical staples |
US10537325B2 (en) | 2016-12-21 | 2020-01-21 | Ethicon Llc | Staple forming pocket arrangement to accommodate different types of staples |
US20200024592A1 (en) * | 2015-05-28 | 2020-01-23 | Bioneer Corporation | Highly active silica magnetic nanoparticles for purifying biomaterial and preparation method thereof |
US10542979B2 (en) | 2016-06-24 | 2020-01-28 | Ethicon Llc | Stamped staples and staple cartridges using the same |
US10548989B2 (en) * | 2015-04-07 | 2020-02-04 | Memorial Sloan Kettering Cancer Center | Nanoparticle immunoconjugates |
US10568626B2 (en) | 2016-12-21 | 2020-02-25 | Ethicon Llc | Surgical instruments with jaw opening features for increasing a jaw opening distance |
US10568652B2 (en) | 2006-09-29 | 2020-02-25 | Ethicon Llc | Surgical staples having attached drivers of different heights and stapling instruments for deploying the same |
US10568625B2 (en) | 2016-12-21 | 2020-02-25 | Ethicon Llc | Staple cartridges and arrangements of staples and staple cavities therein |
US10575868B2 (en) | 2013-03-01 | 2020-03-03 | Ethicon Llc | Surgical instrument with coupler assembly |
US10588633B2 (en) | 2017-06-28 | 2020-03-17 | Ethicon Llc | Surgical instruments with open and closable jaws and axially movable firing member that is initially parked in close proximity to the jaws prior to firing |
US10588632B2 (en) | 2016-12-21 | 2020-03-17 | Ethicon Llc | Surgical end effectors and firing members thereof |
USD879808S1 (en) | 2017-06-20 | 2020-03-31 | Ethicon Llc | Display panel with graphical user interface |
USD879809S1 (en) | 2017-06-20 | 2020-03-31 | Ethicon Llc | Display panel with changeable graphical user interface |
US10617412B2 (en) | 2015-03-06 | 2020-04-14 | Ethicon Llc | System for detecting the mis-insertion of a staple cartridge into a surgical stapler |
US10617418B2 (en) | 2015-08-17 | 2020-04-14 | Ethicon Llc | Implantable layers for a surgical instrument |
US10617413B2 (en) | 2016-04-01 | 2020-04-14 | Ethicon Llc | Closure system arrangements for surgical cutting and stapling devices with separate and distinct firing shafts |
US10624633B2 (en) | 2017-06-20 | 2020-04-21 | Ethicon Llc | Systems and methods for controlling motor velocity of a surgical stapling and cutting instrument |
US10631859B2 (en) | 2017-06-27 | 2020-04-28 | Ethicon Llc | Articulation systems for surgical instruments |
US10646220B2 (en) | 2017-06-20 | 2020-05-12 | Ethicon Llc | Systems and methods for controlling displacement member velocity for a surgical instrument |
US10667809B2 (en) | 2016-12-21 | 2020-06-02 | Ethicon Llc | Staple cartridge and staple cartridge channel comprising windows defined therein |
US10675028B2 (en) | 2006-01-31 | 2020-06-09 | Ethicon Llc | Powered surgical instruments with firing system lockout arrangements |
US10682134B2 (en) | 2017-12-21 | 2020-06-16 | Ethicon Llc | Continuous use self-propelled stapling instrument |
US10687810B2 (en) | 2016-12-21 | 2020-06-23 | Ethicon Llc | Stepped staple cartridge with tissue retention and gap setting features |
US10687813B2 (en) | 2017-12-15 | 2020-06-23 | Ethicon Llc | Adapters with firing stroke sensing arrangements for use in connection with electromechanical surgical instruments |
US10687806B2 (en) | 2015-03-06 | 2020-06-23 | Ethicon Llc | Adaptive tissue compression techniques to adjust closure rates for multiple tissue types |
US10695062B2 (en) | 2010-10-01 | 2020-06-30 | Ethicon Llc | Surgical instrument including a retractable firing member |
US10716614B2 (en) | 2017-06-28 | 2020-07-21 | Ethicon Llc | Surgical shaft assemblies with slip ring assemblies with increased contact pressure |
US10716565B2 (en) | 2017-12-19 | 2020-07-21 | Ethicon Llc | Surgical instruments with dual articulation drivers |
USD890784S1 (en) | 2017-06-20 | 2020-07-21 | Ethicon Llc | Display panel with changeable graphical user interface |
US10729509B2 (en) | 2017-12-19 | 2020-08-04 | Ethicon Llc | Surgical instrument comprising closure and firing locking mechanism |
US10736636B2 (en) | 2014-12-10 | 2020-08-11 | Ethicon Llc | Articulatable surgical instrument system |
US10736972B2 (en) | 2015-05-29 | 2020-08-11 | Memorial Sloan Kettering Cancer Center | Methods of treatment using ultrasmall nanoparticles to induce cell death of nutrient-deprived cancer cells via ferroptosis |
US10743851B2 (en) | 2008-02-14 | 2020-08-18 | Ethicon Llc | Interchangeable tools for surgical instruments |
US10743875B2 (en) | 2017-12-15 | 2020-08-18 | Ethicon Llc | Surgical end effectors with jaw stiffener arrangements configured to permit monitoring of firing member |
US10743874B2 (en) | 2017-12-15 | 2020-08-18 | Ethicon Llc | Sealed adapters for use with electromechanical surgical instruments |
US10743872B2 (en) | 2017-09-29 | 2020-08-18 | Ethicon Llc | System and methods for controlling a display of a surgical instrument |
USD894389S1 (en) | 2016-06-24 | 2020-08-25 | Ethicon Llc | Surgical fastener |
US10751076B2 (en) | 2009-12-24 | 2020-08-25 | Ethicon Llc | Motor-driven surgical cutting instrument with electric actuator directional control assembly |
US10758229B2 (en) | 2016-12-21 | 2020-09-01 | Ethicon Llc | Surgical instrument comprising improved jaw control |
US10758233B2 (en) | 2009-02-05 | 2020-09-01 | Ethicon Llc | Articulatable surgical instrument comprising a firing drive |
US10758230B2 (en) | 2016-12-21 | 2020-09-01 | Ethicon Llc | Surgical instrument with primary and safety processors |
US10765427B2 (en) | 2017-06-28 | 2020-09-08 | Ethicon Llc | Method for articulating a surgical instrument |
US10765424B2 (en) | 2008-02-13 | 2020-09-08 | Ethicon Llc | Surgical stapling instrument |
US10765429B2 (en) | 2017-09-29 | 2020-09-08 | Ethicon Llc | Systems and methods for providing alerts according to the operational state of a surgical instrument |
US10772629B2 (en) | 2017-06-27 | 2020-09-15 | Ethicon Llc | Surgical anvil arrangements |
US10779903B2 (en) | 2017-10-31 | 2020-09-22 | Ethicon Llc | Positive shaft rotation lock activated by jaw closure |
US10779824B2 (en) | 2017-06-28 | 2020-09-22 | Ethicon Llc | Surgical instrument comprising an articulation system lockable by a closure system |
US10779826B2 (en) | 2017-12-15 | 2020-09-22 | Ethicon Llc | Methods of operating surgical end effectors |
US10779820B2 (en) | 2017-06-20 | 2020-09-22 | Ethicon Llc | Systems and methods for controlling motor speed according to user input for a surgical instrument |
US10779821B2 (en) | 2018-08-20 | 2020-09-22 | Ethicon Llc | Surgical stapler anvils with tissue stop features configured to avoid tissue pinch |
US10779825B2 (en) | 2017-12-15 | 2020-09-22 | Ethicon Llc | Adapters with end effector position sensing and control arrangements for use in connection with electromechanical surgical instruments |
US10796471B2 (en) | 2017-09-29 | 2020-10-06 | Ethicon Llc | Systems and methods of displaying a knife position for a surgical instrument |
US10813639B2 (en) | 2017-06-20 | 2020-10-27 | Ethicon Llc | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on system conditions |
US10828028B2 (en) | 2016-04-15 | 2020-11-10 | Ethicon Llc | Surgical instrument with multiple program responses during a firing motion |
US10828033B2 (en) | 2017-12-15 | 2020-11-10 | Ethicon Llc | Handheld electromechanical surgical instruments with improved motor control arrangements for positioning components of an adapter coupled thereto |
US10835330B2 (en) | 2017-12-19 | 2020-11-17 | Ethicon Llc | Method for determining the position of a rotatable jaw of a surgical instrument attachment assembly |
US10842490B2 (en) | 2017-10-31 | 2020-11-24 | Ethicon Llc | Cartridge body design with force reduction based on firing completion |
US10842492B2 (en) | 2018-08-20 | 2020-11-24 | Ethicon Llc | Powered articulatable surgical instruments with clutching and locking arrangements for linking an articulation drive system to a firing drive system |
US10856870B2 (en) | 2018-08-20 | 2020-12-08 | Ethicon Llc | Switching arrangements for motor powered articulatable surgical instruments |
US10856869B2 (en) | 2017-06-27 | 2020-12-08 | Ethicon Llc | Surgical anvil arrangements |
US10869666B2 (en) | 2017-12-15 | 2020-12-22 | Ethicon Llc | Adapters with control systems for controlling multiple motors of an electromechanical surgical instrument |
USD906355S1 (en) | 2017-06-28 | 2020-12-29 | Ethicon Llc | Display screen or portion thereof with a graphical user interface for a surgical instrument |
US10881399B2 (en) | 2017-06-20 | 2021-01-05 | Ethicon Llc | Techniques for adaptive control of motor velocity of a surgical stapling and cutting instrument |
US10881396B2 (en) | 2017-06-20 | 2021-01-05 | Ethicon Llc | Surgical instrument with variable duration trigger arrangement |
USD907647S1 (en) | 2017-09-29 | 2021-01-12 | Ethicon Llc | Display screen or portion thereof with animated graphical user interface |
US10888321B2 (en) | 2017-06-20 | 2021-01-12 | Ethicon Llc | Systems and methods for controlling velocity of a displacement member of a surgical stapling and cutting instrument |
USD907648S1 (en) | 2017-09-29 | 2021-01-12 | Ethicon Llc | Display screen or portion thereof with animated graphical user interface |
US10903685B2 (en) | 2017-06-28 | 2021-01-26 | Ethicon Llc | Surgical shaft assemblies with slip ring assemblies forming capacitive channels |
US10898183B2 (en) | 2017-06-29 | 2021-01-26 | Ethicon Llc | Robotic surgical instrument with closed loop feedback techniques for advancement of closure member during firing |
US10912559B2 (en) | 2018-08-20 | 2021-02-09 | Ethicon Llc | Reinforced deformable anvil tip for surgical stapler anvil |
USD910847S1 (en) | 2017-12-19 | 2021-02-16 | Ethicon Llc | Surgical instrument assembly |
US10925599B2 (en) | 2013-12-23 | 2021-02-23 | Ethicon Llc | Modular surgical instruments |
US10932772B2 (en) | 2017-06-29 | 2021-03-02 | Ethicon Llc | Methods for closed loop velocity control for robotic surgical instrument |
US10945731B2 (en) | 2010-09-30 | 2021-03-16 | Ethicon Llc | Tissue thickness compensator comprising controlled release and expansion |
US10945727B2 (en) | 2016-12-21 | 2021-03-16 | Ethicon Llc | Staple cartridge with deformable driver retention features |
USD914878S1 (en) | 2018-08-20 | 2021-03-30 | Ethicon Llc | Surgical instrument anvil |
US10966718B2 (en) | 2017-12-15 | 2021-04-06 | Ethicon Llc | Dynamic clamping assemblies with improved wear characteristics for use in connection with electromechanical surgical instruments |
US10982217B2 (en) | 2013-03-15 | 2021-04-20 | The Regents Of The University Of California | High-throughput cargo delivery into live cells using photothermal platforms |
US10980539B2 (en) | 2015-09-30 | 2021-04-20 | Ethicon Llc | Implantable adjunct comprising bonded layers |
US10980537B2 (en) | 2017-06-20 | 2021-04-20 | Ethicon Llc | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured time over a specified number of shaft rotations |
US10987102B2 (en) | 2010-09-30 | 2021-04-27 | Ethicon Llc | Tissue thickness compensator comprising a plurality of layers |
USD917500S1 (en) | 2017-09-29 | 2021-04-27 | Ethicon Llc | Display screen or portion thereof with graphical user interface |
US10986997B2 (en) | 2013-12-31 | 2021-04-27 | Memorial Sloan Kettering Cancer Center | Systems, methods, and apparatus for multichannel imaging of fluorescent sources in real time |
US10993715B2 (en) | 2016-12-21 | 2021-05-04 | Ethicon Llc | Staple cartridge comprising staples with different clamping breadths |
US10993716B2 (en) | 2017-06-27 | 2021-05-04 | Ethicon Llc | Surgical anvil arrangements |
US11007022B2 (en) | 2017-06-29 | 2021-05-18 | Ethicon Llc | Closed loop velocity control techniques based on sensed tissue parameters for robotic surgical instrument |
US11006955B2 (en) | 2017-12-15 | 2021-05-18 | Ethicon Llc | End effectors with positive jaw opening features for use with adapters for electromechanical surgical instruments |
US11013511B2 (en) | 2007-06-22 | 2021-05-25 | Ethicon Llc | Surgical stapling instrument with an articulatable end effector |
US11020109B2 (en) | 2013-12-23 | 2021-06-01 | Ethicon Llc | Surgical stapling assembly for use with a powered surgical interface |
US11020112B2 (en) | 2017-12-19 | 2021-06-01 | Ethicon Llc | Surgical tools configured for interchangeable use with different controller interfaces |
US11033267B2 (en) | 2017-12-15 | 2021-06-15 | Ethicon Llc | Systems and methods of controlling a clamping member firing rate of a surgical instrument |
US11039836B2 (en) | 2007-01-11 | 2021-06-22 | Cilag Gmbh International | Staple cartridge for use with a surgical stapling instrument |
US11039834B2 (en) | 2018-08-20 | 2021-06-22 | Cilag Gmbh International | Surgical stapler anvils with staple directing protrusions and tissue stability features |
US11045192B2 (en) | 2018-08-20 | 2021-06-29 | Cilag Gmbh International | Fabricating techniques for surgical stapler anvils |
US11045270B2 (en) | 2017-12-19 | 2021-06-29 | Cilag Gmbh International | Robotic attachment comprising exterior drive actuator |
US11051807B2 (en) | 2019-06-28 | 2021-07-06 | Cilag Gmbh International | Packaging assembly including a particulate trap |
US11051813B2 (en) | 2006-01-31 | 2021-07-06 | Cilag Gmbh International | Powered surgical instruments with firing system lockout arrangements |
US11071543B2 (en) | 2017-12-15 | 2021-07-27 | Cilag Gmbh International | Surgical end effectors with clamping assemblies configured to increase jaw aperture ranges |
US11071545B2 (en) | 2014-09-05 | 2021-07-27 | Cilag Gmbh International | Smart cartridge wake up operation and data retention |
US11071554B2 (en) | 2017-06-20 | 2021-07-27 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on magnitude of velocity error measurements |
US11076853B2 (en) | 2017-12-21 | 2021-08-03 | Cilag Gmbh International | Systems and methods of displaying a knife position during transection for a surgical instrument |
US11083458B2 (en) | 2018-08-20 | 2021-08-10 | Cilag Gmbh International | Powered surgical instruments with clutching arrangements to convert linear drive motions to rotary drive motions |
US11090046B2 (en) | 2017-06-20 | 2021-08-17 | Cilag Gmbh International | Systems and methods for controlling displacement member motion of a surgical stapling and cutting instrument |
US11090075B2 (en) | 2017-10-30 | 2021-08-17 | Cilag Gmbh International | Articulation features for surgical end effector |
US11123065B2 (en) | 2013-12-23 | 2021-09-21 | Cilag Gmbh International | Surgical cutting and stapling instruments with independent jaw control features |
US11133106B2 (en) | 2013-08-23 | 2021-09-28 | Cilag Gmbh International | Surgical instrument assembly comprising a retraction assembly |
US11129680B2 (en) | 2017-12-21 | 2021-09-28 | Cilag Gmbh International | Surgical instrument comprising a projector |
US11134942B2 (en) | 2016-12-21 | 2021-10-05 | Cilag Gmbh International | Surgical stapling instruments and staple-forming anvils |
US11134944B2 (en) | 2017-10-30 | 2021-10-05 | Cilag Gmbh International | Surgical stapler knife motion controls |
US11141153B2 (en) | 2014-10-29 | 2021-10-12 | Cilag Gmbh International | Staple cartridges comprising driver arrangements |
US11147551B2 (en) | 2019-03-25 | 2021-10-19 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11147553B2 (en) | 2019-03-25 | 2021-10-19 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11154301B2 (en) | 2015-02-27 | 2021-10-26 | Cilag Gmbh International | Modular stapling assembly |
WO2021173629A3 (en) * | 2020-02-28 | 2021-11-04 | NanoBio Designs, LLC | Molecular detection via assembly of particle complexes |
US11168353B2 (en) | 2011-02-18 | 2021-11-09 | Bio-Rad Laboratories, Inc. | Compositions and methods for molecular labeling |
US11172929B2 (en) | 2019-03-25 | 2021-11-16 | Cilag Gmbh International | Articulation drive arrangements for surgical systems |
US11174509B2 (en) | 2013-12-12 | 2021-11-16 | Bio-Rad Laboratories, Inc. | Distinguishing rare variations in a nucleic acid sequence from a sample |
US11179150B2 (en) | 2016-04-15 | 2021-11-23 | Cilag Gmbh International | Systems and methods for controlling a surgical stapling and cutting instrument |
US11187702B2 (en) | 2003-03-14 | 2021-11-30 | Bio-Rad Laboratories, Inc. | Enzyme quantification |
US11197671B2 (en) | 2012-06-28 | 2021-12-14 | Cilag Gmbh International | Stapling assembly comprising a lockout |
US11197670B2 (en) | 2017-12-15 | 2021-12-14 | Cilag Gmbh International | Surgical end effectors with pivotal jaws configured to touch at their respective distal ends when fully closed |
US11202633B2 (en) | 2014-09-26 | 2021-12-21 | Cilag Gmbh International | Surgical stapling buttresses and adjunct materials |
US11207065B2 (en) | 2018-08-20 | 2021-12-28 | Cilag Gmbh International | Method for fabricating surgical stapler anvils |
US11207064B2 (en) | 2011-05-27 | 2021-12-28 | Cilag Gmbh International | Automated end effector component reloading system for use with a robotic system |
US11213293B2 (en) | 2016-02-09 | 2022-01-04 | Cilag Gmbh International | Articulatable surgical instruments with single articulation link arrangements |
US11213295B2 (en) | 2015-09-02 | 2022-01-04 | Cilag Gmbh International | Surgical staple configurations with camming surfaces located between portions supporting surgical staples |
US11219456B2 (en) | 2015-08-26 | 2022-01-11 | Cilag Gmbh International | Surgical staple strips for permitting varying staple properties and enabling easy cartridge loading |
US11219455B2 (en) | 2019-06-28 | 2022-01-11 | Cilag Gmbh International | Surgical instrument including a lockout key |
US11224876B2 (en) | 2007-04-19 | 2022-01-18 | Brandeis University | Manipulation of fluids, fluid components and reactions in microfluidic systems |
US11224427B2 (en) | 2006-01-31 | 2022-01-18 | Cilag Gmbh International | Surgical stapling system including a console and retraction assembly |
US11224426B2 (en) | 2016-02-12 | 2022-01-18 | Cilag Gmbh International | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US11224428B2 (en) | 2016-12-21 | 2022-01-18 | Cilag Gmbh International | Surgical stapling systems |
US11224497B2 (en) | 2019-06-28 | 2022-01-18 | Cilag Gmbh International | Surgical systems with multiple RFID tags |
US11229437B2 (en) | 2019-06-28 | 2022-01-25 | Cilag Gmbh International | Method for authenticating the compatibility of a staple cartridge with a surgical instrument |
US11234698B2 (en) | 2019-12-19 | 2022-02-01 | Cilag Gmbh International | Stapling system comprising a clamp lockout and a firing lockout |
US11241230B2 (en) | 2012-06-28 | 2022-02-08 | Cilag Gmbh International | Clip applier tool for use with a robotic surgical system |
US11246678B2 (en) | 2019-06-28 | 2022-02-15 | Cilag Gmbh International | Surgical stapling system having a frangible RFID tag |
US11246590B2 (en) | 2005-08-31 | 2022-02-15 | Cilag Gmbh International | Staple cartridge including staple drivers having different unfired heights |
US11246592B2 (en) | 2017-06-28 | 2022-02-15 | Cilag Gmbh International | Surgical instrument comprising an articulation system lockable to a frame |
US11253256B2 (en) | 2018-08-20 | 2022-02-22 | Cilag Gmbh International | Articulatable motor powered surgical instruments with dedicated articulation motor arrangements |
US11254968B2 (en) | 2010-02-12 | 2022-02-22 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
US11253254B2 (en) | 2019-04-30 | 2022-02-22 | Cilag Gmbh International | Shaft rotation actuator on a surgical instrument |
US11259805B2 (en) | 2017-06-28 | 2022-03-01 | Cilag Gmbh International | Surgical instrument comprising firing member supports |
US11259803B2 (en) | 2019-06-28 | 2022-03-01 | Cilag Gmbh International | Surgical stapling system having an information encryption protocol |
US11259799B2 (en) | 2014-03-26 | 2022-03-01 | Cilag Gmbh International | Interface systems for use with surgical instruments |
US11266409B2 (en) | 2014-04-16 | 2022-03-08 | Cilag Gmbh International | Fastener cartridge comprising a sled including longitudinally-staggered ramps |
US11266405B2 (en) | 2017-06-27 | 2022-03-08 | Cilag Gmbh International | Surgical anvil manufacturing methods |
US11272927B2 (en) | 2008-02-15 | 2022-03-15 | Cilag Gmbh International | Layer arrangements for surgical staple cartridges |
US11278279B2 (en) | 2006-01-31 | 2022-03-22 | Cilag Gmbh International | Surgical instrument assembly |
US11284898B2 (en) | 2014-09-18 | 2022-03-29 | Cilag Gmbh International | Surgical instrument including a deployable knife |
US11291451B2 (en) | 2019-06-28 | 2022-04-05 | Cilag Gmbh International | Surgical instrument with battery compatibility verification functionality |
US11291447B2 (en) | 2019-12-19 | 2022-04-05 | Cilag Gmbh International | Stapling instrument comprising independent jaw closing and staple firing systems |
US11291449B2 (en) | 2009-12-24 | 2022-04-05 | Cilag Gmbh International | Surgical cutting instrument that analyzes tissue thickness |
US11291440B2 (en) | 2018-08-20 | 2022-04-05 | Cilag Gmbh International | Method for operating a powered articulatable surgical instrument |
US11291441B2 (en) | 2007-01-10 | 2022-04-05 | Cilag Gmbh International | Surgical instrument with wireless communication between control unit and remote sensor |
US11298127B2 (en) | 2019-06-28 | 2022-04-12 | Cilag GmbH Interational | Surgical stapling system having a lockout mechanism for an incompatible cartridge |
US11298132B2 (en) | 2019-06-28 | 2022-04-12 | Cilag GmbH Inlernational | Staple cartridge including a honeycomb extension |
US11298125B2 (en) | 2010-09-30 | 2022-04-12 | Cilag Gmbh International | Tissue stapler having a thickness compensator |
US11304696B2 (en) | 2019-12-19 | 2022-04-19 | Cilag Gmbh International | Surgical instrument comprising a powered articulation system |
US11304695B2 (en) | 2017-08-03 | 2022-04-19 | Cilag Gmbh International | Surgical system shaft interconnection |
US11311294B2 (en) | 2014-09-05 | 2022-04-26 | Cilag Gmbh International | Powered medical device including measurement of closure state of jaws |
US11311290B2 (en) | 2017-12-21 | 2022-04-26 | Cilag Gmbh International | Surgical instrument comprising an end effector dampener |
US11317917B2 (en) | 2016-04-18 | 2022-05-03 | Cilag Gmbh International | Surgical stapling system comprising a lockable firing assembly |
US11317913B2 (en) | 2016-12-21 | 2022-05-03 | Cilag Gmbh International | Lockout arrangements for surgical end effectors and replaceable tool assemblies |
US11324503B2 (en) | 2017-06-27 | 2022-05-10 | Cilag Gmbh International | Surgical firing member arrangements |
US11324501B2 (en) | 2018-08-20 | 2022-05-10 | Cilag Gmbh International | Surgical stapling devices with improved closure members |
US11350928B2 (en) | 2016-04-18 | 2022-06-07 | Cilag Gmbh International | Surgical instrument comprising a tissue thickness lockout and speed control system |
US11351510B2 (en) | 2006-05-11 | 2022-06-07 | Bio-Rad Laboratories, Inc. | Microfluidic devices |
US11376098B2 (en) | 2019-06-28 | 2022-07-05 | Cilag Gmbh International | Surgical instrument system comprising an RFID system |
US11382627B2 (en) | 2014-04-16 | 2022-07-12 | Cilag Gmbh International | Surgical stapling assembly comprising a firing member including a lateral extension |
US11382638B2 (en) | 2017-06-20 | 2022-07-12 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured time over a specified displacement distance |
US11390917B2 (en) | 2010-02-12 | 2022-07-19 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
US11399829B2 (en) | 2017-09-29 | 2022-08-02 | Cilag Gmbh International | Systems and methods of initiating a power shutdown mode for a surgical instrument |
US11399837B2 (en) | 2019-06-28 | 2022-08-02 | Cilag Gmbh International | Mechanisms for motor control adjustments of a motorized surgical instrument |
US11419606B2 (en) | 2016-12-21 | 2022-08-23 | Cilag Gmbh International | Shaft assembly comprising a clutch configured to adapt the output of a rotary firing member to two different systems |
US11426167B2 (en) | 2019-06-28 | 2022-08-30 | Cilag Gmbh International | Mechanisms for proper anvil attachment surgical stapling head assembly |
US11426251B2 (en) | 2019-04-30 | 2022-08-30 | Cilag Gmbh International | Articulation directional lights on a surgical instrument |
US11432816B2 (en) | 2019-04-30 | 2022-09-06 | Cilag Gmbh International | Articulation pin for a surgical instrument |
US11446029B2 (en) | 2019-12-19 | 2022-09-20 | Cilag Gmbh International | Staple cartridge comprising projections extending from a curved deck surface |
US11452526B2 (en) | 2020-10-29 | 2022-09-27 | Cilag Gmbh International | Surgical instrument comprising a staged voltage regulation start-up system |
US11452528B2 (en) | 2019-04-30 | 2022-09-27 | Cilag Gmbh International | Articulation actuators for a surgical instrument |
US11464513B2 (en) | 2012-06-28 | 2022-10-11 | Cilag Gmbh International | Surgical instrument system including replaceable end effectors |
US11464512B2 (en) | 2019-12-19 | 2022-10-11 | Cilag Gmbh International | Staple cartridge comprising a curved deck surface |
USD966512S1 (en) | 2020-06-02 | 2022-10-11 | Cilag Gmbh International | Staple cartridge |
US11464601B2 (en) | 2019-06-28 | 2022-10-11 | Cilag Gmbh International | Surgical instrument comprising an RFID system for tracking a movable component |
USD967421S1 (en) | 2020-06-02 | 2022-10-18 | Cilag Gmbh International | Staple cartridge |
US11471155B2 (en) | 2017-08-03 | 2022-10-18 | Cilag Gmbh International | Surgical system bailout |
US11471157B2 (en) | 2019-04-30 | 2022-10-18 | Cilag Gmbh International | Articulation control mapping for a surgical instrument |
US11478241B2 (en) | 2019-06-28 | 2022-10-25 | Cilag Gmbh International | Staple cartridge including projections |
US11478247B2 (en) | 2010-07-30 | 2022-10-25 | Cilag Gmbh International | Tissue acquisition arrangements and methods for surgical stapling devices |
US11484312B2 (en) | 2005-08-31 | 2022-11-01 | Cilag Gmbh International | Staple cartridge comprising a staple driver arrangement |
US11497492B2 (en) | 2019-06-28 | 2022-11-15 | Cilag Gmbh International | Surgical instrument including an articulation lock |
US11504122B2 (en) | 2019-12-19 | 2022-11-22 | Cilag Gmbh International | Surgical instrument comprising a nested firing member |
US11511242B2 (en) | 2008-07-18 | 2022-11-29 | Bio-Rad Laboratories, Inc. | Droplet libraries |
US11517325B2 (en) | 2017-06-20 | 2022-12-06 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured displacement distance traveled over a specified time interval |
US11517390B2 (en) | 2020-10-29 | 2022-12-06 | Cilag Gmbh International | Surgical instrument comprising a limited travel switch |
US11523821B2 (en) | 2014-09-26 | 2022-12-13 | Cilag Gmbh International | Method for creating a flexible staple line |
US11523822B2 (en) | 2019-06-28 | 2022-12-13 | Cilag Gmbh International | Battery pack including a circuit interrupter |
US11523823B2 (en) | 2016-02-09 | 2022-12-13 | Cilag Gmbh International | Surgical instruments with non-symmetrical articulation arrangements |
US11529139B2 (en) | 2019-12-19 | 2022-12-20 | Cilag Gmbh International | Motor driven surgical instrument |
US11529137B2 (en) | 2019-12-19 | 2022-12-20 | Cilag Gmbh International | Staple cartridge comprising driver retention members |
US11534259B2 (en) | 2020-10-29 | 2022-12-27 | Cilag Gmbh International | Surgical instrument comprising an articulation indicator |
USD974560S1 (en) | 2020-06-02 | 2023-01-03 | Cilag Gmbh International | Staple cartridge |
USD975278S1 (en) | 2020-06-02 | 2023-01-10 | Cilag Gmbh International | Staple cartridge |
USD975850S1 (en) | 2020-06-02 | 2023-01-17 | Cilag Gmbh International | Staple cartridge |
USD975851S1 (en) | 2020-06-02 | 2023-01-17 | Cilag Gmbh International | Staple cartridge |
US11553971B2 (en) | 2019-06-28 | 2023-01-17 | Cilag Gmbh International | Surgical RFID assemblies for display and communication |
US11559580B1 (en) | 2013-09-17 | 2023-01-24 | Blaze Bioscience, Inc. | Tissue-homing peptide conjugates and methods of use thereof |
US11559591B2 (en) | 2017-05-25 | 2023-01-24 | Memorial Sloan Kettering Cancer Center | Ultrasmall nanoparticles labeled with Zirconium-89 and methods thereof |
US11559304B2 (en) | 2019-12-19 | 2023-01-24 | Cilag Gmbh International | Surgical instrument comprising a rapid closure mechanism |
USD976401S1 (en) | 2020-06-02 | 2023-01-24 | Cilag Gmbh International | Staple cartridge |
US11564682B2 (en) | 2007-06-04 | 2023-01-31 | Cilag Gmbh International | Surgical stapler device |
US11564686B2 (en) | 2017-06-28 | 2023-01-31 | Cilag Gmbh International | Surgical shaft assemblies with flexible interfaces |
US11571215B2 (en) | 2010-09-30 | 2023-02-07 | Cilag Gmbh International | Layer of material for a surgical end effector |
US11576672B2 (en) | 2019-12-19 | 2023-02-14 | Cilag Gmbh International | Surgical instrument comprising a closure system including a closure member and an opening member driven by a drive screw |
USD980425S1 (en) | 2020-10-29 | 2023-03-07 | Cilag Gmbh International | Surgical instrument assembly |
US11607239B2 (en) | 2016-04-15 | 2023-03-21 | Cilag Gmbh International | Systems and methods for controlling a surgical stapling and cutting instrument |
US11607219B2 (en) | 2019-12-19 | 2023-03-21 | Cilag Gmbh International | Staple cartridge comprising a detachable tissue cutting knife |
US11617577B2 (en) | 2020-10-29 | 2023-04-04 | Cilag Gmbh International | Surgical instrument comprising a sensor configured to sense whether an articulation drive of the surgical instrument is actuatable |
US11622763B2 (en) | 2013-04-16 | 2023-04-11 | Cilag Gmbh International | Stapling assembly comprising a shiftable drive |
US11627960B2 (en) | 2020-12-02 | 2023-04-18 | Cilag Gmbh International | Powered surgical instruments with smart reload with separately attachable exteriorly mounted wiring connections |
US11627959B2 (en) | 2019-06-28 | 2023-04-18 | Cilag Gmbh International | Surgical instruments including manual and powered system lockouts |
US11638582B2 (en) | 2020-07-28 | 2023-05-02 | Cilag Gmbh International | Surgical instruments with torsion spine drive arrangements |
US11638587B2 (en) | 2019-06-28 | 2023-05-02 | Cilag Gmbh International | RFID identification systems for surgical instruments |
US11648009B2 (en) | 2019-04-30 | 2023-05-16 | Cilag Gmbh International | Rotatable jaw tip for a surgical instrument |
US11648005B2 (en) | 2008-09-23 | 2023-05-16 | Cilag Gmbh International | Robotically-controlled motorized surgical instrument with an end effector |
US11653914B2 (en) | 2017-06-20 | 2023-05-23 | Cilag Gmbh International | Systems and methods for controlling motor velocity of a surgical stapling and cutting instrument according to articulation angle of end effector |
US11653920B2 (en) | 2020-12-02 | 2023-05-23 | Cilag Gmbh International | Powered surgical instruments with communication interfaces through sterile barrier |
US11653915B2 (en) | 2020-12-02 | 2023-05-23 | Cilag Gmbh International | Surgical instruments with sled location detection and adjustment features |
US11660163B2 (en) | 2019-06-28 | 2023-05-30 | Cilag Gmbh International | Surgical system with RFID tags for updating motor assembly parameters |
US11678882B2 (en) | 2020-12-02 | 2023-06-20 | Cilag Gmbh International | Surgical instruments with interactive features to remedy incidental sled movements |
US11678877B2 (en) | 2014-12-18 | 2023-06-20 | Cilag Gmbh International | Surgical instrument including a flexible support configured to support a flexible firing member |
US11684367B2 (en) | 2016-12-21 | 2023-06-27 | Cilag Gmbh International | Stepped assembly having and end-of-life indicator |
US11684434B2 (en) | 2019-06-28 | 2023-06-27 | Cilag Gmbh International | Surgical RFID assemblies for instrument operational setting control |
US11690619B2 (en) | 2016-06-24 | 2023-07-04 | Cilag Gmbh International | Staple cartridge comprising staples having different geometries |
US11696757B2 (en) | 2021-02-26 | 2023-07-11 | Cilag Gmbh International | Monitoring of internal systems to detect and track cartridge motion status |
US11696761B2 (en) | 2019-03-25 | 2023-07-11 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11697713B2 (en) | 2011-12-30 | 2023-07-11 | University Of Washington Through Its Center For Commercialization | Chromophoric polymer dots with narrow-band emission |
US11701111B2 (en) | 2019-12-19 | 2023-07-18 | Cilag Gmbh International | Method for operating a surgical stapling instrument |
US11701113B2 (en) | 2021-02-26 | 2023-07-18 | Cilag Gmbh International | Stapling instrument comprising a separate power antenna and a data transfer antenna |
US11717291B2 (en) | 2021-03-22 | 2023-08-08 | Cilag Gmbh International | Staple cartridge comprising staples configured to apply different tissue compression |
US11717294B2 (en) | 2014-04-16 | 2023-08-08 | Cilag Gmbh International | End effector arrangements comprising indicators |
US11717289B2 (en) | 2020-10-29 | 2023-08-08 | Cilag Gmbh International | Surgical instrument comprising an indicator which indicates that an articulation drive is actuatable |
US11723662B2 (en) | 2021-05-28 | 2023-08-15 | Cilag Gmbh International | Stapling instrument comprising an articulation control display |
US11723657B2 (en) | 2021-02-26 | 2023-08-15 | Cilag Gmbh International | Adjustable communication based on available bandwidth and power capacity |
US11723658B2 (en) | 2021-03-22 | 2023-08-15 | Cilag Gmbh International | Staple cartridge comprising a firing lockout |
US11730473B2 (en) | 2021-02-26 | 2023-08-22 | Cilag Gmbh International | Monitoring of manufacturing life-cycle |
US11737749B2 (en) | 2021-03-22 | 2023-08-29 | Cilag Gmbh International | Surgical stapling instrument comprising a retraction system |
US11737751B2 (en) | 2020-12-02 | 2023-08-29 | Cilag Gmbh International | Devices and methods of managing energy dissipated within sterile barriers of surgical instrument housings |
US11744581B2 (en) | 2020-12-02 | 2023-09-05 | Cilag Gmbh International | Powered surgical instruments with multi-phase tissue treatment |
US11744583B2 (en) | 2021-02-26 | 2023-09-05 | Cilag Gmbh International | Distal communication array to tune frequency of RF systems |
US11749877B2 (en) | 2021-02-26 | 2023-09-05 | Cilag Gmbh International | Stapling instrument comprising a signal antenna |
US11744603B2 (en) | 2021-03-24 | 2023-09-05 | Cilag Gmbh International | Multi-axis pivot joints for surgical instruments and methods for manufacturing same |
US11751869B2 (en) | 2021-02-26 | 2023-09-12 | Cilag Gmbh International | Monitoring of multiple sensors over time to detect moving characteristics of tissue |
US11759202B2 (en) | 2021-03-22 | 2023-09-19 | Cilag Gmbh International | Staple cartridge comprising an implantable layer |
US11766259B2 (en) | 2016-12-21 | 2023-09-26 | Cilag Gmbh International | Method of deforming staples from two different types of staple cartridges with the same surgical stapling instrument |
US11766260B2 (en) | 2016-12-21 | 2023-09-26 | Cilag Gmbh International | Methods of stapling tissue |
US11771419B2 (en) | 2019-06-28 | 2023-10-03 | Cilag Gmbh International | Packaging for a replaceable component of a surgical stapling system |
US11779330B2 (en) | 2020-10-29 | 2023-10-10 | Cilag Gmbh International | Surgical instrument comprising a jaw alignment system |
US11786239B2 (en) | 2021-03-24 | 2023-10-17 | Cilag Gmbh International | Surgical instrument articulation joint arrangements comprising multiple moving linkage features |
US11786243B2 (en) | 2021-03-24 | 2023-10-17 | Cilag Gmbh International | Firing members having flexible portions for adapting to a load during a surgical firing stroke |
US11793514B2 (en) | 2021-02-26 | 2023-10-24 | Cilag Gmbh International | Staple cartridge comprising sensor array which may be embedded in cartridge body |
US11793516B2 (en) | 2021-03-24 | 2023-10-24 | Cilag Gmbh International | Surgical staple cartridge comprising longitudinal support beam |
US11793518B2 (en) | 2006-01-31 | 2023-10-24 | Cilag Gmbh International | Powered surgical instruments with firing system lockout arrangements |
US11793522B2 (en) | 2015-09-30 | 2023-10-24 | Cilag Gmbh International | Staple cartridge assembly including a compressible adjunct |
US11806011B2 (en) | 2021-03-22 | 2023-11-07 | Cilag Gmbh International | Stapling instrument comprising tissue compression systems |
US11812964B2 (en) | 2021-02-26 | 2023-11-14 | Cilag Gmbh International | Staple cartridge comprising a power management circuit |
US11819849B2 (en) | 2007-02-06 | 2023-11-21 | Brandeis University | Manipulation of fluids and reactions in microfluidic systems |
US11826132B2 (en) | 2015-03-06 | 2023-11-28 | Cilag Gmbh International | Time dependent evaluation of sensor data to determine stability, creep, and viscoelastic elements of measures |
US11826048B2 (en) | 2017-06-28 | 2023-11-28 | Cilag Gmbh International | Surgical instrument comprising selectively actuatable rotatable couplers |
US11826012B2 (en) | 2021-03-22 | 2023-11-28 | Cilag Gmbh International | Stapling instrument comprising a pulsed motor-driven firing rack |
US11826042B2 (en) | 2021-03-22 | 2023-11-28 | Cilag Gmbh International | Surgical instrument comprising a firing drive including a selectable leverage mechanism |
US11832816B2 (en) | 2021-03-24 | 2023-12-05 | Cilag Gmbh International | Surgical stapling assembly comprising nonplanar staples and planar staples |
US11844518B2 (en) | 2020-10-29 | 2023-12-19 | Cilag Gmbh International | Method for operating a surgical instrument |
US11844520B2 (en) | 2019-12-19 | 2023-12-19 | Cilag Gmbh International | Staple cartridge comprising driver retention members |
US11849941B2 (en) | 2007-06-29 | 2023-12-26 | Cilag Gmbh International | Staple cartridge having staple cavities extending at a transverse angle relative to a longitudinal cartridge axis |
US11849944B2 (en) | 2021-03-24 | 2023-12-26 | Cilag Gmbh International | Drivers for fastener cartridge assemblies having rotary drive screws |
US11849943B2 (en) | 2020-12-02 | 2023-12-26 | Cilag Gmbh International | Surgical instrument with cartridge release mechanisms |
US11849945B2 (en) | 2021-03-24 | 2023-12-26 | Cilag Gmbh International | Rotary-driven surgical stapling assembly comprising eccentrically driven firing member |
US11849952B2 (en) | 2010-09-30 | 2023-12-26 | Cilag Gmbh International | Staple cartridge comprising staples positioned within a compressible portion thereof |
US11857183B2 (en) | 2021-03-24 | 2024-01-02 | Cilag Gmbh International | Stapling assembly components having metal substrates and plastic bodies |
US11877745B2 (en) | 2021-10-18 | 2024-01-23 | Cilag Gmbh International | Surgical stapling assembly having longitudinally-repeating staple leg clusters |
US11883026B2 (en) | 2014-04-16 | 2024-01-30 | Cilag Gmbh International | Fastener cartridge assemblies and staple retainer cover arrangements |
USD1013170S1 (en) | 2020-10-29 | 2024-01-30 | Cilag Gmbh International | Surgical instrument assembly |
US11890012B2 (en) | 2004-07-28 | 2024-02-06 | Cilag Gmbh International | Staple cartridge comprising cartridge body and attached support |
US11890010B2 (en) | 2020-12-02 | 2024-02-06 | Cllag GmbH International | Dual-sided reinforced reload for surgical instruments |
US11896218B2 (en) | 2021-03-24 | 2024-02-13 | Cilag Gmbh International | Method of using a powered stapling device |
US11896219B2 (en) | 2021-03-24 | 2024-02-13 | Cilag Gmbh International | Mating features between drivers and underside of a cartridge deck |
US11898193B2 (en) | 2011-07-20 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Manipulating droplet size |
US11896217B2 (en) | 2020-10-29 | 2024-02-13 | Cilag Gmbh International | Surgical instrument comprising an articulation lock |
US11903581B2 (en) | 2019-04-30 | 2024-02-20 | Cilag Gmbh International | Methods for stapling tissue using a surgical instrument |
US11903582B2 (en) | 2021-03-24 | 2024-02-20 | Cilag Gmbh International | Leveraging surfaces for cartridge installation |
US11911032B2 (en) | 2019-12-19 | 2024-02-27 | Cilag Gmbh International | Staple cartridge comprising a seating cam |
US11925349B2 (en) | 2021-02-26 | 2024-03-12 | Cilag Gmbh International | Adjustment to transfer parameters to improve available power |
US11931033B2 (en) | 2019-12-19 | 2024-03-19 | Cilag Gmbh International | Staple cartridge comprising a latch lockout |
US11931025B2 (en) | 2020-10-29 | 2024-03-19 | Cilag Gmbh International | Surgical instrument comprising a releasable closure drive lock |
US11937816B2 (en) | 2021-10-28 | 2024-03-26 | Cilag Gmbh International | Electrical lead arrangements for surgical instruments |
US11944296B2 (en) | 2020-12-02 | 2024-04-02 | Cilag Gmbh International | Powered surgical instruments with external connectors |
US11944338B2 (en) | 2015-03-06 | 2024-04-02 | Cilag Gmbh International | Multiple level thresholds to modify operation of powered surgical instruments |
US11944306B2 (en) | 2008-09-19 | 2024-04-02 | Cilag Gmbh International | Surgical stapler including a replaceable staple cartridge |
US11944300B2 (en) | 2017-08-03 | 2024-04-02 | Cilag Gmbh International | Method for operating a surgical system bailout |
US11944336B2 (en) | 2021-03-24 | 2024-04-02 | Cilag Gmbh International | Joint arrangements for multi-planar alignment and support of operational drive shafts in articulatable surgical instruments |
US11950777B2 (en) | 2021-02-26 | 2024-04-09 | Cilag Gmbh International | Staple cartridge comprising an information access control system |
US11950779B2 (en) | 2021-02-26 | 2024-04-09 | Cilag Gmbh International | Method of powering and communicating with a staple cartridge |
US11957795B2 (en) | 2021-12-13 | 2024-04-16 | Cilag Gmbh International | Tissue thickness compensator configured to redistribute compressive forces |
Families Citing this family (97)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040101822A1 (en) * | 2002-11-26 | 2004-05-27 | Ulrich Wiesner | Fluorescent silica-based nanoparticles |
GB0307403D0 (en) | 2003-03-31 | 2003-05-07 | Medical Res Council | Selection by compartmentalised screening |
GB0307428D0 (en) | 2003-03-31 | 2003-05-07 | Medical Res Council | Compartmentalised combinatorial chemistry |
US20060078893A1 (en) | 2004-10-12 | 2006-04-13 | Medical Research Council | Compartmentalised combinatorial chemistry by microfluidic control |
GB0400235D0 (en) * | 2004-01-07 | 2004-02-11 | Univ Sunderland | Nanoparticles as agents for imaging finger prints |
US20050221339A1 (en) | 2004-03-31 | 2005-10-06 | Medical Research Council Harvard University | Compartmentalised screening by microfluidic control |
US7968287B2 (en) | 2004-10-08 | 2011-06-28 | Medical Research Council Harvard University | In vitro evolution in microfluidic systems |
CA2598558C (en) * | 2005-02-14 | 2013-04-02 | Australian Nuclear Science & Technology Organisation | Layered nanoparticles |
CN102343098A (en) * | 2005-03-21 | 2012-02-08 | 加利福尼亚大学董事会 | Functionalized magnetic nanoparticles and methods of use thereof |
JP4774507B2 (en) * | 2005-03-22 | 2011-09-14 | 国立大学法人徳島大学 | Color material composition and colored or luminescent product containing the same |
CN100586482C (en) * | 2005-04-29 | 2010-02-03 | 同济大学 | Lymph dye with silicon dioxide microparticle as supporter and its preparation method |
JP2006328032A (en) * | 2005-05-30 | 2006-12-07 | Fujifilm Holdings Corp | Nucleic acid probe and method for fluorescence detection of multiple-stranded nucleic acid |
WO2007017700A1 (en) | 2005-08-09 | 2007-02-15 | University Of Sunderland | Hydrophobic silica particles and methods of making same |
JP4931015B2 (en) * | 2005-08-30 | 2012-05-16 | 学校法人東京電機大学 | Nanosilicon-containing dissolving tablet and method for producing the same |
EP1760467A1 (en) * | 2005-09-02 | 2007-03-07 | Schering AG | Optically fluorescent nanoparticles |
EP2363205A3 (en) | 2006-01-11 | 2014-06-04 | Raindance Technologies, Inc. | Microfluidic Devices And Methods Of Use In The Formation And Control Of Nanoreactors |
JP2007197382A (en) * | 2006-01-27 | 2007-08-09 | Konica Minolta Medical & Graphic Inc | Semiconductor nanoparticle |
US9562837B2 (en) | 2006-05-11 | 2017-02-07 | Raindance Technologies, Inc. | Systems for handling microfludic droplets |
WO2008021123A1 (en) | 2006-08-07 | 2008-02-21 | President And Fellows Of Harvard College | Fluorocarbon emulsion stabilizing surfactants |
FR2910632B1 (en) * | 2006-12-22 | 2010-08-27 | Commissariat Energie Atomique | OPTICAL PLASMON ENCODING DEVICE AND AUTHENTICATION METHOD EMPLOYING THE SAME |
WO2008138727A1 (en) * | 2007-05-11 | 2008-11-20 | Basf Se | Functionalized nanoparticles |
KR100845010B1 (en) * | 2007-08-29 | 2008-07-08 | 한국생명공학연구원 | Polymer particles for nir/mr bimodal molecular imaging and method for preparing thereof |
WO2009032994A2 (en) * | 2007-09-06 | 2009-03-12 | Emory University | Silica-based nanoparticles and methods of stimulating bone formation and suppressing bone resorption through modulation of nf-kb |
CN101343538B (en) * | 2008-08-25 | 2011-03-23 | 华东理工大学 | Fluorescence silica gel particle and uses thereof |
JP5419199B2 (en) * | 2008-12-08 | 2014-02-19 | 積水化学工業株式会社 | Magnetic inclusion particles, method for producing magnetic inclusion particles, immunoassay particles, and immunochromatography method |
CN102257098A (en) * | 2008-12-25 | 2011-11-23 | 日本板硝子株式会社 | Fluorescent dye-containing particles and manufacturing method thereof |
CN101463252B (en) * | 2009-01-08 | 2012-01-04 | 东南大学 | Preparation of dye doped silicon dioxide fluorescent nanoparticle |
EP3415235A1 (en) | 2009-03-23 | 2018-12-19 | Raindance Technologies Inc. | Manipulation of microfluidic droplets |
WO2010121066A2 (en) * | 2009-04-15 | 2010-10-21 | Cornell Research Foundation, Inc. | Silica nanoparticles incorporating chemiluminescent and absorbing active molecules |
DE102009019411A1 (en) | 2009-04-29 | 2010-11-04 | Bayer Technology Services Gmbh | Process for the UV stabilization of organic substances |
DE102009024685A1 (en) | 2009-06-12 | 2010-12-16 | Gmbu E.V., Fachsektion Dresden | Luminescent composite particle, useful e.g. as marking agent in polymeric films and articles for forgery-proof product identification, comprises organic optical brightener, which is homogeneously embedded in microspherical inorganic oxide |
JP5620154B2 (en) * | 2009-10-15 | 2014-11-05 | 公益財団法人神奈川科学技術アカデミー | Hollow micro object and method for producing the same |
EP2517025B1 (en) | 2009-12-23 | 2019-11-27 | Bio-Rad Laboratories, Inc. | Methods for reducing the exchange of molecules between droplets |
US10351905B2 (en) | 2010-02-12 | 2019-07-16 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
US9366632B2 (en) | 2010-02-12 | 2016-06-14 | Raindance Technologies, Inc. | Digital analyte analysis |
EP2542643A4 (en) * | 2010-03-01 | 2013-08-28 | Univ Florida | Near-ir indocyanine green doped multimodal silica nanoparticles and methods for making the same |
IT1399551B1 (en) | 2010-04-13 | 2013-04-19 | Univ Palermo | NANO SILICATE NANO-EMITTERS FOR IN-VIVO APPLICATIONS AND RELATIVE PRODUCTION PROCESS. |
KR101218204B1 (en) * | 2010-07-09 | 2013-01-03 | 한국과학기술원 | Fluorescence hollow silica nanoparticle and preparation method thereof |
CN101993693B (en) * | 2010-09-28 | 2013-08-07 | 华东理工大学 | Preparation method of mesoporous silica fluorescent nanoparticles for pH ratio probes |
US9562897B2 (en) | 2010-09-30 | 2017-02-07 | Raindance Technologies, Inc. | Sandwich assays in droplets |
US9525092B2 (en) | 2010-11-05 | 2016-12-20 | Pacific Light Technologies Corp. | Solar module employing quantum luminescent lateral transfer concentrator |
EP2646818A4 (en) * | 2010-11-30 | 2016-09-21 | Univ Illinois | Silica nanoparticle agent conjugates |
US9364803B2 (en) | 2011-02-11 | 2016-06-14 | Raindance Technologies, Inc. | Methods for forming mixed droplets |
CA2831278C (en) * | 2011-03-25 | 2020-01-21 | TAS Project Co. Ltd. | Method for quantitatively detecting 8-oxo 2'-deoxyguanosine in aqueous sample solution with high sensitivity |
JP5367915B2 (en) * | 2011-04-26 | 2013-12-11 | 古河電気工業株式会社 | Method for producing functional molecule-containing silica nanoparticles bonded with biomolecules |
CN102320612A (en) * | 2011-05-26 | 2012-01-18 | 东北师范大学 | Preparation method and application of fluorescence mesoporous silica nano-particle |
US8841071B2 (en) | 2011-06-02 | 2014-09-23 | Raindance Technologies, Inc. | Sample multiplexing |
US20120323112A1 (en) * | 2011-06-17 | 2012-12-20 | The Board Of Trustees Of The Leland Stanford Junior University | Nanoparticles for accoustic imaging, methods of making, and methods of accoustic imaging |
WO2013020714A2 (en) * | 2011-08-11 | 2013-02-14 | Qiagen Gmbh | Cell- or virus simulating means comprising encapsulated marker molecules |
GB201117675D0 (en) | 2011-10-13 | 2011-11-23 | Univ St Andrews | Nanocolloids for local temperature monitoring |
US9159872B2 (en) | 2011-11-09 | 2015-10-13 | Pacific Light Technologies Corp. | Semiconductor structure having nanocrystalline core and nanocrystalline shell |
US20130112942A1 (en) | 2011-11-09 | 2013-05-09 | Juanita Kurtin | Composite having semiconductor structures embedded in a matrix |
CN104703625B (en) * | 2012-06-22 | 2017-08-29 | 康奈尔大学 | Mesopore oxide nano particle and preparation and use its method |
ITBO20120444A1 (en) | 2012-08-10 | 2014-02-11 | R D Pharmadvice S R L | METHOD FOR THE PRODUCTION OF THERMOCHEMALUMINESCENT SILICA NANOPARTICLES AND THEIR USE AS MARKERS IN BIOANALYTICAL METHODS |
US9425365B2 (en) | 2012-08-20 | 2016-08-23 | Pacific Light Technologies Corp. | Lighting device having highly luminescent quantum dots |
KR101445596B1 (en) * | 2012-09-27 | 2014-10-07 | 단국대학교 산학협력단 | Measurement method and measurement kit of antibiotics concentration |
US8889457B2 (en) | 2012-12-13 | 2014-11-18 | Pacific Light Technologies Corp. | Composition having dispersion of nano-particles therein and methods of fabricating same |
US11366061B2 (en) | 2013-01-24 | 2022-06-21 | Grace Bio-Labs, Inc. | Protein microarray assay imager |
US9119875B2 (en) | 2013-03-14 | 2015-09-01 | International Business Machines Corporation | Matrix incorporated fluorescent porous and non-porous silica particles for medical imaging |
US9371237B2 (en) | 2013-04-22 | 2016-06-21 | American Talc Company | Methods and systems for controlled conversion of minerals to pigmenting elements |
EP3730929A1 (en) | 2013-08-19 | 2020-10-28 | University Of Houston | Phosphorescent reporters |
JP6080164B2 (en) * | 2013-10-02 | 2017-02-15 | 古河電気工業株式会社 | Fluorescently labeled particles |
US11901041B2 (en) | 2013-10-04 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Digital analysis of nucleic acid modification |
US11193176B2 (en) | 2013-12-31 | 2021-12-07 | Bio-Rad Laboratories, Inc. | Method for detecting and quantifying latent retroviral RNA species |
WO2015160794A1 (en) * | 2014-04-14 | 2015-10-22 | Ecosynthetix Ltd. | Bio-based nanoparticle and composite materials derived therefrom |
WO2015168439A1 (en) | 2014-04-30 | 2015-11-05 | Nitto Denko Corporation | Inorganic oxide coated fluorescent chromophores for use in highly photostable wavelength conversion films |
WO2016012433A1 (en) * | 2014-07-22 | 2016-01-28 | Koninklijke Philips N.V. | Siloxane ligands to be used for dispersing quantum dots in silicone hosts to obtain color converters for led lighting |
BR112017012621A2 (en) | 2014-12-15 | 2018-01-02 | Univ Cornell | cyclic peptides with enhanced nerve binding selectivity, nanoparticles bound with said cyclic peptides, and their use for real time in vivo nerve tissue imaging |
CN106281305A (en) * | 2015-06-10 | 2017-01-04 | 南开大学 | A kind of life-span adjustable fluorescence nano core-shell material and preparation method thereof |
KR101938284B1 (en) * | 2015-06-15 | 2019-01-15 | 주식회사 엘지화학 | Fluorescent complex, light conversion film, light conversioni device and display appratus comprising the same |
US9716211B2 (en) * | 2015-07-22 | 2017-07-25 | Sharp Kabushiki Kaisha | Semiconductor phosphor nanoparticle, semiconductor phosphor nanoparticle-containing glass, light emitting device, and light emitting element |
US10647981B1 (en) | 2015-09-08 | 2020-05-12 | Bio-Rad Laboratories, Inc. | Nucleic acid library generation methods and compositions |
KR20180081743A (en) * | 2015-11-11 | 2018-07-17 | 다우 글로벌 테크놀로지스 엘엘씨 | Luminescent nanoparticles and method for producing the same |
JP2017155069A (en) * | 2016-02-29 | 2017-09-07 | 古河電気工業株式会社 | Silica nanoparticles, manufacturing method of silica nanoparticles, fluid dispersion of silica nanoparticles |
AU2017258415B2 (en) | 2016-04-29 | 2023-03-30 | Cornell University | Compositions and methods for targeted particle penetration, distribution, and response in malignant brain tumors |
US11365333B2 (en) | 2016-05-09 | 2022-06-21 | The Trustees Of The University Of Pennsylvania | Omni-transparent and superhydrophobic coatings assembled from chain-like nanoparticles |
CN105999296B (en) * | 2016-06-07 | 2019-02-05 | 上海纳米技术及应用国家工程研究中心有限公司 | A kind of preparation method of across the blood-brain barrier film fluorescent silicon dioxide nano particle of different-grain diameter |
EP3469601B1 (en) * | 2016-06-14 | 2021-12-08 | University of Washington | Polymer-silica hybrid pdots |
EP3481272A4 (en) | 2016-07-07 | 2020-03-11 | Memorial Sloan Kettering Cancer Center | Imaging systems and methods for particle-driven, knowledge-based, and predictive cancer radiogenomics |
CA3045007A1 (en) | 2016-11-30 | 2018-06-07 | Memorial Sloan Kettering Cancer Center | Inhibitor-functionalized ultrasmall nanoparticles and methods thereof |
CN106596482B (en) * | 2016-12-08 | 2019-04-30 | 哈尔滨师范大学 | Fluorescence silicon nano particles and its application in mercury ion detecting and fingerprint manifestation |
US20200155710A1 (en) * | 2017-04-10 | 2020-05-21 | Cornell University | Sulfur- or heavy atom-containing nanoparticles, methods of making same, and uses thereof |
US20210145985A1 (en) | 2017-06-23 | 2021-05-20 | Memorial Sloan Kettering Cancer Center | Method of imaging in vivo tissues using nanoparticles comprising a reference dye and a sensor dye |
US10729501B2 (en) | 2017-09-29 | 2020-08-04 | Ethicon Llc | Systems and methods for language selection of a surgical instrument |
CN107871677B (en) * | 2017-10-31 | 2020-08-25 | 合肥京东方光电科技有限公司 | Display panel, packaging monitoring device and packaging monitoring method thereof |
US20200383943A1 (en) | 2017-12-04 | 2020-12-10 | Memorial Sloan Kettering Cancer Center | Methods of cancer treatment via regulated ferroptosis |
KR20200122369A (en) * | 2018-02-20 | 2020-10-27 | 가부시키가이샤 큐럭스 | Method for producing luminescent particles, luminescent particles and bio-imaging materials |
US11045555B2 (en) * | 2018-04-20 | 2021-06-29 | The Regents Of The University Of California | Pathogen-specific cargo delivery and diagnostic platform based on mesoporous silica nanoparticles |
WO2019213456A1 (en) * | 2018-05-02 | 2019-11-07 | Cornell University | Ultrasmall nanoparticles and methods of making, using and analyzing same |
EP3787684A1 (en) | 2018-05-02 | 2021-03-10 | Memorial Sloan Kettering Cancer Center | Nanotherapeutic systems and methods using particle-driven photodynamic therapy (pdt) |
US11666411B2 (en) | 2018-05-10 | 2023-06-06 | Memorial Sloan Kettering Cancer Center | Systems for augmented reality surgical and clinical visualization |
CN108715833B (en) * | 2018-06-01 | 2021-09-14 | 天晴干细胞股份有限公司 | Preparation method of microsphere loaded with platelet lysate |
US11320738B2 (en) * | 2018-06-27 | 2022-05-03 | Taiwan Semiconductor Manufacturing Co., Ltd. | Pattern formation method and material for manufacturing semiconductor devices |
CN110760301A (en) * | 2018-07-26 | 2020-02-07 | 合皓股份有限公司 | Siloxane organic fluorescent powder and preparation method thereof |
US20220229065A1 (en) * | 2019-05-24 | 2022-07-21 | Bambu Vault Llc | Sensors and methods for rapid microbial detection |
CN110530832B (en) * | 2019-08-26 | 2022-09-27 | 河南师范大学 | Method for selectively determining 2, 4-dinitrophenol in surface water sample based on fluorescence analysis |
WO2022093793A1 (en) | 2020-10-27 | 2022-05-05 | Elucida Oncology, Inc. | Folate receptor targeted nanoparticle drug conjugates and uses thereof |
Citations (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4279617A (en) * | 1979-02-26 | 1981-07-21 | Technicon Instruments Corporation | Iummunoassay involving agglutination |
US4774339A (en) * | 1987-08-10 | 1988-09-27 | Molecular Probes, Inc. | Chemically reactive dipyrrometheneboron difluoride dyes |
US4810636A (en) * | 1986-12-09 | 1989-03-07 | Miles Inc. | Chromogenic acridinone enzyme substrates |
US4812409A (en) * | 1986-01-31 | 1989-03-14 | Eastman Kodak Company | Hydrolyzable fluorescent substrates and analytical determinations using same |
US5187288A (en) * | 1991-05-22 | 1993-02-16 | Molecular Probes, Inc. | Ethenyl-substituted dipyrrometheneboron difluoride dyes and their synthesis |
US5248782A (en) * | 1990-12-18 | 1993-09-28 | Molecular Probes, Inc. | Long wavelength heteroaryl-substituted dipyrrometheneboron difluoride dyes |
US5260957A (en) * | 1992-10-29 | 1993-11-09 | The Charles Stark Draper Laboratory, Inc. | Quantum dot Laser |
US5274113A (en) * | 1991-11-01 | 1993-12-28 | Molecular Probes, Inc. | Long wavelength chemically reactive dipyrrometheneboron difluoride dyes and conjugates |
US5405752A (en) * | 1988-10-03 | 1995-04-11 | Nilsson; Kurt G. I. | Enzyme conjugate prepared with insoluble nonoparticle |
US5433896A (en) * | 1994-05-20 | 1995-07-18 | Molecular Probes, Inc. | Dibenzopyrrometheneboron difluoride dyes |
US5639603A (en) * | 1991-09-18 | 1997-06-17 | Affymax Technologies N.V. | Synthesizing and screening molecular diversity |
US5753517A (en) * | 1996-03-29 | 1998-05-19 | University Of British Columbia | Quantitative immunochromatographic assays |
US5830912A (en) * | 1996-11-15 | 1998-11-03 | Molecular Probes, Inc. | Derivatives of 6,8-difluoro-7-hydroxycoumarin |
US5981180A (en) * | 1995-10-11 | 1999-11-09 | Luminex Corporation | Multiplexed analysis of clinical specimens apparatus and methods |
US5990479A (en) * | 1997-11-25 | 1999-11-23 | Regents Of The University Of California | Organo Luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes |
US6132773A (en) * | 1996-04-22 | 2000-10-17 | Rhodia Chimie | Method for preparing particles comprising a core and a silica shell |
US6180415B1 (en) * | 1997-02-20 | 2001-01-30 | The Regents Of The University Of California | Plasmon resonant particles, methods and apparatus |
US6207392B1 (en) * | 1997-11-25 | 2001-03-27 | The Regents Of The University Of California | Semiconductor nanocrystal probes for biological applications and process for making and using such probes |
US6251303B1 (en) * | 1998-09-18 | 2001-06-26 | Massachusetts Institute Of Technology | Water-soluble fluorescent nanocrystals |
US6268222B1 (en) * | 1998-01-22 | 2001-07-31 | Luminex Corporation | Microparticles attached to nanoparticles labeled with flourescent dye |
US6274323B1 (en) * | 1999-05-07 | 2001-08-14 | Quantum Dot Corporation | Method of detecting an analyte in a sample using semiconductor nanocrystals as a detectable label |
US6306610B1 (en) * | 1998-09-18 | 2001-10-23 | Massachusetts Institute Of Technology | Biological applications of quantum dots |
US6322901B1 (en) * | 1997-11-13 | 2001-11-27 | Massachusetts Institute Of Technology | Highly luminescent color-selective nano-crystalline materials |
US6326144B1 (en) * | 1998-09-18 | 2001-12-04 | Massachusetts Institute Of Technology | Biological applications of quantum dots |
US6344272B1 (en) * | 1997-03-12 | 2002-02-05 | Wm. Marsh Rice University | Metal nanoshells |
US6426513B1 (en) * | 1998-09-18 | 2002-07-30 | Massachusetts Institute Of Technology | Water-soluble thiol-capped nanocrystals |
US6428811B1 (en) * | 1998-03-11 | 2002-08-06 | Wm. Marsh Rice University | Temperature-sensitive polymer/nanoshell composites for photothermally modulated drug delivery |
US6454789B1 (en) * | 1999-01-15 | 2002-09-24 | Light Science Corporation | Patient portable device for photodynamic therapy |
US6479146B1 (en) * | 1998-03-19 | 2002-11-12 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften, E.V. | Fabrication of multilayer-coated particles and hollow shells via electrostatic self-assembly of nanocomposite multilayers on decomposable colloidal templates |
US6500622B2 (en) * | 2000-03-22 | 2002-12-31 | Quantum Dot Corporation | Methods of using semiconductor nanocrystals in bead-based nucleic acid assays |
US20030017264A1 (en) * | 2001-07-20 | 2003-01-23 | Treadway Joseph A. | Luminescent nanoparticles and methods for their preparation |
US6548264B1 (en) * | 2000-05-17 | 2003-04-15 | University Of Florida | Coated nanoparticles |
US6576219B2 (en) * | 1994-12-09 | 2003-06-10 | The Regents Of The University Of California | Method for enhancing outflow of aqueous humor in treatment of glaucoma |
US20030124564A1 (en) * | 2001-06-29 | 2003-07-03 | Mathias Trau | Synthesis and use of organosilica particles |
US6649138B2 (en) * | 2000-10-13 | 2003-11-18 | Quantum Dot Corporation | Surface-modified semiconductive and metallic nanoparticles having enhanced dispersibility in aqueous media |
Family Cites Families (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3870791A (en) | 1972-04-24 | 1975-03-11 | Heskel M Haddad | Solid state ophthalmic medication delivery method |
US3867519A (en) | 1972-04-27 | 1975-02-18 | Alza Corp | Bioerodible drug delivery device |
US4051842A (en) | 1975-09-15 | 1977-10-04 | International Medical Corporation | Electrode and interfacing pad for electrical physiological systems |
DE2626348C3 (en) | 1976-06-11 | 1980-01-31 | Siemens Ag, 1000 Berlin Und 8000 Muenchen | Implantable dosing device |
US4136177A (en) | 1977-01-31 | 1979-01-23 | American Home Products Corp. | Xanthan gum therapeutic compositions |
US4255415A (en) | 1978-11-22 | 1981-03-10 | Schering Corporation | Polyvinyl alcohol ophthalmic gel |
US4383529A (en) | 1980-11-03 | 1983-05-17 | Wescor, Inc. | Iontophoretic electrode device, method and gel insert |
US4918200A (en) * | 1984-07-16 | 1990-04-17 | Huls America Inc. | Chromogenic and fluorogenic silanes and using the same |
US4665024A (en) | 1984-10-01 | 1987-05-12 | Becton, Dickinson And Company | Fluorescent gram stain |
US4668506A (en) | 1985-08-16 | 1987-05-26 | Bausch & Lomb Incorporated | Sustained-release formulation containing and amino acid polymer |
US4931279A (en) | 1985-08-16 | 1990-06-05 | Bausch & Lomb Incorporated | Sustained release formulation containing an ion-exchange resin |
US4788603A (en) | 1985-10-19 | 1988-11-29 | Fuji Photo Film Co., Ltd. | Camera for sequentially photographing a subject using a reference optical system and a telescopic optical system |
US4810639A (en) * | 1985-12-20 | 1989-03-07 | E. I. Du Pont De Nemours And Company | Immunoassay for CK-MB using bound and soluble antibodies |
US4713224A (en) | 1986-03-31 | 1987-12-15 | The Boc Group, Inc. | One-step process for purifying an inert gas |
AU2348092A (en) | 1991-07-16 | 1993-02-23 | Transmed Biotech Incorporated | Methods and compositions for simultaneous analysis of multiple analytes |
DE69519384T2 (en) | 1994-09-29 | 2001-05-23 | British Telecomm | Optical fiber with quantum dots |
US6361944B1 (en) | 1996-07-29 | 2002-03-26 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
US6451044B1 (en) | 1996-09-20 | 2002-09-17 | Board Of Regents, The University Of Texas System | Method and apparatus for heating inflammed tissue |
US6480746B1 (en) | 1997-08-13 | 2002-11-12 | Surx, Inc. | Noninvasive devices, methods, and systems for shrinking of tissues |
US5795158A (en) | 1996-12-02 | 1998-08-18 | Warinner; Peter | Apparatus to review clinical microbiology |
US5968820A (en) | 1997-02-26 | 1999-10-19 | The Cleveland Clinic Foundation | Method for magnetically separating cells into fractionated flow streams |
US6221586B1 (en) | 1997-04-09 | 2001-04-24 | California Institute Of Technology | Electrochemical sensor using intercalative, redox-active moieties |
US6082205A (en) | 1998-02-06 | 2000-07-04 | Ohio State University | System and device for determining particle characteristics |
US6501091B1 (en) * | 1998-04-01 | 2002-12-31 | Massachusetts Institute Of Technology | Quantum dot white and colored light emitting diodes |
AUPP737298A0 (en) * | 1998-11-30 | 1998-12-24 | University Of Queensland, The | Combinatorial libraries |
GB9910155D0 (en) * | 1999-04-30 | 1999-06-30 | Microbiological Research Agenc | Augmented agglutination assay |
US6686188B2 (en) * | 2000-05-26 | 2004-02-03 | Amersham Plc | Polynucleotide encoding a human myosin-like polypeptide expressed predominantly in heart and muscle |
JPWO2003060037A1 (en) * | 2001-12-27 | 2005-05-19 | 株式会社テクノネットワーク四国 | Silica spheres containing fluorescent dye molecules |
JP2003270154A (en) * | 2001-12-27 | 2003-09-25 | Techno Network Shikoku Co Ltd | Fluorescent dye molecule-containing silica ball |
US20040101822A1 (en) * | 2002-11-26 | 2004-05-27 | Ulrich Wiesner | Fluorescent silica-based nanoparticles |
-
2002
- 2002-11-26 US US10/306,614 patent/US20040101822A1/en not_active Abandoned
-
2003
- 2003-11-26 CN CNA200380109241XA patent/CN1742094A/en active Pending
- 2003-11-26 JP JP2004566499A patent/JP4965804B2/en not_active Expired - Lifetime
- 2003-11-26 JP JP2004568576A patent/JP2006514708A/en active Pending
- 2003-11-26 EP EP20110162895 patent/EP2364840A1/en not_active Ceased
- 2003-11-26 EP EP03815190.8A patent/EP1604031B1/en not_active Expired - Lifetime
- 2003-11-26 AU AU2003303309A patent/AU2003303309B2/en not_active Ceased
- 2003-11-26 WO PCT/US2003/037793 patent/WO2004063387A2/en active Application Filing
- 2003-11-26 KR KR1020057009511A patent/KR20050103186A/en not_active Application Discontinuation
- 2003-11-26 ES ES11156074T patent/ES2753144T3/en not_active Expired - Lifetime
- 2003-11-26 CN CNB2003801092528A patent/CN100443295C/en not_active Expired - Fee Related
- 2003-11-26 US US10/536,569 patent/US8298677B2/en active Active
- 2003-11-26 WO PCT/US2003/037963 patent/WO2004074504A2/en active Application Filing
- 2003-11-26 ES ES03815995T patent/ES2709398T3/en not_active Expired - Lifetime
- 2003-11-26 EP EP03815995.0A patent/EP1572445B1/en not_active Expired - Lifetime
- 2003-11-26 CN CNA200810170588XA patent/CN101387639A/en active Pending
- 2003-11-26 AU AU2003303290A patent/AU2003303290A1/en not_active Abandoned
- 2003-11-26 EP EP11156074.4A patent/EP2369342B1/en not_active Expired - Lifetime
- 2003-11-26 KR KR1020057009530A patent/KR20050109455A/en not_active Application Discontinuation
-
2009
- 2009-10-14 US US12/579,302 patent/US8409876B2/en not_active Expired - Fee Related
- 2009-12-16 JP JP2009285153A patent/JP2010070768A/en active Pending
-
2010
- 2010-11-25 JP JP2010262238A patent/JP2011052228A/en active Pending
-
2014
- 2014-02-10 JP JP2014023357A patent/JP2014133893A/en active Pending
Patent Citations (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4279617A (en) * | 1979-02-26 | 1981-07-21 | Technicon Instruments Corporation | Iummunoassay involving agglutination |
US4812409A (en) * | 1986-01-31 | 1989-03-14 | Eastman Kodak Company | Hydrolyzable fluorescent substrates and analytical determinations using same |
US4810636A (en) * | 1986-12-09 | 1989-03-07 | Miles Inc. | Chromogenic acridinone enzyme substrates |
US4774339A (en) * | 1987-08-10 | 1988-09-27 | Molecular Probes, Inc. | Chemically reactive dipyrrometheneboron difluoride dyes |
US5405752A (en) * | 1988-10-03 | 1995-04-11 | Nilsson; Kurt G. I. | Enzyme conjugate prepared with insoluble nonoparticle |
US5248782A (en) * | 1990-12-18 | 1993-09-28 | Molecular Probes, Inc. | Long wavelength heteroaryl-substituted dipyrrometheneboron difluoride dyes |
US5187288A (en) * | 1991-05-22 | 1993-02-16 | Molecular Probes, Inc. | Ethenyl-substituted dipyrrometheneboron difluoride dyes and their synthesis |
US5639603A (en) * | 1991-09-18 | 1997-06-17 | Affymax Technologies N.V. | Synthesizing and screening molecular diversity |
US5274113A (en) * | 1991-11-01 | 1993-12-28 | Molecular Probes, Inc. | Long wavelength chemically reactive dipyrrometheneboron difluoride dyes and conjugates |
US5260957A (en) * | 1992-10-29 | 1993-11-09 | The Charles Stark Draper Laboratory, Inc. | Quantum dot Laser |
US5433896A (en) * | 1994-05-20 | 1995-07-18 | Molecular Probes, Inc. | Dibenzopyrrometheneboron difluoride dyes |
US6576219B2 (en) * | 1994-12-09 | 2003-06-10 | The Regents Of The University Of California | Method for enhancing outflow of aqueous humor in treatment of glaucoma |
US5981180A (en) * | 1995-10-11 | 1999-11-09 | Luminex Corporation | Multiplexed analysis of clinical specimens apparatus and methods |
US5753517A (en) * | 1996-03-29 | 1998-05-19 | University Of British Columbia | Quantitative immunochromatographic assays |
US6132773A (en) * | 1996-04-22 | 2000-10-17 | Rhodia Chimie | Method for preparing particles comprising a core and a silica shell |
US5830912A (en) * | 1996-11-15 | 1998-11-03 | Molecular Probes, Inc. | Derivatives of 6,8-difluoro-7-hydroxycoumarin |
US6180415B1 (en) * | 1997-02-20 | 2001-01-30 | The Regents Of The University Of California | Plasmon resonant particles, methods and apparatus |
US6344272B1 (en) * | 1997-03-12 | 2002-02-05 | Wm. Marsh Rice University | Metal nanoshells |
US6322901B1 (en) * | 1997-11-13 | 2001-11-27 | Massachusetts Institute Of Technology | Highly luminescent color-selective nano-crystalline materials |
US6207392B1 (en) * | 1997-11-25 | 2001-03-27 | The Regents Of The University Of California | Semiconductor nanocrystal probes for biological applications and process for making and using such probes |
US5990479A (en) * | 1997-11-25 | 1999-11-23 | Regents Of The University Of California | Organo Luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes |
US6423551B1 (en) * | 1997-11-25 | 2002-07-23 | The Regents Of The University Of California | Organo luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes |
US6268222B1 (en) * | 1998-01-22 | 2001-07-31 | Luminex Corporation | Microparticles attached to nanoparticles labeled with flourescent dye |
US6428811B1 (en) * | 1998-03-11 | 2002-08-06 | Wm. Marsh Rice University | Temperature-sensitive polymer/nanoshell composites for photothermally modulated drug delivery |
US6479146B1 (en) * | 1998-03-19 | 2002-11-12 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften, E.V. | Fabrication of multilayer-coated particles and hollow shells via electrostatic self-assembly of nanocomposite multilayers on decomposable colloidal templates |
US6251303B1 (en) * | 1998-09-18 | 2001-06-26 | Massachusetts Institute Of Technology | Water-soluble fluorescent nanocrystals |
US6326144B1 (en) * | 1998-09-18 | 2001-12-04 | Massachusetts Institute Of Technology | Biological applications of quantum dots |
US6426513B1 (en) * | 1998-09-18 | 2002-07-30 | Massachusetts Institute Of Technology | Water-soluble thiol-capped nanocrystals |
US6319426B1 (en) * | 1998-09-18 | 2001-11-20 | Massachusetts Institute Of Technology | Water-soluble fluorescent semiconductor nanocrystals |
US6444143B2 (en) * | 1998-09-18 | 2002-09-03 | Massachusetts Institute Of Technology | Water-soluble fluorescent nanocrystals |
US6306610B1 (en) * | 1998-09-18 | 2001-10-23 | Massachusetts Institute Of Technology | Biological applications of quantum dots |
US6454789B1 (en) * | 1999-01-15 | 2002-09-24 | Light Science Corporation | Patient portable device for photodynamic therapy |
US6274323B1 (en) * | 1999-05-07 | 2001-08-14 | Quantum Dot Corporation | Method of detecting an analyte in a sample using semiconductor nanocrystals as a detectable label |
US6500622B2 (en) * | 2000-03-22 | 2002-12-31 | Quantum Dot Corporation | Methods of using semiconductor nanocrystals in bead-based nucleic acid assays |
US6548264B1 (en) * | 2000-05-17 | 2003-04-15 | University Of Florida | Coated nanoparticles |
US6649138B2 (en) * | 2000-10-13 | 2003-11-18 | Quantum Dot Corporation | Surface-modified semiconductive and metallic nanoparticles having enhanced dispersibility in aqueous media |
US20030124564A1 (en) * | 2001-06-29 | 2003-07-03 | Mathias Trau | Synthesis and use of organosilica particles |
US20030017264A1 (en) * | 2001-07-20 | 2003-01-23 | Treadway Joseph A. | Luminescent nanoparticles and methods for their preparation |
Cited By (1597)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070051674A1 (en) * | 2000-02-04 | 2007-03-08 | Bratten Jack R | Lift station and method |
US11187702B2 (en) | 2003-03-14 | 2021-11-30 | Bio-Rad Laboratories, Inc. | Enzyme quantification |
US20050025820A1 (en) * | 2003-04-25 | 2005-02-03 | Mark Kester | Method and system for systemic delivery of growth arresting, lipid-derived bioactive compounds |
US9028863B2 (en) * | 2003-04-25 | 2015-05-12 | The Penn State Research Foundation | Method and system for systemic delivery of growth arresting, lipid-derived bioactive compounds |
US9326953B2 (en) | 2003-04-25 | 2016-05-03 | The Penn State Research Foundation | Method and system for systemic delivery of growth arresting, lipid-derived bioactive compounds |
US8783541B2 (en) | 2003-05-20 | 2014-07-22 | Frederick E. Shelton, IV | Robotically-controlled surgical end effector system |
US9060770B2 (en) | 2003-05-20 | 2015-06-23 | Ethicon Endo-Surgery, Inc. | Robotically-driven surgical instrument with E-beam driver |
US10203326B2 (en) | 2003-10-02 | 2019-02-12 | Furukawa Electric Co., Ltd. | Method of detecting target substance |
FR2873021A1 (en) * | 2004-07-16 | 2006-01-20 | Oreal | Cosmetic composition, used as a make-up and/or skin care (particularly face, lips and/or keratinous fibers) product, comprises a photo luminescent mineral nanoparticles in a medium |
WO2006011014A1 (en) * | 2004-07-16 | 2006-02-02 | L'oreal | Cosmetic composition containing photoluminescent particles |
US10687817B2 (en) | 2004-07-28 | 2020-06-23 | Ethicon Llc | Stapling device comprising a firing member lockout |
US10716563B2 (en) | 2004-07-28 | 2020-07-21 | Ethicon Llc | Stapling system comprising an instrument assembly including a lockout |
US9737302B2 (en) | 2004-07-28 | 2017-08-22 | Ethicon Llc | Surgical stapling instrument having a restraining member |
US10799240B2 (en) | 2004-07-28 | 2020-10-13 | Ethicon Llc | Surgical instrument comprising a staple firing lockout |
US10314590B2 (en) | 2004-07-28 | 2019-06-11 | Ethicon Llc | Articulating surgical stapling instrument incorporating a two-piece e-beam firing mechanism |
US11135352B2 (en) | 2004-07-28 | 2021-10-05 | Cilag Gmbh International | End effector including a gradually releasable medical adjunct |
US11116502B2 (en) | 2004-07-28 | 2021-09-14 | Cilag Gmbh International | Surgical stapling instrument incorporating a two-piece firing mechanism |
US10292707B2 (en) | 2004-07-28 | 2019-05-21 | Ethicon Llc | Articulating surgical stapling instrument incorporating a firing mechanism |
US10568629B2 (en) | 2004-07-28 | 2020-02-25 | Ethicon Llc | Articulating surgical stapling instrument |
US9737303B2 (en) | 2004-07-28 | 2017-08-22 | Ethicon Llc | Articulating surgical stapling instrument incorporating a two-piece E-beam firing mechanism |
US10485547B2 (en) | 2004-07-28 | 2019-11-26 | Ethicon Llc | Surgical staple cartridges |
US9585663B2 (en) | 2004-07-28 | 2017-03-07 | Ethicon Endo-Surgery, Llc | Surgical stapling instrument configured to apply a compressive pressure to tissue |
US9282966B2 (en) | 2004-07-28 | 2016-03-15 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument |
US11083456B2 (en) | 2004-07-28 | 2021-08-10 | Cilag Gmbh International | Articulating surgical instrument incorporating a two-piece firing mechanism |
US10383634B2 (en) | 2004-07-28 | 2019-08-20 | Ethicon Llc | Stapling system incorporating a firing lockout |
US10293100B2 (en) | 2004-07-28 | 2019-05-21 | Ethicon Llc | Surgical stapling instrument having a medical substance dispenser |
US11684365B2 (en) | 2004-07-28 | 2023-06-27 | Cilag Gmbh International | Replaceable staple cartridges for surgical instruments |
US9844379B2 (en) | 2004-07-28 | 2017-12-19 | Ethicon Llc | Surgical stapling instrument having a clearanced opening |
US11896225B2 (en) | 2004-07-28 | 2024-02-13 | Cilag Gmbh International | Staple cartridge comprising a pan |
US11890012B2 (en) | 2004-07-28 | 2024-02-06 | Cilag Gmbh International | Staple cartridge comprising cartridge body and attached support |
US9510830B2 (en) | 2004-07-28 | 2016-12-06 | Ethicon Endo-Surgery, Llc | Staple cartridge |
US10278702B2 (en) | 2004-07-28 | 2019-05-07 | Ethicon Llc | Stapling system comprising a firing bar and a lockout |
US11882987B2 (en) | 2004-07-28 | 2024-01-30 | Cilag Gmbh International | Articulating surgical stapling instrument incorporating a two-piece E-beam firing mechanism |
US11812960B2 (en) | 2004-07-28 | 2023-11-14 | Cilag Gmbh International | Method of segmenting the operation of a surgical stapling instrument |
US7514725B2 (en) | 2004-11-30 | 2009-04-07 | Spire Corporation | Nanophotovoltaic devices |
US20110237015A1 (en) * | 2004-11-30 | 2011-09-29 | Spire Corporation | Nanophotovoltaic devices |
US7759257B2 (en) | 2004-11-30 | 2010-07-20 | Spire Corporation | Precision synthesis of quantum dot nanostructures for fluorescent and optoelectronic devices |
US8242009B2 (en) | 2004-11-30 | 2012-08-14 | Spire Corporation | Nanophotovoltaic devices |
US20060115917A1 (en) * | 2004-11-30 | 2006-06-01 | Linden Kurt J | Precision synthesis of quantum dot nanostructures for fluorescent and optoelectronic devices |
US20090165852A1 (en) * | 2004-11-30 | 2009-07-02 | Spire Corporation | Nanophotovoltaic devices |
US7306963B2 (en) | 2004-11-30 | 2007-12-11 | Spire Corporation | Precision synthesis of quantum dot nanostructures for fluorescent and optoelectronic devices |
US7772612B2 (en) | 2004-11-30 | 2010-08-10 | Spire Corporation | Nanophotovoltaic devices |
US20100297803A1 (en) * | 2004-11-30 | 2010-11-25 | Spire Corporation | Nanophotovoltaic devices |
US7955965B2 (en) | 2004-11-30 | 2011-06-07 | Spire Corporation | Nanophotovoltaic devices |
US20060113557A1 (en) * | 2004-11-30 | 2006-06-01 | Spire Corporation | Nanophotovoltaic devices |
US20080241266A1 (en) * | 2005-01-14 | 2008-10-02 | Bringley Joseph F | Amine polymer-modified nanoparticulate carriers |
US20060293396A1 (en) * | 2005-01-14 | 2006-12-28 | Eastman Kodak Company | Amine polymer-modified nanoparticulate carriers |
US20090060846A1 (en) * | 2005-03-18 | 2009-03-05 | Washington, University Of | Nanoparticles having reactive ester groups covalently coupled thereto and related methods |
US7462446B2 (en) * | 2005-03-18 | 2008-12-09 | University Of Washington | Magnetic nanoparticle compositions and methods |
US20060216239A1 (en) * | 2005-03-18 | 2006-09-28 | Washington, University Of | Magnetic nanoparticle compositions and methods |
US7666394B2 (en) | 2005-03-18 | 2010-02-23 | University Of Washington | Nanoparticles having reactive ester groups covalently coupled thereto and related methods |
US7272275B2 (en) | 2005-03-31 | 2007-09-18 | Eastman Kodak Company | Polarized light emitting source with an electro-optical addressing architecture |
US20060222286A1 (en) * | 2005-03-31 | 2006-10-05 | Eastman Kodak Company | Polarized light emitting source with an electro-optical addressing architecture |
US20060222292A1 (en) * | 2005-03-31 | 2006-10-05 | Eastman Kodak Company | Placement of lumiphores within a light emitting resonator in a visual display with electro-optical addressing architecture |
US7120332B1 (en) | 2005-03-31 | 2006-10-10 | Eastman Kodak Company | Placement of lumiphores within a light emitting resonator in a visual display with electro-optical addressing architecture |
US20060227840A1 (en) * | 2005-03-31 | 2006-10-12 | Eastman Kodak Company | Visual display with electro-optical addressing architecture |
US7352926B2 (en) | 2005-03-31 | 2008-04-01 | Eastman Kodak Company | Visual display with electro-optical addressing architecture |
US8778310B2 (en) | 2005-04-22 | 2014-07-15 | University Of Washington | Fluorescent chlorotoxin conjugate and method for intra-operative visualization of cancer |
US20080279780A1 (en) * | 2005-04-22 | 2008-11-13 | Washington, University Of | Fluorescent chlorotoxin conjugate and method for intra-operative visualization of cancer |
US20070154965A1 (en) * | 2005-04-22 | 2007-07-05 | Miqin Zhang | Chlorotoxin-labeled nanoparticle compositions and methods for targeting primary brain tumors |
CN101198672B (en) * | 2005-05-02 | 2012-09-05 | 科内尔研究基金会 | Photoluminescent silica-based sensors and methods of use |
US20060245971A1 (en) * | 2005-05-02 | 2006-11-02 | Burns Andrew A | Photoluminescent silica-based sensors and methods of use |
US8084001B2 (en) | 2005-05-02 | 2011-12-27 | Cornell Research Foundation, Inc. | Photoluminescent silica-based sensors and methods of use |
US20060291769A1 (en) * | 2005-05-27 | 2006-12-28 | Eastman Kodak Company | Light emitting source incorporating vertical cavity lasers and other MEMS devices within an electro-optical addressing architecture |
EP1883676A1 (en) * | 2005-05-27 | 2008-02-06 | Ciba Specialty Chemicals Holding Inc. | Functionalized nanoparticles |
US20090099282A1 (en) * | 2005-05-27 | 2009-04-16 | Martin Muller | Functionalized nanoparticles |
US7897407B2 (en) | 2005-07-11 | 2011-03-01 | Rikshospitalet Hf | Multicolored particles |
US20090137060A1 (en) * | 2005-07-11 | 2009-05-28 | Rikshospitalet Hf | Multicolored particles |
US20110135929A1 (en) * | 2005-07-11 | 2011-06-09 | Rikshospitalet Hf | Multicolored particles |
US10070863B2 (en) | 2005-08-31 | 2018-09-11 | Ethicon Llc | Fastener cartridge assembly comprising a fixed anvil |
US11399828B2 (en) | 2005-08-31 | 2022-08-02 | Cilag Gmbh International | Fastener cartridge assembly comprising a fixed anvil and different staple heights |
US9592052B2 (en) | 2005-08-31 | 2017-03-14 | Ethicon Endo-Surgery, Llc | Stapling assembly for forming different formed staple heights |
US9561032B2 (en) | 2005-08-31 | 2017-02-07 | Ethicon Endo-Surgery, Llc | Staple cartridge comprising a staple driver arrangement |
US9839427B2 (en) | 2005-08-31 | 2017-12-12 | Ethicon Llc | Fastener cartridge assembly comprising a fixed anvil and a staple driver arrangement |
US9326768B2 (en) | 2005-08-31 | 2016-05-03 | Ethicon Endo-Surgery, Llc | Staple cartridges for forming staples having differing formed staple heights |
US10842489B2 (en) | 2005-08-31 | 2020-11-24 | Ethicon Llc | Fastener cartridge assembly comprising a cam and driver arrangement |
US10271845B2 (en) | 2005-08-31 | 2019-04-30 | Ethicon Llc | Fastener cartridge assembly comprising a cam and driver arrangement |
US11179153B2 (en) | 2005-08-31 | 2021-11-23 | Cilag Gmbh International | Staple cartridges for forming staples having differing formed staple heights |
US9844373B2 (en) | 2005-08-31 | 2017-12-19 | Ethicon Llc | Fastener cartridge assembly comprising a driver row arrangement |
US9848873B2 (en) | 2005-08-31 | 2017-12-26 | Ethicon Llc | Fastener cartridge assembly comprising a driver and staple cavity arrangement |
US10271846B2 (en) | 2005-08-31 | 2019-04-30 | Ethicon Llc | Staple cartridge for use with a surgical stapler |
US10245035B2 (en) | 2005-08-31 | 2019-04-02 | Ethicon Llc | Stapling assembly configured to produce different formed staple heights |
US11730474B2 (en) | 2005-08-31 | 2023-08-22 | Cilag Gmbh International | Fastener cartridge assembly comprising a movable cartridge and a staple driver arrangement |
US8636187B2 (en) | 2005-08-31 | 2014-01-28 | Ethicon Endo-Surgery, Inc. | Surgical stapling systems that produce formed staples having different lengths |
US10842488B2 (en) | 2005-08-31 | 2020-11-24 | Ethicon Llc | Fastener cartridge assembly comprising a fixed anvil and different staple heights |
US7669746B2 (en) | 2005-08-31 | 2010-03-02 | Ethicon Endo-Surgery, Inc. | Staple cartridges for forming staples having differing formed staple heights |
US10420553B2 (en) | 2005-08-31 | 2019-09-24 | Ethicon Llc | Staple cartridge comprising a staple driver arrangement |
US11576673B2 (en) | 2005-08-31 | 2023-02-14 | Cilag Gmbh International | Stapling assembly for forming staples to different heights |
US7673781B2 (en) | 2005-08-31 | 2010-03-09 | Ethicon Endo-Surgery, Inc. | Surgical stapling device with staple driver that supports multiple wire diameter staples |
US10278697B2 (en) | 2005-08-31 | 2019-05-07 | Ethicon Llc | Staple cartridge comprising a staple driver arrangement |
US8567656B2 (en) | 2005-08-31 | 2013-10-29 | Ethicon Endo-Surgery, Inc. | Staple cartridges for forming staples having differing formed staple heights |
US11172927B2 (en) | 2005-08-31 | 2021-11-16 | Cilag Gmbh International | Staple cartridges for forming staples having differing formed staple heights |
US11484311B2 (en) | 2005-08-31 | 2022-11-01 | Cilag Gmbh International | Staple cartridge comprising a staple driver arrangement |
US9237891B2 (en) | 2005-08-31 | 2016-01-19 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical stapling devices that produce formed staples having different lengths |
US9307988B2 (en) | 2005-08-31 | 2016-04-12 | Ethicon Endo-Surgery, Llc | Staple cartridges for forming staples having differing formed staple heights |
US10932774B2 (en) | 2005-08-31 | 2021-03-02 | Ethicon Llc | Surgical end effector for forming staples to different heights |
US11484312B2 (en) | 2005-08-31 | 2022-11-01 | Cilag Gmbh International | Staple cartridge comprising a staple driver arrangement |
US11246590B2 (en) | 2005-08-31 | 2022-02-15 | Cilag Gmbh International | Staple cartridge including staple drivers having different unfired heights |
US8464923B2 (en) | 2005-08-31 | 2013-06-18 | Ethicon Endo-Surgery, Inc. | Surgical stapling devices for forming staples with different formed heights |
US11090045B2 (en) | 2005-08-31 | 2021-08-17 | Cilag Gmbh International | Staple cartridges for forming staples having differing formed staple heights |
US20110174863A1 (en) * | 2005-08-31 | 2011-07-21 | Ethicon Endo-Surgery, Inc. | Staple cartridges for forming staples having differing formed staple heights |
US10159482B2 (en) | 2005-08-31 | 2018-12-25 | Ethicon Llc | Fastener cartridge assembly comprising a fixed anvil and different staple heights |
US10729436B2 (en) | 2005-08-31 | 2020-08-04 | Ethicon Llc | Robotically-controlled surgical stapling devices that produce formed staples having different lengths |
US20070262116A1 (en) * | 2005-08-31 | 2007-11-15 | Hueil Joseph C | Surgical stapling device with multiple stacked actuator wedge cams for driving staple drivers |
US11771425B2 (en) | 2005-08-31 | 2023-10-03 | Cilag Gmbh International | Stapling assembly for forming staples to different formed heights |
US8317070B2 (en) | 2005-08-31 | 2012-11-27 | Ethicon Endo-Surgery, Inc. | Surgical stapling devices that produce formed staples having different lengths |
US10245032B2 (en) | 2005-08-31 | 2019-04-02 | Ethicon Llc | Staple cartridges for forming staples having differing formed staple heights |
US10869664B2 (en) | 2005-08-31 | 2020-12-22 | Ethicon Llc | End effector for use with a surgical stapling instrument |
US10463369B2 (en) | 2005-08-31 | 2019-11-05 | Ethicon Llc | Disposable end effector for use with a surgical instrument |
US11272928B2 (en) | 2005-08-31 | 2022-03-15 | Cilag GmbH Intemational | Staple cartridges for forming staples having differing formed staple heights |
US11134947B2 (en) | 2005-08-31 | 2021-10-05 | Cilag Gmbh International | Fastener cartridge assembly comprising a camming sled with variable cam arrangements |
US8800838B2 (en) | 2005-08-31 | 2014-08-12 | Ethicon Endo-Surgery, Inc. | Robotically-controlled cable-based surgical end effectors |
US10321909B2 (en) | 2005-08-31 | 2019-06-18 | Ethicon Llc | Staple cartridge comprising a staple including deformable members |
US7934630B2 (en) | 2005-08-31 | 2011-05-03 | Ethicon Endo-Surgery, Inc. | Staple cartridges for forming staples having differing formed staple heights |
US11793512B2 (en) | 2005-08-31 | 2023-10-24 | Cilag Gmbh International | Staple cartridges for forming staples having differing formed staple heights |
US9795382B2 (en) | 2005-08-31 | 2017-10-24 | Ethicon Llc | Fastener cartridge assembly comprising a cam and driver arrangement |
US11839375B2 (en) | 2005-08-31 | 2023-12-12 | Cilag Gmbh International | Fastener cartridge assembly comprising an anvil and different staple heights |
WO2007029980A1 (en) * | 2005-09-08 | 2007-03-15 | Biterials Co., Ltd. | Magnetic nanoparticle having fluorescent and preparation method thereof and use thereof |
KR100821192B1 (en) * | 2005-09-08 | 2008-04-11 | 주식회사바이테리얼즈 | Magnetic nanoparticle having fluorescent and preparation method thereof |
US8642258B2 (en) * | 2005-09-12 | 2014-02-04 | Cristalia Produtos Quimicos Farmaceuticos Ltda. | Immunogenical complex formed by vaccinal antigens encapsulated by nanostructured mesoporous silica |
US20080286371A1 (en) * | 2005-09-12 | 2008-11-20 | Cristalia Produtos Quimicos Farmaceuticos Ltda | Immunogenical Complex Formed by Vaccinal Antigens Encapsulated by Nanostructured Mesoporous Silica |
US10028742B2 (en) | 2005-11-09 | 2018-07-24 | Ethicon Llc | Staple cartridge comprising staples with different unformed heights |
US10149679B2 (en) | 2005-11-09 | 2018-12-11 | Ethicon Llc | Surgical instrument comprising drive systems |
US10993713B2 (en) | 2005-11-09 | 2021-05-04 | Ethicon Llc | Surgical instruments |
US10806449B2 (en) | 2005-11-09 | 2020-10-20 | Ethicon Llc | End effectors for surgical staplers |
US9895147B2 (en) | 2005-11-09 | 2018-02-20 | Ethicon Llc | End effectors for surgical staplers |
US9968356B2 (en) | 2005-11-09 | 2018-05-15 | Ethicon Llc | Surgical instrument drive systems |
US11793511B2 (en) | 2005-11-09 | 2023-10-24 | Cilag Gmbh International | Surgical instruments |
US8974767B2 (en) | 2005-11-16 | 2015-03-10 | Signalomics Gmbh | Fluorescent nanoparticles |
US20090226371A1 (en) * | 2005-11-16 | 2009-09-10 | Signalomics Gmbh | Fluorescent nanoparticles |
US20100327482A1 (en) * | 2005-12-20 | 2010-12-30 | University Of Hawaii | Polymer matrix composites with nano-scale reinforcements |
USRE45911E1 (en) | 2005-12-20 | 2016-03-01 | University Of Hawaii | Polymer matrix composites with nano-scale reinforcements |
US7875212B2 (en) * | 2005-12-20 | 2011-01-25 | University Of Hawaii | Polymer matrix composites with nano-scale reinforcements |
US20080293584A1 (en) * | 2005-12-27 | 2008-11-27 | The Furukawa Electric Co., Ltd. | Fluorescent silica nano-particle, fluorescent nano-material, and biochip and assay using the same |
US9260656B2 (en) * | 2005-12-27 | 2016-02-16 | The Furukawa Electric Co., Ltd. | Fluorescent silica nano-particle, fluorescent nano-material, and biochip and assay using the same |
US8186555B2 (en) | 2006-01-31 | 2012-05-29 | Ethicon Endo-Surgery, Inc. | Motor-driven surgical cutting and fastening instrument with mechanical closure system |
US11890008B2 (en) | 2006-01-31 | 2024-02-06 | Cilag Gmbh International | Surgical instrument with firing lockout |
US11224454B2 (en) | 2006-01-31 | 2022-01-18 | Cilag Gmbh International | Motor-driven surgical cutting and fastening instrument with tactile position feedback |
US8161977B2 (en) | 2006-01-31 | 2012-04-24 | Ethicon Endo-Surgery, Inc. | Accessing data stored in a memory of a surgical instrument |
US8167185B2 (en) | 2006-01-31 | 2012-05-01 | Ethicon Endo-Surgery, Inc. | Surgical instrument having recording capabilities |
US8172124B2 (en) | 2006-01-31 | 2012-05-08 | Ethicon Endo-Surgery, Inc. | Surgical instrument having recording capabilities |
US11224427B2 (en) | 2006-01-31 | 2022-01-18 | Cilag Gmbh International | Surgical stapling system including a console and retraction assembly |
US10278722B2 (en) | 2006-01-31 | 2019-05-07 | Ethicon Llc | Motor-driven surgical cutting and fastening instrument |
US11246616B2 (en) | 2006-01-31 | 2022-02-15 | Cilag Gmbh International | Motor-driven surgical cutting and fastening instrument with tactile position feedback |
US11166717B2 (en) | 2006-01-31 | 2021-11-09 | Cilag Gmbh International | Surgical instrument with firing lockout |
US20110174860A1 (en) * | 2006-01-31 | 2011-07-21 | Ethicon Endo-Surgery, Inc. | Surgical instrument with force-feedback capabilities |
US10842491B2 (en) | 2006-01-31 | 2020-11-24 | Ethicon Llc | Surgical system with an actuation console |
US10893853B2 (en) | 2006-01-31 | 2021-01-19 | Ethicon Llc | Stapling assembly including motor drive systems |
US10806479B2 (en) | 2006-01-31 | 2020-10-20 | Ethicon Llc | Motor-driven surgical cutting and fastening instrument with tactile position feedback |
US11278279B2 (en) | 2006-01-31 | 2022-03-22 | Cilag Gmbh International | Surgical instrument assembly |
US10299817B2 (en) | 2006-01-31 | 2019-05-28 | Ethicon Llc | Motor-driven fastening assembly |
US11801051B2 (en) | 2006-01-31 | 2023-10-31 | Cilag Gmbh International | Accessing data stored in a memory of a surgical instrument |
US10499890B2 (en) | 2006-01-31 | 2019-12-10 | Ethicon Llc | Endoscopic surgical instrument with a handle that can articulate with respect to the shaft |
US10485539B2 (en) | 2006-01-31 | 2019-11-26 | Ethicon Llc | Surgical instrument with firing lockout |
US8292155B2 (en) | 2006-01-31 | 2012-10-23 | Ethicon Endo-Surgery, Inc. | Motor-driven surgical cutting and fastening instrument with tactile position feedback |
US10335144B2 (en) | 2006-01-31 | 2019-07-02 | Ethicon Llc | Surgical instrument |
US10743849B2 (en) | 2006-01-31 | 2020-08-18 | Ethicon Llc | Stapling system including an articulation system |
US10918380B2 (en) | 2006-01-31 | 2021-02-16 | Ethicon Llc | Surgical instrument system including a control system |
US8844789B2 (en) | 2006-01-31 | 2014-09-30 | Ethicon Endo-Surgery, Inc. | Automated end effector component reloading system for use with a robotic system |
US9320520B2 (en) | 2006-01-31 | 2016-04-26 | Ethicon Endo-Surgery, Inc. | Surgical instrument system |
US10709468B2 (en) | 2006-01-31 | 2020-07-14 | Ethicon Llc | Motor-driven surgical cutting and fastening instrument |
US11350916B2 (en) | 2006-01-31 | 2022-06-07 | Cilag Gmbh International | Endoscopic surgical instrument with a handle that can articulate with respect to the shaft |
US10201363B2 (en) | 2006-01-31 | 2019-02-12 | Ethicon Llc | Motor-driven surgical instrument |
US11944299B2 (en) | 2006-01-31 | 2024-04-02 | Cilag Gmbh International | Surgical instrument having force feedback capabilities |
US11364046B2 (en) | 2006-01-31 | 2022-06-21 | Cilag Gmbh International | Motor-driven surgical cutting and fastening instrument with tactile position feedback |
US11793518B2 (en) | 2006-01-31 | 2023-10-24 | Cilag Gmbh International | Powered surgical instruments with firing system lockout arrangements |
US9326769B2 (en) | 2006-01-31 | 2016-05-03 | Ethicon Endo-Surgery, Llc | Surgical instrument |
US8820603B2 (en) | 2006-01-31 | 2014-09-02 | Ethicon Endo-Surgery, Inc. | Accessing data stored in a memory of a surgical instrument |
US10342533B2 (en) | 2006-01-31 | 2019-07-09 | Ethicon Llc | Surgical instrument |
US9326770B2 (en) | 2006-01-31 | 2016-05-03 | Ethicon Endo-Surgery, Llc | Surgical instrument |
US11103269B2 (en) | 2006-01-31 | 2021-08-31 | Cilag Gmbh International | Motor-driven surgical cutting and fastening instrument with tactile position feedback |
US9370358B2 (en) | 2006-01-31 | 2016-06-21 | Ethicon Endo-Surgery, Llc | Motor-driven surgical cutting and fastening instrument with tactile position feedback |
US9113874B2 (en) | 2006-01-31 | 2015-08-25 | Ethicon Endo-Surgery, Inc. | Surgical instrument system |
US11890029B2 (en) | 2006-01-31 | 2024-02-06 | Cilag Gmbh International | Motor-driven surgical cutting and fastening instrument |
US8157153B2 (en) | 2006-01-31 | 2012-04-17 | Ethicon Endo-Surgery, Inc. | Surgical instrument with force-feedback capabilities |
US8820605B2 (en) | 2006-01-31 | 2014-09-02 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical instruments |
US9439649B2 (en) | 2006-01-31 | 2016-09-13 | Ethicon Endo-Surgery, Llc | Surgical instrument having force feedback capabilities |
US10098636B2 (en) | 2006-01-31 | 2018-10-16 | Ethicon Llc | Surgical instrument having force feedback capabilities |
US10463383B2 (en) | 2006-01-31 | 2019-11-05 | Ethicon Llc | Stapling instrument including a sensing system |
US11058420B2 (en) | 2006-01-31 | 2021-07-13 | Cilag Gmbh International | Surgical stapling apparatus comprising a lockout system |
US11883020B2 (en) | 2006-01-31 | 2024-01-30 | Cilag Gmbh International | Surgical instrument having a feedback system |
US10463384B2 (en) | 2006-01-31 | 2019-11-05 | Ethicon Llc | Stapling assembly |
US11051813B2 (en) | 2006-01-31 | 2021-07-06 | Cilag Gmbh International | Powered surgical instruments with firing system lockout arrangements |
US10058963B2 (en) | 2006-01-31 | 2018-08-28 | Ethicon Llc | Automated end effector component reloading system for use with a robotic system |
US10052099B2 (en) | 2006-01-31 | 2018-08-21 | Ethicon Llc | Surgical instrument system comprising a firing system including a rotatable shaft and first and second actuation ramps |
US10052100B2 (en) | 2006-01-31 | 2018-08-21 | Ethicon Llc | Surgical instrument system configured to detect resistive forces experienced by a tissue cutting implement |
US11051811B2 (en) | 2006-01-31 | 2021-07-06 | Ethicon Llc | End effector for use with a surgical instrument |
US10010322B2 (en) | 2006-01-31 | 2018-07-03 | Ethicon Llc | Surgical instrument |
US9743928B2 (en) | 2006-01-31 | 2017-08-29 | Ethicon Endo-Surgery, Inc. | Surgical instrument having a feedback system |
US11020113B2 (en) | 2006-01-31 | 2021-06-01 | Cilag Gmbh International | Surgical instrument having force feedback capabilities |
US10675028B2 (en) | 2006-01-31 | 2020-06-09 | Ethicon Llc | Powered surgical instruments with firing system lockout arrangements |
US10004498B2 (en) | 2006-01-31 | 2018-06-26 | Ethicon Llc | Surgical instrument comprising a plurality of articulation joints |
US11612393B2 (en) | 2006-01-31 | 2023-03-28 | Cilag Gmbh International | Robotically-controlled end effector |
US10952728B2 (en) | 2006-01-31 | 2021-03-23 | Ethicon Llc | Powered surgical instruments with firing system lockout arrangements |
US9451958B2 (en) | 2006-01-31 | 2016-09-27 | Ethicon Endo-Surgery, Llc | Surgical instrument with firing actuator lockout |
US8763879B2 (en) | 2006-01-31 | 2014-07-01 | Ethicon Endo-Surgery, Inc. | Accessing data stored in a memory of surgical instrument |
US10959722B2 (en) | 2006-01-31 | 2021-03-30 | Ethicon Llc | Surgical instrument for deploying fasteners by way of rotational motion |
US10653435B2 (en) | 2006-01-31 | 2020-05-19 | Ethicon Llc | Motor-driven surgical cutting and fastening instrument with tactile position feedback |
US11000275B2 (en) | 2006-01-31 | 2021-05-11 | Ethicon Llc | Surgical instrument |
US11648008B2 (en) | 2006-01-31 | 2023-05-16 | Cilag Gmbh International | Surgical instrument having force feedback capabilities |
US11648024B2 (en) | 2006-01-31 | 2023-05-16 | Cilag Gmbh International | Motor-driven surgical cutting and fastening instrument with position feedback |
US11660110B2 (en) | 2006-01-31 | 2023-05-30 | Cilag Gmbh International | Motor-driven surgical cutting and fastening instrument with tactile position feedback |
US9861359B2 (en) | 2006-01-31 | 2018-01-09 | Ethicon Llc | Powered surgical instruments with firing system lockout arrangements |
US10993717B2 (en) | 2006-01-31 | 2021-05-04 | Ethicon Llc | Surgical stapling system comprising a control system |
US8752747B2 (en) | 2006-01-31 | 2014-06-17 | Ethicon Endo-Surgery, Inc. | Surgical instrument having recording capabilities |
US9517068B2 (en) | 2006-01-31 | 2016-12-13 | Ethicon Endo-Surgery, Llc | Surgical instrument with automatically-returned firing member |
US10653417B2 (en) | 2006-01-31 | 2020-05-19 | Ethicon Llc | Surgical instrument |
US10426463B2 (en) | 2006-01-31 | 2019-10-01 | Ehticon LLC | Surgical instrument having a feedback system |
US8746529B2 (en) | 2006-01-31 | 2014-06-10 | Ethicon Endo-Surgery, Inc. | Accessing data stored in a memory of a surgical instrument |
US9327056B2 (en) | 2006-02-14 | 2016-05-03 | Washington State University | Bone replacement materials |
US20070203584A1 (en) * | 2006-02-14 | 2007-08-30 | Amit Bandyopadhyay | Bone replacement materials |
US10661390B2 (en) | 2006-02-14 | 2020-05-26 | Washington State University | Bone replacement materials |
US9301759B2 (en) | 2006-03-23 | 2016-04-05 | Ethicon Endo-Surgery, Llc | Robotically-controlled surgical instrument with selectively articulatable end effector |
US8911471B2 (en) | 2006-03-23 | 2014-12-16 | Ethicon Endo-Surgery, Inc. | Articulatable surgical device |
US9492167B2 (en) | 2006-03-23 | 2016-11-15 | Ethicon Endo-Surgery, Llc | Articulatable surgical device with rotary driven cutting member |
US8992422B2 (en) | 2006-03-23 | 2015-03-31 | Ethicon Endo-Surgery, Inc. | Robotically-controlled endoscopic accessory channel |
US10213262B2 (en) | 2006-03-23 | 2019-02-26 | Ethicon Llc | Manipulatable surgical systems with selectively articulatable fastening device |
US9149274B2 (en) | 2006-03-23 | 2015-10-06 | Ethicon Endo-Surgery, Inc. | Articulating endoscopic accessory channel |
US10064688B2 (en) | 2006-03-23 | 2018-09-04 | Ethicon Llc | Surgical system with selectively articulatable end effector |
US10070861B2 (en) | 2006-03-23 | 2018-09-11 | Ethicon Llc | Articulatable surgical device |
US9402626B2 (en) | 2006-03-23 | 2016-08-02 | Ethicon Endo-Surgery, Llc | Rotary actuatable surgical fastener and cutter |
US9795716B2 (en) | 2006-04-25 | 2017-10-24 | Washington State University | Resorbable ceramics with controlled strength loss rates |
US8916198B2 (en) * | 2006-04-25 | 2014-12-23 | Washington State University | Mesoporous calcium silicate compositions and methods for synthesis of mesoporous calcium silicate for controlled release of bioactive agents |
US9539359B2 (en) | 2006-04-25 | 2017-01-10 | Washington State University | Mesoporous calcium silicate compositions and methods for synthesis of mesoporous calcium silicate for controlled release of bioactive agents |
US20090068272A1 (en) * | 2006-04-25 | 2009-03-12 | Washington State University | Mesoporous calcium silicate compositions and methods for synthesis of mesoporous calcium silicate for controlled release of bioactive agents |
US20090276056A1 (en) * | 2006-04-25 | 2009-11-05 | Washington State University | Resorbable ceramics with controlled strength loss rates |
US9028871B2 (en) | 2006-04-25 | 2015-05-12 | Washington State University | Resorbable ceramics with controlled strength loss rates |
US11351510B2 (en) | 2006-05-11 | 2022-06-07 | Bio-Rad Laboratories, Inc. | Microfluidic devices |
US20080043230A1 (en) * | 2006-05-31 | 2008-02-21 | Gerhard Krampert | Method for spatially high-resolution imaging |
EP1862794A1 (en) * | 2006-05-31 | 2007-12-05 | Carl Zeiss MicroImaging GmbH | Method for high resolution spatial images |
US20090202816A1 (en) * | 2006-06-06 | 2009-08-13 | Florida State University Research Foundation, Inc. | Stabilized silica colloid |
US10087082B2 (en) | 2006-06-06 | 2018-10-02 | Florida State University Research Foundation, Inc. | Stabilized silica colloid |
US9320521B2 (en) | 2006-06-27 | 2016-04-26 | Ethicon Endo-Surgery, Llc | Surgical instrument |
US10420560B2 (en) | 2006-06-27 | 2019-09-24 | Ethicon Llc | Manually driven surgical cutting and fastening instrument |
US10314589B2 (en) | 2006-06-27 | 2019-06-11 | Ethicon Llc | Surgical instrument including a shifting assembly |
US11272938B2 (en) | 2006-06-27 | 2022-03-15 | Cilag Gmbh International | Surgical instrument including dedicated firing and retraction assemblies |
US20100040693A1 (en) * | 2006-08-09 | 2010-02-18 | Korea Research Institute Of Bioscience And Biotech | Silica capsules having nano-holes or nano-pores on their surfaces and method for preparing the same |
US20080086051A1 (en) * | 2006-09-20 | 2008-04-10 | Ethicon Endo-Surgery, Inc. | System, storage medium for a computer program, and method for displaying medical images |
US20080073163A1 (en) * | 2006-09-22 | 2008-03-27 | Weir Michael P | Micro-electromechanical device |
US9079762B2 (en) | 2006-09-22 | 2015-07-14 | Ethicon Endo-Surgery, Inc. | Micro-electromechanical device |
US8485412B2 (en) | 2006-09-29 | 2013-07-16 | Ethicon Endo-Surgery, Inc. | Surgical staples having attached drivers and stapling instruments for deploying the same |
US10172616B2 (en) | 2006-09-29 | 2019-01-08 | Ethicon Llc | Surgical staple cartridge |
US10568652B2 (en) | 2006-09-29 | 2020-02-25 | Ethicon Llc | Surgical staples having attached drivers of different heights and stapling instruments for deploying the same |
US8899465B2 (en) | 2006-09-29 | 2014-12-02 | Ethicon Endo-Surgery, Inc. | Staple cartridge comprising drivers for deploying a plurality of staples |
US7966799B2 (en) | 2006-09-29 | 2011-06-28 | Ethicon Endo-Surgery, Inc. | Method of manufacturing staples |
US9706991B2 (en) | 2006-09-29 | 2017-07-18 | Ethicon Endo-Surgery, Inc. | Staple cartridge comprising staples including a lateral base |
US9603595B2 (en) | 2006-09-29 | 2017-03-28 | Ethicon Endo-Surgery, Llc | Surgical instrument comprising an adjustable system configured to accommodate different jaw heights |
US10595862B2 (en) | 2006-09-29 | 2020-03-24 | Ethicon Llc | Staple cartridge including a compressible member |
US8220690B2 (en) | 2006-09-29 | 2012-07-17 | Ethicon Endo-Surgery, Inc. | Connected surgical staples and stapling instruments for deploying the same |
US8348131B2 (en) | 2006-09-29 | 2013-01-08 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument with mechanical indicator to show levels of tissue compression |
US8808325B2 (en) | 2006-09-29 | 2014-08-19 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument with staples having crown features for increasing formed staple footprint |
US8360297B2 (en) | 2006-09-29 | 2013-01-29 | Ethicon Endo-Surgery, Inc. | Surgical cutting and stapling instrument with self adjusting anvil |
US9179911B2 (en) | 2006-09-29 | 2015-11-10 | Ethicon Endo-Surgery, Inc. | End effector for use with a surgical fastening instrument |
US10695053B2 (en) | 2006-09-29 | 2020-06-30 | Ethicon Llc | Surgical end effectors with staple cartridges |
US10448952B2 (en) | 2006-09-29 | 2019-10-22 | Ethicon Llc | End effector for use with a surgical fastening instrument |
US8763875B2 (en) | 2006-09-29 | 2014-07-01 | Ethicon Endo-Surgery, Inc. | End effector for use with a surgical fastening instrument |
US11678876B2 (en) | 2006-09-29 | 2023-06-20 | Cilag Gmbh International | Powered surgical instrument |
US8720766B2 (en) | 2006-09-29 | 2014-05-13 | Ethicon Endo-Surgery, Inc. | Surgical stapling instruments and staples |
US11633182B2 (en) | 2006-09-29 | 2023-04-25 | Cilag Gmbh International | Surgical stapling assemblies |
US7665647B2 (en) | 2006-09-29 | 2010-02-23 | Ethicon Endo-Surgery, Inc. | Surgical cutting and stapling device with closure apparatus for limiting maximum tissue compression force |
US8365976B2 (en) | 2006-09-29 | 2013-02-05 | Ethicon Endo-Surgery, Inc. | Surgical staples having dissolvable, bioabsorbable or biofragmentable portions and stapling instruments for deploying the same |
US11622785B2 (en) | 2006-09-29 | 2023-04-11 | Cilag Gmbh International | Surgical staples having attached drivers and stapling instruments for deploying the same |
US8973804B2 (en) | 2006-09-29 | 2015-03-10 | Ethicon Endo-Surgery, Inc. | Cartridge assembly having a buttressing member |
US11571231B2 (en) | 2006-09-29 | 2023-02-07 | Cilag Gmbh International | Staple cartridge having a driver for driving multiple staples |
US11406379B2 (en) | 2006-09-29 | 2022-08-09 | Cilag Gmbh International | Surgical end effectors with staple cartridges |
US9408604B2 (en) | 2006-09-29 | 2016-08-09 | Ethicon Endo-Surgery, Llc | Surgical instrument comprising a firing system including a compliant portion |
US8499993B2 (en) | 2006-09-29 | 2013-08-06 | Ethicon Endo-Surgery, Inc. | Surgical staple cartridge |
US7794475B2 (en) | 2006-09-29 | 2010-09-14 | Ethicon Endo-Surgery, Inc. | Surgical staples having compressible or crushable members for securing tissue therein and stapling instruments for deploying the same |
US10130359B2 (en) | 2006-09-29 | 2018-11-20 | Ethicon Llc | Method for forming a staple |
US11382626B2 (en) | 2006-10-03 | 2022-07-12 | Cilag Gmbh International | Surgical system including a knife bar supported for rotational and axial travel |
US10206678B2 (en) | 2006-10-03 | 2019-02-19 | Ethicon Llc | Surgical stapling instrument with lockout features to prevent advancement of a firing assembly unless an unfired surgical staple cartridge is operably mounted in an end effector portion of the instrument |
US11877748B2 (en) | 2006-10-03 | 2024-01-23 | Cilag Gmbh International | Robotically-driven surgical instrument with E-beam driver |
US10342541B2 (en) | 2006-10-03 | 2019-07-09 | Ethicon Llc | Surgical instruments with E-beam driver and rotary drive arrangements |
US20100297725A1 (en) * | 2006-11-01 | 2010-11-25 | Ventana Medical Systems, Inc. | Haptens, hapten conjugates, compositions thereof and method for their preparation and use |
US8618265B2 (en) | 2006-11-01 | 2013-12-31 | Ventana Medical Systems, Inc. | Haptens, hapten conjugates, compositions thereof and method for their preparation and use |
US8846320B2 (en) | 2006-11-01 | 2014-09-30 | Ventana Medical Systems, Inc. | Haptens, hapten conjugates, compositions thereof and method for their preparation and use |
US20100184087A1 (en) * | 2006-11-01 | 2010-07-22 | Ventana Medical Systems, Inc. | Haptens, hapten conjugates, compositions thereof and method for their preparation and use |
US9719986B2 (en) | 2006-11-01 | 2017-08-01 | Ventana Medical Systems, Inc. | Haptens, hapten conjugates, compositions thereof preparation and method for their preparation and use |
FR2909869A1 (en) * | 2006-12-13 | 2008-06-20 | Oreal | Use of hybrid particles for dyeing keratinous fibers, obtained from an organosilane compound carrying a colored species |
WO2008071772A2 (en) * | 2006-12-13 | 2008-06-19 | L'oreal | Use of coloured or fluorescent hybrid particles for treating keratin fibres |
WO2008071772A3 (en) * | 2006-12-13 | 2008-10-02 | Oreal | Use of coloured or fluorescent hybrid particles for treating keratin fibres |
US7713265B2 (en) | 2006-12-22 | 2010-05-11 | Ethicon Endo-Surgery, Inc. | Apparatus and method for medically treating a tattoo |
US20080167521A1 (en) * | 2007-01-09 | 2008-07-10 | Sheetz Jane A | Method of in vivo monitoring using an imaging system including scanned beam imaging unit |
US8801606B2 (en) | 2007-01-09 | 2014-08-12 | Ethicon Endo-Surgery, Inc. | Method of in vivo monitoring using an imaging system including scanned beam imaging unit |
US8273015B2 (en) | 2007-01-09 | 2012-09-25 | Ethicon Endo-Surgery, Inc. | Methods for imaging the anatomy with an anatomically secured scanner assembly |
US8746530B2 (en) | 2007-01-10 | 2014-06-10 | Ethicon Endo-Surgery, Inc. | Surgical instrument with wireless communication between control unit and remote sensor |
US8459520B2 (en) | 2007-01-10 | 2013-06-11 | Ethicon Endo-Surgery, Inc. | Surgical instrument with wireless communication between control unit and remote sensor |
US11006951B2 (en) | 2007-01-10 | 2021-05-18 | Ethicon Llc | Surgical instrument with wireless communication between control unit and sensor transponders |
US11000277B2 (en) | 2007-01-10 | 2021-05-11 | Ethicon Llc | Surgical instrument with wireless communication between control unit and remote sensor |
US10433918B2 (en) | 2007-01-10 | 2019-10-08 | Ethicon Llc | Surgical instrument system configured to evaluate the load applied to a firing member at the initiation of a firing stroke |
US11134943B2 (en) | 2007-01-10 | 2021-10-05 | Cilag Gmbh International | Powered surgical instrument including a control unit and sensor |
US10441369B2 (en) | 2007-01-10 | 2019-10-15 | Ethicon Llc | Articulatable surgical instrument configured for detachable use with a robotic system |
US8652120B2 (en) | 2007-01-10 | 2014-02-18 | Ethicon Endo-Surgery, Inc. | Surgical instrument with wireless communication between control unit and sensor transponders |
US11849947B2 (en) | 2007-01-10 | 2023-12-26 | Cilag Gmbh International | Surgical system including a control circuit and a passively-powered transponder |
US11931032B2 (en) | 2007-01-10 | 2024-03-19 | Cilag Gmbh International | Surgical instrument with wireless communication between a control unit of a robotic system and remote sensor |
US10952727B2 (en) | 2007-01-10 | 2021-03-23 | Ethicon Llc | Surgical instrument for assessing the state of a staple cartridge |
US10945729B2 (en) | 2007-01-10 | 2021-03-16 | Ethicon Llc | Interlock and surgical instrument including same |
US11844521B2 (en) | 2007-01-10 | 2023-12-19 | Cilag Gmbh International | Surgical instrument for use with a robotic system |
US11064998B2 (en) | 2007-01-10 | 2021-07-20 | Cilag Gmbh International | Surgical instrument with wireless communication between a control unit of a robotic system and remote sensor |
US11166720B2 (en) | 2007-01-10 | 2021-11-09 | Cilag Gmbh International | Surgical instrument including a control module for assessing an end effector |
US11937814B2 (en) | 2007-01-10 | 2024-03-26 | Cilag Gmbh International | Surgical instrument for use with a robotic system |
US10278780B2 (en) | 2007-01-10 | 2019-05-07 | Ethicon Llc | Surgical instrument for use with robotic system |
US11812961B2 (en) | 2007-01-10 | 2023-11-14 | Cilag Gmbh International | Surgical instrument including a motor control system |
US10918386B2 (en) | 2007-01-10 | 2021-02-16 | Ethicon Llc | Interlock and surgical instrument including same |
US9757123B2 (en) | 2007-01-10 | 2017-09-12 | Ethicon Llc | Powered surgical instrument having a transmission system |
US11666332B2 (en) | 2007-01-10 | 2023-06-06 | Cilag Gmbh International | Surgical instrument comprising a control circuit configured to adjust the operation of a motor |
US8684253B2 (en) | 2007-01-10 | 2014-04-01 | Ethicon Endo-Surgery, Inc. | Surgical instrument with wireless communication between a control unit of a robotic system and remote sensor |
US10517682B2 (en) | 2007-01-10 | 2019-12-31 | Ethicon Llc | Surgical instrument with wireless communication between control unit and remote sensor |
US8840603B2 (en) | 2007-01-10 | 2014-09-23 | Ethicon Endo-Surgery, Inc. | Surgical instrument with wireless communication between control unit and sensor transponders |
US10517590B2 (en) | 2007-01-10 | 2019-12-31 | Ethicon Llc | Powered surgical instrument having a transmission system |
US11918211B2 (en) | 2007-01-10 | 2024-03-05 | Cilag Gmbh International | Surgical stapling instrument for use with a robotic system |
US11291441B2 (en) | 2007-01-10 | 2022-04-05 | Cilag Gmbh International | Surgical instrument with wireless communication between control unit and remote sensor |
US10751138B2 (en) | 2007-01-10 | 2020-08-25 | Ethicon Llc | Surgical instrument for use with a robotic system |
US8517243B2 (en) | 2007-01-10 | 2013-08-27 | Ethicon Endo-Surgery, Inc. | Surgical instrument with wireless communication between control unit and remote sensor |
US11771426B2 (en) | 2007-01-10 | 2023-10-03 | Cilag Gmbh International | Surgical instrument with wireless communication |
US8479969B2 (en) | 2007-01-10 | 2013-07-09 | Ethicon Endo-Surgery, Inc. | Drive interface for operably coupling a manipulatable surgical tool to a robot |
US11350929B2 (en) | 2007-01-10 | 2022-06-07 | Cilag Gmbh International | Surgical instrument with wireless communication between control unit and sensor transponders |
US9730692B2 (en) | 2007-01-11 | 2017-08-15 | Ethicon Llc | Surgical stapling device with a curved staple cartridge |
US8540128B2 (en) | 2007-01-11 | 2013-09-24 | Ethicon Endo-Surgery, Inc. | Surgical stapling device with a curved end effector |
US9603598B2 (en) | 2007-01-11 | 2017-03-28 | Ethicon Endo-Surgery, Llc | Surgical stapling device with a curved end effector |
US11039836B2 (en) | 2007-01-11 | 2021-06-22 | Cilag Gmbh International | Staple cartridge for use with a surgical stapling instrument |
US9655624B2 (en) | 2007-01-11 | 2017-05-23 | Ethicon Llc | Surgical stapling device with a curved end effector |
US9675355B2 (en) | 2007-01-11 | 2017-06-13 | Ethicon Llc | Surgical stapling device with a curved end effector |
US9700321B2 (en) | 2007-01-11 | 2017-07-11 | Ethicon Llc | Surgical stapling device having supports for a flexible drive mechanism |
US9999431B2 (en) | 2007-01-11 | 2018-06-19 | Ethicon Endo-Surgery, Llc | Surgical stapling device having supports for a flexible drive mechanism |
US9724091B2 (en) | 2007-01-11 | 2017-08-08 | Ethicon Llc | Surgical stapling device |
US11839352B2 (en) | 2007-01-11 | 2023-12-12 | Cilag Gmbh International | Surgical stapling device with an end effector |
US9750501B2 (en) | 2007-01-11 | 2017-09-05 | Ethicon Endo-Surgery, Llc | Surgical stapling devices having laterally movable anvils |
US10912575B2 (en) | 2007-01-11 | 2021-02-09 | Ethicon Llc | Surgical stapling device having supports for a flexible drive mechanism |
US9775613B2 (en) | 2007-01-11 | 2017-10-03 | Ethicon Llc | Surgical stapling device with a curved end effector |
US11819849B2 (en) | 2007-02-06 | 2023-11-21 | Brandeis University | Manipulation of fluids and reactions in microfluidic systems |
US20100119500A1 (en) * | 2007-02-28 | 2010-05-13 | Mika Jokinen | Method for preparing silica compositions, silica compositions and uses thereof |
US9757130B2 (en) | 2007-02-28 | 2017-09-12 | Ethicon Llc | Stapling assembly for forming different formed staple heights |
US20080221434A1 (en) * | 2007-03-09 | 2008-09-11 | Voegele James W | Displaying an internal image of a body lumen of a patient |
US8216214B2 (en) | 2007-03-12 | 2012-07-10 | Ethicon Endo-Surgery, Inc. | Power modulation of a scanning beam for imaging, therapy, and/or diagnosis |
US20080226034A1 (en) * | 2007-03-12 | 2008-09-18 | Weir Michael P | Power modulation of a scanning beam for imaging, therapy, and/or diagnosis |
US9872682B2 (en) | 2007-03-15 | 2018-01-23 | Ethicon Llc | Surgical stapling instrument having a releasable buttress material |
US7735703B2 (en) | 2007-03-15 | 2010-06-15 | Ethicon Endo-Surgery, Inc. | Re-loadable surgical stapling instrument |
US8727197B2 (en) | 2007-03-15 | 2014-05-20 | Ethicon Endo-Surgery, Inc. | Staple cartridge cavity configuration with cooperative surgical staple |
US8925788B2 (en) | 2007-03-15 | 2015-01-06 | Ethicon Endo-Surgery, Inc. | End effectors for surgical stapling instruments |
US20090001128A1 (en) * | 2007-03-15 | 2009-01-01 | Weisenburgh Ii William B | Washer for use with a surgical stapling instrument |
US20090001125A1 (en) * | 2007-03-15 | 2009-01-01 | Hess Christopher J | Surgical stapling instrument having a releasable buttress material |
US8186560B2 (en) | 2007-03-15 | 2012-05-29 | Ethicon Endo-Surgery, Inc. | Surgical stapling systems and staple cartridges for deploying surgical staples with tissue compression features |
US7673782B2 (en) | 2007-03-15 | 2010-03-09 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument having a releasable buttress material |
US7669747B2 (en) | 2007-03-15 | 2010-03-02 | Ethicon Endo-Surgery, Inc. | Washer for use with a surgical stapling instrument |
US10702267B2 (en) | 2007-03-15 | 2020-07-07 | Ethicon Llc | Surgical stapling instrument having a releasable buttress material |
US20090001130A1 (en) * | 2007-03-15 | 2009-01-01 | Hess Christopher J | Surgical procedure using a cutting and stapling instrument having releasable staple-forming pockets |
US8590762B2 (en) | 2007-03-15 | 2013-11-26 | Ethicon Endo-Surgery, Inc. | Staple cartridge cavity configurations |
US9289206B2 (en) | 2007-03-15 | 2016-03-22 | Ethicon Endo-Surgery, Llc | Lateral securement members for surgical staple cartridges |
US8668130B2 (en) | 2007-03-15 | 2014-03-11 | Ethicon Endo-Surgery, Inc. | Surgical stapling systems and staple cartridges for deploying surgical staples with tissue compression features |
US8672208B2 (en) | 2007-03-15 | 2014-03-18 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument having a releasable buttress material |
US11337693B2 (en) | 2007-03-15 | 2022-05-24 | Cilag Gmbh International | Surgical stapling instrument having a releasable buttress material |
US8991676B2 (en) | 2007-03-15 | 2015-03-31 | Ethicon Endo-Surgery, Inc. | Surgical staple having a slidable crown |
US20080234544A1 (en) * | 2007-03-20 | 2008-09-25 | Ethicon Endo-Sugery, Inc. | Displaying images interior and exterior to a body lumen of a patient |
US20080234566A1 (en) * | 2007-03-21 | 2008-09-25 | Ethicon Endo-Surgery, Inc. | Recognizing a real world fiducial in a patient image data |
US8457718B2 (en) | 2007-03-21 | 2013-06-04 | Ethicon Endo-Surgery, Inc. | Recognizing a real world fiducial in a patient image data |
US20080232656A1 (en) * | 2007-03-22 | 2008-09-25 | Ethicon Endo-Surgery, Inc. | Recognizing a real world fiducial in image data of a patient |
US8081810B2 (en) | 2007-03-22 | 2011-12-20 | Ethicon Endo-Surgery, Inc. | Recognizing a real world fiducial in image data of a patient |
US20080242967A1 (en) * | 2007-03-27 | 2008-10-02 | Ethicon Endo-Surgery, Inc. | Medical imaging and therapy utilizing a scanned beam system operating at multiple wavelengths |
US10398433B2 (en) | 2007-03-28 | 2019-09-03 | Ethicon Llc | Laparoscopic clamp load measuring devices |
US20080255425A1 (en) * | 2007-04-13 | 2008-10-16 | Ethicon Endo-Surgery, Inc. | Nanoparticle treated medical devices |
US8626271B2 (en) * | 2007-04-13 | 2014-01-07 | Ethicon Endo-Surgery, Inc. | System and method using fluorescence to examine within a patient's anatomy |
US7995045B2 (en) | 2007-04-13 | 2011-08-09 | Ethicon Endo-Surgery, Inc. | Combined SBI and conventional image processor |
US8062215B2 (en) | 2007-04-13 | 2011-11-22 | Ethicon Endo-Surgery, Inc. | Fluorescent nanoparticle scope |
US20080252778A1 (en) * | 2007-04-13 | 2008-10-16 | Ethicon Endo-Surgery, Inc. | Combined SBI and conventional image processor |
US20080255537A1 (en) * | 2007-04-13 | 2008-10-16 | Ethicon Endo-Surgery, Inc. | Biocompatible nanoparticle compositions and methods |
US20080255414A1 (en) * | 2007-04-13 | 2008-10-16 | Ethicon Endo-Surgery, Inc. | Fluorescent nanoparticle scope |
WO2008127880A1 (en) * | 2007-04-13 | 2008-10-23 | Ethicon Endo-Surgery, Inc | A system and method using fluorescence to examine within a patient's anatomy |
US8239007B2 (en) | 2007-04-13 | 2012-08-07 | Ethicon Endo-Surgert, Inc. | Biocompatible nanoparticle compositions and methods |
WO2008128051A2 (en) * | 2007-04-13 | 2008-10-23 | Ethicon Endo-Surgery, Inc | Fluorescent nanoparticle compositions, methods, and devices |
US8239008B2 (en) | 2007-04-13 | 2012-08-07 | Ethicon Endo-Surgery, Inc. | Sentinel node identification using fluorescent nanoparticles |
US20080255458A1 (en) * | 2007-04-13 | 2008-10-16 | Ethicon Endo-Surgery, Inc. | System and method using fluorescence to examine within a patient's anatomy |
US20080255403A1 (en) * | 2007-04-13 | 2008-10-16 | Ethicon Endo-Surgery, Inc. | Magnetic nanoparticle therapies |
US20080255460A1 (en) * | 2007-04-13 | 2008-10-16 | Ethicon Endo-Surgery, Inc. | Nanoparticle tissue based identification and illumination |
WO2008128051A3 (en) * | 2007-04-13 | 2010-10-28 | Ethicon Endo-Surgery, Inc | Fluorescent nanoparticle compositions, methods and devices |
US20080255459A1 (en) * | 2007-04-13 | 2008-10-16 | Ethicon Endo-Surgery, Inc. | Sentinel node identification using fluorescent nanoparticles |
US9937129B2 (en) | 2007-04-16 | 2018-04-10 | The Regents Of The University Of California | Materials and methods for delivering compositions to selected tissues |
US11618024B2 (en) | 2007-04-19 | 2023-04-04 | President And Fellows Of Harvard College | Manipulation of fluids, fluid components and reactions in microfluidic systems |
US11224876B2 (en) | 2007-04-19 | 2022-01-18 | Brandeis University | Manipulation of fluids, fluid components and reactions in microfluidic systems |
US20090289225A1 (en) * | 2007-04-19 | 2009-11-26 | Naiyong Jing | Reducing fluorescent self-quenching with nanoparticles |
US20080275305A1 (en) * | 2007-05-01 | 2008-11-06 | Ethicon Endo-Surgery, Inc. | Medical scanned beam imager and components associated therewith |
US20080274463A1 (en) * | 2007-05-04 | 2008-11-06 | Ventana Medical Systems, Inc. | Method for quantifying biomolecules conjugated to a nanoparticle |
US7682789B2 (en) * | 2007-05-04 | 2010-03-23 | Ventana Medical Systems, Inc. | Method for quantifying biomolecules conjugated to a nanoparticle |
US9575067B2 (en) | 2007-05-23 | 2017-02-21 | Ventana Medical Systems, Inc. | Polymeric carriers for immunohistochemistry and in situ hybridization |
US8486620B2 (en) | 2007-05-23 | 2013-07-16 | Ventana Medical Systems, Inc. | Polymeric carriers for immunohistochemistry and in situ hybridization |
US9103822B2 (en) | 2007-05-23 | 2015-08-11 | Ventana Medical Systems, Inc. | Polymeric carriers for immunohistochemistry and in situ hybridization |
US8445191B2 (en) | 2007-05-23 | 2013-05-21 | Ventana Medical Systems, Inc. | Polymeric carriers for immunohistochemistry and in situ hybridization |
US9017954B2 (en) | 2007-05-23 | 2015-04-28 | Ventana Medical Systems, Inc. | Polymeric carriers for immunohistochemistry and in situ hybridization |
US10327765B2 (en) | 2007-06-04 | 2019-06-25 | Ethicon Llc | Drive systems for surgical instruments |
US10368863B2 (en) | 2007-06-04 | 2019-08-06 | Ethicon Llc | Robotically-controlled shaft based rotary drive systems for surgical instruments |
US9987003B2 (en) | 2007-06-04 | 2018-06-05 | Ethicon Llc | Robotic actuator assembly |
US9585658B2 (en) | 2007-06-04 | 2017-03-07 | Ethicon Endo-Surgery, Llc | Stapling systems |
US10363033B2 (en) | 2007-06-04 | 2019-07-30 | Ethicon Llc | Robotically-controlled surgical instruments |
US8616431B2 (en) | 2007-06-04 | 2013-12-31 | Ethicon Endo-Surgery, Inc. | Shiftable drive interface for robotically-controlled surgical tool |
US9750498B2 (en) | 2007-06-04 | 2017-09-05 | Ethicon Endo Surgery, Llc | Drive systems for surgical instruments |
US11648006B2 (en) | 2007-06-04 | 2023-05-16 | Cilag Gmbh International | Robotically-controlled shaft based rotary drive systems for surgical instruments |
US11564682B2 (en) | 2007-06-04 | 2023-01-31 | Cilag Gmbh International | Surgical stapler device |
US11672531B2 (en) | 2007-06-04 | 2023-06-13 | Cilag Gmbh International | Rotary drive systems for surgical instruments |
US11857181B2 (en) | 2007-06-04 | 2024-01-02 | Cilag Gmbh International | Robotically-controlled shaft based rotary drive systems for surgical instruments |
US8931682B2 (en) | 2007-06-04 | 2015-01-13 | Ethicon Endo-Surgery, Inc. | Robotically-controlled shaft based rotary drive systems for surgical instruments |
US11559302B2 (en) | 2007-06-04 | 2023-01-24 | Cilag Gmbh International | Surgical instrument including a firing member movable at different speeds |
US11911028B2 (en) | 2007-06-04 | 2024-02-27 | Cilag Gmbh International | Surgical instruments for use with a robotic surgical system |
US11134938B2 (en) | 2007-06-04 | 2021-10-05 | Cilag Gmbh International | Robotically-controlled shaft based rotary drive systems for surgical instruments |
US8196796B2 (en) | 2007-06-04 | 2012-06-12 | Ethicon Endo-Surgery, Inc. | Shaft based rotary drive system for surgical instruments |
US8534528B2 (en) | 2007-06-04 | 2013-09-17 | Ethicon Endo-Surgery, Inc. | Surgical instrument having a multiple rate directional switching mechanism |
US9795381B2 (en) | 2007-06-04 | 2017-10-24 | Ethicon Endo-Surgery, Llc | Robotically-controlled shaft based rotary drive systems for surgical instruments |
US9186143B2 (en) | 2007-06-04 | 2015-11-17 | Ethicon Endo-Surgery, Inc. | Robotically-controlled shaft based rotary drive systems for surgical instruments |
US11147549B2 (en) | 2007-06-04 | 2021-10-19 | Cilag Gmbh International | Stapling instrument including a firing system and a closure system |
US8424740B2 (en) | 2007-06-04 | 2013-04-23 | Ethicon Endo-Surgery, Inc. | Surgical instrument having a directional switching mechanism |
US11154298B2 (en) | 2007-06-04 | 2021-10-26 | Cilag Gmbh International | Stapling system for use with a robotic surgical system |
US10299787B2 (en) | 2007-06-04 | 2019-05-28 | Ethicon Llc | Stapling system comprising rotary inputs |
US10441280B2 (en) | 2007-06-04 | 2019-10-15 | Ethicon Llc | Robotically-controlled shaft based rotary drive systems for surgical instruments |
US8160678B2 (en) | 2007-06-18 | 2012-04-17 | Ethicon Endo-Surgery, Inc. | Methods and devices for repairing damaged or diseased tissue using a scanning beam assembly |
US20080312490A1 (en) * | 2007-06-18 | 2008-12-18 | Ethicon Endo-Surgery, Inc. | Methods and devices for repairing damaged or diseased tissue using a scanning beam assembly |
US9662110B2 (en) | 2007-06-22 | 2017-05-30 | Ethicon Endo-Surgery, Llc | Surgical stapling instrument with an articulatable end effector |
US11013511B2 (en) | 2007-06-22 | 2021-05-25 | Ethicon Llc | Surgical stapling instrument with an articulatable end effector |
US9138225B2 (en) | 2007-06-22 | 2015-09-22 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument with an articulatable end effector |
US11849941B2 (en) | 2007-06-29 | 2023-12-26 | Cilag Gmbh International | Staple cartridge having staple cavities extending at a transverse angle relative to a longitudinal cartridge axis |
US7558455B2 (en) | 2007-06-29 | 2009-07-07 | Ethicon Endo-Surgery, Inc | Receiver aperture broadening for scanned beam imaging |
US11925346B2 (en) | 2007-06-29 | 2024-03-12 | Cilag Gmbh International | Surgical staple cartridge including tissue supporting surfaces |
US7982776B2 (en) | 2007-07-13 | 2011-07-19 | Ethicon Endo-Surgery, Inc. | SBI motion artifact removal apparatus and method |
WO2009017695A1 (en) * | 2007-07-26 | 2009-02-05 | The Regents Of The University Of California | A single cell surgery tool and a cell transfection device utilizing the photothermal properties of thin films and/or metal nanoparticles |
US9125552B2 (en) | 2007-07-31 | 2015-09-08 | Ethicon Endo-Surgery, Inc. | Optical scanning module and means for attaching the module to medical instruments for introducing the module into the anatomy |
US20090035802A1 (en) * | 2007-07-31 | 2009-02-05 | Digital Bio Technology, Co., Ltd. | Method for detection and enumeration of cell surface markers |
US20090043109A1 (en) * | 2007-08-07 | 2009-02-12 | Spangler Brenda D | Asymmetric one- and two-photon fluorophores for simultaneous detection of multiple analytes using a common excitation source |
US20090054761A1 (en) * | 2007-08-22 | 2009-02-26 | Ethicon Endo-Surgery, Inc. | Medical system, method, and storage medium concerning a natural orifice transluminal medical procedure |
US8155728B2 (en) | 2007-08-22 | 2012-04-10 | Ethicon Endo-Surgery, Inc. | Medical system, method, and storage medium concerning a natural orifice transluminal medical procedure |
US20090062658A1 (en) * | 2007-08-27 | 2009-03-05 | Dunki-Jacobs Robert J | Position tracking and control for a scanning assembly |
US7983739B2 (en) | 2007-08-27 | 2011-07-19 | Ethicon Endo-Surgery, Inc. | Position tracking and control for a scanning assembly |
US7925333B2 (en) | 2007-08-28 | 2011-04-12 | Ethicon Endo-Surgery, Inc. | Medical device including scanned beam unit with operational control features |
US20090062659A1 (en) * | 2007-08-28 | 2009-03-05 | Weir Michael P | Medical device including scanned beam unit with operational control features |
US20090060381A1 (en) * | 2007-08-31 | 2009-03-05 | Ethicon Endo-Surgery, Inc. | Dynamic range and amplitude control for imaging |
US20110028662A1 (en) * | 2007-08-31 | 2011-02-03 | Hybrid Silica Technologies, Inc. | Peg-coated core-shell silica nanoparticles and methods of manufacture and use |
US8519609B2 (en) | 2007-11-08 | 2013-08-27 | Merck Patent Gmbh | Process for the preparation of coated phosphors |
US20100264809A1 (en) * | 2007-11-08 | 2010-10-21 | Merck Patent Gmbh | Process for the preparation of coated phosphors |
WO2009059677A1 (en) * | 2007-11-08 | 2009-05-14 | Merck Patent Gmbh | Method for the production of coated luminescent substances |
WO2009073193A2 (en) * | 2007-12-03 | 2009-06-11 | The Johns Hopkins University | Methods of synthesis and use of chemospheres |
WO2009073193A3 (en) * | 2007-12-03 | 2009-12-23 | The Johns Hopkins University | Methods of synthesis and use of chemospheres |
US20110104052A1 (en) * | 2007-12-03 | 2011-05-05 | The Johns Hopkins University | Methods of synthesis and use of chemospheres |
US9265729B2 (en) * | 2007-12-06 | 2016-02-23 | The University Of Tokushima | Nanofunctional silica particles and manufacturing method thereof |
US20100310872A1 (en) * | 2007-12-06 | 2010-12-09 | The University Of Tokushima | Nanofunctional silica particles and manufacturing method thereof |
US20100311871A1 (en) * | 2008-02-12 | 2010-12-09 | Nissan Chemical Industries, Ltd. | Colloidal silica particles, process for producing the same, and organic solvent-dispersed silica sol, polymerizable compound-dispersed silica sol, and dicarboxylic anhydride-dispersed silica sol each obtained from the same |
US9527749B2 (en) * | 2008-02-12 | 2016-12-27 | Nissan Chemical Industries, Ltd. | Colloidal silica particles, process for producing the same, and organic solvent-dispersed silica sol, polymerizable compound-dispersed silica sol, and dicarboxylic anhydride-dispersed silica sol each obtained from the same |
US9284197B2 (en) * | 2008-02-12 | 2016-03-15 | Nissan Chemical Industries, Ltd. | Colloidal silica particles, process for producing the same, and organic solvent-dispersed silica sol, polymerizable compound-dispersed silica sol, and dicarboxylic anhydride-dispersed silica sol each obtained from the same |
US20160145110A1 (en) * | 2008-02-12 | 2016-05-26 | Nissan Chemical Industries, Ltd. | Colloidal silica particles, process for producing the same, and organic solvent-dispersed silica sol, polymerizable compound-dispersed silica sol, and dicarboxylic anhydride-dispersed silica sol each obtained from the same |
US10765424B2 (en) | 2008-02-13 | 2020-09-08 | Ethicon Llc | Surgical stapling instrument |
US10888329B2 (en) | 2008-02-14 | 2021-01-12 | Ethicon Llc | Detachable motor powered surgical instrument |
US8584919B2 (en) | 2008-02-14 | 2013-11-19 | Ethicon Endo-Sugery, Inc. | Surgical stapling apparatus with load-sensitive firing mechanism |
US10238385B2 (en) | 2008-02-14 | 2019-03-26 | Ethicon Llc | Surgical instrument system for evaluating tissue impedance |
US9072515B2 (en) | 2008-02-14 | 2015-07-07 | Ethicon Endo-Surgery, Inc. | Surgical stapling apparatus |
US10888330B2 (en) | 2008-02-14 | 2021-01-12 | Ethicon Llc | Surgical system |
US9084601B2 (en) | 2008-02-14 | 2015-07-21 | Ethicon Endo-Surgery, Inc. | Detachable motor powered surgical instrument |
US10905427B2 (en) | 2008-02-14 | 2021-02-02 | Ethicon Llc | Surgical System |
US10874396B2 (en) | 2008-02-14 | 2020-12-29 | Ethicon Llc | Stapling instrument for use with a surgical robot |
US9498219B2 (en) | 2008-02-14 | 2016-11-22 | Ethicon Endo-Surgery, Llc | Detachable motor powered surgical instrument |
US8998058B2 (en) | 2008-02-14 | 2015-04-07 | Ethicon Endo-Surgery, Inc. | Detachable motor powered surgical instrument |
US10463370B2 (en) | 2008-02-14 | 2019-11-05 | Ethicon Llc | Motorized surgical instrument |
US10206676B2 (en) | 2008-02-14 | 2019-02-19 | Ethicon Llc | Surgical cutting and fastening instrument |
US10542974B2 (en) | 2008-02-14 | 2020-01-28 | Ethicon Llc | Surgical instrument including a control system |
US10307163B2 (en) | 2008-02-14 | 2019-06-04 | Ethicon Llc | Detachable motor powered surgical instrument |
US10806450B2 (en) | 2008-02-14 | 2020-10-20 | Ethicon Llc | Surgical cutting and fastening instrument having a control system |
US9179912B2 (en) | 2008-02-14 | 2015-11-10 | Ethicon Endo-Surgery, Inc. | Robotically-controlled motorized surgical cutting and fastening instrument |
US8459525B2 (en) | 2008-02-14 | 2013-06-11 | Ethicon Endo-Sugery, Inc. | Motorized surgical cutting and fastening instrument having a magnetic drive train torque limiting device |
US10779822B2 (en) | 2008-02-14 | 2020-09-22 | Ethicon Llc | System including a surgical cutting and fastening instrument |
US9522029B2 (en) | 2008-02-14 | 2016-12-20 | Ethicon Endo-Surgery, Llc | Motorized surgical cutting and fastening instrument having handle based power source |
US11446034B2 (en) | 2008-02-14 | 2022-09-20 | Cilag Gmbh International | Surgical stapling assembly comprising first and second actuation systems configured to perform different functions |
US11464514B2 (en) | 2008-02-14 | 2022-10-11 | Cilag Gmbh International | Motorized surgical stapling system including a sensing array |
US8196795B2 (en) | 2008-02-14 | 2012-06-12 | Ethicon Endo-Surgery, Inc. | Disposable motor-driven loading unit for use with a surgical cutting and stapling apparatus |
US10898195B2 (en) | 2008-02-14 | 2021-01-26 | Ethicon Llc | Detachable motor powered surgical instrument |
US11484307B2 (en) | 2008-02-14 | 2022-11-01 | Cilag Gmbh International | Loading unit coupleable to a surgical stapling system |
US11717285B2 (en) | 2008-02-14 | 2023-08-08 | Cilag Gmbh International | Surgical cutting and fastening instrument having RF electrodes |
US10765432B2 (en) | 2008-02-14 | 2020-09-08 | Ethicon Llc | Surgical device including a control system |
US11801047B2 (en) | 2008-02-14 | 2023-10-31 | Cilag Gmbh International | Surgical stapling system comprising a control circuit configured to selectively monitor tissue impedance and adjust control of a motor |
US10898194B2 (en) | 2008-02-14 | 2021-01-26 | Ethicon Llc | Detachable motor powered surgical instrument |
US8752749B2 (en) | 2008-02-14 | 2014-06-17 | Ethicon Endo-Surgery, Inc. | Robotically-controlled disposable motor-driven loading unit |
US8540130B2 (en) | 2008-02-14 | 2013-09-24 | Ethicon Endo-Surgery, Inc. | Disposable motor-driven loading unit for use with a surgical cutting and stapling apparatus |
US8573461B2 (en) | 2008-02-14 | 2013-11-05 | Ethicon Endo-Surgery, Inc. | Surgical stapling instruments with cam-driven staple deployment arrangements |
US8573465B2 (en) | 2008-02-14 | 2013-11-05 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical end effector system with rotary actuated closure systems |
US9204878B2 (en) | 2008-02-14 | 2015-12-08 | Ethicon Endo-Surgery, Inc. | Surgical stapling apparatus with interlockable firing system |
US10238387B2 (en) | 2008-02-14 | 2019-03-26 | Ethicon Llc | Surgical instrument comprising a control system |
US8991677B2 (en) | 2008-02-14 | 2015-03-31 | Ethicon Endo-Surgery, Inc. | Detachable motor powered surgical instrument |
US10470763B2 (en) | 2008-02-14 | 2019-11-12 | Ethicon Llc | Surgical cutting and fastening instrument including a sensing system |
US10905426B2 (en) | 2008-02-14 | 2021-02-02 | Ethicon Llc | Detachable motor powered surgical instrument |
US10743870B2 (en) | 2008-02-14 | 2020-08-18 | Ethicon Llc | Surgical stapling apparatus with interlockable firing system |
US11571212B2 (en) | 2008-02-14 | 2023-02-07 | Cilag Gmbh International | Surgical stapling system including an impedance sensor |
US10743851B2 (en) | 2008-02-14 | 2020-08-18 | Ethicon Llc | Interchangeable tools for surgical instruments |
US10004505B2 (en) | 2008-02-14 | 2018-06-26 | Ethicon Llc | Detachable motor powered surgical instrument |
US9867618B2 (en) | 2008-02-14 | 2018-01-16 | Ethicon Llc | Surgical stapling apparatus including firing force regulation |
US8113410B2 (en) | 2008-02-14 | 2012-02-14 | Ethicon Endo-Surgery, Inc. | Surgical stapling apparatus with control features |
US10722232B2 (en) | 2008-02-14 | 2020-07-28 | Ethicon Llc | Surgical instrument for use with different cartridges |
US9872684B2 (en) | 2008-02-14 | 2018-01-23 | Ethicon Llc | Surgical stapling apparatus including firing force regulation |
US10716568B2 (en) | 2008-02-14 | 2020-07-21 | Ethicon Llc | Surgical stapling apparatus with control features operable with one hand |
US9877723B2 (en) | 2008-02-14 | 2018-01-30 | Ethicon Llc | Surgical stapling assembly comprising a selector arrangement |
US10265067B2 (en) | 2008-02-14 | 2019-04-23 | Ethicon Llc | Surgical instrument including a regulator and a control system |
US10925605B2 (en) | 2008-02-14 | 2021-02-23 | Ethicon Llc | Surgical stapling system |
US9095339B2 (en) | 2008-02-14 | 2015-08-04 | Ethicon Endo-Surgery, Inc. | Detachable motor powered surgical instrument |
US9999426B2 (en) | 2008-02-14 | 2018-06-19 | Ethicon Llc | Detachable motor powered surgical instrument |
US8657178B2 (en) | 2008-02-14 | 2014-02-25 | Ethicon Endo-Surgery, Inc. | Surgical stapling apparatus |
US8657174B2 (en) | 2008-02-14 | 2014-02-25 | Ethicon Endo-Surgery, Inc. | Motorized surgical cutting and fastening instrument having handle based power source |
US9901344B2 (en) | 2008-02-14 | 2018-02-27 | Ethicon Llc | Stapling assembly |
US9901345B2 (en) | 2008-02-14 | 2018-02-27 | Ethicon Llc | Stapling assembly |
US9901346B2 (en) | 2008-02-14 | 2018-02-27 | Ethicon Llc | Stapling assembly |
US11638583B2 (en) | 2008-02-14 | 2023-05-02 | Cilag Gmbh International | Motorized surgical system having a plurality of power sources |
US10682141B2 (en) | 2008-02-14 | 2020-06-16 | Ethicon Llc | Surgical device including a control system |
US10682142B2 (en) | 2008-02-14 | 2020-06-16 | Ethicon Llc | Surgical stapling apparatus including an articulation system |
US9211121B2 (en) | 2008-02-14 | 2015-12-15 | Ethicon Endo-Surgery, Inc. | Surgical stapling apparatus |
US9980729B2 (en) | 2008-02-14 | 2018-05-29 | Ethicon Endo-Surgery, Llc | Detachable motor powered surgical instrument |
US8636736B2 (en) | 2008-02-14 | 2014-01-28 | Ethicon Endo-Surgery, Inc. | Motorized surgical cutting and fastening instrument |
US10639036B2 (en) | 2008-02-14 | 2020-05-05 | Ethicon Llc | Robotically-controlled motorized surgical cutting and fastening instrument |
US8622274B2 (en) | 2008-02-14 | 2014-01-07 | Ethicon Endo-Surgery, Inc. | Motorized cutting and fastening instrument having control circuit for optimizing battery usage |
US9962158B2 (en) | 2008-02-14 | 2018-05-08 | Ethicon Llc | Surgical stapling apparatuses with lockable end effector positioning systems |
US10660640B2 (en) | 2008-02-14 | 2020-05-26 | Ethicon Llc | Motorized surgical cutting and fastening instrument |
US11612395B2 (en) | 2008-02-14 | 2023-03-28 | Cilag Gmbh International | Surgical system including a control system having an RFID tag reader |
US10390823B2 (en) | 2008-02-15 | 2019-08-27 | Ethicon Llc | End effector comprising an adjunct |
US9585657B2 (en) | 2008-02-15 | 2017-03-07 | Ethicon Endo-Surgery, Llc | Actuator for releasing a layer of material from a surgical end effector |
US20100317537A1 (en) * | 2008-02-15 | 2010-12-16 | University Of Florida Research Foundation, Inc. | Biophysical parameters for systems biology |
US10856866B2 (en) | 2008-02-15 | 2020-12-08 | Ethicon Llc | Surgical end effector having buttress retention features |
US11272927B2 (en) | 2008-02-15 | 2022-03-15 | Cilag Gmbh International | Layer arrangements for surgical staple cartridges |
US9770245B2 (en) | 2008-02-15 | 2017-09-26 | Ethicon Llc | Layer arrangements for surgical staple cartridges |
US11058418B2 (en) | 2008-02-15 | 2021-07-13 | Cilag Gmbh International | Surgical end effector having buttress retention features |
US11154297B2 (en) | 2008-02-15 | 2021-10-26 | Cilag Gmbh International | Layer arrangements for surgical staple cartridges |
US20110288234A1 (en) * | 2008-02-19 | 2011-11-24 | The Research Foundation on State University of NY | Silica nanoparticles postloaded with photosensitizers for drug delivery in photodynamic therapy |
EP2098187A1 (en) | 2008-03-03 | 2009-09-09 | Ethicon Endo-Surgery, Inc. | Intraluminal tissue markers |
US20090217932A1 (en) * | 2008-03-03 | 2009-09-03 | Ethicon Endo-Surgery, Inc. | Intraluminal tissue markers |
US8050520B2 (en) | 2008-03-27 | 2011-11-01 | Ethicon Endo-Surgery, Inc. | Method for creating a pixel image from sampled data of a scanned beam imager |
US8332014B2 (en) | 2008-04-25 | 2012-12-11 | Ethicon Endo-Surgery, Inc. | Scanned beam device and method using same which measures the reflectance of patient tissue |
US9603952B2 (en) | 2008-05-15 | 2017-03-28 | Morphotek, Inc. | Treatment of metastatic tumors |
US9023595B2 (en) | 2008-05-15 | 2015-05-05 | Morphotek, Inc. | Treatment of metastatic tumors |
US10718693B2 (en) | 2008-06-05 | 2020-07-21 | Ventana Medical Systems, Inc. | Compositions comprising nanomaterials and method for using such compositions for histochemical processes |
US20140178929A1 (en) * | 2008-06-05 | 2014-06-26 | Ventana Medical Systems, Inc. | Compositions comprising nanomaterials and method for using such compositions for histochemical processes |
US8703490B2 (en) | 2008-06-05 | 2014-04-22 | Ventana Medical Systems, Inc. | Compositions comprising nanomaterials and method for using such compositions for histochemical processes |
US20110111233A1 (en) * | 2008-07-07 | 2011-05-12 | Kazuya Tsukada | Inorganic nanoparticle labeling agent |
US11511242B2 (en) | 2008-07-18 | 2022-11-29 | Bio-Rad Laboratories, Inc. | Droplet libraries |
US11534727B2 (en) | 2008-07-18 | 2022-12-27 | Bio-Rad Laboratories, Inc. | Droplet libraries |
US11596908B2 (en) | 2008-07-18 | 2023-03-07 | Bio-Rad Laboratories, Inc. | Droplet libraries |
WO2010021512A3 (en) * | 2008-08-22 | 2010-04-15 | Snu R&Db Foundation | Silica-based fluorescent nanoparticles |
WO2010021512A2 (en) * | 2008-08-22 | 2010-02-25 | Snu R&Db Foundation | Silica-based fluorescent nanoparticles |
CN101457139B (en) * | 2008-08-22 | 2012-06-13 | 吉林大学 | High quantum production rate luminescent silicon ball with controllable structure and preparation method thereof |
US11123071B2 (en) | 2008-09-19 | 2021-09-21 | Cilag Gmbh International | Staple cartridge for us with a surgical instrument |
US10258336B2 (en) | 2008-09-19 | 2019-04-16 | Ethicon Llc | Stapling system configured to produce different formed staple heights |
US11944306B2 (en) | 2008-09-19 | 2024-04-02 | Cilag Gmbh International | Surgical stapler including a replaceable staple cartridge |
US11045189B2 (en) | 2008-09-23 | 2021-06-29 | Cilag Gmbh International | Robotically-controlled motorized surgical instrument with an end effector |
US9050083B2 (en) | 2008-09-23 | 2015-06-09 | Ethicon Endo-Surgery, Inc. | Motorized surgical instrument |
US11871923B2 (en) | 2008-09-23 | 2024-01-16 | Cilag Gmbh International | Motorized surgical instrument |
US10420549B2 (en) | 2008-09-23 | 2019-09-24 | Ethicon Llc | Motorized surgical instrument |
US11648005B2 (en) | 2008-09-23 | 2023-05-16 | Cilag Gmbh International | Robotically-controlled motorized surgical instrument with an end effector |
US10045778B2 (en) | 2008-09-23 | 2018-08-14 | Ethicon Llc | Robotically-controlled motorized surgical instrument with an end effector |
US8602287B2 (en) | 2008-09-23 | 2013-12-10 | Ethicon Endo-Surgery, Inc. | Motor driven surgical cutting instrument |
US11617575B2 (en) | 2008-09-23 | 2023-04-04 | Cilag Gmbh International | Motor-driven surgical cutting instrument |
US10765425B2 (en) | 2008-09-23 | 2020-09-08 | Ethicon Llc | Robotically-controlled motorized surgical instrument with an end effector |
US10736628B2 (en) | 2008-09-23 | 2020-08-11 | Ethicon Llc | Motor-driven surgical cutting instrument |
US10130361B2 (en) | 2008-09-23 | 2018-11-20 | Ethicon Llc | Robotically-controller motorized surgical tool with an end effector |
US10238389B2 (en) | 2008-09-23 | 2019-03-26 | Ethicon Llc | Robotically-controlled motorized surgical instrument with an end effector |
US11103241B2 (en) | 2008-09-23 | 2021-08-31 | Cilag Gmbh International | Motor-driven surgical cutting instrument |
US9386983B2 (en) | 2008-09-23 | 2016-07-12 | Ethicon Endo-Surgery, Llc | Robotically-controlled motorized surgical instrument |
US9655614B2 (en) | 2008-09-23 | 2017-05-23 | Ethicon Endo-Surgery, Llc | Robotically-controlled motorized surgical instrument with an end effector |
US11684361B2 (en) | 2008-09-23 | 2023-06-27 | Cilag Gmbh International | Motor-driven surgical cutting instrument |
US11406380B2 (en) | 2008-09-23 | 2022-08-09 | Cilag Gmbh International | Motorized surgical instrument |
US9028519B2 (en) | 2008-09-23 | 2015-05-12 | Ethicon Endo-Surgery, Inc. | Motorized surgical instrument |
US10485537B2 (en) | 2008-09-23 | 2019-11-26 | Ethicon Llc | Motorized surgical instrument |
US11812954B2 (en) | 2008-09-23 | 2023-11-14 | Cilag Gmbh International | Robotically-controlled motorized surgical instrument with an end effector |
US11517304B2 (en) | 2008-09-23 | 2022-12-06 | Cilag Gmbh International | Motor-driven surgical cutting instrument |
US10456133B2 (en) | 2008-09-23 | 2019-10-29 | Ethicon Llc | Motorized surgical instrument |
US8602288B2 (en) | 2008-09-23 | 2013-12-10 | Ethicon Endo-Surgery. Inc. | Robotically-controlled motorized surgical end effector system with rotary actuated closure systems having variable actuation speeds |
US9005230B2 (en) | 2008-09-23 | 2015-04-14 | Ethicon Endo-Surgery, Inc. | Motorized surgical instrument |
US9549732B2 (en) | 2008-09-23 | 2017-01-24 | Ethicon Endo-Surgery, Llc | Motor-driven surgical cutting instrument |
US11617576B2 (en) | 2008-09-23 | 2023-04-04 | Cilag Gmbh International | Motor-driven surgical cutting instrument |
US10105136B2 (en) | 2008-09-23 | 2018-10-23 | Ethicon Llc | Robotically-controlled motorized surgical instrument with an end effector |
US10898184B2 (en) | 2008-09-23 | 2021-01-26 | Ethicon Llc | Motor-driven surgical cutting instrument |
US10980535B2 (en) | 2008-09-23 | 2021-04-20 | Ethicon Llc | Motorized surgical instrument with an end effector |
US11730477B2 (en) | 2008-10-10 | 2023-08-22 | Cilag Gmbh International | Powered surgical system with manually retractable firing system |
US11793521B2 (en) | 2008-10-10 | 2023-10-24 | Cilag Gmbh International | Powered surgical cutting and stapling apparatus with manually retractable firing system |
US11583279B2 (en) | 2008-10-10 | 2023-02-21 | Cilag Gmbh International | Powered surgical cutting and stapling apparatus with manually retractable firing system |
US9370364B2 (en) | 2008-10-10 | 2016-06-21 | Ethicon Endo-Surgery, Llc | Powered surgical cutting and stapling apparatus with manually retractable firing system |
US8608045B2 (en) | 2008-10-10 | 2013-12-17 | Ethicon Endo-Sugery, Inc. | Powered surgical cutting and stapling apparatus with manually retractable firing system |
US10932778B2 (en) | 2008-10-10 | 2021-03-02 | Ethicon Llc | Powered surgical cutting and stapling apparatus with manually retractable firing system |
US20100089970A1 (en) * | 2008-10-10 | 2010-04-15 | Ethicon Endo-Surgery, Inc. | Powered surgical cutting and stapling apparatus with manually retractable firing system |
US10149683B2 (en) | 2008-10-10 | 2018-12-11 | Ethicon Llc | Powered surgical cutting and stapling apparatus with manually retractable firing system |
US10758233B2 (en) | 2009-02-05 | 2020-09-01 | Ethicon Llc | Articulatable surgical instrument comprising a firing drive |
US8397971B2 (en) | 2009-02-05 | 2013-03-19 | Ethicon Endo-Surgery, Inc. | Sterilizable surgical instrument |
US11129615B2 (en) | 2009-02-05 | 2021-09-28 | Cilag Gmbh International | Surgical stapling system |
US8414577B2 (en) | 2009-02-05 | 2013-04-09 | Ethicon Endo-Surgery, Inc. | Surgical instruments and components for use in sterile environments |
US9393015B2 (en) | 2009-02-06 | 2016-07-19 | Ethicon Endo-Surgery, Llc | Motor driven surgical fastener device with cutting member reversing mechanism |
US10420550B2 (en) | 2009-02-06 | 2019-09-24 | Ethicon Llc | Motor driven surgical fastener device with switching system configured to prevent firing initiation until activated |
US9486214B2 (en) | 2009-02-06 | 2016-11-08 | Ethicon Endo-Surgery, Llc | Motor driven surgical fastener device with switching system configured to prevent firing initiation until activated |
US20110300222A1 (en) * | 2009-02-20 | 2011-12-08 | The Regents Of The University Of California | Luminescent porous silicon nanoparticles, methods of making and using same |
US20100260686A1 (en) * | 2009-04-09 | 2010-10-14 | Washington, University Of | Nanoparticles for brain tumor imaging |
US8961825B2 (en) | 2009-04-15 | 2015-02-24 | Cornell University | Fluorescent silica nanoparticles through silica densification |
EP2448864A4 (en) * | 2009-06-30 | 2015-10-14 | Nalco Co | Silica-based particle composition |
US20100330366A1 (en) * | 2009-06-30 | 2010-12-30 | Keiser Bruce A | Silica-based particle composition |
US11419955B2 (en) | 2009-07-02 | 2022-08-23 | Sloan-Kettering Institute For Cancer Research | Multimodal silica-based nanoparticles |
US10548998B2 (en) | 2009-07-02 | 2020-02-04 | Sloan-Kettering Institute For Cancer Research | Multimodal silica-based nanoparticles |
US9999694B2 (en) | 2009-07-02 | 2018-06-19 | Sloan-Kettering Institute For Cancer Research | Multimodal silica-based nanoparticles |
US9625456B2 (en) | 2009-07-02 | 2017-04-18 | Sloan-Kettering Institute For Cancer Research | Fluorescent silica-based nanoparticles |
US10548997B2 (en) | 2009-07-02 | 2020-02-04 | Sloan-Kettering Institute For Cancer Research | Fluorescent silica-based nanoparticles |
US10520500B2 (en) * | 2009-10-09 | 2019-12-31 | Abdeslam El Harrak | Labelled silica-based nanomaterial with enhanced properties and uses thereof |
US20130064776A1 (en) * | 2009-10-09 | 2013-03-14 | Universite De Strasbourg | Labelled silica-based nanomaterial with enhanced properties and uses thereof |
US10191060B2 (en) | 2009-11-09 | 2019-01-29 | University Of Washington | Functionalized chromophoric polymer dots and bioconjugates thereof |
US11835526B2 (en) | 2009-11-09 | 2023-12-05 | University Of Washington | Functionalized chromophoric polymer dots and bioconjugates thereof |
US20110110858A1 (en) * | 2009-11-11 | 2011-05-12 | Omer Aras | Gold nanoparticle imaging agents and uses thereof |
US10751076B2 (en) | 2009-12-24 | 2020-08-25 | Ethicon Llc | Motor-driven surgical cutting instrument with electric actuator directional control assembly |
US11291449B2 (en) | 2009-12-24 | 2022-04-05 | Cilag Gmbh International | Surgical cutting instrument that analyzes tissue thickness |
US9260957B2 (en) * | 2009-12-24 | 2016-02-16 | Total Sa | Use of nanoparticles for labelling oil field injection waters |
US20130084643A1 (en) * | 2009-12-24 | 2013-04-04 | Total Sa | Use of nanoparticles for labelling oil field injection waters |
US8513031B2 (en) * | 2009-12-25 | 2013-08-20 | Konica Minolta Medical & Graphic, Inc. | Fluorescent substance-containing silica nanoparticles with coating having high bulk refractive index |
US20120252140A1 (en) * | 2009-12-25 | 2012-10-04 | Konica Minolta Medical & Graphic, Inc. | Fluorescent substance-containing silica nanoparticles and biosubstance labeling agent |
US9068084B2 (en) | 2010-01-19 | 2015-06-30 | Wuxi Zodolabs Biotech Co., Ltd. | Silica nanoparticles doped with dye having negative charge and preparing method thereof |
US10183975B2 (en) | 2010-02-04 | 2019-01-22 | Morphotek, Inc. | Chlorotoxin polypeptides and conjugates and uses thereof |
US9018347B2 (en) | 2010-02-04 | 2015-04-28 | Morphotek, Inc. | Chlorotoxin polypeptides and conjugates and uses thereof |
US9637526B2 (en) | 2010-02-04 | 2017-05-02 | Morphotek, Inc. | Chlorotoxin polypeptides and conjugates and uses thereof |
US9234015B2 (en) | 2010-02-04 | 2016-01-12 | Morphotek, Inc. | Chlorotoxin polypeptides and conjugates and uses thereof |
US11390917B2 (en) | 2010-02-12 | 2022-07-19 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
US11254968B2 (en) | 2010-02-12 | 2022-02-22 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
US20110203023P1 (en) * | 2010-02-16 | 2011-08-18 | Menachem Bronstein | Gypsophila Plant Named 'Pearl Blossom'' |
US20110214488A1 (en) * | 2010-03-04 | 2011-09-08 | Rose Peter E | Colloidal-crystal quantum dots as tracers in underground formations |
US10125601B2 (en) * | 2010-03-04 | 2018-11-13 | University Of Utah Research Foundation | Colloidal-crystal quantum dots as tracers in underground formations |
US10822381B2 (en) | 2010-05-11 | 2020-11-03 | Fred Hutchinson Cancer Research Center | Chlorotoxin variants, conjugates, and methods for their use |
US9944683B2 (en) | 2010-05-11 | 2018-04-17 | Fred Hutchinson Cancer Research Center | Chlorotoxin variants, conjugates, and methods for their use |
US11478247B2 (en) | 2010-07-30 | 2022-10-25 | Cilag Gmbh International | Tissue acquisition arrangements and methods for surgical stapling devices |
US8789741B2 (en) | 2010-09-24 | 2014-07-29 | Ethicon Endo-Surgery, Inc. | Surgical instrument with trigger assembly for generating multiple actuation motions |
US9301753B2 (en) | 2010-09-30 | 2016-04-05 | Ethicon Endo-Surgery, Llc | Expandable tissue thickness compensator |
US11857187B2 (en) | 2010-09-30 | 2024-01-02 | Cilag Gmbh International | Tissue thickness compensator comprising controlled release and expansion |
US11925354B2 (en) | 2010-09-30 | 2024-03-12 | Cilag Gmbh International | Staple cartridge comprising staples positioned within a compressible portion thereof |
US11944292B2 (en) | 2010-09-30 | 2024-04-02 | Cilag Gmbh International | Anvil layer attached to a proximal end of an end effector |
US10869669B2 (en) | 2010-09-30 | 2020-12-22 | Ethicon Llc | Surgical instrument assembly |
US10835251B2 (en) | 2010-09-30 | 2020-11-17 | Ethicon Llc | Surgical instrument assembly including an end effector configurable in different positions |
US10123798B2 (en) | 2010-09-30 | 2018-11-13 | Ethicon Llc | Tissue thickness compensator comprising controlled release and expansion |
US10136890B2 (en) | 2010-09-30 | 2018-11-27 | Ethicon Llc | Staple cartridge comprising a variable thickness compressible portion |
US8893949B2 (en) | 2010-09-30 | 2014-11-25 | Ethicon Endo-Surgery, Inc. | Surgical stapler with floating anvil |
US9788834B2 (en) | 2010-09-30 | 2017-10-17 | Ethicon Llc | Layer comprising deployable attachment members |
US9332974B2 (en) | 2010-09-30 | 2016-05-10 | Ethicon Endo-Surgery, Llc | Layered tissue thickness compensator |
US9833242B2 (en) | 2010-09-30 | 2017-12-05 | Ethicon Endo-Surgery, Llc | Tissue thickness compensators |
US9345477B2 (en) | 2010-09-30 | 2016-05-24 | Ethicon Endo-Surgery, Llc | Tissue stapler having a thickness compensator comprising incorporating a hemostatic agent |
US9566061B2 (en) | 2010-09-30 | 2017-02-14 | Ethicon Endo-Surgery, Llc | Fastener cartridge comprising a releasably attached tissue thickness compensator |
US9301752B2 (en) | 2010-09-30 | 2016-04-05 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator comprising a plurality of capsules |
US10258330B2 (en) | 2010-09-30 | 2019-04-16 | Ethicon Llc | End effector including an implantable arrangement |
US11911027B2 (en) | 2010-09-30 | 2024-02-27 | Cilag Gmbh International | Adhesive film laminate |
US9801634B2 (en) | 2010-09-30 | 2017-10-31 | Ethicon Llc | Tissue thickness compensator for a surgical stapler |
US10258332B2 (en) | 2010-09-30 | 2019-04-16 | Ethicon Llc | Stapling system comprising an adjunct and a flowable adhesive |
US10888328B2 (en) | 2010-09-30 | 2021-01-12 | Ethicon Llc | Surgical end effector |
US11406377B2 (en) | 2010-09-30 | 2022-08-09 | Cilag Gmbh International | Adhesive film laminate |
US10265074B2 (en) | 2010-09-30 | 2019-04-23 | Ethicon Llc | Implantable layers for surgical stapling devices |
US9358005B2 (en) | 2010-09-30 | 2016-06-07 | Ethicon Endo-Surgery, Llc | End effector layer including holding features |
US9833238B2 (en) | 2010-09-30 | 2017-12-05 | Ethicon Endo-Surgery, Llc | Retainer assembly including a tissue thickness compensator |
US8978954B2 (en) | 2010-09-30 | 2015-03-17 | Ethicon Endo-Surgery, Inc. | Staple cartridge comprising an adjustable distal portion |
US10265072B2 (en) | 2010-09-30 | 2019-04-23 | Ethicon Llc | Surgical stapling system comprising an end effector including an implantable layer |
US11812965B2 (en) | 2010-09-30 | 2023-11-14 | Cilag Gmbh International | Layer of material for a surgical end effector |
US10213198B2 (en) | 2010-09-30 | 2019-02-26 | Ethicon Llc | Actuator for releasing a tissue thickness compensator from a fastener cartridge |
US9833236B2 (en) | 2010-09-30 | 2017-12-05 | Ethicon Llc | Tissue thickness compensator for surgical staplers |
US11298125B2 (en) | 2010-09-30 | 2022-04-12 | Cilag Gmbh International | Tissue stapler having a thickness compensator |
US10548600B2 (en) | 2010-09-30 | 2020-02-04 | Ethicon Llc | Multiple thickness implantable layers for surgical stapling devices |
US10987102B2 (en) | 2010-09-30 | 2021-04-27 | Ethicon Llc | Tissue thickness compensator comprising a plurality of layers |
US9808247B2 (en) | 2010-09-30 | 2017-11-07 | Ethicon Llc | Stapling system comprising implantable layers |
US11737754B2 (en) | 2010-09-30 | 2023-08-29 | Cilag Gmbh International | Surgical stapler with floating anvil |
US9307965B2 (en) | 2010-09-30 | 2016-04-12 | Ethicon Endo-Surgery, Llc | Tissue stapler having a thickness compensator incorporating an anti-microbial agent |
US9364233B2 (en) | 2010-09-30 | 2016-06-14 | Ethicon Endo-Surgery, Llc | Tissue thickness compensators for circular surgical staplers |
US9924947B2 (en) | 2010-09-30 | 2018-03-27 | Ethicon Llc | Staple cartridge comprising a compressible portion |
US9220500B2 (en) | 2010-09-30 | 2015-12-29 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator comprising structure to produce a resilient load |
US9700317B2 (en) | 2010-09-30 | 2017-07-11 | Ethicon Endo-Surgery, Llc | Fastener cartridge comprising a releasable tissue thickness compensator |
US11154296B2 (en) | 2010-09-30 | 2021-10-26 | Cilag Gmbh International | Anvil layer attached to a proximal end of an end effector |
US9839420B2 (en) | 2010-09-30 | 2017-12-12 | Ethicon Llc | Tissue thickness compensator comprising at least one medicament |
US10149682B2 (en) | 2010-09-30 | 2018-12-11 | Ethicon Llc | Stapling system including an actuation system |
US11849952B2 (en) | 2010-09-30 | 2023-12-26 | Cilag Gmbh International | Staple cartridge comprising staples positioned within a compressible portion thereof |
US9282962B2 (en) | 2010-09-30 | 2016-03-15 | Ethicon Endo-Surgery, Llc | Adhesive film laminate |
US10898193B2 (en) | 2010-09-30 | 2021-01-26 | Ethicon Llc | End effector for use with a surgical instrument |
US11850310B2 (en) | 2010-09-30 | 2023-12-26 | Cilag Gmbh International | Staple cartridge including an adjunct |
US10064624B2 (en) | 2010-09-30 | 2018-09-04 | Ethicon Llc | End effector with implantable layer |
US10485536B2 (en) | 2010-09-30 | 2019-11-26 | Ethicon Llc | Tissue stapler having an anti-microbial agent |
US10194910B2 (en) | 2010-09-30 | 2019-02-05 | Ethicon Llc | Stapling assemblies comprising a layer |
US10588623B2 (en) | 2010-09-30 | 2020-03-17 | Ethicon Llc | Adhesive film laminate |
US9386988B2 (en) | 2010-09-30 | 2016-07-12 | Ethicon End-Surgery, LLC | Retainer assembly including a tissue thickness compensator |
US9795383B2 (en) | 2010-09-30 | 2017-10-24 | Ethicon Llc | Tissue thickness compensator comprising resilient members |
US11684360B2 (en) | 2010-09-30 | 2023-06-27 | Cilag Gmbh International | Staple cartridge comprising a variable thickness compressible portion |
US9320518B2 (en) | 2010-09-30 | 2016-04-26 | Ethicon Endo-Surgery, Llc | Tissue stapler having a thickness compensator incorporating an oxygen generating agent |
US10743877B2 (en) | 2010-09-30 | 2020-08-18 | Ethicon Llc | Surgical stapler with floating anvil |
US10182819B2 (en) | 2010-09-30 | 2019-01-22 | Ethicon Llc | Implantable layer assemblies |
US9844372B2 (en) | 2010-09-30 | 2017-12-19 | Ethicon Llc | Retainer assembly including a tissue thickness compensator |
US9220501B2 (en) | 2010-09-30 | 2015-12-29 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensators |
US9277919B2 (en) | 2010-09-30 | 2016-03-08 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator comprising fibers to produce a resilient load |
US11540824B2 (en) | 2010-09-30 | 2023-01-03 | Cilag Gmbh International | Tissue thickness compensator |
US10335150B2 (en) | 2010-09-30 | 2019-07-02 | Ethicon Llc | Staple cartridge comprising an implantable layer |
US11559496B2 (en) | 2010-09-30 | 2023-01-24 | Cilag Gmbh International | Tissue thickness compensator configured to redistribute compressive forces |
US10335148B2 (en) | 2010-09-30 | 2019-07-02 | Ethicon Llc | Staple cartridge including a tissue thickness compensator for a surgical stapler |
US10028743B2 (en) | 2010-09-30 | 2018-07-24 | Ethicon Llc | Staple cartridge assembly comprising an implantable layer |
US9433419B2 (en) | 2010-09-30 | 2016-09-06 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator comprising a plurality of layers |
US9629814B2 (en) | 2010-09-30 | 2017-04-25 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator configured to redistribute compressive forces |
US9826978B2 (en) | 2010-09-30 | 2017-11-28 | Ethicon Llc | End effectors with same side closure and firing motions |
US10463372B2 (en) | 2010-09-30 | 2019-11-05 | Ethicon Llc | Staple cartridge comprising multiple regions |
US9615826B2 (en) | 2010-09-30 | 2017-04-11 | Ethicon Endo-Surgery, Llc | Multiple thickness implantable layers for surgical stapling devices |
US9272406B2 (en) | 2010-09-30 | 2016-03-01 | Ethicon Endo-Surgery, Llc | Fastener cartridge comprising a cutting member for releasing a tissue thickness compensator |
US9848875B2 (en) | 2010-09-30 | 2017-12-26 | Ethicon Llc | Anvil layer attached to a proximal end of an end effector |
US10363031B2 (en) | 2010-09-30 | 2019-07-30 | Ethicon Llc | Tissue thickness compensators for surgical staplers |
US11571215B2 (en) | 2010-09-30 | 2023-02-07 | Cilag Gmbh International | Layer of material for a surgical end effector |
US11083452B2 (en) | 2010-09-30 | 2021-08-10 | Cilag Gmbh International | Staple cartridge including a tissue thickness compensator |
US9480476B2 (en) | 2010-09-30 | 2016-11-01 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator comprising resilient members |
US11672536B2 (en) | 2010-09-30 | 2023-06-13 | Cilag Gmbh International | Layer of material for a surgical end effector |
US9861361B2 (en) | 2010-09-30 | 2018-01-09 | Ethicon Llc | Releasable tissue thickness compensator and fastener cartridge having the same |
US11583277B2 (en) | 2010-09-30 | 2023-02-21 | Cilag Gmbh International | Layer of material for a surgical end effector |
US9592050B2 (en) | 2010-09-30 | 2017-03-14 | Ethicon Endo-Surgery, Llc | End effector comprising a distal tissue abutment member |
US9883861B2 (en) | 2010-09-30 | 2018-02-06 | Ethicon Llc | Retainer assembly including a tissue thickness compensator |
US10945731B2 (en) | 2010-09-30 | 2021-03-16 | Ethicon Llc | Tissue thickness compensator comprising controlled release and expansion |
US11883025B2 (en) | 2010-09-30 | 2024-01-30 | Cilag Gmbh International | Tissue thickness compensator comprising a plurality of layers |
US9592053B2 (en) | 2010-09-30 | 2017-03-14 | Ethicon Endo-Surgery, Llc | Staple cartridge comprising multiple regions |
US9314246B2 (en) | 2010-09-30 | 2016-04-19 | Ethicon Endo-Surgery, Llc | Tissue stapler having a thickness compensator incorporating an anti-inflammatory agent |
US11395651B2 (en) | 2010-09-30 | 2022-07-26 | Cilag Gmbh International | Adhesive film laminate |
US9814462B2 (en) | 2010-09-30 | 2017-11-14 | Ethicon Llc | Assembly for fastening tissue comprising a compressible layer |
US10624861B2 (en) | 2010-09-30 | 2020-04-21 | Ethicon Llc | Tissue thickness compensator configured to redistribute compressive forces |
US9232941B2 (en) | 2010-09-30 | 2016-01-12 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator comprising a reservoir |
US9572574B2 (en) | 2010-09-30 | 2017-02-21 | Ethicon Endo-Surgery, Llc | Tissue thickness compensators comprising therapeutic agents |
US10398436B2 (en) | 2010-09-30 | 2019-09-03 | Ethicon Llc | Staple cartridge comprising staples positioned within a compressible portion thereof |
US11602340B2 (en) | 2010-09-30 | 2023-03-14 | Cilag Gmbh International | Adhesive film laminate |
US10405854B2 (en) | 2010-09-30 | 2019-09-10 | Ethicon Llc | Surgical stapling cartridge with layer retention features |
US10695062B2 (en) | 2010-10-01 | 2020-06-30 | Ethicon Llc | Surgical instrument including a retractable firing member |
US11529142B2 (en) | 2010-10-01 | 2022-12-20 | Cilag Gmbh International | Surgical instrument having a power control circuit |
US11747327B2 (en) | 2011-02-18 | 2023-09-05 | Bio-Rad Laboratories, Inc. | Compositions and methods for molecular labeling |
US11168353B2 (en) | 2011-02-18 | 2021-11-09 | Bio-Rad Laboratories, Inc. | Compositions and methods for molecular labeling |
US11768198B2 (en) | 2011-02-18 | 2023-09-26 | Bio-Rad Laboratories, Inc. | Compositions and methods for molecular labeling |
US9579283B2 (en) | 2011-04-28 | 2017-02-28 | Stc.Unm | Porous nanoparticle-supported lipid bilayers (protocells) for targeted delivery and methods of using same |
US9241714B2 (en) | 2011-04-29 | 2016-01-26 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator and method for making the same |
US11504116B2 (en) | 2011-04-29 | 2022-11-22 | Cilag Gmbh International | Layer of material for a surgical end effector |
US9211120B2 (en) | 2011-04-29 | 2015-12-15 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator comprising a plurality of medicaments |
US10117652B2 (en) | 2011-04-29 | 2018-11-06 | Ethicon Llc | End effector comprising a tissue thickness compensator and progressively released attachment members |
US9351730B2 (en) | 2011-04-29 | 2016-05-31 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator comprising channels |
US10435661B2 (en) | 2011-05-13 | 2019-10-08 | The Regents Of The University Of California | Photothermal substrates for selective transfection of cells |
US11129616B2 (en) | 2011-05-27 | 2021-09-28 | Cilag Gmbh International | Surgical stapling system |
US10736634B2 (en) | 2011-05-27 | 2020-08-11 | Ethicon Llc | Robotically-driven surgical instrument including a drive system |
US10780539B2 (en) | 2011-05-27 | 2020-09-22 | Ethicon Llc | Stapling instrument for use with a robotic system |
US10426478B2 (en) | 2011-05-27 | 2019-10-01 | Ethicon Llc | Surgical stapling systems |
US11612394B2 (en) | 2011-05-27 | 2023-03-28 | Cilag Gmbh International | Automated end effector component reloading system for use with a robotic system |
US10420561B2 (en) | 2011-05-27 | 2019-09-24 | Ethicon Llc | Robotically-driven surgical instrument |
US11439470B2 (en) | 2011-05-27 | 2022-09-13 | Cilag Gmbh International | Robotically-controlled surgical instrument with selectively articulatable end effector |
US10231794B2 (en) | 2011-05-27 | 2019-03-19 | Ethicon Llc | Surgical stapling instruments with rotatable staple deployment arrangements |
US10485546B2 (en) | 2011-05-27 | 2019-11-26 | Ethicon Llc | Robotically-driven surgical assembly |
US10524790B2 (en) | 2011-05-27 | 2020-01-07 | Ethicon Llc | Robotically-controlled surgical stapling devices that produce formed staples having different lengths |
US10980534B2 (en) | 2011-05-27 | 2021-04-20 | Ethicon Llc | Robotically-controlled motorized surgical instrument with an end effector |
US10071452B2 (en) | 2011-05-27 | 2018-09-11 | Ethicon Llc | Automated end effector component reloading system for use with a robotic system |
US11266410B2 (en) | 2011-05-27 | 2022-03-08 | Cilag Gmbh International | Surgical device for use with a robotic system |
US10335151B2 (en) | 2011-05-27 | 2019-07-02 | Ethicon Llc | Robotically-driven surgical instrument |
US10813641B2 (en) | 2011-05-27 | 2020-10-27 | Ethicon Llc | Robotically-driven surgical instrument |
US10130366B2 (en) | 2011-05-27 | 2018-11-20 | Ethicon Llc | Automated reloading devices for replacing used end effectors on robotic surgical systems |
US9271799B2 (en) | 2011-05-27 | 2016-03-01 | Ethicon Endo-Surgery, Llc | Robotic surgical system with removable motor housing |
US9913648B2 (en) | 2011-05-27 | 2018-03-13 | Ethicon Endo-Surgery, Llc | Surgical system |
US11918208B2 (en) | 2011-05-27 | 2024-03-05 | Cilag Gmbh International | Robotically-controlled shaft based rotary drive systems for surgical instruments |
US9072535B2 (en) | 2011-05-27 | 2015-07-07 | Ethicon Endo-Surgery, Inc. | Surgical stapling instruments with rotatable staple deployment arrangements |
US10383633B2 (en) | 2011-05-27 | 2019-08-20 | Ethicon Llc | Robotically-driven surgical assembly |
US9775614B2 (en) | 2011-05-27 | 2017-10-03 | Ethicon Endo-Surgery, Llc | Surgical stapling instruments with rotatable staple deployment arrangements |
US11207064B2 (en) | 2011-05-27 | 2021-12-28 | Cilag Gmbh International | Automated end effector component reloading system for use with a robotic system |
US10617420B2 (en) | 2011-05-27 | 2020-04-14 | Ethicon Llc | Surgical system comprising drive systems |
US11583278B2 (en) | 2011-05-27 | 2023-02-21 | Cilag Gmbh International | Surgical stapling system having multi-direction articulation |
US10004506B2 (en) | 2011-05-27 | 2018-06-26 | Ethicon Llc | Surgical system |
US11754499B2 (en) | 2011-06-02 | 2023-09-12 | Bio-Rad Laboratories, Inc. | Enzyme quantification |
US9532949B2 (en) | 2011-07-19 | 2017-01-03 | Stc.Unm | Intraperitoneally-administered nanocarriers that release their therapeutic load based on the inflammatory environment of cancers |
US11898193B2 (en) | 2011-07-20 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Manipulating droplet size |
US20170115300A1 (en) * | 2011-09-09 | 2017-04-27 | Konica Minolta, Inc. | Biological substance detection method |
JP2016027340A (en) * | 2011-09-09 | 2016-02-18 | コニカミノルタ株式会社 | Fluorescent labelling compound for detecting biological substance |
US10551386B2 (en) * | 2011-09-09 | 2020-02-04 | Konica Minolta, Inc. | Biological substance detection method |
US20140220598A1 (en) * | 2011-09-09 | 2014-08-07 | Tohoku University | Biological substance detection method |
US9055941B2 (en) | 2011-09-23 | 2015-06-16 | Ethicon Endo-Surgery, Inc. | Staple cartridge including collapsible deck |
US9592054B2 (en) | 2011-09-23 | 2017-03-14 | Ethicon Endo-Surgery, Llc | Surgical stapler with stationary staple drivers |
US9216019B2 (en) | 2011-09-23 | 2015-12-22 | Ethicon Endo-Surgery, Inc. | Surgical stapler with stationary staple drivers |
US9050084B2 (en) | 2011-09-23 | 2015-06-09 | Ethicon Endo-Surgery, Inc. | Staple cartridge including collapsible deck arrangement |
US9687237B2 (en) | 2011-09-23 | 2017-06-27 | Ethicon Endo-Surgery, Llc | Staple cartridge including collapsible deck arrangement |
CN103013016A (en) * | 2011-09-28 | 2013-04-03 | 国家纳米科学中心 | Medical carrier and medical composition and preparation method thereof |
US11697713B2 (en) | 2011-12-30 | 2023-07-11 | University Of Washington Through Its Center For Commercialization | Chromophoric polymer dots with narrow-band emission |
US9042765B2 (en) | 2012-01-16 | 2015-05-26 | Samsung Electronics Co., Ltd. | Image forming apparatus with improved heat transmission |
US9730697B2 (en) | 2012-02-13 | 2017-08-15 | Ethicon Endo-Surgery, Llc | Surgical cutting and fastening instrument with apparatus for determining cartridge and firing motion status |
US10695063B2 (en) | 2012-02-13 | 2020-06-30 | Ethicon Llc | Surgical cutting and fastening instrument with apparatus for determining cartridge and firing motion status |
US9044230B2 (en) | 2012-02-13 | 2015-06-02 | Ethicon Endo-Surgery, Inc. | Surgical cutting and fastening instrument with apparatus for determining cartridge and firing motion status |
US9198662B2 (en) | 2012-03-28 | 2015-12-01 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator having improved visibility |
US9320523B2 (en) | 2012-03-28 | 2016-04-26 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator comprising tissue ingrowth features |
US11918220B2 (en) | 2012-03-28 | 2024-03-05 | Cilag Gmbh International | Tissue thickness compensator comprising tissue ingrowth features |
US9307989B2 (en) | 2012-03-28 | 2016-04-12 | Ethicon Endo-Surgery, Llc | Tissue stapler having a thickness compensator incorportating a hydrophobic agent |
US9314247B2 (en) | 2012-03-28 | 2016-04-19 | Ethicon Endo-Surgery, Llc | Tissue stapler having a thickness compensator incorporating a hydrophilic agent |
US9204880B2 (en) | 2012-03-28 | 2015-12-08 | Ethicon Endo-Surgery, Inc. | Tissue thickness compensator comprising capsules defining a low pressure environment |
US9632081B2 (en) | 2012-03-28 | 2017-04-25 | Konica Minolta, Inc. | Detection method for biological substance |
US9414838B2 (en) | 2012-03-28 | 2016-08-16 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator comprised of a plurality of materials |
EP2833144A4 (en) * | 2012-03-28 | 2015-08-26 | Konica Minolta Inc | Method for detection biological substance |
US9724098B2 (en) | 2012-03-28 | 2017-08-08 | Ethicon Endo-Surgery, Llc | Staple cartridge comprising an implantable layer |
JPWO2013146694A1 (en) * | 2012-03-28 | 2015-12-14 | コニカミノルタ株式会社 | Detection method of biological material |
US9918716B2 (en) | 2012-03-28 | 2018-03-20 | Ethicon Llc | Staple cartridge comprising implantable layers |
US9517063B2 (en) | 2012-03-28 | 2016-12-13 | Ethicon Endo-Surgery, Llc | Movable member for use with a tissue thickness compensator |
US10441285B2 (en) | 2012-03-28 | 2019-10-15 | Ethicon Llc | Tissue thickness compensator comprising tissue ingrowth features |
US10667808B2 (en) | 2012-03-28 | 2020-06-02 | Ethicon Llc | Staple cartridge comprising an absorbable adjunct |
US9974538B2 (en) | 2012-03-28 | 2018-05-22 | Ethicon Llc | Staple cartridge comprising a compressible layer |
US11793509B2 (en) | 2012-03-28 | 2023-10-24 | Cilag Gmbh International | Staple cartridge including an implantable layer |
US11406378B2 (en) | 2012-03-28 | 2022-08-09 | Cilag Gmbh International | Staple cartridge comprising a compressible tissue thickness compensator |
US10064621B2 (en) | 2012-06-15 | 2018-09-04 | Ethicon Llc | Articulatable surgical instrument comprising a firing drive |
US9101358B2 (en) | 2012-06-15 | 2015-08-11 | Ethicon Endo-Surgery, Inc. | Articulatable surgical instrument comprising a firing drive |
US10959725B2 (en) | 2012-06-15 | 2021-03-30 | Ethicon Llc | Articulatable surgical instrument comprising a firing drive |
US11707273B2 (en) | 2012-06-15 | 2023-07-25 | Cilag Gmbh International | Articulatable surgical instrument comprising a firing drive |
US11534162B2 (en) | 2012-06-28 | 2022-12-27 | Cilag GmbH Inlernational | Robotically powered surgical device with manually-actuatable reversing system |
US10874391B2 (en) | 2012-06-28 | 2020-12-29 | Ethicon Llc | Surgical instrument system including replaceable end effectors |
US11918213B2 (en) | 2012-06-28 | 2024-03-05 | Cilag Gmbh International | Surgical stapler including couplers for attaching a shaft to an end effector |
US9408606B2 (en) | 2012-06-28 | 2016-08-09 | Ethicon Endo-Surgery, Llc | Robotically powered surgical device with manually-actuatable reversing system |
US11540829B2 (en) | 2012-06-28 | 2023-01-03 | Cilag Gmbh International | Surgical instrument system including replaceable end effectors |
US11806013B2 (en) | 2012-06-28 | 2023-11-07 | Cilag Gmbh International | Firing system arrangements for surgical instruments |
US10258333B2 (en) | 2012-06-28 | 2019-04-16 | Ethicon Llc | Surgical fastening apparatus with a rotary end effector drive shaft for selective engagement with a motorized drive system |
US11202631B2 (en) | 2012-06-28 | 2021-12-21 | Cilag Gmbh International | Stapling assembly comprising a firing lockout |
US11197671B2 (en) | 2012-06-28 | 2021-12-14 | Cilag Gmbh International | Stapling assembly comprising a lockout |
US9364230B2 (en) | 2012-06-28 | 2016-06-14 | Ethicon Endo-Surgery, Llc | Surgical stapling instruments with rotary joint assemblies |
US11154299B2 (en) | 2012-06-28 | 2021-10-26 | Cilag Gmbh International | Stapling assembly comprising a firing lockout |
US11857189B2 (en) | 2012-06-28 | 2024-01-02 | Cilag Gmbh International | Surgical instrument including first and second articulation joints |
US10485541B2 (en) | 2012-06-28 | 2019-11-26 | Ethicon Llc | Robotically powered surgical device with manually-actuatable reversing system |
US11141156B2 (en) | 2012-06-28 | 2021-10-12 | Cilag Gmbh International | Surgical stapling assembly comprising flexible output shaft |
US11464513B2 (en) | 2012-06-28 | 2022-10-11 | Cilag Gmbh International | Surgical instrument system including replaceable end effectors |
US11278284B2 (en) | 2012-06-28 | 2022-03-22 | Cilag Gmbh International | Rotary drive arrangements for surgical instruments |
US11510671B2 (en) | 2012-06-28 | 2022-11-29 | Cilag Gmbh International | Firing system lockout arrangements for surgical instruments |
US11141155B2 (en) | 2012-06-28 | 2021-10-12 | Cilag Gmbh International | Drive system for surgical tool |
US9289256B2 (en) | 2012-06-28 | 2016-03-22 | Ethicon Endo-Surgery, Llc | Surgical end effectors having angled tissue-contacting surfaces |
US9649111B2 (en) | 2012-06-28 | 2017-05-16 | Ethicon Endo-Surgery, Llc | Replaceable clip cartridge for a clip applier |
US9561038B2 (en) | 2012-06-28 | 2017-02-07 | Ethicon Endo-Surgery, Llc | Interchangeable clip applier |
US8747238B2 (en) | 2012-06-28 | 2014-06-10 | Ethicon Endo-Surgery, Inc. | Rotary drive shaft assemblies for surgical instruments with articulatable end effectors |
US9282974B2 (en) | 2012-06-28 | 2016-03-15 | Ethicon Endo-Surgery, Llc | Empty clip cartridge lockout |
US9119657B2 (en) | 2012-06-28 | 2015-09-01 | Ethicon Endo-Surgery, Inc. | Rotary actuatable closure arrangement for surgical end effector |
US10420555B2 (en) | 2012-06-28 | 2019-09-24 | Ethicon Llc | Hand held rotary powered surgical instruments with end effectors that are articulatable about multiple axes |
US11779420B2 (en) | 2012-06-28 | 2023-10-10 | Cilag Gmbh International | Robotic surgical attachments having manually-actuated retraction assemblies |
US11241230B2 (en) | 2012-06-28 | 2022-02-08 | Cilag Gmbh International | Clip applier tool for use with a robotic surgical system |
US11007004B2 (en) | 2012-06-28 | 2021-05-18 | Ethicon Llc | Powered multi-axial articulable electrosurgical device with external dissection features |
US9101385B2 (en) | 2012-06-28 | 2015-08-11 | Ethicon Endo-Surgery, Inc. | Electrode connections for rotary driven surgical tools |
US10639115B2 (en) | 2012-06-28 | 2020-05-05 | Ethicon Llc | Surgical end effectors having angled tissue-contacting surfaces |
US11622766B2 (en) | 2012-06-28 | 2023-04-11 | Cilag Gmbh International | Empty clip cartridge lockout |
US10932775B2 (en) | 2012-06-28 | 2021-03-02 | Ethicon Llc | Firing system lockout arrangements for surgical instruments |
US11109860B2 (en) | 2012-06-28 | 2021-09-07 | Cilag Gmbh International | Surgical end effectors for use with hand-held and robotically-controlled rotary powered surgical systems |
US9204879B2 (en) | 2012-06-28 | 2015-12-08 | Ethicon Endo-Surgery, Inc. | Flexible drive member |
US9907620B2 (en) | 2012-06-28 | 2018-03-06 | Ethicon Endo-Surgery, Llc | Surgical end effectors having angled tissue-contacting surfaces |
US9072536B2 (en) | 2012-06-28 | 2015-07-07 | Ethicon Endo-Surgery, Inc. | Differential locking arrangements for rotary powered surgical instruments |
US11083457B2 (en) | 2012-06-28 | 2021-08-10 | Cilag Gmbh International | Surgical instrument system including replaceable end effectors |
US10413294B2 (en) | 2012-06-28 | 2019-09-17 | Ethicon Llc | Shaft assembly arrangements for surgical instruments |
US11058423B2 (en) | 2012-06-28 | 2021-07-13 | Cilag Gmbh International | Stapling system including first and second closure systems for use with a surgical robot |
US10383630B2 (en) | 2012-06-28 | 2019-08-20 | Ethicon Llc | Surgical stapling device with rotary driven firing member |
US10687812B2 (en) | 2012-06-28 | 2020-06-23 | Ethicon Llc | Surgical instrument system including replaceable end effectors |
US9028494B2 (en) | 2012-06-28 | 2015-05-12 | Ethicon Endo-Surgery, Inc. | Interchangeable end effector coupling arrangement |
US11602346B2 (en) | 2012-06-28 | 2023-03-14 | Cilag Gmbh International | Robotically powered surgical device with manually-actuatable reversing system |
US11039837B2 (en) | 2012-06-28 | 2021-06-22 | Cilag Gmbh International | Firing system lockout arrangements for surgical instruments |
US9226751B2 (en) | 2012-06-28 | 2016-01-05 | Ethicon Endo-Surgery, Inc. | Surgical instrument system including replaceable end effectors |
US9125662B2 (en) | 2012-06-28 | 2015-09-08 | Ethicon Endo-Surgery, Inc. | Multi-axis articulating and rotating surgical tools |
US11373755B2 (en) | 2012-08-23 | 2022-06-28 | Cilag Gmbh International | Surgical device drive system including a ratchet mechanism |
US9988686B2 (en) | 2012-09-27 | 2018-06-05 | Cynvenio Biosystems, Inc. | Stimulus-sensitive microparticles and methods of use |
WO2014052875A1 (en) | 2012-09-27 | 2014-04-03 | Cynvenio Biosystems, Inc. | Stimulus-sensitive microparticles and methods of use |
EP2903603A4 (en) * | 2012-09-27 | 2016-08-10 | Cynvenio Biosystems Inc | Stimulus-sensitive microparticles and methods of use |
CN104981236A (en) * | 2012-09-27 | 2015-10-14 | 辛温尼奥生物系统公司 | Stimulus-sensitive microparticles and methods of use |
CN102921014A (en) * | 2012-11-15 | 2013-02-13 | 中国科学院化学研究所 | Biocompatible nano composite drug carrier with synergistic anti-tumor effect, drug with synergistic anti-tumor effect and preparation methods of biocompatible nano composite drug carrier and drug |
US10557846B2 (en) | 2012-11-16 | 2020-02-11 | Quantamatrix Inc. | Encoded polymeric microparticles |
JP2016501286A (en) * | 2012-11-16 | 2016-01-18 | エスエヌユー アールアンドディービー ファウンデーショ | Coded polymer particles |
US10156559B2 (en) | 2012-12-10 | 2018-12-18 | Fred Hutchinson Cancer Research Center | Lipocalin fusion partners |
US8873041B1 (en) | 2013-01-29 | 2014-10-28 | Bayspec, Inc. | Raman spectroscopy using multiple excitation wavelengths |
US9386984B2 (en) | 2013-02-08 | 2016-07-12 | Ethicon Endo-Surgery, Llc | Staple cartridge comprising a releasable cover |
US10092292B2 (en) | 2013-02-28 | 2018-10-09 | Ethicon Llc | Staple forming features for surgical stapling instrument |
US11246618B2 (en) | 2013-03-01 | 2022-02-15 | Cilag Gmbh International | Surgical instrument soft stop |
US9782169B2 (en) | 2013-03-01 | 2017-10-10 | Ethicon Llc | Rotary powered articulation joints for surgical instruments |
US10575868B2 (en) | 2013-03-01 | 2020-03-03 | Ethicon Llc | Surgical instrument with coupler assembly |
US9358003B2 (en) | 2013-03-01 | 2016-06-07 | Ethicon Endo-Surgery, Llc | Electromechanical surgical device with signal relay arrangement |
US9468438B2 (en) | 2013-03-01 | 2016-10-18 | Eticon Endo-Surgery, LLC | Sensor straightened end effector during removal through trocar |
US11529138B2 (en) | 2013-03-01 | 2022-12-20 | Cilag Gmbh International | Powered surgical instrument including a rotary drive screw |
US10226249B2 (en) | 2013-03-01 | 2019-03-12 | Ethicon Llc | Articulatable surgical instruments with conductive pathways for signal communication |
US9307986B2 (en) | 2013-03-01 | 2016-04-12 | Ethicon Endo-Surgery, Llc | Surgical instrument soft stop |
US10285695B2 (en) | 2013-03-01 | 2019-05-14 | Ethicon Llc | Articulatable surgical instruments with conductive pathways |
US9326767B2 (en) | 2013-03-01 | 2016-05-03 | Ethicon Endo-Surgery, Llc | Joystick switch assemblies for surgical instruments |
US9700309B2 (en) | 2013-03-01 | 2017-07-11 | Ethicon Llc | Articulatable surgical instruments with conductive pathways for signal communication |
US9398911B2 (en) | 2013-03-01 | 2016-07-26 | Ethicon Endo-Surgery, Llc | Rotary powered surgical instruments with multiple degrees of freedom |
US9554794B2 (en) | 2013-03-01 | 2017-01-31 | Ethicon Endo-Surgery, Llc | Multiple processor motor control for modular surgical instruments |
US9345481B2 (en) | 2013-03-13 | 2016-05-24 | Ethicon Endo-Surgery, Llc | Staple cartridge tissue thickness sensor system |
US9808244B2 (en) | 2013-03-14 | 2017-11-07 | Ethicon Llc | Sensor arrangements for absolute positioning system for surgical instruments |
US9883860B2 (en) | 2013-03-14 | 2018-02-06 | Ethicon Llc | Interchangeable shaft assemblies for use with a surgical instrument |
US10617416B2 (en) | 2013-03-14 | 2020-04-14 | Ethicon Llc | Control systems for surgical instruments |
US9351726B2 (en) | 2013-03-14 | 2016-05-31 | Ethicon Endo-Surgery, Llc | Articulation control system for articulatable surgical instruments |
US9351727B2 (en) | 2013-03-14 | 2016-05-31 | Ethicon Endo-Surgery, Llc | Drive train control arrangements for modular surgical instruments |
US9888919B2 (en) | 2013-03-14 | 2018-02-13 | Ethicon Llc | Method and system for operating a surgical instrument |
US10238391B2 (en) | 2013-03-14 | 2019-03-26 | Ethicon Llc | Drive train control arrangements for modular surgical instruments |
US10514381B2 (en) | 2013-03-14 | 2019-12-24 | University Of Washington Through Its Center For Commercialization | Polymer dot compositions and related methods |
US9629623B2 (en) | 2013-03-14 | 2017-04-25 | Ethicon Endo-Surgery, Llc | Drive system lockout arrangements for modular surgical instruments |
US11266406B2 (en) | 2013-03-14 | 2022-03-08 | Cilag Gmbh International | Control systems for surgical instruments |
US9332987B2 (en) | 2013-03-14 | 2016-05-10 | Ethicon Endo-Surgery, Llc | Control arrangements for a drive member of a surgical instrument |
US9629629B2 (en) | 2013-03-14 | 2017-04-25 | Ethicon Endo-Surgey, LLC | Control systems for surgical instruments |
US10893867B2 (en) | 2013-03-14 | 2021-01-19 | Ethicon Llc | Drive train control arrangements for modular surgical instruments |
EP2972349B1 (en) * | 2013-03-14 | 2019-10-23 | University Of Washington Through Its Center For Commercialization | Polymer dot compositions and related methods |
US10470762B2 (en) | 2013-03-14 | 2019-11-12 | Ethicon Llc | Multi-function motor for a surgical instrument |
US9687230B2 (en) | 2013-03-14 | 2017-06-27 | Ethicon Llc | Articulatable surgical instrument comprising a firing drive |
WO2014153051A1 (en) | 2013-03-14 | 2014-09-25 | University Of Washington Through Its Center For Commercialization | Polymer dot compositions and related methods |
US10982217B2 (en) | 2013-03-15 | 2021-04-20 | The Regents Of The University Of California | High-throughput cargo delivery into live cells using photothermal platforms |
US10039847B2 (en) | 2013-03-15 | 2018-08-07 | Sloan-Kettering Institute For Cancer Research | Multimodal silica-based nanoparticles |
US9784730B2 (en) | 2013-03-21 | 2017-10-10 | University Of Washington Through Its Center For Commercialization | Nanoparticle for targeting brain tumors and delivery of O6-benzylguanine |
US9332984B2 (en) | 2013-03-27 | 2016-05-10 | Ethicon Endo-Surgery, Llc | Fastener cartridge assemblies |
US9572577B2 (en) | 2013-03-27 | 2017-02-21 | Ethicon Endo-Surgery, Llc | Fastener cartridge comprising a tissue thickness compensator including openings therein |
US9795384B2 (en) | 2013-03-27 | 2017-10-24 | Ethicon Llc | Fastener cartridge comprising a tissue thickness compensator and a gap setting element |
US10888318B2 (en) | 2013-04-16 | 2021-01-12 | Ethicon Llc | Powered surgical stapler |
US9844368B2 (en) | 2013-04-16 | 2017-12-19 | Ethicon Llc | Surgical system comprising first and second drive systems |
US11633183B2 (en) | 2013-04-16 | 2023-04-25 | Cilag International GmbH | Stapling assembly comprising a retraction drive |
US9867612B2 (en) | 2013-04-16 | 2018-01-16 | Ethicon Llc | Powered surgical stapler |
US11622763B2 (en) | 2013-04-16 | 2023-04-11 | Cilag Gmbh International | Stapling assembly comprising a shiftable drive |
US10702266B2 (en) | 2013-04-16 | 2020-07-07 | Ethicon Llc | Surgical instrument system |
US10405857B2 (en) | 2013-04-16 | 2019-09-10 | Ethicon Llc | Powered linear surgical stapler |
US11564679B2 (en) | 2013-04-16 | 2023-01-31 | Cilag Gmbh International | Powered surgical stapler |
US11406381B2 (en) | 2013-04-16 | 2022-08-09 | Cilag Gmbh International | Powered surgical stapler |
US11638581B2 (en) | 2013-04-16 | 2023-05-02 | Cilag Gmbh International | Powered surgical stapler |
US11690615B2 (en) | 2013-04-16 | 2023-07-04 | Cilag Gmbh International | Surgical system including an electric motor and a surgical instrument |
US9826976B2 (en) | 2013-04-16 | 2017-11-28 | Ethicon Llc | Motor driven surgical instruments with lockable dual drive shafts |
US9814460B2 (en) | 2013-04-16 | 2017-11-14 | Ethicon Llc | Modular motor driven surgical instruments with status indication arrangements |
US11395652B2 (en) | 2013-04-16 | 2022-07-26 | Cilag Gmbh International | Powered surgical stapler |
US10149680B2 (en) | 2013-04-16 | 2018-12-11 | Ethicon Llc | Surgical instrument comprising a gap setting system |
US9801626B2 (en) | 2013-04-16 | 2017-10-31 | Ethicon Llc | Modular motor driven surgical instruments with alignment features for aligning rotary drive shafts with surgical end effector shafts |
US10136887B2 (en) | 2013-04-16 | 2018-11-27 | Ethicon Llc | Drive system decoupling arrangement for a surgical instrument |
US9649110B2 (en) | 2013-04-16 | 2017-05-16 | Ethicon Llc | Surgical instrument comprising a closing drive and a firing drive operated from the same rotatable output |
US9574644B2 (en) | 2013-05-30 | 2017-02-21 | Ethicon Endo-Surgery, Llc | Power module for use with a surgical instrument |
US10869665B2 (en) | 2013-08-23 | 2020-12-22 | Ethicon Llc | Surgical instrument system including a control system |
US11389160B2 (en) | 2013-08-23 | 2022-07-19 | Cilag Gmbh International | Surgical system comprising a display |
US11504119B2 (en) | 2013-08-23 | 2022-11-22 | Cilag Gmbh International | Surgical instrument including an electronic firing lockout |
US11109858B2 (en) | 2013-08-23 | 2021-09-07 | Cilag Gmbh International | Surgical instrument including a display which displays the position of a firing element |
US9775609B2 (en) | 2013-08-23 | 2017-10-03 | Ethicon Llc | Tamper proof circuit for surgical instrument battery pack |
US9283054B2 (en) | 2013-08-23 | 2016-03-15 | Ethicon Endo-Surgery, Llc | Interactive displays |
US10898190B2 (en) | 2013-08-23 | 2021-01-26 | Ethicon Llc | Secondary battery arrangements for powered surgical instruments |
US10441281B2 (en) | 2013-08-23 | 2019-10-15 | Ethicon Llc | surgical instrument including securing and aligning features |
US10624634B2 (en) | 2013-08-23 | 2020-04-21 | Ethicon Llc | Firing trigger lockout arrangements for surgical instruments |
US11026680B2 (en) | 2013-08-23 | 2021-06-08 | Cilag Gmbh International | Surgical instrument configured to operate in different states |
US11918209B2 (en) | 2013-08-23 | 2024-03-05 | Cilag Gmbh International | Torque optimization for surgical instruments |
US11133106B2 (en) | 2013-08-23 | 2021-09-28 | Cilag Gmbh International | Surgical instrument assembly comprising a retraction assembly |
US9445813B2 (en) | 2013-08-23 | 2016-09-20 | Ethicon Endo-Surgery, Llc | Closure indicator systems for surgical instruments |
US9808249B2 (en) | 2013-08-23 | 2017-11-07 | Ethicon Llc | Attachment portions for surgical instrument assemblies |
US11376001B2 (en) | 2013-08-23 | 2022-07-05 | Cilag Gmbh International | Surgical stapling device with rotary multi-turn retraction mechanism |
US9987006B2 (en) | 2013-08-23 | 2018-06-05 | Ethicon Llc | Shroud retention arrangement for sterilizable surgical instruments |
US10201349B2 (en) | 2013-08-23 | 2019-02-12 | Ethicon Llc | End effector detection and firing rate modulation systems for surgical instruments |
US9924942B2 (en) | 2013-08-23 | 2018-03-27 | Ethicon Llc | Motor-powered articulatable surgical instruments |
US11134940B2 (en) | 2013-08-23 | 2021-10-05 | Cilag Gmbh International | Surgical instrument including a variable speed firing member |
US9510828B2 (en) | 2013-08-23 | 2016-12-06 | Ethicon Endo-Surgery, Llc | Conductor arrangements for electrically powered surgical instruments with rotatable end effectors |
US9700310B2 (en) | 2013-08-23 | 2017-07-11 | Ethicon Llc | Firing member retraction devices for powered surgical instruments |
US11000274B2 (en) | 2013-08-23 | 2021-05-11 | Ethicon Llc | Powered surgical instrument |
US10828032B2 (en) | 2013-08-23 | 2020-11-10 | Ethicon Llc | End effector detection systems for surgical instruments |
US11701110B2 (en) | 2013-08-23 | 2023-07-18 | Cilag Gmbh International | Surgical instrument including a drive assembly movable in a non-motorized mode of operation |
US11559580B1 (en) | 2013-09-17 | 2023-01-24 | Blaze Bioscience, Inc. | Tissue-homing peptide conjugates and methods of use thereof |
US11174509B2 (en) | 2013-12-12 | 2021-11-16 | Bio-Rad Laboratories, Inc. | Distinguishing rare variations in a nucleic acid sequence from a sample |
US20150177153A1 (en) * | 2013-12-20 | 2015-06-25 | Sicpa Holding Sa | Thermoluminescent composite particle and marking comprising same |
US11719644B2 (en) * | 2013-12-20 | 2023-08-08 | Sicpa Holding Sa | Thermoluminescent composite particle and marking comprising same |
US11583273B2 (en) | 2013-12-23 | 2023-02-21 | Cilag Gmbh International | Surgical stapling system including a firing beam extending through an articulation region |
US10265065B2 (en) | 2013-12-23 | 2019-04-23 | Ethicon Llc | Surgical staples and staple cartridges |
US11026677B2 (en) | 2013-12-23 | 2021-06-08 | Cilag Gmbh International | Surgical stapling assembly |
US10925599B2 (en) | 2013-12-23 | 2021-02-23 | Ethicon Llc | Modular surgical instruments |
US11364028B2 (en) | 2013-12-23 | 2022-06-21 | Cilag Gmbh International | Modular surgical system |
US11123065B2 (en) | 2013-12-23 | 2021-09-21 | Cilag Gmbh International | Surgical cutting and stapling instruments with independent jaw control features |
US11020109B2 (en) | 2013-12-23 | 2021-06-01 | Ethicon Llc | Surgical stapling assembly for use with a powered surgical interface |
US11779327B2 (en) | 2013-12-23 | 2023-10-10 | Cilag Gmbh International | Surgical stapling system including a push bar |
US11950776B2 (en) | 2013-12-23 | 2024-04-09 | Cilag Gmbh International | Modular surgical instruments |
US11759201B2 (en) | 2013-12-23 | 2023-09-19 | Cilag Gmbh International | Surgical stapling system comprising an end effector including an anvil with an anvil cap |
US10588624B2 (en) | 2013-12-23 | 2020-03-17 | Ethicon Llc | Surgical staples, staple cartridges and surgical end effectors |
US11896223B2 (en) | 2013-12-23 | 2024-02-13 | Cilag Gmbh International | Surgical cutting and stapling instruments with independent jaw control features |
US11246587B2 (en) | 2013-12-23 | 2022-02-15 | Cilag Gmbh International | Surgical cutting and stapling instruments |
US10986997B2 (en) | 2013-12-31 | 2021-04-27 | Memorial Sloan Kettering Cancer Center | Systems, methods, and apparatus for multichannel imaging of fluorescent sources in real time |
US20150202848A1 (en) * | 2014-01-22 | 2015-07-23 | Samsung Display Co., Ltd. | Display device |
US11020115B2 (en) | 2014-02-12 | 2021-06-01 | Cilag Gmbh International | Deliverable surgical instrument |
US9962161B2 (en) | 2014-02-12 | 2018-05-08 | Ethicon Llc | Deliverable surgical instrument |
US9884456B2 (en) | 2014-02-24 | 2018-02-06 | Ethicon Llc | Implantable layers and methods for altering one or more properties of implantable layers for use with fastening instruments |
US9693777B2 (en) | 2014-02-24 | 2017-07-04 | Ethicon Llc | Implantable layers comprising a pressed region |
US9839422B2 (en) | 2014-02-24 | 2017-12-12 | Ethicon Llc | Implantable layers and methods for altering implantable layers for use with surgical fastening instruments |
US10426481B2 (en) | 2014-02-24 | 2019-10-01 | Ethicon Llc | Implantable layer assemblies |
US9757124B2 (en) | 2014-02-24 | 2017-09-12 | Ethicon Llc | Implantable layer assemblies |
US9775608B2 (en) | 2014-02-24 | 2017-10-03 | Ethicon Llc | Fastening system comprising a firing member lockout |
US9839423B2 (en) | 2014-02-24 | 2017-12-12 | Ethicon Llc | Implantable layers and methods for modifying the shape of the implantable layers for use with a surgical fastening instrument |
US9750499B2 (en) | 2014-03-26 | 2017-09-05 | Ethicon Llc | Surgical stapling instrument system |
US11259799B2 (en) | 2014-03-26 | 2022-03-01 | Cilag Gmbh International | Interface systems for use with surgical instruments |
US9743929B2 (en) | 2014-03-26 | 2017-08-29 | Ethicon Llc | Modular powered surgical instrument with detachable shaft assemblies |
US10201364B2 (en) | 2014-03-26 | 2019-02-12 | Ethicon Llc | Surgical instrument comprising a rotatable shaft |
US9820738B2 (en) | 2014-03-26 | 2017-11-21 | Ethicon Llc | Surgical instrument comprising interactive systems |
US9826977B2 (en) | 2014-03-26 | 2017-11-28 | Ethicon Llc | Sterilization verification circuit |
US10117653B2 (en) | 2014-03-26 | 2018-11-06 | Ethicon Llc | Systems and methods for controlling a segmented circuit |
US9913642B2 (en) | 2014-03-26 | 2018-03-13 | Ethicon Llc | Surgical instrument comprising a sensor system |
US10588626B2 (en) | 2014-03-26 | 2020-03-17 | Ethicon Llc | Surgical instrument displaying subsequent step of use |
US10004497B2 (en) | 2014-03-26 | 2018-06-26 | Ethicon Llc | Interface systems for use with surgical instruments |
US11497488B2 (en) | 2014-03-26 | 2022-11-15 | Cilag Gmbh International | Systems and methods for controlling a segmented circuit |
US10863981B2 (en) | 2014-03-26 | 2020-12-15 | Ethicon Llc | Interface systems for use with surgical instruments |
US10013049B2 (en) | 2014-03-26 | 2018-07-03 | Ethicon Llc | Power management through sleep options of segmented circuit and wake up control |
US9804618B2 (en) | 2014-03-26 | 2017-10-31 | Ethicon Llc | Systems and methods for controlling a segmented circuit |
US10136889B2 (en) | 2014-03-26 | 2018-11-27 | Ethicon Llc | Systems and methods for controlling a segmented circuit |
US10898185B2 (en) | 2014-03-26 | 2021-01-26 | Ethicon Llc | Surgical instrument power management through sleep and wake up control |
US10028761B2 (en) | 2014-03-26 | 2018-07-24 | Ethicon Llc | Feedback algorithms for manual bailout systems for surgical instruments |
US9730695B2 (en) | 2014-03-26 | 2017-08-15 | Ethicon Endo-Surgery, Llc | Power management through segmented circuit |
US9690362B2 (en) | 2014-03-26 | 2017-06-27 | Ethicon Llc | Surgical instrument control circuit having a safety processor |
US9733663B2 (en) | 2014-03-26 | 2017-08-15 | Ethicon Llc | Power management through segmented circuit and variable voltage protection |
US10472651B2 (en) | 2014-03-28 | 2019-11-12 | The Regents Of The University Of California | Efficient delivery of large cargos into cells on a porous substrate |
US11185330B2 (en) | 2014-04-16 | 2021-11-30 | Cilag Gmbh International | Fastener cartridge assemblies and staple retainer cover arrangements |
US9844369B2 (en) | 2014-04-16 | 2017-12-19 | Ethicon Llc | Surgical end effectors with firing element monitoring arrangements |
US9833241B2 (en) | 2014-04-16 | 2017-12-05 | Ethicon Llc | Surgical fastener cartridges with driver stabilizing arrangements |
US11925353B2 (en) | 2014-04-16 | 2024-03-12 | Cilag Gmbh International | Surgical stapling instrument comprising internal passage between stapling cartridge and elongate channel |
US11596406B2 (en) | 2014-04-16 | 2023-03-07 | Cilag Gmbh International | Fastener cartridges including extensions having different configurations |
US9877721B2 (en) | 2014-04-16 | 2018-01-30 | Ethicon Llc | Fastener cartridge comprising tissue control features |
US11717294B2 (en) | 2014-04-16 | 2023-08-08 | Cilag Gmbh International | End effector arrangements comprising indicators |
US11298134B2 (en) | 2014-04-16 | 2022-04-12 | Cilag Gmbh International | Fastener cartridge comprising non-uniform fasteners |
US10327776B2 (en) | 2014-04-16 | 2019-06-25 | Ethicon Llc | Surgical stapling buttresses and adjunct materials |
US11517315B2 (en) | 2014-04-16 | 2022-12-06 | Cilag Gmbh International | Fastener cartridges including extensions having different configurations |
US10542988B2 (en) | 2014-04-16 | 2020-01-28 | Ethicon Llc | End effector comprising an anvil including projections extending therefrom |
US11918222B2 (en) | 2014-04-16 | 2024-03-05 | Cilag Gmbh International | Stapling assembly having firing member viewing windows |
US10299792B2 (en) | 2014-04-16 | 2019-05-28 | Ethicon Llc | Fastener cartridge comprising non-uniform fasteners |
US11266409B2 (en) | 2014-04-16 | 2022-03-08 | Cilag Gmbh International | Fastener cartridge comprising a sled including longitudinally-staggered ramps |
US11382625B2 (en) | 2014-04-16 | 2022-07-12 | Cilag Gmbh International | Fastener cartridge comprising non-uniform fasteners |
US10470768B2 (en) | 2014-04-16 | 2019-11-12 | Ethicon Llc | Fastener cartridge including a layer attached thereto |
US11382627B2 (en) | 2014-04-16 | 2022-07-12 | Cilag Gmbh International | Surgical stapling assembly comprising a firing member including a lateral extension |
US11944307B2 (en) | 2014-04-16 | 2024-04-02 | Cilag Gmbh International | Surgical stapling system including jaw windows |
US10010324B2 (en) | 2014-04-16 | 2018-07-03 | Ethicon Llc | Fastener cartridge compromising fastener cavities including fastener control features |
US10561422B2 (en) | 2014-04-16 | 2020-02-18 | Ethicon Llc | Fastener cartridge comprising deployable tissue engaging members |
US11883026B2 (en) | 2014-04-16 | 2024-01-30 | Cilag Gmbh International | Fastener cartridge assemblies and staple retainer cover arrangements |
US10485881B2 (en) | 2014-05-29 | 2019-11-26 | Memorial Sloan Kettering Cancer Center | Nanoparticle drug conjugates |
US10111963B2 (en) | 2014-05-29 | 2018-10-30 | Memorial Sloan Kettering Cancer Center | Nanoparticle drug conjugates |
US10045781B2 (en) | 2014-06-13 | 2018-08-14 | Ethicon Llc | Closure lockout systems for surgical instruments |
US9757128B2 (en) | 2014-09-05 | 2017-09-12 | Ethicon Llc | Multiple sensors with one sensor affecting a second sensor's output or interpretation |
US11071545B2 (en) | 2014-09-05 | 2021-07-27 | Cilag Gmbh International | Smart cartridge wake up operation and data retention |
US11076854B2 (en) | 2014-09-05 | 2021-08-03 | Cilag Gmbh International | Smart cartridge wake up operation and data retention |
US10111679B2 (en) | 2014-09-05 | 2018-10-30 | Ethicon Llc | Circuitry and sensors for powered medical device |
US9724094B2 (en) | 2014-09-05 | 2017-08-08 | Ethicon Llc | Adjunct with integrated sensors to quantify tissue compression |
US10135242B2 (en) | 2014-09-05 | 2018-11-20 | Ethicon Llc | Smart cartridge wake up operation and data retention |
US9737301B2 (en) | 2014-09-05 | 2017-08-22 | Ethicon Llc | Monitoring device degradation based on component evaluation |
US11389162B2 (en) | 2014-09-05 | 2022-07-19 | Cilag Gmbh International | Smart cartridge wake up operation and data retention |
US10905423B2 (en) | 2014-09-05 | 2021-02-02 | Ethicon Llc | Smart cartridge wake up operation and data retention |
US9788836B2 (en) | 2014-09-05 | 2017-10-17 | Ethicon Llc | Multiple motor control for powered medical device |
US11717297B2 (en) | 2014-09-05 | 2023-08-08 | Cilag Gmbh International | Smart cartridge wake up operation and data retention |
US10016199B2 (en) | 2014-09-05 | 2018-07-10 | Ethicon Llc | Polarity of hall magnet to identify cartridge type |
US11653918B2 (en) | 2014-09-05 | 2023-05-23 | Cilag Gmbh International | Local display of tissue parameter stabilization |
US11311294B2 (en) | 2014-09-05 | 2022-04-26 | Cilag Gmbh International | Powered medical device including measurement of closure state of jaws |
US11406386B2 (en) | 2014-09-05 | 2022-08-09 | Cilag Gmbh International | End effector including magnetic and impedance sensors |
US11284898B2 (en) | 2014-09-18 | 2022-03-29 | Cilag Gmbh International | Surgical instrument including a deployable knife |
US11202633B2 (en) | 2014-09-26 | 2021-12-21 | Cilag Gmbh International | Surgical stapling buttresses and adjunct materials |
US10751053B2 (en) | 2014-09-26 | 2020-08-25 | Ethicon Llc | Fastener cartridges for applying expandable fastener lines |
US9801628B2 (en) | 2014-09-26 | 2017-10-31 | Ethicon Llc | Surgical staple and driver arrangements for staple cartridges |
US9801627B2 (en) | 2014-09-26 | 2017-10-31 | Ethicon Llc | Fastener cartridge for creating a flexible staple line |
US11523821B2 (en) | 2014-09-26 | 2022-12-13 | Cilag Gmbh International | Method for creating a flexible staple line |
US10206677B2 (en) | 2014-09-26 | 2019-02-19 | Ethicon Llc | Surgical staple and driver arrangements for staple cartridges |
US10327764B2 (en) | 2014-09-26 | 2019-06-25 | Ethicon Llc | Method for creating a flexible staple line |
US10426477B2 (en) | 2014-09-26 | 2019-10-01 | Ethicon Llc | Staple cartridge assembly including a ramp |
US10426476B2 (en) | 2014-09-26 | 2019-10-01 | Ethicon Llc | Circular fastener cartridges for applying radially expandable fastener lines |
US10076325B2 (en) | 2014-10-13 | 2018-09-18 | Ethicon Llc | Surgical stapling apparatus comprising a tissue stop |
US10736630B2 (en) | 2014-10-13 | 2020-08-11 | Ethicon Llc | Staple cartridge |
US11185325B2 (en) | 2014-10-16 | 2021-11-30 | Cilag Gmbh International | End effector including different tissue gaps |
US10905418B2 (en) | 2014-10-16 | 2021-02-02 | Ethicon Llc | Staple cartridge comprising a tissue thickness compensator |
US11701114B2 (en) | 2014-10-16 | 2023-07-18 | Cilag Gmbh International | Staple cartridge |
US9924944B2 (en) | 2014-10-16 | 2018-03-27 | Ethicon Llc | Staple cartridge comprising an adjunct material |
US10052104B2 (en) | 2014-10-16 | 2018-08-21 | Ethicon Llc | Staple cartridge comprising a tissue thickness compensator |
US11918210B2 (en) | 2014-10-16 | 2024-03-05 | Cilag Gmbh International | Staple cartridge comprising a cartridge body including a plurality of wells |
US11931031B2 (en) | 2014-10-16 | 2024-03-19 | Cilag Gmbh International | Staple cartridge comprising a deck including an upper surface and a lower surface |
US11864760B2 (en) | 2014-10-29 | 2024-01-09 | Cilag Gmbh International | Staple cartridges comprising driver arrangements |
US11141153B2 (en) | 2014-10-29 | 2021-10-12 | Cilag Gmbh International | Staple cartridges comprising driver arrangements |
US11241229B2 (en) | 2014-10-29 | 2022-02-08 | Cilag Gmbh International | Staple cartridges comprising driver arrangements |
US10517594B2 (en) | 2014-10-29 | 2019-12-31 | Ethicon Llc | Cartridge assemblies for surgical staplers |
US11931038B2 (en) | 2014-10-29 | 2024-03-19 | Cilag Gmbh International | Cartridge assemblies for surgical staplers |
US11457918B2 (en) | 2014-10-29 | 2022-10-04 | Cilag Gmbh International | Cartridge assemblies for surgical staplers |
US11337698B2 (en) | 2014-11-06 | 2022-05-24 | Cilag Gmbh International | Staple cartridge comprising a releasable adjunct material |
US9844376B2 (en) | 2014-11-06 | 2017-12-19 | Ethicon Llc | Staple cartridge comprising a releasable adjunct material |
US10617417B2 (en) | 2014-11-06 | 2020-04-14 | Ethicon Llc | Staple cartridge comprising a releasable adjunct material |
US11382628B2 (en) | 2014-12-10 | 2022-07-12 | Cilag Gmbh International | Articulatable surgical instrument system |
US10736636B2 (en) | 2014-12-10 | 2020-08-11 | Ethicon Llc | Articulatable surgical instrument system |
US10743873B2 (en) | 2014-12-18 | 2020-08-18 | Ethicon Llc | Drive arrangements for articulatable surgical instruments |
US10085748B2 (en) | 2014-12-18 | 2018-10-02 | Ethicon Llc | Locking arrangements for detachable shaft assemblies with articulatable surgical end effectors |
US9844374B2 (en) | 2014-12-18 | 2017-12-19 | Ethicon Llc | Surgical instrument systems comprising an articulatable end effector and means for adjusting the firing stroke of a firing member |
US11547403B2 (en) | 2014-12-18 | 2023-01-10 | Cilag Gmbh International | Surgical instrument having a laminate firing actuator and lateral buckling supports |
US10117649B2 (en) | 2014-12-18 | 2018-11-06 | Ethicon Llc | Surgical instrument assembly comprising a lockable articulation system |
US11812958B2 (en) | 2014-12-18 | 2023-11-14 | Cilag Gmbh International | Locking arrangements for detachable shaft assemblies with articulatable surgical end effectors |
US10945728B2 (en) | 2014-12-18 | 2021-03-16 | Ethicon Llc | Locking arrangements for detachable shaft assemblies with articulatable surgical end effectors |
US11547404B2 (en) | 2014-12-18 | 2023-01-10 | Cilag Gmbh International | Surgical instrument assembly comprising a flexible articulation system |
US10806448B2 (en) | 2014-12-18 | 2020-10-20 | Ethicon Llc | Surgical instrument assembly comprising a flexible articulation system |
US9943309B2 (en) | 2014-12-18 | 2018-04-17 | Ethicon Llc | Surgical instruments with articulatable end effectors and movable firing beam support arrangements |
US9968355B2 (en) | 2014-12-18 | 2018-05-15 | Ethicon Llc | Surgical instruments with articulatable end effectors and improved firing beam support arrangements |
US11678877B2 (en) | 2014-12-18 | 2023-06-20 | Cilag Gmbh International | Surgical instrument including a flexible support configured to support a flexible firing member |
US10245027B2 (en) | 2014-12-18 | 2019-04-02 | Ethicon Llc | Surgical instrument with an anvil that is selectively movable about a discrete non-movable axis relative to a staple cartridge |
US9987000B2 (en) | 2014-12-18 | 2018-06-05 | Ethicon Llc | Surgical instrument assembly comprising a flexible articulation system |
US10188385B2 (en) | 2014-12-18 | 2019-01-29 | Ethicon Llc | Surgical instrument system comprising lockable systems |
US9844375B2 (en) | 2014-12-18 | 2017-12-19 | Ethicon Llc | Drive arrangements for articulatable surgical instruments |
US10004501B2 (en) | 2014-12-18 | 2018-06-26 | Ethicon Llc | Surgical instruments with improved closure arrangements |
US10695058B2 (en) | 2014-12-18 | 2020-06-30 | Ethicon Llc | Surgical instrument systems comprising an articulatable end effector and means for adjusting the firing stroke of a firing member |
US11571207B2 (en) | 2014-12-18 | 2023-02-07 | Cilag Gmbh International | Surgical system including lateral supports for a flexible drive member |
US11399831B2 (en) | 2014-12-18 | 2022-08-02 | Cilag Gmbh International | Drive arrangements for articulatable surgical instruments |
US11517311B2 (en) | 2014-12-18 | 2022-12-06 | Cilag Gmbh International | Surgical instrument systems comprising an articulatable end effector and means for adjusting the firing stroke of a firing member |
US11083453B2 (en) | 2014-12-18 | 2021-08-10 | Cilag Gmbh International | Surgical stapling system including a flexible firing actuator and lateral buckling supports |
US11553911B2 (en) | 2014-12-18 | 2023-01-17 | Cilag Gmbh International | Surgical instrument assembly comprising a flexible articulation system |
US11324506B2 (en) | 2015-02-27 | 2022-05-10 | Cilag Gmbh International | Modular stapling assembly |
US10182816B2 (en) | 2015-02-27 | 2019-01-22 | Ethicon Llc | Charging system that enables emergency resolutions for charging a battery |
US9993258B2 (en) | 2015-02-27 | 2018-06-12 | Ethicon Llc | Adaptable surgical instrument handle |
US10045779B2 (en) | 2015-02-27 | 2018-08-14 | Ethicon Llc | Surgical instrument system comprising an inspection station |
US9931118B2 (en) | 2015-02-27 | 2018-04-03 | Ethicon Endo-Surgery, Llc | Reinforced battery for a surgical instrument |
US10245028B2 (en) | 2015-02-27 | 2019-04-02 | Ethicon Llc | Power adapter for a surgical instrument |
US11154301B2 (en) | 2015-02-27 | 2021-10-26 | Cilag Gmbh International | Modular stapling assembly |
US11744588B2 (en) | 2015-02-27 | 2023-09-05 | Cilag Gmbh International | Surgical stapling instrument including a removably attachable battery pack |
US10321907B2 (en) | 2015-02-27 | 2019-06-18 | Ethicon Llc | System for monitoring whether a surgical instrument needs to be serviced |
US10226250B2 (en) | 2015-02-27 | 2019-03-12 | Ethicon Llc | Modular stapling assembly |
US10159483B2 (en) | 2015-02-27 | 2018-12-25 | Ethicon Llc | Surgical apparatus configured to track an end-of-life parameter |
US10180463B2 (en) | 2015-02-27 | 2019-01-15 | Ethicon Llc | Surgical apparatus configured to assess whether a performance parameter of the surgical apparatus is within an acceptable performance band |
US9895148B2 (en) | 2015-03-06 | 2018-02-20 | Ethicon Endo-Surgery, Llc | Monitoring speed control and precision incrementing of motor for powered surgical instruments |
US11426160B2 (en) | 2015-03-06 | 2022-08-30 | Cilag Gmbh International | Smart sensors with local signal processing |
US9993248B2 (en) | 2015-03-06 | 2018-06-12 | Ethicon Endo-Surgery, Llc | Smart sensors with local signal processing |
US11944338B2 (en) | 2015-03-06 | 2024-04-02 | Cilag Gmbh International | Multiple level thresholds to modify operation of powered surgical instruments |
US11350843B2 (en) | 2015-03-06 | 2022-06-07 | Cilag Gmbh International | Time dependent evaluation of sensor data to determine stability, creep, and viscoelastic elements of measures |
US10548504B2 (en) | 2015-03-06 | 2020-02-04 | Ethicon Llc | Overlaid multi sensor radio frequency (RF) electrode system to measure tissue compression |
US10524787B2 (en) | 2015-03-06 | 2020-01-07 | Ethicon Llc | Powered surgical instrument with parameter-based firing rate |
US10617412B2 (en) | 2015-03-06 | 2020-04-14 | Ethicon Llc | System for detecting the mis-insertion of a staple cartridge into a surgical stapler |
US10687806B2 (en) | 2015-03-06 | 2020-06-23 | Ethicon Llc | Adaptive tissue compression techniques to adjust closure rates for multiple tissue types |
US11224423B2 (en) | 2015-03-06 | 2022-01-18 | Cilag Gmbh International | Smart sensors with local signal processing |
US9808246B2 (en) | 2015-03-06 | 2017-11-07 | Ethicon Endo-Surgery, Llc | Method of operating a powered surgical instrument |
US10729432B2 (en) | 2015-03-06 | 2020-08-04 | Ethicon Llc | Methods for operating a powered surgical instrument |
US10045776B2 (en) | 2015-03-06 | 2018-08-14 | Ethicon Llc | Control techniques and sub-processor contained within modular shaft with select control processing from handle |
US10966627B2 (en) | 2015-03-06 | 2021-04-06 | Ethicon Llc | Time dependent evaluation of sensor data to determine stability, creep, and viscoelastic elements of measures |
US10206605B2 (en) | 2015-03-06 | 2019-02-19 | Ethicon Llc | Time dependent evaluation of sensor data to determine stability, creep, and viscoelastic elements of measures |
US10052044B2 (en) | 2015-03-06 | 2018-08-21 | Ethicon Llc | Time dependent evaluation of sensor data to determine stability, creep, and viscoelastic elements of measures |
US10772625B2 (en) | 2015-03-06 | 2020-09-15 | Ethicon Llc | Signal and power communication system positioned on a rotatable shaft |
US9901342B2 (en) | 2015-03-06 | 2018-02-27 | Ethicon Endo-Surgery, Llc | Signal and power communication system positioned on a rotatable shaft |
US11109859B2 (en) | 2015-03-06 | 2021-09-07 | Cilag Gmbh International | Surgical instrument comprising a lockable battery housing |
US9924961B2 (en) | 2015-03-06 | 2018-03-27 | Ethicon Endo-Surgery, Llc | Interactive feedback system for powered surgical instruments |
US10245033B2 (en) | 2015-03-06 | 2019-04-02 | Ethicon Llc | Surgical instrument comprising a lockable battery housing |
US10531887B2 (en) | 2015-03-06 | 2020-01-14 | Ethicon Llc | Powered surgical instrument including speed display |
US11826132B2 (en) | 2015-03-06 | 2023-11-28 | Cilag Gmbh International | Time dependent evaluation of sensor data to determine stability, creep, and viscoelastic elements of measures |
US11918212B2 (en) | 2015-03-31 | 2024-03-05 | Cilag Gmbh International | Surgical instrument with selectively disengageable drive systems |
US10390825B2 (en) | 2015-03-31 | 2019-08-27 | Ethicon Llc | Surgical instrument with progressive rotary drive systems |
US10433844B2 (en) | 2015-03-31 | 2019-10-08 | Ethicon Llc | Surgical instrument with selectively disengageable threaded drive systems |
US10213201B2 (en) | 2015-03-31 | 2019-02-26 | Ethicon Llc | Stapling end effector configured to compensate for an uneven gap between a first jaw and a second jaw |
US10548989B2 (en) * | 2015-04-07 | 2020-02-04 | Memorial Sloan Kettering Cancer Center | Nanoparticle immunoconjugates |
US10724031B2 (en) * | 2015-05-28 | 2020-07-28 | Bioneer Corporation | Highly active silica magnetic nanoparticles for purifying biomaterial and preparation method thereof |
US20200024592A1 (en) * | 2015-05-28 | 2020-01-23 | Bioneer Corporation | Highly active silica magnetic nanoparticles for purifying biomaterial and preparation method thereof |
US10736972B2 (en) | 2015-05-29 | 2020-08-11 | Memorial Sloan Kettering Cancer Center | Methods of treatment using ultrasmall nanoparticles to induce cell death of nutrient-deprived cancer cells via ferroptosis |
US11246946B2 (en) | 2015-05-29 | 2022-02-15 | Memorial Sloan Kettering Cancer Center | Methods of treatment using ultrasmall nanoparticles to induce cell death of nutrient-deprived cancer cells via ferroptosis |
US11931425B2 (en) | 2015-05-29 | 2024-03-19 | Memorial Sloan Kettering Cancer Center | Methods of treatment using ultrasmall nanoparticles to induce cell death of nutrient-deprived cancer cells via ferroptosis |
US10052102B2 (en) | 2015-06-18 | 2018-08-21 | Ethicon Llc | Surgical end effectors with dual cam actuated jaw closing features |
US11629264B2 (en) * | 2015-06-18 | 2023-04-18 | Sicpa Holding Sa | Thermoluminescent and superparamagnetic composite particle and marking comprising same |
US20180155564A1 (en) * | 2015-06-18 | 2018-06-07 | Sicpa Holding Sa | Thermoluminescent and superparamagnetic composite particle and marking comprising same |
US11058425B2 (en) | 2015-08-17 | 2021-07-13 | Ethicon Llc | Implantable layers for a surgical instrument |
US10835249B2 (en) | 2015-08-17 | 2020-11-17 | Ethicon Llc | Implantable layers for a surgical instrument |
US10617418B2 (en) | 2015-08-17 | 2020-04-14 | Ethicon Llc | Implantable layers for a surgical instrument |
US10166026B2 (en) | 2015-08-26 | 2019-01-01 | Ethicon Llc | Staple cartridge assembly including features for controlling the rotation of staples when being ejected therefrom |
US10966724B2 (en) | 2015-08-26 | 2021-04-06 | Ethicon Llc | Surgical staples comprising a guide |
US10098642B2 (en) | 2015-08-26 | 2018-10-16 | Ethicon Llc | Surgical staples comprising features for improved fastening of tissue |
US10980538B2 (en) | 2015-08-26 | 2021-04-20 | Ethicon Llc | Surgical stapling configurations for curved and circular stapling instruments |
US11219456B2 (en) | 2015-08-26 | 2022-01-11 | Cilag Gmbh International | Surgical staple strips for permitting varying staple properties and enabling easy cartridge loading |
US10390829B2 (en) | 2015-08-26 | 2019-08-27 | Ethicon Llc | Staples comprising a cover |
US10470769B2 (en) | 2015-08-26 | 2019-11-12 | Ethicon Llc | Staple cartridge assembly comprising staple alignment features on a firing member |
US10517599B2 (en) | 2015-08-26 | 2019-12-31 | Ethicon Llc | Staple cartridge assembly comprising staple cavities for providing better staple guidance |
US11510675B2 (en) | 2015-08-26 | 2022-11-29 | Cilag Gmbh International | Surgical end effector assembly including a connector strip interconnecting a plurality of staples |
US10357251B2 (en) | 2015-08-26 | 2019-07-23 | Ethicon Llc | Surgical staples comprising hardness variations for improved fastening of tissue |
US11103248B2 (en) | 2015-08-26 | 2021-08-31 | Cilag Gmbh International | Surgical staples for minimizing staple roll |
US11058426B2 (en) | 2015-08-26 | 2021-07-13 | Cilag Gmbh International | Staple cartridge assembly comprising various tissue compression gaps and staple forming gaps |
US10213203B2 (en) | 2015-08-26 | 2019-02-26 | Ethicon Llc | Staple cartridge assembly without a bottom cover |
US10433845B2 (en) | 2015-08-26 | 2019-10-08 | Ethicon Llc | Surgical staple strips for permitting varying staple properties and enabling easy cartridge loading |
US10188394B2 (en) | 2015-08-26 | 2019-01-29 | Ethicon Llc | Staples configured to support an implantable adjunct |
US11051817B2 (en) | 2015-08-26 | 2021-07-06 | Cilag Gmbh International | Method for forming a staple against an anvil of a surgical stapling instrument |
US10172619B2 (en) | 2015-09-02 | 2019-01-08 | Ethicon Llc | Surgical staple driver arrays |
US11382624B2 (en) | 2015-09-02 | 2022-07-12 | Cilag Gmbh International | Surgical staple cartridge with improved staple driver configurations |
US11589868B2 (en) | 2015-09-02 | 2023-02-28 | Cilag Gmbh International | Surgical staple configurations with camming surfaces located between portions supporting surgical staples |
US10314587B2 (en) | 2015-09-02 | 2019-06-11 | Ethicon Llc | Surgical staple cartridge with improved staple driver configurations |
US10251648B2 (en) | 2015-09-02 | 2019-04-09 | Ethicon Llc | Surgical staple cartridge staple drivers with central support features |
US11213295B2 (en) | 2015-09-02 | 2022-01-04 | Cilag Gmbh International | Surgical staple configurations with camming surfaces located between portions supporting surgical staples |
US10238390B2 (en) | 2015-09-02 | 2019-03-26 | Ethicon Llc | Surgical staple cartridges with driver arrangements for establishing herringbone staple patterns |
US10357252B2 (en) | 2015-09-02 | 2019-07-23 | Ethicon Llc | Surgical staple configurations with camming surfaces located between portions supporting surgical staples |
US10863986B2 (en) | 2015-09-23 | 2020-12-15 | Ethicon Llc | Surgical stapler having downstream current-based motor control |
US10085751B2 (en) | 2015-09-23 | 2018-10-02 | Ethicon Llc | Surgical stapler having temperature-based motor control |
US11344299B2 (en) | 2015-09-23 | 2022-05-31 | Cilag Gmbh International | Surgical stapler having downstream current-based motor control |
US11026678B2 (en) | 2015-09-23 | 2021-06-08 | Cilag Gmbh International | Surgical stapler having motor control based on an electrical parameter related to a motor current |
US10105139B2 (en) | 2015-09-23 | 2018-10-23 | Ethicon Llc | Surgical stapler having downstream current-based motor control |
US10363036B2 (en) | 2015-09-23 | 2019-07-30 | Ethicon Llc | Surgical stapler having force-based motor control |
US11849946B2 (en) | 2015-09-23 | 2023-12-26 | Cilag Gmbh International | Surgical stapler having downstream current-based motor control |
US11490889B2 (en) | 2015-09-23 | 2022-11-08 | Cilag Gmbh International | Surgical stapler having motor control based on an electrical parameter related to a motor current |
US10327769B2 (en) | 2015-09-23 | 2019-06-25 | Ethicon Llc | Surgical stapler having motor control based on a drive system component |
US10076326B2 (en) | 2015-09-23 | 2018-09-18 | Ethicon Llc | Surgical stapler having current mirror-based motor control |
US10238386B2 (en) | 2015-09-23 | 2019-03-26 | Ethicon Llc | Surgical stapler having motor control based on an electrical parameter related to a motor current |
US10299878B2 (en) | 2015-09-25 | 2019-05-28 | Ethicon Llc | Implantable adjunct systems for determining adjunct skew |
US11076929B2 (en) | 2015-09-25 | 2021-08-03 | Cilag Gmbh International | Implantable adjunct systems for determining adjunct skew |
US10327777B2 (en) | 2015-09-30 | 2019-06-25 | Ethicon Llc | Implantable layer comprising plastically deformed fibers |
US10271849B2 (en) | 2015-09-30 | 2019-04-30 | Ethicon Llc | Woven constructs with interlocked standing fibers |
US11944308B2 (en) | 2015-09-30 | 2024-04-02 | Cilag Gmbh International | Compressible adjunct with crossing spacer fibers |
US10524788B2 (en) | 2015-09-30 | 2020-01-07 | Ethicon Llc | Compressible adjunct with attachment regions |
US11712244B2 (en) | 2015-09-30 | 2023-08-01 | Cilag Gmbh International | Implantable layer with spacer fibers |
US10478188B2 (en) | 2015-09-30 | 2019-11-19 | Ethicon Llc | Implantable layer comprising a constricted configuration |
US10433846B2 (en) | 2015-09-30 | 2019-10-08 | Ethicon Llc | Compressible adjunct with crossing spacer fibers |
US10980539B2 (en) | 2015-09-30 | 2021-04-20 | Ethicon Llc | Implantable adjunct comprising bonded layers |
US10307160B2 (en) | 2015-09-30 | 2019-06-04 | Ethicon Llc | Compressible adjunct assemblies with attachment layers |
US11690623B2 (en) | 2015-09-30 | 2023-07-04 | Cilag Gmbh International | Method for applying an implantable layer to a fastener cartridge |
US11553916B2 (en) | 2015-09-30 | 2023-01-17 | Cilag Gmbh International | Compressible adjunct with crossing spacer fibers |
US11903586B2 (en) | 2015-09-30 | 2024-02-20 | Cilag Gmbh International | Compressible adjunct with crossing spacer fibers |
US11890015B2 (en) | 2015-09-30 | 2024-02-06 | Cilag Gmbh International | Compressible adjunct with crossing spacer fibers |
US10561420B2 (en) | 2015-09-30 | 2020-02-18 | Ethicon Llc | Tubular absorbable constructs |
US10603039B2 (en) | 2015-09-30 | 2020-03-31 | Ethicon Llc | Progressively releasable implantable adjunct for use with a surgical stapling instrument |
US10736633B2 (en) | 2015-09-30 | 2020-08-11 | Ethicon Llc | Compressible adjunct with looping members |
US10172620B2 (en) | 2015-09-30 | 2019-01-08 | Ethicon Llc | Compressible adjuncts with bonding nodes |
US10285699B2 (en) | 2015-09-30 | 2019-05-14 | Ethicon Llc | Compressible adjunct |
US10932779B2 (en) | 2015-09-30 | 2021-03-02 | Ethicon Llc | Compressible adjunct with crossing spacer fibers |
US11793522B2 (en) | 2015-09-30 | 2023-10-24 | Cilag Gmbh International | Staple cartridge assembly including a compressible adjunct |
US10292704B2 (en) | 2015-12-30 | 2019-05-21 | Ethicon Llc | Mechanisms for compensating for battery pack failure in powered surgical instruments |
US11129613B2 (en) | 2015-12-30 | 2021-09-28 | Cilag Gmbh International | Surgical instruments with separable motors and motor control circuits |
US11759208B2 (en) | 2015-12-30 | 2023-09-19 | Cilag Gmbh International | Mechanisms for compensating for battery pack failure in powered surgical instruments |
US10368865B2 (en) | 2015-12-30 | 2019-08-06 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US11484309B2 (en) | 2015-12-30 | 2022-11-01 | Cilag Gmbh International | Surgical stapling system comprising a controller configured to cause a motor to reset a firing sequence |
US11083454B2 (en) | 2015-12-30 | 2021-08-10 | Cilag Gmbh International | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US11058422B2 (en) | 2015-12-30 | 2021-07-13 | Cilag Gmbh International | Mechanisms for compensating for battery pack failure in powered surgical instruments |
US10265068B2 (en) | 2015-12-30 | 2019-04-23 | Ethicon Llc | Surgical instruments with separable motors and motor control circuits |
US10413291B2 (en) | 2016-02-09 | 2019-09-17 | Ethicon Llc | Surgical instrument articulation mechanism with slotted secondary constraint |
US10245029B2 (en) | 2016-02-09 | 2019-04-02 | Ethicon Llc | Surgical instrument with articulating and axially translatable end effector |
US10245030B2 (en) | 2016-02-09 | 2019-04-02 | Ethicon Llc | Surgical instruments with tensioning arrangements for cable driven articulation systems |
US10470764B2 (en) | 2016-02-09 | 2019-11-12 | Ethicon Llc | Surgical instruments with closure stroke reduction arrangements |
US10588625B2 (en) | 2016-02-09 | 2020-03-17 | Ethicon Llc | Articulatable surgical instruments with off-axis firing beam arrangements |
US10433837B2 (en) | 2016-02-09 | 2019-10-08 | Ethicon Llc | Surgical instruments with multiple link articulation arrangements |
US11213293B2 (en) | 2016-02-09 | 2022-01-04 | Cilag Gmbh International | Articulatable surgical instruments with single articulation link arrangements |
US11730471B2 (en) | 2016-02-09 | 2023-08-22 | Cilag Gmbh International | Articulatable surgical instruments with single articulation link arrangements |
US10653413B2 (en) | 2016-02-09 | 2020-05-19 | Ethicon Llc | Surgical instruments with an end effector that is highly articulatable relative to an elongate shaft assembly |
US11523823B2 (en) | 2016-02-09 | 2022-12-13 | Cilag Gmbh International | Surgical instruments with non-symmetrical articulation arrangements |
US10448948B2 (en) | 2016-02-12 | 2019-10-22 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US11224426B2 (en) | 2016-02-12 | 2022-01-18 | Cilag Gmbh International | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US11779336B2 (en) | 2016-02-12 | 2023-10-10 | Cilag Gmbh International | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US11826045B2 (en) | 2016-02-12 | 2023-11-28 | Cilag Gmbh International | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US10258331B2 (en) | 2016-02-12 | 2019-04-16 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US11344303B2 (en) | 2016-02-12 | 2022-05-31 | Cilag Gmbh International | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US10617413B2 (en) | 2016-04-01 | 2020-04-14 | Ethicon Llc | Closure system arrangements for surgical cutting and stapling devices with separate and distinct firing shafts |
US10376263B2 (en) | 2016-04-01 | 2019-08-13 | Ethicon Llc | Anvil modification members for surgical staplers |
US11642125B2 (en) | 2016-04-15 | 2023-05-09 | Cilag Gmbh International | Robotic surgical system including a user interface and a control circuit |
US11311292B2 (en) | 2016-04-15 | 2022-04-26 | Cilag Gmbh International | Surgical instrument with detection sensors |
US11179150B2 (en) | 2016-04-15 | 2021-11-23 | Cilag Gmbh International | Systems and methods for controlling a surgical stapling and cutting instrument |
US10357247B2 (en) | 2016-04-15 | 2019-07-23 | Ethicon Llc | Surgical instrument with multiple program responses during a firing motion |
US11517306B2 (en) | 2016-04-15 | 2022-12-06 | Cilag Gmbh International | Surgical instrument with detection sensors |
US11026684B2 (en) | 2016-04-15 | 2021-06-08 | Ethicon Llc | Surgical instrument with multiple program responses during a firing motion |
US10405859B2 (en) | 2016-04-15 | 2019-09-10 | Ethicon Llc | Surgical instrument with adjustable stop/start control during a firing motion |
US11284891B2 (en) | 2016-04-15 | 2022-03-29 | Cilag Gmbh International | Surgical instrument with multiple program responses during a firing motion |
US11607239B2 (en) | 2016-04-15 | 2023-03-21 | Cilag Gmbh International | Systems and methods for controlling a surgical stapling and cutting instrument |
US10335145B2 (en) | 2016-04-15 | 2019-07-02 | Ethicon Llc | Modular surgical instrument with configurable operating mode |
US11191545B2 (en) | 2016-04-15 | 2021-12-07 | Cilag Gmbh International | Staple formation detection mechanisms |
US10456137B2 (en) | 2016-04-15 | 2019-10-29 | Ethicon Llc | Staple formation detection mechanisms |
US11317910B2 (en) | 2016-04-15 | 2022-05-03 | Cilag Gmbh International | Surgical instrument with detection sensors |
US11051810B2 (en) | 2016-04-15 | 2021-07-06 | Cilag Gmbh International | Modular surgical instrument with configurable operating mode |
US11931028B2 (en) | 2016-04-15 | 2024-03-19 | Cilag Gmbh International | Surgical instrument with multiple program responses during a firing motion |
US10492783B2 (en) | 2016-04-15 | 2019-12-03 | Ethicon, Llc | Surgical instrument with improved stop/start control during a firing motion |
US11350932B2 (en) | 2016-04-15 | 2022-06-07 | Cilag Gmbh International | Surgical instrument with improved stop/start control during a firing motion |
US11771454B2 (en) | 2016-04-15 | 2023-10-03 | Cilag Gmbh International | Stapling assembly including a controller for monitoring a clamping laod |
US10426467B2 (en) | 2016-04-15 | 2019-10-01 | Ethicon Llc | Surgical instrument with detection sensors |
US10828028B2 (en) | 2016-04-15 | 2020-11-10 | Ethicon Llc | Surgical instrument with multiple program responses during a firing motion |
US11559303B2 (en) | 2016-04-18 | 2023-01-24 | Cilag Gmbh International | Cartridge lockout arrangements for rotary powered surgical cutting and stapling instruments |
US11147554B2 (en) | 2016-04-18 | 2021-10-19 | Cilag Gmbh International | Surgical instrument system comprising a magnetic lockout |
US10368867B2 (en) | 2016-04-18 | 2019-08-06 | Ethicon Llc | Surgical instrument comprising a lockout |
US11811253B2 (en) | 2016-04-18 | 2023-11-07 | Cilag Gmbh International | Surgical robotic system with fault state detection configurations based on motor current draw |
US10363037B2 (en) | 2016-04-18 | 2019-07-30 | Ethicon Llc | Surgical instrument system comprising a magnetic lockout |
US10478181B2 (en) | 2016-04-18 | 2019-11-19 | Ethicon Llc | Cartridge lockout arrangements for rotary powered surgical cutting and stapling instruments |
US11350928B2 (en) | 2016-04-18 | 2022-06-07 | Cilag Gmbh International | Surgical instrument comprising a tissue thickness lockout and speed control system |
US10426469B2 (en) | 2016-04-18 | 2019-10-01 | Ethicon Llc | Surgical instrument comprising a primary firing lockout and a secondary firing lockout |
US10433840B2 (en) | 2016-04-18 | 2019-10-08 | Ethicon Llc | Surgical instrument comprising a replaceable cartridge jaw |
US11317917B2 (en) | 2016-04-18 | 2022-05-03 | Cilag Gmbh International | Surgical stapling system comprising a lockable firing assembly |
JP2019525379A (en) * | 2016-06-06 | 2019-09-05 | ダウ グローバル テクノロジーズ エルエルシー | LIGHT EMITTING DEVICE AND ELECTRONIC DEVICE EQUIPPED WITH THE SAME |
WO2017210754A1 (en) * | 2016-06-10 | 2017-12-14 | The University Of Queensland | Detecting an analyte |
CN109564218A (en) * | 2016-06-10 | 2019-04-02 | 昆士兰大学 | Test and analyze object |
US11867699B2 (en) | 2016-06-10 | 2024-01-09 | The University Of Queensland | Detecting an analyte |
US11690619B2 (en) | 2016-06-24 | 2023-07-04 | Cilag Gmbh International | Staple cartridge comprising staples having different geometries |
USD847989S1 (en) | 2016-06-24 | 2019-05-07 | Ethicon Llc | Surgical fastener cartridge |
US10542979B2 (en) | 2016-06-24 | 2020-01-28 | Ethicon Llc | Stamped staples and staple cartridges using the same |
US11000278B2 (en) | 2016-06-24 | 2021-05-11 | Ethicon Llc | Staple cartridge comprising wire staples and stamped staples |
USD850617S1 (en) | 2016-06-24 | 2019-06-04 | Ethicon Llc | Surgical fastener cartridge |
USD894389S1 (en) | 2016-06-24 | 2020-08-25 | Ethicon Llc | Surgical fastener |
US10702270B2 (en) | 2016-06-24 | 2020-07-07 | Ethicon Llc | Stapling system for use with wire staples and stamped staples |
USD948043S1 (en) | 2016-06-24 | 2022-04-05 | Cilag Gmbh International | Surgical fastener |
US11786246B2 (en) | 2016-06-24 | 2023-10-17 | Cilag Gmbh International | Stapling system for use with wire staples and stamped staples |
US10675024B2 (en) | 2016-06-24 | 2020-06-09 | Ethicon Llc | Staple cartridge comprising overdriven staples |
USD896379S1 (en) | 2016-06-24 | 2020-09-15 | Ethicon Llc | Surgical fastener cartridge |
US10893863B2 (en) | 2016-06-24 | 2021-01-19 | Ethicon Llc | Staple cartridge comprising offset longitudinal staple rows |
USD896380S1 (en) | 2016-06-24 | 2020-09-15 | Ethicon Llc | Surgical fastener cartridge |
US10843139B2 (en) | 2016-06-28 | 2020-11-24 | The Trustees Of The University Of Pennsylvania | Superoleophobic membranes for oil/water separation |
WO2018005595A1 (en) * | 2016-06-28 | 2018-01-04 | The Trustees Of The University Of Pennsylvania | Superoleophobic membranes for oil/water separation |
WO2018060722A1 (en) * | 2016-09-30 | 2018-04-05 | Sumitomo Chemical Company Limited | Composite particle |
US10617414B2 (en) | 2016-12-21 | 2020-04-14 | Ethicon Llc | Closure member arrangements for surgical instruments |
US11918215B2 (en) | 2016-12-21 | 2024-03-05 | Cilag Gmbh International | Staple cartridge with array of staple pockets |
US10588632B2 (en) | 2016-12-21 | 2020-03-17 | Ethicon Llc | Surgical end effectors and firing members thereof |
US11160553B2 (en) | 2016-12-21 | 2021-11-02 | Cilag Gmbh International | Surgical stapling systems |
US10959727B2 (en) | 2016-12-21 | 2021-03-30 | Ethicon Llc | Articulatable surgical end effector with asymmetric shaft arrangement |
US10687809B2 (en) | 2016-12-21 | 2020-06-23 | Ethicon Llc | Surgical staple cartridge with movable camming member configured to disengage firing member lockout features |
US11653917B2 (en) | 2016-12-21 | 2023-05-23 | Cilag Gmbh International | Surgical stapling systems |
US10448950B2 (en) | 2016-12-21 | 2019-10-22 | Ethicon Llc | Surgical staplers with independently actuatable closing and firing systems |
US10945727B2 (en) | 2016-12-21 | 2021-03-16 | Ethicon Llc | Staple cartridge with deformable driver retention features |
US10624635B2 (en) | 2016-12-21 | 2020-04-21 | Ethicon Llc | Firing members with non-parallel jaw engagement features for surgical end effectors |
US11419606B2 (en) | 2016-12-21 | 2022-08-23 | Cilag Gmbh International | Shaft assembly comprising a clutch configured to adapt the output of a rotary firing member to two different systems |
US11849948B2 (en) | 2016-12-21 | 2023-12-26 | Cilag Gmbh International | Method for resetting a fuse of a surgical instrument shaft |
US11096689B2 (en) | 2016-12-21 | 2021-08-24 | Cilag Gmbh International | Shaft assembly comprising a lockout |
US11090048B2 (en) | 2016-12-21 | 2021-08-17 | Cilag Gmbh International | Method for resetting a fuse of a surgical instrument shaft |
US10835245B2 (en) | 2016-12-21 | 2020-11-17 | Ethicon Llc | Method for attaching a shaft assembly to a surgical instrument and, alternatively, to a surgical robot |
US10537325B2 (en) | 2016-12-21 | 2020-01-21 | Ethicon Llc | Staple forming pocket arrangement to accommodate different types of staples |
US10588631B2 (en) | 2016-12-21 | 2020-03-17 | Ethicon Llc | Surgical instruments with positive jaw opening features |
US10639035B2 (en) | 2016-12-21 | 2020-05-05 | Ethicon Llc | Surgical stapling instruments and replaceable tool assemblies thereof |
US10426471B2 (en) | 2016-12-21 | 2019-10-01 | Ethicon Llc | Surgical instrument with multiple failure response modes |
US10639034B2 (en) | 2016-12-21 | 2020-05-05 | Ethicon Llc | Surgical instruments with lockout arrangements for preventing firing system actuation unless an unspent staple cartridge is present |
US10973516B2 (en) | 2016-12-21 | 2021-04-13 | Ethicon Llc | Surgical end effectors and adaptable firing members therefor |
US11000276B2 (en) | 2016-12-21 | 2021-05-11 | Ethicon Llc | Stepped staple cartridge with asymmetrical staples |
US11160551B2 (en) | 2016-12-21 | 2021-11-02 | Cilag Gmbh International | Articulatable surgical stapling instruments |
US10667809B2 (en) | 2016-12-21 | 2020-06-02 | Ethicon Llc | Staple cartridge and staple cartridge channel comprising windows defined therein |
US10588630B2 (en) | 2016-12-21 | 2020-03-17 | Ethicon Llc | Surgical tool assemblies with closure stroke reduction features |
US10603036B2 (en) | 2016-12-21 | 2020-03-31 | Ethicon Llc | Articulatable surgical instrument with independent pivotable linkage distal of an articulation lock |
US10918385B2 (en) | 2016-12-21 | 2021-02-16 | Ethicon Llc | Surgical system comprising a firing member rotatable into an articulation state to articulate an end effector of the surgical system |
US10667810B2 (en) | 2016-12-21 | 2020-06-02 | Ethicon Llc | Closure members with cam surface arrangements for surgical instruments with separate and distinct closure and firing systems |
US10542982B2 (en) | 2016-12-21 | 2020-01-28 | Ethicon Llc | Shaft assembly comprising first and second articulation lockouts |
US10980536B2 (en) | 2016-12-21 | 2021-04-20 | Ethicon Llc | No-cartridge and spent cartridge lockout arrangements for surgical staplers |
US10758229B2 (en) | 2016-12-21 | 2020-09-01 | Ethicon Llc | Surgical instrument comprising improved jaw control |
US10582928B2 (en) | 2016-12-21 | 2020-03-10 | Ethicon Llc | Articulation lock arrangements for locking an end effector in an articulated position in response to actuation of a jaw closure system |
US11684367B2 (en) | 2016-12-21 | 2023-06-27 | Cilag Gmbh International | Stepped assembly having and end-of-life indicator |
US10758230B2 (en) | 2016-12-21 | 2020-09-01 | Ethicon Llc | Surgical instrument with primary and safety processors |
US10813638B2 (en) | 2016-12-21 | 2020-10-27 | Ethicon Llc | Surgical end effectors with expandable tissue stop arrangements |
US11369376B2 (en) | 2016-12-21 | 2022-06-28 | Cilag Gmbh International | Surgical stapling systems |
US11179155B2 (en) | 2016-12-21 | 2021-11-23 | Cilag Gmbh International | Anvil arrangements for surgical staplers |
US11134942B2 (en) | 2016-12-21 | 2021-10-05 | Cilag Gmbh International | Surgical stapling instruments and staple-forming anvils |
US10537324B2 (en) | 2016-12-21 | 2020-01-21 | Ethicon Llc | Stepped staple cartridge with asymmetrical staples |
US10568625B2 (en) | 2016-12-21 | 2020-02-25 | Ethicon Llc | Staple cartridges and arrangements of staples and staple cavities therein |
US11497499B2 (en) | 2016-12-21 | 2022-11-15 | Cilag Gmbh International | Articulatable surgical stapling instruments |
US10695055B2 (en) | 2016-12-21 | 2020-06-30 | Ethicon Llc | Firing assembly comprising a lockout |
US11701115B2 (en) | 2016-12-21 | 2023-07-18 | Cilag Gmbh International | Methods of stapling tissue |
US10687810B2 (en) | 2016-12-21 | 2020-06-23 | Ethicon Llc | Stepped staple cartridge with tissue retention and gap setting features |
US10568624B2 (en) | 2016-12-21 | 2020-02-25 | Ethicon Llc | Surgical instruments with jaws that are pivotable about a fixed axis and include separate and distinct closure and firing systems |
US10905422B2 (en) | 2016-12-21 | 2021-02-02 | Ethicon Llc | Surgical instrument for use with a robotic surgical system |
US11350935B2 (en) | 2016-12-21 | 2022-06-07 | Cilag Gmbh International | Surgical tool assemblies with closure stroke reduction features |
US10779823B2 (en) | 2016-12-21 | 2020-09-22 | Ethicon Llc | Firing member pin angle |
US10524789B2 (en) | 2016-12-21 | 2020-01-07 | Ethicon Llc | Laterally actuatable articulation lock arrangements for locking an end effector of a surgical instrument in an articulated configuration |
US10485543B2 (en) | 2016-12-21 | 2019-11-26 | Ethicon Llc | Anvil having a knife slot width |
US10856868B2 (en) | 2016-12-21 | 2020-12-08 | Ethicon Llc | Firing member pin configurations |
US11191539B2 (en) | 2016-12-21 | 2021-12-07 | Cilag Gmbh International | Shaft assembly comprising a manually-operable retraction system for use with a motorized surgical instrument system |
US10835247B2 (en) | 2016-12-21 | 2020-11-17 | Ethicon Llc | Lockout arrangements for surgical end effectors |
US11191540B2 (en) | 2016-12-21 | 2021-12-07 | Cilag Gmbh International | Protective cover arrangements for a joint interface between a movable jaw and actuator shaft of a surgical instrument |
US11191543B2 (en) | 2016-12-21 | 2021-12-07 | Cilag Gmbh International | Assembly comprising a lock |
US10492785B2 (en) | 2016-12-21 | 2019-12-03 | Ethicon Llc | Shaft assembly comprising a lockout |
US10682138B2 (en) | 2016-12-21 | 2020-06-16 | Ethicon Llc | Bilaterally asymmetric staple forming pocket pairs |
US11350934B2 (en) | 2016-12-21 | 2022-06-07 | Cilag Gmbh International | Staple forming pocket arrangement to accommodate different types of staples |
US10736629B2 (en) | 2016-12-21 | 2020-08-11 | Ethicon Llc | Surgical tool assemblies with clutching arrangements for shifting between closure systems with closure stroke reduction features and articulation and firing systems |
US10667811B2 (en) | 2016-12-21 | 2020-06-02 | Ethicon Llc | Surgical stapling instruments and staple-forming anvils |
US11317913B2 (en) | 2016-12-21 | 2022-05-03 | Cilag Gmbh International | Lockout arrangements for surgical end effectors and replaceable tool assemblies |
US11931034B2 (en) | 2016-12-21 | 2024-03-19 | Cilag Gmbh International | Surgical stapling instruments with smart staple cartridges |
US10898186B2 (en) | 2016-12-21 | 2021-01-26 | Ethicon Llc | Staple forming pocket arrangements comprising primary sidewalls and pocket sidewalls |
US10517595B2 (en) | 2016-12-21 | 2019-12-31 | Ethicon Llc | Jaw actuated lock arrangements for preventing advancement of a firing member in a surgical end effector unless an unfired cartridge is installed in the end effector |
US10517596B2 (en) | 2016-12-21 | 2019-12-31 | Ethicon Llc | Articulatable surgical instruments with articulation stroke amplification features |
US11766260B2 (en) | 2016-12-21 | 2023-09-26 | Cilag Gmbh International | Methods of stapling tissue |
US10881401B2 (en) | 2016-12-21 | 2021-01-05 | Ethicon Llc | Staple firing member comprising a missing cartridge and/or spent cartridge lockout |
US11766259B2 (en) | 2016-12-21 | 2023-09-26 | Cilag Gmbh International | Method of deforming staples from two different types of staple cartridges with the same surgical stapling instrument |
US11571210B2 (en) | 2016-12-21 | 2023-02-07 | Cilag Gmbh International | Firing assembly comprising a multiple failed-state fuse |
US10888322B2 (en) | 2016-12-21 | 2021-01-12 | Ethicon Llc | Surgical instrument comprising a cutting member |
US10993715B2 (en) | 2016-12-21 | 2021-05-04 | Ethicon Llc | Staple cartridge comprising staples with different clamping breadths |
US10499914B2 (en) | 2016-12-21 | 2019-12-10 | Ethicon Llc | Staple forming pocket arrangements |
US10568626B2 (en) | 2016-12-21 | 2020-02-25 | Ethicon Llc | Surgical instruments with jaw opening features for increasing a jaw opening distance |
US11564688B2 (en) | 2016-12-21 | 2023-01-31 | Cilag Gmbh International | Robotic surgical tool having a retraction mechanism |
US10675025B2 (en) | 2016-12-21 | 2020-06-09 | Ethicon Llc | Shaft assembly comprising separately actuatable and retractable systems |
US10675026B2 (en) | 2016-12-21 | 2020-06-09 | Ethicon Llc | Methods of stapling tissue |
US10610224B2 (en) | 2016-12-21 | 2020-04-07 | Ethicon Llc | Lockout arrangements for surgical end effectors and replaceable tool assemblies |
US10893864B2 (en) | 2016-12-21 | 2021-01-19 | Ethicon | Staple cartridges and arrangements of staples and staple cavities therein |
US11224428B2 (en) | 2016-12-21 | 2022-01-18 | Cilag Gmbh International | Surgical stapling systems |
US11559591B2 (en) | 2017-05-25 | 2023-01-24 | Memorial Sloan Kettering Cancer Center | Ultrasmall nanoparticles labeled with Zirconium-89 and methods thereof |
US11959921B2 (en) | 2017-06-12 | 2024-04-16 | The University Of Queensland | Dendritic mesoporous silica nanoparticles synthesized via a facile one-pot surfactant-free process |
US11382638B2 (en) | 2017-06-20 | 2022-07-12 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured time over a specified displacement distance |
US10980537B2 (en) | 2017-06-20 | 2021-04-20 | Ethicon Llc | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured time over a specified number of shaft rotations |
US10888321B2 (en) | 2017-06-20 | 2021-01-12 | Ethicon Llc | Systems and methods for controlling velocity of a displacement member of a surgical stapling and cutting instrument |
US10624633B2 (en) | 2017-06-20 | 2020-04-21 | Ethicon Llc | Systems and methods for controlling motor velocity of a surgical stapling and cutting instrument |
US10595882B2 (en) | 2017-06-20 | 2020-03-24 | Ethicon Llc | Methods for closed loop control of motor velocity of a surgical stapling and cutting instrument |
US10390841B2 (en) | 2017-06-20 | 2019-08-27 | Ethicon Llc | Control of motor velocity of a surgical stapling and cutting instrument based on angle of articulation |
US11517325B2 (en) | 2017-06-20 | 2022-12-06 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured displacement distance traveled over a specified time interval |
US11672532B2 (en) | 2017-06-20 | 2023-06-13 | Cilag Gmbh International | Techniques for adaptive control of motor velocity of a surgical stapling and cutting instrument |
USD890784S1 (en) | 2017-06-20 | 2020-07-21 | Ethicon Llc | Display panel with changeable graphical user interface |
US10881396B2 (en) | 2017-06-20 | 2021-01-05 | Ethicon Llc | Surgical instrument with variable duration trigger arrangement |
US10646220B2 (en) | 2017-06-20 | 2020-05-12 | Ethicon Llc | Systems and methods for controlling displacement member velocity for a surgical instrument |
US10881399B2 (en) | 2017-06-20 | 2021-01-05 | Ethicon Llc | Techniques for adaptive control of motor velocity of a surgical stapling and cutting instrument |
US11071554B2 (en) | 2017-06-20 | 2021-07-27 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on magnitude of velocity error measurements |
US11090046B2 (en) | 2017-06-20 | 2021-08-17 | Cilag Gmbh International | Systems and methods for controlling displacement member motion of a surgical stapling and cutting instrument |
US11653914B2 (en) | 2017-06-20 | 2023-05-23 | Cilag Gmbh International | Systems and methods for controlling motor velocity of a surgical stapling and cutting instrument according to articulation angle of end effector |
US10368864B2 (en) | 2017-06-20 | 2019-08-06 | Ethicon Llc | Systems and methods for controlling displaying motor velocity for a surgical instrument |
US10327767B2 (en) | 2017-06-20 | 2019-06-25 | Ethicon Llc | Control of motor velocity of a surgical stapling and cutting instrument based on angle of articulation |
US11871939B2 (en) | 2017-06-20 | 2024-01-16 | Cilag Gmbh International | Method for closed loop control of motor velocity of a surgical stapling and cutting instrument |
US10307170B2 (en) | 2017-06-20 | 2019-06-04 | Ethicon Llc | Method for closed loop control of motor velocity of a surgical stapling and cutting instrument |
US11213302B2 (en) | 2017-06-20 | 2022-01-04 | Cilag Gmbh International | Method for closed loop control of motor velocity of a surgical stapling and cutting instrument |
US10779820B2 (en) | 2017-06-20 | 2020-09-22 | Ethicon Llc | Systems and methods for controlling motor speed according to user input for a surgical instrument |
USD879808S1 (en) | 2017-06-20 | 2020-03-31 | Ethicon Llc | Display panel with graphical user interface |
US10813639B2 (en) | 2017-06-20 | 2020-10-27 | Ethicon Llc | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on system conditions |
USD879809S1 (en) | 2017-06-20 | 2020-03-31 | Ethicon Llc | Display panel with changeable graphical user interface |
US11793513B2 (en) | 2017-06-20 | 2023-10-24 | Cilag Gmbh International | Systems and methods for controlling motor speed according to user input for a surgical instrument |
US11141154B2 (en) | 2017-06-27 | 2021-10-12 | Cilag Gmbh International | Surgical end effectors and anvils |
US10772629B2 (en) | 2017-06-27 | 2020-09-15 | Ethicon Llc | Surgical anvil arrangements |
US11766258B2 (en) | 2017-06-27 | 2023-09-26 | Cilag Gmbh International | Surgical anvil arrangements |
US11266405B2 (en) | 2017-06-27 | 2022-03-08 | Cilag Gmbh International | Surgical anvil manufacturing methods |
US11324503B2 (en) | 2017-06-27 | 2022-05-10 | Cilag Gmbh International | Surgical firing member arrangements |
US11090049B2 (en) | 2017-06-27 | 2021-08-17 | Cilag Gmbh International | Staple forming pocket arrangements |
US10856869B2 (en) | 2017-06-27 | 2020-12-08 | Ethicon Llc | Surgical anvil arrangements |
US10993716B2 (en) | 2017-06-27 | 2021-05-04 | Ethicon Llc | Surgical anvil arrangements |
US10631859B2 (en) | 2017-06-27 | 2020-04-28 | Ethicon Llc | Articulation systems for surgical instruments |
USD854151S1 (en) | 2017-06-28 | 2019-07-16 | Ethicon Llc | Surgical instrument shaft |
US11083455B2 (en) | 2017-06-28 | 2021-08-10 | Cilag Gmbh International | Surgical instrument comprising an articulation system ratio |
US10903685B2 (en) | 2017-06-28 | 2021-01-26 | Ethicon Llc | Surgical shaft assemblies with slip ring assemblies forming capacitive channels |
US10786253B2 (en) | 2017-06-28 | 2020-09-29 | Ethicon Llc | Surgical end effectors with improved jaw aperture arrangements |
US11058424B2 (en) | 2017-06-28 | 2021-07-13 | Cilag Gmbh International | Surgical instrument comprising an offset articulation joint |
US11246592B2 (en) | 2017-06-28 | 2022-02-15 | Cilag Gmbh International | Surgical instrument comprising an articulation system lockable to a frame |
US11696759B2 (en) | 2017-06-28 | 2023-07-11 | Cilag Gmbh International | Surgical stapling instruments comprising shortened staple cartridge noses |
US10695057B2 (en) | 2017-06-28 | 2020-06-30 | Ethicon Llc | Surgical instrument lockout arrangement |
US11259805B2 (en) | 2017-06-28 | 2022-03-01 | Cilag Gmbh International | Surgical instrument comprising firing member supports |
US10765427B2 (en) | 2017-06-28 | 2020-09-08 | Ethicon Llc | Method for articulating a surgical instrument |
US11484310B2 (en) | 2017-06-28 | 2022-11-01 | Cilag Gmbh International | Surgical instrument comprising a shaft including a closure tube profile |
US11020114B2 (en) | 2017-06-28 | 2021-06-01 | Cilag Gmbh International | Surgical instruments with articulatable end effector with axially shortened articulation joint configurations |
US10716614B2 (en) | 2017-06-28 | 2020-07-21 | Ethicon Llc | Surgical shaft assemblies with slip ring assemblies with increased contact pressure |
US11000279B2 (en) | 2017-06-28 | 2021-05-11 | Ethicon Llc | Surgical instrument comprising an articulation system ratio |
US11478242B2 (en) | 2017-06-28 | 2022-10-25 | Cilag Gmbh International | Jaw retainer arrangement for retaining a pivotable surgical instrument jaw in pivotable retaining engagement with a second surgical instrument jaw |
US11642128B2 (en) | 2017-06-28 | 2023-05-09 | Cilag Gmbh International | Method for articulating a surgical instrument |
US10758232B2 (en) | 2017-06-28 | 2020-09-01 | Ethicon Llc | Surgical instrument with positive jaw opening features |
US11529140B2 (en) | 2017-06-28 | 2022-12-20 | Cilag Gmbh International | Surgical instrument lockout arrangement |
USD869655S1 (en) | 2017-06-28 | 2019-12-10 | Ethicon Llc | Surgical fastener cartridge |
USD906355S1 (en) | 2017-06-28 | 2020-12-29 | Ethicon Llc | Display screen or portion thereof with a graphical user interface for a surgical instrument |
US11826048B2 (en) | 2017-06-28 | 2023-11-28 | Cilag Gmbh International | Surgical instrument comprising selectively actuatable rotatable couplers |
US10211586B2 (en) | 2017-06-28 | 2019-02-19 | Ethicon Llc | Surgical shaft assemblies with watertight housings |
US10588633B2 (en) | 2017-06-28 | 2020-03-17 | Ethicon Llc | Surgical instruments with open and closable jaws and axially movable firing member that is initially parked in close proximity to the jaws prior to firing |
US11678880B2 (en) | 2017-06-28 | 2023-06-20 | Cilag Gmbh International | Surgical instrument comprising a shaft including a housing arrangement |
US10639037B2 (en) | 2017-06-28 | 2020-05-05 | Ethicon Llc | Surgical instrument with axially movable closure member |
US11389161B2 (en) | 2017-06-28 | 2022-07-19 | Cilag Gmbh International | Surgical instrument comprising selectively actuatable rotatable couplers |
USD1018577S1 (en) | 2017-06-28 | 2024-03-19 | Cilag Gmbh International | Display screen or portion thereof with a graphical user interface for a surgical instrument |
USD851762S1 (en) | 2017-06-28 | 2019-06-18 | Ethicon Llc | Anvil |
US11564686B2 (en) | 2017-06-28 | 2023-01-31 | Cilag Gmbh International | Surgical shaft assemblies with flexible interfaces |
US10779824B2 (en) | 2017-06-28 | 2020-09-22 | Ethicon Llc | Surgical instrument comprising an articulation system lockable by a closure system |
US11890005B2 (en) | 2017-06-29 | 2024-02-06 | Cilag Gmbh International | Methods for closed loop velocity control for robotic surgical instrument |
US10932772B2 (en) | 2017-06-29 | 2021-03-02 | Ethicon Llc | Methods for closed loop velocity control for robotic surgical instrument |
US10398434B2 (en) | 2017-06-29 | 2019-09-03 | Ethicon Llc | Closed loop velocity control of closure member for robotic surgical instrument |
US11007022B2 (en) | 2017-06-29 | 2021-05-18 | Ethicon Llc | Closed loop velocity control techniques based on sensed tissue parameters for robotic surgical instrument |
US10258418B2 (en) | 2017-06-29 | 2019-04-16 | Ethicon Llc | System for controlling articulation forces |
US10898183B2 (en) | 2017-06-29 | 2021-01-26 | Ethicon Llc | Robotic surgical instrument with closed loop feedback techniques for advancement of closure member during firing |
US11471155B2 (en) | 2017-08-03 | 2022-10-18 | Cilag Gmbh International | Surgical system bailout |
US11944300B2 (en) | 2017-08-03 | 2024-04-02 | Cilag Gmbh International | Method for operating a surgical system bailout |
US11304695B2 (en) | 2017-08-03 | 2022-04-19 | Cilag Gmbh International | Surgical system shaft interconnection |
USD917500S1 (en) | 2017-09-29 | 2021-04-27 | Ethicon Llc | Display screen or portion thereof with graphical user interface |
USD907647S1 (en) | 2017-09-29 | 2021-01-12 | Ethicon Llc | Display screen or portion thereof with animated graphical user interface |
USD907648S1 (en) | 2017-09-29 | 2021-01-12 | Ethicon Llc | Display screen or portion thereof with animated graphical user interface |
US10765429B2 (en) | 2017-09-29 | 2020-09-08 | Ethicon Llc | Systems and methods for providing alerts according to the operational state of a surgical instrument |
US10743872B2 (en) | 2017-09-29 | 2020-08-18 | Ethicon Llc | System and methods for controlling a display of a surgical instrument |
US10796471B2 (en) | 2017-09-29 | 2020-10-06 | Ethicon Llc | Systems and methods of displaying a knife position for a surgical instrument |
US11399829B2 (en) | 2017-09-29 | 2022-08-02 | Cilag Gmbh International | Systems and methods of initiating a power shutdown mode for a surgical instrument |
US11090075B2 (en) | 2017-10-30 | 2021-08-17 | Cilag Gmbh International | Articulation features for surgical end effector |
US11134944B2 (en) | 2017-10-30 | 2021-10-05 | Cilag Gmbh International | Surgical stapler knife motion controls |
US10842490B2 (en) | 2017-10-31 | 2020-11-24 | Ethicon Llc | Cartridge body design with force reduction based on firing completion |
US10779903B2 (en) | 2017-10-31 | 2020-09-22 | Ethicon Llc | Positive shaft rotation lock activated by jaw closure |
US11478244B2 (en) | 2017-10-31 | 2022-10-25 | Cilag Gmbh International | Cartridge body design with force reduction based on firing completion |
US10779826B2 (en) | 2017-12-15 | 2020-09-22 | Ethicon Llc | Methods of operating surgical end effectors |
US10779825B2 (en) | 2017-12-15 | 2020-09-22 | Ethicon Llc | Adapters with end effector position sensing and control arrangements for use in connection with electromechanical surgical instruments |
US10966718B2 (en) | 2017-12-15 | 2021-04-06 | Ethicon Llc | Dynamic clamping assemblies with improved wear characteristics for use in connection with electromechanical surgical instruments |
US11071543B2 (en) | 2017-12-15 | 2021-07-27 | Cilag Gmbh International | Surgical end effectors with clamping assemblies configured to increase jaw aperture ranges |
US10743875B2 (en) | 2017-12-15 | 2020-08-18 | Ethicon Llc | Surgical end effectors with jaw stiffener arrangements configured to permit monitoring of firing member |
US11006955B2 (en) | 2017-12-15 | 2021-05-18 | Ethicon Llc | End effectors with positive jaw opening features for use with adapters for electromechanical surgical instruments |
US11033267B2 (en) | 2017-12-15 | 2021-06-15 | Ethicon Llc | Systems and methods of controlling a clamping member firing rate of a surgical instrument |
US10687813B2 (en) | 2017-12-15 | 2020-06-23 | Ethicon Llc | Adapters with firing stroke sensing arrangements for use in connection with electromechanical surgical instruments |
US10743874B2 (en) | 2017-12-15 | 2020-08-18 | Ethicon Llc | Sealed adapters for use with electromechanical surgical instruments |
US10828033B2 (en) | 2017-12-15 | 2020-11-10 | Ethicon Llc | Handheld electromechanical surgical instruments with improved motor control arrangements for positioning components of an adapter coupled thereto |
US11197670B2 (en) | 2017-12-15 | 2021-12-14 | Cilag Gmbh International | Surgical end effectors with pivotal jaws configured to touch at their respective distal ends when fully closed |
US10869666B2 (en) | 2017-12-15 | 2020-12-22 | Ethicon Llc | Adapters with control systems for controlling multiple motors of an electromechanical surgical instrument |
US11896222B2 (en) | 2017-12-15 | 2024-02-13 | Cilag Gmbh International | Methods of operating surgical end effectors |
US11020112B2 (en) | 2017-12-19 | 2021-06-01 | Ethicon Llc | Surgical tools configured for interchangeable use with different controller interfaces |
US10716565B2 (en) | 2017-12-19 | 2020-07-21 | Ethicon Llc | Surgical instruments with dual articulation drivers |
USD910847S1 (en) | 2017-12-19 | 2021-02-16 | Ethicon Llc | Surgical instrument assembly |
US10729509B2 (en) | 2017-12-19 | 2020-08-04 | Ethicon Llc | Surgical instrument comprising closure and firing locking mechanism |
WO2019123156A1 (en) * | 2017-12-19 | 2019-06-27 | 3M Innovative Properties Company | Compositions and methods to detect microorganisms |
US11045270B2 (en) | 2017-12-19 | 2021-06-29 | Cilag Gmbh International | Robotic attachment comprising exterior drive actuator |
US11284953B2 (en) | 2017-12-19 | 2022-03-29 | Cilag Gmbh International | Method for determining the position of a rotatable jaw of a surgical instrument attachment assembly |
US10835330B2 (en) | 2017-12-19 | 2020-11-17 | Ethicon Llc | Method for determining the position of a rotatable jaw of a surgical instrument attachment assembly |
US11364027B2 (en) | 2017-12-21 | 2022-06-21 | Cilag Gmbh International | Surgical instrument comprising speed control |
US11576668B2 (en) | 2017-12-21 | 2023-02-14 | Cilag Gmbh International | Staple instrument comprising a firing path display |
US11583274B2 (en) | 2017-12-21 | 2023-02-21 | Cilag Gmbh International | Self-guiding stapling instrument |
US11129680B2 (en) | 2017-12-21 | 2021-09-28 | Cilag Gmbh International | Surgical instrument comprising a projector |
US11849939B2 (en) | 2017-12-21 | 2023-12-26 | Cilag Gmbh International | Continuous use self-propelled stapling instrument |
US11337691B2 (en) | 2017-12-21 | 2022-05-24 | Cilag Gmbh International | Surgical instrument configured to determine firing path |
US10743868B2 (en) | 2017-12-21 | 2020-08-18 | Ethicon Llc | Surgical instrument comprising a pivotable distal head |
US11883019B2 (en) | 2017-12-21 | 2024-01-30 | Cilag Gmbh International | Stapling instrument comprising a staple feeding system |
US11179152B2 (en) | 2017-12-21 | 2021-11-23 | Cilag Gmbh International | Surgical instrument comprising a tissue grasping system |
US11179151B2 (en) | 2017-12-21 | 2021-11-23 | Cilag Gmbh International | Surgical instrument comprising a display |
US11369368B2 (en) | 2017-12-21 | 2022-06-28 | Cilag Gmbh International | Surgical instrument comprising synchronized drive systems |
US11751867B2 (en) | 2017-12-21 | 2023-09-12 | Cilag Gmbh International | Surgical instrument comprising sequenced systems |
US11311290B2 (en) | 2017-12-21 | 2022-04-26 | Cilag Gmbh International | Surgical instrument comprising an end effector dampener |
US10682134B2 (en) | 2017-12-21 | 2020-06-16 | Ethicon Llc | Continuous use self-propelled stapling instrument |
US11076853B2 (en) | 2017-12-21 | 2021-08-03 | Cilag Gmbh International | Systems and methods of displaying a knife position during transection for a surgical instrument |
US10856870B2 (en) | 2018-08-20 | 2020-12-08 | Ethicon Llc | Switching arrangements for motor powered articulatable surgical instruments |
USD914878S1 (en) | 2018-08-20 | 2021-03-30 | Ethicon Llc | Surgical instrument anvil |
US11291440B2 (en) | 2018-08-20 | 2022-04-05 | Cilag Gmbh International | Method for operating a powered articulatable surgical instrument |
US10779821B2 (en) | 2018-08-20 | 2020-09-22 | Ethicon Llc | Surgical stapler anvils with tissue stop features configured to avoid tissue pinch |
US11207065B2 (en) | 2018-08-20 | 2021-12-28 | Cilag Gmbh International | Method for fabricating surgical stapler anvils |
US11324501B2 (en) | 2018-08-20 | 2022-05-10 | Cilag Gmbh International | Surgical stapling devices with improved closure members |
US11039834B2 (en) | 2018-08-20 | 2021-06-22 | Cilag Gmbh International | Surgical stapler anvils with staple directing protrusions and tissue stability features |
US11045192B2 (en) | 2018-08-20 | 2021-06-29 | Cilag Gmbh International | Fabricating techniques for surgical stapler anvils |
US11083458B2 (en) | 2018-08-20 | 2021-08-10 | Cilag Gmbh International | Powered surgical instruments with clutching arrangements to convert linear drive motions to rotary drive motions |
US10912559B2 (en) | 2018-08-20 | 2021-02-09 | Ethicon Llc | Reinforced deformable anvil tip for surgical stapler anvil |
US11253256B2 (en) | 2018-08-20 | 2022-02-22 | Cilag Gmbh International | Articulatable motor powered surgical instruments with dedicated articulation motor arrangements |
US10842492B2 (en) | 2018-08-20 | 2020-11-24 | Ethicon Llc | Powered articulatable surgical instruments with clutching and locking arrangements for linking an articulation drive system to a firing drive system |
US11147553B2 (en) | 2019-03-25 | 2021-10-19 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11696761B2 (en) | 2019-03-25 | 2023-07-11 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11172929B2 (en) | 2019-03-25 | 2021-11-16 | Cilag Gmbh International | Articulation drive arrangements for surgical systems |
US11147551B2 (en) | 2019-03-25 | 2021-10-19 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11452528B2 (en) | 2019-04-30 | 2022-09-27 | Cilag Gmbh International | Articulation actuators for a surgical instrument |
US11903581B2 (en) | 2019-04-30 | 2024-02-20 | Cilag Gmbh International | Methods for stapling tissue using a surgical instrument |
US11432816B2 (en) | 2019-04-30 | 2022-09-06 | Cilag Gmbh International | Articulation pin for a surgical instrument |
US11471157B2 (en) | 2019-04-30 | 2022-10-18 | Cilag Gmbh International | Articulation control mapping for a surgical instrument |
US11426251B2 (en) | 2019-04-30 | 2022-08-30 | Cilag Gmbh International | Articulation directional lights on a surgical instrument |
US11253254B2 (en) | 2019-04-30 | 2022-02-22 | Cilag Gmbh International | Shaft rotation actuator on a surgical instrument |
US11648009B2 (en) | 2019-04-30 | 2023-05-16 | Cilag Gmbh International | Rotatable jaw tip for a surgical instrument |
US11219455B2 (en) | 2019-06-28 | 2022-01-11 | Cilag Gmbh International | Surgical instrument including a lockout key |
US11224497B2 (en) | 2019-06-28 | 2022-01-18 | Cilag Gmbh International | Surgical systems with multiple RFID tags |
US11478241B2 (en) | 2019-06-28 | 2022-10-25 | Cilag Gmbh International | Staple cartridge including projections |
US11497492B2 (en) | 2019-06-28 | 2022-11-15 | Cilag Gmbh International | Surgical instrument including an articulation lock |
US11298132B2 (en) | 2019-06-28 | 2022-04-12 | Cilag GmbH Inlernational | Staple cartridge including a honeycomb extension |
US11464601B2 (en) | 2019-06-28 | 2022-10-11 | Cilag Gmbh International | Surgical instrument comprising an RFID system for tracking a movable component |
US11350938B2 (en) | 2019-06-28 | 2022-06-07 | Cilag Gmbh International | Surgical instrument comprising an aligned rfid sensor |
US11744593B2 (en) | 2019-06-28 | 2023-09-05 | Cilag Gmbh International | Method for authenticating the compatibility of a staple cartridge with a surgical instrument |
US11553971B2 (en) | 2019-06-28 | 2023-01-17 | Cilag Gmbh International | Surgical RFID assemblies for display and communication |
US11246678B2 (en) | 2019-06-28 | 2022-02-15 | Cilag Gmbh International | Surgical stapling system having a frangible RFID tag |
US11627959B2 (en) | 2019-06-28 | 2023-04-18 | Cilag Gmbh International | Surgical instruments including manual and powered system lockouts |
US11298127B2 (en) | 2019-06-28 | 2022-04-12 | Cilag GmbH Interational | Surgical stapling system having a lockout mechanism for an incompatible cartridge |
US11376098B2 (en) | 2019-06-28 | 2022-07-05 | Cilag Gmbh International | Surgical instrument system comprising an RFID system |
US11259803B2 (en) | 2019-06-28 | 2022-03-01 | Cilag Gmbh International | Surgical stapling system having an information encryption protocol |
US11553919B2 (en) | 2019-06-28 | 2023-01-17 | Cilag Gmbh International | Method for authenticating the compatibility of a staple cartridge with a surgical instrument |
US11426167B2 (en) | 2019-06-28 | 2022-08-30 | Cilag Gmbh International | Mechanisms for proper anvil attachment surgical stapling head assembly |
US11523822B2 (en) | 2019-06-28 | 2022-12-13 | Cilag Gmbh International | Battery pack including a circuit interrupter |
US11051807B2 (en) | 2019-06-28 | 2021-07-06 | Cilag Gmbh International | Packaging assembly including a particulate trap |
US11684369B2 (en) | 2019-06-28 | 2023-06-27 | Cilag Gmbh International | Method of using multiple RFID chips with a surgical assembly |
US11684434B2 (en) | 2019-06-28 | 2023-06-27 | Cilag Gmbh International | Surgical RFID assemblies for instrument operational setting control |
US11291451B2 (en) | 2019-06-28 | 2022-04-05 | Cilag Gmbh International | Surgical instrument with battery compatibility verification functionality |
US11638587B2 (en) | 2019-06-28 | 2023-05-02 | Cilag Gmbh International | RFID identification systems for surgical instruments |
US11771419B2 (en) | 2019-06-28 | 2023-10-03 | Cilag Gmbh International | Packaging for a replaceable component of a surgical stapling system |
US11241235B2 (en) | 2019-06-28 | 2022-02-08 | Cilag Gmbh International | Method of using multiple RFID chips with a surgical assembly |
US11229437B2 (en) | 2019-06-28 | 2022-01-25 | Cilag Gmbh International | Method for authenticating the compatibility of a staple cartridge with a surgical instrument |
US11399837B2 (en) | 2019-06-28 | 2022-08-02 | Cilag Gmbh International | Mechanisms for motor control adjustments of a motorized surgical instrument |
US11660163B2 (en) | 2019-06-28 | 2023-05-30 | Cilag Gmbh International | Surgical system with RFID tags for updating motor assembly parameters |
US11234698B2 (en) | 2019-12-19 | 2022-02-01 | Cilag Gmbh International | Stapling system comprising a clamp lockout and a firing lockout |
US11446029B2 (en) | 2019-12-19 | 2022-09-20 | Cilag Gmbh International | Staple cartridge comprising projections extending from a curved deck surface |
US11529137B2 (en) | 2019-12-19 | 2022-12-20 | Cilag Gmbh International | Staple cartridge comprising driver retention members |
US11844520B2 (en) | 2019-12-19 | 2023-12-19 | Cilag Gmbh International | Staple cartridge comprising driver retention members |
US11911032B2 (en) | 2019-12-19 | 2024-02-27 | Cilag Gmbh International | Staple cartridge comprising a seating cam |
US11304696B2 (en) | 2019-12-19 | 2022-04-19 | Cilag Gmbh International | Surgical instrument comprising a powered articulation system |
US11291447B2 (en) | 2019-12-19 | 2022-04-05 | Cilag Gmbh International | Stapling instrument comprising independent jaw closing and staple firing systems |
US11529139B2 (en) | 2019-12-19 | 2022-12-20 | Cilag Gmbh International | Motor driven surgical instrument |
US11701111B2 (en) | 2019-12-19 | 2023-07-18 | Cilag Gmbh International | Method for operating a surgical stapling instrument |
US11464512B2 (en) | 2019-12-19 | 2022-10-11 | Cilag Gmbh International | Staple cartridge comprising a curved deck surface |
US11607219B2 (en) | 2019-12-19 | 2023-03-21 | Cilag Gmbh International | Staple cartridge comprising a detachable tissue cutting knife |
US11576672B2 (en) | 2019-12-19 | 2023-02-14 | Cilag Gmbh International | Surgical instrument comprising a closure system including a closure member and an opening member driven by a drive screw |
US11559304B2 (en) | 2019-12-19 | 2023-01-24 | Cilag Gmbh International | Surgical instrument comprising a rapid closure mechanism |
US11931033B2 (en) | 2019-12-19 | 2024-03-19 | Cilag Gmbh International | Staple cartridge comprising a latch lockout |
US11504122B2 (en) | 2019-12-19 | 2022-11-22 | Cilag Gmbh International | Surgical instrument comprising a nested firing member |
WO2021173629A3 (en) * | 2020-02-28 | 2021-11-04 | NanoBio Designs, LLC | Molecular detection via assembly of particle complexes |
USD974560S1 (en) | 2020-06-02 | 2023-01-03 | Cilag Gmbh International | Staple cartridge |
USD967421S1 (en) | 2020-06-02 | 2022-10-18 | Cilag Gmbh International | Staple cartridge |
USD966512S1 (en) | 2020-06-02 | 2022-10-11 | Cilag Gmbh International | Staple cartridge |
USD976401S1 (en) | 2020-06-02 | 2023-01-24 | Cilag Gmbh International | Staple cartridge |
USD975851S1 (en) | 2020-06-02 | 2023-01-17 | Cilag Gmbh International | Staple cartridge |
USD975850S1 (en) | 2020-06-02 | 2023-01-17 | Cilag Gmbh International | Staple cartridge |
USD975278S1 (en) | 2020-06-02 | 2023-01-10 | Cilag Gmbh International | Staple cartridge |
US11737748B2 (en) | 2020-07-28 | 2023-08-29 | Cilag Gmbh International | Surgical instruments with double spherical articulation joints with pivotable links |
US11864756B2 (en) | 2020-07-28 | 2024-01-09 | Cilag Gmbh International | Surgical instruments with flexible ball chain drive arrangements |
US11883024B2 (en) | 2020-07-28 | 2024-01-30 | Cilag Gmbh International | Method of operating a surgical instrument |
US11660090B2 (en) | 2020-07-28 | 2023-05-30 | Cllag GmbH International | Surgical instruments with segmented flexible drive arrangements |
US11638582B2 (en) | 2020-07-28 | 2023-05-02 | Cilag Gmbh International | Surgical instruments with torsion spine drive arrangements |
US11857182B2 (en) | 2020-07-28 | 2024-01-02 | Cilag Gmbh International | Surgical instruments with combination function articulation joint arrangements |
US11871925B2 (en) | 2020-07-28 | 2024-01-16 | Cilag Gmbh International | Surgical instruments with dual spherical articulation joint arrangements |
US11826013B2 (en) | 2020-07-28 | 2023-11-28 | Cilag Gmbh International | Surgical instruments with firing member closure features |
US11896217B2 (en) | 2020-10-29 | 2024-02-13 | Cilag Gmbh International | Surgical instrument comprising an articulation lock |
US11617577B2 (en) | 2020-10-29 | 2023-04-04 | Cilag Gmbh International | Surgical instrument comprising a sensor configured to sense whether an articulation drive of the surgical instrument is actuatable |
US11844518B2 (en) | 2020-10-29 | 2023-12-19 | Cilag Gmbh International | Method for operating a surgical instrument |
US11452526B2 (en) | 2020-10-29 | 2022-09-27 | Cilag Gmbh International | Surgical instrument comprising a staged voltage regulation start-up system |
US11779330B2 (en) | 2020-10-29 | 2023-10-10 | Cilag Gmbh International | Surgical instrument comprising a jaw alignment system |
USD1013170S1 (en) | 2020-10-29 | 2024-01-30 | Cilag Gmbh International | Surgical instrument assembly |
US11517390B2 (en) | 2020-10-29 | 2022-12-06 | Cilag Gmbh International | Surgical instrument comprising a limited travel switch |
USD980425S1 (en) | 2020-10-29 | 2023-03-07 | Cilag Gmbh International | Surgical instrument assembly |
US11931025B2 (en) | 2020-10-29 | 2024-03-19 | Cilag Gmbh International | Surgical instrument comprising a releasable closure drive lock |
US11534259B2 (en) | 2020-10-29 | 2022-12-27 | Cilag Gmbh International | Surgical instrument comprising an articulation indicator |
US11717289B2 (en) | 2020-10-29 | 2023-08-08 | Cilag Gmbh International | Surgical instrument comprising an indicator which indicates that an articulation drive is actuatable |
US11737751B2 (en) | 2020-12-02 | 2023-08-29 | Cilag Gmbh International | Devices and methods of managing energy dissipated within sterile barriers of surgical instrument housings |
US11627960B2 (en) | 2020-12-02 | 2023-04-18 | Cilag Gmbh International | Powered surgical instruments with smart reload with separately attachable exteriorly mounted wiring connections |
US11890010B2 (en) | 2020-12-02 | 2024-02-06 | Cllag GmbH International | Dual-sided reinforced reload for surgical instruments |
US11653920B2 (en) | 2020-12-02 | 2023-05-23 | Cilag Gmbh International | Powered surgical instruments with communication interfaces through sterile barrier |
US11744581B2 (en) | 2020-12-02 | 2023-09-05 | Cilag Gmbh International | Powered surgical instruments with multi-phase tissue treatment |
US11944296B2 (en) | 2020-12-02 | 2024-04-02 | Cilag Gmbh International | Powered surgical instruments with external connectors |
US11653915B2 (en) | 2020-12-02 | 2023-05-23 | Cilag Gmbh International | Surgical instruments with sled location detection and adjustment features |
US11678882B2 (en) | 2020-12-02 | 2023-06-20 | Cilag Gmbh International | Surgical instruments with interactive features to remedy incidental sled movements |
US11849943B2 (en) | 2020-12-02 | 2023-12-26 | Cilag Gmbh International | Surgical instrument with cartridge release mechanisms |
US11751869B2 (en) | 2021-02-26 | 2023-09-12 | Cilag Gmbh International | Monitoring of multiple sensors over time to detect moving characteristics of tissue |
US11730473B2 (en) | 2021-02-26 | 2023-08-22 | Cilag Gmbh International | Monitoring of manufacturing life-cycle |
US11793514B2 (en) | 2021-02-26 | 2023-10-24 | Cilag Gmbh International | Staple cartridge comprising sensor array which may be embedded in cartridge body |
US11749877B2 (en) | 2021-02-26 | 2023-09-05 | Cilag Gmbh International | Stapling instrument comprising a signal antenna |
US11701113B2 (en) | 2021-02-26 | 2023-07-18 | Cilag Gmbh International | Stapling instrument comprising a separate power antenna and a data transfer antenna |
US11950777B2 (en) | 2021-02-26 | 2024-04-09 | Cilag Gmbh International | Staple cartridge comprising an information access control system |
US11950779B2 (en) | 2021-02-26 | 2024-04-09 | Cilag Gmbh International | Method of powering and communicating with a staple cartridge |
US11812964B2 (en) | 2021-02-26 | 2023-11-14 | Cilag Gmbh International | Staple cartridge comprising a power management circuit |
US11696757B2 (en) | 2021-02-26 | 2023-07-11 | Cilag Gmbh International | Monitoring of internal systems to detect and track cartridge motion status |
US11723657B2 (en) | 2021-02-26 | 2023-08-15 | Cilag Gmbh International | Adjustable communication based on available bandwidth and power capacity |
US11925349B2 (en) | 2021-02-26 | 2024-03-12 | Cilag Gmbh International | Adjustment to transfer parameters to improve available power |
US11744583B2 (en) | 2021-02-26 | 2023-09-05 | Cilag Gmbh International | Distal communication array to tune frequency of RF systems |
US11717291B2 (en) | 2021-03-22 | 2023-08-08 | Cilag Gmbh International | Staple cartridge comprising staples configured to apply different tissue compression |
US11737749B2 (en) | 2021-03-22 | 2023-08-29 | Cilag Gmbh International | Surgical stapling instrument comprising a retraction system |
US11723658B2 (en) | 2021-03-22 | 2023-08-15 | Cilag Gmbh International | Staple cartridge comprising a firing lockout |
US11826012B2 (en) | 2021-03-22 | 2023-11-28 | Cilag Gmbh International | Stapling instrument comprising a pulsed motor-driven firing rack |
US11806011B2 (en) | 2021-03-22 | 2023-11-07 | Cilag Gmbh International | Stapling instrument comprising tissue compression systems |
US11826042B2 (en) | 2021-03-22 | 2023-11-28 | Cilag Gmbh International | Surgical instrument comprising a firing drive including a selectable leverage mechanism |
US11759202B2 (en) | 2021-03-22 | 2023-09-19 | Cilag Gmbh International | Staple cartridge comprising an implantable layer |
US11896218B2 (en) | 2021-03-24 | 2024-02-13 | Cilag Gmbh International | Method of using a powered stapling device |
US11786239B2 (en) | 2021-03-24 | 2023-10-17 | Cilag Gmbh International | Surgical instrument articulation joint arrangements comprising multiple moving linkage features |
US11832816B2 (en) | 2021-03-24 | 2023-12-05 | Cilag Gmbh International | Surgical stapling assembly comprising nonplanar staples and planar staples |
US11786243B2 (en) | 2021-03-24 | 2023-10-17 | Cilag Gmbh International | Firing members having flexible portions for adapting to a load during a surgical firing stroke |
US11849944B2 (en) | 2021-03-24 | 2023-12-26 | Cilag Gmbh International | Drivers for fastener cartridge assemblies having rotary drive screws |
US11793516B2 (en) | 2021-03-24 | 2023-10-24 | Cilag Gmbh International | Surgical staple cartridge comprising longitudinal support beam |
US11744603B2 (en) | 2021-03-24 | 2023-09-05 | Cilag Gmbh International | Multi-axis pivot joints for surgical instruments and methods for manufacturing same |
US11896219B2 (en) | 2021-03-24 | 2024-02-13 | Cilag Gmbh International | Mating features between drivers and underside of a cartridge deck |
US11857183B2 (en) | 2021-03-24 | 2024-01-02 | Cilag Gmbh International | Stapling assembly components having metal substrates and plastic bodies |
US11944336B2 (en) | 2021-03-24 | 2024-04-02 | Cilag Gmbh International | Joint arrangements for multi-planar alignment and support of operational drive shafts in articulatable surgical instruments |
US11903582B2 (en) | 2021-03-24 | 2024-02-20 | Cilag Gmbh International | Leveraging surfaces for cartridge installation |
US11849945B2 (en) | 2021-03-24 | 2023-12-26 | Cilag Gmbh International | Rotary-driven surgical stapling assembly comprising eccentrically driven firing member |
US11826047B2 (en) | 2021-05-28 | 2023-11-28 | Cilag Gmbh International | Stapling instrument comprising jaw mounts |
US11723662B2 (en) | 2021-05-28 | 2023-08-15 | Cilag Gmbh International | Stapling instrument comprising an articulation control display |
US11918217B2 (en) | 2021-05-28 | 2024-03-05 | Cilag Gmbh International | Stapling instrument comprising a staple cartridge insertion stop |
US11957344B2 (en) | 2021-09-27 | 2024-04-16 | Cilag Gmbh International | Surgical stapler having rows of obliquely oriented staples |
US11877745B2 (en) | 2021-10-18 | 2024-01-23 | Cilag Gmbh International | Surgical stapling assembly having longitudinally-repeating staple leg clusters |
US11957337B2 (en) | 2021-10-18 | 2024-04-16 | Cilag Gmbh International | Surgical stapling assembly with offset ramped drive surfaces |
US11937816B2 (en) | 2021-10-28 | 2024-03-26 | Cilag Gmbh International | Electrical lead arrangements for surgical instruments |
US11957339B2 (en) | 2021-11-09 | 2024-04-16 | Cilag Gmbh International | Method for fabricating surgical stapler anvils |
US11957795B2 (en) | 2021-12-13 | 2024-04-16 | Cilag Gmbh International | Tissue thickness compensator configured to redistribute compressive forces |
US11957345B2 (en) | 2022-12-19 | 2024-04-16 | Cilag Gmbh International | Articulatable surgical instruments with conductive pathways for signal communication |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8409876B2 (en) | Fluorescent silica-based nanoparticles | |
US10548997B2 (en) | Fluorescent silica-based nanoparticles | |
Jazayeri et al. | Various methods of gold nanoparticles (GNPs) conjugation to antibodies | |
Jung et al. | Fabrication of silica nanotubes by using self-assembled gels and their applications in environmental and biological fields | |
AU2006249323B2 (en) | Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications | |
US20080261805A1 (en) | Photocatalytic Titanium Dioxide Microparticle, Dispersion Liquid Thereof and Process for Producing the Same | |
Parracino et al. | State-of-the-art strategies for the biofunctionalization of photoactive inorganic nanoparticles for nanomedicine | |
JP2023500677A (en) | Ultra-small nanoparticles and methods for their production, use and analysis | |
JP2010083803A (en) | Gold fine particle, method for producing the same and use thereof | |
JP3826402B2 (en) | Dispersion containing photocatalytic titanium dioxide composite fine particles | |
AU2014221249B2 (en) | Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications | |
Shringirishi et al. | Gold nanoparticles: Promising and potential nanomaterial | |
Amirthalingam | Multi-functionalization of micro-and nanoparticles for cancer theranostics | |
AU2012211421B2 (en) | Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications | |
Auwalu et al. | Fluorescent Nanomaterials for Detection and Discrimination of Amino Acids | |
Penon Esteva | Synthesis and functionalization of nano-and micro-particles for sensing and therapy in living cells | |
Ghosh | Surface functionalized hybrid nanomaterials: Implications in biosensing and therapeutics | |
Nakamura | Approaches to the biofunctionalization of spherical silica nanomaterials | |
Yapar | Novel Gold Nanoparticles for Dipeptide Recognition in Water | |
Lodeiro et al. | Bioinspired Functionalized Nanoparticles as Tools for Detection, Quantification and Targeting of Biomolecules | |
Yang | Functionalised silica coated nanoparticle hybrids for drug delivery and imaging |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: CORNELL RESEARCH FOUNDATION, INC., NEW YORK Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:WIESNER, ULRICH;OW, HOOISWENG;REEL/FRAME:013844/0627;SIGNING DATES FROM 20030129 TO 20030130 |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |