WO2005025634A9 - Biointerface membranes incorporating bioactive agents - Google Patents
Biointerface membranes incorporating bioactive agentsInfo
- Publication number
- WO2005025634A9 WO2005025634A9 PCT/US2004/015846 US2004015846W WO2005025634A9 WO 2005025634 A9 WO2005025634 A9 WO 2005025634A9 US 2004015846 W US2004015846 W US 2004015846W WO 2005025634 A9 WO2005025634 A9 WO 2005025634A9
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- biointerface membrane
- biointerface
- membrane
- bioactive agent
- membrane according
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1486—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using enzyme electrodes, e.g. with immobilised oxidase
- A61B5/14865—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using enzyme electrodes, e.g. with immobilised oxidase invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/146—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/08—Methods for forming porous structures using a negative form which is filled and then removed by pyrolysis or dissolution
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y80/00—Products made by additive manufacturing
-
- 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
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/48707—Physical analysis of biological material of liquid biological material by electrical means
Definitions
- the present invention relates generally to biointerface membranes that can be utilized with implantable devices, such as devices for the detection of analyte concentrations in a biological sample, cell transplantation devices, drug delivery devices and electrical signal delivering or measuring devices.
- implantable devices such as devices for the detection of analyte concentrations in a biological sample, cell transplantation devices, drug delivery devices and electrical signal delivering or measuring devices.
- the present invention further relates to methods for determining analyte levels using implantable devices including these membranes More particularly, the invention relates to novel biointerface membranes, to devices and implantable devices including these membranes, and to methods for monitoring glucose levels in a biological fluid sample using an implantable analyte detection device.
- analyte sensing devices One of the most heavily investigated analyte sensing devices is the implantable glucose device for detecting glucose levels in patients with diabetes Despite the increasing number of individuals diagnosed with diabetes and recent advances in the field of implantable glucose monitoring devices, currently used devices are unable to provide data safely and reliably for long periods of time (for example, months or years). See Moatti-Sirat et al., Diabetologia, 35-224-30 (1992). There are two commonly used types of implantable glucose sensing devices. These types include those that are implanted lntravascularly and those that are implanted m tissue.
- FBR foreign body response
- FIG 1 is a schematic drawing that illustrates a classical FBR to a conventional cell-impermeable synthetic membrane 10 implanted under the skin There are three main layers of a FBR.
- the innermost FBR layer 12, adjacent to the device, is composed generally of macrophages and foreign body giant cells 14 (herein referred to as the "barrier cell layer") These cells form a monolayer of closely opposed cells over the entire surface of a microscopically smooth membrane, a macroscopically smooth (but microscopically rough) membrane, or a microporous (I e., average pore size of less than about 1 ⁇ m) membrane.
- a membrane can be adhesive or non-adhesive to cells, however, its relatively smooth surface causes the downward tissue contracture 21 (discussed below) to translate directly to the cells at the device-tissue interface 26
- the intermediate FBR layer 16 (herein referred to as the "fibrous zone"), lying distal to the first layer with respect to the device, is a wide zone (about 30 to 100 ⁇ m) composed primarily of fibroblasts 18, fibrous matrixes, and contractile fibrous tissue 20
- the organization of the fibrous zone, and particularly the contractile fibrous tissue 20 contributes to the formation of the monolayer of closely opposed cells due to the contractile forces 21 around the surface of the foreign body (for example, membrane 10)
- the outermost FBR layer 22 is loose connective granular tissue containing new blood vessels 24 (herein referred to as the "vascular zone”) Over time, this FBR tissue becomes muscular in nature and contracts around the foreign body so that the foreign body remains tightly encapsulated.
- the downward forces 21 press against the tissue-device interface 26, and without any counteracting forces, aid in the formation of a barrier cell layer 14 that blocks and/or refracts the transport of analytes 23 (for example, glucose) across the tissue-device interface 26.
- analytes 23 for example, glucose
- a consistent feature of the innermost layers 12, 16 is that they are devoid of blood vessels. This has led to widely supported speculation that poor transport of molecules across the device-tissue interface 26 is due to a lack of vascula ⁇ zation near the interface See Scharp et al , World J Surg., 8.221-229 (1984); and Colton et al , J. Biomech. Eng , 113.152-170 (1991).
- the pro-inflammatory agent includes a xenogemc carrier In an aspect of the first embodiment, the pro-inflammatory agent includes a Lipopolysaccharide In an aspect of the first embodiment, the pro-inflammatory agent includes a protein.
- the bioactive agent is incorporated into the biointerface membrane via a carrier matrix.
- the carrier matrix is selected from the group consisting of collagen, a particulate matrix, a non-resorbable matrix, resorbable matrix, a controlled-release matrix, a gel, and mixtures thereof.
- the bioactive agent is cross-linked with a material that forms the biointerface membrane.
- the bioactive agent is sorbed into the biointerface membrane by a process selected from the group consisting of absorption, adsorption, imbibing, and combinations thereof.
- the bioactive agent is deposited in or on a surface of the biointerface membrane by a process selected from the group consisting of coating, cavity filling, solvent casting, and combinations thereof.
- the bioactive agent is configured to be released for a time period of from about one day to about one year In an aspect of the first embodiment, the bioactive agent is configured to be released for a time period of from about one week to about four weeks.
- an analyte measuring device including a biointerface membrane including a nonresorbable solid portion and a bioactive agent, wherein the nonresorbable solid portion includes a plurality of interconnected cavities adapted to support a tissue ingrowth in vivo, and wherein the bioactive agent is incorporated into the biointerface membrane and is adapted to modify a tissue response.
- an implantable glucose-measuring device including a biointerface membrane including a nonresorbable solid portion and a bioactive agent, wherein the nonresorbable solid portion includes a plurality of interconnected cavities adapted to support a tissue ingrowth in vivo, and wherein the bioactive agent is incorporated into the biointerface membrane and is adapted to modify a tissue response.
- a cell transplantation device including a biointerface membrane including a nonresorbable solid portion and a bioactive agent, wherein the nonresorbable solid portion includes a plurality of interconnected cavities adapted to support a tissue ingrowth in vivo, and wherein the bioactive agent is incorporated into the biointerface membrane and is adapted to modify a tissue response
- an implantable drug delivery device is provided including a biointerface membrane including a nonresorbable solid portion and a bioactive agent, wherein the nonresorbable solid portion includes a plurality of interconnected cavities adapted to support a tissue ingrowth in vivo, and wherein the bioactive agent is incorporated into the biointerface membrane and is adapted to modify a tissue response
- the drug delivery device is selected from the group consisting of a pump, a microcapsule, and a macrocapsule
- the cavities include a nominal pore size of between about 0.6 and 20 ⁇ m
- the solid portion includes frames of elongated strands of material that are less than about 6 ⁇ m in all but the longest dimension.
- an implantable device including a sensing region for sensing an analyte and a biointerface membrane adjacent to the sensing region, wherein the membrane is configured to modify an in vivo tissue response by a porous architecture and by incorporation of a bioactive agent in the membrane.
- a biointerface membrane suitable for implantation in a soft tissue including a plurality of interconnected cavities and a solid portion, wherein the plurality of interconnected cavities and the solid portion are configured to redirect a fibrous tissue contracture, thereby interfering with barrier cell layer formation within or around the first domain, and wherein the biointerface membrane further includes a bioactive agent adapted to modify a tissue response
- an implantable glucose device including a nonresorbable biointerface membrane adapted to modify an in vivo tissue response, the membrane including a porous membrane architecture and having a bioactive agent incorporated therein.
- a biointerface membrane for use with an implantable device including: a first domain distal to the implantable device, wherein the first domain includes an open-cell configuration; a second domain proximal to the implantable device, wherein the second domain is impermeable to cells or cell processes; and a bioactive agent incorporated within the membrane.
- the first domain supports tissue ingrowth and interferes with barrier-cell layer formation.
- a method of monitoring an analyte concentration including the steps of: providing a host; providing an implantable device, the implantable device including a housing including electronic circuitry, and at least one sensing region operably connected to the electronic circuitry of the housing, the sensing region including a biointerface membrane, the biointerface membrane including a first domain distal to the implantable device, wherein the first domain includes an open-cell configuration, the biointerface membrane including a second domain proximal to the implantable device, wherein the second domain is impermeable to cells or cell processes, and wherein the biointerface membrane includes a bioactive agent incorporated into the biointerface membrane; implanting the device in the host whereby the bioactive agent is delivered to the tissue of the host; and measuring an analyte concentration.
- the device is implanted in a tissue site selected from the group consisting of subcutaneous, abdominal, peritoneal, brain, and mtramedullary.
- Fig. 1 is an illustration of classical three-layered foreign body response to a conventional synthetic membrane implanted under the skin.
- Fig. 2A is a cross-sectional schematic view of a membrane of a preferred embodiment that facilitates vascula ⁇ zation of the first domain without barrier cell layer formation
- Fig. 2B is a cross-sectional schematic view of the membrane of Fig. 2A showing contractile forces caused by the fibrous tissue of the FBR.
- Fig. 1 is an illustration of classical three-layered foreign body response to a conventional synthetic membrane implanted under the skin.
- Fig. 2A is a cross-sectional schematic view of a membrane of a preferred embodiment that facilitates vascula ⁇ zation of the first domain without barrier cell layer formation
- Fig. 2B is a cross-sectional schematic view of the membrane of Fig. 2A showing contract
- Fig. 4A is a perspective view of an assembled glucose-measuring device, including sensing and biointerface membranes incorporated thereon.
- Fig. 4B is an exploded perspective view of the glucose-measuring device of Fig.
- Fig. 5 is a bar graph that shows average number of vessels (per high-powered field of vision) of porous silicone materials embedded with Monobutyrin after three weeks of implantation.
- Fig. 6 is a graph that shows release kinetics over time in PBS solution for porous silicone with Dexamethasone incorporated therein.
- the following description and examples illustrate a preferred embodiment of the present invention in detail. Those of skill in the art will recognize that there are numerous variations and modifications of this invention that are encompassed by its scope. Accordingly, the description of a preferred embodiment should not be deemed to limit the scope of the present invention. Definitions [0056] In order to facilitate an understanding of the preferred embodiment, a number of terms are defined below. [0057] The term "comprising" as used herein is synonymous with "including,”
- biointerface membrane as used herein is a broad term and is used in its ordinary sense, including, without limitation, to refer to a permeable membrane that functions as an interface between host tissue and an implantable device.
- the biointerface membrane includes both macro-architectures and micro-architectures.
- carrier cell layer as used herein is a broad term and is used in its ordinary sense, including, without limitation, to refer to a part of a foreign body response that forms a cohesive monolayer of cells (for example, macrophages and foreign body giant cells) that substantially block the transport of molecules and other substances to the implantable device
- cell processes as used herein is a broad term and is used in its ordinary sense, including, without limitation, to refer to pseudopodia of a cell
- cellular attachment as used herein is a broad term and is used in its ordinary sense, including, without limitation, to refer to adhesion of cells and/or cell processes to a material at the molecular level, and/or attachment of cells and/or cell processes to microporous material surfaces or macroporous material surfaces
- BIOPORETM cell culture support marketed by Milhpore (Bedford, MA), and as described in
- solid portions as used herein is a broad term and is used in its ordinary sense, including, without limitation, to refer to portions of a membrane's material having a mechanical structure that demarcates cavities, voids, or other non-solid portions.
- co-continuous as used herein is a broad term and is used in its ordinary sense, including, without limitation, to desc ⁇ be a solid portion or cavity wherein an unbroken curved line in three dimensions can be drawn between two sides of a membrane.
- biostable as used herein is a broad term and is used in its ordinary sense, including, without limitation, to describe materials that are relatively resistant to degradation by processes that are encountered in vivo
- bioresorbable or “bioabsorbable” as used here are broad terms and are used in their ordinary sense, including, without limitation, to describe materials that can be absorbed, or lose substance, m a biological system.
- nonbioresorbable or “nonbioabsorbable” as used here are broad terms and are used in their ordinary sense, including, without limitation, to desc ⁇ be materials that are not substantially absorbed, or do not substantially lose substance, in a biological system.
- oxygen antenna domain or "oxygen reservoir” as used here are broad terms and are used in their ordinary sense, including, without limitation, to refer to a domain composed of a material that has a higher oxygen solubility than an aqueous media such that it concentrates oxygen from the biological fluid surrounding a biocompatible membrane
- properties of silicone (and/or silicone compositions) enable domains formed from silicone to act as an oxygen antenna domain.
- the oxygen antenna domain enhances function in a glucose-measuring device by applying a higher flux of oxygen to certain locations
- analyte as used herein is a broad term and is used in its ordinary sense, including, without limitation, to refer to a substance or chemical constituent in a biological fluid (for example, blood, interstitial fluid, cerebral spinal fluid, lymph fluid or urine) that can be analyzed
- Analytes can include naturally occurring substances, artificial substances, metabolites, and/or reaction products.
- the analyte for measurement by the sensor heads, devices, and methods is glucose.
- analytes are contemplated as well, including but not limited to acarboxyprothrombin; acylcarnitine; adenine phospho ⁇ bosyl transferase; adenosine deammase; albumin; alpha-fetoprotem; amino acid profiles (arginine (Krebs cycle), histidine/urocanic acid, homocysteme, phenylalamne/tyrosme, tryptophan), andrenostenedione, antipy ⁇ ne, arabimtol enantiomers, arginase, benzoylecgonme (cocaine); biotinidase, biopte ⁇ n, c- reactive protein; carnitine; carnosinase; CD4; ceruloplasmin; chenodeoxychohc acid; chloroquine, cholesterol; chohnesterase; conjugated 1- ⁇ hydroxy-chohc acid, cortisol, creatine kinase;
- the analyte can be naturally present in the biological fluid, for example, a metabolic product, a hormone, an antigen, an antibody, and the like.
- the analyte can be introduced into the body, for example, a contrast agent for imaging, a radioisotope, a chemical agent, a fluorocarbon-based synthetic blood, or a drug or pharmaceutical composition, including but not limited to insulin, ethanol; cannabis (marijuana, tetrahydrocannabinol, hashish); inhalants (nitrous oxide, amyl nitrite, butyl nitrite, chlorohydrocarbons, hydrocarbons); cocaine (crack cocaine); stimulants (amphetamines, methamphetamines, Ritalin, Cylert, Preludin, Didrex, PreState, Voraml, Sandrex, Plegme); depressants (barbituates, methaqualone, tranquihzers such as Valium, Lib ⁇ um, Miltown, Se
- Analytes such as neurochemicals and other chemicals generated within the body can also be analyzed, such as, for example, ascorbic acid, uric acid, dopamme, noradrena ne, 3- methoxytyramine (3MT), 3,4-d ⁇ hydroxyphenylacet ⁇ c acid (DOPAC), homovanil c acid (HVA), 5- hydroxytryptamine (5HT), and 5-hydroxy ⁇ ndoleacet ⁇ c acid (FHIAA).
- analyte-measurmg device is a broad term and is used in its ordinary sense, including, without limitation, to refer to any mechanism (for example, an enzymatic mechanism or a non-enzymatic mechanism) by which an analyte can be quantified.
- An example is a glucose-measuring device mco ⁇ orating a membrane that contains glucose oxidase that catalyzes the conversion of oxygen and glucose to hydrogen peroxide and gluconate- Glucose + 0 2 ⁇ Gluconate + H 2 0 2
- glucose oxidase that catalyzes the conversion of oxygen and glucose to hydrogen peroxide and gluconate- Glucose + 0 2 ⁇ Gluconate + H 2 0 2
- glucose concentration for each glucose molecule consumed, there is a proportional change in the co-reactant 0 and the product H 2 0 2 . Current change in either the co- reactant or the product can be monitored to determine glucose concentration
- the term "host” as used herein is a broad term and is used in its ordinary sense, including, without limitation, to refer to mammals, preferably humans.
- continuous analyte sensing is a broad term and is used in its ordinary sense, including, without limitation, to describe the period in which monitoring of analyte concentration is continuously, continually, and/or intermittently (but regularly) performed, for example, from about every 5 seconds or less to about 10 minutes or more, preferably from about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, or 60 second to about 1.25, 1.50, 1.75, 2 00, 2.25, 2 50, 2.75, 3.00, 3.25, 3.50, 3.75, 4.00, 4.25, 4.50, 4.75, 5.00, 5.25, 5.50, 5.75, 6.00, 6.25, 6.50, 6.75, 7.00, 7.25, 7.50, 7.75, 8.00, 8.25, 8.50, 8.75, 9.00, 9 25, 9.50 or 9.75 minutes.
- sensing region is a broad term and is used m its ordinary sense, including, without limitation, to refer to the area of an analyte-monito ⁇ ng device responsible for the detection of a particular analyte.
- the sensing region can comprise a non-conductive body, a working electrode (anode), a reference electrode, and a counter electrode (cathode) passing through and secured within the device body, forming an electrochemically reactive surface at one location on the body and an electronic connection at another location on the body, and a sensing membrane affixed to the body and covering the electrochemically reactive surface.
- the counter electrode preferably has a greater electrochemically reactive surface area than the working electrode.
- a biological sample for example, blood or interstitial fluid, or a component thereof contacts, either directly or after passage through one or more membranes, an enzyme, for example, glucose oxidase.
- an enzyme for example, glucose oxidase.
- the reaction of the biological sample or component thereof results m the formation of reaction products that permit a determination of the analyte level, for example, glucose, in the biological sample.
- the sensing membrane further comprises an enzyme domain, for example, an enzyme layer, and an electrolyte phase, for example, a free-flowing liquid phase comprising an electrolyte-contammg fluid described further below.
- electrochemically reactive surface is a broad term and is used m its ordinary sense, including, without limitation, to refer to the surface of an electrode where an electrochemical reaction takes place.
- hydrogen peroxide produced by an enzyme-catalyzed reaction of an analyte being detected reacts can create a measurable electronic current.
- glucose oxidase produces H 2 0 2 peroxide as a byproduct
- the H 2 0 2 reacts with the surface of the working electrode to produce two protons (2H + ), two electrons (2e " ) and one molecule of oxygen (0 2 ), which produces the electronic current being detected.
- sensing membrane In a counter electrode, a reducible species, for example, 0 2 is reduced at the electrode surface so as to balance the current generated by the working electrode.
- sensing membrane As used herein is a broad term and is used m its ordinary sense, including, without limitation, to refer to a permeable or semi-permeable membrane that can comprise one or more domains and that is constructed of materials having a thickness of a few microns or more, and that are permeable to reactants and/or co-reactants employed in determining the analyte of interest.
- a sensing membrane can comprise an immobilized glucose oxidase enzyme, which catalyzes an electrochemical reaction with glucose and oxygen to permit measurement of a concentration of glucose.
- proximal is a broad term and is used in its ordinary sense, including, without limitation, to describe a region near to a point of reference, such as an origin or a point of attachment
- distal is a broad term and is used in its ordinary sense, including, without limitation, to describe a region spaced relatively far from a point of reference, such as an origin or a point of attachment
- operably connected and “operably linked” as used herein are broad terms and are used in their ordinary sense, including, without limitation, to describe one or more components linked to another component(s) in a manner that facilitates transmission of signals between the components
- one or more electrodes can be used to detect an analyte in a sample and convert that information into a signal, the signal can then be transmitted to an electronic circuit
- the electrode is “operably linked” to the electronic circuit
- bioactive agent as used here
- glucose changes can be tracked in vivo, although significant time delays are typically incurred However, after a few days to two or more weeks of implantation, these devices typically lose their function. See, for example, U.S. Pat No. 5,791,344 and Gross et al and "Performance Evaluation of the MiniMed Continuous Monitoring System During Patient home Use," Diabetes Technology and Therapeutics, (2000) 2(l).49-56, which have reported a glucose oxidase device, approved for use in humans by the Food and Drug Administration, that functions well for several days following implantation but loses function quickly after 3 days.
- the preferred embodiments employ biointerface membrane architectures that promote vascula ⁇ zation within the membrane and that interfere with barrier cell layer formation
- the biointerface membranes are robust and suitable for long-term implantation and long-term analyte transport in vivo.
- the membranes can be used in a variety of implantable devices, for example, analyte measuring devices, particularly glucose-measuring devices, cell transplantation devices, drug delivery devices, and electrical signal delivery and measuring devices.
- the device interface can include a sensing membrane that has different domains and/or layers that can cover and protect an underlying enzyme membrane and the electrodes of the glucose -measuring device.
- Biointerface Membranes [0087] The biointerface membranes of the preferred embodiments comprise two or more domains, and mco ⁇ orate a bioactive agent.
- a first domain is provided that includes an architecture, including cavity size, configuration, and/or overall thickness, that encourages vascular tissue ingrowth, disrupts downward tissue contracture, and/or discourages barrier cell formation.
- a second domain is provided that is impermeable to cells and/or cell processes.
- FIG. 1A is a cross-sectional schematic view of a membrane 30 in vivo in one exemplary embodiment, wherein the membrane comprises a first domain 32 and second domain 34.
- the architecture of the membrane provides a robust, long-term implantable membrane that facilitates the transport of analytes through vascula ⁇ zed tissue ingrowth without the formation of a barrier cell layer.
- the first domain 32 comprises a solid portion 36 and a plurality of interconnected three-dimensional cavities 38 formed therein
- the cavities 38 have sufficient size and structure to allow invasive cells, such as fibroblasts 35, a fibrous matrix 37, and blood vessels 39 to enter into the apertures 40 that define the entryway into each cavity 38, and to pass through the interconnected cavities toward the interface 42 between the first and second domains.
- the cavities comprise an architecture that encourages the ingrowth of vascular tissue in vivo, as indicated by the blood vessels 39 formed throughout the cavities Because of the vascula ⁇ zation within the cavities, solutes 33 (for example, oxygen, glucose and other analytes) pass through the first domain with relative ease, and/or the diffusion distance (namely, distance that the glucose diffuses) is reduced.
- the biointerface membranes of the preferred embodiments preferably include a bioactive agent, which is inco ⁇ orated into at least one of the first and second domains 32, 34 of the biointerface membrane, or which is inco ⁇ orated into the device and adapted to diffuse through the first and/or second domains, in order to modify the tissue response of the host to the membrane
- a bioactive agent which is inco ⁇ orated into at least one of the first and second domains 32, 34 of the biointerface membrane, or which is inco ⁇ orated into the device and adapted to diffuse through the first and/or second domains, in order to modify the tissue response of the host to the membrane
- the architectures of the first and second domains have been shown to support vascula ⁇ zed tissue ingrowth, to interfere with and resist barrier cell layer formation, and to facilitate the transport of analytes across the membrane.
- the bioactive agent can further enhance vascula ⁇ zed tissue ingrowth, resistance to barrier cell layer formation, and thereby facilitate the passage of analytes 33 across the
- the first domain of the biointerface membrane includes an architecture that supports tissue ingrowth, disrupts contractile forces typically found in a foreign body response, encourages vascula ⁇ ty within the membrane, and disrupts the formation of a barrier cell layer
- the first domain also referred to as the cell disruptive domain, comprises an open-celled configuration comprising interconnected cavities and solid portions.
- the distribution of the solid portion and cavities of the first domain preferably includes a substantially co-continuous solid domain and includes more than one cavity in three dimensions substantially throughout the entirety of the first domain.
- cells can enter into the cavities; however, they cannot travel through or wholly exist withm the solid portions.
- the cavities permit most substances to pass through, including, for example, cells and molecules [0092]
- Fig. 2B is an illustration of the membrane of
- Fig 2A showing contractile forces caused by the fibrous tissue, for example, from the fibroblasts and fibrous matrix, of the FBR.
- the architecture of the first domain including the cavity mterconnectivity and multiple-cavity depth, (namely, two or more cavities in three dimensions throughout a substantial portion of the first domain) can affect the tissue contracture that typically occurs around a foreign body [0093]
- a contraction of the FBC around the device as a whole produces downward forces on the device can be helpful in reducing motion artifacts, such as are described in copending U.S.
- Patent Application 10/646,333 filed August 22, 2003 and entitled "OPTIMIZED DEVICE GEOMETRY FOR AN IMPLANTABLE GLUCOSE DEVICE"
- the architecture of the first domain of the biointerface membrane, including the interconnected cavities and solid portion is advantageous because the contractile forces caused by the downward tissue contracture that can otherwise cause cells to flatten against the device and occlude the transport of analytes, is instead translated to, disrupted by, and/or counteracted by the forces 41 that contract around the solid portions 36 (for example, throughout the interconnected cavities 38) away from the device That is, the architecture of the solid portions 36 and cavities 38 of the first domain cause contractile forces 41 to disperse away from the interface between the first domain 32 and second domain 34.
- Fig 1 Without the organized contracture of fibrous tissue toward the tissue-device interface 42 typically found in a FBC (Fig 1), macrophages and foreign body giant cells do not form a substantial monolayer of cohesive cells (namely, a barrier cell layer) and therefore the transport of molecules across the second domain and/or membrane is not blocked, as indicated by free transport of analyte 33 through the first and second domains in Figs. 2A and 2B [0094]
- Various methods are suitable for use in manufacturing the first domain in order to create an architecture with preferred dimensions and overall structure.
- the first domain can be manufactured by forming particles, for example, sugar granules, salt granules, and other natural or synthetic uniform or non-uniform particles, in a mold, wherein the particles have shapes and sizes substantially corresponding to the desired cavity dimensions
- the particles are made to coalesce to provide the desired mterconnectivity between the cavities.
- the desired material for the solid portion can be introduced into the mold using methods common in the art of polymer processing, for example, injecting, pressing, vacuuming, or pouring. After the solid portion material is cured or solidified, the coalesced particles are then dissolved, melted, etched, or otherwise removed, leaving interconnecting cavities within the solid portion.
- sieving can be used to determine the dimensions of the particles, which substantially correspond to the dimensions of resulting cavities
- sieving also referred to as screening
- the particles are added to the sieve and then shaken to produce overs and unders.
- the overs are the particles that remain on the screen and the unders are the particles that pass through the screen.
- Other methods and apparatus known in the art are also suitable for use in determining particle size, for example, air classifiers, which apply opposing air flows and centrifugal forces to separate particles having sizes down to 2 ⁇ m, can be used to determine particle size when particles are smaller than 100 ⁇ m.
- the cavity size of the cavities 38 of the first domain is substantially defined by the particle s ⁇ ze(s) used in creating the cavities.
- the particles used to form the cavities can be substantially spherical, thus the dimensions below describe a diameter of the particle and/or a diameter of the cavity.
- the particles used to form the cavities can be non-spherical (for example, rectangular, square, diamond, or other geometric or non-geometric shapes), thus the dimensions below describe one dimension (for example, shortest, average, or longest) of the particle and/or cavity.
- a variety of different particle sizes can be used in the manufacture of the first domain.
- the dimensions of the particles can be somewhat smaller or larger than the dimensions of the resulting cavities, due to dissolution or other precipitation that can occur during the manufacturing process.
- porous domains Although one method of manufacturing porous domains is described above, a variety of methods known to one of ordinary skill in the art can be employed to create the structures of preferred embodiments.
- molds can be used in the place of the particles described above, such as coral, self-assembly beads, etched or broken silicon pieces, glass frit pieces, and the like.
- the dimensions of the mold can define the cavity sizes, which can be determined by measuring the cavities of a model final product, and/or by other measuring techniques known in the art, for example, by a bubble point test. In U S.
- Patent No 3,929,971 discloses a method of making a synthetic membrane having a porous microstructure by converting calcium carbonate coral materials to hydroxyapatite while at the same time retaining the unique microstructure of the coral material.
- Other methods of forming a three-dimensional first domain can be used, for example holographic lithography, stereohthography, and the like, wherein cavity sizes are defined and precisely formed by the lithographic or other such process to form a lattice of unit cells, as described in co-pending U.S. Provisional Patent Application 60/544,722, entitled "Macro-Micro Architecture for Biointerface Membrane" and as described by Pekka ⁇ nen et al. in U.S. Patent No.
- the first domain 32 can be defined using alternative methods.
- fibrous non-woven or woven materials, or other such materials, such as electrospun, scattered, or aggregate materials are manufactured by forming the solid portions without particularly defining the cavities therebetween.
- structural elements that provide the three-dimensional conformation can include fibers, strands, globules, cones, and/or rods of amo ⁇ hous or uniform geometry that are smooth or rough.
- the solid portion of the first domain can include a plurality of strands, which generally define apertures formed by a frame of the interconnected strands.
- the apertures of the material form a framework of interconnected cavities.
- the first domain is defined by a cavity size of about 0.6 to about 1000 ⁇ m in at least one dimension.
- the porous biointerface mate ⁇ als can be loosely categorized into at least two groups: those having a microarchitecture and those having a macro-architecture.
- Figs. 2A and 2B illustrate one preferred embodiment wherein the biointerface material includes a macro-architecture as defined herein.
- the cavity size of a macro- architecture provides a configuration and overall thickness that encourages vascular tissue ingrowth and disrupts tissue contracture that is believed to cause barrier cell formation in vivo (as indicated by the blood vessels 39 formed throughout the cavities), while providing a long-term, robust structure.
- a substantial number of the cavities 38 are greater than or equal to about 20 ⁇ m in one dimension. In some other embodiments, a substantial number of the cavities are greater than or equal to about 30, 40, 50, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 240, 280, 320, 360, 400, 500, 600, 700 ⁇ m, and preferably less than about 1000 ⁇ m in one dimension.
- the macro-architecture is associated the numerous advantages as described above, in some embodiments it can create an opportunity for foreign body giant cells to flatten against the second domain and/or implantable device 34 and potentially create a layer of barrier cells that can block some or all analyte transport. It is therefore advantageous to inco ⁇ orate a bioactive agent into the macro-architecture in order to modify the tissue response of the host to the membrane.
- the biointerface material can also be formed with a micro-architecture as defined herein Generally, at least some of the cavities of a micro-architecture have a sufficient size and structure to allow inflammatory cells to partially or completely enter into the cavities.
- the microarchitecture of preferred embodiments is defined by the actual size of the cavity, wherein the cavities are formed from a mold, for example, such as described in more detail above
- the majority of the mold dimensions whether particles, beads, crystals, coral, self-assembly beads, etched or broken silicon pieces, glass frit pieces, or other mold elements that form cavities, are less than about 20 ⁇ m in at least one dimension.
- the micro-architecture is defined by a strand size of less than 6 ⁇ m in all but the longest dimension, and a sufficient number of cavities are provided of a size and structure to allow inflammatory cells, for example, macrophages, to completely enter through the apertures that define the cavities, without extensive ingrowth of vascular and connective tissues.
- the micro-architecture is characterized, or defined, by standard pore size tests, such as the bubble point test. The micro-architecture is selected with a nominal pore size of from about 0.6 ⁇ m to about 20 ⁇ m.
- the nominal pore size from about 1, 2, 3, 4, 5, 6, 7, 8, or 9 ⁇ m to about 10, 11, 12, 13, 14, 15, 16, 17, 18, or 19 ⁇ m. It has been found that a porous polymer membrane having an average nominal pore size of about 0.6 to about 20 ⁇ m functions satisfactorily in creating a vascular bed within the micro-architecture at the device-tissue interface.
- nominal pore size m the context of the micro-architecture 52 in certain embodiments is derived from methods of analysis common to membrane, such as the ability of the membrane to filter particles of a particular size, or the resistance of the membrane to the flow of fluids Because of the amo ⁇ hous, random, and irregular nature of most of these commercially available membranes, the "nominal pore size” designation may not actually indicate the size or shape of the apertures and cavities, which in reality have a high degree of variability Accordingly, as used herein with reference to the micro-architecture, the term “nominal pore size” is a manufacturer's convention used to identify a particular membrane of a particular commercial source which has a certain bubble point; as used herein, the term “pore” does not describe the size of the cavities of the material m the preferred embodiments.
- biointerface membranes with a micro-architecture as defined herein are advantageous for inducing close vascular structures, maintaining rounded inflammatory cell mo ⁇ hology, preventing barrier cell layer formation, and preventing organized fibroblasts and connective tissue from entering into the membrane.
- crushing and delamination of a micro-architecture biointerface material can occur, which allows foreign body giant cells to flatten against the implantable device and potentially create a barrier layer of cells that block some or all analyte transport It can therefore be advantageous to inco ⁇ orate a bioactive agent into the micro-architecture in order to modify the tissue response of the host to the membrane.
- the optimum dimensions, architecture (for example, micro-architecture or macro-architecture), and overall structural integrity of the membrane can be adjusted according to the parameters of the device that it supports For example, if the membrane is employed with a glucose-measuring device, the mechanical requirements of the membrane can be greater for devices having greater overall weight and surface area when compared to those that are relatively smaller [0107] With regard to the depth of cavities, improved vascular tissue ingrowth is observed when the first domain has a thickness that accommodates a depth of at least two cavities throughout a substantial portion of the thickness.
- Improved vascularization results at least in part from multi-layered mterconnectivity of the cavities, such as in the preferred embodiments, as compared to a surface topography such as seen in the prior art, for example, wherein the first domain has a depth of only one cavity throughout a substantial portion thereof.
- the multi-layered mterconnectivity of the cavities enables vascula ⁇ zed tissue to grow into various layers of cavities in a manner that provides mechanical anchoring of the device with the surrounding tissue. Such anchoring resists movement that can occur in vivo, which results in reduced sheer stress and scar tissue formation.
- the optimum depth or number of cavities can vary depending upon the parameters of the device that it supports.
- the anchoring that is required of the membrane is greater for devices having greater overall weight and surface area as compared to those that are relatively smaller [0108]
- the thickness of the first domain can be optimized for decreased time-to- vascula ⁇ ze in vivo, that is, vascular tissue ingrowth can occur somewhat faster with a membrane that has a thin first domain as compared to a membrane that has a relatively thicker first domain Decreased time-to-vascula ⁇ ze results in faster stabilization and functionality of the biointerface in vivo.
- consistent and increasing functionality of the device is at least in part a function of consistent and stable glucose transport across the biointerface membrane, which is at least in part a function of the vascularization thereof.
- quicker start-up time and/or shortened time lag (as when, for example, the diffusion path of the glucose through the membrane is reduced) can be achieved by decreasing the thickness of the first domain.
- the thickness of the first domain is typically from about 20 ⁇ m to about 2000 ⁇ m, preferably from about 30, 40, 50, 60, 70, 80, 90, or 100 ⁇ m to about 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, or 1900 ⁇ m, and most preferably from about 150, 200, 250, 300, 350, or 400 ⁇ m to about 450, 500, 550, 600, 650, 700, or 750 ⁇ m
- a thinner or thicker cell disruptive domain can be desired
- the solid portion preferably includes one or more materials such as silicone, polytetrafluoroethylene, expanded polytetrafluoroethylene, polyethylene-co-tetrafluoroethylene, polyolefin, polyester, polycarbonate, biostable polytetrafluoroethylene, homopolymers, copolymers, te ⁇ olymers of polyurethanes, polypropylene (PP),
- the second domain is impermeable to cells or cell processes, and is composed of a biostable material
- the second domain is comprised of polyurethane and a hydrophilic polymer, such as is described m co-pending U.S. Application No. 09/916,858 filed July 27, 2001
- the hydrophilic polymer can include polyvinylpyrrolidone.
- the second domain is polyurethane comprising about 5 weight percent or more polyvinylpyrrolidone and about 45 weight percent or more polyvinylpyrrolidone
- the second domain comprises about 20 weight percent or more polyvinylpyrrolidone and about 35 weight percent or more polyvinylpyrrolidone
- the second domain is polyurethane comprising about 27 weight percent polyvinylpyrrolidone. In certain embodiments, however, the second domain can comprise about 5 weight percent or more than about 45 weight percent polyvinylpyrrolidone.
- the second domain can be formed from materials such as copolymers or blends of copolymers with hydrophilic polymers such as polyvinylpyrrolidone (PVP), polyhydroxyethyl methacrylate, polyvinylalcohol, polyacryhc acid, polyethers such as polyethylene glycol, and block copolymers thereof, including, for example, di-block, t ⁇ -block, alternating, random and graft copolymers (block copolymers are disclosed in U S. Patent Nos 4,803,243 and 4,686,044).
- hydrophilic polymers such as polyvinylpyrrolidone (PVP), polyhydroxyethyl methacrylate, polyvinylalcohol, polyacryhc acid, polyethers such as polyethylene glycol, and block copolymers thereof, including, for example, di-block, t ⁇ -block, alternating, random and graft copolymers (block copolymers are disclosed in U S. Patent Nos 4,803,243
- the second domain can comprise a silicone composition with a hydrophile such as Polyethylene Glycol (PEG) covalently inco ⁇ orated or grafted therein, such as described in co-pendmg U.S. Patent Application 10/695,636, entitled, "SILICONE COMPOSITION FOR BIOCOMPATIBLE MEMBRANE.”
- the second domain is comprised of a silicone copolymer including a hydrophilic component, which can be formed as a unitary structure with the first domain or a separate structure adhered thereto.
- the materials preferred for the second domain prevent or hinder cell entry or contact with device elements underlying the membrane and prevent or hinder the adherence of cells, thereby further discouraging formation of a barrier cell layer.
- the thickness of the cell impermeable biomate ⁇ al of the second domain is typically about l ⁇ m or more, preferably from about 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 ⁇ m to about 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, or 200 ⁇ m. In some embodiments, thicker or thinner cell impermeable domains can be desired.
- the function of the cell impermeable domain is accomplished by the implantable device, or a portion of the implantable device, which may or may not include a distinct domain or layer.
- the characteristics of the cell impermeable membrane prevent or hinder cells from entering the membrane, but permit or facilitate transport of the analyte of interest or a substance indicative of the concentration or presence of the analyte
- the second domain similar to the first domain, is preferably constructed of a biodurable material (for example, a material durable for a period of several years in vivo) that is impermeable to host cells, for example, macrophages, such as described above
- the biointerface membrane is employed in an implantable glucose-measuring device
- the biointerface membrane is permeable to oxygen and glucose or a substance indicative of the concentration of glucose
- the membrane is employed in a drug delivery device or other device for delivering a substance to the body
- the cell impermeable membrane is permeable to the drug
- the architectures of the first and second domains support vascula ⁇ zed tissue growth in or around the biointerface membrane, interfere with and resist barrier cell layer formation, and allow the transport of analytes across the membrane.
- certain outside influences for example, faulty surgical techniques, acute or chronic movement of the implant, or other surgery-, patient-, and/or implantation site-related conditions, can create acute and/or chronic inflammation at the implant site
- the biointerface membrane architecture alone may not be sufficient to overcome the acute and/or chronic inflammation.
- the membrane architecture can benefit from additional mechanisms that aid in reducing this acute and/or chronic inflammation that can produce a barrier cell layer and/or a fibrotic capsule surrounding the implant, resulting in compromised solute transport through the membrane.
- the inflammatory response to biomate ⁇ al implants can be divided into two phases.
- the first phase consists of mobilization of mast cells and then infiltration of predominantly polymo ⁇ honuclear (PMN) cells.
- This phase is termed the acute inflammatory phase
- chronic cell types that comprise the second phase of inflammation replace the PMNs.
- Macrophage and lymphocyte cells predominate during this phase. While not wishing to be bound by any particular theory, it is believed that short-term stimulation of vascularization, or short-term inhibition of scar formation or barrier cell layer formation, provides protection from scar tissue formation, thereby providing a stable platform for sustained maintenance of the altered foreign body response.
- bioactive intervention can modify the foreign body response in the early weeks of foreign body capsule formation, thereby fundamentally altering the long-term behavior of the foreign body capsule. Additionally, it is believed that the biointerface membranes of the preferred embodiments can advantageously benefit from bioactive intervention to overcome sensitivity of the membrane to implant procedure, motion of the implant, or other factors, which are known to otherwise cause inflammation, scar formation, and hinder device function in vivo.
- preferred bioactive agents include SIP (Sph ⁇ ngos ⁇ ne-1 -phosphate), Monobutyrin, Cyclospo ⁇ n A, Ant ⁇ -thrombospond ⁇ n-2, Rapamycm (and its derivatives), and Dexamethasone
- bioactive agents include SIP (Sph ⁇ ngos ⁇ ne-1 -phosphate), Monobutyrin, Cyclospo ⁇ n A, Ant ⁇ -thrombospond ⁇ n-2, Rapamycm (and its derivatives), and Dexamethasone
- bioactive agents suitable for use in the preferred embodiments are loosely organized into two groups anti-barrier cell agents and vascularization agents These designations reflect functions that are believed to provide short-term solute transport through the biointerface membrane, and additionally extend the life of a healthy vascular bed and hence solute transport through the biointerface membrane long term in vivo
- bioactive agents generally comprise one or more varying mechanisms for modifying tissue response and can be generally categorized into one or both of the above-cited categories Anti-barrier
- Suitable anti-inflammatory agents include but are not limited to, for example, nonsteroidal anti-inflammatory drugs (NSAJDs) such as acetometaphen, ammosalicyhc acid, aspirin, celecoxib, chohne magnesium t ⁇ sahcylate, diclofenac potasium, diclofenac sodium, diflunisal, etodolac, fenoprofen, flurbiprofen, lbuprofen, lndomethacin, interleukin (EL)- 10, IL-6 mutein, ant ⁇ -IL-6 iNOS inhibitors (for example, L-NAME or L-NMDA), Interferon, ketoprofen, ketorolac, leflunomide, melenamic acid, mycophenohc acid, mizo ⁇ bine, nabumetone, naproxen, naproxen sodium, oxaprozm, piroxicam, rofecoxib, salsalate, sulinda
- lmmunosuppressive and/or immunomodulatory agents interfere directly with several key mechanisms necessary for involvement of different cellular elements in the inflammatory response.
- Suitable lmmunosuppressive and/or immunomodulatory agents include anti- prohferative, cell-cycle inhibitors, (for example, pachtaxel, cytochalasm D, lnfiximab), taxol, actmomycm, mitomycin, thospromote VEGF, estradiols, NO donors, QP-2, tacrohmus, tramlast, actinomycm, everolimus, methothrexate, mycophenohc acid, angiopeptin, vinc ⁇ sting, mitomycine, statins, C MYC antisense, sirohmus (and analogs), RestenASE, 2-chloro-deoxyadenosme, PCNA Ribozyme, batimstat, prolyl hydroxylase inhibitors, PPAR ⁇ hg
- anti-infective agents are substances capable of acting against infection by inhibiting the spread of an infectious agent or by killing the infectious agent outright, which can serve to reduce lmmuno-response without inflammatory response at the implant site
- Anti-infective agents include, but are not limited to, anthelmmtics (mebendazole), antibiotics including aminoclycosides (gentamicin, neomycm, tobramycm), antifungal antibiotics (amphote ⁇ cin b, fluconazole, g ⁇ seofulvm, ltraconazole, ketoconazole, nystatin, micatm, tolnaftate), cephalospo ⁇ ns (cefaclor, cefazohn, cefotaxime, ceftazidime, ceft ⁇ axone, cefuroxime, cephalexin), beta-lactam antibiotics (cefo
- vascularization agents include substances with direct or indirect angiogemc properties. In some cases, vascularization agents may additionally affect formation of barrier cells in vivo.
- indirect angiogenesis it is meant that the angiogenesis can be mediated through inflammatory or immune stimulatory pathways. It is not fully known how agents that induce local vascularization indirectly inhibit barrier-cell formation, however it is believed that some barrier-cell effects can result indirectly from the effects of vascularization agents.
- Vascularization agents include mechanisms that promote neovascula ⁇ zation and accelerate wound healing around the membrane and/or minimize periods of ischemia by increasing vascularization close to the tissue-device interface.
- Sph ⁇ ngos ⁇ ne-1 -Phosphate which is a phospholipid possessing potent angiogemc activity
- SIP Sph ⁇ ngos ⁇ ne-1 -Phosphate
- Monobutyrin which is a potent vasodilator and angiogemc lipid product of adipocytes, is inco ⁇ orated into a biointerface membrane of a preferred embodiment
- an anti-sense molecule for example, thrombospond ⁇ n-2 anti-sense
- increases vascularization is inco ⁇ orated into a biointerface membrane.
- Vascularization agents can include mechanisms that promote inflammation, which is believed to cause accelerated neovascula ⁇ zation and wound healing in vivo
- a xenogenic carrier for example, bovine collagen, which by its foreign nature invokes an immune response, stimulates neovascula ⁇ zation, and is inco ⁇ orated into a biointerface membrane of the preferred embodiments
- Lipopolysaccharide which is a potent immunostimulant, is inco ⁇ orated into a biointerface membrane.
- angiogemc agents are substances capable of stimulating neovascula ⁇ zation, which can accelerate and sustain the development of a vascula ⁇ zed tissue bed at the tissue-device interface
- Angiogemc agents include, but are not limited to, Basic Fibroblast Growth Factor (bFGF), (also known as Heparin Binding Growth Factor-II and Fibroblast Growth Factor II), Acidic Fibroblast Growth Factor (aFGF), (also known as Heparin Binding Growth Factor- I and Fibroblast Growth Factor-I), Vascular Endothehal Growth Factor (VEGF), Platelet Derived Endothehal Cell Growth Factor BB (PDEGF-BB), Ang ⁇ opo ⁇ et ⁇ n-1, Transforming Growth Factor li::
- TGF-Beta Transforming Growth Factor Alpha (TGF-Alpha), Hepatocyte Growth Factor, Tumor Necrosis Factor-Alpha (TNF-Alpha), Placental Growth Factor (PLGF), Angiogenin, Interleuk -8 (IL-8), Hypoxia Inducible Factor-I (HIF-1), Angiotensin-Converting Enzyme (ACE) Inhibitor Quinapnlat, Angiotropin, Thrombospondm, Peptide KGHK, Low Oxygen Tension, Lactic Acid, Insulin, Copper Sulphate, Estradiol, prostaglandms, cox inhibitors, endothehal cell binding agents (for example, deco ⁇ n or vimentin), glempin, hydrogen peroxide, nicotine, and Growth Hormone.
- TGF-Beta Transforming Growth Factor Alpha
- TGF-Alpha Hepatocyte Growth Factor
- Tumor Necrosis Factor-Alpha TNF-Alpha
- pro-inflammatory agents are substances capable of stimulating an immune response in host tissue, which can accelerate or sustain formation of a mature vascula ⁇ zed tissue bed.
- pro-inflammatory agents are generally irritants or other substances that induce chronic inflammation and chronic granular response at the wound-site. While not wishing to be bound by theory, it is believed that formation of high tissue granulation induces blood vessels, which supply an adequate, or rich supply of analytes to the device-tissue interface.
- Pro- inflammatory agents include, but are not limited to, xenogenic carriers, Lipopolysaccha ⁇ des, S. aureus peptidoglycan, and proteins.
- bioactive Agent Delivery Systems and Methods There are a variety of systems and methods by which the bioactive agent is inco ⁇ orated into the biointerface membranes of the preferred embodiments.
- the bioactive agent is inco ⁇ orated at the time of manufacture of the biointerface membrane.
- the bioactive agent can be blended prior to cunng the biointerface membrane, or subsequent to biointerface membrane manufacture, for example, by coating, imbibing, solvent- casting, or so ⁇ tion of the bioactive agent into the biointerface membrane.
- bioactive agent is preferably inco ⁇ orated into the biointerface membrane
- the bioactive agent can be administered concurrently with, prior to, or after implantation of the device systemically, for example, by oral administration, or locally, for example, by subcutaneous injection near the implantation site.
- a combination of bioactive agent inco ⁇ orated in the biointerface membrane and bioactive agent administration locally and/or systemically can be preferred in certain embodiments.
- the biointerface membranes of the preferred embodiments preferably include a bioactive agent, which is inco ⁇ orated into at least one of the first and second domains of the biointerface membrane, and/or which is inco ⁇ orated into the device and adapted to diffuse through the first and/or second domains, in order to modify the tissue response of the host to the membrane.
- the bioactive agent is inco ⁇ orated only into a portion of the biointerface membrane adjacent to the sensing region of the device, over the entire surface of the device except over the sensing region, or any combination thereof, which can be helpful in controlling different mechanisms and/or stages of the maturation of the FBC.
- the bioactive agent is inco ⁇ orated into the implantable device proximal to the biointerface membrane, such that the bioactive agent diffuses through the biointerface membrane to the host tissue
- the bioactive agent can include a carrier matrix, wherein the matrix includes one or more of collagen, a particulate matrix, a resorbable or non-resorbable matrix, a controlled- release matrix, and/or a gel.
- the carrier matrix includes a reservoir, wherein a bioactive agent is encapsulated within a microcapsule.
- the carrier matrix can include a system in which a bioactive agent is physically entrapped within a polymer network.
- the bioactive agent is cross-linked with the biointerface membrane, while in others the bioactive agent is sorbed into the biointerface membrane, for example, by adso ⁇ tion, abso ⁇ tion, or imbibing
- the bioactive agent can be deposited in or on the biointerface membrane, for example, by coating, filling, or solvent casting.
- ionic and nomonic surfactants are used to inco ⁇ orate the bioactive agent into the biointerface membrane
- the bioactive agent can be inco ⁇ orated into a polymer using techniques such as described above, and the polymer can be used to form the biointerface membrane, coatings on the biointerface membrane, portions of the biointerface membrane, and/or a portion of an implantable device [0142]
- the biointerface membrane can be manufactured using techniques known in the art.
- the bioactive agent can be sorbed into the biointerface membrane, for example, by soaking the biointerface membrane for a length of time (for example, from about an hour or less to about a week or more, preferably from about 4, 8, 12, 16, or 20 hours to about 1, 2, 3, 4, 5, or 7 days) Abso ⁇ tion of Dexamethasone into a porous silicone membrane is described in the experimental section.
- the bioactive agent can be blended into uncured polymer prior to forming the biointerface membrane.
- the biointerface membrane is then cured and the bioactive agent thereby cross-linked and/or encapsulated within the polymer that forms the biointerface membrane.
- Monobutyrin was covalently bonded to a silicone matrix in such a manner that is slowly cleavable under in vivo conditions
- the alcohol groups of Monobutyrin react with a silanol group, resulting in a C-O-Si bond.
- This bond is known to be susceptible to hydrolysis, and is therefore cleaved to yield the original alcohol and silanol
- the Monobutyrin is released from the silicone matrix according to the rate of hydrolysis.
- Other bioactive agents such as Dexamethasone, comprise alcohol groups and can be bound to a silicone matrix in a similar manner.
- microspheres are used to encapsulate the bioactive agent.
- the microspheres can be formed of biodegradable polymers, most preferably synthetic polymers or natural polymers such as proteins and polysaccharides.
- polymer is used to refer to both to synthetic polymers and proteins.
- U S Patent 6,281,015 discloses some systems and methods that can be used in conjunction with the preferred embodiments
- bioactive agents can be inco ⁇ orated in (1) the polymer matrix forming the microspheres, (2) m ⁇ cropart ⁇ cle(s) surrounded by the polymer which forms the microspheres, (3) a polymer core within a protein microsphere, (4) a polymer coating around a polymer microsphere, (5) mixed in with microspheres aggregated into a larger form, or (6) a combination thereof.
- Bioactive agents can be inco ⁇ orated as particulates or by co-dissolving the factors with the polymer Stabilizers can be inco ⁇ orated by addition of the stabilizers to the factor solution prior to formation of the microspheres.
- the bioactive agent can be inco ⁇ orated into a hydrogel and coated or otherwise deposited in or on the biointerface membrane.
- Some hydrogels suitable for use in the preferred embodiments include cross-linked, hydrophilic, three-dimensional polymer networks that are highly permeable to the bioactive agent and are triggered to release the bioactive agent based on a stimulus.
- the bioactive agent can be inco ⁇ orated into the biointerface membrane by solvent casting, wherein a solution including dissolved bioactive agent is disposed on the surface of the biointerface membrane, after which the solvent is removed to form a coating on the membrane surface.
- the interconnected cavities of the biointerface membrane are filled with the bioactive agent
- a bioactive agent with or without a carrier matrix, fills the cavities of the membrane, depending on the loading and release properties desired, which are discussed in more detail below.
- the bioactive agent can be compounded into a plug of material, which is placed within the implantable device, such as is described in U.S. Patent Nos. 4,506,680 and 5,282,844.
- the bioactive agents of the preferred embodiments can be optimized for short- and/or long-term release.
- the bioactive agents of the preferred embodiments are designed to aid or overcome factors associated with short-term effects (for example, acute inflammation) of the foreign body response, which can begin as early as the time of implantation and extend up to about one month after implantation.
- the bioactive agents of the preferred embodiments are designed to aid or overcome factors associated with long-term effects, for example, chronic inflammation, barrier cell layer formation, or build-up of fibrotic tissue of the foreign body response, which can begin as early as about one week after implantation and extend for the life of the implant, for example, months to years.
- the bioactive agents of the preferred embodiments combine short- and long-term release to exploit the benefits of both [0150]
- "controlled,” “sustained,” or “extended” release of the factors can be continuous or discontinuous, linear or non-linear. This can be accomplished using one or more types of polymer compositions, drug loadings, selections of excipients or degradation enhancers, or other modifications, administered alone, in combination or sequentially to produce the desired effect.
- Short-term release of the bioactive agent in the preferred embodiments generally refers to release over a period of from about 1 day or less to about 2, 3, 4, 5, 6, or 7 days, 2 or 3 weeks, 1 month, or more More preferably, the short-term release of the bioactive agent occurs over from about 14, 15, 16, 17, or 18 days up to about 19, 20, or 21 days.
- Conventional devices such as implantable analyte measurmg-devices, drug delivery devices, and cell transplantation devices that require transport of solutes across the device- tissue interface for proper function, tend to lose their function after the first few days following implantation. At least one reason for this loss of function is the lack of direct contact with circulating fluid for appropriate analyte transport to the device.
- short-term release of certain bioactive agents can increase the circulating fluid to the device for an extended period of time.
- bioactive agents for example vascularization agents
- short-term release of the bioactive agent can have a positive effect of the functionality of porous biointerface membranes during the initial tissue ingrowth period prior to formation of a capillary bed.
- a "sleep period" can occur which begins as early as the first day after implantation and extends as far as one month after implantation.
- shorter sleep periods are more common.
- neovascularization alone is generally not sufficient to provide sufficient analyte transport at the device-tissue interface, in combination with other mechanisms, enhanced neovascularization can result in enhanced transport of analytes from the host to the implanted device. Therefore in some embodiments, short-term release of certain bioactive agents, for example angiogenic agents, can have a positive effect on neovascularization and thereby enhance transport of analytes at the device- tissue interface. [0155] Additionally, it is believed that short-term release of the bioactive agent can be sufficient to reduce or prevent barrier cell layer formation.
- Short-term release of anti- inflammatory agents can be sufficient to rescue a biointerface membrane from the negative effects associated with such acute inflammation, rendering adequate analyte transport.
- Long-term release of the bioactive agent in the preferred embodiments generally occurs over a period of from about 1 month to about 2 years or more, preferably from at least about 2 months to at least about 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23 months, and more preferably from at least about 3 months to at least about 4, 5, 6, 7, 8, 9, 10, 11, or 12 months.
- Long-term glucose-measuring device experiments demonstrate that many biointerface materials experience a distinct and continual decline in sensitivity, for example, reduced analyte transport, beginning at three months after implantation in some cases.
- this decline in analyte transport can be a result of barrier cell layer formation, cellular growth at the membrane, and/or thickening of the fibrous elements of the foreign body capsule.
- Other contributing factors can include chronic inflammation, which is believed to be due to micro-motion or macro-motion of the device; delamination of the biointerface membrane, which is believed to be due to cellular ingrowth within and under the biointerface membrane; compression of the biointerface membrane due to increasing compression of the foreign body capsule around the device; and distortion of the biointerface membrane, which is believed to be a result of a combination of compression and cellular ingrowth, for example.
- long-term release of certain bioactive agents can modulate the foreign body response sufficiently to prevent long-term thickening of the foreign body capsule, reduce or prevent barrier cell layer formation, reduce or prevent chronic inflammation, reduce or prevent extensive cellular ingrowth, and/or reduce or prevent compression of the foreign body capsule on the biointerface membrane.
- the amount of loading of the bioactive agent into the biointerface membrane can depend upon several factors For example, the bioactive agent dosage and duration can vary with the intended use of the biointerface membrane, for example, cell transplantation, analyte measuring-device, and the like; differences among patients in the effective dose of bioactive agent, location and methods of loading the bioactive agent; and release rates associated with bioactive agents and optionally their carrier matrix. Therefore, one skilled in the art will appreciate the variability in the levels of loading the bioactive agent, for the reasons described above.
- the preferred level of loading of the bioactive agent into the biointerface membrane can vary depending upon the nature of the bioactive agent.
- the level of loading of the bioactive agent is preferably sufficiently high such that a biological effect is observed. Above this threshold, bioactive agent can be loaded into the biointerface membrane so as to imbibe up to 100% of the solid portions, cover all accessible surfaces of the membrane, and/or fill up to 100% of the accessible cavity space.
- the level of loading (based on the weight of bioactive agent(s), biointerface membrane, and other substances present) is from about 1 ppm or less to about 1000 ppm or more, preferably from about 2, 3, 4, or 5 ppm up to about 10, 25, 50, 75, 100, 200, 300, 400, 500, 600, 700, 800, or 900 ppm
- the level of loading can be 1 wt. % or less up to about 50 wt. % or more, preferably from about 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, or 20 wt. % up to about 25, 30, 35, 40, or 45 wt. %.
- the gel concentration can be optimized, for example, loaded with one or more test loadings of the bioactive agent It is generally preferred that the gel contain from about 0.1 or less to about 50 wt % or more of the bioactive agent(s), preferably from about 0.2, 0 3, 0.4, 0 5, 0 6, 0.7, 0.8, or 0.9 wt % to about 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, or 45 wt % or more bioactive agent(s), more preferably from about 1, 2, or 3 wt. % to about 4 or 5 wt.
- bioactive agent(s) % of the bioactive agent(s)
- Substances that are not bioactive can also be inco ⁇ orated into the matrix.
- the bioactive agent can be released by diffusion through aqueous filled channels generated in the dosage form by the dissolution of the agent or by voids created by the removal of the polymer solvent or a pore forming agent during the original micro-encapsulation. Alternatively, release can be enhanced due to the degradation of the polymer. With time, the polymer erodes and generates increased porosity and microstructure within the device. This creates additional pathways for release of the bioactive agent.
- Biointerface membranes of the preferred embodiments are suitable for use with implantable devices in contact with a biological fluid.
- the biointerface membranes can be utilized with implantable devices and methods for monitoring and determining analyte levels in a biological fluid, such as measurement of glucose levels for individuals having diabetes
- the analyte-measu ⁇ ng device is a continuous device.
- the device can analyze a plurality of intermittent biological samples.
- the analyte-measu ⁇ ng device can use any method of analyte-measurement, including enzymatic, chemical, physical, electrochemical, spectrophotomet ⁇ c, pola ⁇ met ⁇ c, calo ⁇ met ⁇ c, radiomet ⁇ c, or the like.
- analyte-measurement including enzymatic, chemical, physical, electrochemical, spectrophotomet ⁇ c, pola ⁇ met ⁇ c, calo ⁇ met ⁇ c, radiomet ⁇ c, or the like.
- biointerface membranes are suitable for use in a variety of devices, including, for example, those that detect and quantify other analytes present in biological fluids (including, but not limited to, cholesterol, amino acids, and lactate), cell transplantation devices (see, e.g., U.S. Pat. Nos. 6,015,572, 5,964,745, and 6,083,523), drug delivery devices (see, e.g., U.S. Pat. Nos. 5,458,631, 5,820,589, and 5,972,369) and electrical delivery and/or measuring devices such as implantable pulse generation cardiac pacing devices (see, e.g., U S. Pat. Nos.
- biointerface membranes can be utilized in conjunction with transplanted cells, for example, transplanted genetic engineered cells of Langerhans, either allo, auto or xeno geneic in origin, as pancreatic beta cells to increase the diffusion of nutrients to the islets, but additionally utilizing a biointerface membrane of the preferred embodiment on a measuring-device proximal to the transplanted cells to sense glucose in the tissues of the patient to monitor the viability of the implanted cells.
- implantable devices that include the biointerface membranes of the preferred embodiments are implanted in soft tissue, for example, abdominal, subcutaneous, and peritoneal tissues, the bram, the mtramedullary space, and other suitable organs or body tissues [0166]
- the biointerface membranes of the preferred embodiments can be employed with a variety of known continuous glucose measuring-devices.
- the biointerface membrane can be employed in conjunction with a continuous glucose measuring-device that comprises a subcutaneous measuring- device such as is described in U S Patent 6,579,690 to Bonnecaze et al and U.S.
- the continuous glucose measuring-device comprises a refillable subcutaneous measuring-device such as is described in U.S Patent 6,512,939 to Colvin et al.
- the disclosed embodiments are applicable to a variety of continuous glucose measuring-device configurations.
- Implantable devices for detecting the presence of an analyte or analyte concentrations in a biological system can utilize the biointerface membranes of the preferred embodiments to increase local vascularization and interfere with the formation of a barrier cell layer, thereby assuring that the measuring-device receives analyte concentrations representative of that in the vasculature
- Drug delivery devices can utilize the biointerface membranes of the preferred embodiments to protect the drug housed within the device from host inflammatory or immune cells that might potentially damage or destroy the drug.
- Fig. 3 is a graph of signal output from a glucose-measuring device implanted in a human, wherein the device included a biointerface membrane without a bioactive agent inco ⁇ orated therein.
- the graph shows the data signal produced by the device from time of implant up to about 21 days after implant.
- the x-axis represents time in days; the y-axis presents the data signal from the device output in counts.
- counts is a broad term and is used in its ordinary sense, including, without limitation, a unit of measurement of a digital signal.
- a raw data signal measured in counts is directly related to a voltage (converted by an A/D converter), which is directly related to current.
- the glucose-measuring device of this experiment is described in more detail with reference to Figs. 4A and 4B. [0169] Referring to Fig.
- the device associated with the signal output was implanted during day 1
- the associated signal output is shown beginning at day 1 and substantially tracks the rise and fall of the patient's glucose levels during the first few days after implant. It is noted that approximately 5 days after device implant, the signal output experienced a temporary decrease in sensitivity, sometimes referred to as a "sleep period.” It is believed that this loss in sensitivity is due to migration of cells, which consume glucose and oxygen during formation of a vascula ⁇ zed foreign body capsule (tissue bed) into and around the biointerface membrane In this example, the sleep period continues for approximately 7 days during which time the glucose-measuring device does not accurately track the patient's glucose levels Approximately 12 days after implant, the signal output resumes function, as indicated by the rise and fall of the signal output, which correlates with the rise and fall the patient's glucose levels.
- bioactive agents that enhance local vascularization and inhibit inflammatory cells within or around the biointerface membranes of the preferred embodiments on implanted devices, accelerated maturation of a vascula ⁇ zed tissue bed and decreased inflammatory response will occur, which increases the rate at which devices become functional, reducing or eliminating the loss insensitivity seen in the experiment above.
- the bioactive agents that are inco ⁇ orated into the biointerface membrane 30 used on implantable devices of certain preferred embodiments are chosen to optimize the rate of biointerface formation.
- the bioactive agents that are inco ⁇ orated into the biointerface membrane 30 used on implantable devices are chosen to optimize reliable biointerface formation In some situations, stable device function does not occur due to faulty surgical techniques, acute or chronic movement of the implant, or other surgery-, patient-, or implantation site-related complications, which can create acute and/or chronic inflammation at the implant site and subsequent formation of barrier cell layer and/or thick fibrotic tissue build-up.
- bioactive agents described in the preferred embodiments for example anti-inflammatory agents and or anti-bamer cell agents, can provide sufficient biological activity to reduce the effects of site-related complications, and thereby increase reliability of device functionality
- the bioactive agents that are inco ⁇ orated into the biointerface membrane 30 used on implantable devices are chosen to optimize the stability of the biointerface Even after devices have been implanted for some length of time and begin to function, it is observed that device stability can be lost gradually or suddenly It is believed that this loss of stability or function can be attributed the biointerface, based on post-explantation histological examinations This conclusion is further supported by the observation that devices typically function in vitro after removal from animals or humans It is therefore believed that delivery of bioactive agents described in the preferred embodiments can increase the stability of the biointerface so that device calibration values remain sufficiently stable so as to provide accurate measurements [0173]
- Figs 4A and 4B are perspective views of an implantable glucose measuring- device of a preferred
- Oxidation of H 2 0 2 by the working electrode is balanced by reduction of ambient oxygen, enzyme generated H 2 0 2 , or other reducible species at the counter electrode
- the H 2 0 2 produced from the glucose oxidase reaction further reacts at the surface of working electrode and produces two protons (2H + ), two electrons (2e " ), and one oxygen molecule (0 2 ).
- a potentiostat is employed to monitor the electrochemical reaction at the electroactive surface(s)
- the potentiostat applies a constant potential to the working and reference electrodes to determine a current value.
- the current that is produced at the working electrode (and flows through the circuitry to the counter electrode) is substantially proportional to the amount of H 2 0 that diffuses to the working electrode.
- the sensing membrane 64 includes an enzyme, for example, glucose oxidase, and covers the electrolyte phase.
- the sensing membrane 64 preferably includes a resistance domain most distal from the electrochemically reactive surfaces, an enzyme domain less distal from the electrochemically reactive surfaces than the resistance domain, and an electrolyte domain adjacent to the electrochemically reactive surfaces.
- a sensing membrane 64 modified for other devices for example, by including fewer or additional domains, is within the scope of the preferred embodiments.
- Patent Appl. No 09/916,711 entitled, "SENSOR HEAD FOR USE WITH IMPLANTABLE DEVICES,” describes membranes that can be used in some embodiments of the sensing membrane 64.
- the sensing membrane 64 can additionally include an interference domain that blocks some interfering species; such as described in the above-cited co-pending patent application.
- Co-pending U.S Patent Application 10/695,636, entitled, “SILICONE COMPOSITION FOR BIOCOMPATIBLE MEMBRANE” also describes membranes that can be used for the sensing membrane 64 of the preferred embodiments.
- the biointerface membrane 30 includes a biointerface membrane of a preferred embodiment, which covers the sensing membrane and supports tissue ingrowth, interferes with the formation of a barrier cell layer, and protects the sensitive regions of the measuring-device 60 from host inflammatory response.
- the biointerface membrane 30 is a formed from a nonresorbable membrane and includes a porous architecture with a bioactive agent inco ⁇ orated therein.
- the biointerface membranes of the preferred embodiments can inco ⁇ orate a variety of mechanisms, including materials, architecture, cavity size, and inco ⁇ oration of one or bioactive agents, which can be function alone or in combination to enhance wound healing, which when inco ⁇ orated into an analyte measuring-device, result in enhanced device performance.
- an anchoring material (not shown) is formed substantially around the device body in order to stabilize the device in vivo. Controlled release of a bioactive agent from the biointerface membrane 30, such as an anti-inflammatory agent, is provided for a period of time up to about one month, which is believed to be sufficient to reduce the effects of tissue trauma at the device interface prior to stabilization of the device in vivo.
- Eq and Eqs (equivalents); mEq (milhequivalents); M (molar); mM (milhmolar) ⁇ M (micromolar); N (Normal); mol (moles); mmol (milhmoles); ⁇ mol (micromoles), nmol (nanomoles); g (grams); mg (milligrams); ⁇ g (micrograms); Kg (kilograms); L (liters); mL (milhhters); dL (deciliter
- Example 1 Preparation of Biointerface Membrane with Porous Silicone
- a porous silicone cell disruptive (first) domain was prepared by mixing approximately 1 kg of sugar crystals with approximately 36 grams of water for 3-6 minutes. The mixture was then pressed into a mold and baked at 80°C for 2 hours The silicone was vacuumed into the mold for 6 minutes and cured at 80°C for at least 2 hours The sugar was dissolved using heat and deionized water, resulting in a flat sheet, porous membrane.
- Crystal size crystals having an average diameter of about 90, 106, 150, 180, and 220 ⁇ m
- the cell-impermeable (second) domain was prepared by placing approximately
- DMAC dimethylacetamide
- a polycarbonate urethane solution 1325 g, CHRONOFLEXTM AR 25% solids in DMAC and a viscosity of 5100 cp
- polyvinylpyrrolidone 125 g, PLASDONETM K-90D
- the bowl was then fitted to a planetary mixer with a paddle type blade and the contents were stirred for one hour at room temperature
- the cell-impermeable domain coating solution was then coated onto a PET release liner (Douglas Hansen Co , Inc.
- the biointerface membrane was prepared by pressing the porous silicone onto the cast cell- impermeable domain.
- the advantages of using porous silicone included the mechanical robustness of the material, the ability to mold it into various structural architectures, the ability to load lipid- soluble bioactive agents into the membrane without a carrier, the ability to fill the large pores of the material with collagen-coupled bioactive agents, and the high oxygen solubility of silicone that allowed the membrane to act as an oxygen antenna domain.
- bioactive agents can be inco ⁇ orated into the biomate ⁇ als of preferred embodiments.
- such bioactive agent containing biomate ⁇ als can be employed in an implantable glucose device for various pu ⁇ oses, such as extending the life of the device or to facilitate short-term function.
- the following experiments were performed with a porous silicone biointerface membrane prepared as described above, in combination with bioactive agents, for the pu ⁇ ose of accelerated device initiation and long-term sustentation.
- Example 2 Neovascularizing agents in biointerface membranes [0188] In a first experiment, disks were employed, which were prepared for three-week implantation into the subcutaneous space of rats to test a neovascularizing agent.
- Monobutyrin was chosen based on its hydrophobic characteristics and ability to promote neovascularization This experiment consisted of soaking the porous silicone prepared as described above in the concentrated solution of the bioactive compound at elevated temperature. This facilitated a partitioning of the agent into the porous silicone dependent upon its solubility in silicone rubber Porous silicone disks were exposed to phosphate buffer mixed with Monobutyrin (500 mg/ml) for four days at 47°C These disks were then autoclaved in the same solution, then rinsed in sterile saline immediately prior to implant. Disks were implanted into the subcutaneous dorsal space. Rats were euthanized and disks explanted at 3 weeks.
- Fig. 5 is a bar graph that shows average number of vessels (per high-powered field of vision) of porous silicone (PS) materials embedded with and without Monobutyrin (MBN) after three weeks of implantation.
- PS porous silicone
- MBN Monobutyrin
- Example 3 Anti-Inflammatory agents in biointerface membranes [0190] Dexamethasone was loaded into a porous silicone biointerface membrane by so ⁇ tion. In this experiment, lOOmg of Dexamethasone was mixed with 10 mL of Butanone (solvent) and the mixture heated to about 70°C-80°C to dissolve the Dexamethasone in the solvent The solution was then centnfuged to ensure solubility.
- the supernatant was pipetted from the solution and placed in a clean glass vial.
- Disks of porous silicone were placed in the Dexamethasone solution at 40°C for 5 days, after which the disks were air-dried.
- the disks were sprayed with 70% isopropanol to remove trapped air from the porous silicone, attached to glucose sensors, and sterilized m 0.5% glutaraldehyde for 24 hours After rinsing, the glucose sensors were placed in a 40 mL phosphate buffer solution conical. These conicals were placed on a shaker table with a setting of about 7 or 8.
- Fig. 6 is a graph that shows the cumulative amount of Dexamethasone released over time as described above. Namely, during the first 19 days, about 0.4mg of Dexamethasone was released in PBS solution. The amount of Dexamethasone released is at least partially dependent upon the surface area of the biointerface membrane, including throughout the cavities of the cell disruptive domain.
- Dexamethasone released over time can modify a tissue response to the biointerface membrane in vivo, thereby substantially overcoming the effects of a "sleep period", 2) aid in preventing barrier cell layer formation, and or 3) rescuing a biointerface membrane from the negative effects associated with such acute inflammation, rendering adequate analyte transport to an implantable device [0192]
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE602004030902T DE602004030902D1 (en) | 2003-05-21 | 2004-05-19 | BIOINTERFACE MEMBRANES WITH BIOACTIVE AGENTS |
JP2006514910A JP2006525853A (en) | 2003-05-21 | 2004-05-19 | Biointerface membrane incorporating bioactive agent |
AT04809390T ATE494018T1 (en) | 2003-05-21 | 2004-05-19 | BIOINTERFACE MEMBRANES WITH BIOACTIVE AGENTS |
EP04809390A EP1624908B8 (en) | 2003-05-21 | 2004-05-19 | Biointerface membranes incorporating bioactive agents |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US47267303P | 2003-05-21 | 2003-05-21 | |
US60/472,673 | 2003-05-21 | ||
US10/647,065 | 2003-08-22 | ||
US10/647,065 US7192450B2 (en) | 2003-05-21 | 2003-08-22 | Porous membranes for use with implantable devices |
US54472204P | 2004-02-12 | 2004-02-12 | |
US60/544,722 | 2004-02-12 |
Publications (3)
Publication Number | Publication Date |
---|---|
WO2005025634A2 WO2005025634A2 (en) | 2005-03-24 |
WO2005025634A9 true WO2005025634A9 (en) | 2005-07-07 |
WO2005025634A3 WO2005025634A3 (en) | 2005-10-06 |
Family
ID=34119759
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2004/015846 WO2005025634A2 (en) | 2003-05-21 | 2004-05-19 | Biointerface membranes incorporating bioactive agents |
Country Status (6)
Country | Link |
---|---|
US (5) | US7875293B2 (en) |
EP (1) | EP1624908B8 (en) |
JP (1) | JP2006525853A (en) |
AT (1) | ATE494018T1 (en) |
DE (1) | DE602004030902D1 (en) |
WO (1) | WO2005025634A2 (en) |
Families Citing this family (374)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5593852A (en) * | 1993-12-02 | 1997-01-14 | Heller; Adam | Subcutaneous glucose electrode |
US8527026B2 (en) | 1997-03-04 | 2013-09-03 | Dexcom, Inc. | Device and method for determining analyte levels |
US7192450B2 (en) * | 2003-05-21 | 2007-03-20 | Dexcom, Inc. | Porous membranes for use with implantable devices |
US7657297B2 (en) * | 2004-05-03 | 2010-02-02 | Dexcom, Inc. | Implantable analyte sensor |
US6001067A (en) * | 1997-03-04 | 1999-12-14 | Shults; Mark C. | Device and method for determining analyte levels |
US6134461A (en) | 1998-03-04 | 2000-10-17 | E. Heller & Company | Electrochemical analyte |
US8974386B2 (en) | 1998-04-30 | 2015-03-10 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US6175752B1 (en) | 1998-04-30 | 2001-01-16 | Therasense, Inc. | Analyte monitoring device and methods of use |
US8465425B2 (en) | 1998-04-30 | 2013-06-18 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US9066695B2 (en) | 1998-04-30 | 2015-06-30 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US6949816B2 (en) | 2003-04-21 | 2005-09-27 | Motorola, Inc. | Semiconductor component having first surface area for electrically coupling to a semiconductor chip and second surface area for electrically coupling to a substrate, and method of manufacturing same |
US8480580B2 (en) | 1998-04-30 | 2013-07-09 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US8688188B2 (en) | 1998-04-30 | 2014-04-01 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US8346337B2 (en) | 1998-04-30 | 2013-01-01 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods of use |
US6560471B1 (en) | 2001-01-02 | 2003-05-06 | Therasense, Inc. | Analyte monitoring device and methods of use |
US7041468B2 (en) | 2001-04-02 | 2006-05-09 | Therasense, Inc. | Blood glucose tracking apparatus and methods |
US6932894B2 (en) | 2001-05-15 | 2005-08-23 | Therasense, Inc. | Biosensor membranes composed of polymers containing heterocyclic nitrogens |
US20030032874A1 (en) | 2001-07-27 | 2003-02-13 | Dexcom, Inc. | Sensor head for use with implantable devices |
US6702857B2 (en) | 2001-07-27 | 2004-03-09 | Dexcom, Inc. | Membrane for use with implantable devices |
US8364229B2 (en) | 2003-07-25 | 2013-01-29 | Dexcom, Inc. | Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise |
US7828728B2 (en) * | 2003-07-25 | 2010-11-09 | Dexcom, Inc. | Analyte sensor |
US7613491B2 (en) | 2002-05-22 | 2009-11-03 | Dexcom, Inc. | Silicone based membranes for use in implantable glucose sensors |
US9247901B2 (en) | 2003-08-22 | 2016-02-02 | Dexcom, Inc. | Systems and methods for replacing signal artifacts in a glucose sensor data stream |
US8260393B2 (en) | 2003-07-25 | 2012-09-04 | Dexcom, Inc. | Systems and methods for replacing signal data artifacts in a glucose sensor data stream |
US9282925B2 (en) | 2002-02-12 | 2016-03-15 | Dexcom, Inc. | Systems and methods for replacing signal artifacts in a glucose sensor data stream |
US8010174B2 (en) | 2003-08-22 | 2011-08-30 | Dexcom, Inc. | Systems and methods for replacing signal artifacts in a glucose sensor data stream |
US8858434B2 (en) | 2004-07-13 | 2014-10-14 | Dexcom, Inc. | Transcutaneous analyte sensor |
US7226978B2 (en) * | 2002-05-22 | 2007-06-05 | Dexcom, Inc. | Techniques to improve polyurethane membranes for implantable glucose sensors |
US20060258761A1 (en) * | 2002-05-22 | 2006-11-16 | Robert Boock | Silicone based membranes for use in implantable glucose sensors |
US7727181B2 (en) * | 2002-10-09 | 2010-06-01 | Abbott Diabetes Care Inc. | Fluid delivery device with autocalibration |
EP2322798A1 (en) | 2002-10-09 | 2011-05-18 | Abbott Diabetes Care Inc. | Device and method for delivering medical fluids using a shape memory alloy |
US7993108B2 (en) | 2002-10-09 | 2011-08-09 | Abbott Diabetes Care Inc. | Variable volume, shape memory actuated insulin dispensing pump |
US7381184B2 (en) | 2002-11-05 | 2008-06-03 | Abbott Diabetes Care Inc. | Sensor inserter assembly |
WO2004061420A2 (en) | 2002-12-31 | 2004-07-22 | Therasense, Inc. | Continuous glucose monitoring system and methods of use |
US7134999B2 (en) * | 2003-04-04 | 2006-11-14 | Dexcom, Inc. | Optimized sensor geometry for an implantable glucose sensor |
US7587287B2 (en) * | 2003-04-04 | 2009-09-08 | Abbott Diabetes Care Inc. | Method and system for transferring analyte test data |
US7679407B2 (en) * | 2003-04-28 | 2010-03-16 | Abbott Diabetes Care Inc. | Method and apparatus for providing peak detection circuitry for data communication systems |
US7875293B2 (en) * | 2003-05-21 | 2011-01-25 | Dexcom, Inc. | Biointerface membranes incorporating bioactive agents |
US8460243B2 (en) * | 2003-06-10 | 2013-06-11 | Abbott Diabetes Care Inc. | Glucose measuring module and insulin pump combination |
US8066639B2 (en) | 2003-06-10 | 2011-11-29 | Abbott Diabetes Care Inc. | Glucose measuring device for use in personal area network |
US8071028B2 (en) * | 2003-06-12 | 2011-12-06 | Abbott Diabetes Care Inc. | Method and apparatus for providing power management in data communication systems |
US7695239B2 (en) * | 2003-07-14 | 2010-04-13 | Fortrend Engineering Corporation | End effector gripper arms having corner grippers which reorient reticle during transfer |
US7722536B2 (en) * | 2003-07-15 | 2010-05-25 | Abbott Diabetes Care Inc. | Glucose measuring device integrated into a holster for a personal area network device |
WO2005010518A1 (en) * | 2003-07-23 | 2005-02-03 | Dexcom, Inc. | Rolled electrode array and its method for manufacture |
EP1648298A4 (en) * | 2003-07-25 | 2010-01-13 | Dexcom Inc | Oxygen enhancing membrane systems for implantable devices |
US20050176136A1 (en) * | 2003-11-19 | 2005-08-11 | Dexcom, Inc. | Afinity domain for analyte sensor |
US8423113B2 (en) | 2003-07-25 | 2013-04-16 | Dexcom, Inc. | Systems and methods for processing sensor data |
US7761130B2 (en) * | 2003-07-25 | 2010-07-20 | Dexcom, Inc. | Dual electrode system for a continuous analyte sensor |
US9763609B2 (en) | 2003-07-25 | 2017-09-19 | Dexcom, Inc. | Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise |
WO2005012873A2 (en) * | 2003-07-25 | 2005-02-10 | Dexcom, Inc. | Electrode systems for electrochemical sensors |
US7467003B2 (en) * | 2003-12-05 | 2008-12-16 | Dexcom, Inc. | Dual electrode system for a continuous analyte sensor |
US7651596B2 (en) | 2005-04-08 | 2010-01-26 | Dexcom, Inc. | Cellulosic-based interference domain for an analyte sensor |
WO2005019795A2 (en) * | 2003-07-25 | 2005-03-03 | Dexcom, Inc. | Electrochemical sensors including electrode systems with increased oxygen generation |
US7774145B2 (en) | 2003-08-01 | 2010-08-10 | Dexcom, Inc. | Transcutaneous analyte sensor |
US8886273B2 (en) | 2003-08-01 | 2014-11-11 | Dexcom, Inc. | Analyte sensor |
US7494465B2 (en) | 2004-07-13 | 2009-02-24 | Dexcom, Inc. | Transcutaneous analyte sensor |
US20190357827A1 (en) | 2003-08-01 | 2019-11-28 | Dexcom, Inc. | Analyte sensor |
US9135402B2 (en) | 2007-12-17 | 2015-09-15 | Dexcom, Inc. | Systems and methods for processing sensor data |
US8761856B2 (en) | 2003-08-01 | 2014-06-24 | Dexcom, Inc. | System and methods for processing analyte sensor data |
US7591801B2 (en) | 2004-02-26 | 2009-09-22 | Dexcom, Inc. | Integrated delivery device for continuous glucose sensor |
US7986986B2 (en) | 2003-08-01 | 2011-07-26 | Dexcom, Inc. | System and methods for processing analyte sensor data |
US8369919B2 (en) * | 2003-08-01 | 2013-02-05 | Dexcom, Inc. | Systems and methods for processing sensor data |
US8160669B2 (en) | 2003-08-01 | 2012-04-17 | Dexcom, Inc. | Transcutaneous analyte sensor |
US8060173B2 (en) | 2003-08-01 | 2011-11-15 | Dexcom, Inc. | System and methods for processing analyte sensor data |
US8275437B2 (en) * | 2003-08-01 | 2012-09-25 | Dexcom, Inc. | Transcutaneous analyte sensor |
US8788006B2 (en) | 2003-08-01 | 2014-07-22 | Dexcom, Inc. | System and methods for processing analyte sensor data |
US8233959B2 (en) * | 2003-08-22 | 2012-07-31 | Dexcom, Inc. | Systems and methods for processing analyte sensor data |
US7920906B2 (en) | 2005-03-10 | 2011-04-05 | Dexcom, Inc. | System and methods for processing analyte sensor data for sensor calibration |
US20140121989A1 (en) | 2003-08-22 | 2014-05-01 | Dexcom, Inc. | Systems and methods for processing analyte sensor data |
US7299082B2 (en) | 2003-10-31 | 2007-11-20 | Abbott Diabetes Care, Inc. | Method of calibrating an analyte-measurement device, and associated methods, devices and systems |
USD902408S1 (en) | 2003-11-05 | 2020-11-17 | Abbott Diabetes Care Inc. | Analyte sensor control unit |
EP1689321B1 (en) | 2003-11-07 | 2017-01-04 | The University of Connecticut | Artificial tissue systems and uses thereof |
US8615282B2 (en) | 2004-07-13 | 2013-12-24 | Dexcom, Inc. | Analyte sensor |
WO2005051170A2 (en) | 2003-11-19 | 2005-06-09 | Dexcom, Inc. | Integrated receiver for continuous analyte sensor |
US9247900B2 (en) | 2004-07-13 | 2016-02-02 | Dexcom, Inc. | Analyte sensor |
US8532730B2 (en) | 2006-10-04 | 2013-09-10 | Dexcom, Inc. | Analyte sensor |
US8423114B2 (en) * | 2006-10-04 | 2013-04-16 | Dexcom, Inc. | Dual electrode system for a continuous analyte sensor |
US8364231B2 (en) | 2006-10-04 | 2013-01-29 | Dexcom, Inc. | Analyte sensor |
US11633133B2 (en) | 2003-12-05 | 2023-04-25 | Dexcom, Inc. | Dual electrode system for a continuous analyte sensor |
DE602004029092D1 (en) | 2003-12-05 | 2010-10-21 | Dexcom Inc | CALIBRATION METHODS FOR A CONTINUOUSLY WORKING ANALYTIC SENSOR |
EP2329763B1 (en) | 2003-12-09 | 2017-06-21 | DexCom, Inc. | Signal processing for continuous analyte sensor |
US7637868B2 (en) * | 2004-01-12 | 2009-12-29 | Dexcom, Inc. | Composite material for implantable device |
US20050182451A1 (en) * | 2004-01-12 | 2005-08-18 | Adam Griffin | Implantable device with improved radio frequency capabilities |
US7699964B2 (en) | 2004-02-09 | 2010-04-20 | Abbott Diabetes Care Inc. | Membrane suitable for use in an analyte sensor, analyte sensor, and associated method |
US8165651B2 (en) | 2004-02-09 | 2012-04-24 | Abbott Diabetes Care Inc. | Analyte sensor, and associated system and method employing a catalytic agent |
WO2005079257A2 (en) * | 2004-02-12 | 2005-09-01 | Dexcom, Inc. | Biointerface with macro- and micro- architecture |
EP1718198A4 (en) | 2004-02-17 | 2008-06-04 | Therasense Inc | Method and system for providing data communication in continuous glucose monitoring and management system |
US8808228B2 (en) * | 2004-02-26 | 2014-08-19 | Dexcom, Inc. | Integrated medicament delivery device for use with continuous analyte sensor |
US20050245799A1 (en) * | 2004-05-03 | 2005-11-03 | Dexcom, Inc. | Implantable analyte sensor |
US8792955B2 (en) | 2004-05-03 | 2014-07-29 | Dexcom, Inc. | Transcutaneous analyte sensor |
US8277713B2 (en) * | 2004-05-03 | 2012-10-02 | Dexcom, Inc. | Implantable analyte sensor |
WO2005119524A2 (en) | 2004-06-04 | 2005-12-15 | Therasense, Inc. | Diabetes care host-client architecture and data management system |
US8565848B2 (en) | 2004-07-13 | 2013-10-22 | Dexcom, Inc. | Transcutaneous analyte sensor |
US20060270922A1 (en) * | 2004-07-13 | 2006-11-30 | Brauker James H | Analyte sensor |
EP2335581A1 (en) | 2004-07-13 | 2011-06-22 | DexCom, Inc. | Transcutaneous analyte sensor |
US7783333B2 (en) | 2004-07-13 | 2010-08-24 | Dexcom, Inc. | Transcutaneous medical device with variable stiffness |
US8452368B2 (en) | 2004-07-13 | 2013-05-28 | Dexcom, Inc. | Transcutaneous analyte sensor |
US8029441B2 (en) | 2006-02-28 | 2011-10-04 | Abbott Diabetes Care Inc. | Analyte sensor transmitter unit configuration for a data monitoring and management system |
US20090105569A1 (en) * | 2006-04-28 | 2009-04-23 | Abbott Diabetes Care, Inc. | Introducer Assembly and Methods of Use |
US8571624B2 (en) | 2004-12-29 | 2013-10-29 | Abbott Diabetes Care Inc. | Method and apparatus for mounting a data transmission device in a communication system |
US9636450B2 (en) | 2007-02-19 | 2017-05-02 | Udo Hoss | Pump system modular components for delivering medication and analyte sensing at seperate insertion sites |
US9743862B2 (en) | 2011-03-31 | 2017-08-29 | Abbott Diabetes Care Inc. | Systems and methods for transcutaneously implanting medical devices |
US7697967B2 (en) | 2005-12-28 | 2010-04-13 | Abbott Diabetes Care Inc. | Method and apparatus for providing analyte sensor insertion |
US20070027381A1 (en) * | 2005-07-29 | 2007-02-01 | Therasense, Inc. | Inserter and methods of use |
US9398882B2 (en) | 2005-09-30 | 2016-07-26 | Abbott Diabetes Care Inc. | Method and apparatus for providing analyte sensor and data processing device |
US8613703B2 (en) | 2007-05-31 | 2013-12-24 | Abbott Diabetes Care Inc. | Insertion devices and methods |
US9788771B2 (en) | 2006-10-23 | 2017-10-17 | Abbott Diabetes Care Inc. | Variable speed sensor insertion devices and methods of use |
US7731657B2 (en) * | 2005-08-30 | 2010-06-08 | Abbott Diabetes Care Inc. | Analyte sensor introducer and methods of use |
US8512243B2 (en) | 2005-09-30 | 2013-08-20 | Abbott Diabetes Care Inc. | Integrated introducer and transmitter assembly and methods of use |
US9572534B2 (en) | 2010-06-29 | 2017-02-21 | Abbott Diabetes Care Inc. | Devices, systems and methods for on-skin or on-body mounting of medical devices |
US9259175B2 (en) | 2006-10-23 | 2016-02-16 | Abbott Diabetes Care, Inc. | Flexible patch for fluid delivery and monitoring body analytes |
US8333714B2 (en) * | 2006-09-10 | 2012-12-18 | Abbott Diabetes Care Inc. | Method and system for providing an integrated analyte sensor insertion device and data processing unit |
US7883464B2 (en) | 2005-09-30 | 2011-02-08 | Abbott Diabetes Care Inc. | Integrated transmitter unit and sensor introducer mechanism and methods of use |
US10226207B2 (en) | 2004-12-29 | 2019-03-12 | Abbott Diabetes Care Inc. | Sensor inserter having introducer |
US9351669B2 (en) | 2009-09-30 | 2016-05-31 | Abbott Diabetes Care Inc. | Interconnect for on-body analyte monitoring device |
US7545272B2 (en) | 2005-02-08 | 2009-06-09 | Therasense, Inc. | RF tag on test strips, test strip vials and boxes |
US8133178B2 (en) | 2006-02-22 | 2012-03-13 | Dexcom, Inc. | Analyte sensor |
CN101180093B (en) * | 2005-03-21 | 2012-07-18 | 雅培糖尿病护理公司 | Method and system for providing integrated medication infusion and analyte monitoring system |
US8744546B2 (en) * | 2005-05-05 | 2014-06-03 | Dexcom, Inc. | Cellulosic-based resistance domain for an analyte sensor |
US20060252027A1 (en) * | 2005-05-05 | 2006-11-09 | Petisce James R | Cellulosic-based resistance domain for an analyte sensor |
US8060174B2 (en) | 2005-04-15 | 2011-11-15 | Dexcom, Inc. | Analyte sensing biointerface |
US8112240B2 (en) | 2005-04-29 | 2012-02-07 | Abbott Diabetes Care Inc. | Method and apparatus for providing leak detection in data monitoring and management systems |
US7768408B2 (en) | 2005-05-17 | 2010-08-03 | Abbott Diabetes Care Inc. | Method and system for providing data management in data monitoring system |
US7620437B2 (en) | 2005-06-03 | 2009-11-17 | Abbott Diabetes Care Inc. | Method and apparatus for providing rechargeable power in data monitoring and management systems |
GB0515477D0 (en) * | 2005-07-28 | 2005-08-31 | Smith & Nephew | Composition |
EP1921980A4 (en) | 2005-08-31 | 2010-03-10 | Univ Virginia | Improving the accuracy of continuous glucose sensors |
US8880138B2 (en) * | 2005-09-30 | 2014-11-04 | Abbott Diabetes Care Inc. | Device for channeling fluid and methods of use |
US7756561B2 (en) | 2005-09-30 | 2010-07-13 | Abbott Diabetes Care Inc. | Method and apparatus for providing rechargeable power in data monitoring and management systems |
US9521968B2 (en) | 2005-09-30 | 2016-12-20 | Abbott Diabetes Care Inc. | Analyte sensor retention mechanism and methods of use |
US7583190B2 (en) | 2005-10-31 | 2009-09-01 | Abbott Diabetes Care Inc. | Method and apparatus for providing data communication in data monitoring and management systems |
US7766829B2 (en) | 2005-11-04 | 2010-08-03 | Abbott Diabetes Care Inc. | Method and system for providing basal profile modification in analyte monitoring and management systems |
US11298058B2 (en) | 2005-12-28 | 2022-04-12 | Abbott Diabetes Care Inc. | Method and apparatus for providing analyte sensor insertion |
US8515518B2 (en) | 2005-12-28 | 2013-08-20 | Abbott Diabetes Care Inc. | Analyte monitoring |
US8160670B2 (en) | 2005-12-28 | 2012-04-17 | Abbott Diabetes Care Inc. | Analyte monitoring: stabilizer for subcutaneous glucose sensor with incorporated antiglycolytic agent |
US8353881B2 (en) * | 2005-12-28 | 2013-01-15 | Abbott Diabetes Care Inc. | Infusion sets for the delivery of a therapeutic substance to a patient |
CA2636034A1 (en) * | 2005-12-28 | 2007-10-25 | Abbott Diabetes Care Inc. | Medical device insertion |
WO2007084516A2 (en) * | 2006-01-18 | 2007-07-26 | Dexcom, Inc. | Membranes for an analyte sensor |
US7736310B2 (en) * | 2006-01-30 | 2010-06-15 | Abbott Diabetes Care Inc. | On-body medical device securement |
US8344966B2 (en) * | 2006-01-31 | 2013-01-01 | Abbott Diabetes Care Inc. | Method and system for providing a fault tolerant display unit in an electronic device |
ES2961309T3 (en) | 2006-02-22 | 2024-03-11 | Dexcom Inc | Analyte sensor |
US7885698B2 (en) | 2006-02-28 | 2011-02-08 | Abbott Diabetes Care Inc. | Method and system for providing continuous calibration of implantable analyte sensors |
US7981034B2 (en) | 2006-02-28 | 2011-07-19 | Abbott Diabetes Care Inc. | Smart messages and alerts for an infusion delivery and management system |
US7826879B2 (en) * | 2006-02-28 | 2010-11-02 | Abbott Diabetes Care Inc. | Analyte sensors and methods of use |
EP4218548A1 (en) | 2006-03-09 | 2023-08-02 | Dexcom, Inc. | Systems and methods for processing analyte sensor data |
US9339217B2 (en) | 2011-11-25 | 2016-05-17 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods of use |
US8583205B2 (en) | 2008-03-28 | 2013-11-12 | Abbott Diabetes Care Inc. | Analyte sensor calibration management |
US8224415B2 (en) * | 2009-01-29 | 2012-07-17 | Abbott Diabetes Care Inc. | Method and device for providing offset model based calibration for analyte sensor |
US7653425B2 (en) | 2006-08-09 | 2010-01-26 | Abbott Diabetes Care Inc. | Method and system for providing calibration of an analyte sensor in an analyte monitoring system |
US9675290B2 (en) | 2012-10-30 | 2017-06-13 | Abbott Diabetes Care Inc. | Sensitivity calibration of in vivo sensors used to measure analyte concentration |
US8473022B2 (en) | 2008-01-31 | 2013-06-25 | Abbott Diabetes Care Inc. | Analyte sensor with time lag compensation |
US7618369B2 (en) | 2006-10-02 | 2009-11-17 | Abbott Diabetes Care Inc. | Method and system for dynamically updating calibration parameters for an analyte sensor |
US7620438B2 (en) | 2006-03-31 | 2009-11-17 | Abbott Diabetes Care Inc. | Method and system for powering an electronic device |
US7801582B2 (en) * | 2006-03-31 | 2010-09-21 | Abbott Diabetes Care Inc. | Analyte monitoring and management system and methods therefor |
US8374668B1 (en) | 2007-10-23 | 2013-02-12 | Abbott Diabetes Care Inc. | Analyte sensor with lag compensation |
US8226891B2 (en) | 2006-03-31 | 2012-07-24 | Abbott Diabetes Care Inc. | Analyte monitoring devices and methods therefor |
US8219173B2 (en) | 2008-09-30 | 2012-07-10 | Abbott Diabetes Care Inc. | Optimizing analyte sensor calibration |
US7630748B2 (en) | 2006-10-25 | 2009-12-08 | Abbott Diabetes Care Inc. | Method and system for providing analyte monitoring |
US9392969B2 (en) | 2008-08-31 | 2016-07-19 | Abbott Diabetes Care Inc. | Closed loop control and signal attenuation detection |
US8346335B2 (en) | 2008-03-28 | 2013-01-01 | Abbott Diabetes Care Inc. | Analyte sensor calibration management |
US8140312B2 (en) | 2007-05-14 | 2012-03-20 | Abbott Diabetes Care Inc. | Method and system for determining analyte levels |
WO2007143225A2 (en) * | 2006-06-07 | 2007-12-13 | Abbott Diabetes Care, Inc. | Analyte monitoring system and method |
US20080004601A1 (en) * | 2006-06-28 | 2008-01-03 | Abbott Diabetes Care, Inc. | Analyte Monitoring and Therapy Management System and Methods Therefor |
US20090171269A1 (en) * | 2006-06-29 | 2009-07-02 | Abbott Diabetes Care, Inc. | Infusion Device and Methods Therefor |
US20090105571A1 (en) * | 2006-06-30 | 2009-04-23 | Abbott Diabetes Care, Inc. | Method and System for Providing Data Communication in Data Management Systems |
US9119582B2 (en) | 2006-06-30 | 2015-09-01 | Abbott Diabetes Care, Inc. | Integrated analyte sensor and infusion device and methods therefor |
US8206296B2 (en) | 2006-08-07 | 2012-06-26 | Abbott Diabetes Care Inc. | Method and system for providing integrated analyte monitoring and infusion system therapy management |
US8932216B2 (en) * | 2006-08-07 | 2015-01-13 | Abbott Diabetes Care Inc. | Method and system for providing data management in integrated analyte monitoring and infusion system |
US7831287B2 (en) * | 2006-10-04 | 2010-11-09 | Dexcom, Inc. | Dual electrode system for a continuous analyte sensor |
CN102772212A (en) | 2006-10-26 | 2012-11-14 | 雅培糖尿病护理公司 | Method, device and system for detection of sensitivity decline in analyte sensors |
US8579853B2 (en) | 2006-10-31 | 2013-11-12 | Abbott Diabetes Care Inc. | Infusion devices and methods |
US8121857B2 (en) * | 2007-02-15 | 2012-02-21 | Abbott Diabetes Care Inc. | Device and method for automatic data acquisition and/or detection |
US20080199894A1 (en) * | 2007-02-15 | 2008-08-21 | Abbott Diabetes Care, Inc. | Device and method for automatic data acquisition and/or detection |
US8930203B2 (en) | 2007-02-18 | 2015-01-06 | Abbott Diabetes Care Inc. | Multi-function analyte test device and methods therefor |
US8732188B2 (en) | 2007-02-18 | 2014-05-20 | Abbott Diabetes Care Inc. | Method and system for providing contextual based medication dosage determination |
US8123686B2 (en) | 2007-03-01 | 2012-02-28 | Abbott Diabetes Care Inc. | Method and apparatus for providing rolling data in communication systems |
AU2008230832A1 (en) | 2007-03-26 | 2008-10-02 | Dexcom, Inc. | Analyte sensor |
US10111608B2 (en) * | 2007-04-14 | 2018-10-30 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in medical communication system |
CA2683930A1 (en) | 2007-04-14 | 2008-10-23 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in medical communication system |
EP2146623B1 (en) | 2007-04-14 | 2014-01-08 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in medical communication system |
EP2146625B1 (en) | 2007-04-14 | 2019-08-14 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in medical communication system |
CA2683721C (en) | 2007-04-14 | 2017-05-23 | Abbott Diabetes Care Inc. | Method and apparatus for providing dynamic multi-stage signal amplification in a medical device |
CA2683959C (en) * | 2007-04-14 | 2017-08-29 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in medical communication system |
US8665091B2 (en) | 2007-05-08 | 2014-03-04 | Abbott Diabetes Care Inc. | Method and device for determining elapsed sensor life |
US7928850B2 (en) | 2007-05-08 | 2011-04-19 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods |
US8456301B2 (en) | 2007-05-08 | 2013-06-04 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods |
US8461985B2 (en) | 2007-05-08 | 2013-06-11 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods |
US8560038B2 (en) | 2007-05-14 | 2013-10-15 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US8444560B2 (en) | 2007-05-14 | 2013-05-21 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US8260558B2 (en) | 2007-05-14 | 2012-09-04 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US8103471B2 (en) | 2007-05-14 | 2012-01-24 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US7996158B2 (en) | 2007-05-14 | 2011-08-09 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US8239166B2 (en) | 2007-05-14 | 2012-08-07 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US8600681B2 (en) | 2007-05-14 | 2013-12-03 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US9125548B2 (en) * | 2007-05-14 | 2015-09-08 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US10002233B2 (en) * | 2007-05-14 | 2018-06-19 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
US20200037874A1 (en) | 2007-05-18 | 2020-02-06 | Dexcom, Inc. | Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise |
US20080306444A1 (en) | 2007-06-08 | 2008-12-11 | Dexcom, Inc. | Integrated medicament delivery device for use with continuous analyte sensor |
US8133553B2 (en) | 2007-06-18 | 2012-03-13 | Zimmer, Inc. | Process for forming a ceramic layer |
US8309521B2 (en) | 2007-06-19 | 2012-11-13 | Zimmer, Inc. | Spacer with a coating thereon for use with an implant device |
US8617069B2 (en) * | 2007-06-21 | 2013-12-31 | Abbott Diabetes Care Inc. | Health monitor |
AU2008265541B2 (en) | 2007-06-21 | 2014-07-17 | Abbott Diabetes Care, Inc. | Health management devices and methods |
US20080319294A1 (en) * | 2007-06-21 | 2008-12-25 | Abbott Diabetes Care, Inc. | Health management devices and methods |
US8641618B2 (en) * | 2007-06-27 | 2014-02-04 | Abbott Diabetes Care Inc. | Method and structure for securing a monitoring device element |
US8085151B2 (en) * | 2007-06-28 | 2011-12-27 | Abbott Diabetes Care Inc. | Signal converting cradle for medical condition monitoring and management system |
US8160900B2 (en) * | 2007-06-29 | 2012-04-17 | Abbott Diabetes Care Inc. | Analyte monitoring and management device and method to analyze the frequency of user interaction with the device |
US8834366B2 (en) | 2007-07-31 | 2014-09-16 | Abbott Diabetes Care Inc. | Method and apparatus for providing analyte sensor calibration |
US7768386B2 (en) * | 2007-07-31 | 2010-08-03 | Abbott Diabetes Care Inc. | Method and apparatus for providing data processing and control in a medical communication system |
EP4159114B1 (en) | 2007-10-09 | 2024-04-10 | DexCom, Inc. | Integrated insulin delivery system with continuous glucose sensor |
US8608049B2 (en) * | 2007-10-10 | 2013-12-17 | Zimmer, Inc. | Method for bonding a tantalum structure to a cobalt-alloy substrate |
US20110230973A1 (en) * | 2007-10-10 | 2011-09-22 | Zimmer, Inc. | Method for bonding a tantalum structure to a cobalt-alloy substrate |
DE102007051059B4 (en) * | 2007-10-18 | 2014-04-03 | NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen | Biocompound material for the controlled release of active substances |
US8216138B1 (en) | 2007-10-23 | 2012-07-10 | Abbott Diabetes Care Inc. | Correlation of alternative site blood and interstitial fluid glucose concentrations to venous glucose concentration |
US8377031B2 (en) | 2007-10-23 | 2013-02-19 | Abbott Diabetes Care Inc. | Closed loop control system with safety parameters and methods |
US8409093B2 (en) * | 2007-10-23 | 2013-04-02 | Abbott Diabetes Care Inc. | Assessing measures of glycemic variability |
US8417312B2 (en) | 2007-10-25 | 2013-04-09 | Dexcom, Inc. | Systems and methods for processing sensor data |
CA2702799A1 (en) | 2007-10-25 | 2009-04-30 | Dexcom, Inc. | Systems and methods for processing sensor data |
CA2704032C (en) * | 2007-10-29 | 2016-10-18 | Zimmer, Inc. | Medical implants and methods for delivering biologically active agents |
US8290559B2 (en) | 2007-12-17 | 2012-10-16 | Dexcom, Inc. | Systems and methods for processing sensor data |
US20090164239A1 (en) | 2007-12-19 | 2009-06-25 | Abbott Diabetes Care, Inc. | Dynamic Display Of Glucose Information |
US20090164190A1 (en) * | 2007-12-19 | 2009-06-25 | Abbott Diabetes Care, Inc. | Physiological condition simulation device and method |
US20090187256A1 (en) * | 2008-01-21 | 2009-07-23 | Zimmer, Inc. | Method for forming an integral porous region in a cast implant |
JP5232484B2 (en) * | 2008-01-31 | 2013-07-10 | 日本特殊陶業株式会社 | Biological implant |
US20090198286A1 (en) * | 2008-02-05 | 2009-08-06 | Zimmer, Inc. | Bone fracture fixation system |
US20090299156A1 (en) * | 2008-02-20 | 2009-12-03 | Dexcom, Inc. | Continuous medicament sensor system for in vivo use |
EP2252196A4 (en) | 2008-02-21 | 2013-05-15 | Dexcom Inc | Systems and methods for processing, transmitting and displaying sensor data |
US11730407B2 (en) | 2008-03-28 | 2023-08-22 | Dexcom, Inc. | Polymer membranes for continuous analyte sensors |
US8682408B2 (en) * | 2008-03-28 | 2014-03-25 | Dexcom, Inc. | Polymer membranes for continuous analyte sensors |
US8583204B2 (en) | 2008-03-28 | 2013-11-12 | Dexcom, Inc. | Polymer membranes for continuous analyte sensors |
WO2009121026A1 (en) | 2008-03-28 | 2009-10-01 | Dexcom, Inc. | Polymer membranes for continuous analyte sensors |
US20090259118A1 (en) * | 2008-03-31 | 2009-10-15 | Abbott Diabetes Care Inc. | Shallow Implantable Analyte Sensor with Rapid Physiological Response |
JP5328203B2 (en) | 2008-03-31 | 2013-10-30 | ユニ・チャーム株式会社 | Disposable absorbent wearing articles |
US8252229B2 (en) * | 2008-04-10 | 2012-08-28 | Abbott Diabetes Care Inc. | Method and system for sterilizing an analyte sensor |
US8924159B2 (en) | 2008-05-30 | 2014-12-30 | Abbott Diabetes Care Inc. | Method and apparatus for providing glycemic control |
US8591410B2 (en) * | 2008-05-30 | 2013-11-26 | Abbott Diabetes Care Inc. | Method and apparatus for providing glycemic control |
US7826382B2 (en) | 2008-05-30 | 2010-11-02 | Abbott Diabetes Care Inc. | Close proximity communication device and methods |
US20090300616A1 (en) * | 2008-05-30 | 2009-12-03 | Abbott Diabetes Care, Inc. | Automated task execution for an analyte monitoring system |
US8876755B2 (en) | 2008-07-14 | 2014-11-04 | Abbott Diabetes Care Inc. | Closed loop control system interface and methods |
EP2149957B1 (en) * | 2008-07-30 | 2017-06-14 | Harman Becker Automotive Systems GmbH | Priority based power distribution arrangement |
US8734422B2 (en) | 2008-08-31 | 2014-05-27 | Abbott Diabetes Care Inc. | Closed loop control with improved alarm functions |
US20100057040A1 (en) | 2008-08-31 | 2010-03-04 | Abbott Diabetes Care, Inc. | Robust Closed Loop Control And Methods |
US8622988B2 (en) | 2008-08-31 | 2014-01-07 | Abbott Diabetes Care Inc. | Variable rate closed loop control and methods |
US9943644B2 (en) * | 2008-08-31 | 2018-04-17 | Abbott Diabetes Care Inc. | Closed loop control with reference measurement and methods thereof |
EP3795987B1 (en) | 2008-09-19 | 2023-10-25 | Dexcom, Inc. | Particle-containing membrane and particulate electrode for analyte sensors |
US20100082364A1 (en) * | 2008-09-30 | 2010-04-01 | Abbott Diabetes Care, Inc. | Medical Information Management |
US8986208B2 (en) | 2008-09-30 | 2015-03-24 | Abbott Diabetes Care Inc. | Analyte sensor sensitivity attenuation mitigation |
US9326707B2 (en) | 2008-11-10 | 2016-05-03 | Abbott Diabetes Care Inc. | Alarm characterization for analyte monitoring devices and systems |
US8103456B2 (en) | 2009-01-29 | 2012-01-24 | Abbott Diabetes Care Inc. | Method and device for early signal attenuation detection using blood glucose measurements |
US8560082B2 (en) | 2009-01-30 | 2013-10-15 | Abbott Diabetes Care Inc. | Computerized determination of insulin pump therapy parameters using real time and retrospective data processing |
US9402544B2 (en) | 2009-02-03 | 2016-08-02 | Abbott Diabetes Care Inc. | Analyte sensor and apparatus for insertion of the sensor |
US10136816B2 (en) | 2009-08-31 | 2018-11-27 | Abbott Diabetes Care Inc. | Medical devices and methods |
WO2010114942A1 (en) * | 2009-03-31 | 2010-10-07 | Abbott Diabetes Care Inc. | Precise fluid dispensing method and device |
US8497777B2 (en) | 2009-04-15 | 2013-07-30 | Abbott Diabetes Care Inc. | Analyte monitoring system having an alert |
WO2010127050A1 (en) | 2009-04-28 | 2010-11-04 | Abbott Diabetes Care Inc. | Error detection in critical repeating data in a wireless sensor system |
WO2010127052A1 (en) * | 2009-04-28 | 2010-11-04 | Abbott Diabetes Care Inc. | Dynamic analyte sensor calibration based on sensor stability profile |
WO2010129375A1 (en) | 2009-04-28 | 2010-11-11 | Abbott Diabetes Care Inc. | Closed loop blood glucose control algorithm analysis |
EP2425209A4 (en) | 2009-04-29 | 2013-01-09 | Abbott Diabetes Care Inc | Method and system for providing real time analyte sensor calibration with retrospective backfill |
WO2010127187A1 (en) | 2009-04-29 | 2010-11-04 | Abbott Diabetes Care Inc. | Method and system for providing data communication in continuous glucose monitoring and management system |
PT2295132T (en) | 2009-05-15 | 2016-11-15 | Interface Biologics Inc | Antithrombogenic hollow fiber membranes, potting material and blood tubing |
US9184490B2 (en) | 2009-05-29 | 2015-11-10 | Abbott Diabetes Care Inc. | Medical device antenna systems having external antenna configurations |
US8613892B2 (en) | 2009-06-30 | 2013-12-24 | Abbott Diabetes Care Inc. | Analyte meter with a moveable head and methods of using the same |
ES2888427T3 (en) | 2009-07-23 | 2022-01-04 | Abbott Diabetes Care Inc | Real-time management of data related to the physiological control of glucose levels |
EP3689237B1 (en) | 2009-07-23 | 2021-05-19 | Abbott Diabetes Care, Inc. | Method of manufacturing and system for continuous analyte measurement |
WO2011012848A1 (en) | 2009-07-27 | 2011-02-03 | Suresensors Ltd | Improvements relating to sensor devices |
WO2011014851A1 (en) | 2009-07-31 | 2011-02-03 | Abbott Diabetes Care Inc. | Method and apparatus for providing analyte monitoring system calibration accuracy |
US9314195B2 (en) | 2009-08-31 | 2016-04-19 | Abbott Diabetes Care Inc. | Analyte signal processing device and methods |
WO2011026148A1 (en) | 2009-08-31 | 2011-03-03 | Abbott Diabetes Care Inc. | Analyte monitoring system and methods for managing power and noise |
ES2950160T3 (en) | 2009-08-31 | 2023-10-05 | Abbott Diabetes Care Inc | Displays for a medical device |
WO2011041469A1 (en) | 2009-09-29 | 2011-04-07 | Abbott Diabetes Care Inc. | Method and apparatus for providing notification function in analyte monitoring systems |
US8185181B2 (en) | 2009-10-30 | 2012-05-22 | Abbott Diabetes Care Inc. | Method and apparatus for detecting false hypoglycemic conditions |
US8372423B2 (en) | 2009-11-25 | 2013-02-12 | Healionics Corporation | Implantable medical devices having microporous surface layers and method for reducing foreign body response to the same |
CA2781518C (en) | 2009-11-25 | 2016-08-23 | Healionics Corporation | Granules of porous biocompatible materials |
US20110184258A1 (en) * | 2010-01-28 | 2011-07-28 | Abbott Diabetes Care Inc. | Balloon Catheter Analyte Measurement Sensors and Methods for Using the Same |
USD924406S1 (en) | 2010-02-01 | 2021-07-06 | Abbott Diabetes Care Inc. | Analyte sensor inserter |
WO2011112753A1 (en) | 2010-03-10 | 2011-09-15 | Abbott Diabetes Care Inc. | Systems, devices and methods for managing glucose levels |
EP4245220A3 (en) | 2010-03-24 | 2023-12-20 | Abbott Diabetes Care, Inc. | Medical device inserters |
FR2960783B1 (en) * | 2010-06-04 | 2012-07-27 | Ass Pour Les Transferts De Technologies Du Mans | FUNCTIONALIZED MEMBRANE FOR ENCAPSULATING CHAMBER OF CELLS PRODUCING AT LEAST ONE SUBSTANCE OF THERAPEUTIC INTEREST AND BIOARTIFICIAL ORGAN COMPRISING SUCH A MEMBRANE |
US8635046B2 (en) | 2010-06-23 | 2014-01-21 | Abbott Diabetes Care Inc. | Method and system for evaluating analyte sensor response characteristics |
US11064921B2 (en) | 2010-06-29 | 2021-07-20 | Abbott Diabetes Care Inc. | Devices, systems and methods for on-skin or on-body mounting of medical devices |
US10092229B2 (en) | 2010-06-29 | 2018-10-09 | Abbott Diabetes Care Inc. | Calibration of analyte measurement system |
US9475709B2 (en) | 2010-08-25 | 2016-10-25 | Lockheed Martin Corporation | Perforated graphene deionization or desalination |
WO2012048168A2 (en) | 2010-10-07 | 2012-04-12 | Abbott Diabetes Care Inc. | Analyte monitoring devices and methods |
US20140114436A1 (en) * | 2011-02-17 | 2014-04-24 | Patrick A. Tresco | Medical devices and methods for improving the biocompatibility of medical devices |
CA3177983A1 (en) | 2011-02-28 | 2012-11-15 | Abbott Diabetes Care Inc. | Devices, systems, and methods associated with analyte monitoring devices and devices incorporating the same |
US10136845B2 (en) | 2011-02-28 | 2018-11-27 | Abbott Diabetes Care Inc. | Devices, systems, and methods associated with analyte monitoring devices and devices incorporating the same |
EP4233718A3 (en) | 2011-04-08 | 2023-10-04 | DexCom, Inc. | Systems and methods for processing and transmitting sensor data |
JP6141827B2 (en) | 2011-04-15 | 2017-06-07 | デックスコム・インコーポレーテッド | Method of operating a system for measuring an analyte and sensor system configured to implement the method |
KR20140082642A (en) | 2011-07-26 | 2014-07-02 | 글리젠스 인코포레이티드 | Tissue implantable sensor with hermetically sealed housing |
EP3888551A1 (en) | 2011-09-23 | 2021-10-06 | Dexcom, Inc. | Systems and methods for processing and transmitting sensor data |
WO2013066873A1 (en) | 2011-10-31 | 2013-05-10 | Abbott Diabetes Care Inc. | Electronic devices having integrated reset systems and methods thereof |
US9622691B2 (en) | 2011-10-31 | 2017-04-18 | Abbott Diabetes Care Inc. | Model based variable risk false glucose threshold alarm prevention mechanism |
EP2775918B1 (en) | 2011-11-07 | 2020-02-12 | Abbott Diabetes Care Inc. | Analyte monitoring device and methods |
US8710993B2 (en) | 2011-11-23 | 2014-04-29 | Abbott Diabetes Care Inc. | Mitigating single point failure of devices in an analyte monitoring system and methods thereof |
US9317656B2 (en) | 2011-11-23 | 2016-04-19 | Abbott Diabetes Care Inc. | Compatibility mechanisms for devices in a continuous analyte monitoring system and methods thereof |
CA2840642C (en) | 2011-12-11 | 2022-01-18 | Abbott Diabetes Care Inc. | Analyte sensor devices, connections, and methods |
US9446031B2 (en) | 2012-01-18 | 2016-09-20 | National University Of Singapore | Compositions and methods for neovascularization |
US9615779B2 (en) | 2012-04-04 | 2017-04-11 | Dexcom, Inc. | Transcutaneous analyte sensors, applicators therefor, and associated methods |
US9744617B2 (en) | 2014-01-31 | 2017-08-29 | Lockheed Martin Corporation | Methods for perforating multi-layer graphene through ion bombardment |
US9870895B2 (en) | 2014-01-31 | 2018-01-16 | Lockheed Martin Corporation | Methods for perforating two-dimensional materials using a broad ion field |
US10376845B2 (en) | 2016-04-14 | 2019-08-13 | Lockheed Martin Corporation | Membranes with tunable selectivity |
US9834809B2 (en) | 2014-02-28 | 2017-12-05 | Lockheed Martin Corporation | Syringe for obtaining nano-sized materials for selective assays and related methods of use |
US10653824B2 (en) | 2012-05-25 | 2020-05-19 | Lockheed Martin Corporation | Two-dimensional materials and uses thereof |
US9610546B2 (en) | 2014-03-12 | 2017-04-04 | Lockheed Martin Corporation | Separation membranes formed from perforated graphene and methods for use thereof |
US10453573B2 (en) | 2012-06-05 | 2019-10-22 | Dexcom, Inc. | Dynamic report building |
US10598627B2 (en) | 2012-06-29 | 2020-03-24 | Dexcom, Inc. | Devices, systems, and methods to compensate for effects of temperature on implantable sensors |
US10881339B2 (en) | 2012-06-29 | 2021-01-05 | Dexcom, Inc. | Use of sensor redundancy to detect sensor failures |
US20140012511A1 (en) | 2012-07-09 | 2014-01-09 | Dexcom, Inc. | Systems and methods for leveraging smartphone features in continuous glucose monitoring |
US10561353B2 (en) * | 2016-06-01 | 2020-02-18 | Glysens Incorporated | Biocompatible implantable sensor apparatus and methods |
US10660550B2 (en) | 2015-12-29 | 2020-05-26 | Glysens Incorporated | Implantable sensor apparatus and methods |
EP2890297B1 (en) | 2012-08-30 | 2018-04-11 | Abbott Diabetes Care, Inc. | Dropout detection in continuous analyte monitoring data during data excursions |
US9968306B2 (en) | 2012-09-17 | 2018-05-15 | Abbott Diabetes Care Inc. | Methods and apparatuses for providing adverse condition notification with enhanced wireless communication range in analyte monitoring systems |
EP2901153A4 (en) | 2012-09-26 | 2016-04-27 | Abbott Diabetes Care Inc | Method and apparatus for improving lag correction during in vivo measurement of analyte concentration with analyte concentration variability and range data |
US9788765B2 (en) | 2012-09-28 | 2017-10-17 | Dexcom, Inc. | Zwitterion surface modifications for continuous sensors |
US20140129151A1 (en) | 2012-11-07 | 2014-05-08 | Dexcom, Inc. | Systems and methods for managing glycemic variability |
US9427182B2 (en) * | 2012-12-28 | 2016-08-30 | Senseonics, Incorporated | Analyte permeable membrane systems for oxidative and optical stability |
US11109779B2 (en) | 2012-12-28 | 2021-09-07 | Senseonics, Incorporated | Chemical modification of analyte permeable membrane for enhanced oxidative stability |
US9801541B2 (en) | 2012-12-31 | 2017-10-31 | Dexcom, Inc. | Remote monitoring of analyte measurements |
US9730620B2 (en) | 2012-12-31 | 2017-08-15 | Dexcom, Inc. | Remote monitoring of analyte measurements |
WO2014164621A1 (en) | 2013-03-12 | 2014-10-09 | Lockheed Martin Corporation | Method for forming filter with uniform aperture size |
US9788354B2 (en) | 2013-03-14 | 2017-10-10 | Dexcom, Inc. | Systems and methods for processing and transmitting sensor data |
US10405961B2 (en) | 2013-03-14 | 2019-09-10 | Cell and Molecular Tissue Engineering, LLC | Coated surgical mesh, and corresponding systems and methods |
EP4220654A1 (en) | 2013-03-14 | 2023-08-02 | Dexcom, Inc. | Systems and methods for processing and transmitting sensor data |
US10130288B2 (en) | 2013-03-14 | 2018-11-20 | Cell and Molecular Tissue Engineering, LLC | Coated sensors, and corresponding systems and methods |
US10335075B2 (en) | 2013-03-14 | 2019-07-02 | Dexcom, Inc. | Advanced calibration for analyte sensors |
US10433773B1 (en) | 2013-03-15 | 2019-10-08 | Abbott Diabetes Care Inc. | Noise rejection methods and apparatus for sparsely sampled analyte sensor data |
US9474475B1 (en) | 2013-03-15 | 2016-10-25 | Abbott Diabetes Care Inc. | Multi-rate analyte sensor data collection with sample rate configurable signal processing |
US10076285B2 (en) | 2013-03-15 | 2018-09-18 | Abbott Diabetes Care Inc. | Sensor fault detection using analyte sensor data pattern comparison |
US9572918B2 (en) | 2013-06-21 | 2017-02-21 | Lockheed Martin Corporation | Graphene-based filter for isolating a substance from blood |
WO2015087326A1 (en) | 2013-12-10 | 2015-06-18 | Nova Plasma Ltd. | Container, apparatus and method for handling an implant |
CA2933166C (en) | 2013-12-31 | 2020-10-27 | Abbott Diabetes Care Inc. | Self-powered analyte sensor and devices using the same |
KR20160142282A (en) | 2014-01-31 | 2016-12-12 | 록히드 마틴 코포레이션 | Processes for forming composite structures with a two-dimensional material using a porous, non-sacrificial supporting layer |
JP2017512129A (en) | 2014-03-12 | 2017-05-18 | ロッキード・マーチン・コーポレーション | Separation membranes formed from perforated graphene |
EP4151150A1 (en) | 2014-03-30 | 2023-03-22 | Abbott Diabetes Care, Inc. | Method and apparatus for determining meal start and peak events in analyte monitoring systems |
EP4257044A2 (en) | 2014-04-10 | 2023-10-11 | DexCom, Inc. | Sensor for continuous analyte monitoring |
EA201790508A1 (en) | 2014-09-02 | 2017-08-31 | Локхид Мартин Корпорейшн | HEMODIALYSIS AND HEMOPHILTRATION MEMBRANES BASED ON TWO-DIMENSIONAL MEMBRANE MATERIAL AND METHODS OF THEIR APPLICATION |
WO2016181396A1 (en) * | 2015-05-11 | 2016-11-17 | Nova Plasma Ltd. | Apparatus and method for handling an implant |
WO2016183493A1 (en) | 2015-05-14 | 2016-11-17 | Abbott Diabetes Care Inc. | Compact medical device inserters and related systems and methods |
US10213139B2 (en) | 2015-05-14 | 2019-02-26 | Abbott Diabetes Care Inc. | Systems, devices, and methods for assembling an applicator and sensor control device |
US20180125780A1 (en) | 2015-05-15 | 2018-05-10 | The Methodist Hospital System | Implantable nanochannel delivery devices |
AU2016291569B2 (en) | 2015-07-10 | 2021-07-08 | Abbott Diabetes Care Inc. | System, device and method of dynamic glucose profile response to physiological parameters |
CA2994549A1 (en) | 2015-08-05 | 2017-02-09 | Lockheed Martin Corporation | Perforatable sheets of graphene-based material |
JP2018530499A (en) | 2015-08-06 | 2018-10-18 | ロッキード・マーチン・コーポレーション | Nanoparticle modification and perforation of graphene |
AU2016341945B2 (en) | 2015-10-21 | 2019-06-13 | Dexcom, Inc. | Transcutaneous analyte sensors, applicators therefor, and associated methods |
WO2017116692A1 (en) | 2015-12-28 | 2017-07-06 | Dexcom, Inc. | Systems and methods for remote and host monitoring communications |
US20170188922A1 (en) | 2015-12-30 | 2017-07-06 | Dexcom, Inc. | Biointerface layer for analyte sensors |
US10561349B2 (en) | 2016-03-31 | 2020-02-18 | Dexcom, Inc. | Systems and methods for display device and sensor electronics unit communication |
WO2017180133A1 (en) | 2016-04-14 | 2017-10-19 | Lockheed Martin Corporation | Methods for in situ monitoring and control of defect formation or healing |
WO2017180134A1 (en) | 2016-04-14 | 2017-10-19 | Lockheed Martin Corporation | Methods for in vivo and in vitro use of graphene and other two-dimensional materials |
JP2019521055A (en) | 2016-04-14 | 2019-07-25 | ロッキード・マーチン・コーポレーション | Selective interface relaxation of graphene defects |
JP2019517909A (en) | 2016-04-14 | 2019-06-27 | ロッキード・マーチン・コーポレーション | Two-dimensional membrane structure having a flow path |
SG11201808962RA (en) | 2016-04-14 | 2018-11-29 | Lockheed Corp | Method for treating graphene sheets for large-scale transfer using free-float method |
FI3455269T3 (en) | 2016-05-10 | 2023-11-30 | Evonik Canada Inc | Implantable glucose sensors having a biostable surface |
US10638962B2 (en) * | 2016-06-29 | 2020-05-05 | Glysens Incorporated | Bio-adaptable implantable sensor apparatus and methods |
WO2018075663A1 (en) | 2016-10-18 | 2018-04-26 | Interface Biologics, Inc. | Plasticized pvc admixtures with surface modifying macromolecules and articles made therefrom |
WO2018136898A1 (en) | 2017-01-23 | 2018-07-26 | Abbott Diabetes Care Inc. | Systems, devices and methods for analyte sensor insertion |
WO2018175489A1 (en) | 2017-03-21 | 2018-09-27 | Abbott Diabetes Care Inc. | Methods, devices and system for providing diabetic condition diagnosis and therapy |
ES2963745T3 (en) | 2017-06-23 | 2024-04-01 | Dexcom Inc | Transcutaneous analyte sensors, applicators thereof and needle cone that include anti-twist function |
US10638979B2 (en) | 2017-07-10 | 2020-05-05 | Glysens Incorporated | Analyte sensor data evaluation and error reduction apparatus and methods |
IL272671B2 (en) | 2017-08-16 | 2024-01-01 | Nova Plasma Ltd | Plasma treating an implant |
CA3116829A1 (en) * | 2017-10-17 | 2019-04-25 | The Methodist Hospital System | Delivery devices |
US11331022B2 (en) | 2017-10-24 | 2022-05-17 | Dexcom, Inc. | Pre-connected analyte sensors |
AU2018354120A1 (en) | 2017-10-24 | 2020-04-23 | Dexcom, Inc. | Pre-connected analyte sensors |
US11278668B2 (en) | 2017-12-22 | 2022-03-22 | Glysens Incorporated | Analyte sensor and medicant delivery data evaluation and error reduction apparatus and methods |
US11255839B2 (en) | 2018-01-04 | 2022-02-22 | Glysens Incorporated | Apparatus and methods for analyte sensor mismatch correction |
WO2019157421A1 (en) * | 2018-02-09 | 2019-08-15 | W. L. Gore & Associates, Inc. | Implantable access chamber and associated methods of use |
RU2754453C1 (en) | 2018-02-28 | 2021-09-02 | Ф. Хоффманн-Ля Рош Аг | Biocompatibility-ensuring coating for continuous analyte measurement |
EP3873342A4 (en) | 2018-11-02 | 2022-08-10 | Senseonics, Incorporated | Drug eluting matrix on analyte indicator |
USD1002852S1 (en) | 2019-06-06 | 2023-10-24 | Abbott Diabetes Care Inc. | Analyte sensor device |
CN113750290A (en) * | 2020-06-03 | 2021-12-07 | 深圳先进技术研究院 | Polyether-ether-ketone composite implant and preparation method and application thereof |
USD999913S1 (en) | 2020-12-21 | 2023-09-26 | Abbott Diabetes Care Inc | Analyte sensor inserter |
US20220296867A1 (en) | 2021-03-19 | 2022-09-22 | Dexcom, Inc. | Drug releasing membrane for analyte sensor |
AU2022249389A1 (en) | 2021-04-02 | 2023-11-02 | Dexcom, Inc. | Personalized modeling of blood glucose concentration impacted by individualized sensor characteristics and individualized physiological characteristics |
WO2023043908A1 (en) | 2021-09-15 | 2023-03-23 | Dexcom, Inc. | Bioactive releasing membrane for analyte sensor |
CN114748208B (en) * | 2022-04-15 | 2024-01-12 | 柔脉医疗(深圳)有限公司 | Tissue engineering scaffold capable of in-situ detecting multiple chemical and biological components |
US20240090802A1 (en) | 2022-09-02 | 2024-03-21 | Dexcom, Inc. | Continuous analyte sensor devices and methods |
Family Cites Families (397)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19852258A1 (en) | 1998-11-11 | 2000-05-18 | Agfa Gevaert Ag | Radiation-sensitive recording material for the production of waterless offset printing plates |
US3016448A (en) * | 1959-09-04 | 1962-01-09 | Western Electric Co | Automatic wiring machine |
USRE31916E (en) * | 1970-11-10 | 1985-06-18 | Becton Dickinson & Company | Electrochemical detection cell |
GB1412983A (en) | 1971-11-30 | 1975-11-05 | Debell & Richardson | Method of producing porous plastic materials |
US3943918A (en) * | 1971-12-02 | 1976-03-16 | Tel-Pac, Inc. | Disposable physiological telemetric device |
US3957651A (en) * | 1971-12-16 | 1976-05-18 | Chemical Systems Incorporated | Microporous polyester membranes and polymer assisted phase inversion process for their manufacture |
US3775182A (en) | 1972-02-25 | 1973-11-27 | Du Pont | Tubular electrochemical cell with coiled electrodes and compressed central spindle |
GB1442303A (en) | 1972-09-08 | 1976-07-14 | Radiometer As | Cell for electro-chemical analysis |
CS164231B2 (en) | 1972-09-28 | 1975-11-07 | ||
US3929971A (en) | 1973-03-30 | 1975-12-30 | Research Corp | Porous biomaterials and method of making same |
US3898984A (en) * | 1974-02-04 | 1975-08-12 | Us Navy | Ambulatory patient monitoring system |
US3966580A (en) | 1974-09-16 | 1976-06-29 | The University Of Utah | Novel protein-immobilizing hydrophobic polymeric membrane, process for producing same and apparatus employing same |
US3979274A (en) | 1975-09-24 | 1976-09-07 | The Yellow Springs Instrument Company, Inc. | Membrane for enzyme electrodes |
CH591237A5 (en) | 1975-11-06 | 1977-09-15 | Bbc Brown Boveri & Cie | |
US4040908A (en) | 1976-03-12 | 1977-08-09 | Children's Hospital Medical Center | Polarographic analysis of cholesterol and other macromolecular substances |
US4024312A (en) | 1976-06-23 | 1977-05-17 | Johnson & Johnson | Pressure-sensitive adhesive tape having extensible and elastic backing composed of a block copolymer |
JPS5921500B2 (en) | 1978-01-28 | 1984-05-21 | 東洋紡績株式会社 | Enzyme membrane for oxygen electrode |
US4172770A (en) | 1978-03-27 | 1979-10-30 | Technicon Instruments Corporation | Flow-through electrochemical system analytical method |
US4259540A (en) | 1978-05-30 | 1981-03-31 | Bell Telephone Laboratories, Incorporated | Filled cables |
US4215703A (en) | 1978-08-29 | 1980-08-05 | Willson James K V | Variable stiffness guide wire |
US4255500A (en) | 1979-03-29 | 1981-03-10 | General Electric Company | Vibration resistant electrochemical cell having deformed casing and method of making same |
US4253469A (en) * | 1979-04-20 | 1981-03-03 | The Narda Microwave Corporation | Implantable temperature probe |
DE2932761A1 (en) | 1979-08-13 | 1981-02-26 | Akzo Gmbh | POLYCARBONATE-POLYAETHER-COPOLYMER MEMBRANE |
JPS5627643A (en) | 1979-08-14 | 1981-03-18 | Toshiba Corp | Electrochemical measuring device |
US4260725A (en) * | 1979-12-10 | 1981-04-07 | Bausch & Lomb Incorporated | Hydrophilic contact lens made from polysiloxanes which are thermally bonded to polymerizable groups and which contain hydrophilic sidechains |
US4403984A (en) * | 1979-12-28 | 1983-09-13 | Biotek, Inc. | System for demand-based adminstration of insulin |
US4861830A (en) | 1980-02-29 | 1989-08-29 | Th. Goldschmidt Ag | Polymer systems suitable for blood-contacting surfaces of a biomedical device, and methods for forming |
SE419903B (en) | 1980-03-05 | 1981-08-31 | Enfors Sven Olof | enzyme electrode |
CA1174284A (en) | 1980-09-02 | 1984-09-11 | Medtronic, Inc. | Body implantable lead |
IE51643B1 (en) | 1980-10-15 | 1987-01-21 | Smith & Nephew Ass | Coated articles and materials suitable for coating |
US4353888A (en) | 1980-12-23 | 1982-10-12 | Sefton Michael V | Encapsulation of live animal cells |
US4436094A (en) | 1981-03-09 | 1984-03-13 | Evreka, Inc. | Monitor for continuous in vivo measurement of glucose concentration |
US4442841A (en) * | 1981-04-30 | 1984-04-17 | Mitsubishi Rayon Company Limited | Electrode for living bodies |
US4431004A (en) | 1981-10-27 | 1984-02-14 | Bessman Samuel P | Implantable glucose sensor |
US4415666A (en) | 1981-11-05 | 1983-11-15 | Miles Laboratories, Inc. | Enzyme electrode membrane |
US4418148A (en) | 1981-11-05 | 1983-11-29 | Miles Laboratories, Inc. | Multilayer enzyme electrode membrane |
US4494950A (en) * | 1982-01-19 | 1985-01-22 | The Johns Hopkins University | Plural module medication delivery system |
EP0098592A3 (en) | 1982-07-06 | 1985-08-21 | Fujisawa Pharmaceutical Co., Ltd. | Portable artificial pancreas |
DE3228551A1 (en) * | 1982-07-30 | 1984-02-02 | Siemens AG, 1000 Berlin und 8000 München | METHOD FOR DETERMINING SUGAR CONCENTRATION |
US4571292A (en) * | 1982-08-12 | 1986-02-18 | Case Western Reserve University | Apparatus for electrochemical measurements |
WO1984001715A1 (en) | 1982-10-25 | 1984-05-10 | Hellgren Lars G I | Enzyme composition for therapeutical and/or non-therapeutical cleaning, the use thereof and preparation of the composition |
US5059654A (en) | 1983-02-14 | 1991-10-22 | Cuno Inc. | Affinity matrices of modified polysaccharide supports |
US4506680A (en) | 1983-03-17 | 1985-03-26 | Medtronic, Inc. | Drug dispensing body implantable lead |
CA1226036A (en) | 1983-05-05 | 1987-08-25 | Irving J. Higgins | Analytical equipment and sensor electrodes therefor |
US4484987A (en) | 1983-05-19 | 1984-11-27 | The Regents Of The University Of California | Method and membrane applicable to implantable sensor |
US4650547A (en) | 1983-05-19 | 1987-03-17 | The Regents Of The University Of California | Method and membrane applicable to implantable sensor |
US4663824A (en) | 1983-07-05 | 1987-05-12 | Matsushita Electric Industrial Co., Ltd. | Aluminum electrolytic capacitor and a manufacturing method therefor |
US4554927A (en) | 1983-08-30 | 1985-11-26 | Thermometrics Inc. | Pressure and temperature sensor |
GB2149918A (en) | 1983-11-03 | 1985-06-19 | John Anderson | Sudden infant death syndrome monitor |
US4753652A (en) | 1984-05-04 | 1988-06-28 | Children's Medical Center Corporation | Biomaterial implants which resist calcification |
US4883057A (en) | 1984-05-09 | 1989-11-28 | Research Foundation, The City University Of New York | Cathodic electrochemical current arrangement with telemetric application |
US5171689A (en) | 1984-11-08 | 1992-12-15 | Matsushita Electric Industrial Co., Ltd. | Solid state bio-sensor |
US4702732A (en) | 1984-12-24 | 1987-10-27 | Trustees Of Boston University | Electrodes, electrode assemblies, methods, and systems for tissue stimulation and transdermal delivery of pharmacologically active ligands |
US4963595A (en) | 1985-01-04 | 1990-10-16 | Thoratec Laboratories Corporation | Polysiloxane-polylactone block copolymers |
US5235003A (en) | 1985-01-04 | 1993-08-10 | Thoratec Laboratories Corporation | Polysiloxane-polylactone block copolymers |
US4577642A (en) | 1985-02-27 | 1986-03-25 | Medtronic, Inc. | Drug dispensing body implantable lead employing molecular sieves and methods of fabrication |
US4781798A (en) | 1985-04-19 | 1988-11-01 | The Regents Of The University Of California | Transparent multi-oxygen sensor array and method of using same |
US4671288A (en) | 1985-06-13 | 1987-06-09 | The Regents Of The University Of California | Electrochemical cell sensor for continuous short-term use in tissues and blood |
US4680268A (en) * | 1985-09-18 | 1987-07-14 | Children's Hospital Medical Center | Implantable gas-containing biosensor and method for measuring an analyte such as glucose |
US4890620A (en) | 1985-09-20 | 1990-01-02 | The Regents Of The University Of California | Two-dimensional diffusion glucose substrate sensing electrode |
US4689309A (en) | 1985-09-30 | 1987-08-25 | Miles Laboratories, Inc. | Test device, method of manufacturing same and method of determining a component in a sample |
US4839296A (en) * | 1985-10-18 | 1989-06-13 | Chem-Elec, Inc. | Blood plasma test method |
US4776944A (en) | 1986-03-20 | 1988-10-11 | Jiri Janata | Chemical selective sensors utilizing admittance modulated membranes |
JPS62225513A (en) | 1986-03-26 | 1987-10-03 | Shin Etsu Chem Co Ltd | Block-graft copolymer and production thereof |
US4994167A (en) | 1986-04-15 | 1991-02-19 | Markwell Medical Institute, Inc. | Biological fluid measuring device |
US4757022A (en) | 1986-04-15 | 1988-07-12 | Markwell Medical Institute, Inc. | Biological fluid measuring device |
US4703756A (en) | 1986-05-06 | 1987-11-03 | The Regents Of The University Of California | Complete glucose monitoring system with an implantable, telemetered sensor module |
US4731726A (en) * | 1986-05-19 | 1988-03-15 | Healthware Corporation | Patient-operated glucose monitor and diabetes management system |
GB8612861D0 (en) | 1986-05-27 | 1986-07-02 | Cambridge Life Sciences | Immobilised enzyme biosensors |
US4935346A (en) | 1986-08-13 | 1990-06-19 | Lifescan, Inc. | Minimum procedure system for the determination of analytes |
US5002572A (en) | 1986-09-11 | 1991-03-26 | Picha George J | Biological implant with textured surface |
AU617667B2 (en) | 1986-11-04 | 1991-12-05 | Allergan, Inc. | Open-cell, silicone-elastomer medical implant and method for making |
US5007929B1 (en) | 1986-11-04 | 1994-08-30 | Medical Products Dev | Open-cell silicone-elastomer medical implant |
AT391063B (en) | 1987-01-08 | 1990-08-10 | Blum Gmbh Julius | CONNECTING FITTING FOR FASTENING THE RAILING OF A DRAWER |
US4935345A (en) | 1987-04-07 | 1990-06-19 | Arizona Board Of Regents | Implantable microelectronic biochemical sensor incorporating thin film thermopile |
US4759828A (en) | 1987-04-09 | 1988-07-26 | Nova Biomedical Corporation | Glucose electrode and method of determining glucose |
US5540828A (en) | 1987-06-08 | 1996-07-30 | Yacynych; Alexander | Method for making electrochemical sensors and biosensors having a polymer modified surface |
US4810470A (en) | 1987-06-19 | 1989-03-07 | Miles Inc. | Volume independent diagnostic device |
JPH07122624B2 (en) | 1987-07-06 | 1995-12-25 | ダイキン工業株式会社 | Biosensor |
US4805625A (en) * | 1987-07-08 | 1989-02-21 | Ad-Tech Medical Instrument Corporation | Sphenoidal electrode and insertion method |
FI77569C (en) | 1987-07-13 | 1989-04-10 | Huhtamaeki Oy | ANORDINATION FOR THE PURPOSE OF THE OPERATIONS AND THE OPERATIONS OF ELLER EN VAEVNAD. |
US4974929A (en) | 1987-09-22 | 1990-12-04 | Baxter International, Inc. | Fiber optical probe connector for physiologic measurement devices |
GB8725936D0 (en) | 1987-11-05 | 1987-12-09 | Genetics Int Inc | Sensing system |
US4852573A (en) * | 1987-12-04 | 1989-08-01 | Kennedy Philip R | Implantable neural electrode |
US4849458A (en) | 1988-06-17 | 1989-07-18 | Matrix Medica, Inc. | Segmented polyether polyurethane |
EP0353328A1 (en) | 1988-08-03 | 1990-02-07 | Dräger Nederland B.V. | A polarographic-amperometric three-electrode sensor |
US5458631A (en) * | 1989-01-06 | 1995-10-17 | Xavier; Ravi | Implantable catheter with electrical pulse nerve stimulators and drug delivery system |
US5269891A (en) | 1989-03-09 | 1993-12-14 | Novo Nordisk A/S | Method and apparatus for determination of a constituent in a fluid |
JPH02298855A (en) | 1989-03-20 | 1990-12-11 | Assoc Univ Inc | Electrochemical biosensor using immobilized enzyme and redox polymer |
US4986671A (en) | 1989-04-12 | 1991-01-22 | Luxtron Corporation | Three-parameter optical fiber sensor and system |
US4953552A (en) * | 1989-04-21 | 1990-09-04 | Demarzo Arthur P | Blood glucose monitoring system |
US4927407A (en) | 1989-06-19 | 1990-05-22 | Regents Of The University Of Minnesota | Cardiac assist pump with steady rate supply of fluid lubricant |
CH677149A5 (en) | 1989-07-07 | 1991-04-15 | Disetronic Ag | |
US4986271A (en) * | 1989-07-19 | 1991-01-22 | The University Of New Mexico | Vivo refillable glucose sensor |
US5431160A (en) | 1989-07-19 | 1995-07-11 | University Of New Mexico | Miniature implantable refillable glucose sensor and material therefor |
US5264104A (en) | 1989-08-02 | 1993-11-23 | Gregg Brian A | Enzyme electrodes |
US5101814A (en) | 1989-08-11 | 1992-04-07 | Palti Yoram Prof | System for monitoring and controlling blood glucose |
US5190041A (en) | 1989-08-11 | 1993-03-02 | Palti Yoram Prof | System for monitoring and controlling blood glucose |
US5050612A (en) * | 1989-09-12 | 1991-09-24 | Matsumura Kenneth N | Device for computer-assisted monitoring of the body |
JPH03133440A (en) * | 1989-10-18 | 1991-06-06 | Nishitomo:Kk | Clinical thermometer for ladies |
US5067491A (en) | 1989-12-08 | 1991-11-26 | Becton, Dickinson And Company | Barrier coating on blood contacting devices |
US5985129A (en) | 1989-12-14 | 1999-11-16 | The Regents Of The University Of California | Method for increasing the service life of an implantable sensor |
US5265608A (en) * | 1990-02-22 | 1993-11-30 | Medtronic, Inc. | Steroid eluting electrode for peripheral nerve stimulation |
US5031618A (en) | 1990-03-07 | 1991-07-16 | Medtronic, Inc. | Position-responsive neuro stimulator |
US5316008A (en) * | 1990-04-06 | 1994-05-31 | Casio Computer Co., Ltd. | Measurement of electrocardiographic wave and sphygmus |
US5165407A (en) | 1990-04-19 | 1992-11-24 | The University Of Kansas | Implantable glucose sensor |
US5331555A (en) * | 1990-05-11 | 1994-07-19 | Sharp Kabushiki Kaisha | Electronic apparatus |
IT1248934B (en) | 1990-06-01 | 1995-02-11 | Fidia Spa | BIOCOMPATIBLE PERFORATED MEMBRANES, PROCESSES FOR THEIR PREPARATION, THEIR USE AS A SUPPORT FOR THE IN VITRO GROWTH OF EPITHELIAL CELLS, ARTIFICIAL LEATHER THUS OBTAINED AND THEIR USE IN LEATHER TRANSPLANTS |
US5282844A (en) * | 1990-06-15 | 1994-02-01 | Medtronic, Inc. | High impedance, low polarization, low threshold miniature steriod eluting pacing lead electrodes |
DK0546021T3 (en) | 1990-08-28 | 1996-03-18 | Meadox Medicals Inc | Self-supporting woven blood vessel graft |
US5380536A (en) | 1990-10-15 | 1995-01-10 | The Board Of Regents, The University Of Texas System | Biocompatible microcapsules |
EP0507933B1 (en) | 1990-10-31 | 1996-05-22 | Baxter International Inc. | Close vascularization implant material |
US5713888A (en) | 1990-10-31 | 1998-02-03 | Baxter International, Inc. | Tissue implant systems |
US5314471A (en) | 1991-07-24 | 1994-05-24 | Baxter International Inc. | Tissue inplant systems and methods for sustaining viable high cell densities within a host |
US5344454A (en) | 1991-07-24 | 1994-09-06 | Baxter International Inc. | Closed porous chambers for implanting tissue in a host |
US5733336A (en) | 1990-10-31 | 1998-03-31 | Baxter International, Inc. | Ported tissue implant systems and methods of using same |
US5348788A (en) | 1991-01-30 | 1994-09-20 | Interpore Orthopaedics, Inc. | Mesh sheet with microscopic projections and holes |
US5593852A (en) | 1993-12-02 | 1997-01-14 | Heller; Adam | Subcutaneous glucose electrode |
JPH04278450A (en) | 1991-03-04 | 1992-10-05 | Adam Heller | Biosensor and method for analyzing subject |
US5397848A (en) | 1991-04-25 | 1995-03-14 | Allergan, Inc. | Enhancing the hydrophilicity of silicone polymers |
US5271736A (en) | 1991-05-13 | 1993-12-21 | Applied Medical Research | Collagen disruptive morphology for implants |
JP3118015B2 (en) | 1991-05-17 | 2000-12-18 | アークレイ株式会社 | Biosensor and separation and quantification method using the same |
FI88223C (en) | 1991-05-22 | 1993-04-13 | Polar Electro Oy | Telemetric transmitter unit |
JP3084642B2 (en) | 1991-05-30 | 2000-09-04 | 株式会社ジェルテック | Pad for dressing and method of manufacturing the same |
US5453278A (en) | 1991-07-24 | 1995-09-26 | Baxter International Inc. | Laminated barriers for tissue implants |
DE4130742A1 (en) | 1991-09-16 | 1993-03-18 | Inst Diabetestechnologie Gemei | METHOD AND ARRANGEMENT FOR DETERMINING THE CONCENTRATION OF INGREDIENTS IN BODY LIQUIDS |
EP0610254B1 (en) * | 1991-09-20 | 2004-09-01 | Amgen Inc. | Glial derived neurotrophic factor |
US5222980A (en) * | 1991-09-27 | 1993-06-29 | Medtronic, Inc. | Implantable heart-assist device |
US5322063A (en) | 1991-10-04 | 1994-06-21 | Eli Lilly And Company | Hydrophilic polyurethane membranes for electrochemical glucose sensors |
US5605162A (en) | 1991-10-15 | 1997-02-25 | Advanced Cardiovascular Systems, Inc. | Method for using a variable stiffness guidewire |
US5249576A (en) * | 1991-10-24 | 1993-10-05 | Boc Health Care, Inc. | Universal pulse oximeter probe |
US5866217A (en) | 1991-11-04 | 1999-02-02 | Possis Medical, Inc. | Silicone composite vascular graft |
US5310469A (en) | 1991-12-31 | 1994-05-10 | Abbott Laboratories | Biosensor with a membrane containing biologically active material |
DE69215204T2 (en) | 1992-01-29 | 1997-03-13 | Hewlett Packard Gmbh | Process and system for monitoring vital functions |
WO1993014693A1 (en) * | 1992-02-01 | 1993-08-05 | The Victoria University Of Manchester | Electrode |
NL9200207A (en) | 1992-02-05 | 1993-09-01 | Nedap Nv | IMPLANTABLE BIOMEDICAL SENSOR DEVICE, IN PARTICULAR FOR MEASUREMENT OF THE GLUCOSE CONCENTRATION. |
US5284140A (en) | 1992-02-11 | 1994-02-08 | Eli Lilly And Company | Acrylic copolymer membranes for biosensors |
US5382514A (en) * | 1992-03-31 | 1995-01-17 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | In vivo angiogenesis assay |
US5589563A (en) | 1992-04-24 | 1996-12-31 | The Polymer Technology Group | Surface-modifying endgroups for biomedical polymers |
ATE169941T1 (en) | 1992-04-24 | 1998-09-15 | Polymer Technology Group Inc | COPOLYMERS, AND NON-POROUS SEMI-PERMEABLE MEMBRANES MADE THEREOF AND THEIR USE FOR FILTERING MOLECULES IN A GIVEN MOLECULAR WEIGHT RANGE |
GB9211402D0 (en) | 1992-05-29 | 1992-07-15 | Univ Manchester | Sensor devices |
US5330521A (en) | 1992-06-29 | 1994-07-19 | Cohen Donald M | Low resistance implantable electrical leads |
JP2541081B2 (en) | 1992-08-28 | 1996-10-09 | 日本電気株式会社 | Biosensor and method of manufacturing and using biosensor |
EP1130387A1 (en) | 1992-10-01 | 2001-09-05 | Australian Membrane And Biotechnology Research Institute | Linker lipid for sensor membranes |
GB9221099D0 (en) | 1992-10-07 | 1992-11-18 | Ecossensors Ltd | Improvements in and relating to gas permeable membranes for amperometric gas electrodes |
US5387327A (en) * | 1992-10-19 | 1995-02-07 | Duquesne University Of The Holy Ghost | Implantable non-enzymatic electrochemical glucose sensor |
US5399671A (en) * | 1992-11-18 | 1995-03-21 | Kluger; Ronald | Specifically crosslinked hemoglobin with free functionality |
US6256522B1 (en) | 1992-11-23 | 2001-07-03 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Sensors for continuous monitoring of biochemicals and related method |
ZA938555B (en) | 1992-11-23 | 1994-08-02 | Lilly Co Eli | Technique to improve the performance of electrochemical sensors |
US5285513A (en) | 1992-11-30 | 1994-02-08 | At&T Bell Laboratories | Optical fiber cable provided with stabilized waterblocking material |
US5299571A (en) * | 1993-01-22 | 1994-04-05 | Eli Lilly And Company | Apparatus and method for implantation of sensors |
DE4329898A1 (en) * | 1993-09-04 | 1995-04-06 | Marcus Dr Besson | Wireless medical diagnostic and monitoring device |
WO1995008355A1 (en) * | 1993-09-24 | 1995-03-30 | Baxter International Inc. | Methods for enhancing vascularization of implant devices |
US5582184A (en) | 1993-10-13 | 1996-12-10 | Integ Incorporated | Interstitial fluid collection and constituent measurement |
JP3971454B2 (en) * | 1993-10-29 | 2007-09-05 | ザ トラスティーズ オブ ボストン ユニバーシティ | Physiologically stable compositions of butyric acid, butyrate, and derivatives as anti-neoplastic agents |
KR970010981B1 (en) | 1993-11-04 | 1997-07-05 | 엘지전자 주식회사 | Alcohol concentration measuring bio-sensor, manufacturing method and related apparatus |
US5545220A (en) | 1993-11-04 | 1996-08-13 | Lipomatrix Incorporated | Implantable prosthesis with open cell textured surface and method for forming same |
US5791344A (en) | 1993-11-19 | 1998-08-11 | Alfred E. Mann Foundation For Scientific Research | Patient monitoring system |
US5497772A (en) * | 1993-11-19 | 1996-03-12 | Alfred E. Mann Foundation For Scientific Research | Glucose monitoring system |
US5443080A (en) | 1993-12-22 | 1995-08-22 | Americate Transtech, Inc. | Integrated system for biological fluid constituent analysis |
US5437824A (en) | 1993-12-23 | 1995-08-01 | Moghan Medical Corp. | Method of forming a molded silicone foam implant having open-celled interstices |
US5549675A (en) | 1994-01-11 | 1996-08-27 | Baxter International, Inc. | Method for implanting tissue in a host |
DE4401400A1 (en) * | 1994-01-19 | 1995-07-20 | Ernst Prof Dr Pfeiffer | Method and arrangement for continuously monitoring the concentration of a metabolite |
US5391250A (en) | 1994-03-15 | 1995-02-21 | Minimed Inc. | Method of fabricating thin film sensors |
US5390671A (en) * | 1994-03-15 | 1995-02-21 | Minimed Inc. | Transcutaneous sensor insertion set |
AUPM506894A0 (en) * | 1994-04-14 | 1994-05-05 | Memtec Limited | Novel electrochemical cells |
US5569186A (en) | 1994-04-25 | 1996-10-29 | Minimed Inc. | Closed loop infusion pump system with removable glucose sensor |
US5584876A (en) | 1994-04-29 | 1996-12-17 | W. L. Gore & Associates, Inc. | Cell excluding sheath for vascular grafts |
DE4415896A1 (en) * | 1994-05-05 | 1995-11-09 | Boehringer Mannheim Gmbh | Analysis system for monitoring the concentration of an analyte in the blood of a patient |
US5484404A (en) | 1994-05-06 | 1996-01-16 | Alfred E. Mann Foundation For Scientific Research | Replaceable catheter system for physiological sensors, tissue stimulating electrodes and/or implantable fluid delivery systems |
EP0685735B1 (en) | 1994-06-03 | 2002-01-16 | Metrohm Ag | Voltammetric apparaus, indicating electrode arrangement for such apparatus, especially as a part of a tape cassette, and voltammetric method for serial analysis |
DE4422068A1 (en) * | 1994-06-23 | 1996-01-04 | Siemens Ag | Electro-catalytic glucose sensor in catheter form |
US5494562A (en) * | 1994-06-27 | 1996-02-27 | Ciba Corning Diagnostics Corp. | Electrochemical sensors |
US5529066A (en) * | 1994-06-27 | 1996-06-25 | Cb-Carmel Biotechnology Ltd. | Implantable capsule for enhancing cell electric signals |
US5480711A (en) * | 1994-07-12 | 1996-01-02 | Ruefer; Bruce G. | Nano-porous PTFE biomaterial |
US5513636A (en) * | 1994-08-12 | 1996-05-07 | Cb-Carmel Biotechnology Ltd. | Implantable sensor chip |
US5462051A (en) * | 1994-08-31 | 1995-10-31 | Colin Corporation | Medical communication system |
AT402452B (en) | 1994-09-14 | 1997-05-26 | Avl Verbrennungskraft Messtech | PLANAR SENSOR FOR DETECTING A CHEMICAL PARAMETER OF A SAMPLE |
US5624537A (en) | 1994-09-20 | 1997-04-29 | The University Of British Columbia - University-Industry Liaison Office | Biosensor and interface membrane |
US5807406A (en) | 1994-10-07 | 1998-09-15 | Baxter International Inc. | Porous microfabricated polymer membrane structures |
CA2159052C (en) | 1994-10-28 | 2007-03-06 | Rainer Alex | Injection device |
IE72524B1 (en) * | 1994-11-04 | 1997-04-23 | Elan Med Tech | Analyte-controlled liquid delivery device and analyte monitor |
US5590651A (en) | 1995-01-17 | 1997-01-07 | Temple University - Of The Commonwealth System Of Higher Education | Breathable liquid elimination analysis |
US5697366A (en) | 1995-01-27 | 1997-12-16 | Optical Sensors Incorporated | In situ calibration system for sensors located in a physiologic line |
US5837728A (en) | 1995-01-27 | 1998-11-17 | Molecular Design International | 9-cis retinoic acid esters and amides and uses thereof |
US5568806A (en) | 1995-02-16 | 1996-10-29 | Minimed Inc. | Transcutaneous sensor insertion set |
US5586553A (en) | 1995-02-16 | 1996-12-24 | Minimed Inc. | Transcutaneous sensor insertion set |
US5882494A (en) | 1995-03-27 | 1999-03-16 | Minimed, Inc. | Polyurethane/polyurea compositions containing silicone for biosensor membranes |
US5620579A (en) | 1995-05-05 | 1997-04-15 | Bayer Corporation | Apparatus for reduction of bias in amperometric sensors |
US5743262A (en) * | 1995-06-07 | 1998-04-28 | Masimo Corporation | Blood glucose monitoring system |
US5626561A (en) | 1995-06-07 | 1997-05-06 | Gore Hybrid Technologies, Inc. | Implantable containment apparatus for a therapeutical device and method for loading and reloading the device therein |
JPH10503964A (en) | 1995-06-07 | 1998-04-14 | ゴア ハイブリッド テクノロジーズ,インコーポレイティド | Implantable containment device for a therapeutic device and method for loading and reloading the device therein |
US5656707A (en) | 1995-06-16 | 1997-08-12 | Regents Of The University Of Minnesota | Highly cross-linked polymeric supports |
US5995860A (en) * | 1995-07-06 | 1999-11-30 | Thomas Jefferson University | Implantable sensor and system for measurement and control of blood constituent levels |
US6001471A (en) | 1995-08-11 | 1999-12-14 | 3M Innovative Properties Company | Removable adhesive tape with controlled sequential release |
US5628890A (en) | 1995-09-27 | 1997-05-13 | Medisense, Inc. | Electrochemical sensor |
US5972199A (en) | 1995-10-11 | 1999-10-26 | E. Heller & Company | Electrochemical analyte sensors using thermostable peroxidase |
US5855613A (en) | 1995-10-13 | 1999-01-05 | Islet Sheet Medical, Inc. | Retrievable bioartificial implants having dimensions allowing rapid diffusion of oxygen and rapid biological response to physiological change |
US6011984A (en) | 1995-11-22 | 2000-01-04 | Minimed Inc. | Detection of biological molecules using chemical amplification and optical sensors |
US5711861A (en) | 1995-11-22 | 1998-01-27 | Ward; W. Kenneth | Device for monitoring changes in analyte concentration |
US6063637A (en) | 1995-12-13 | 2000-05-16 | California Institute Of Technology | Sensors for sugars and other metal binding analytes |
CA2212826C (en) | 1995-12-28 | 2002-02-19 | Cygnus, Inc. | Methods for monitoring a physiological analyte |
US5833603A (en) | 1996-03-13 | 1998-11-10 | Lipomatrix, Inc. | Implantable biosensing transponder |
US20010011711A1 (en) * | 1996-05-03 | 2001-08-09 | Graham Nicholson | Container for nuclear fuel transportation |
US5776324A (en) | 1996-05-17 | 1998-07-07 | Encelle, Inc. | Electrochemical biosensors |
US5964261A (en) | 1996-05-29 | 1999-10-12 | Baxter International Inc. | Implantation assembly |
WO1998001071A1 (en) | 1996-07-08 | 1998-01-15 | Animas Corporation | Implantable sensor and system for in vivo measurement and control of fluid constituent levels |
JP2943700B2 (en) | 1996-07-10 | 1999-08-30 | 日本電気株式会社 | Biosensor |
US6325978B1 (en) | 1998-08-04 | 2001-12-04 | Ntc Technology Inc. | Oxygen monitoring and apparatus |
US6054142A (en) | 1996-08-01 | 2000-04-25 | Cyto Therapeutics, Inc. | Biocompatible devices with foam scaffolds |
US5804048A (en) * | 1996-08-15 | 1998-09-08 | Via Medical Corporation | Electrode assembly for assaying glucose |
DE19642453C2 (en) | 1996-10-15 | 1998-07-23 | Bosch Gmbh Robert | Arrangement for gas sensor electrodes |
DK0944731T3 (en) * | 1996-11-14 | 2006-05-22 | Radiometer Medical Aps | enzyme Sensor |
US5811487A (en) | 1996-12-16 | 1998-09-22 | Dow Corning Corporation | Thickening silicones with elastomeric silicone polyethers |
US5964993A (en) | 1996-12-19 | 1999-10-12 | Implanted Biosystems Inc. | Glucose sensor |
US5914026A (en) | 1997-01-06 | 1999-06-22 | Implanted Biosystems Inc. | Implantable sensor employing an auxiliary electrode |
US6607509B2 (en) | 1997-12-31 | 2003-08-19 | Medtronic Minimed, Inc. | Insertion device for an insertion set and method of using the same |
US5851197A (en) | 1997-02-05 | 1998-12-22 | Minimed Inc. | Injector for a subcutaneous infusion set |
US6093172A (en) | 1997-02-05 | 2000-07-25 | Minimed Inc. | Injector for a subcutaneous insertion set |
US6891317B2 (en) | 2001-05-22 | 2005-05-10 | Sri International | Rolled electroactive polymers |
US6208894B1 (en) | 1997-02-26 | 2001-03-27 | Alfred E. Mann Foundation For Scientific Research And Advanced Bionics | System of implantable devices for monitoring and/or affecting body parameters |
US7657297B2 (en) | 2004-05-03 | 2010-02-02 | Dexcom, Inc. | Implantable analyte sensor |
US6558321B1 (en) | 1997-03-04 | 2003-05-06 | Dexcom, Inc. | Systems and methods for remote monitoring and modulation of medical devices |
US6741877B1 (en) | 1997-03-04 | 2004-05-25 | Dexcom, Inc. | Device and method for determining analyte levels |
US6862465B2 (en) | 1997-03-04 | 2005-03-01 | Dexcom, Inc. | Device and method for determining analyte levels |
US6001067A (en) | 1997-03-04 | 1999-12-14 | Shults; Mark C. | Device and method for determining analyte levels |
US7192450B2 (en) * | 2003-05-21 | 2007-03-20 | Dexcom, Inc. | Porous membranes for use with implantable devices |
US20050033132A1 (en) | 1997-03-04 | 2005-02-10 | Shults Mark C. | Analyte measuring device |
FR2760962B1 (en) | 1997-03-20 | 1999-05-14 | Sillonville Francis Klefstad | REMOTE MEDICAL ASSISTANCE AND SURVEILLANCE SYSTEM |
US5961451A (en) | 1997-04-07 | 1999-10-05 | Motorola, Inc. | Noninvasive apparatus having a retaining member to retain a removable biosensor |
US6059946A (en) * | 1997-04-14 | 2000-05-09 | Matsushita Electric Industrial Co., Ltd. | Biosensor |
US5944661A (en) * | 1997-04-16 | 1999-08-31 | Giner, Inc. | Potential and diffusion controlled solid electrolyte sensor for continuous measurement of very low levels of transdermal alcohol |
AT404992B (en) | 1997-04-17 | 1999-04-26 | Avl List Gmbh | SENSOR FOR DETERMINING AN ENZYME SUBSTRATE |
US6115634A (en) | 1997-04-30 | 2000-09-05 | Medtronic, Inc. | Implantable medical device and method of manufacture |
US5779665A (en) | 1997-05-08 | 1998-07-14 | Minimed Inc. | Transdermal introducer assembly |
WO1998058250A2 (en) | 1997-06-16 | 1998-12-23 | Elan Corporation, Plc | Methods of calibrating and testing a sensor for in vivo measurement of an analyte and devices for use in such methods |
US6093167A (en) | 1997-06-16 | 2000-07-25 | Medtronic, Inc. | System for pancreatic stimulation and glucose measurement |
US6013711A (en) | 1997-06-18 | 2000-01-11 | Ck Witco Corporation | Hydrophilic polysiloxane compositions |
US5861019A (en) | 1997-07-25 | 1999-01-19 | Medtronic Inc. | Implantable medical device microstrip telemetry antenna |
US5871514A (en) | 1997-08-01 | 1999-02-16 | Medtronic, Inc. | Attachment apparatus for an implantable medical device employing ultrasonic energy |
GB9717906D0 (en) | 1997-08-23 | 1997-10-29 | Univ Manchester | Sensor Devices And Analytical Methods |
US6731976B2 (en) | 1997-09-03 | 2004-05-04 | Medtronic, Inc. | Device and method to measure and communicate body parameters |
US5999848A (en) | 1997-09-12 | 1999-12-07 | Alfred E. Mann Foundation | Daisy chainable sensors and stimulators for implantation in living tissue |
US5917346A (en) | 1997-09-12 | 1999-06-29 | Alfred E. Mann Foundation | Low power current to frequency converter circuit for use in implantable sensors |
US6259937B1 (en) | 1997-09-12 | 2001-07-10 | Alfred E. Mann Foundation | Implantable substrate sensor |
WO1999017095A1 (en) * | 1997-09-30 | 1999-04-08 | M-Biotech, Inc. | Biosensor |
US6296615B1 (en) | 1999-03-05 | 2001-10-02 | Data Sciences International, Inc. | Catheter with physiological sensor |
US5967986A (en) | 1997-11-25 | 1999-10-19 | Vascusense, Inc. | Endoluminal implant with fluid flow sensing capability |
US6409674B1 (en) | 1998-09-24 | 2002-06-25 | Data Sciences International, Inc. | Implantable sensor with wireless communication |
US6585763B1 (en) | 1997-10-14 | 2003-07-01 | Vascusense, Inc. | Implantable therapeutic device and method |
US6119028A (en) * | 1997-10-20 | 2000-09-12 | Alfred E. Mann Foundation | Implantable enzyme-based monitoring systems having improved longevity due to improved exterior surfaces |
US6104280A (en) | 1997-10-20 | 2000-08-15 | Micron Technology, Inc. | Method of manufacturing and testing an electronic device, and an electronic device |
US6081736A (en) * | 1997-10-20 | 2000-06-27 | Alfred E. Mann Foundation | Implantable enzyme-based monitoring systems adapted for long term use |
US6088608A (en) | 1997-10-20 | 2000-07-11 | Alfred E. Mann Foundation | Electrochemical sensor and integrity tests therefor |
CA2575064C (en) | 1997-12-31 | 2010-02-02 | Medtronic Minimed, Inc. | Insertion device for an insertion set and method of using the same |
US6134461A (en) | 1998-03-04 | 2000-10-17 | E. Heller & Company | Electrochemical analyte |
US6103033A (en) | 1998-03-04 | 2000-08-15 | Therasense, Inc. | Process for producing an electrochemical biosensor |
US6013113A (en) | 1998-03-06 | 2000-01-11 | Wilson Greatbatch Ltd. | Slotted insulator for unsealed electrode edges in electrochemical cells |
CA2265119C (en) * | 1998-03-13 | 2002-12-03 | Cygnus, Inc. | Biosensor, iontophoretic sampling system, and methods of use thereof |
US5904708A (en) | 1998-03-19 | 1999-05-18 | Medtronic, Inc. | System and method for deriving relative physiologic signals |
GB9805896D0 (en) | 1998-03-20 | 1998-05-13 | Eglise David | Remote analysis system |
JP3104672B2 (en) | 1998-03-31 | 2000-10-30 | 日本電気株式会社 | Current detection type sensor element and method of manufacturing the same |
US6091975A (en) * | 1998-04-01 | 2000-07-18 | Alza Corporation | Minimally invasive detecting device |
US6175767B1 (en) * | 1998-04-01 | 2001-01-16 | James H. Doyle, Sr. | Multichannel implantable inner ear stimulator |
US6537318B1 (en) | 1998-04-06 | 2003-03-25 | Konjac Technologies, Llc | Use of glucomannan hydrocolloid as filler material in prostheses |
US6241863B1 (en) | 1998-04-27 | 2001-06-05 | Harold G. Monbouquette | Amperometric biosensors based on redox enzymes |
US6175752B1 (en) | 1998-04-30 | 2001-01-16 | Therasense, Inc. | Analyte monitoring device and methods of use |
EP1077636B1 (en) | 1998-05-13 | 2004-01-21 | Cygnus, Inc. | Signal processing for measurement of physiological analytes |
PT1077634E (en) | 1998-05-13 | 2003-12-31 | Cygnus Therapeutic Systems | MONITORING OF PHYSIOLOGICAL SUBSTANCES TO BE ANALYZED |
US6129757A (en) | 1998-05-18 | 2000-10-10 | Scimed Life Systems | Implantable members for receiving therapeutically useful compositions |
US7540875B2 (en) | 1998-06-01 | 2009-06-02 | Avatar Design & Development, Inc. | Surgical cutting tool with automatically retractable blade assembly |
US6187062B1 (en) | 1998-06-16 | 2001-02-13 | Alcatel | Current collection through thermally sprayed tabs at the ends of a spirally wound electrochemical cell |
US6248067B1 (en) | 1999-02-05 | 2001-06-19 | Minimed Inc. | Analyte sensor and holter-type monitor system and method of using the same |
US6330464B1 (en) | 1998-08-26 | 2001-12-11 | Sensors For Medicine & Science | Optical-based sensing devices |
US6201980B1 (en) | 1998-10-05 | 2001-03-13 | The Regents Of The University Of California | Implantable medical sensor system |
US6591125B1 (en) | 2000-06-27 | 2003-07-08 | Therasense, Inc. | Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator |
US6338790B1 (en) | 1998-10-08 | 2002-01-15 | Therasense, Inc. | Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator |
US6016448A (en) | 1998-10-27 | 2000-01-18 | Medtronic, Inc. | Multilevel ERI for implantable medical devices |
US6156013A (en) | 1998-11-04 | 2000-12-05 | Mahurkar; Sakharam D. | Safety syringe |
US6641565B1 (en) | 1998-11-13 | 2003-11-04 | Elan Pharma International Limited | drug delivery systems and methods |
US20030099682A1 (en) * | 1998-11-20 | 2003-05-29 | Francis Moussy | Apparatus and method for control of tissue/implant interactions |
CA2351734A1 (en) * | 1998-11-20 | 2000-06-02 | University Of Connecticut | Generic integrated implantable potentiostat telemetry unit for electrochemical sensors |
US6066083A (en) * | 1998-11-27 | 2000-05-23 | Syntheon Llc | Implantable brachytherapy device having at least partial deactivation capability |
US6447448B1 (en) | 1998-12-31 | 2002-09-10 | Ball Semiconductor, Inc. | Miniature implanted orthopedic sensors |
US6309384B1 (en) | 1999-02-01 | 2001-10-30 | Adiana, Inc. | Method and apparatus for tubal occlusion |
US6360888B1 (en) | 1999-02-25 | 2002-03-26 | Minimed Inc. | Glucose sensor package system |
US6424847B1 (en) | 1999-02-25 | 2002-07-23 | Medtronic Minimed, Inc. | Glucose monitor calibration methods |
US6230059B1 (en) | 1999-03-17 | 2001-05-08 | Medtronic, Inc. | Implantable monitor |
US6285897B1 (en) * | 1999-04-07 | 2001-09-04 | Endonetics, Inc. | Remote physiological monitoring system |
US6189536B1 (en) | 1999-04-15 | 2001-02-20 | Medtronic Inc. | Method for protecting implantable devices |
CA2369336A1 (en) | 1999-04-22 | 2000-11-02 | Cygnus, Inc. | Hydrogel in an iontophoretic device to measure glucose |
US6475750B1 (en) | 1999-05-11 | 2002-11-05 | M-Biotech, Inc. | Glucose biosensor |
US6300002B1 (en) | 1999-05-13 | 2001-10-09 | Moltech Power Systems, Inc. | Notched electrode and method of making same |
US6546268B1 (en) | 1999-06-02 | 2003-04-08 | Ball Semiconductor, Inc. | Glucose sensor |
AU5747100A (en) | 1999-06-18 | 2001-01-09 | Therasense, Inc. | Mass transport limited in vivo analyte sensor |
US6991643B2 (en) * | 2000-12-20 | 2006-01-31 | Usgi Medical Inc. | Multi-barbed device for retaining tissue in apposition and methods of use |
US6368274B1 (en) | 1999-07-01 | 2002-04-09 | Medtronic Minimed, Inc. | Reusable analyte sensor site and method of using the same |
US7247138B2 (en) * | 1999-07-01 | 2007-07-24 | Medtronic Minimed, Inc. | Reusable analyte sensor site and method of using the same |
US6413393B1 (en) | 1999-07-07 | 2002-07-02 | Minimed, Inc. | Sensor including UV-absorbing polymer and method of manufacture |
US20020019330A1 (en) * | 1999-08-11 | 2002-02-14 | Richard Murray | Novel methods of diagnosis of angiogenesis, compositions, and methods of screening for angiogenesis modulators |
US6471689B1 (en) | 1999-08-16 | 2002-10-29 | Thomas Jefferson University | Implantable drug delivery catheter system with capillary interface |
US6346583B1 (en) | 1999-08-25 | 2002-02-12 | General Electric Company | Polar solvent compatible polyethersiloxane elastomers |
US6312469B1 (en) | 1999-09-13 | 2001-11-06 | Medtronic Inc. | Lamina prosthesis for delivery of medical treatment |
US6343225B1 (en) * | 1999-09-14 | 2002-01-29 | Implanted Biosystems, Inc. | Implantable glucose sensor |
US6541107B1 (en) | 1999-10-25 | 2003-04-01 | Dow Corning Corporation | Nanoporous silicone resins having low dielectric constants |
US6517508B1 (en) * | 1999-11-03 | 2003-02-11 | Dsu Medical Corporation | Set for blood processing |
US6527729B1 (en) | 1999-11-10 | 2003-03-04 | Pacesetter, Inc. | Method for monitoring patient using acoustic sensor |
JP3426549B2 (en) | 1999-11-12 | 2003-07-14 | 本田技研工業株式会社 | Exhaust pipe connection structure |
GB9928071D0 (en) * | 1999-11-29 | 2000-01-26 | Polybiomed Ltd | Blood compatible medical articles |
WO2001040272A2 (en) | 1999-12-01 | 2001-06-07 | Selective Genetics, Inc. | In situ bioreactors and methods of use thereof |
US6520997B1 (en) | 1999-12-08 | 2003-02-18 | Baxter International Inc. | Porous three dimensional structure |
US6813519B2 (en) | 2000-01-21 | 2004-11-02 | Medtronic Minimed, Inc. | Ambulatory medical apparatus and method using a robust communication protocol |
US6895263B2 (en) * | 2000-02-23 | 2005-05-17 | Medtronic Minimed, Inc. | Real time self-adjusting calibration algorithm |
US6743253B2 (en) | 2000-02-29 | 2004-06-01 | Biomod Surfaces | Polyurethane-sealed biocompatible device and method for its preparation |
US6551496B1 (en) | 2000-03-03 | 2003-04-22 | Ysi Incorporated | Microstructured bilateral sensor |
GB2367661B (en) * | 2000-03-09 | 2004-11-24 | Ibm | A method and system for managing objects |
US6365670B1 (en) | 2000-03-10 | 2002-04-02 | Wacker Silicones Corporation | Organopolysiloxane gels for use in cosmetics |
US6405066B1 (en) | 2000-03-17 | 2002-06-11 | The Regents Of The University Of California | Implantable analyte sensor |
AU2001263022A1 (en) | 2000-05-12 | 2001-11-26 | Therasense, Inc. | Electrodes with multilayer membranes and methods of using and making the electrodes |
US6442413B1 (en) * | 2000-05-15 | 2002-08-27 | James H. Silver | Implantable sensor |
US6459917B1 (en) | 2000-05-22 | 2002-10-01 | Ashok Gowda | Apparatus for access to interstitial fluid, blood, or blood plasma components |
JP3701608B2 (en) | 2000-05-23 | 2005-10-05 | ラジオメーター・メディカル・アー・ペー・エス | Sensor membrane, method for its preparation, sensor and layered membrane structure for such a sensor |
US6991652B2 (en) | 2000-06-13 | 2006-01-31 | Burg Karen J L | Tissue engineering composite |
US6773565B2 (en) * | 2000-06-22 | 2004-08-10 | Kabushiki Kaisha Riken | NOx sensor |
US6400974B1 (en) | 2000-06-29 | 2002-06-04 | Sensors For Medicine And Science, Inc. | Implanted sensor processing system and method for processing implanted sensor output |
US6569521B1 (en) | 2000-07-06 | 2003-05-27 | 3M Innovative Properties Company | Stretch releasing pressure sensitive adhesive tape and articles |
US6477392B1 (en) | 2000-07-14 | 2002-11-05 | Futrex Inc. | Calibration of near infrared quantitative measurement device using optical measurement cross-products |
US6683535B1 (en) | 2000-08-09 | 2004-01-27 | Alderon Industries, Llc | Water detection system and method |
DK1695727T3 (en) | 2000-11-09 | 2008-12-01 | Insulet Corp | Device for transcutaneous administration |
US6695860B1 (en) | 2000-11-13 | 2004-02-24 | Isense Corp. | Transcutaneous sensor insertion device |
US6642015B2 (en) | 2000-12-29 | 2003-11-04 | Minimed Inc. | Hydrophilic polymeric material for coating biosensors |
WO2002053193A2 (en) | 2001-01-02 | 2002-07-11 | The Charles Stark Draper Laboratory, Inc. | Tissue engineering of three-dimensional vascularized using microfabricated polymer assembly technology |
US6560471B1 (en) | 2001-01-02 | 2003-05-06 | Therasense, Inc. | Analyte monitoring device and methods of use |
US6793802B2 (en) * | 2001-01-04 | 2004-09-21 | Tyson Bioresearch, Inc. | Biosensors having improved sample application and measuring properties and uses thereof |
US7128904B2 (en) * | 2001-01-16 | 2006-10-31 | The Regents Of The University Of Michigan | Material containing metal ion ligand complex producing nitric oxide in contact with blood |
US6968743B2 (en) | 2001-01-22 | 2005-11-29 | Integrated Sensing Systems, Inc. | Implantable sensing device for physiologic parameter measurement |
US6547839B2 (en) | 2001-01-23 | 2003-04-15 | Skc Co., Ltd. | Method of making an electrochemical cell by the application of polysiloxane onto at least one of the cell components |
US7014610B2 (en) | 2001-02-09 | 2006-03-21 | Medtronic, Inc. | Echogenic devices and methods of making and using such devices |
US6721587B2 (en) | 2001-02-15 | 2004-04-13 | Regents Of The University Of California | Membrane and electrode structure for implantable sensor |
WO2002072167A1 (en) | 2001-03-13 | 2002-09-19 | Implant Sciences Corporation. | Drug eluting encapsulated stent |
FR2822383B1 (en) | 2001-03-23 | 2004-12-17 | Perouse Lab | PROSTHESIS FOR PLASTIC RECONSTRUCTION WITH IMPROVED HYDROPHILICITY PROPERTIES, AND METHOD FOR OBTAINING SAME |
US6379622B1 (en) * | 2001-04-11 | 2002-04-30 | Motorola, Inc. | Sensor incorporating a quantum dot as a reference |
US6454710B1 (en) | 2001-04-11 | 2002-09-24 | Motorola, Inc. | Devices and methods for monitoring an analyte |
US6528584B2 (en) * | 2001-04-12 | 2003-03-04 | The University Of Akron | Multi-component polymeric networks containing poly(ethylene glycol) |
US6613379B2 (en) | 2001-05-08 | 2003-09-02 | Isense Corp. | Implantable analyte sensor |
US6793632B2 (en) * | 2001-06-12 | 2004-09-21 | Lifescan, Inc. | Percutaneous biological fluid constituent sampling and measurement devices and methods |
US6501976B1 (en) | 2001-06-12 | 2002-12-31 | Lifescan, Inc. | Percutaneous biological fluid sampling and analyte measurement devices and methods |
JP2003022761A (en) * | 2001-07-06 | 2003-01-24 | Matsushita Electric Ind Co Ltd | Electron gun, cathode-ray tube using it, and manufacturing method of electron gun |
US20030032874A1 (en) | 2001-07-27 | 2003-02-13 | Dexcom, Inc. | Sensor head for use with implantable devices |
US6702857B2 (en) | 2001-07-27 | 2004-03-09 | Dexcom, Inc. | Membrane for use with implantable devices |
US20030025361A1 (en) * | 2001-07-31 | 2003-02-06 | Liu Lausan Chung-Hsin | Chair folding structure |
US6913626B2 (en) | 2001-08-14 | 2005-07-05 | Mcghan Jim J. | Medical implant having bioabsorbable textured surface |
US7025760B2 (en) | 2001-09-07 | 2006-04-11 | Medtronic Minimed, Inc. | Method and system for non-vascular sensor implantation |
US6809507B2 (en) | 2001-10-23 | 2004-10-26 | Medtronic Minimed, Inc. | Implantable sensor electrodes and electronic circuitry |
US6705833B2 (en) | 2001-11-15 | 2004-03-16 | Hewlett-Packard Development Company, L.P. | Airflow flapper valve |
US20040030294A1 (en) | 2001-11-28 | 2004-02-12 | Mahurkar Sakharam D. | Retractable needle single use safety syringe |
US6952604B2 (en) * | 2001-12-21 | 2005-10-04 | Becton, Dickinson And Company | Minimally-invasive system and method for monitoring analyte levels |
US7018336B2 (en) | 2001-12-27 | 2006-03-28 | Medtronic Minimed, Inc. | Implantable sensor flush sleeve |
US8364229B2 (en) | 2003-07-25 | 2013-01-29 | Dexcom, Inc. | Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise |
US8010174B2 (en) | 2003-08-22 | 2011-08-30 | Dexcom, Inc. | Systems and methods for replacing signal artifacts in a glucose sensor data stream |
US8858434B2 (en) | 2004-07-13 | 2014-10-14 | Dexcom, Inc. | Transcutaneous analyte sensor |
ATE507766T1 (en) | 2002-03-22 | 2011-05-15 | Animas Technologies Llc | PERFORMANCE IMPROVEMENT OF AN ANALYTE MONITORING DEVICE |
AU2003253590A1 (en) * | 2002-03-29 | 2003-11-10 | Board Of Regents For The Oklahoma Agricultural And Mechanical Colleges, Acting For And On Behalf Of Oklahoma State University | Implantable biosensor from stratified nanostructured membranes |
US7133712B2 (en) | 2002-04-05 | 2006-11-07 | Eyelab Group, Llc | Method and apparatus for non-invasive monitoring of blood substances using self-sampled tears |
US7153265B2 (en) | 2002-04-22 | 2006-12-26 | Medtronic Minimed, Inc. | Anti-inflammatory biosensor for reduced biofouling and enhanced sensor performance |
US7226978B2 (en) | 2002-05-22 | 2007-06-05 | Dexcom, Inc. | Techniques to improve polyurethane membranes for implantable glucose sensors |
WO2003101862A1 (en) | 2002-05-31 | 2003-12-11 | Dow Corning Toray Silicone Co.,Ltd. | Cartridge for moisture-curable sealant |
US6835387B2 (en) * | 2002-06-11 | 2004-12-28 | Scimed Life Systems, Inc. | Sustained release of superoxide dismutase mimics from implantable or insertable medical devices |
JP2005531759A (en) * | 2002-06-28 | 2005-10-20 | ノヴェンバー アクティエンゲゼルシャフト | Electrochemical detection apparatus and method |
US7233649B2 (en) * | 2002-07-12 | 2007-06-19 | Utstarcom, Inc. | Faster modem method and apparatus |
US20040010207A1 (en) | 2002-07-15 | 2004-01-15 | Flaherty J. Christopher | Self-contained, automatic transcutaneous physiologic sensing system |
US20040068230A1 (en) | 2002-07-24 | 2004-04-08 | Medtronic Minimed, Inc. | System for providing blood glucose measurements to an infusion device |
US20050272989A1 (en) | 2004-06-04 | 2005-12-08 | Medtronic Minimed, Inc. | Analyte sensors and methods for making and using them |
WO2004061420A2 (en) | 2002-12-31 | 2004-07-22 | Therasense, Inc. | Continuous glucose monitoring system and methods of use |
US6965791B1 (en) | 2003-03-26 | 2005-11-15 | Sorenson Medical, Inc. | Implantable biosensor system, apparatus and method |
WO2004085098A2 (en) * | 2003-03-27 | 2004-10-07 | Purdue Research Foundation | Metallic nanoparticles as orthopedic biomaterial |
US7134999B2 (en) | 2003-04-04 | 2006-11-14 | Dexcom, Inc. | Optimized sensor geometry for an implantable glucose sensor |
US7875293B2 (en) | 2003-05-21 | 2011-01-25 | Dexcom, Inc. | Biointerface membranes incorporating bioactive agents |
WO2005010518A1 (en) | 2003-07-23 | 2005-02-03 | Dexcom, Inc. | Rolled electrode array and its method for manufacture |
WO2005012873A2 (en) | 2003-07-25 | 2005-02-10 | Dexcom, Inc. | Electrode systems for electrochemical sensors |
WO2005012871A2 (en) | 2003-07-25 | 2005-02-10 | Dexcom, Inc. | Increasing bias for oxygen production in an electrode system |
EP1648298A4 (en) | 2003-07-25 | 2010-01-13 | Dexcom Inc | Oxygen enhancing membrane systems for implantable devices |
WO2005019795A2 (en) | 2003-07-25 | 2005-03-03 | Dexcom, Inc. | Electrochemical sensors including electrode systems with increased oxygen generation |
US8060173B2 (en) | 2003-08-01 | 2011-11-15 | Dexcom, Inc. | System and methods for processing analyte sensor data |
US7494465B2 (en) * | 2004-07-13 | 2009-02-24 | Dexcom, Inc. | Transcutaneous analyte sensor |
US7591801B2 (en) | 2004-02-26 | 2009-09-22 | Dexcom, Inc. | Integrated delivery device for continuous glucose sensor |
US20050090607A1 (en) * | 2003-10-28 | 2005-04-28 | Dexcom, Inc. | Silicone composition for biocompatible membrane |
WO2005079257A2 (en) * | 2004-02-12 | 2005-09-01 | Dexcom, Inc. | Biointerface with macro- and micro- architecture |
US8277713B2 (en) | 2004-05-03 | 2012-10-02 | Dexcom, Inc. | Implantable analyte sensor |
US20050245799A1 (en) * | 2004-05-03 | 2005-11-03 | Dexcom, Inc. | Implantable analyte sensor |
US20060015020A1 (en) | 2004-07-06 | 2006-01-19 | Dexcom, Inc. | Systems and methods for manufacture of an analyte-measuring device including a membrane system |
US20080242961A1 (en) | 2004-07-13 | 2008-10-02 | Dexcom, Inc. | Transcutaneous analyte sensor |
US20060270922A1 (en) * | 2004-07-13 | 2006-11-30 | Brauker James H | Analyte sensor |
US7783333B2 (en) | 2004-07-13 | 2010-08-24 | Dexcom, Inc. | Transcutaneous medical device with variable stiffness |
WO2006113618A1 (en) | 2005-04-15 | 2006-10-26 | Dexcom, Inc. | Analyte sensing biointerface |
US8060174B2 (en) | 2005-04-15 | 2011-11-15 | Dexcom, Inc. | Analyte sensing biointerface |
US7725148B2 (en) * | 2005-09-23 | 2010-05-25 | Medtronic Minimed, Inc. | Sensor with layered electrodes |
-
2004
- 2004-05-10 US US10/842,716 patent/US7875293B2/en active Active
- 2004-05-19 DE DE602004030902T patent/DE602004030902D1/en active Active
- 2004-05-19 WO PCT/US2004/015846 patent/WO2005025634A2/en active Application Filing
- 2004-05-19 EP EP04809390A patent/EP1624908B8/en not_active Not-in-force
- 2004-05-19 JP JP2006514910A patent/JP2006525853A/en active Pending
- 2004-05-19 AT AT04809390T patent/ATE494018T1/en not_active IP Right Cessation
-
2006
- 2006-05-03 US US11/416,734 patent/US20060204536A1/en not_active Abandoned
- 2006-05-03 US US11/416,825 patent/US20060198864A1/en not_active Abandoned
-
2014
- 2014-05-29 US US14/290,842 patent/US20140275900A1/en not_active Abandoned
-
2020
- 2020-08-20 US US16/998,841 patent/US20200375515A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
EP1624908B1 (en) | 2011-01-05 |
US20050031689A1 (en) | 2005-02-10 |
DE602004030902D1 (en) | 2011-02-17 |
ATE494018T1 (en) | 2011-01-15 |
US20060198864A1 (en) | 2006-09-07 |
EP1624908A2 (en) | 2006-02-15 |
EP1624908B8 (en) | 2011-06-15 |
JP2006525853A (en) | 2006-11-16 |
WO2005025634A3 (en) | 2005-10-06 |
WO2005025634A2 (en) | 2005-03-24 |
US20140275900A1 (en) | 2014-09-18 |
US20060204536A1 (en) | 2006-09-14 |
US7875293B2 (en) | 2011-01-25 |
US20200375515A1 (en) | 2020-12-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20200375515A1 (en) | Biointerface membranes incorporating bioactive agents | |
US7860545B2 (en) | Analyte measuring device | |
US20200359949A1 (en) | Analyte sensor | |
US8118877B2 (en) | Porous membranes for use with implantable devices | |
US7364592B2 (en) | Biointerface membrane with macro-and micro-architecture | |
JP7114289B2 (en) | Zwitterionic surface modification for continuous sensors | |
EP4218570A2 (en) | Polymer membranes for continuous analyte sensors | |
US20240108258A1 (en) | Analyte sensor | |
WO2023043908A1 (en) | Bioactive releasing membrane for analyte sensor |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BW BY BZ CA CH CN CO CR CU CZ DK DM DZ EC EE EG ES FI GB GD GE GM HR HU ID IL IN IS JP KE KG KP KZ LC LK LR LS LT LU LV MA MD MK MN MW MX MZ NA NI NO NZ PG PH PL PT RO RU SC SD SE SG SK SY TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): GM KE LS MW MZ NA SD SZ TZ UG ZM ZW AM AZ BY KG MD RU TJ TM AT BE BG CH CY DE DK EE ES FI FR GB GR HU IE IT MC NL PL PT RO SE SI SK TR BF CF CG CI CM GA GN GQ GW ML MR SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
COP | Corrected version of pamphlet |
Free format text: PAGES 1/7-7/7, DRAWINGS, REPLACED BY NEW PAGES 1/7-7/7 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2004809390 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2006514910 Country of ref document: JP |
|
WWP | Wipo information: published in national office |
Ref document number: 2004809390 Country of ref document: EP |