US20060068208A1 - Techniques to improve polyurethane membranes for implantable glucose sensors - Google Patents

Techniques to improve polyurethane membranes for implantable glucose sensors Download PDF

Info

Publication number
US20060068208A1
US20060068208A1 US11/280,102 US28010205A US2006068208A1 US 20060068208 A1 US20060068208 A1 US 20060068208A1 US 28010205 A US28010205 A US 28010205A US 2006068208 A1 US2006068208 A1 US 2006068208A1
Authority
US
United States
Prior art keywords
polymer
membrane
glucose
hydrophobic
hydrophilic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US11/280,102
Inventor
Mark Tapsak
Rathbun Rhodes
Mark Shults
Jason McClure
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dexcom Inc
Original Assignee
Dexcom Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dexcom Inc filed Critical Dexcom Inc
Priority to US11/280,102 priority Critical patent/US20060068208A1/en
Assigned to DEXCOM, INC. reassignment DEXCOM, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: RHODES, RATHBUN K., SHULTS, MARK C., MCCLURE, JASON D., TAPSAK, MARK A.
Publication of US20060068208A1 publication Critical patent/US20060068208A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D69/00Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • B01D69/14Dynamic membranes
    • B01D69/141Heterogeneous membranes, e.g. containing dispersed material; Mixed matrix membranes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1486Measuring 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
    • A61B5/14865Measuring 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14532Measuring 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1468Measuring 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 chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1473Measuring 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 chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1486Measuring 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L31/00Materials 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
    • A61L31/12Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D69/00Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • B01D69/14Dynamic membranes
    • B01D69/141Heterogeneous membranes, e.g. containing dispersed material; Mixed matrix membranes
    • B01D69/1411Heterogeneous membranes, e.g. containing dispersed material; Mixed matrix membranes containing dispersed material in a continuous matrix
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D71/00Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06Organic material
    • B01D71/54Polyureas; Polyurethanes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D71/00Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06Organic material
    • B01D71/76Macromolecular material not specifically provided for in a single one of groups B01D71/08 - B01D71/74
    • B01D71/80Block polymers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05DPROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D3/00Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials
    • B05D3/007After-treatment
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05DPROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D5/00Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001Enzyme electrodes
    • C12Q1/002Electrode membranes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001Enzyme electrodes
    • C12Q1/005Enzyme electrodes involving specific analytes or enzymes
    • C12Q1/006Enzyme electrodes involving specific analytes or enzymes for glucose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02Details of sensors specially adapted for in-vivo measurements
    • A61B2562/028Microscale sensors, e.g. electromechanical sensors [MEMS]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/12Manufacturing methods specially adapted for producing sensors for in-vivo measurements
    • A61B2562/125Manufacturing methods specially adapted for producing sensors for in-vivo measurements characterised by the manufacture of electrodes
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00Stock material or miscellaneous articles
    • Y10T428/31504Composite [nonstructural laminate]
    • Y10T428/31551Of polyamidoester [polyurethane, polyisocyanate, polycarbamate, etc.]

Definitions

  • the present invention relates generally to membranes for use in combination with implantable devices for evaluating an analyte in a body fluid. More particularly, the invention relates to membranes for controlling the diffusion of glucose therethrough to a glucose sensor.
  • a biosensor is a device that uses biological recognition properties for the selective analysis of various analytes or biomolecules. Generally, the sensor will produce a signal that is quantitatively related to the concentration of the analyte.
  • a great deal of research has been directed toward the development of a glucose sensor that would function in vivo to monitor a patient's blood glucose level. Such a glucose sensor is useful in the treatment of diabetes mellitus.
  • an implantable glucose sensor that would continuously monitor the patient's blood glucose level would provide a physician with more accurate information in order to develop optimal therapy.
  • One type of glucose sensor is the amperometric electrochemical glucose sensor.
  • an electrochemical glucose sensor employs the use of a glucose oxidase enzyme to catalyze the reaction between glucose and oxygen and subsequently generate an electrical signal.
  • the reaction catalyzed by glucose oxidase yields gluconic acid and hydrogen peroxide as shown in the reaction below (equation 1): glucose + O 2 ⁇ ⁇ oxidase ⁇ glucose ⁇ ⁇ gluconic ⁇ ⁇ acid + H 2 ⁇ O 2
  • the hydrogen peroxide reacts electrochemically as shown below in equation 2: H 2 ⁇ O 2 ⁇ 2 ⁇ ⁇ H + + O 2 + 2 ⁇ e -
  • the current measured by the sensor is generated by the oxidation of the hydrogen peroxide at a platinum working electrode.
  • the hydrogen peroxide is stoichiometrically related to the amount of glucose that reacts with the enzyme.
  • the ultimate current is also proportional to the amount of glucose that reacts with the enzyme.
  • the current will be proportional to the oxygen concentration, not the glucose concentration.
  • glucose must be the limiting reagent, i.e., the oxygen concentration must be in excess for all potential glucose concentrations. Unfortunately, this requirement is not easily achieved.
  • U.S. Pat. No. 5,322,063 to Allen et al. teaches that various compositions of hydrophilic polyurethanes can be used in order to control the ratios of the diffusion coefficients of oxygen to glucose in an implantable glucose sensor.
  • various polyurethane compositions were synthesized that were capable of absorbing from 10 to 50% of their dry weight of water.
  • the polyurethanes were rendered hydrophilic by incorporating polyethyleneoxide as their soft segment diols.
  • One disadvantage of this invention is that the primary backbone structure of the polyurethane is sufficiently different so that more than one casting solvent may be required to fabricate the membranes. This reduces the ease with which the membranes may be manufactured and may further reduce the reproducibility of the membrane.
  • U.S. Pat. Nos. 5,777,060 and 5,882,494, each to Van Antwerp also disclose homogeneous membranes having hydrophilic domains dispersed throughout a hydrophobic matrix to reduce the amount of glucose diffusion to the working electrode of a biosensor.
  • U.S. Pat. No. 5,882,494 to Van Antwerp discloses a membrane including the reaction products of a diisocyanate, a hydrophilic diol or diamine, and a silicone material.
  • polymeric membranes that can be prepared from (a) a diisocyanate, (b) a hydrophilic polymer, (c) a siloxane polymer having functional groups at the chain termini, and optionally (d) a chain extender.
  • Polymerization of these membranes typically requires heating of the reaction mixture for periods of time from 1 to 4 hours, depending on whether polymerization of the reactants is carried out in bulk or in a solvent system. Therefore, it would be beneficial to provide a method of preparing a homogenous membrane from commercial polymers.
  • one skilled in the art cannot simply change the polymer composition and be able to predict the oxygen to glucose permeability ratios. Therefore, a large number of polymers would need to be synthesized and coating or casting techniques optimized before a desired specific oxygen to glucose permeability ratio could be obtained.
  • a further membrane is disclosed in U.S. Pat. No. 6,200,772 B1 to Vadgama et al. that has hydrophilic domains dispersed substantially throughout a hydrophobic matrix for limiting the amount of glucose diffusing to a working electrode.
  • the patent describes a sensor device that includes a membrane comprised of modified polyurethane that is substantially non-porous and incorporates a non-ionic surfactant as a modifier.
  • the non-ionic surfactant is disclosed as preferably including a poly-oxyalkylene chain, such as one derived from multiple units of poly-oxyethylene groups.
  • the non-ionic surfactant may be incorporated into the polyurethane by admixture or through compounding to distribute it throughout the polyurethane.
  • the non-ionic surfactant is, according to the specification, preferably incorporated into the polyurethane by allowing it to react chemically with the polyurethane so that it becomes chemically bound into its molecular structure. Like most reactive polymer resins, complete reaction of the surfactant into the polyurethane may never occur. Therefore, a disadvantage of this membrane is that it can leach the surfactant over time and cause irritation at the implant site or change its permeability to glucose.
  • PCT Application WO 92/13271 discloses an implantable fluid measuring device for determining the presence and the amounts of substances in a biological fluid that includes a membrane for limiting the amount of a substance that passes therethrough.
  • this application discloses a membrane including a blend of two substantially similar polyurethane urea copolymers, one having a glucose permeability that is somewhat higher than preferred and the other having a glucose permeability that is somewhat lower than preferred.
  • FIG. 1 shows a photomicrograph at 200 ⁇ magnification of a prior art cast polymer blend following hydration.
  • a disadvantage of the prior art membranes is that, upon thermodynamic separation from the hydrophobic portions, the hydrophilic components form undesirable structures that appear circular 1 and elliptical 2 when viewed with a light microscope when the membrane 3 is hydrated, but not when it is dry. These hydrated structures can be detected by photomicroscopy under magnifications in the range of between 200 ⁇ -400 ⁇ , for example. They have been shown by the present inventors to be non-uniform in their dimensions throughout the membrane, with some being of the same size and same order of dimensions as the electrode size.
  • a continuous path 16 by which glucose may traverse along the hydrophilic segments 10 that are dispersed in hydrophobic sections 12 of the membrane.
  • glucose is able to traverse a fairly continuous path along assembled hydrophilic segments 10 from the side 18 of the membrane in contact with the body fluid containing glucose to the sensing side 20 proximal to sensor 22 , where an electrode 24 is placed at position 26 where glucose diffusion occurs adjacent surface 20 .
  • glucose diffusion occurs along hydrophilic segments 10 that comprise a hydrated structure 28 having a size and overall dimensions x that are of the same order of magnitude as electrode 24 . Therefore, glucose diffusion would be substantially constant across the dimension adjacent electrode 24 , but the number of glucose diffusion paths would be limited.
  • electrode 30 is located at position 34 , which is adjacent to a locally high concentration of a hydrophobic region 12 of prior art membrane 14 .
  • glucose diffusion cannot adequately occur, or is severely limited across the dimension adjacent the electrode surface. Consequently, one would expect that the locally high concentration of the hydrophobic regions adjacent to working electrode 30 would limit the ability of the sensing device to obtain accurate glucose measurements.
  • FIG. 2C shows another cross-section of prior art membrane 14 .
  • glucose is able to traverse a fairly continuous path 36 from side 18 to side 20 proximal to the sensing device.
  • electrode 38 is located at position 40 such that glucose diffusion is variable across the dimension adjacent the electrical surface.
  • most of the electrode surface is associated with a locally high concentration of hydrophobic region and a small portion is associated with hydrophilic segments 10 along glucose diffusion path 36 .
  • glucose diffusing along path 36 a would not be associated with the electrode.
  • the large non-uniform structures of the prior art membranes can limit the number of glucose diffusion paths and the ability of the sensing device to obtain accurate glucose measurements.
  • the present invention provides an implantable membrane for controlling the diffusion of an analyte therethrough to a biosensor with which it is associated.
  • the membrane of the present invention satisfies a need in the art by providing a homogenous membrane with both hydrophilic and hydrophobic regions to control the diffusion of glucose and oxygen to a biosensor, the membrane being fabricated easily and reproducibly from commercially available materials.
  • the invention provides a biocompatible membrane that regulates the transport of analytes that includes: (a) a matrix including a first polymer; and (b) a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which when hydrated are not observable using photomicroscopy at 400 ⁇ magnification or less.
  • a polymeric membrane for regulation of glucose and oxygen in a subcutaneous glucose measuring device that includes: (a) a matrix including a first polymer; and (b) a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which are not photomicroscopically observable when hydrated at 400 ⁇ magnification or less.
  • Yet another aspect of the present invention is directed to a polymeric membrane for regulating the transport of analytes, the membrane including at least one block copolymer AB, wherein B forms a network of microdomains which are not photomicroscopically observable when hydrated at 400 ⁇ magnification or less.
  • a membrane and sensor combination the sensor being adapted for evaluating an analyte within a body fluid
  • the membrane having: (a) a matrix including a first polymer; and (b) a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which are not photomicroscopically observable when hydrated at 400 ⁇ magnification or less.
  • the invention further provides an implantable device for measuring an analyte in a hydrophilic body fluid, including: (a) a polymeric membrane having (i) a matrix including a first polymer; and (ii) a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which are not photomicroscopically observable when hydrated at 400 ⁇ magnification or less; and (b) a proximal layer of enzyme reactive with the analyte.
  • a method for preparing an implantable membrane according to the invention including the steps of: (a) forming a composition including a dispersion of a second polymer within a matrix of a first polymer, the dispersion forming a network of microdomains which are not photomicroscopically observable when hydrated at 400 ⁇ magnification or less; (b) maintaining the composition at a temperature sufficient to maintain the first polymer and the second polymer substantially soluble; (c) applying the composition at this temperature to a substrate to form a film thereon; and (d) permitting the resultant film to dry to form the membrane.
  • FIG. 1 is a photomicrograph of a cross-section of prior art membrane at 200 ⁇ magnification following hydration with water for two hours.
  • FIG. 2A is a schematic representation of a cross-section of a prior art membrane having large hydrated structures dispersed substantially throughout a hydrophobic matrix, the hydrated structures being photomicroscopically observable at 400 ⁇ magnification or less.
  • the figure illustrates the positioning of a working electrode relative to a glucose diffusion pathway.
  • FIG. 2B is another schematic representation of a cross-section of the prior art membrane of FIG. 2A , where the working electrode is placed in association with a locally high concentration of the hydrophobic matrix.
  • FIG. 2C is yet another schematic representation of a cross-section of the prior art membrane of FIG. 2A where glucose diffusion is variable across the dimension adjacent the electrode surface.
  • FIG. 3 is a photomicrograph of a cross-section of a membrane of the present invention at 200 ⁇ magnification following hydration with water for two hours.
  • FIG. 4 is a schematic representation of a cross-section illustrating one particular form of the membrane of the present invention that shows a network of microdomains which are not photomicroscopically observable at 400 ⁇ or less magnification dispersed through a hydrophobic matrix, where the membrane is positioned in association with a sensor that includes a working electrode.
  • FIG. 5 is a schematic representation of a cross-section of the membrane of FIG. 3 in combination with an enzyme containing layer positioned more adjacent to a sensor 50 .
  • FIG. 6 is a graph showing sensor output versus the percent of the hydrophobic-hydrophilic copolymer component in the coating blend.
  • FIG. 7 is a graph showing the percent standard deviation of the sensor current versus the percent of the hydrophobic-hydrophilic copolymer component in the coating blend.
  • analyte refers to a substance or chemical constituent in a biological fluid (e.g. blood or urine) that is intended to be analyzed.
  • a preferred analyte for measurement by analyte detecting devices including the membrane of the present invention is glucose.
  • sensor refers to the component or region of a device by which an analyte can be evaluated.
  • continuous glucose sensing refers to the period in which monitoring of plasma glucose concentration is repeatedly performed over short periods of time, for example, 10 seconds to about every 15 minutes.
  • domain refers to regions of the membrane of the present invention that may be layers, uniform or non-uniform gradients (e.g. anisotropic) or provided as portions of the membrane. Furthermore, the region possesses physical properties distinctly different from other portions of the membrane.
  • glucose and “accurately” means, for example, 85% of measured glucose values are within the “A” and “B” region of a standard Clarke Error Grid when the sensor measurements are compared to a standard reference measurement. It is understood that like any analytical device, calibration, calibration validation and recalibration are required for the most accurate operation of the device.
  • the term “host” refers to humans and other animals.
  • the invention will primarily be referred to in terms of assay of glucose and solutions such as blood that tend to contain a large excess of glucose over oxygen.
  • the membrane is not limited solely to the assay of glucose in a biological fluid, but may be used for the assay of other compounds.
  • the sensor primarily referred to is an electrochemical sensor that directly measures hydrogen peroxide.
  • non-electrochemical based sensors that use optical detectors or other suitable detectors may be used to evaluate an analyte.
  • Membranes of the prior art have generally been unreliable at limiting the passage of glucose to implantable glucose sensors. This has presented a problem in the past in that the amount of glucose coming into contact with the immobilized enzyme exceeds the amount of oxygen available. As a result, the oxygen concentration is the rate-limiting component of the reaction, rather than the glucose concentration, such that the accuracy of the glucose measurement in the body fluid is compromised.
  • a disadvantage of prior art membranes for regulating analyte transport therethrough has been their tendency to form large undesirable structures (see FIG. 1 ) that are observable when the membrane is hydrated.
  • these hydrated structures can be detected by photomicroscopy under magnifications in the range of between 200 ⁇ -400 ⁇ , for example. They have been shown by the present inventors to be non-uniform in their dimensions through the membrane, with some being of the same size and same order of dimensions as the electrode size.
  • These large structures have been found to be problematic in that they can result in a locally high concentration of either hydrophobic or hydrophilic material in association with the working electrode, which can lead to inaccurate glucose readings. Moreover, they can greatly reduce the number of glucose diffusion paths available.
  • the membrane of the present invention seeks to circumvent these problems associated with prior art membranes by providing a reliable homogeneous membrane that regulates the transport of glucose or other analytes therethrough, the membrane having (a) a matrix including a first polymer; and (b) a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which when hydrated are not observable using photomicroscopy at 400 ⁇ magnification or less.
  • the membrane is substantially free of observable domains.
  • FIG. 3 shows a photomicrograph of a cross-section of a membrane 5 according to the present invention following hydration at two hours.
  • the membrane is devoid of any undesirable, large elliptical or spherical structures, such as were observable in hydrated prior art membranes at similar magnifications. It is noted that particles 6 in membrane 5 are dust particles.
  • glucose permeability and diffusion is related to the ratio of hydrophobic to hydrophilic constituents and their distribution throughout the membrane, with diffusion occurring substantially along assembled hydrophilic segments from the side of the membrane in contact with the host to the sensing side.
  • membrane 42 of the present invention in accordance with a particular arrangement, is schematically shown having hydrophilic segments 44 dispersed substantially throughout a hydrophobic matrix 46 and presenting a surface 48 to a hydrophilic body fluid.
  • the hydrophilic body fluid contains the sample to be assayed.
  • the body fluid contains both glucose and oxygen.
  • Membrane 42 restricts the rate at which glucose enters and passes through the membrane and/or may increase the rate at which oxygen enters and passes through membrane 42 .
  • hydrophilic segments 44 While not wishing to be bound by any one theory, it is likely that glucose diffuses substantially along hydrophilic segments 44 , but is generally excluded from the hydrophobic matrix 46 . It is noted that while the hydrophilic segments 44 are shown as comprising discrete microdomains in FIG. 4 , small amounts of hydrophobic polymer may be present therein, particularly at the interface with the hydrophobic matrix 46 . Similarly, small amounts of hydrophilic polymer may be present in the hydrophobic matrix 46 , particularly at the interface with hydrophilic segments 44 .
  • inventive membrane 42 is shown in combination with a sensor 50 , which is positioned adjacent to the membrane. It is noted that additional membranes or layers may be situated between membrane 42 and sensor 50 , as will be discussed in further detail below. Diffusion of the sample along paths 52 through membrane 42 into association with a working electrode 54 of sensor 50 causes development of a signal that is proportional to the amount of analyte in the sample. Determination of the analyte may be made by calculations based upon similar measurements made on standard solutions containing known concentrations of the analyte.
  • one or more electrodes may be used to detect the amount of analyte in the sample and convert that information into a signal; the signal may then be transmitted to electronic circuitry required to process biological information obtained from the host.
  • U.S. Pat. Nos. 4,757,022, 5,497,772 and 4,787,398 describe suitable electronic circuitry that may be utilized with implantable devices of the present invention.
  • the present invention solves a need in the art by providing a reliable membrane for controlling glucose diffusion therethrough.
  • glucose can traverse along hydrophilic segments 44 from the side 48 of the membrane in contact with a body fluid to the side 56 proximal to sensor 50 .
  • the hydrophilic microdomains 44 are likely distributed substantially evenly throughout the membrane.
  • these microdomains are likely substantially uniform in size throughout the membrane.
  • the size and order to dimensions of these microdomains is considerably less than the that of the working electrode 54 of sensor 50 .
  • the electrode is in association with a useful amount of both the hydrophobic 46 and hydrophilic 44 regions of the membrane to allow effective control over the amount of glucose diffusing to the electrode.
  • the number of paths available for glucose to permeate the membrane and diffuse from side 48 to the sensing side 56 would be greater for the inventive membrane than for prior art membranes. Consequently, more accurate and reproducible glucose readings are attainable across the entire inventive membrane.
  • FIG. 5 shows a preferred embodiment of the present invention wherein membrane 42 is used in combination with a proximal membrane layer 58 that comprises an enzyme that is reactive with the analyte.
  • a proximal membrane layer 58 that comprises an enzyme that is reactive with the analyte.
  • diffusion of the sample from side 48 through the membrane 42 into contact with the immobilized enzyme in layer 58 leads to an enzymatic reaction in which the reaction products may be measured.
  • the analyte is glucose.
  • the enzyme immobilized in layer 58 is glucose oxidase.
  • glucose oxidase catalyzes the conversion of oxygen and glucose to hydrogen peroxide and gluconic acid. Because for each glucose molecule metabolized, there is proportional change in the co-reactant O 2 and the product H 2 O 2 , one can monitor the change in either the co-reactant or the product to determine glucose concentration. With further reference to FIG. 5 , diffusion of the resulting hydrogen peroxide through layer 58 to the sensor 50 , (e.g. electrochemically reactive surfaces), causes the development of an electrical current that can be detected. This enables determination of the glucose by calculations based upon similar measurements made on standard solutions containing known concentrations of glucose.
  • the sensor 50 e.g. electrochemically reactive surfaces
  • the present invention contemplates the use of a layer impregnated with other oxidases, e.g. galactose oxidase or uricase.
  • oxidases e.g. galactose oxidase or uricase.
  • the sensor's response must neither be limited by enzyme activity nor cofactor concentration. Because enzymes, including glucose oxidase, are subject to deactivation as a function of ambient conditions, this behavior needs to be accounted for in constructing sensors for long-term use.
  • enzyme layer 58 When the membrane of the present invention is combined with an enzyme layer 58 as shown in FIG. 5 , it is the enzyme layer that is located more proximally to the sensor 50 (e.g. electrochemically reactive surfaces). It is noted that enzyme-containing layer 58 must be of sufficient permeability to 1) freely pass glucose to active enzyme and 2) to permit the rapid passage of hydrogen peroxide to the sensor (electrode surface). A failure to permit the rapid passage of glucose to the active enzyme or hydrogen peroxide from the active enzyme to the electrode surface can cause a time delay in the measured signal and thereby lead to inaccurate results.
  • the enzyme layer is comprised of aqueous polyurethane-based latex into which the enzyme is immobilized.
  • inventive membrane 42 may itself contain immobilized enzymes for promoting a reaction between glucose and oxygen, it is preferred that the enzyme be located in a separate layer, such as layer 58 shown in FIG. 5 .
  • a disadvantage of providing enzyme in a layer that is semi-permeable to glucose is that the calibration factors of the sensor may change over time as the working enzyme degrades.
  • enzyme is dispersed throughout a membrane freely permeable to glucose (i.e. layer 58 in FIG. 5 )
  • such a membrane is likely to yield calibration factors that are more stable over the life of a sensor.
  • the first polymer of the membrane includes homopolymer A and the second polymer includes copolymer AB.
  • the first polymer includes copolymer AB and the second polymer includes copolymer AB.
  • the amount of B in copolymer AB of the first polymer is different than the amount of B in copolymer AB of the second polymer.
  • the membrane may be formed from a blend of two AB copolymers, where one of the copolymers contains more of a hydrophilic B polymer component than the blended targeted amount and the other copolymer contains less of a hydrophilic B polymer component than the blended targeted amount.
  • the first polymer includes homopolymer A and the second polymer includes homopolymer B.
  • the invention also provides a polymeric membrane for regulating the transport of analytes that includes at least one block copolymer AB, wherein B forms a network of microdomains which are not photomicroscopically observable when hydrated at 400 ⁇ magnification or less.
  • the ratio of A to B in copolymer AB is 70:30 to 90:10.
  • homopolymer A is preferably a hydrophobic A polymer.
  • copolymer AB is preferably a hydrophobic-hydrophilic copolymer component that includes the reaction products of a hydrophobic A polymer and a hydrophilic B polymer. Suitable materials for preparing membranes the present invention are described below.
  • copolymer AB may be a random or ordered block copolymer.
  • the random or ordered block copolymer may be selected from the following: ABA block copolymer, BAB block copolymer, AB random alternating block copolymer, AB regularly alternating block copolymer and combinations thereof.
  • the senor, membrane, and methods of the present invention may be used to determine the level of glucose or other analytes in a host.
  • the level of glucose is a particularly important measurement for individuals having diabetes in that effective treatment depends on the accuracy of this measurement.
  • the invention provides a method of measuring glucose in a biological fluid that includes the steps of: (a) providing (i) a host, and (ii) an implantable device for measuring an analyte in a hydrophilic body fluid, where the device includes a polymeric membrane having a matrix including a first polymer and a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which are not photomicroscopically observable when hydrated at 400 ⁇ magnification or less; and a proximal layer of enzyme reactive with the analyte; and (b) implanting the device in the host.
  • the device is implanted subcutaneously.
  • the invention also provides a method of measuring glucose in a biological fluid that includes the following steps: (a) providing (i) a host, and (ii) an implantable device for measuring an analyte in a hydrophilic body fluid, that includes a polymeric membrane including a matrix including a first polymer and a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which are not photomicroscopically observable when hydrated at 400 ⁇ magnification or less; and a proximal layer of enzyme reactive with the analyte, the device being capable of accurate continuous glucose sensing; and (b) implanting the device in the host.
  • the implant is placed subcutaneously in the host.
  • Glucose sensors that use, for example, glucose oxidase to effect a reaction of glucose and oxygen are known in the art, and are within the skill of one in the art to fabricate (see, for example, U.S. Pat. Nos. 5,165,407, 4,890,620, 5,390,671, 5,391,250, 6,001,067 as well as copending, commonly owned U.S. patent application Ser. No. 09/916,858. It is noted that the present invention does not depend on a particular configuration of the sensor, but is rather dependent on the use of the inventive membrane to cover or encapsulate the sensor elements.
  • the glucose concentration as opposed to oxygen concentration, must be the limiting factor.
  • oxygen must be present within the membrane in excess of the glucose.
  • the oxygen must be in sufficient excess so that it is also available for electrochemical reactions occurring at the amperometric electrode surfaces.
  • the inventive membrane is designed so that oxygen can pass readily into and through the membrane and so that a reduced amount of glucose diffuses into and through the membrane into contact with an immobilized glucose oxidase enzyme.
  • the inventive membrane allows the ratio of oxygen to glucose to be changed from a concentration ratio in the body fluid of about approximately 50 and 100 parts of glucose to 1 of oxygen to a new ratio in which there is a stoichiometric excess of oxygen in the enzyme layer.
  • an implantable glucose sensor system is not limited by the concentration of oxygen present in subcutaneous tissues and can therefore operate under the premise that the glucose oxidase reaction behaves as a 1-substrate (glucose) dependent process.
  • the present invention provides a semi-permeable membrane that controls the flux of oxygen and glucose to an underlying enzyme layer, rendering the necessary supply of oxygen in non-rate-limiting excess.
  • the membrane of the present invention is a polymer membrane with oxygen-to-glucose permeability ratios of approximately 200:1; as a result, 1-dimensional reactant diffusion is adequate to provide excess oxygen at all reasonable glucose and oxygen concentrations found in a subcutaneous matrix [Rhodes, et al., Anal. Chem., 66: 1520-1529 (1994)].
  • a hydrophilic or “water loving” solute such as glucose is readily partitioned into a hydrophilic material, but is generally excluded from a hydrophobic material.
  • oxygen can be soluble in both hydrophilic and hydrophobic materials.
  • the membrane of the invention is formed from a blend of polymers including (i) a hydrophobic A polymer component; and (ii) a hydrophobic-hydrophilic copolymer component blended with component (i) that forms hydrophilic B domains that control the diffusion of an analyte therethrough, wherein the copolymer component includes a random or ordered block copolymer. Suitable block copolymers are described above. One is able to modify the glucose permeability and the glucose diffusion characteristics of the membrane by simply varying the polymer composition.
  • the hydrophobic A polymer is a polyurethane.
  • the polyurethane is polyetherurethaneurea.
  • a polyurethane is a polymer produced by the condensation reaction of a diisocyanate and a difunctional hydroxyl-containing material.
  • a polyurethaneurea is a polymer produced by the condensation reaction of a diisocyanate and a difunctional amine-containing material.
  • Preferred diisocyanates include aliphatic diisocyanates containing from 4 to 8 methylene units. Diisocyanates containing cycloaliphatic moieties, may also be useful in the preparation of the polymer and copolymer components of the membrane of the present invention.
  • the invention is not limited to the use of polyurethanes as the hydrophobic polymer A component.
  • the material that forms the basis of the hydrophobic matrix of the inventive membrane may be any of those known in the art as appropriate for use as membranes in sensor devices and having sufficient permeability to allow relevant compounds to pass through it, for example, to allow an oxygen molecule to pass through the inventive membrane from the sample under examination in order to reach the active enzyme or electrochemical electrodes.
  • Examples of materials which may be used to make a non-polyurethane type membrane include vinyl polymers, polyethers, polyesters, polyamides, inorganic polymers such as polysiloxanes and polycarbosiloxanes, natural polymers such as cellulosic and protein based materials and mixtures or combinations thereof.
  • the hydrophobic-hydrophilic copolymer component includes the reaction products of a hydrophobic A polymer component and a hydrophilic B polymer component.
  • the hydrophilic B polymer component is desirably polyethylene oxide.
  • one useful hydrophobic-hydrophilic copolymer component is a polyurethane polymer that includes about 20% hydrophilic polyethyelene oxide.
  • the polyethylene oxide portion of the copolymer is thermodynamically driven to separate from the hydrophobic portions of the copolymer and the hydrophobic A polymer component.
  • the 20% polyethylene oxide based soft segment portion of the copolymer used to form the final blend controls the water pick-up and subsequent glucose permeability of the membrane of the present invention.
  • the polyethylene oxide may have an average molecular weight of from 200 to 3000 with a preferred molecular weight range of 600 to 1500 and preferably constitutes about 20% by weight of the copolymer component used to form the membrane of the present invention.
  • the membrane of the present invention has a thickness of about 5 to about 100 microns.
  • the membrane of the present invention is constructed of a polyetherurethaneurea/polyetherurethaneurea-block-polyethylene glycol blend and has a thickness of not more than about 100 microns, more preferably not less than about 10 microns, and not more than about 80 microns, and most preferably, not less than about 20 microns, and not more than about 60 microns.
  • the membrane of the present invention can be made by casting from solutions, optionally with inclusion of additives to modify the properties and the resulting cast film or to facilitate the casting process.
  • the present invention provides a method for preparing the implantable membrane of the invention.
  • the method includes the steps of: (a) forming a composition including a dispersion of a second polymer within a matrix of a first polymer, the dispersion forming a network of microdomains which are not photomicroscopically observable when hydrated at 400 ⁇ magnification or less; (b) maintaining the composition at a temperature sufficient to maintain the first polymer and the second polymer substantially soluble; (c) applying the composition at the temperature to a substrate to form a film thereon; and (d) permitting the resultant film to dry to form the membrane.
  • the forming step includes forming a mixture or a blend.
  • the first polymer is a polyurethane and the second polymer is polyethylene oxide.
  • the second polymer may be a random or ordered block copolymer selected from the following: ABA block copolymer, BAB block copolymer, AB random alternating block copolymer, AB regularly alternating block copolymer and combinations thereof.
  • the composition comprised of a dispersion of the second polymer within the matrix of a first polymer is heated to a temperature of about 70° C. to maintain the first and second polymers substantially soluble.
  • a hydrophobic polymer A component and a hydrophobic-hydrophilic copolymer AB component is desirably exposed to a temperature of about 70° C. to maintain the polymer and copolymers substantially soluble.
  • the blend is heated well above room temperature in order to keep the hydrophilic and hydrophobic components soluble with each other and the solvent.
  • the invention contemplates permitting the coated film formed on the substrate to dry at a temperature from about 120° C. to about 150° C.
  • the elevated temperature further serves to drive the solvent from the coating as quickly as possible. This inhibits the hydrophilic and hydrophobic portions of the membrane from segregating and forming large undesired structures.
  • the membrane and sensor combinations of the present invention provide a significant advantage over the prior art in that they provide accurate sensor operation at temperatures from about 30° C. to about 45° C. for a period of time exceeding about 30 days to exceeding about a year.
  • the inventive membrane may be cast from a coating solution.
  • the coating solution is prepared by placing approximately 281 gm of dimethylacetamide (DMAC) into a 3 L stainless steel bowl to which a solution of polyetherurethaneurea (344 gm of Chronothane H (Cardiotech International, Inc., Woburn, Mass.), 29,750 cp @ 25% solids in DMAC) is added. To this mixture is added another polyetherurethaneurea (approximately 312 gm, Chronothane 1020 (Cardiotech International, Inc., Woburn, Mass.), 6275 cp @ 25% solids in DMAC).
  • DMAC dimethylacetamide
  • the bowl is then fitted to a planetary mixer with a paddle-type blade and the contents are stirred for 30 minutes at room temperature.
  • Coatings solutions prepared in this manner are then coated at between room temperature to about 70° C. onto a PET release liner (Douglas Hansen Co., Inc., Minneapolis, Mn.) using a knife-over-roll set at a 0.012 inch gap.
  • the film is continuously dried at 120° C. to about 150° C. The final film thickness is approximately 0.0015 inches.
  • a 1 ⁇ 4′′ by 1 ⁇ 4′′ piece of membrane is first immersed in deionized water for a minimum of 2 hours at room temperature. After this time, the sample is placed onto a microscope slide along with one drop of water. A glass cover slide is then placed over the membrane and gentle pressure is applied in order to remove excess liquid from underneath the cover glass. In this way, the membrane does not dry during its evaluation.
  • the hydrated membrane sample is first observed at 40X-magnification using a light microscope (Nikon Eclipse E400). If air bubbles are present on the top or bottom of the film, the cover glass is gently pressed again with a tissue in order to remove them. Magnification is then increased to 200 ⁇ ; and the hydrated membrane is continuously observed while changing the focus from the top to bottom of the film. This is followed by an increase in magnification to 400 ⁇ , with the membrane again being continuously observed while changing the focus from the top to bottom of the film.
  • Example 2 further demonstrates that, provided the coating solution is preheated to about 70° C., either a standard (120°) or elevated (150° C.) drying temperature were sufficient to drive the DMAC solvent from the coated film quickly to further inhibit the hydrophilic and hydrophobic portions of the polyurethane membrane from segregating into large domains.
  • the invention was evaluated by performing a coating experiment where standard coating conditions (room temperature coating solution and 120° C. drying temperature of the coated film) were compared to conditions where the coating solution temperature was elevated and/or the drying temperature of the coated film was elevated.
  • standard coating conditions room temperature coating solution and 120° C. drying temperature of the coated film
  • Membranes prepared under the EE condition described in Example 2 were evaluated for their ability to allow glucose and hydrogen peroxide to get through the membrane to a sensor.
  • a series of polyurethane blends of the present invention were generated wherein the percentage of Chronothane H in a coating blend was varied.
  • one of these blends (57.5% Chronothane H in coating blend) was prepared under both the EE condition and the SS condition as described in Example 2.
  • FIG. 6 shows that the sensor output generated with a series of polyurethane blends of the present invention was dependent upon the percentage of the Chronothane H.
  • the sensor output increased as the percentage of Chronothane H in the coating blend increased.
  • the percentage of Chronothane H in the coating blend was 57.5%, the sensor output was three times greater for the membrane prepared under the optimized EE coating condition as compared to the non-optimized SS coating condition.
  • FIG. 7 demonstrates that, regardless of the percent Chronothane H in the coating blend, an inventive membrane prepared under the EE condition shows a fairly constant percent standard deviation of sensor output. Moreover, a membrane prepared with 57.5% Chronothane H in the coating blend under the SS condition showed a percent standard deviation of sensor output approximately twice that of an EE membrane prepared with the same percentage of Chronothane H in the blend. It is noted that given that the sensor output is a true measure of the amount of glucose getting through the membrane to the sensor, the results indicate that the permeability of glucose and H 2 O 2 is relatively constant throughout a given inventive membrane prepared under optimized coating conditions (i.e., EE conditions). This is important from a manufacturing standpoint.

Abstract

The invention provides an implantable membrane for regulating the transport of analytes therethrough that includes a matrix including a first polymer; and a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which when hydrated are not observable using photomicroscopy at 400× magnification or less. In one aspect, the homogeneous membrane of the present invention has hydrophilic domains dispersed substantially throughout a hydrophobic matrix to provide an optimum balance between oxygen and glucose transport to an electrochemical glucose sensor.

Description

    RELATED APPLICATION
  • This application is a division of application Ser. No. 10/153,356 filed May 22, 2002, the disclosure of which is hereby incorporated by reference in its entirety and is made a portion of this application.
  • FIELD OF THE INVENTION
  • The present invention relates generally to membranes for use in combination with implantable devices for evaluating an analyte in a body fluid. More particularly, the invention relates to membranes for controlling the diffusion of glucose therethrough to a glucose sensor.
  • BACKGROUND OF THE INVENTION
  • A biosensor is a device that uses biological recognition properties for the selective analysis of various analytes or biomolecules. Generally, the sensor will produce a signal that is quantitatively related to the concentration of the analyte. In particular, a great deal of research has been directed toward the development of a glucose sensor that would function in vivo to monitor a patient's blood glucose level. Such a glucose sensor is useful in the treatment of diabetes mellitus. In particular, an implantable glucose sensor that would continuously monitor the patient's blood glucose level would provide a physician with more accurate information in order to develop optimal therapy. One type of glucose sensor is the amperometric electrochemical glucose sensor. Typically, an electrochemical glucose sensor employs the use of a glucose oxidase enzyme to catalyze the reaction between glucose and oxygen and subsequently generate an electrical signal. The reaction catalyzed by glucose oxidase yields gluconic acid and hydrogen peroxide as shown in the reaction below (equation 1): glucose + O 2 oxidase` glucose gluconic acid + H 2 O 2
    The hydrogen peroxide reacts electrochemically as shown below in equation 2: H 2 O 2 2 H + + O 2 + 2 e -
  • The current measured by the sensor is generated by the oxidation of the hydrogen peroxide at a platinum working electrode. According to equation 1, if there is excess oxygen for equation 1, then the hydrogen peroxide is stoichiometrically related to the amount of glucose that reacts with the enzyme. In this instance, the ultimate current is also proportional to the amount of glucose that reacts with the enzyme. However, if there is insufficient oxygen for all of the glucose to react with the enzyme, then the current will be proportional to the oxygen concentration, not the glucose concentration. For the glucose sensor to be useful, glucose must be the limiting reagent, i.e., the oxygen concentration must be in excess for all potential glucose concentrations. Unfortunately, this requirement is not easily achieved. For example, in the subcutaneous tissue the concentration of oxygen is much less that of glucose. As a consequence, oxygen can become a limiting reactant, giving rise to a problem with oxygen deficit. Attempts have been made to circumvent this problem in order to allow the sensor to continuously operate in an environment with an excess of oxygen.
  • Several attempts have been made to use membranes of various types in an effort to design a membrane that regulates the transport of oxygen and glucose to the sensing elements of glucose oxidase-based glucose sensors. One approach has been to develop homogenous membranes having hydrophilic domains dispersed substantially throughout a hydrophobic matrix to circumvent the oxygen deficit problem, where glucose diffusion is facilitated by the hydrophilic segments.
  • For example, U.S. Pat. No. 5,322,063 to Allen et al. teaches that various compositions of hydrophilic polyurethanes can be used in order to control the ratios of the diffusion coefficients of oxygen to glucose in an implantable glucose sensor. In particular, various polyurethane compositions were synthesized that were capable of absorbing from 10 to 50% of their dry weight of water. The polyurethanes were rendered hydrophilic by incorporating polyethyleneoxide as their soft segment diols. One disadvantage of this invention is that the primary backbone structure of the polyurethane is sufficiently different so that more than one casting solvent may be required to fabricate the membranes. This reduces the ease with which the membranes may be manufactured and may further reduce the reproducibility of the membrane. Furthermore, neither the percent of the polyethyleneoxide soft segment nor the percent water pickup of the polyurethanes disclosed by Allen directly correlate to the oxygen to glucose permeability ratios. Therefore, one skilled in the art cannot simply change the polymer composition and be able to predict the oxygen to glucose permeability ratios. As a result, a large number of polymers would need to be synthesized before a desired specific oxygen to glucose permeability ratio could be obtained.
  • U.S. Pat. Nos. 5,777,060 and 5,882,494, each to Van Antwerp, also disclose homogeneous membranes having hydrophilic domains dispersed throughout a hydrophobic matrix to reduce the amount of glucose diffusion to the working electrode of a biosensor. For example, U.S. Pat. No. 5,882,494 to Van Antwerp discloses a membrane including the reaction products of a diisocyanate, a hydrophilic diol or diamine, and a silicone material. In addition, U.S. Pat. No. 5,777,060 to Van Antwerp discloses polymeric membranes that can be prepared from (a) a diisocyanate, (b) a hydrophilic polymer, (c) a siloxane polymer having functional groups at the chain termini, and optionally (d) a chain extender. Polymerization of these membranes typically requires heating of the reaction mixture for periods of time from 1 to 4 hours, depending on whether polymerization of the reactants is carried out in bulk or in a solvent system. Therefore, it would be beneficial to provide a method of preparing a homogenous membrane from commercial polymers. Moreover, as mentioned above, one skilled in the art cannot simply change the polymer composition and be able to predict the oxygen to glucose permeability ratios. Therefore, a large number of polymers would need to be synthesized and coating or casting techniques optimized before a desired specific oxygen to glucose permeability ratio could be obtained.
  • A further membrane is disclosed in U.S. Pat. No. 6,200,772 B1 to Vadgama et al. that has hydrophilic domains dispersed substantially throughout a hydrophobic matrix for limiting the amount of glucose diffusing to a working electrode. In particular, the patent describes a sensor device that includes a membrane comprised of modified polyurethane that is substantially non-porous and incorporates a non-ionic surfactant as a modifier. The non-ionic surfactant is disclosed as preferably including a poly-oxyalkylene chain, such as one derived from multiple units of poly-oxyethylene groups. As described, the non-ionic surfactant may be incorporated into the polyurethane by admixture or through compounding to distribute it throughout the polyurethane. The non-ionic surfactant is, according to the specification, preferably incorporated into the polyurethane by allowing it to react chemically with the polyurethane so that it becomes chemically bound into its molecular structure. Like most reactive polymer resins, complete reaction of the surfactant into the polyurethane may never occur. Therefore, a disadvantage of this membrane is that it can leach the surfactant over time and cause irritation at the implant site or change its permeability to glucose.
  • PCT Application WO 92/13271 discloses an implantable fluid measuring device for determining the presence and the amounts of substances in a biological fluid that includes a membrane for limiting the amount of a substance that passes therethrough. In particular, this application discloses a membrane including a blend of two substantially similar polyurethane urea copolymers, one having a glucose permeability that is somewhat higher than preferred and the other having a glucose permeability that is somewhat lower than preferred.
  • An important factor in obtaining a useful implantable sensor for detection of glucose or other analytes is the need for optimization of materials and methods in order to obtain predictable in vitro and in vivo function. The ability of the sensor to function in a predictable and reliable manner in vitro is dependent on consistent fabrication techniques. Repeatability of fabrication has been a problem associated with prior art membranes that attempt to regulate the transport of analytes to the sensing elements.
  • We refer now to FIG. 1, which shows a photomicrograph at 200× magnification of a prior art cast polymer blend following hydration. A disadvantage of the prior art membranes is that, upon thermodynamic separation from the hydrophobic portions, the hydrophilic components form undesirable structures that appear circular 1 and elliptical 2 when viewed with a light microscope when the membrane 3 is hydrated, but not when it is dry. These hydrated structures can be detected by photomicroscopy under magnifications in the range of between 200×-400×, for example. They have been shown by the present inventors to be non-uniform in their dimensions throughout the membrane, with some being of the same size and same order of dimensions as the electrode size. It is believed that these large domains present a problem in that they result in a locally high concentration of either hydrophobic or hydrophilic material in association with the electrode. This can result in glucose diffusion being limited or variable across the dimension adjacent the sensing electrode. Moreover, these large hydrated structures can severely limit the number of glucose diffusion paths available. It is noted that particles 4 in membrane 3 are dust particles.
  • With reference now to a schematic representation of a known membrane 14 in FIG. 2A, one can consider by way of example a continuous path 16 by which glucose may traverse along the hydrophilic segments 10 that are dispersed in hydrophobic sections 12 of the membrane. For path 16, glucose is able to traverse a fairly continuous path along assembled hydrophilic segments 10 from the side 18 of the membrane in contact with the body fluid containing glucose to the sensing side 20 proximal to sensor 22, where an electrode 24 is placed at position 26 where glucose diffusion occurs adjacent surface 20. In particular, in that portion of the membrane 14 proximal to position 26, glucose diffusion occurs along hydrophilic segments 10 that comprise a hydrated structure 28 having a size and overall dimensions x that are of the same order of magnitude as electrode 24. Therefore, glucose diffusion would be substantially constant across the dimension adjacent electrode 24, but the number of glucose diffusion paths would be limited.
  • Referring now to FIG. 2B, one can consider an example where glucose traversing prior art membrane 14 from side 18 in contact with the body fluid to the sensing side 20 cannot adequately reach electrode 30. In particular, electrode 30 is located at position 34, which is adjacent to a locally high concentration of a hydrophobic region 12 of prior art membrane 14. In this instance, glucose diffusion cannot adequately occur, or is severely limited across the dimension adjacent the electrode surface. Consequently, one would expect that the locally high concentration of the hydrophobic regions adjacent to working electrode 30 would limit the ability of the sensing device to obtain accurate glucose measurements. The random chance that the membrane could be placed in the 2A configuration as opposed to 2B leads to wide variability in sensor performance.
  • We also refer to FIG. 2C, which shows another cross-section of prior art membrane 14. In this instance, glucose is able to traverse a fairly continuous path 36 from side 18 to side 20 proximal to the sensing device. However, electrode 38 is located at position 40 such that glucose diffusion is variable across the dimension adjacent the electrical surface. In particular, most of the electrode surface is associated with a locally high concentration of hydrophobic region and a small portion is associated with hydrophilic segments 10 along glucose diffusion path 36. Furthermore, glucose diffusing along path 36 a would not be associated with the electrode. Again, the large non-uniform structures of the prior art membranes can limit the number of glucose diffusion paths and the ability of the sensing device to obtain accurate glucose measurements.
  • It would be beneficial to form more homogeneous membranes for controlling glucose transport from commercially available polymers that have a similar backbone structure. This would result in a more reproducible membrane. In particular, it is desired that one would be able to predict the resulting glucose permeability of the resulting membrane by simply varying the polymer composition. In this way, the glucose diffusion characteristics of the membrane could be modified, without greatly changing the manufacturing parameters for the membrane. In particular, there is a need for homogeneous membranes having hydrophilic segments dispersed throughout a hydrophobic matrix that are easy to fabricate reproducibly from readily available reagents. Of particular importance would be the development of membranes where the hydrophilic portions were distributed evenly throughout the membrane, and where their size and dimensions were on an order considerably less than the size and dimensions of the electrode of the sensing device to allow the electrode to be in association with a useful amount of both hydrophobic and hydrophilic portions. The ability of the membranes to be synthesized and manufactured in reasonable quantities and at reasonable prices would be a further advantage.
  • SUMMARY OF THE INVENTION
  • The present invention provides an implantable membrane for controlling the diffusion of an analyte therethrough to a biosensor with which it is associated. In particular, the membrane of the present invention satisfies a need in the art by providing a homogenous membrane with both hydrophilic and hydrophobic regions to control the diffusion of glucose and oxygen to a biosensor, the membrane being fabricated easily and reproducibly from commercially available materials.
  • The invention provides a biocompatible membrane that regulates the transport of analytes that includes: (a) a matrix including a first polymer; and (b) a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which when hydrated are not observable using photomicroscopy at 400× magnification or less.
  • Further provided by the invention is a polymeric membrane for regulation of glucose and oxygen in a subcutaneous glucose measuring device that includes: (a) a matrix including a first polymer; and (b) a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which are not photomicroscopically observable when hydrated at 400× magnification or less.
  • Yet another aspect of the present invention is directed to a polymeric membrane for regulating the transport of analytes, the membrane including at least one block copolymer AB, wherein B forms a network of microdomains which are not photomicroscopically observable when hydrated at 400× magnification or less.
  • Also provided is a membrane and sensor combination, the sensor being adapted for evaluating an analyte within a body fluid, the membrane having: (a) a matrix including a first polymer; and (b) a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which are not photomicroscopically observable when hydrated at 400× magnification or less.
  • The invention further provides an implantable device for measuring an analyte in a hydrophilic body fluid, including: (a) a polymeric membrane having (i) a matrix including a first polymer; and (ii) a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which are not photomicroscopically observable when hydrated at 400× magnification or less; and (b) a proximal layer of enzyme reactive with the analyte.
  • Moreover, a method for preparing an implantable membrane according to the invention is provided, the method including the steps of: (a) forming a composition including a dispersion of a second polymer within a matrix of a first polymer, the dispersion forming a network of microdomains which are not photomicroscopically observable when hydrated at 400× magnification or less; (b) maintaining the composition at a temperature sufficient to maintain the first polymer and the second polymer substantially soluble; (c) applying the composition at this temperature to a substrate to form a film thereon; and (d) permitting the resultant film to dry to form the membrane.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1 is a photomicrograph of a cross-section of prior art membrane at 200× magnification following hydration with water for two hours.
  • FIG. 2A is a schematic representation of a cross-section of a prior art membrane having large hydrated structures dispersed substantially throughout a hydrophobic matrix, the hydrated structures being photomicroscopically observable at 400× magnification or less. The figure illustrates the positioning of a working electrode relative to a glucose diffusion pathway.
  • FIG. 2B is another schematic representation of a cross-section of the prior art membrane of FIG. 2A, where the working electrode is placed in association with a locally high concentration of the hydrophobic matrix.
  • FIG. 2C is yet another schematic representation of a cross-section of the prior art membrane of FIG. 2A where glucose diffusion is variable across the dimension adjacent the electrode surface.
  • FIG. 3 is a photomicrograph of a cross-section of a membrane of the present invention at 200× magnification following hydration with water for two hours.
  • FIG. 4 is a schematic representation of a cross-section illustrating one particular form of the membrane of the present invention that shows a network of microdomains which are not photomicroscopically observable at 400× or less magnification dispersed through a hydrophobic matrix, where the membrane is positioned in association with a sensor that includes a working electrode.
  • FIG. 5 is a schematic representation of a cross-section of the membrane of FIG. 3 in combination with an enzyme containing layer positioned more adjacent to a sensor 50.
  • FIG. 6 is a graph showing sensor output versus the percent of the hydrophobic-hydrophilic copolymer component in the coating blend.
  • FIG. 7 is a graph showing the percent standard deviation of the sensor current versus the percent of the hydrophobic-hydrophilic copolymer component in the coating blend.
  • DETAILED WRITTEN DESCRIPTION
  • In order to facilitate understanding of the present invention, a number of terms are defined below.
  • The term “analyte” refers to a substance or chemical constituent in a biological fluid (e.g. blood or urine) that is intended to be analyzed. A preferred analyte for measurement by analyte detecting devices including the membrane of the present invention is glucose.
  • The term “sensor” refers to the component or region of a device by which an analyte can be evaluated.
  • By the terms “evaluated”, “monitored”, “analyzed”, and the like, it is meant that an analyte may be detected and/or measured.
  • The phrase “continuous glucose sensing” refers to the period in which monitoring of plasma glucose concentration is repeatedly performed over short periods of time, for example, 10 seconds to about every 15 minutes.
  • The term “domain” refers to regions of the membrane of the present invention that may be layers, uniform or non-uniform gradients (e.g. anisotropic) or provided as portions of the membrane. Furthermore, the region possesses physical properties distinctly different from other portions of the membrane.
  • The terms “accurate” and “accurately” means, for example, 85% of measured glucose values are within the “A” and “B” region of a standard Clarke Error Grid when the sensor measurements are compared to a standard reference measurement. It is understood that like any analytical device, calibration, calibration validation and recalibration are required for the most accurate operation of the device.
  • The term “host” refers to humans and other animals.
  • In the disclosure that follows, the invention will primarily be referred to in terms of assay of glucose and solutions such as blood that tend to contain a large excess of glucose over oxygen. However, it is well within the contemplation of the present invention that the membrane is not limited solely to the assay of glucose in a biological fluid, but may be used for the assay of other compounds. In addition, the sensor primarily referred to is an electrochemical sensor that directly measures hydrogen peroxide. However, it is well within the contemplation of the present invention that non-electrochemical based sensors that use optical detectors or other suitable detectors may be used to evaluate an analyte.
  • Membranes of the prior art have generally been unreliable at limiting the passage of glucose to implantable glucose sensors. This has presented a problem in the past in that the amount of glucose coming into contact with the immobilized enzyme exceeds the amount of oxygen available. As a result, the oxygen concentration is the rate-limiting component of the reaction, rather than the glucose concentration, such that the accuracy of the glucose measurement in the body fluid is compromised.
  • As described above, in contrast to the present invention, a disadvantage of prior art membranes for regulating analyte transport therethrough has been their tendency to form large undesirable structures (see FIG. 1) that are observable when the membrane is hydrated. In particular, these hydrated structures can be detected by photomicroscopy under magnifications in the range of between 200×-400×, for example. They have been shown by the present inventors to be non-uniform in their dimensions through the membrane, with some being of the same size and same order of dimensions as the electrode size. These large structures have been found to be problematic in that they can result in a locally high concentration of either hydrophobic or hydrophilic material in association with the working electrode, which can lead to inaccurate glucose readings. Moreover, they can greatly reduce the number of glucose diffusion paths available.
  • The membrane of the present invention seeks to circumvent these problems associated with prior art membranes by providing a reliable homogeneous membrane that regulates the transport of glucose or other analytes therethrough, the membrane having (a) a matrix including a first polymer; and (b) a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which when hydrated are not observable using photomicroscopy at 400× magnification or less. In one embodiment of the invention, the membrane is substantially free of observable domains.
  • We refer now to FIG. 3, which shows a photomicrograph of a cross-section of a membrane 5 according to the present invention following hydration at two hours. As shown in FIG. 3, the membrane is devoid of any undesirable, large elliptical or spherical structures, such as were observable in hydrated prior art membranes at similar magnifications. It is noted that particles 6 in membrane 5 are dust particles.
  • For purposes of the present invention, it is likely that glucose permeability and diffusion is related to the ratio of hydrophobic to hydrophilic constituents and their distribution throughout the membrane, with diffusion occurring substantially along assembled hydrophilic segments from the side of the membrane in contact with the host to the sensing side.
  • Referring now to FIG. 4, membrane 42 of the present invention, in accordance with a particular arrangement, is schematically shown having hydrophilic segments 44 dispersed substantially throughout a hydrophobic matrix 46 and presenting a surface 48 to a hydrophilic body fluid. The hydrophilic body fluid contains the sample to be assayed. In one embodiment, the body fluid contains both glucose and oxygen. Membrane 42 restricts the rate at which glucose enters and passes through the membrane and/or may increase the rate at which oxygen enters and passes through membrane 42.
  • While not wishing to be bound by any one theory, it is likely that glucose diffuses substantially along hydrophilic segments 44, but is generally excluded from the hydrophobic matrix 46. It is noted that while the hydrophilic segments 44 are shown as comprising discrete microdomains in FIG. 4, small amounts of hydrophobic polymer may be present therein, particularly at the interface with the hydrophobic matrix 46. Similarly, small amounts of hydrophilic polymer may be present in the hydrophobic matrix 46, particularly at the interface with hydrophilic segments 44.
  • In the embodiment shown in FIG. 4, inventive membrane 42 is shown in combination with a sensor 50, which is positioned adjacent to the membrane. It is noted that additional membranes or layers may be situated between membrane 42 and sensor 50, as will be discussed in further detail below. Diffusion of the sample along paths 52 through membrane 42 into association with a working electrode 54 of sensor 50 causes development of a signal that is proportional to the amount of analyte in the sample. Determination of the analyte may be made by calculations based upon similar measurements made on standard solutions containing known concentrations of the analyte. For example, one or more electrodes may be used to detect the amount of analyte in the sample and convert that information into a signal; the signal may then be transmitted to electronic circuitry required to process biological information obtained from the host. U.S. Pat. Nos. 4,757,022, 5,497,772 and 4,787,398 describe suitable electronic circuitry that may be utilized with implantable devices of the present invention.
  • The present invention solves a need in the art by providing a reliable membrane for controlling glucose diffusion therethrough. As shown in FIG. 4, glucose can traverse along hydrophilic segments 44 from the side 48 of the membrane in contact with a body fluid to the side 56 proximal to sensor 50. The hydrophilic microdomains 44 are likely distributed substantially evenly throughout the membrane. Furthermore, these microdomains are likely substantially uniform in size throughout the membrane. The size and order to dimensions of these microdomains is considerably less than the that of the working electrode 54 of sensor 50. As such, the electrode is in association with a useful amount of both the hydrophobic 46 and hydrophilic 44 regions of the membrane to allow effective control over the amount of glucose diffusing to the electrode. Moreover, as shown in FIG. 4, the number of paths available for glucose to permeate the membrane and diffuse from side 48 to the sensing side 56 would be greater for the inventive membrane than for prior art membranes. Consequently, more accurate and reproducible glucose readings are attainable across the entire inventive membrane.
  • FIG. 5 shows a preferred embodiment of the present invention wherein membrane 42 is used in combination with a proximal membrane layer 58 that comprises an enzyme that is reactive with the analyte. In this instance, diffusion of the sample from side 48 through the membrane 42 into contact with the immobilized enzyme in layer 58 leads to an enzymatic reaction in which the reaction products may be measured. For example, in one embodiment the analyte is glucose. In a further embodiment, the enzyme immobilized in layer 58 is glucose oxidase.
  • As described above, glucose oxidase catalyzes the conversion of oxygen and glucose to hydrogen peroxide and gluconic acid. Because for each glucose molecule metabolized, there is proportional change in the co-reactant O2 and the product H2O2, one can monitor the change in either the co-reactant or the product to determine glucose concentration. With further reference to FIG. 5, diffusion of the resulting hydrogen peroxide through layer 58 to the sensor 50, (e.g. electrochemically reactive surfaces), causes the development of an electrical current that can be detected. This enables determination of the glucose by calculations based upon similar measurements made on standard solutions containing known concentrations of glucose.
  • In addition to glucose oxidase, the present invention contemplates the use of a layer impregnated with other oxidases, e.g. galactose oxidase or uricase. For an enzyme-based electrochemical glucose sensor to perform well, the sensor's response must neither be limited by enzyme activity nor cofactor concentration. Because enzymes, including glucose oxidase, are subject to deactivation as a function of ambient conditions, this behavior needs to be accounted for in constructing sensors for long-term use.
  • When the membrane of the present invention is combined with an enzyme layer 58 as shown in FIG. 5, it is the enzyme layer that is located more proximally to the sensor 50 (e.g. electrochemically reactive surfaces). It is noted that enzyme-containing layer 58 must be of sufficient permeability to 1) freely pass glucose to active enzyme and 2) to permit the rapid passage of hydrogen peroxide to the sensor (electrode surface). A failure to permit the rapid passage of glucose to the active enzyme or hydrogen peroxide from the active enzyme to the electrode surface can cause a time delay in the measured signal and thereby lead to inaccurate results.
  • Preferably, the enzyme layer is comprised of aqueous polyurethane-based latex into which the enzyme is immobilized.
  • It is noted that while the inventive membrane 42 may itself contain immobilized enzymes for promoting a reaction between glucose and oxygen, it is preferred that the enzyme be located in a separate layer, such as layer 58 shown in FIG. 5. As described above, it is known that enzyme actively reacting with glucose is more susceptible to irreversible inactivation. Therefore, a disadvantage of providing enzyme in a layer that is semi-permeable to glucose, is that the calibration factors of the sensor may change over time as the working enzyme degrades. In contrast, when enzyme is dispersed throughout a membrane freely permeable to glucose (i.e. layer 58 in FIG. 5), such a membrane is likely to yield calibration factors that are more stable over the life of a sensor.
  • In one preferred embodiment of the invention, the first polymer of the membrane includes homopolymer A and the second polymer includes copolymer AB.
  • In another embodiment, the first polymer includes copolymer AB and the second polymer includes copolymer AB. Preferably, the amount of B in copolymer AB of the first polymer is different than the amount of B in copolymer AB of the second polymer. In particular, the membrane may be formed from a blend of two AB copolymers, where one of the copolymers contains more of a hydrophilic B polymer component than the blended targeted amount and the other copolymer contains less of a hydrophilic B polymer component than the blended targeted amount.
  • In yet another embodiment of the invention, the first polymer includes homopolymer A and the second polymer includes homopolymer B.
  • As described above, the invention also provides a polymeric membrane for regulating the transport of analytes that includes at least one block copolymer AB, wherein B forms a network of microdomains which are not photomicroscopically observable when hydrated at 400× magnification or less. In one embodiment, the ratio of A to B in copolymer AB is 70:30 to 90:10.
  • For each of the inventive embodiments herein described, homopolymer A is preferably a hydrophobic A polymer. Moreover, copolymer AB is preferably a hydrophobic-hydrophilic copolymer component that includes the reaction products of a hydrophobic A polymer and a hydrophilic B polymer. Suitable materials for preparing membranes the present invention are described below.
  • For purposes of the present invention, copolymer AB may be a random or ordered block copolymer. Specifically, the random or ordered block copolymer may be selected from the following: ABA block copolymer, BAB block copolymer, AB random alternating block copolymer, AB regularly alternating block copolymer and combinations thereof.
  • In a preferred embodiment, the sensor, membrane, and methods of the present invention may be used to determine the level of glucose or other analytes in a host. The level of glucose is a particularly important measurement for individuals having diabetes in that effective treatment depends on the accuracy of this measurement.
  • In particular, the invention provides a method of measuring glucose in a biological fluid that includes the steps of: (a) providing (i) a host, and (ii) an implantable device for measuring an analyte in a hydrophilic body fluid, where the device includes a polymeric membrane having a matrix including a first polymer and a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which are not photomicroscopically observable when hydrated at 400× magnification or less; and a proximal layer of enzyme reactive with the analyte; and (b) implanting the device in the host. In one embodiment, the device is implanted subcutaneously.
  • The invention also provides a method of measuring glucose in a biological fluid that includes the following steps: (a) providing (i) a host, and (ii) an implantable device for measuring an analyte in a hydrophilic body fluid, that includes a polymeric membrane including a matrix including a first polymer and a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which are not photomicroscopically observable when hydrated at 400× magnification or less; and a proximal layer of enzyme reactive with the analyte, the device being capable of accurate continuous glucose sensing; and (b) implanting the device in the host. Desirably, the implant is placed subcutaneously in the host.
  • Glucose sensors that use, for example, glucose oxidase to effect a reaction of glucose and oxygen are known in the art, and are within the skill of one in the art to fabricate (see, for example, U.S. Pat. Nos. 5,165,407, 4,890,620, 5,390,671, 5,391,250, 6,001,067 as well as copending, commonly owned U.S. patent application Ser. No. 09/916,858. It is noted that the present invention does not depend on a particular configuration of the sensor, but is rather dependent on the use of the inventive membrane to cover or encapsulate the sensor elements.
  • For the electrochemical glucose sensor to provide useful results, the glucose concentration, as opposed to oxygen concentration, must be the limiting factor. In order to make the system sensitive to glucose concentration, oxygen must be present within the membrane in excess of the glucose. In addition, the oxygen must be in sufficient excess so that it is also available for electrochemical reactions occurring at the amperometric electrode surfaces. In a preferred embodiment, the inventive membrane is designed so that oxygen can pass readily into and through the membrane and so that a reduced amount of glucose diffuses into and through the membrane into contact with an immobilized glucose oxidase enzyme. The inventive membrane allows the ratio of oxygen to glucose to be changed from a concentration ratio in the body fluid of about approximately 50 and 100 parts of glucose to 1 of oxygen to a new ratio in which there is a stoichiometric excess of oxygen in the enzyme layer. Through the use of the inventive membrane, an implantable glucose sensor system is not limited by the concentration of oxygen present in subcutaneous tissues and can therefore operate under the premise that the glucose oxidase reaction behaves as a 1-substrate (glucose) dependent process.
  • The present invention provides a semi-permeable membrane that controls the flux of oxygen and glucose to an underlying enzyme layer, rendering the necessary supply of oxygen in non-rate-limiting excess. As a result, the upper limit of linearity of glucose measurement is extended to a much higher value than that which could be achieved without the membrane of the present invention. In particular, in one embodiment the membrane of the present invention is a polymer membrane with oxygen-to-glucose permeability ratios of approximately 200:1; as a result, 1-dimensional reactant diffusion is adequate to provide excess oxygen at all reasonable glucose and oxygen concentrations found in a subcutaneous matrix [Rhodes, et al., Anal. Chem., 66: 1520-1529 (1994)].
  • A hydrophilic or “water loving” solute such as glucose is readily partitioned into a hydrophilic material, but is generally excluded from a hydrophobic material. However, oxygen can be soluble in both hydrophilic and hydrophobic materials. These factors affect entry and transport of components in the inventive membrane. The hydrophobic portions of the inventive membrane hinder the rate of entry of glucose into the membrane, and therefore to the proximal enzyme layer while providing access of oxygen through both the hydrophilic and hydrophobic portions to the underlying enzyme.
  • In one preferred embodiment, the membrane of the invention is formed from a blend of polymers including (i) a hydrophobic A polymer component; and (ii) a hydrophobic-hydrophilic copolymer component blended with component (i) that forms hydrophilic B domains that control the diffusion of an analyte therethrough, wherein the copolymer component includes a random or ordered block copolymer. Suitable block copolymers are described above. One is able to modify the glucose permeability and the glucose diffusion characteristics of the membrane by simply varying the polymer composition.
  • In one preferred embodiment, the hydrophobic A polymer is a polyurethane. In a most preferred embodiment, the polyurethane is polyetherurethaneurea. A polyurethane is a polymer produced by the condensation reaction of a diisocyanate and a difunctional hydroxyl-containing material. A polyurethaneurea is a polymer produced by the condensation reaction of a diisocyanate and a difunctional amine-containing material. Preferred diisocyanates include aliphatic diisocyanates containing from 4 to 8 methylene units. Diisocyanates containing cycloaliphatic moieties, may also be useful in the preparation of the polymer and copolymer components of the membrane of the present invention. The invention is not limited to the use of polyurethanes as the hydrophobic polymer A component. The material that forms the basis of the hydrophobic matrix of the inventive membrane may be any of those known in the art as appropriate for use as membranes in sensor devices and having sufficient permeability to allow relevant compounds to pass through it, for example, to allow an oxygen molecule to pass through the inventive membrane from the sample under examination in order to reach the active enzyme or electrochemical electrodes. Examples of materials which may be used to make a non-polyurethane type membrane include vinyl polymers, polyethers, polyesters, polyamides, inorganic polymers such as polysiloxanes and polycarbosiloxanes, natural polymers such as cellulosic and protein based materials and mixtures or combinations thereof.
  • As described above, the hydrophobic-hydrophilic copolymer component includes the reaction products of a hydrophobic A polymer component and a hydrophilic B polymer component. The hydrophilic B polymer component is desirably polyethylene oxide. For example, one useful hydrophobic-hydrophilic copolymer component is a polyurethane polymer that includes about 20% hydrophilic polyethyelene oxide. The polyethylene oxide portion of the copolymer is thermodynamically driven to separate from the hydrophobic portions of the copolymer and the hydrophobic A polymer component. The 20% polyethylene oxide based soft segment portion of the copolymer used to form the final blend controls the water pick-up and subsequent glucose permeability of the membrane of the present invention.
  • The polyethylene oxide may have an average molecular weight of from 200 to 3000 with a preferred molecular weight range of 600 to 1500 and preferably constitutes about 20% by weight of the copolymer component used to form the membrane of the present invention.
  • It is desired that the membrane of the present invention have a thickness of about 5 to about 100 microns. In preferred embodiments, the membrane of the present invention is constructed of a polyetherurethaneurea/polyetherurethaneurea-block-polyethylene glycol blend and has a thickness of not more than about 100 microns, more preferably not less than about 10 microns, and not more than about 80 microns, and most preferably, not less than about 20 microns, and not more than about 60 microns.
  • The membrane of the present invention can be made by casting from solutions, optionally with inclusion of additives to modify the properties and the resulting cast film or to facilitate the casting process.
  • The present invention provides a method for preparing the implantable membrane of the invention. The method includes the steps of: (a) forming a composition including a dispersion of a second polymer within a matrix of a first polymer, the dispersion forming a network of microdomains which are not photomicroscopically observable when hydrated at 400× magnification or less; (b) maintaining the composition at a temperature sufficient to maintain the first polymer and the second polymer substantially soluble; (c) applying the composition at the temperature to a substrate to form a film thereon; and (d) permitting the resultant film to dry to form the membrane. In one embodiment, the forming step includes forming a mixture or a blend. As described above, in preferred embodiments, the first polymer is a polyurethane and the second polymer is polyethylene oxide. In general, the second polymer may be a random or ordered block copolymer selected from the following: ABA block copolymer, BAB block copolymer, AB random alternating block copolymer, AB regularly alternating block copolymer and combinations thereof.
  • In one embodiment, the composition comprised of a dispersion of the second polymer within the matrix of a first polymer is heated to a temperature of about 70° C. to maintain the first and second polymers substantially soluble. For example, the combination of a hydrophobic polymer A component and a hydrophobic-hydrophilic copolymer AB component is desirably exposed to a temperature of about 70° C. to maintain the polymer and copolymers substantially soluble. In particular, the blend is heated well above room temperature in order to keep the hydrophilic and hydrophobic components soluble with each other and the solvent.
  • The invention contemplates permitting the coated film formed on the substrate to dry at a temperature from about 120° C. to about 150° C. The elevated temperature further serves to drive the solvent from the coating as quickly as possible. This inhibits the hydrophilic and hydrophobic portions of the membrane from segregating and forming large undesired structures.
  • The membrane and sensor combinations of the present invention provide a significant advantage over the prior art in that they provide accurate sensor operation at temperatures from about 30° C. to about 45° C. for a period of time exceeding about 30 days to exceeding about a year.
  • EXAMPLES Example 1
  • A Method for Preparing a Membrane of the Present Invention
  • The inventive membrane may be cast from a coating solution. The coating solution is prepared by placing approximately 281 gm of dimethylacetamide (DMAC) into a 3 L stainless steel bowl to which a solution of polyetherurethaneurea (344 gm of Chronothane H (Cardiotech International, Inc., Woburn, Mass.), 29,750 cp @ 25% solids in DMAC) is added. To this mixture is added another polyetherurethaneurea (approximately 312 gm, Chronothane 1020 (Cardiotech International, Inc., Woburn, Mass.), 6275 cp @ 25% solids in DMAC). The bowl is then fitted to a planetary mixer with a paddle-type blade and the contents are stirred for 30 minutes at room temperature. Coatings solutions prepared in this manner are then coated at between room temperature to about 70° C. onto a PET release liner (Douglas Hansen Co., Inc., Minneapolis, Mn.) using a knife-over-roll set at a 0.012 inch gap. The film is continuously dried at 120° C. to about 150° C. The final film thickness is approximately 0.0015 inches.
  • Observations of Membrane Using Photomicroscopy at 400× Magnification or Less
  • A ¼″ by ¼″ piece of membrane is first immersed in deionized water for a minimum of 2 hours at room temperature. After this time, the sample is placed onto a microscope slide along with one drop of water. A glass cover slide is then placed over the membrane and gentle pressure is applied in order to remove excess liquid from underneath the cover glass. In this way, the membrane does not dry during its evaluation. The hydrated membrane sample is first observed at 40X-magnification using a light microscope (Nikon Eclipse E400). If air bubbles are present on the top or bottom of the film, the cover glass is gently pressed again with a tissue in order to remove them. Magnification is then increased to 200×; and the hydrated membrane is continuously observed while changing the focus from the top to bottom of the film. This is followed by an increase in magnification to 400×, with the membrane again being continuously observed while changing the focus from the top to bottom of the film.
  • Results
  • Based on the results of an optical micrograph of a sample membrane prepared by using a room temperature coating solution and drying of the coated film at 120° C., the micrograph being captured as described above, it was noticed that both circular and elliptical domains were present throughout the hydrated section of membrane. At the same magnification, the domains were not observable in dry membrane. Giving that in an electrochemical sensor, the electrodes included therein are typically of the same size and same order of dimensions as the observed circular and elliptical domains, such domains are not desired. These domains present a problem in that they result in a locally high concentration of either hydrophilic or hydrophobic material in association with the electrodes.
  • Example 2
  • Optimizing the Coating Solution Conditions
  • This example demonstrates that preheating the coating solution to a temperature of 70° C. prior to coating eliminates the presence of both the circular and elliptical domains that were present throughout the hydrated cross-section of a membrane prepared using a room temperature coating solution and drying of the coated film at 120° C. Example 2 further demonstrates that, provided the coating solution is preheated to about 70° C., either a standard (120°) or elevated (150° C.) drying temperature were sufficient to drive the DMAC solvent from the coated film quickly to further inhibit the hydrophilic and hydrophobic portions of the polyurethane membrane from segregating into large domains.
  • In particular, the invention was evaluated by performing a coating experiment where standard coating conditions (room temperature coating solution and 120° C. drying temperature of the coated film) were compared to conditions where the coating solution temperature was elevated and/or the drying temperature of the coated film was elevated. Four experimental conditions were run as follows:
      • SS-room temperature solution and standard (120° C.) oven temperature.
      • SE-room temperature solution and elevated (150° C.) oven temperature.
      • ES-preheated (70° C.) solution and standard (120° C.) oven temperature.
      • EE-preheated (70° C.) solution and elevated (150° C.) oven temperature.
        Results
  • Samples of each of the four membranes listed above were then hydrated for 2 hours, and then observed under the microscope. Performance specifications were achieved when the micrograph of the membrane prepared under a given condition showed an absence of circular and/or elliptical domains that result in an undesirable, discontinuous hydrophilic and hydrophobic membrane structure. Table 1 below summarizes these results where (+) indicates a membrane meeting desired performance specifications and (−) is indicative of a membrane showing the undesirable circular and/or elliptical domains. In summary, for both the ES and EE conditions, where the coating solution was preheated to 70° C. prior to coating on a substrate, no hydrated domains were observed at a 200× magnification. Furthermore, regardless of the drying temperature used for the coated film, when the coating solution was not preheated (conditions SS and SE), the hydrated structures were observed. Therefore, it is likely that preheating the coating solution effectively inhibits the hydrophilic and hydrophobic segments of the polyurethane from segregating into large domains.
    TABLE 1
    Coating Condition Result
    SS
    SE
    ES (Inventive) +
    EE (Inventive) +
  • Example 3
  • Evaluation of The Inventive Membranes for Their Permeability to Glucose and H2O2
  • Membranes prepared under the EE condition described in Example 2 were evaluated for their ability to allow glucose and hydrogen peroxide to get through the membrane to a sensor. In particular, a series of polyurethane blends of the present invention were generated wherein the percentage of Chronothane H in a coating blend was varied. Furthermore, one of these blends (57.5% Chronothane H in coating blend) was prepared under both the EE condition and the SS condition as described in Example 2. FIG. 6 shows that the sensor output generated with a series of polyurethane blends of the present invention was dependent upon the percentage of the Chronothane H. In particular, the sensor output increased as the percentage of Chronothane H in the coating blend increased. With further reference to FIG. 6, when the percentage of Chronothane H in the coating blend was 57.5%, the sensor output was three times greater for the membrane prepared under the optimized EE coating condition as compared to the non-optimized SS coating condition.
  • Furthermore, FIG. 7 demonstrates that, regardless of the percent Chronothane H in the coating blend, an inventive membrane prepared under the EE condition shows a fairly constant percent standard deviation of sensor output. Moreover, a membrane prepared with 57.5% Chronothane H in the coating blend under the SS condition showed a percent standard deviation of sensor output approximately twice that of an EE membrane prepared with the same percentage of Chronothane H in the blend. It is noted that given that the sensor output is a true measure of the amount of glucose getting through the membrane to the sensor, the results indicate that the permeability of glucose and H2O2 is relatively constant throughout a given inventive membrane prepared under optimized coating conditions (i.e., EE conditions). This is important from a manufacturing standpoint.
  • Having described the particular, preferred embodiments of the invention herein, it should be appreciated that modifications may be made therethrough without departing from the contemplated scope of the invention. The true scope of the invention is set forth in the claims appended hereto.

Claims (21)

1. A method of fabricating a device for measuring a concentration of an analyte, the method comprising the steps of:
providing a sensor configured to measure the analyte or a product of a reaction representative of the analyte;
forming a composition comprising a blend of a first polymer and a second polymer, wherein the first polymer is at least partially hydrophilic and the second polymer is at least partially hydrophobic;
maintaining the composition at a temperature sufficient to maintain solubility of the first polymer and the second polymer;
forming a film from the composition at the temperature;
drying the film to form a membrane; and
coupling the membrane to the sensor.
2. The method of claim 1, wherein the first polymer and the second polymer have similar backbone structures.
3. The method of claim 1, wherein the first polymer and the second polymer have miscible backbone structures.
4. The method of claim 1, wherein the first polymer and the second polymer have soluble backbone structures.
5. The method of claim 1, wherein the step of forming a composition comprises forming a physical mixture.
6. The method of claim 1, the step of forming a composition comprises forming a mixture substantially without chemical reaction of the first polymer and the second polymer.
7. The method of claim 1, wherein the step of forming a film comprises casting a film onto a substrate.
8. The method of claim 1, wherein the step of forming a film comprises casting a film onto the sensor.
9. The method of claim 1, wherein the step of maintaining the composition at a temperature comprises heating the composition at a temperature of at least about 70° C.
10. The method of claim 9, wherein the step of drying the film comprises drying at a temperature of at least about 120° C.
11. The method of claim 1, wherein the first polymer comprises a substantially hydrophobic homopolymer and the second polymer comprises a hydrophobic-hydrophilic copolymer.
12. The method of claim 1, wherein the first polymer comprises a hydrophobic-hydrophilic copolymer and the second polymer comprises a hydrophobic-hydrophilic copolymer.
13. The method of claim 1, wherein the first polymer comprises a hydrophobic homopolymer and the second polymer comprises a hydrophilic homopolymer.
14. The method of claim 1, wherein the first polymer comprises polyethylene oxide.
15. The method of claim 1, wherein the second polymer comprises polyurethane.
16. The method of claim 1, wherein the second polymer comprises polysiloxane.
17. An implantable sensor formed in accordance with the method of claim 1.
18. A glucose sensor formed in accordance with the method of claim 1.
19. A method for forming a sensor, the method comprising the steps of:
providing a sensor configured to measure an analyte or a product of a reaction representative of the analyte;
forming a composition comprising a matrix comprising a substantially hydrophobic polymer, and a hydrophobic-hydrophilic polymer dispersed throughout the matrix;
maintaining the composition at a temperature sufficient to maintain solubility of the a substantially hydrophobic polymer and the hydrophobic-hydrophilic polymer;
casting a film from the composition at the temperature; and
drying the film to form a membrane.
20. The method of claim 19, further comprising the step of measuring the analyte, wherein the membrane restricts a flux of the analyte through the membrane.
21. The method of claim 20, wherein the sensor comprises an electrochemically reactive surface area, and wherein the analyte substantially uniformly flows through the membrane when the membrane is placed in an aqueous environment.
US11/280,102 2002-05-22 2005-11-16 Techniques to improve polyurethane membranes for implantable glucose sensors Abandoned US20060068208A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US11/280,102 US20060068208A1 (en) 2002-05-22 2005-11-16 Techniques to improve polyurethane membranes for implantable glucose sensors

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10/153,356 US7226978B2 (en) 2002-05-22 2002-05-22 Techniques to improve polyurethane membranes for implantable glucose sensors
US11/280,102 US20060068208A1 (en) 2002-05-22 2005-11-16 Techniques to improve polyurethane membranes for implantable glucose sensors

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US10/153,356 Division US7226978B2 (en) 2002-05-22 2002-05-22 Techniques to improve polyurethane membranes for implantable glucose sensors

Publications (1)

Publication Number Publication Date
US20060068208A1 true US20060068208A1 (en) 2006-03-30

Family

ID=29548646

Family Applications (10)

Application Number Title Priority Date Filing Date
US10/153,356 Expired - Lifetime US7226978B2 (en) 2002-05-22 2002-05-22 Techniques to improve polyurethane membranes for implantable glucose sensors
US11/280,672 Active 2024-11-12 US8050731B2 (en) 2002-05-22 2005-11-16 Techniques to improve polyurethane membranes for implantable glucose sensors
US11/280,102 Abandoned US20060068208A1 (en) 2002-05-22 2005-11-16 Techniques to improve polyurethane membranes for implantable glucose sensors
US12/688,737 Expired - Lifetime US8053018B2 (en) 2002-05-22 2010-01-15 Techniques to improve polyurethane membranes for implantable glucose sensors
US13/283,397 Abandoned US20120040101A1 (en) 2002-05-22 2011-10-27 Techniques to improve polyurethane membranes for implantable glucose sensors
US13/631,780 Expired - Lifetime US8865249B2 (en) 2002-05-22 2012-09-28 Techniques to improve polyurethane membranes for implantable glucose sensors
US14/482,458 Expired - Lifetime US9179869B2 (en) 2002-05-22 2014-09-10 Techniques to improve polyurethane membranes for implantable glucose sensors
US14/875,539 Expired - Lifetime US9801574B2 (en) 2002-05-22 2015-10-05 Techniques to improve polyurethane membranes for implantable glucose sensors
US15/716,998 Expired - Lifetime US10154807B2 (en) 2002-05-22 2017-09-27 Techniques to improve polyurethane membranes for implantable glucose sensors
US16/185,957 Abandoned US20190083018A1 (en) 2002-05-22 2018-11-09 Techniques to improve polyurethane membranes for implantable glucose sensors

Family Applications Before (2)

Application Number Title Priority Date Filing Date
US10/153,356 Expired - Lifetime US7226978B2 (en) 2002-05-22 2002-05-22 Techniques to improve polyurethane membranes for implantable glucose sensors
US11/280,672 Active 2024-11-12 US8050731B2 (en) 2002-05-22 2005-11-16 Techniques to improve polyurethane membranes for implantable glucose sensors

Family Applications After (7)

Application Number Title Priority Date Filing Date
US12/688,737 Expired - Lifetime US8053018B2 (en) 2002-05-22 2010-01-15 Techniques to improve polyurethane membranes for implantable glucose sensors
US13/283,397 Abandoned US20120040101A1 (en) 2002-05-22 2011-10-27 Techniques to improve polyurethane membranes for implantable glucose sensors
US13/631,780 Expired - Lifetime US8865249B2 (en) 2002-05-22 2012-09-28 Techniques to improve polyurethane membranes for implantable glucose sensors
US14/482,458 Expired - Lifetime US9179869B2 (en) 2002-05-22 2014-09-10 Techniques to improve polyurethane membranes for implantable glucose sensors
US14/875,539 Expired - Lifetime US9801574B2 (en) 2002-05-22 2015-10-05 Techniques to improve polyurethane membranes for implantable glucose sensors
US15/716,998 Expired - Lifetime US10154807B2 (en) 2002-05-22 2017-09-27 Techniques to improve polyurethane membranes for implantable glucose sensors
US16/185,957 Abandoned US20190083018A1 (en) 2002-05-22 2018-11-09 Techniques to improve polyurethane membranes for implantable glucose sensors

Country Status (5)

Country Link
US (10) US7226978B2 (en)
EP (1) EP1506307A1 (en)
JP (1) JP4317519B2 (en)
AU (1) AU2003229330A1 (en)
WO (1) WO2003100083A1 (en)

Cited By (73)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060036145A1 (en) * 2004-07-13 2006-02-16 Dexcom, Inc. Transcutaneous analyte sensor
US20060222566A1 (en) * 2003-08-01 2006-10-05 Brauker James H Transcutaneous analyte sensor
WO2007102842A2 (en) 2006-03-09 2007-09-13 Dexcom, Inc. Systems and methods for processing analyte sensor data
US20080292026A1 (en) * 2006-08-25 2008-11-27 Alcatel Lucent Digital signal receiver with q-monitor
US20090045055A1 (en) * 2001-07-27 2009-02-19 Dexcom, Inc. Sensor head for use with implantable devices
US20090247855A1 (en) * 2008-03-28 2009-10-01 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US7792562B2 (en) 1997-03-04 2010-09-07 Dexcom, Inc. Device and method for determining analyte levels
US7811231B2 (en) 2002-12-31 2010-10-12 Abbott Diabetes Care Inc. Continuous glucose monitoring system and methods of use
US7828728B2 (en) 2003-07-25 2010-11-09 Dexcom, Inc. Analyte sensor
US7860544B2 (en) 1998-04-30 2010-12-28 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US7857760B2 (en) 2004-07-13 2010-12-28 Dexcom, Inc. Analyte sensor
US7920907B2 (en) 2006-06-07 2011-04-05 Abbott Diabetes Care Inc. Analyte monitoring system and method
US7976778B2 (en) 2001-04-02 2011-07-12 Abbott Diabetes Care Inc. Blood glucose tracking apparatus
US8050731B2 (en) 2002-05-22 2011-11-01 Dexcom, Inc. Techniques to improve polyurethane membranes for implantable glucose sensors
US8064977B2 (en) 2002-05-22 2011-11-22 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US8160669B2 (en) 2003-08-01 2012-04-17 Dexcom, Inc. Transcutaneous analyte sensor
US8229535B2 (en) 2008-02-21 2012-07-24 Dexcom, Inc. Systems and methods for blood glucose monitoring and alert delivery
US8255033B2 (en) 2003-07-25 2012-08-28 Dexcom, Inc. Oxygen enhancing membrane systems for implantable devices
US8277713B2 (en) 2004-05-03 2012-10-02 Dexcom, Inc. Implantable analyte sensor
US8280475B2 (en) 2004-07-13 2012-10-02 Dexcom, Inc. Transcutaneous analyte sensor
US8287454B2 (en) 1998-04-30 2012-10-16 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
US8465425B2 (en) 1998-04-30 2013-06-18 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
WO2013152090A2 (en) 2012-04-04 2013-10-10 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
US8560039B2 (en) 2008-09-19 2013-10-15 Dexcom, Inc. Particle-containing membrane and particulate electrode for analyte sensors
US8565848B2 (en) 2004-07-13 2013-10-22 Dexcom, Inc. Transcutaneous analyte sensor
US8583204B2 (en) 2008-03-28 2013-11-12 Dexcom, Inc. Polymer membranes for continuous analyte sensors
WO2013184566A2 (en) 2012-06-05 2013-12-12 Dexcom, Inc. Systems and methods for processing analyte data and generating reports
US8612159B2 (en) 1998-04-30 2013-12-17 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
WO2014004460A1 (en) 2012-06-29 2014-01-03 Dexcom, Inc. Use of sensor redundancy to detect sensor failures
WO2014011488A2 (en) 2012-07-09 2014-01-16 Dexcom, Inc. Systems and methods for leveraging smartphone features in continuous glucose monitoring
US8652043B2 (en) 2001-01-02 2014-02-18 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8682408B2 (en) 2008-03-28 2014-03-25 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US8688188B2 (en) 1998-04-30 2014-04-01 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
WO2014052080A1 (en) 2012-09-28 2014-04-03 Dexcom, Inc. Zwitterion surface modifications for continuous sensors
US8744546B2 (en) 2005-05-05 2014-06-03 Dexcom, Inc. Cellulosic-based resistance domain for an analyte sensor
WO2014158327A2 (en) 2013-03-14 2014-10-02 Dexcom, Inc. Advanced calibration for analyte sensors
WO2014158405A2 (en) 2013-03-14 2014-10-02 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
EP2796093A1 (en) 2007-03-26 2014-10-29 DexCom, Inc. Analyte sensor
EP2796090A1 (en) 2006-10-04 2014-10-29 DexCom, Inc. Analyte sensor
US8974386B2 (en) 1998-04-30 2015-03-10 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
WO2015156966A1 (en) 2014-04-10 2015-10-15 Dexcom, Inc. Sensors for continuous analyte monitoring, and related methods
WO2016085556A1 (en) * 2014-09-12 2016-06-02 Cell and Molecular Tissue Engineering, LLC Coated implants, and corresponding systems and methods
US9439589B2 (en) 1997-03-04 2016-09-13 Dexcom, Inc. Device and method for determining analyte levels
EP3092949A1 (en) 2011-09-23 2016-11-16 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
US9795331B2 (en) 2005-12-28 2017-10-24 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
US10130288B2 (en) 2013-03-14 2018-11-20 Cell and Molecular Tissue Engineering, LLC Coated sensors, and corresponding systems and methods
US10405961B2 (en) 2013-03-14 2019-09-10 Cell and Molecular Tissue Engineering, LLC Coated surgical mesh, and corresponding systems and methods
EP3536241A1 (en) 2011-04-08 2019-09-11 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
US10524703B2 (en) 2004-07-13 2020-01-07 Dexcom, Inc. Transcutaneous analyte sensor
US10561349B2 (en) 2016-03-31 2020-02-18 Dexcom, Inc. Systems and methods for display device and sensor electronics unit communication
US10610136B2 (en) 2005-03-10 2020-04-07 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
EP3654348A1 (en) 2012-11-07 2020-05-20 Dexcom, Inc. Systems and methods for managing glycemic variability
US10813577B2 (en) 2005-06-21 2020-10-27 Dexcom, Inc. Analyte sensor
US10856736B2 (en) 2012-12-31 2020-12-08 Dexcom, Inc. Remote monitoring of analyte measurements
US10860687B2 (en) 2012-12-31 2020-12-08 Dexcom, Inc. Remote monitoring of analyte measurements
US10932672B2 (en) 2015-12-28 2021-03-02 Dexcom, Inc. Systems and methods for remote and host monitoring communications
US10980461B2 (en) 2008-11-07 2021-04-20 Dexcom, Inc. Advanced analyte sensor calibration and error detection
US10985804B2 (en) 2013-03-14 2021-04-20 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
US11000215B1 (en) 2003-12-05 2021-05-11 Dexcom, Inc. Analyte sensor
US11112377B2 (en) 2015-12-30 2021-09-07 Dexcom, Inc. Enzyme immobilized adhesive layer for analyte sensors
EP3925522A1 (en) 2017-06-23 2021-12-22 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
US11298058B2 (en) 2005-12-28 2022-04-12 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
US11331022B2 (en) 2017-10-24 2022-05-17 Dexcom, Inc. Pre-connected analyte sensors
US11350862B2 (en) 2017-10-24 2022-06-07 Dexcom, Inc. Pre-connected analyte sensors
EP4046571A1 (en) 2015-10-21 2022-08-24 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
EP4098177A1 (en) 2007-10-09 2022-12-07 DexCom, Inc. Integrated insulin delivery system with continuous glucose sensor
EP4218548A1 (en) 2006-03-09 2023-08-02 Dexcom, Inc. Systems and methods for processing analyte sensor data
US11730407B2 (en) 2008-03-28 2023-08-22 Dexcom, Inc. Polymer membranes for continuous analyte sensors
EP4250312A2 (en) 2007-10-25 2023-09-27 DexCom, Inc. Systems and methods for processing sensor data
US11892426B2 (en) 2012-06-29 2024-02-06 Dexcom, Inc. Devices, systems, and methods to compensate for effects of temperature on implantable sensors
US11918354B2 (en) 2019-12-31 2024-03-05 Dexcom, Inc. Particle-containing membrane and particulate electrode for analyte sensors

Families Citing this family (318)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5593852A (en) 1993-12-02 1997-01-14 Heller; Adam Subcutaneous glucose electrode
US20050033132A1 (en) 1997-03-04 2005-02-10 Shults Mark C. Analyte measuring device
US7192450B2 (en) 2003-05-21 2007-03-20 Dexcom, Inc. Porous membranes for use with implantable devices
US9155496B2 (en) * 1997-03-04 2015-10-13 Dexcom, Inc. Low oxygen in vivo analyte sensor
US6036924A (en) 1997-12-04 2000-03-14 Hewlett-Packard Company Cassette of lancet cartridges for sampling blood
US6134461A (en) 1998-03-04 2000-10-17 E. Heller & Company Electrochemical analyte
US6391005B1 (en) 1998-03-30 2002-05-21 Agilent Technologies, Inc. Apparatus and method for penetration with shaft having a sensor for sensing penetration depth
US8641644B2 (en) 2000-11-21 2014-02-04 Sanofi-Aventis Deutschland Gmbh Blood testing apparatus having a rotatable cartridge with multiple lancing elements and testing means
US7041068B2 (en) 2001-06-12 2006-05-09 Pelikan Technologies, Inc. Sampling module device and method
EP1395185B1 (en) 2001-06-12 2010-10-27 Pelikan Technologies Inc. Electric lancet actuator
US8337419B2 (en) 2002-04-19 2012-12-25 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
WO2002100254A2 (en) 2001-06-12 2002-12-19 Pelikan Technologies, Inc. Method and apparatus for lancet launching device integrated onto a blood-sampling cartridge
US7682318B2 (en) 2001-06-12 2010-03-23 Pelikan Technologies, Inc. Blood sampling apparatus and method
US9795747B2 (en) 2010-06-02 2017-10-24 Sanofi-Aventis Deutschland Gmbh Methods and apparatus for lancet actuation
US9226699B2 (en) 2002-04-19 2016-01-05 Sanofi-Aventis Deutschland Gmbh Body fluid sampling module with a continuous compression tissue interface surface
ES2357887T3 (en) 2001-06-12 2011-05-03 Pelikan Technologies Inc. APPARATUS FOR IMPROVING THE BLOOD OBTAINING SUCCESS RATE FROM A CAPILLARY PUNCTURE.
US7344507B2 (en) 2002-04-19 2008-03-18 Pelikan Technologies, Inc. Method and apparatus for lancet actuation
US7981056B2 (en) 2002-04-19 2011-07-19 Pelikan Technologies, Inc. Methods and apparatus for lancet actuation
CA2448902C (en) 2001-06-12 2010-09-07 Pelikan Technologies, Inc. Self optimizing lancing device with adaptation means to temporal variations in cutaneous properties
US9427532B2 (en) 2001-06-12 2016-08-30 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
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
US9282925B2 (en) 2002-02-12 2016-03-15 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
US8010174B2 (en) 2003-08-22 2011-08-30 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
US9247901B2 (en) 2003-08-22 2016-02-02 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
US7892183B2 (en) 2002-04-19 2011-02-22 Pelikan Technologies, Inc. Method and apparatus for body fluid sampling and analyte sensing
US7297122B2 (en) 2002-04-19 2007-11-20 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7976476B2 (en) 2002-04-19 2011-07-12 Pelikan Technologies, Inc. Device and method for variable speed lancet
US7229458B2 (en) 2002-04-19 2007-06-12 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7371247B2 (en) 2002-04-19 2008-05-13 Pelikan Technologies, Inc Method and apparatus for penetrating tissue
US7232451B2 (en) 2002-04-19 2007-06-19 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7198606B2 (en) 2002-04-19 2007-04-03 Pelikan Technologies, Inc. Method and apparatus for a multi-use body fluid sampling device with analyte sensing
US8702624B2 (en) 2006-09-29 2014-04-22 Sanofi-Aventis Deutschland Gmbh Analyte measurement device with a single shot actuator
US7717863B2 (en) 2002-04-19 2010-05-18 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7291117B2 (en) 2002-04-19 2007-11-06 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7648468B2 (en) 2002-04-19 2010-01-19 Pelikon Technologies, Inc. Method and apparatus for penetrating tissue
US7547287B2 (en) 2002-04-19 2009-06-16 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US9795334B2 (en) 2002-04-19 2017-10-24 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8784335B2 (en) 2002-04-19 2014-07-22 Sanofi-Aventis Deutschland Gmbh Body fluid sampling device with a capacitive sensor
US7674232B2 (en) 2002-04-19 2010-03-09 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7491178B2 (en) 2002-04-19 2009-02-17 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8267870B2 (en) 2002-04-19 2012-09-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for body fluid sampling with hybrid actuation
US8579831B2 (en) 2002-04-19 2013-11-12 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8372016B2 (en) 2002-04-19 2013-02-12 Sanofi-Aventis Deutschland Gmbh Method and apparatus for body fluid sampling and analyte sensing
US7909778B2 (en) 2002-04-19 2011-03-22 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8360992B2 (en) 2002-04-19 2013-01-29 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US9314194B2 (en) 2002-04-19 2016-04-19 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US7901362B2 (en) 2002-04-19 2011-03-08 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7331931B2 (en) 2002-04-19 2008-02-19 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US9248267B2 (en) 2002-04-19 2016-02-02 Sanofi-Aventis Deustchland Gmbh Tissue penetration device
US8221334B2 (en) 2002-04-19 2012-07-17 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7993108B2 (en) 2002-10-09 2011-08-09 Abbott Diabetes Care Inc. Variable volume, shape memory actuated insulin dispensing pump
CA2501825C (en) 2002-10-09 2009-12-01 Therasense, Inc. Fluid delivery device, system and method
US7727181B2 (en) * 2002-10-09 2010-06-01 Abbott Diabetes Care Inc. Fluid delivery device with autocalibration
US7381184B2 (en) 2002-11-05 2008-06-03 Abbott Diabetes Care Inc. Sensor inserter assembly
US7842234B2 (en) 2002-12-02 2010-11-30 Epocal Inc. Diagnostic devices incorporating fluidics and methods of manufacture
US7767068B2 (en) * 2002-12-02 2010-08-03 Epocal Inc. Heterogeneous membrane electrodes
US8574895B2 (en) 2002-12-30 2013-11-05 Sanofi-Aventis Deutschland Gmbh Method and apparatus using optical techniques to measure analyte levels
US7587287B2 (en) 2003-04-04 2009-09-08 Abbott Diabetes Care Inc. Method and system for transferring analyte test data
US7134999B2 (en) 2003-04-04 2006-11-14 Dexcom, Inc. Optimized sensor geometry for an implantable glucose sensor
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
EP1628567B1 (en) 2003-05-30 2010-08-04 Pelikan Technologies Inc. Method and apparatus for fluid injection
ES2490740T3 (en) 2003-06-06 2014-09-04 Sanofi-Aventis Deutschland Gmbh Apparatus for blood fluid sampling and analyte detection
US8066639B2 (en) 2003-06-10 2011-11-29 Abbott Diabetes Care Inc. Glucose measuring device for use in personal area network
US8460243B2 (en) 2003-06-10 2013-06-11 Abbott Diabetes Care Inc. Glucose measuring module and insulin pump combination
WO2006001797A1 (en) 2004-06-14 2006-01-05 Pelikan Technologies, Inc. Low pain penetrating
US8071028B2 (en) 2003-06-12 2011-12-06 Abbott Diabetes Care Inc. Method and apparatus for providing power management in data communication systems
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
US9763609B2 (en) * 2003-07-25 2017-09-19 Dexcom, Inc. Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise
US7591801B2 (en) 2004-02-26 2009-09-22 Dexcom, Inc. Integrated delivery device for continuous glucose sensor
US8369919B2 (en) 2003-08-01 2013-02-05 Dexcom, Inc. Systems and methods for processing sensor data
US6931327B2 (en) 2003-08-01 2005-08-16 Dexcom, Inc. System and methods for processing analyte sensor data
US8275437B2 (en) 2003-08-01 2012-09-25 Dexcom, Inc. Transcutaneous analyte sensor
US8676287B2 (en) 2003-08-01 2014-03-18 Dexcom, Inc. System and methods for processing analyte sensor data
US8761856B2 (en) 2003-08-01 2014-06-24 Dexcom, Inc. System and methods for processing analyte sensor data
US8886273B2 (en) 2003-08-01 2014-11-11 Dexcom, Inc. Analyte sensor
US8285354B2 (en) 2003-08-01 2012-10-09 Dexcom, Inc. System and methods for processing analyte sensor data
US20140121989A1 (en) 2003-08-22 2014-05-01 Dexcom, Inc. Systems and methods for processing analyte sensor data
EP1671096A4 (en) 2003-09-29 2009-09-16 Pelikan Technologies Inc Method and apparatus for an improved sample capture device
EP1680014A4 (en) 2003-10-14 2009-01-21 Pelikan Technologies Inc Method and apparatus for a variable user interface
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
US8364231B2 (en) 2006-10-04 2013-01-29 Dexcom, Inc. Analyte sensor
WO2005057175A2 (en) 2003-12-09 2005-06-23 Dexcom, Inc. Signal processing for continuous analyte sensor
US7822454B1 (en) 2005-01-03 2010-10-26 Pelikan Technologies, Inc. Fluid sampling device with improved analyte detecting member configuration
WO2005065414A2 (en) 2003-12-31 2005-07-21 Pelikan Technologies, Inc. Method and apparatus for improving fluidic flow and sample capture
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
CA2556331A1 (en) 2004-02-17 2005-09-29 Therasense, Inc. Method and system for providing data communication in continuous glucose monitoring and management system
GB0411162D0 (en) * 2004-05-19 2004-06-23 Precisense As Optical sensor for in vivo detection of analyte
US8828203B2 (en) 2004-05-20 2014-09-09 Sanofi-Aventis Deutschland Gmbh Printable hydrogels for biosensors
WO2005120365A1 (en) 2004-06-03 2005-12-22 Pelikan Technologies, Inc. Method and apparatus for a fluid sampling device
US9775553B2 (en) 2004-06-03 2017-10-03 Sanofi-Aventis Deutschland Gmbh Method and apparatus for a fluid sampling device
CA3090413C (en) 2004-06-04 2023-10-10 Abbott Diabetes Care Inc. Glucose monitoring and graphical representations in a data management system
EP2335584B1 (en) 2004-07-13 2015-06-17 DexCom, Inc. Transcutaneous analyte sensor
JP2008510154A (en) * 2004-08-16 2008-04-03 ノボ ノルディスク アクティーゼルスカブ Multiphase biocompatible semipermeable membrane for biosensors
US8097725B2 (en) 2004-12-03 2012-01-17 Roche Diagnostics Operations, Inc. Luminescent indicator dye and optical sensor
US9398882B2 (en) 2005-09-30 2016-07-26 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor and data processing device
US9351669B2 (en) 2009-09-30 2016-05-31 Abbott Diabetes Care Inc. Interconnect for on-body analyte monitoring device
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
US9743862B2 (en) 2011-03-31 2017-08-29 Abbott Diabetes Care Inc. Systems and methods for transcutaneously implanting medical devices
US9788771B2 (en) 2006-10-23 2017-10-17 Abbott Diabetes Care Inc. Variable speed sensor insertion devices 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
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
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
US7731657B2 (en) 2005-08-30 2010-06-08 Abbott Diabetes Care Inc. Analyte sensor introducer and methods of use
US20090082693A1 (en) * 2004-12-29 2009-03-26 Therasense, Inc. Method and apparatus for providing temperature sensor module in a data communication system
US20110054275A1 (en) * 2009-08-31 2011-03-03 Abbott Diabetes Care Inc. Mounting Unit Having a Sensor and Associated Circuitry
US9259175B2 (en) 2006-10-23 2016-02-16 Abbott Diabetes Care, Inc. Flexible patch for fluid delivery and monitoring body analytes
US20090105569A1 (en) 2006-04-28 2009-04-23 Abbott Diabetes Care, Inc. Introducer Assembly and Methods of Use
US7883464B2 (en) 2005-09-30 2011-02-08 Abbott Diabetes Care Inc. Integrated transmitter unit and sensor introducer mechanism and methods of use
US8029441B2 (en) 2006-02-28 2011-10-04 Abbott Diabetes Care Inc. Analyte sensor transmitter unit configuration for a data monitoring and management 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
US10226207B2 (en) 2004-12-29 2019-03-12 Abbott Diabetes Care Inc. Sensor inserter having introducer
US8652831B2 (en) 2004-12-30 2014-02-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for analyte measurement test time
US7545272B2 (en) 2005-02-08 2009-06-09 Therasense, Inc. RF tag on test strips, test strip vials and boxes
EP1863559A4 (en) 2005-03-21 2008-07-30 Abbott Diabetes Care Inc Method and system for providing integrated medication infusion and analyte monitoring system
US8182590B2 (en) * 2005-04-29 2012-05-22 University Of Rochester Ultrathin porous nanoscale membranes, methods of making, and uses thereof
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
WO2006119252A2 (en) * 2005-04-29 2006-11-09 University Of Rochester Ultrathin nanoscale membranes, methods of making, and uses thereof
US7768408B2 (en) 2005-05-17 2010-08-03 Abbott Diabetes Care Inc. Method and system for providing data management in data monitoring system
EP1885871B1 (en) 2005-05-17 2012-05-30 Radiometer Medical ApS Enzyme sensor with a cover membrane layer covered by a hydrophilic polymer
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
DE102005037979B4 (en) * 2005-08-11 2011-01-05 Jürgen Prof. Dr. Heinze Sensor with multiphase, segmented polymer network
CA2620586A1 (en) 2005-08-31 2007-03-08 Boris P. Kovatchev Improving the accuracy of continuous glucose sensors
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
US8880138B2 (en) 2005-09-30 2014-11-04 Abbott Diabetes Care Inc. Device for channeling fluid 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
EP1792563A1 (en) * 2005-12-02 2007-06-06 F.Hoffmann-La Roche Ag Analysis system comprising an OLED display element
GB2445531B (en) * 2005-12-09 2010-06-30 Council Scient Ind Res A melt transurethane process for the preparation of polyurethanes
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
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
EP1973464B1 (en) 2006-01-17 2018-03-14 DexCom, Inc. Low oxygen in vivo analyte sensor
US9757061B2 (en) 2006-01-17 2017-09-12 Dexcom, Inc. Low oxygen in vivo 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
EP3649925A1 (en) 2006-02-22 2020-05-13 DexCom, Inc. Analyte sensor
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
US7885698B2 (en) 2006-02-28 2011-02-08 Abbott Diabetes Care Inc. Method and system for providing continuous calibration of implantable analyte sensors
US8119394B2 (en) * 2006-03-14 2012-02-21 University Of Rochester Cell culture devices having ultrathin porous membrane and uses thereof
US8226891B2 (en) 2006-03-31 2012-07-24 Abbott Diabetes Care Inc. Analyte monitoring devices and methods therefor
US8374668B1 (en) 2007-10-23 2013-02-12 Abbott Diabetes Care Inc. Analyte sensor with lag compensation
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
US9339217B2 (en) 2011-11-25 2016-05-17 Abbott Diabetes Care Inc. Analyte monitoring system and methods of use
US7620438B2 (en) 2006-03-31 2009-11-17 Abbott Diabetes Care Inc. Method and system for powering an electronic device
US9675290B2 (en) 2012-10-30 2017-06-13 Abbott Diabetes Care Inc. Sensitivity calibration of in vivo sensors used to measure analyte concentration
US9326709B2 (en) 2010-03-10 2016-05-03 Abbott Diabetes Care Inc. Systems, devices and methods for managing glucose levels
US9392969B2 (en) 2008-08-31 2016-07-19 Abbott Diabetes Care Inc. Closed loop control and signal attenuation detection
US8473022B2 (en) 2008-01-31 2013-06-25 Abbott Diabetes Care Inc. Analyte sensor with time lag compensation
US8346335B2 (en) 2008-03-28 2013-01-01 Abbott Diabetes Care Inc. Analyte sensor calibration management
US7630748B2 (en) 2006-10-25 2009-12-08 Abbott Diabetes Care Inc. Method and system for providing analyte monitoring
US8224415B2 (en) 2009-01-29 2012-07-17 Abbott Diabetes Care Inc. Method and device for providing offset model based calibration for analyte sensor
US8219173B2 (en) 2008-09-30 2012-07-10 Abbott Diabetes Care Inc. Optimizing analyte sensor calibration
US7618369B2 (en) 2006-10-02 2009-11-17 Abbott Diabetes Care Inc. Method and system for dynamically updating calibration parameters for an analyte sensor
US8140312B2 (en) 2007-05-14 2012-03-20 Abbott Diabetes Care Inc. Method and system for determining analyte levels
US7801582B2 (en) 2006-03-31 2010-09-21 Abbott Diabetes Care Inc. Analyte monitoring and management system and methods therefor
US9119582B2 (en) 2006-06-30 2015-09-01 Abbott Diabetes Care, Inc. Integrated analyte sensor and infusion device and methods therefor
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
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
WO2008018879A1 (en) * 2006-08-10 2008-02-14 The Regents Of The University Of California Membranes with controlled permeability to polar and apolar molecules in solution and methods of making same
US7871456B2 (en) * 2006-08-10 2011-01-18 The Regents Of The University Of California Membranes with controlled permeability to polar and apolar molecules in solution and methods of making same
US20080069858A1 (en) * 2006-09-20 2008-03-20 Boston Scientific Scimed, Inc. Medical devices having biodegradable polymeric regions with overlying hard, thin layers
US8229546B2 (en) * 2006-10-18 2012-07-24 Cma Microdialysis Ab Microdialysis catheter and a method of making a microdialysis catheter
AU2007308804A1 (en) 2006-10-26 2008-05-02 Abbott Diabetes Care, Inc. Method, system and computer program product for real-time 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
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
WO2008130896A1 (en) 2007-04-14 2008-10-30 Abbott Diabetes Care, Inc. Method and apparatus for providing data processing and control in medical communication system
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
US9008743B2 (en) 2007-04-14 2015-04-14 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US7768387B2 (en) 2007-04-14 2010-08-03 Abbott Diabetes Care Inc. Method and apparatus for providing dynamic multi-stage signal amplification in a medical device
WO2009096992A1 (en) 2007-04-14 2009-08-06 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
US8456301B2 (en) 2007-05-08 2013-06-04 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US7928850B2 (en) 2007-05-08 2011-04-19 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
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
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
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
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
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
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
US20200037874A1 (en) * 2007-05-18 2020-02-06 Dexcom, Inc. Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise
WO2008150917A1 (en) 2007-05-31 2008-12-11 Abbott Diabetes Care, Inc. Insertion devices and methods
EP3533387A3 (en) 2007-06-21 2019-11-13 Abbott Diabetes Care, Inc. Health management devices and methods
CA2690870C (en) 2007-06-21 2017-07-11 Abbott Diabetes Care Inc. Health monitor
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
EP2185730A4 (en) 2007-08-23 2010-10-27 Intrexon Corp Methods and compositions for diagnosing disease
KR101666228B1 (en) 2007-09-28 2016-10-13 인트렉손 코포레이션 Therapeutic gene-switch constructs and bioreactors for the expression of biotherapeutic molecules, and uses thereof
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
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
US8417312B2 (en) 2007-10-25 2013-04-09 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
EP2982383B1 (en) 2008-04-10 2019-05-15 Abbott Diabetes Care, Inc. Method for sterilizing an analyte sensor
WO2009126900A1 (en) 2008-04-11 2009-10-15 Pelikan Technologies, Inc. Method and apparatus for analyte detecting device
US7826382B2 (en) 2008-05-30 2010-11-02 Abbott Diabetes Care Inc. Close proximity communication device and methods
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
US8876755B2 (en) 2008-07-14 2014-11-04 Abbott Diabetes Care Inc. Closed loop control system interface and methods
US9943644B2 (en) 2008-08-31 2018-04-17 Abbott Diabetes Care Inc. Closed loop control with reference measurement and methods thereof
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
US8734422B2 (en) 2008-08-31 2014-05-27 Abbott Diabetes Care Inc. Closed loop control with improved alarm functions
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
US9375169B2 (en) 2009-01-30 2016-06-28 Sanofi-Aventis Deutschland Gmbh Cam drive for managing disposable penetrating member actions with a single motor and motor and control system
US9402544B2 (en) 2009-02-03 2016-08-02 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US8497777B2 (en) 2009-04-15 2013-07-30 Abbott Diabetes Care Inc. Analyte monitoring system having an alert
WO2010121229A1 (en) 2009-04-16 2010-10-21 Abbott Diabetes Care Inc. Analyte sensor calibration management
US9226701B2 (en) 2009-04-28 2016-01-05 Abbott Diabetes Care Inc. Error detection in critical repeating data in a wireless sensor system
US8467972B2 (en) 2009-04-28 2013-06-18 Abbott Diabetes Care Inc. Closed loop blood glucose control algorithm analysis
EP2424426B1 (en) 2009-04-29 2020-01-08 Abbott Diabetes Care, Inc. Method and system for providing data communication in continuous glucose monitoring and management system
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
WO2010138856A1 (en) 2009-05-29 2010-12-02 Abbott Diabetes Care Inc. Medical device antenna systems having external antenna configurations
US9517023B2 (en) * 2009-06-01 2016-12-13 Profusa, Inc. Method and system for directing a localized biological response to an implant
US8613892B2 (en) 2009-06-30 2013-12-24 Abbott Diabetes Care Inc. Analyte meter with a moveable head and methods of using the same
EP3970610A3 (en) 2009-07-02 2022-05-18 Dexcom, Inc. Analyte sensors and methods of manufacturing same
EP3932309A1 (en) 2009-07-23 2022-01-05 Abbott Diabetes Care, Inc. Continuous analyte measurement system
EP3173014B1 (en) 2009-07-23 2021-08-18 Abbott Diabetes Care, Inc. Real time management of data relating to physiological control of glucose levels
WO2011014851A1 (en) 2009-07-31 2011-02-03 Abbott Diabetes Care Inc. Method and apparatus for providing analyte monitoring system calibration accuracy
AU2010286917B2 (en) 2009-08-31 2016-03-10 Abbott Diabetes Care Inc. Medical devices and methods
EP2473098A4 (en) 2009-08-31 2014-04-09 Abbott Diabetes Care Inc Analyte signal processing device and methods
ES2912584T3 (en) 2009-08-31 2022-05-26 Abbott Diabetes Care Inc A glucose monitoring system and method
EP2473099A4 (en) 2009-08-31 2015-01-14 Abbott Diabetes Care Inc Analyte monitoring system and methods for managing power and noise
US9320461B2 (en) 2009-09-29 2016-04-26 Abbott Diabetes Care Inc. Method and apparatus for providing notification function in analyte monitoring systems
WO2011053881A1 (en) 2009-10-30 2011-05-05 Abbott Diabetes Care Inc. Method and apparatus for detecting false hypoglycemic conditions
WO2011075575A1 (en) 2009-12-17 2011-06-23 Bayer Healthcare Llc Transdermal systems, devices, and methods to optically analyze an analyte
USD924406S1 (en) 2010-02-01 2021-07-06 Abbott Diabetes Care Inc. Analyte sensor inserter
CN102548476A (en) 2010-03-24 2012-07-04 雅培糖尿病护理公司 Medical device inserters and processes of inserting and using medical devices
US8965476B2 (en) 2010-04-16 2015-02-24 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US10010272B2 (en) 2010-05-27 2018-07-03 Profusa, Inc. Tissue-integrating electronic apparatus
US8635046B2 (en) 2010-06-23 2014-01-21 Abbott Diabetes Care Inc. Method and system for evaluating analyte sensor response characteristics
US10092229B2 (en) 2010-06-29 2018-10-09 Abbott Diabetes Care Inc. Calibration of analyte measurement system
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
EP2600761A4 (en) 2010-08-06 2014-08-13 Microchips Inc Biosensor membrane composition, biosensor, and methods for making same
JP5827999B2 (en) 2010-10-06 2015-12-02 プロフューザ,インコーポレイティド Tissue accumulation sensor
EP2624745A4 (en) 2010-10-07 2018-05-23 Abbott Diabetes Care, Inc. Analyte monitoring devices and methods
JP5644447B2 (en) * 2010-12-06 2014-12-24 ソニー株式会社 Microscope, region determination method, and program
EP3583901A3 (en) 2011-02-28 2020-01-15 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
PL2697388T3 (en) * 2011-03-28 2015-11-30 Hoffmann La Roche Improved diffusion layer for an enzymatic in-vivo sensor
CA2843008A1 (en) 2011-07-26 2013-01-31 Glysens Incorporated Tissue implantable sensor with hermetically sealed housing
EP2747650B1 (en) 2011-08-26 2023-04-05 Dexcom, Inc. Polymer membranes for continuous analyte sensors
CN102499696B (en) * 2011-09-23 2015-08-19 长沙三诺生物传感技术股份有限公司 Biological enzyme sensor of a kind of human implantable and preparation method thereof
US9069536B2 (en) 2011-10-31 2015-06-30 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
JP6443802B2 (en) 2011-11-07 2018-12-26 アボット ダイアベティス ケア インコーポレイテッドAbbott Diabetes Care Inc. Analyte monitoring apparatus and method
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
FI4056105T3 (en) 2011-12-11 2023-12-28 Abbott Diabetes Care Inc Analyte sensor devices
WO2013138369A1 (en) 2012-03-16 2013-09-19 Dexcom, Inc. Systems and methods for processing analyte sensor data
CN104334740B (en) * 2012-03-27 2017-05-24 霍夫曼-拉罗奇有限公司 Improved spacer membrane for an enzymatic in-vivo sensor
US10660550B2 (en) 2015-12-29 2020-05-26 Glysens Incorporated Implantable sensor apparatus and methods
US10561353B2 (en) 2016-06-01 2020-02-18 Glysens Incorporated Biocompatible implantable sensor apparatus and methods
US10132793B2 (en) 2012-08-30 2018-11-20 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
US9907492B2 (en) 2012-09-26 2018-03-06 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
EP2967454B1 (en) 2013-03-14 2020-04-22 Profusa, Inc. Method and device for correcting optical signals
US9121050B2 (en) 2013-03-15 2015-09-01 American Sterilizer Company Non-enzyme based detection method for electronic monitoring of biological indicator
US9474475B1 (en) 2013-03-15 2016-10-25 Abbott Diabetes Care Inc. Multi-rate analyte sensor data collection with sample rate configurable signal processing
WO2014152034A1 (en) 2013-03-15 2014-09-25 Abbott Diabetes Care Inc. Sensor fault detection using analyte sensor data pattern comparison
US10433773B1 (en) 2013-03-15 2019-10-08 Abbott Diabetes Care Inc. Noise rejection methods and apparatus for sparsely sampled analyte sensor data
US8858884B2 (en) 2013-03-15 2014-10-14 American Sterilizer Company Coupled enzyme-based method for electronic monitoring of biological indicator
EP3003131B1 (en) 2013-06-06 2020-05-27 Profusa, Inc. Apparatus for detecting optical signals from implanted sensors
WO2015102745A1 (en) 2013-12-31 2015-07-09 Abbott Diabetes Care Inc. Self-powered analyte sensor and devices using the same
WO2015153482A1 (en) 2014-03-30 2015-10-08 Abbott Diabetes Care Inc. Method and apparatus for determining meal start and peak events in analyte monitoring systems
WO2016109163A1 (en) 2014-12-31 2016-07-07 Theranova, Llc Methods and devices for analyte sensing in potential spaces
US10213139B2 (en) 2015-05-14 2019-02-26 Abbott Diabetes Care Inc. Systems, devices, and methods for assembling an applicator and sensor control device
US10674944B2 (en) 2015-05-14 2020-06-09 Abbott Diabetes Care Inc. Compact medical device inserters and related systems and methods
US11553883B2 (en) 2015-07-10 2023-01-17 Abbott Diabetes Care Inc. System, device and method of dynamic glucose profile response to physiological parameters
CN108291889B (en) * 2015-11-27 2021-03-12 雷迪奥米特医学公司 Outer layer for enzyme sensor
WO2017195035A1 (en) 2016-05-10 2017-11-16 Interface Biologics, 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
WO2018119400A1 (en) 2016-12-22 2018-06-28 Profusa, Inc. System and single-channel luminescent sensor for and method of determining analyte value
WO2018136898A1 (en) 2017-01-23 2018-07-26 Abbott Diabetes Care Inc. Systems, devices and methods for analyte sensor insertion
US11596330B2 (en) 2017-03-21 2023-03-07 Abbott Diabetes Care Inc. Methods, devices and system for providing diabetic condition diagnosis and therapy
US10638979B2 (en) 2017-07-10 2020-05-05 Glysens Incorporated Analyte sensor data evaluation and error reduction apparatus and methods
CN111278358B (en) 2017-08-28 2022-10-28 帝斯曼知识产权资产管理有限公司 Synthetic membrane compositions comprising fluorinated polyurethanes
WO2019046281A1 (en) 2017-08-28 2019-03-07 Dsm Ip Assets, B.V. Synthetic membrane composition comprising polyurethane blend
US11643551B2 (en) 2017-08-28 2023-05-09 Dsm Ip Assets B.V. Synthetic membrane composition comprising a polyurethane and a polyoxazoline
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
WO2019176339A1 (en) * 2018-03-13 2019-09-19 Phcホールディングス株式会社 Protective film material for biosensor probe
WO2019195661A1 (en) 2018-04-06 2019-10-10 Zense-Life Inc. Continuous glucose monitoring device
US11013438B2 (en) 2018-04-06 2021-05-25 Zense-Life Inc. Enhanced enzyme membrane for a working electrode of a continuous biological sensor
US20210355312A1 (en) * 2018-09-27 2021-11-18 l-SENS, INC. Polymer blend for controlling blood glucose influx, and continuous glucose monitoring biosensor comprising same
USD1002852S1 (en) 2019-06-06 2023-10-24 Abbott Diabetes Care Inc. Analyte sensor device
WO2021042079A1 (en) * 2019-08-30 2021-03-04 TT1 Products, Inc. Biomarker monitoring fitness system
CN113521399B (en) * 2020-04-16 2022-10-25 三诺生物传感股份有限公司 Biocompatible film, preparation method thereof and implantable biosensor
US11284818B2 (en) 2020-08-31 2022-03-29 TT1 Products, Inc. Glucose exposure diagnostics and therapeutics related thereto
USD999913S1 (en) 2020-12-21 2023-09-26 Abbott Diabetes Care Inc Analyte sensor inserter
CN113311054A (en) * 2021-04-29 2021-08-27 苏州中星医疗技术有限公司 Glucose biosensor
CN113317785B (en) * 2021-04-29 2022-10-28 苏州中星医疗技术有限公司 Selective-permeation biocompatible membrane and preparation method and application thereof
USD1004777S1 (en) 2021-09-01 2023-11-14 TT1 Products, Inc. Wrist reader
CN113717607B (en) * 2021-09-02 2022-09-13 苏州中星医疗技术有限公司 Biocompatible membrane, block polymer thereof and application
WO2023152224A1 (en) 2022-02-10 2023-08-17 Dsm Ip Assets B.V. Polyurethane membrane for sensor
CN115651525B (en) * 2022-12-09 2023-03-21 乐普(北京)医疗器械股份有限公司 Glucose diffusion-limited polymer outer membrane and preparation method and application thereof

Citations (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4890620A (en) * 1985-09-20 1990-01-02 The Regents Of The University Of California Two-dimensional diffusion glucose substrate sensing electrode
US5611900A (en) * 1995-07-20 1997-03-18 Michigan State University Microbiosensor used in-situ
US5965380A (en) * 1993-12-02 1999-10-12 E. Heller & Company Subcutaneous glucose electrode
US6007845A (en) * 1994-07-22 1999-12-28 Massachusetts Institute Of Technology Nanoparticles and microparticles of non-linear hydrophilic-hydrophobic multiblock copolymers
US6022463A (en) * 1996-05-16 2000-02-08 Sendx Medical, Inc. Sensors with subminiature through holes
US6071406A (en) * 1996-11-12 2000-06-06 Whatman, Inc. Hydrophilic polymeric phase inversion membrane
US6233471B1 (en) * 1998-05-13 2001-05-15 Cygnus, Inc. Signal processing for measurement of physiological analysis
US6241863B1 (en) * 1998-04-27 2001-06-05 Harold G. Monbouquette Amperometric biosensors based on redox enzymes
US6721587B2 (en) * 2001-02-15 2004-04-13 Regents Of The University Of California Membrane and electrode structure for implantable sensor
US20050245799A1 (en) * 2004-05-03 2005-11-03 Dexcom, Inc. Implantable analyte sensor
US20050242479A1 (en) * 2004-05-03 2005-11-03 Petisce James R Implantable analyte sensor
US20050245795A1 (en) * 2004-05-03 2005-11-03 Dexcom, Inc. Implantable analyte sensor
US20050251083A1 (en) * 2004-02-12 2005-11-10 Victoria Carr-Brendel Biointerface with macro-and micro-architecture
US20060015020A1 (en) * 2004-07-06 2006-01-19 Dexcom, Inc. Systems and methods for manufacture of an analyte-measuring device including a membrane system
US20060020191A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060016700A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060040402A1 (en) * 2003-08-01 2006-02-23 Brauker James H System and methods for processing analyte sensor data
US7074307B2 (en) * 2003-07-25 2006-07-11 Dexcom, Inc. Electrode systems for electrochemical sensors
US7226978B2 (en) * 2002-05-22 2007-06-05 Dexcom, Inc. Techniques to improve polyurethane membranes for implantable glucose sensors

Family Cites Families (459)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US538028A (en) * 1895-04-23 Apparatus for treatment of bone-black
US947227A (en) * 1906-07-19 1910-01-25 Victor Talking Machine Co Sound-reproducing device.
DE19852258A1 (en) 1998-11-11 2000-05-18 Agfa Gevaert Ag Radiation-sensitive recording material for the production of waterless offset printing plates
US3562352A (en) * 1968-09-06 1971-02-09 Avco Corp Polysiloxane-polyurethane block copolymers
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
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
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
US4136250A (en) * 1977-07-20 1979-01-23 Ciba-Geigy Corporation Polysiloxane hydrogels
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
US4255500A (en) 1979-03-29 1981-03-10 General Electric Company Vibration resistant electrochemical cell having deformed casing and method of making same
US4292423A (en) 1979-04-19 1981-09-29 Wacker-Chemie Gmbh Process for the preparation of organopolysiloxanes
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
US4403984A (en) 1979-12-28 1983-09-13 Biotek, Inc. System for demand-based adminstration of insulin
US5120813A (en) 1980-02-29 1992-06-09 Th. Goldschmidt Ag Moisture vapor permeable materials
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
US4686137A (en) 1980-02-29 1987-08-11 Thoratec Laboratories Corp. Moisture vapor permeable materials
SE419903B (en) 1980-03-05 1981-08-31 Enfors Sven Olof enzyme electrode
JPS5949803B2 (en) 1980-04-18 1984-12-05 日本ステアグライド販売株式会社 easy chair
DE3173564D1 (en) 1980-09-02 1986-03-06 Medtronic Inc Subcutaneously implantable lead with drug dispenser means
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
JPS5929693Y2 (en) 1980-12-25 1984-08-25 オリンパス光学工業株式会社 Cell collection device for endoscope
US4436094A (en) 1981-03-09 1984-03-13 Evreka, Inc. Monitor for continuous in vivo measurement of glucose concentration
JPS57156005A (en) 1981-03-20 1982-09-27 Nitto Electric Ind Co Ltd Selective permeable membrane
JPS57156004A (en) 1981-03-20 1982-09-27 Nitto Electric Ind Co Ltd Gas separating membrane
JPS57156005U (en) 1981-03-26 1982-09-30
JPS57156004U (en) 1981-03-26 1982-09-30
JPS5949805B2 (en) 1981-04-16 1984-12-05 永大化工株式会社 Bed sore prevention bed
DE3278334D1 (en) 1981-10-23 1988-05-19 Genetics Int Inc Sensor for components of a liquid mixture
US4431004A (en) 1981-10-27 1984-02-14 Bessman Samuel P Implantable glucose sensor
US4418148A (en) 1981-11-05 1983-11-29 Miles Laboratories, Inc. Multilayer enzyme electrode membrane
US4415666A (en) 1981-11-05 1983-11-15 Miles Laboratories, Inc. Enzyme electrode membrane
JPS5886172A (en) 1981-11-18 1983-05-23 テルモ株式会社 Medical substance moving apparatus
US4494950A (en) * 1982-01-19 1985-01-22 The Johns Hopkins University Plural module medication delivery system
JPS58163402A (en) 1982-03-20 1983-09-28 Nitto Electric Ind Co Ltd Gas separation membrane
JPS58163403A (en) 1982-03-23 1983-09-28 Nitto Electric Ind Co Ltd Gas separation membrane
US4493714A (en) * 1982-05-06 1985-01-15 Teijin Limited Ultrathin film, process for production thereof, and use thereof for concentrating a specified gas in a gaseous mixture
EP0098592A3 (en) 1982-07-06 1985-08-21 Fujisawa Pharmaceutical Co., Ltd. Portable artificial pancreas
JPS5929693A (en) 1982-08-10 1984-02-16 Asahi Glass Co Ltd Fluorine-containing diisocyanate containing siloxane bond
JPS5949803A (en) 1982-09-17 1984-03-22 Teijin Ltd Permselective membrane for separation of gas
JPS5949805A (en) 1982-09-17 1984-03-22 Teijin Ltd Permselective membrane for separation of gas
JPS5949803U (en) 1982-09-27 1984-04-02 リンナイ株式会社 Oven cooking device operating device
JPS5949805U (en) 1982-09-27 1984-04-02 株式会社東芝 High frequency heating cooking device
JPS5959221A (en) 1982-09-29 1984-04-05 Teijin Ltd Prearation of composite perrmeable membrane for separating gas
JPS5959221U (en) 1982-10-12 1984-04-18 和光産業株式会社 Plate fixing device in multi-blade fan assembly machine
JPS591929Y2 (en) 1982-10-25 1984-01-19 ロ−レルバンクマシン株式会社 Cumulative coin support rod of coin wrapping machine
DE3379589D1 (en) 1982-10-25 1989-05-18 Hellgren Lars G I Enzyme composition for cleaning, the use thereof and preparation of the composition
JPS5987004A (en) 1982-11-08 1984-05-19 Nitto Electric Ind Co Ltd Gas separation membrane
JPS58163403U (en) 1982-11-27 1983-10-31 ナイガイ株式会社 Single drive source packaging machine
JPS5987004U (en) 1982-12-01 1984-06-12 古河電気工業株式会社 Airtight penetration for optical transmission line
US5059654A (en) 1983-02-14 1991-10-22 Cuno Inc. Affinity matrices of modified polysaccharide supports
JPS59128406U (en) 1983-02-19 1984-08-29 倉敷化工株式会社 Suspension rubber bushing for automobiles
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
CA1219040A (en) 1983-05-05 1987-03-10 Elliot V. Plotkin Measurement of enzyme-catalysed reactions
JPS59209609A (en) 1983-05-12 1984-11-28 Teijin Ltd Permselective membrane
JPS59209608A (en) 1983-05-12 1984-11-28 Teijin Ltd Permselective membrane
JPS59209610A (en) 1983-05-12 1984-11-28 Teijin Ltd Permselective membrane
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
US4554927A (en) 1983-08-30 1985-11-26 Thermometrics Inc. Pressure and temperature sensor
JPS6084530A (en) 1983-10-17 1985-05-13 Hitachi Ltd Liquid crystal display element
GB2149918A (en) 1983-11-03 1985-06-19 John Anderson Sudden infant death syndrome monitor
JPS60146219A (en) 1984-01-11 1985-08-01 Toray Ind Inc Contact lens
JPS60136214U (en) 1984-02-23 1985-09-10 いすゞ自動車株式会社 Height adjustment device for vehicles with air spring suspension
US4527999A (en) 1984-03-23 1985-07-09 Abcor, Inc. Separation membrane and method of preparing and using same
US4753652A (en) 1984-05-04 1988-06-28 Children's Medical Center Corporation Biomaterial implants which resist calcification
JPS60245623A (en) 1984-05-18 1985-12-05 Nippon Yunikaa Kk Production of flexible polyether-urethane foam of low gas permeability
US4644046A (en) * 1984-06-20 1987-02-17 Teijin Limited Ultrathin film, process for production thereof, and use thereof for concentrating a specific gas from a gas mixture
CA1258496A (en) 1984-07-30 1989-08-15 Teruyoshi Uchida Insulated noble metal wire and porous membrane as po.sub.2 bioelectrode
US5171689A (en) 1984-11-08 1992-12-15 Matsushita Electric Industrial Co., Ltd. Solid state bio-sensor
US4602922A (en) 1984-11-09 1986-07-29 Research Foundation Of State University Of New York Method of making membranes for gas separation and the composite membranes
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
JPS61238319A (en) 1985-04-17 1986-10-23 Dainippon Ink & Chem Inc Selective gas permeable membrane
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
GB8514176D0 (en) 1985-06-05 1985-07-10 Ici Plc Membrane
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
JPS6274406A (en) 1985-09-30 1987-04-06 Teijin Ltd Separating membrane
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
JPS6283849A (en) 1985-10-04 1987-04-17 Reiji Yoshinaka Method of purifying collagen
JPS6274406U (en) 1985-10-29 1987-05-13
JPS62102815A (en) 1985-10-30 1987-05-13 Agency Of Ind Science & Technol Gas permselective membrane
US4647643A (en) * 1985-11-08 1987-03-03 Becton, Dickinson And Company Soft non-blocking polyurethanes
JPS6283849U (en) 1985-11-12 1987-05-28
US4798876A (en) 1985-11-12 1989-01-17 Tyndale Plains-Hunter Ltd. Hydrophilic polyurethane composition
JPH0341047Y2 (en) 1985-12-19 1991-08-29
US4684538A (en) 1986-02-21 1987-08-04 Loctite Corporation Polysiloxane urethane compounds and adhesive compositions, and method of making and using the same
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
JPH0696106B2 (en) 1986-03-31 1994-11-30 帝人株式会社 Gas separation membrane
US4685463A (en) 1986-04-03 1987-08-11 Williams R Bruce Device for continuous in vivo measurement of blood glucose concentrations
US4757022A (en) 1986-04-15 1988-07-12 Markwell Medical Institute, Inc. Biological fluid measuring device
US4994167A (en) 1986-04-15 1991-02-19 Markwell Medical Institute, Inc. Biological fluid measuring device
US4909908A (en) * 1986-04-24 1990-03-20 Pepi Ross Electrochemical cncentration detector method
US4795542A (en) * 1986-04-24 1989-01-03 St. Jude Medical, Inc. Electrochemical concentration detector 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
US4763658A (en) 1986-06-04 1988-08-16 Solutech, Inc. Dialysis system 2nd method
US4726381A (en) * 1986-06-04 1988-02-23 Solutech, Inc. Dialysis system and method
US4781733A (en) 1986-07-23 1988-11-01 Bend Research, Inc. Semipermeable thin-film membranes comprising siloxane, alkoxysilyl and aryloxysilyl oligomers and copolymers
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
JPS63130661A (en) 1986-11-20 1988-06-02 Toppan Printing Co Ltd Non-porous moisture-permeable waterproof film
DE3700119A1 (en) 1987-01-03 1988-07-14 Inst Diabetestechnologie Gemei IMPLANTABLE ELECTROCHEMICAL SENSOR
AT391063B (en) 1987-01-08 1990-08-10 Blum Gmbh Julius CONNECTING FITTING FOR FASTENING THE RAILING OF A DRAWER
JPS63130661U (en) 1987-02-18 1988-08-26
US4935345A (en) 1987-04-07 1990-06-19 Arizona Board Of Regents Implantable microelectronic biochemical sensor incorporating thin film thermopile
US5352348A (en) 1987-04-09 1994-10-04 Nova Biomedical Corporation Method of using enzyme electrode
US4759828A (en) 1987-04-09 1988-07-26 Nova Biomedical Corporation Glucose electrode and method of determining glucose
IT1215491B (en) 1987-05-15 1990-02-14 Enricerche Spa BIOSENSOR WITH ENZYMATIC MEMBRANE CHEMICALLY CONNECTED TO A SEMICONDUCTIVE DEVICE.
US4880883A (en) 1987-06-03 1989-11-14 Wisconsin Alumni Research Foundation Biocompatible polyurethanes modified with lower alkyl sulfonate and lower alkyl carboxylate
US5540828A (en) 1987-06-08 1996-07-30 Yacynych; Alexander Method for making electrochemical sensors and biosensors having a polymer modified surface
US5286364A (en) * 1987-06-08 1994-02-15 Rutgers University Surface-modified electochemical biosensor
US4810470A (en) 1987-06-19 1989-03-07 Miles Inc. Volume independent diagnostic device
US4786657A (en) 1987-07-02 1988-11-22 Minnesota Mining And Manufacturing Company Polyurethanes and polyurethane/polyureas crosslinked using 2-glyceryl acrylate or 2-glyceryl methacrylate
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.
JPH07114937B2 (en) 1987-07-13 1995-12-13 帝人株式会社 Separation membrane
JPH0824830B2 (en) 1987-07-13 1996-03-13 帝人株式会社 Separation membrane
DE3725728A1 (en) 1987-08-04 1989-02-16 Freudenberg Carl Fa MEDICAL DEVICE AND METHOD FOR THE PRODUCTION THEREOF
US5221724A (en) 1987-08-12 1993-06-22 Wisconsin Alumni Research Foundation Polysiloxane polyurea urethanes
US4974929A (en) 1987-09-22 1990-12-04 Baxter International, Inc. Fiber optical probe connector for physiologic measurement devices
NL8702370A (en) 1987-10-05 1989-05-01 Groningen Science Park METHOD AND SYSTEM FOR GLUCOSE DETERMINATION AND USEABLE MEASURING CELL ASSEMBLY.
DE3736652A1 (en) 1987-10-29 1989-05-11 Bayer Ag PROCESS FOR PREPARING COATINGS
US5242835A (en) 1987-11-03 1993-09-07 Radiometer A/S Method and apparatus for determining the concentration of oxygen
GB8725936D0 (en) 1987-11-05 1987-12-09 Genetics Int Inc Sensing system
US5128408A (en) 1987-11-16 1992-07-07 Toyo Boseki Kabushiki Kaisha Gas-permeable material with excellent compatibility with blood
US4852573A (en) 1987-12-04 1989-08-01 Kennedy Philip R Implantable neural electrode
US5070169A (en) 1988-02-26 1991-12-03 Ciba-Geigy Corporation Wettable, flexible, oxygen permeable contact lens containing block copolymer polysiloxane-polyoxyalkylene backbone units and use thereof
US4822336A (en) 1988-03-04 1989-04-18 Ditraglia John Blood glucose level sensing
US4793555A (en) 1988-04-22 1988-12-27 Dow Corning Corporation Container, method and composition for controlling the release of a volatile liquid from an aqueous mixture
US5008115A (en) * 1988-04-22 1991-04-16 Dow Corning Corporation Matrix for release of active ingredients
US4951657A (en) 1988-04-22 1990-08-28 Dow Corning Corporation Heat sealable membrane for transdermal drug release
US4908208A (en) * 1988-04-22 1990-03-13 Dow Corning Corporation Matrix for release of active ingredients
US5342693A (en) 1988-06-08 1994-08-30 Cardiopulmonics, Inc. Multifunctional thrombo-resistant coating and methods of manufacture
US4849458A (en) 1988-06-17 1989-07-18 Matrix Medica, Inc. Segmented polyether polyurethane
CA1299653C (en) 1988-07-07 1992-04-28 Markwell Medical Institute, Inc. Biological fluid measuring device
EP0353328A1 (en) 1988-08-03 1990-02-07 Dräger Nederland B.V. A polarographic-amperometric three-electrode sensor
US4983702A (en) 1988-09-28 1991-01-08 Ciba-Geigy Corporation Crosslinked siloxane-urethane polymer contact lens
US5200051A (en) 1988-11-14 1993-04-06 I-Stat Corporation Wholly microfabricated biosensors and process for the manufacture and use thereof
US5212050A (en) 1988-11-14 1993-05-18 Mier Randall M Method of forming a permselective layer
US5063081A (en) 1988-11-14 1991-11-05 I-Stat Corporation Method of manufacturing a plurality of uniform microfabricated sensing devices having an immobilized ligand receptor
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
US5034461A (en) 1989-06-07 1991-07-23 Bausch & Lomb Incorporated Novel prepolymers useful in biomedical devices
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
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
US5190041A (en) 1989-08-11 1993-03-02 Palti Yoram Prof System for monitoring and controlling blood glucose
US5101814A (en) 1989-08-11 1992-04-07 Palti Yoram Prof System for monitoring and controlling blood glucose
FR2650756B1 (en) 1989-08-11 1991-10-31 Inst Francais Du Petrole GAS SEPARATION MEMBRANE
US5050612A (en) 1989-09-12 1991-09-24 Matsumura Kenneth N Device for computer-assisted monitoring of the body
US5002590A (en) * 1989-09-19 1991-03-26 Bend Research, Inc. Countercurrent dehydration by hollow fibers
JPH03133440A (en) 1989-10-18 1991-06-06 Nishitomo:Kk Clinical thermometer for ladies
US5140985A (en) 1989-12-11 1992-08-25 Schroeder Jon M Noninvasive blood glucose measuring device
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
FR2656423A1 (en) 1989-12-22 1991-06-28 Rhone Poulenc Chimie Electrochemical biosensor
US5183549A (en) * 1990-01-26 1993-02-02 Commtech International Management Corporation Multi-analyte sensing electrolytic cell
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
GB9009409D0 (en) 1990-04-26 1990-06-20 Dow Corning Film-forming copolymers and their use in water vapour permeable coatings
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
US5250439A (en) 1990-07-19 1993-10-05 Miles Inc. Use of conductive sensors in diagnostic assays
US5202261A (en) 1990-07-19 1993-04-13 Miles Inc. Conductive sensors and their use in diagnostic assays
US5746898A (en) 1990-08-10 1998-05-05 Siemens Aktiengesellschaft Electrochemical-enzymatic sensor
WO1992003107A1 (en) 1990-08-28 1992-03-05 Meadox Medicals, Inc. Self-supporting woven vascular graft
US5380536A (en) 1990-10-15 1995-01-10 The Board Of Regents, The University Of Texas System Biocompatible microcapsules
US5344454A (en) 1991-07-24 1994-09-06 Baxter International Inc. Closed porous chambers for implanting tissue in a host
WO1992007525A1 (en) 1990-10-31 1992-05-14 Baxter International Inc. Close vascularization implant material
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
US5713888A (en) 1990-10-31 1998-02-03 Baxter International, Inc. Tissue implant systems
US5545223A (en) 1990-10-31 1996-08-13 Baxter International, Inc. Ported tissue implant systems and methods of using same
DE69228957T2 (en) 1991-01-16 1999-10-07 Toyo Boseki Blood compatible material
AU1356792A (en) * 1991-01-25 1992-08-27 Markwell Medical Institute, Inc. Implantable biological fluid measuring device
US5348788A (en) 1991-01-30 1994-09-20 Interpore Orthopaedics, Inc. Mesh sheet with microscopic projections and holes
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
JPH08196626A (en) 1991-04-25 1996-08-06 Toyobo Co Ltd Blood compatible artificial pulmonary membrane
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
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
US5322063A (en) 1991-10-04 1994-06-21 Eli Lilly And Company Hydrophilic polyurethane membranes for electrochemical glucose sensors
US5155149A (en) 1991-10-10 1992-10-13 Boc Health Care, Inc. Silicone polyurethane copolymers containing oxygen sensitive phosphorescent dye compounds
US5866217A (en) 1991-11-04 1999-02-02 Possis Medical, Inc. Silicone composite vascular graft
US5296144A (en) * 1992-01-02 1994-03-22 World Trade Corporation Composite membrane of a hydrophilic asymmetric membrane coated with an organosiloxane block copolymer
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
JPH05279447A (en) 1992-03-31 1993-10-26 Mitsubishi Rayon Co Ltd Silicon-based block copolymer and membrane made thereof
ES2167332T3 (en) 1992-04-01 2002-05-16 Baxter Int PROCEDURE AND SYSTEMS FOR THE IMPLANT OF LIVE CELLS IN GUESTS ORGANISMS.
JP3857306B2 (en) 1992-04-24 2006-12-13 ザ ポリマー テクノロジー グループ,インコーポレイティド Copolymers and their non-porous, semi-permeable membranes and their use to permeate molecules of a given molecular weight range
US5589563A (en) 1992-04-24 1996-12-31 The Polymer Technology Group Surface-modifying endgroups for biomedical polymers
GB9211402D0 (en) 1992-05-29 1992-07-15 Univ Manchester Sensor devices
US5208313A (en) 1992-07-16 1993-05-04 Surface Coatings, Inc. Waterproof breathable polyurethane membranes and porous substrates protected therewith
JP2541081B2 (en) 1992-08-28 1996-10-09 日本電気株式会社 Biosensor and method of manufacturing and using biosensor
EP1130388A1 (en) 1992-10-01 2001-09-05 Australian Membrane And Biotechnology Research Institute Improved 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
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
US5299571A (en) 1993-01-22 1994-04-05 Eli Lilly And Company Apparatus and method for implantation of sensors
US5389430A (en) 1993-02-05 1995-02-14 Th. Goldschmidt Ag Textiles coated with waterproof, moisture vapor permeable polymers
DE4329898A1 (en) 1993-09-04 1995-04-06 Marcus Dr Besson Wireless medical diagnostic and monitoring device
JPH08503715A (en) 1993-09-24 1996-04-23 バクスター、インターナショナル、インコーポレイテッド Method for promoting vascularization of implantable devices
US5582184A (en) 1993-10-13 1996-12-10 Integ Incorporated Interstitial fluid collection and constituent measurement
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
US5497772A (en) * 1993-11-19 1996-03-12 Alfred E. Mann Foundation For Scientific Research Glucose monitoring system
US5791344A (en) 1993-11-19 1998-08-11 Alfred E. Mann Foundation For Scientific Research Patient 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
US5390671A (en) * 1994-03-15 1995-02-21 Minimed Inc. Transcutaneous sensor insertion set
US5391250A (en) 1994-03-15 1995-02-21 Minimed Inc. Method of fabricating thin film sensors
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
DE59509994D1 (en) 1994-06-03 2002-02-21 Metrohm Ag Herisau Device for voltammetry, indicator electrode arrangement for such a device, in particular as part of a tape cassette, and row analysis method for voltammetry
US5494562A (en) * 1994-06-27 1996-02-27 Ciba Corning Diagnostics Corp. Electrochemical sensors
CN1157560A (en) 1994-07-08 1997-08-20 巴克斯特国际有限公司 Implanted device containing tumor cells for treatment of cancer
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
DK0792454T3 (en) * 1994-11-14 2002-06-03 Bayer Ag Randomly segmented thermoplastic polyurethanes as matrix for electrochemical analysis of Ca ++ ions
US5837728A (en) * 1995-01-27 1998-11-17 Molecular Design International 9-cis retinoic acid esters and amides and uses thereof
US5697366A (en) 1995-01-27 1997-12-16 Optical Sensors Incorporated In situ calibration system for sensors located in a physiologic line
US5586553A (en) 1995-02-16 1996-12-24 Minimed Inc. Transcutaneous sensor insertion set
US5568806A (en) 1995-02-16 1996-10-29 Minimed Inc. Transcutaneous sensor insertion set
US5882494A (en) 1995-03-27 1999-03-16 Minimed, Inc. Polyurethane/polyurea compositions containing silicone for biosensor membranes
US5786439A (en) 1996-10-24 1998-07-28 Minimed Inc. Hydrophilic, swellable coatings for biosensors
DE29624309U1 (en) * 1995-04-04 2002-01-03 Novartis Ag Duration supporting lenses
WO1996032076A1 (en) 1995-04-11 1996-10-17 Baxter Internatonal Inc. Tissue implant systems
US5620579A (en) 1995-05-05 1997-04-15 Bayer Corporation Apparatus for reduction of bias in amperometric sensors
US6060640A (en) 1995-05-19 2000-05-09 Baxter International Inc. Multiple-layer, formed-in-place immunoisolation membrane structures for implantation of cells in host tissue
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
US5743262A (en) 1995-06-07 1998-04-28 Masimo Corporation Blood glucose monitoring system
CA2190628C (en) 1995-06-07 2000-05-30 Mark D. Butler An implantable containment apparatus for a therapeutical 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
US5700902A (en) * 1995-07-27 1997-12-23 Circe Biomedical, Inc. Block copolymers
JP2000501069A (en) 1995-09-21 2000-02-02 ノバルティス・アクチエンゲゼルシャフト Polymer-bound fluorophores as photoion sensors
CA2232588A1 (en) 1995-09-26 1997-04-03 Ameron International Corporation Polysiloxane polyurethane compositions
US5628890A (en) 1995-09-27 1997-05-13 Medisense, Inc. Electrochemical sensor
US6689265B2 (en) * 1995-10-11 2004-02-10 Therasense, Inc. Electrochemical analyte sensors using thermostable soybean peroxidase
US5972199A (en) 1995-10-11 1999-10-26 E. Heller & Company Electrochemical analyte sensors using thermostable peroxidase
US5665222A (en) 1995-10-11 1997-09-09 E. Heller & Company Soybean peroxidase electrochemical sensor
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
AU1058297A (en) * 1995-11-22 1997-06-11 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
US6002954A (en) 1995-11-22 1999-12-14 The Regents Of The University Of California Detection of biological molecules using boronate-based chemical amplification and optical sensors
US6063637A (en) 1995-12-13 2000-05-16 California Institute Of Technology Sensors for sugars and other metal binding analytes
DE69623647T2 (en) 1995-12-22 2003-05-28 Novartis Ag POLYURETHANE MADE OF POLYSILOXANE-POLYOL MACROMER
CA2212826C (en) 1995-12-28 2002-02-19 Cygnus, Inc. Methods for monitoring a physiological analyte
US5795453A (en) 1996-01-23 1998-08-18 Gilmartin; Markas A. T. Electrodes and metallo isoindole ringed compounds
US5833603A (en) * 1996-03-13 1998-11-10 Lipomatrix, Inc. Implantable biosensing transponder
US6407195B2 (en) 1996-04-25 2002-06-18 3M Innovative Properties Company Tackified polydiorganosiloxane oligourea segmented copolymers and a process for making same
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
EP0923335B1 (en) * 1996-07-08 2006-08-23 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
US5703359A (en) 1996-07-29 1997-12-30 Leybold Inficon, Inc. Composite membrane and support assembly
US6054142A (en) 1996-08-01 2000-04-25 Cyto Therapeutics, Inc. Biocompatible devices with foam scaffolds
US6018013A (en) 1996-09-03 2000-01-25 Nkk Corporation Coating composition and method for producing precoated steel sheets
DE19642453C2 (en) * 1996-10-15 1998-07-23 Bosch Gmbh Robert Arrangement for gas sensor electrodes
AU5461298A (en) 1996-12-04 1998-06-29 Enact Health Management Systems System for downloading and reporting medical information
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
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
US6862465B2 (en) 1997-03-04 2005-03-01 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
US20050033132A1 (en) * 1997-03-04 2005-02-10 Shults Mark C. Analyte measuring device
US6741877B1 (en) * 1997-03-04 2004-05-25 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
US7899511B2 (en) 2004-07-13 2011-03-01 Dexcom, Inc. Low oxygen in vivo analyte sensor
US6558321B1 (en) * 1997-03-04 2003-05-06 Dexcom, Inc. Systems and methods for remote monitoring and modulation of medical devices
FR2760962B1 (en) 1997-03-20 1999-05-14 Sillonville Francis Klefstad REMOTE MEDICAL ASSISTANCE AND SURVEILLANCE SYSTEM
US6270455B1 (en) 1997-03-28 2001-08-07 Health Hero Network, Inc. Networked system for interactive communications and remote monitoring of drug delivery
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
US6558351B1 (en) 1999-06-03 2003-05-06 Medtronic Minimed, Inc. Closed loop system for controlling insulin infusion
US6093167A (en) 1997-06-16 2000-07-25 Medtronic, Inc. System for pancreatic stimulation and glucose measurement
JP2002505008A (en) * 1997-06-16 2002-02-12 エラン コーポレーション ピーエルシー Methods for calibrating and testing sensors for in vivo measurement of analytes and devices for use in such methods
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
US6259937B1 (en) 1997-09-12 2001-07-10 Alfred E. Mann Foundation Implantable substrate sensor
US5999848A (en) 1997-09-12 1999-12-07 Alfred E. Mann Foundation Daisy chainable sensors and stimulators for implantation in living tissue
US6409674B1 (en) * 1998-09-24 2002-06-25 Data Sciences International, Inc. Implantable sensor with wireless communication
US6088608A (en) 1997-10-20 2000-07-11 Alfred E. Mann Foundation Electrochemical sensor and integrity tests therefor
US6081736A (en) * 1997-10-20 2000-06-27 Alfred E. Mann Foundation Implantable enzyme-based monitoring systems adapted for long term use
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
US6030827A (en) * 1998-01-23 2000-02-29 I-Stat Corporation Microfabricated aperture-based sensor
US6134461A (en) 1998-03-04 2000-10-17 E. Heller & Company Electrochemical analyte
US6013113A (en) * 1998-03-06 2000-01-11 Wilson Greatbatch Ltd. Slotted insulator for unsealed electrode edges in electrochemical cells
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
US6091975A (en) 1998-04-01 2000-07-18 Alza Corporation Minimally invasive detecting device
US6537318B1 (en) * 1998-04-06 2003-03-25 Konjac Technologies, Llc Use of glucomannan hydrocolloid as filler material in prostheses
US6175752B1 (en) * 1998-04-30 2001-01-16 Therasense, 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
ATE245937T1 (en) 1998-05-13 2003-08-15 Cygnus Therapeutic Systems MONITORING PHYSIOLOGICAL ANALYTES
US6129757A (en) 1998-05-18 2000-10-10 Scimed Life Systems Implantable members for receiving therapeutically useful compositions
US6187062B1 (en) * 1998-06-16 2001-02-13 Alcatel Current collection through thermally sprayed tabs at the ends of a spirally wound electrochemical cell
GB2339912B (en) 1998-07-20 2002-06-05 Univ Bristol Apparatus and method for measuring the moisture level within enamel dentine or tooth tissue
US6248067B1 (en) 1999-02-05 2001-06-19 Minimed Inc. Analyte sensor and holter-type monitor system and method of using the same
TW495608B (en) * 1998-08-26 2002-07-21 Sensors For Med & Science Inc Optical-based sensing devices
US6201980B1 (en) * 1998-10-05 2001-03-13 The Regents Of The University Of California Implantable medical sensor system
US6338790B1 (en) * 1998-10-08 2002-01-15 Therasense, Inc. Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
ATE514372T1 (en) 1998-10-08 2011-07-15 Medtronic Minimed Inc LICENSE PLATE MONITORING SYSTEM WITH REMOTE MEASUREMENT
US6016448A (en) * 1998-10-27 2000-01-18 Medtronic, Inc. Multilevel ERI for implantable medical devices
CA2352571C (en) 1998-12-02 2007-02-27 Gary S. Sayler In vivo biosensor apparatus and method of use
WO2000038570A1 (en) * 1998-12-31 2000-07-06 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
WO2000059373A1 (en) 1999-04-07 2000-10-12 Spectrx, Inc. Assay device for measuring characteristics of a fluid on a continual basis
JP2002542498A (en) 1999-04-22 2002-12-10 シグナス, インコーポレイテッド Methods and devices for removing interfering species
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
US6413393B1 (en) 1999-07-07 2002-07-02 Minimed, Inc. Sensor including UV-absorbing polymer and method of manufacture
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
US6343225B1 (en) * 1999-09-14 2002-01-29 Implanted Biosystems, Inc. Implantable glucose sensor
EP1214596A1 (en) 1999-09-15 2002-06-19 The Regents Of The University Of California Glucose sensing molecules having selected fluorescent properties
US6541107B1 (en) * 1999-10-25 2003-04-01 Dow Corning Corporation Nanoporous silicone resins having low dielectric constants
US6527729B1 (en) * 1999-11-10 2003-03-04 Pacesetter, Inc. Method for monitoring patient using acoustic sensor
US6520997B1 (en) 1999-12-08 2003-02-18 Baxter International Inc. Porous three dimensional structure
US6895263B2 (en) 2000-02-23 2005-05-17 Medtronic Minimed, Inc. Real time self-adjusting calibration algorithm
CA2399842C (en) 2000-03-02 2006-11-14 Microchips, Inc. Microfabricated devices for the storage and selective exposure of chemicals and devices
US6551496B1 (en) * 2000-03-03 2003-04-22 Ysi Incorporated Microstructured bilateral sensor
US6365670B1 (en) 2000-03-10 2002-04-02 Wacker Silicones Corporation Organopolysiloxane gels for use in cosmetics
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
US7769420B2 (en) 2000-05-15 2010-08-03 Silver James H Sensors for detecting substances indicative of stroke, ischemia, or myocardial infarction
US7181261B2 (en) 2000-05-15 2007-02-20 Silver James H Implantable, retrievable, thrombus minimizing sensors
US6395325B1 (en) 2000-05-16 2002-05-28 Scimed Life Systems, Inc. Porous membranes
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
US7092014B1 (en) * 2000-06-28 2006-08-15 Microsoft Corporation Scene capturing and view rendering based on a longitudinally aligned camera array
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
US6477392B1 (en) * 2000-07-14 2002-11-05 Futrex Inc. Calibration of near infrared quantitative measurement device using optical measurement cross-products
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
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
FR2822383B1 (en) 2001-03-23 2004-12-17 Perouse Lab PROSTHESIS FOR PLASTIC RECONSTRUCTION WITH IMPROVED HYDROPHILICITY PROPERTIES, AND METHOD FOR OBTAINING SAME
US6454710B1 (en) * 2001-04-11 2002-09-24 Motorola, Inc. Devices and methods for monitoring an analyte
DE10119036C1 (en) * 2001-04-18 2002-12-12 Disetronic Licensing Ag Immersion sensor for measuring the concentration of an analyte using an oxidase
US20020162792A1 (en) 2001-05-01 2002-11-07 Zepf Robert F. Polymer membrane meshes
US6613379B2 (en) 2001-05-08 2003-09-02 Isense Corp. Implantable analyte sensor
AU2002361545B2 (en) 2001-06-28 2007-03-15 Microchips, Inc. Methods for hermetically sealing microchip reservoir devices
US6702857B2 (en) * 2001-07-27 2004-03-09 Dexcom, Inc. Membrane for use with implantable devices
US20030032874A1 (en) * 2001-07-27 2003-02-13 Dexcom, Inc. Sensor head for use with implantable devices
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
WO2003051191A1 (en) 2001-12-17 2003-06-26 Danfoss A/S Method and device for monitoring analyte concentration by optical detection
US7018336B2 (en) * 2001-12-27 2006-03-28 Medtronic Minimed, Inc. Implantable sensor flush sleeve
WO2003061475A1 (en) 2002-01-23 2003-07-31 Danfoss A/S Method and device for monitoring analyte concentration by use of differential osmotic pressure measurement
US8010174B2 (en) * 2003-08-22 2011-08-30 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
CA2480550C (en) 2002-03-22 2011-07-12 Cygnus, Inc. Improving performance of an analyte monitoring device
AU2003221808A1 (en) 2002-04-05 2003-10-27 Powerzyme, Inc. Analyte sensor
US7813780B2 (en) 2005-12-13 2010-10-12 Medtronic Minimed, Inc. Biosensors and methods for making and using them
US20070227907A1 (en) 2006-04-04 2007-10-04 Rajiv Shah Methods and materials for controlling the electrochemistry of analyte sensors
US7008979B2 (en) 2002-04-30 2006-03-07 Hydromer, Inc. Coating composition for multiple hydrophilic applications
DE10393060D2 (en) 2002-05-09 2005-05-04 Hemoteq Gmbh Reduction of the noise emission of thin-walled components in magnetic resonance instruments
US7166235B2 (en) 2002-05-09 2007-01-23 The Procter & Gamble Company Compositions comprising anionic functionalized polyorganosiloxanes for hydrophobically modifying surfaces and enhancing delivery of active agents to surfaces treated therewith
US6801041B2 (en) 2002-05-14 2004-10-05 Abbott Laboratories Sensor having electrode for determining the rate of flow of a fluid
US20060258761A1 (en) 2002-05-22 2006-11-16 Robert Boock Silicone based membranes for use in implantable glucose sensors
US20030225324A1 (en) 2002-06-03 2003-12-04 Anderson Edward J. Noninvasive detection of a physiologic Parameter within a body tissue of a patient
US8996090B2 (en) * 2002-06-03 2015-03-31 Exostat Medical, Inc. Noninvasive detection of a physiologic parameter within a body tissue of a patient
AU2003245862A1 (en) 2002-07-12 2004-02-02 Novo Nordisk A/S Minimising calibration problems of in vivo glucose sensors
US20040180391A1 (en) 2002-10-11 2004-09-16 Miklos Gratzl Sliver type autonomous biosensors
US7120483B2 (en) 2003-01-13 2006-10-10 Isense Corporation Methods for analyte sensing and measurement
US7134999B2 (en) * 2003-04-04 2006-11-14 Dexcom, Inc. Optimized sensor geometry for an implantable glucose sensor
US7279174B2 (en) * 2003-05-08 2007-10-09 Advanced Cardiovascular Systems, Inc. Stent coatings comprising hydrophilic additives
AU2004238026A1 (en) 2003-05-16 2004-11-25 Cinvention Ag Medical implants comprising biocompatible coatings
US7875293B2 (en) 2003-05-21 2011-01-25 Dexcom, Inc. Biointerface membranes incorporating bioactive agents
US7687586B2 (en) 2003-05-21 2010-03-30 Isense Corporation Biosensor membrane material
US20050118344A1 (en) 2003-12-01 2005-06-02 Pacetti Stephen D. Temperature controlled crimping
WO2005010518A1 (en) 2003-07-23 2005-02-03 Dexcom, Inc. Rolled electrode array and its method for manufacture
US20050056552A1 (en) 2003-07-25 2005-03-17 Simpson Peter C. Increasing bias for oxygen production in an electrode system
US20050176136A1 (en) 2003-11-19 2005-08-11 Dexcom, Inc. Afinity domain for analyte sensor
US7366556B2 (en) 2003-12-05 2008-04-29 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
WO2005019795A2 (en) * 2003-07-25 2005-03-03 Dexcom, Inc. Electrochemical sensors including electrode systems with increased oxygen generation
EP1648298A4 (en) 2003-07-25 2010-01-13 Dexcom Inc Oxygen enhancing membrane systems for implantable devices
WO2007120442A2 (en) 2003-07-25 2007-10-25 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US7519408B2 (en) 2003-11-19 2009-04-14 Dexcom, Inc. Integrated receiver for continuous analyte sensor
US7591801B2 (en) 2004-02-26 2009-09-22 Dexcom, Inc. Integrated delivery device for continuous glucose sensor
US7433727B2 (en) 2003-09-24 2008-10-07 Legacy Good Samaritan Hospital And Medical Center Implantable biosensor
DE602004026763D1 (en) * 2003-09-30 2010-06-02 Roche Diagnostics Gmbh SENSOR WITH IMPROVED BIOKOMPATIBILITY
US20050090607A1 (en) 2003-10-28 2005-04-28 Dexcom, Inc. Silicone composition for biocompatible membrane
ATE480761T1 (en) 2003-12-05 2010-09-15 Dexcom Inc CALIBRATION METHODS FOR A CONTINUOUSLY WORKING ANALYTICAL SENSOR
ATE474219T1 (en) 2003-12-08 2010-07-15 Dexcom Inc SYSTEMS AND METHODS FOR IMPROVING ELECTROCHEMICAL ANALYT SENSORS
WO2005057175A2 (en) 2003-12-09 2005-06-23 Dexcom, Inc. Signal processing for continuous analyte sensor
CN101039975A (en) 2004-01-08 2007-09-19 荷兰聚合物研究所基金会 Polyurethanes, polyurethaneureas and polyureas and use thereof
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
AU2005220150A1 (en) 2004-02-13 2005-09-15 The University Of North Carolina At Chapel Hill Functional materials and novel methods for the fabrication of microfluidic devices
US20050197554A1 (en) 2004-02-26 2005-09-08 Michael Polcha Composite thin-film glucose sensor
DE602005022704D1 (en) 2004-06-09 2010-09-16 Dickinson And Co SENSOR FOR SEVERAL ANALYTICS
US7640048B2 (en) 2004-07-13 2009-12-29 Dexcom, Inc. Analyte sensor
WO2006127023A2 (en) 2004-08-24 2006-11-30 University Of South Florida Epoxy enhanced polymer membrane to increase durability of biosensors
US7244443B2 (en) 2004-08-31 2007-07-17 Advanced Cardiovascular Systems, Inc. Polymers of fluorinated monomers and hydrophilic monomers
US9011831B2 (en) 2004-09-30 2015-04-21 Advanced Cardiovascular Systems, Inc. Methacrylate copolymers for medical devices
CA2586927A1 (en) 2004-11-09 2006-05-18 Angiotech Biocoatings Corp. Antimicrobial needle coating for extended infusion
CN100367906C (en) * 2004-12-08 2008-02-13 圣美迪诺医疗科技(湖州)有限公司 Endermic implantating biological sensors
US7604818B2 (en) 2004-12-22 2009-10-20 Advanced Cardiovascular Systems, Inc. Polymers of fluorinated monomers and hydrocarbon monomers
KR20070104574A (en) 2004-12-30 2007-10-26 신벤션 아게 Combination comprising an agent providing a signal, an implant material and a drug
US20060171980A1 (en) 2005-02-01 2006-08-03 Helmus Michael N Implantable or insertable medical devices having optimal surface energy
WO2006110193A2 (en) 2005-04-08 2006-10-19 Dexcom, Inc. Cellulosic-based interference domain for an analyte sensor
US20060263839A1 (en) 2005-05-17 2006-11-23 Isense Corporation Combined drug delivery and analyte sensor apparatus
US20060275859A1 (en) 2005-05-17 2006-12-07 Kjaer Thomas Enzyme sensor including a water-containing spacer layer
JP4763777B2 (en) 2005-05-17 2011-08-31 ラジオメーター・メディカル・アー・ペー・エス Enzyme sensor comprising a cover membrane layer coated with a hydrophilic polymer
US20070129524A1 (en) 2005-12-06 2007-06-07 Sunkara Hari B Thermoplastic polyurethanes comprising polytrimethylene ether soft segments
EP2004796B1 (en) 2006-01-18 2015-04-08 DexCom, Inc. Membranes for an analyte sensor
CA2577760A1 (en) 2006-02-27 2007-08-27 Tyco Healthcare Group Lp Pressurized dip coating system
US20070233013A1 (en) 2006-03-31 2007-10-04 Schoenberg Stephen J Covers for tissue engaging members
US8114023B2 (en) * 2006-07-28 2012-02-14 Legacy Emanuel Hospital & Health Center Analyte sensing and response system
US7871456B2 (en) * 2006-08-10 2011-01-18 The Regents Of The University Of California Membranes with controlled permeability to polar and apolar molecules in solution and methods of making same
CA2701006C (en) 2006-09-27 2016-07-12 University Of Connecticut Implantable biosensor and methods of use thereof
DE102007057553B4 (en) * 2007-11-30 2012-02-16 Siemens Ag A method of examining a human or animal body and medical imaging device therefor
CN101342465B (en) * 2008-09-01 2011-11-09 天津工业大学 Hollow fiber porous film and process for producing same

Patent Citations (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4890620A (en) * 1985-09-20 1990-01-02 The Regents Of The University Of California Two-dimensional diffusion glucose substrate sensing electrode
US5965380A (en) * 1993-12-02 1999-10-12 E. Heller & Company Subcutaneous glucose electrode
US6007845A (en) * 1994-07-22 1999-12-28 Massachusetts Institute Of Technology Nanoparticles and microparticles of non-linear hydrophilic-hydrophobic multiblock copolymers
US5611900A (en) * 1995-07-20 1997-03-18 Michigan State University Microbiosensor used in-situ
US6022463A (en) * 1996-05-16 2000-02-08 Sendx Medical, Inc. Sensors with subminiature through holes
US6071406A (en) * 1996-11-12 2000-06-06 Whatman, Inc. Hydrophilic polymeric phase inversion membrane
US6241863B1 (en) * 1998-04-27 2001-06-05 Harold G. Monbouquette Amperometric biosensors based on redox enzymes
US6233471B1 (en) * 1998-05-13 2001-05-15 Cygnus, Inc. Signal processing for measurement of physiological analysis
US6721587B2 (en) * 2001-02-15 2004-04-13 Regents Of The University Of California Membrane and electrode structure for implantable sensor
US7226978B2 (en) * 2002-05-22 2007-06-05 Dexcom, Inc. Techniques to improve polyurethane membranes for implantable glucose sensors
US7074307B2 (en) * 2003-07-25 2006-07-11 Dexcom, Inc. Electrode systems for electrochemical sensors
US20060040402A1 (en) * 2003-08-01 2006-02-23 Brauker James H System and methods for processing analyte sensor data
US20050251083A1 (en) * 2004-02-12 2005-11-10 Victoria Carr-Brendel Biointerface with macro-and micro-architecture
US20050245799A1 (en) * 2004-05-03 2005-11-03 Dexcom, Inc. Implantable analyte sensor
US20050242479A1 (en) * 2004-05-03 2005-11-03 Petisce James R Implantable analyte sensor
US20050245795A1 (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
US20060020188A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060020190A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060020189A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060020187A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060019327A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060020192A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060036145A1 (en) * 2004-07-13 2006-02-16 Dexcom, Inc. Transcutaneous analyte sensor
US20060036143A1 (en) * 2004-07-13 2006-02-16 Dexcom, Inc. Transcutaneous analyte sensor
US20060036144A1 (en) * 2004-07-13 2006-02-16 Dexcom, Inc. Transcutaneous analyte sensor
US20060036141A1 (en) * 2004-07-13 2006-02-16 Dexcom, Inc. Transcutaneous analyte sensor
US20060036140A1 (en) * 2004-07-13 2006-02-16 Dexcom, Inc. Transcutaneous analyte sensor
US20060036142A1 (en) * 2004-07-13 2006-02-16 Dexcom, Inc. Transcutaneous analyte sensor
US20060036139A1 (en) * 2004-07-13 2006-02-16 Dexcom, Inc. Transcutaneous analyte sensor
US20060020186A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060016700A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US20060020191A1 (en) * 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor

Cited By (294)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7835777B2 (en) 1997-03-04 2010-11-16 Dexcom, Inc. Device and method for determining analyte levels
US8527025B1 (en) 1997-03-04 2013-09-03 Dexcom, Inc. Device and method for determining analyte levels
US9339223B2 (en) 1997-03-04 2016-05-17 Dexcom, Inc. Device and method for determining analyte levels
US9439589B2 (en) 1997-03-04 2016-09-13 Dexcom, Inc. Device and method for determining analyte levels
US8676288B2 (en) 1997-03-04 2014-03-18 Dexcom, Inc. Device and method for determining analyte levels
US7974672B2 (en) 1997-03-04 2011-07-05 Dexcom, Inc. Device and method for determining analyte levels
US7792562B2 (en) 1997-03-04 2010-09-07 Dexcom, Inc. Device and method for determining analyte levels
US7970448B2 (en) 1997-03-04 2011-06-28 Dexcom, Inc. Device and method for determining analyte levels
US9931067B2 (en) 1997-03-04 2018-04-03 Dexcom, Inc. Device and method for determining analyte levels
US8380273B2 (en) 1998-04-30 2013-02-19 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8275439B2 (en) 1998-04-30 2012-09-25 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8840553B2 (en) 1998-04-30 2014-09-23 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US7869853B1 (en) 1998-04-30 2011-01-11 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US7885699B2 (en) 1998-04-30 2011-02-08 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
US8672844B2 (en) 1998-04-30 2014-03-18 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8734346B2 (en) 1998-04-30 2014-05-27 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8734348B2 (en) 1998-04-30 2014-05-27 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8622906B2 (en) 1998-04-30 2014-01-07 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8617071B2 (en) 1998-04-30 2013-12-31 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8738109B2 (en) 1998-04-30 2014-05-27 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8670815B2 (en) 1998-04-30 2014-03-11 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8612159B2 (en) 1998-04-30 2013-12-17 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8880137B2 (en) 1998-04-30 2014-11-04 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8666469B2 (en) 1998-04-30 2014-03-04 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8162829B2 (en) 1998-04-30 2012-04-24 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8175673B2 (en) 1998-04-30 2012-05-08 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8177716B2 (en) 1998-04-30 2012-05-15 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8660627B2 (en) 1998-04-30 2014-02-25 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8224413B2 (en) 1998-04-30 2012-07-17 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8226555B2 (en) 1998-04-30 2012-07-24 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9011331B2 (en) 1998-04-30 2015-04-21 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8226557B2 (en) 1998-04-30 2012-07-24 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8226558B2 (en) 1998-04-30 2012-07-24 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8231532B2 (en) 1998-04-30 2012-07-31 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8597189B2 (en) 1998-04-30 2013-12-03 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8235896B2 (en) 1998-04-30 2012-08-07 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9014773B2 (en) 1998-04-30 2015-04-21 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8774887B2 (en) 1998-04-30 2014-07-08 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US10478108B2 (en) 1998-04-30 2019-11-19 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9326714B2 (en) 1998-04-30 2016-05-03 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8255031B2 (en) 1998-04-30 2012-08-28 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8260392B2 (en) 1998-04-30 2012-09-04 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8265726B2 (en) 1998-04-30 2012-09-11 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9042953B2 (en) 1998-04-30 2015-05-26 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US7860544B2 (en) 1998-04-30 2010-12-28 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8273022B2 (en) 1998-04-30 2012-09-25 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9066694B2 (en) 1998-04-30 2015-06-30 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9066697B2 (en) 1998-04-30 2015-06-30 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8287454B2 (en) 1998-04-30 2012-10-16 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8306598B2 (en) 1998-04-30 2012-11-06 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8346336B2 (en) 1998-04-30 2013-01-01 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
US8353829B2 (en) 1998-04-30 2013-01-15 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8357091B2 (en) 1998-04-30 2013-01-22 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8366614B2 (en) 1998-04-30 2013-02-05 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8372005B2 (en) 1998-04-30 2013-02-12 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8974386B2 (en) 1998-04-30 2015-03-10 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8391945B2 (en) 1998-04-30 2013-03-05 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8409131B2 (en) 1998-04-30 2013-04-02 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9072477B2 (en) 1998-04-30 2015-07-07 Abbott Diabetes Care 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
US8473021B2 (en) 1998-04-30 2013-06-25 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8480580B2 (en) 1998-04-30 2013-07-09 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8649841B2 (en) 1998-04-30 2014-02-11 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8744545B2 (en) 1998-04-30 2014-06-03 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8641619B2 (en) 1998-04-30 2014-02-04 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
US8652043B2 (en) 2001-01-02 2014-02-18 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9498159B2 (en) 2001-01-02 2016-11-22 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8668645B2 (en) 2001-01-02 2014-03-11 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9610034B2 (en) 2001-01-02 2017-04-04 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9011332B2 (en) 2001-01-02 2015-04-21 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8765059B2 (en) 2001-04-02 2014-07-01 Abbott Diabetes Care Inc. Blood glucose tracking apparatus
US8268243B2 (en) 2001-04-02 2012-09-18 Abbott Diabetes Care Inc. Blood glucose tracking apparatus and methods
US8236242B2 (en) 2001-04-02 2012-08-07 Abbott Diabetes Care Inc. Blood glucose tracking apparatus and methods
US9477811B2 (en) 2001-04-02 2016-10-25 Abbott Diabetes Care Inc. Blood glucose tracking apparatus and methods
US7976778B2 (en) 2001-04-02 2011-07-12 Abbott Diabetes Care Inc. Blood glucose tracking apparatus
US9328371B2 (en) 2001-07-27 2016-05-03 Dexcom, Inc. Sensor head for use with implantable devices
US9804114B2 (en) 2001-07-27 2017-10-31 Dexcom, Inc. Sensor head for use with implantable devices
US20090045055A1 (en) * 2001-07-27 2009-02-19 Dexcom, Inc. Sensor head for use with implantable devices
US8509871B2 (en) 2001-07-27 2013-08-13 Dexcom, Inc. Sensor head for use with implantable devices
US8053018B2 (en) 2002-05-22 2011-11-08 Dexcom, Inc. Techniques to improve polyurethane membranes for implantable glucose sensors
US9801574B2 (en) 2002-05-22 2017-10-31 Dexcom, Inc. Techniques to improve polyurethane membranes for implantable glucose sensors
US9549693B2 (en) 2002-05-22 2017-01-24 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US20120040101A1 (en) * 2002-05-22 2012-02-16 Dexcom, Inc. Techniques to improve polyurethane membranes for implantable glucose sensors
US8064977B2 (en) 2002-05-22 2011-11-22 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US11020026B2 (en) 2002-05-22 2021-06-01 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US8050731B2 (en) 2002-05-22 2011-11-01 Dexcom, Inc. Techniques to improve polyurethane membranes for implantable glucose sensors
US10154807B2 (en) 2002-05-22 2018-12-18 Dexcom, Inc. Techniques to improve polyurethane membranes for implantable glucose sensors
US8865249B2 (en) 2002-05-22 2014-10-21 Dexcom, Inc. Techniques to improve polyurethane membranes for implantable glucose sensors
US9179869B2 (en) 2002-05-22 2015-11-10 Dexcom, Inc. Techniques to improve polyurethane membranes for implantable glucose sensors
US8543184B2 (en) 2002-05-22 2013-09-24 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US10052051B2 (en) 2002-05-22 2018-08-21 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US7811231B2 (en) 2002-12-31 2010-10-12 Abbott Diabetes Care Inc. Continuous glucose monitoring system and methods of use
US9962091B2 (en) 2002-12-31 2018-05-08 Abbott Diabetes Care Inc. Continuous glucose monitoring system and methods of use
US8187183B2 (en) 2002-12-31 2012-05-29 Abbott Diabetes Care Inc. Continuous glucose monitoring system and methods of use
US8622903B2 (en) 2002-12-31 2014-01-07 Abbott Diabetes Care Inc. Continuous glucose monitoring system and methods of use
US9597027B2 (en) 2003-07-25 2017-03-21 Dexcom, Inc. Oxygen enhancing membrane systems for implantable devices
US8909314B2 (en) 2003-07-25 2014-12-09 Dexcom, Inc. Oxygen enhancing membrane systems for implantable devices
US8255033B2 (en) 2003-07-25 2012-08-28 Dexcom, Inc. Oxygen enhancing membrane systems for implantable devices
US8255032B2 (en) 2003-07-25 2012-08-28 Dexcom, Inc. Oxygen enhancing membrane systems for implantable devices
US8255030B2 (en) 2003-07-25 2012-08-28 Dexcom, Inc. Oxygen enhancing membrane systems for implantable devices
US7828728B2 (en) 2003-07-25 2010-11-09 Dexcom, Inc. Analyte sensor
US9993186B2 (en) 2003-07-25 2018-06-12 Dexcom, Inc. Oxygen enhancing membrane systems for implantable devices
US10610140B2 (en) 2003-07-25 2020-04-07 Dexcom, Inc. Oxygen enhancing membrane systems for implantable devices
US8915849B2 (en) 2003-08-01 2014-12-23 Dexcom, Inc. Transcutaneous analyte sensor
US20060222566A1 (en) * 2003-08-01 2006-10-05 Brauker James H Transcutaneous analyte sensor
US8160669B2 (en) 2003-08-01 2012-04-17 Dexcom, Inc. Transcutaneous analyte sensor
US8000901B2 (en) 2003-08-01 2011-08-16 Dexcom, Inc. Transcutaneous analyte sensor
US8788007B2 (en) 2003-08-01 2014-07-22 Dexcom, Inc. Transcutaneous analyte sensor
US11020031B1 (en) 2003-12-05 2021-06-01 Dexcom, Inc. Analyte sensor
US11000215B1 (en) 2003-12-05 2021-05-11 Dexcom, Inc. Analyte sensor
US8277713B2 (en) 2004-05-03 2012-10-02 Dexcom, Inc. Implantable analyte sensor
US11883164B2 (en) 2004-07-13 2024-01-30 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US11064917B2 (en) 2004-07-13 2021-07-20 Dexcom, Inc. Analyte sensor
US10918314B2 (en) 2004-07-13 2021-02-16 Dexcom, Inc. Analyte sensor
US10932700B2 (en) 2004-07-13 2021-03-02 Dexcom, Inc. Analyte sensor
US10980452B2 (en) 2004-07-13 2021-04-20 Dexcom, Inc. Analyte sensor
US10993641B2 (en) 2004-07-13 2021-05-04 Dexcom, Inc. Analyte sensor
US9055901B2 (en) 2004-07-13 2015-06-16 Dexcom, Inc. Transcutaneous analyte sensor
US8565848B2 (en) 2004-07-13 2013-10-22 Dexcom, Inc. Transcutaneous analyte sensor
US10993642B2 (en) 2004-07-13 2021-05-04 Dexcom, Inc. Analyte sensor
US10799158B2 (en) 2004-07-13 2020-10-13 Dexcom, Inc. Analyte sensor
US8452368B2 (en) 2004-07-13 2013-05-28 Dexcom, Inc. Transcutaneous analyte sensor
US10709362B2 (en) 2004-07-13 2020-07-14 Dexcom, Inc. Analyte sensor
US7857760B2 (en) 2004-07-13 2010-12-28 Dexcom, Inc. Analyte sensor
US7905833B2 (en) 2004-07-13 2011-03-15 Dexcom, Inc. Transcutaneous analyte sensor
US9775543B2 (en) 2004-07-13 2017-10-03 Dexcom, Inc. Transcutaneous analyte sensor
US10918315B2 (en) 2004-07-13 2021-02-16 Dexcom, Inc. Analyte sensor
US8280475B2 (en) 2004-07-13 2012-10-02 Dexcom, Inc. Transcutaneous analyte sensor
US10524703B2 (en) 2004-07-13 2020-01-07 Dexcom, Inc. Transcutaneous analyte sensor
US10813576B2 (en) 2004-07-13 2020-10-27 Dexcom, Inc. Analyte sensor
US10918313B2 (en) 2004-07-13 2021-02-16 Dexcom, Inc. Analyte sensor
US8750955B2 (en) 2004-07-13 2014-06-10 Dexcom, Inc. Analyte sensor
US10722152B2 (en) 2004-07-13 2020-07-28 Dexcom, Inc. Analyte sensor
US11045120B2 (en) 2004-07-13 2021-06-29 Dexcom, Inc. Analyte sensor
US10799159B2 (en) 2004-07-13 2020-10-13 Dexcom, Inc. Analyte sensor
US8231531B2 (en) 2004-07-13 2012-07-31 Dexcom, Inc. Analyte sensor
US11026605B1 (en) 2004-07-13 2021-06-08 Dexcom, Inc. Analyte sensor
US10827956B2 (en) 2004-07-13 2020-11-10 Dexcom, Inc. Analyte sensor
US20060036145A1 (en) * 2004-07-13 2006-02-16 Dexcom, Inc. Transcutaneous analyte sensor
US10709363B2 (en) 2004-07-13 2020-07-14 Dexcom, Inc. Analyte sensor
US8663109B2 (en) 2004-07-13 2014-03-04 Dexcom, Inc. Transcutaneous analyte sensor
US10918317B2 (en) 2005-03-10 2021-02-16 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10610135B2 (en) 2005-03-10 2020-04-07 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10918318B2 (en) 2005-03-10 2021-02-16 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US11051726B2 (en) 2005-03-10 2021-07-06 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10743801B2 (en) 2005-03-10 2020-08-18 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10716498B2 (en) 2005-03-10 2020-07-21 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10709364B2 (en) 2005-03-10 2020-07-14 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10617336B2 (en) 2005-03-10 2020-04-14 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10610137B2 (en) 2005-03-10 2020-04-07 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10925524B2 (en) 2005-03-10 2021-02-23 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10610136B2 (en) 2005-03-10 2020-04-07 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10856787B2 (en) 2005-03-10 2020-12-08 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10898114B2 (en) 2005-03-10 2021-01-26 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10918316B2 (en) 2005-03-10 2021-02-16 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US11000213B2 (en) 2005-03-10 2021-05-11 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10300507B2 (en) 2005-05-05 2019-05-28 Dexcom, Inc. Cellulosic-based resistance domain for an analyte sensor
US8744546B2 (en) 2005-05-05 2014-06-03 Dexcom, Inc. Cellulosic-based resistance domain for an analyte sensor
US10813577B2 (en) 2005-06-21 2020-10-27 Dexcom, Inc. Analyte sensor
US11272867B2 (en) 2005-11-01 2022-03-15 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US11911151B1 (en) 2005-11-01 2024-02-27 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US10201301B2 (en) 2005-11-01 2019-02-12 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US10231654B2 (en) 2005-11-01 2019-03-19 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US10952652B2 (en) 2005-11-01 2021-03-23 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9326716B2 (en) 2005-11-01 2016-05-03 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8915850B2 (en) 2005-11-01 2014-12-23 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US11103165B2 (en) 2005-11-01 2021-08-31 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8920319B2 (en) 2005-11-01 2014-12-30 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US11399748B2 (en) 2005-11-01 2022-08-02 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US11363975B2 (en) 2005-11-01 2022-06-21 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9078607B2 (en) 2005-11-01 2015-07-14 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US11298058B2 (en) 2005-12-28 2022-04-12 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
US10307091B2 (en) 2005-12-28 2019-06-04 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
US9795331B2 (en) 2005-12-28 2017-10-24 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
WO2007102842A2 (en) 2006-03-09 2007-09-13 Dexcom, Inc. Systems and methods for processing analyte sensor data
EP3513708A1 (en) 2006-03-09 2019-07-24 Dexcom, Inc. Systems and methods for processing analyte sensor data
EP4218548A1 (en) 2006-03-09 2023-08-02 Dexcom, Inc. Systems and methods for processing analyte sensor data
US7920907B2 (en) 2006-06-07 2011-04-05 Abbott Diabetes Care Inc. Analyte monitoring system and method
US20080292026A1 (en) * 2006-08-25 2008-11-27 Alcatel Lucent Digital signal receiver with q-monitor
EP2796090A1 (en) 2006-10-04 2014-10-29 DexCom, Inc. Analyte sensor
US11382539B2 (en) 2006-10-04 2022-07-12 Dexcom, Inc. Analyte sensor
EP2796093A1 (en) 2007-03-26 2014-10-29 DexCom, Inc. Analyte sensor
EP4159114A1 (en) 2007-10-09 2023-04-05 DexCom, Inc. Integrated insulin delivery system with continuous glucose sensor
EP4098177A1 (en) 2007-10-09 2022-12-07 DexCom, Inc. Integrated insulin delivery system with continuous glucose sensor
EP4250312A2 (en) 2007-10-25 2023-09-27 DexCom, Inc. Systems and methods for processing sensor data
US9143569B2 (en) 2008-02-21 2015-09-22 Dexcom, Inc. Systems and methods for processing, transmitting and displaying sensor data
US11102306B2 (en) 2008-02-21 2021-08-24 Dexcom, Inc. Systems and methods for processing, transmitting and displaying sensor data
US9020572B2 (en) 2008-02-21 2015-04-28 Dexcom, Inc. Systems and methods for processing, transmitting and displaying sensor data
US8591455B2 (en) 2008-02-21 2013-11-26 Dexcom, Inc. Systems and methods for customizing delivery of sensor data
US8229535B2 (en) 2008-02-21 2012-07-24 Dexcom, Inc. Systems and methods for blood glucose monitoring and alert delivery
US9693721B2 (en) 2008-03-28 2017-07-04 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US10143410B2 (en) 2008-03-28 2018-12-04 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US9566026B2 (en) 2008-03-28 2017-02-14 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US8954128B2 (en) 2008-03-28 2015-02-10 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US11730407B2 (en) 2008-03-28 2023-08-22 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US9549699B2 (en) 2008-03-28 2017-01-24 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US20090247855A1 (en) * 2008-03-28 2009-10-01 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
US9572523B2 (en) 2008-03-28 2017-02-21 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US9173606B2 (en) 2008-03-28 2015-11-03 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US9173607B2 (en) 2008-03-28 2015-11-03 Dexcom, Inc. Polymer membranes for continuous analyte sensors
EP3387993A2 (en) 2008-03-28 2018-10-17 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US11147483B2 (en) 2008-03-28 2021-10-19 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US8560039B2 (en) 2008-09-19 2013-10-15 Dexcom, Inc. Particle-containing membrane and particulate electrode for analyte sensors
EP4227675A2 (en) 2008-09-19 2023-08-16 DexCom, Inc. Particle-containing membrane and particulate electrode for analyte sensors
US10028683B2 (en) 2008-09-19 2018-07-24 Dexcom, Inc. Particle-containing membrane and particulate electrode for analyte sensors
US10028684B2 (en) 2008-09-19 2018-07-24 Dexcom, Inc. Particle-containing membrane and particulate electrode for analyte sensors
US9339222B2 (en) 2008-09-19 2016-05-17 Dexcom, Inc. Particle-containing membrane and particulate electrode for analyte sensors
EP3795987A1 (en) 2008-09-19 2021-03-24 Dexcom, Inc. Particle-containing membrane and particulate electrode for analyte sensors
US10561352B2 (en) 2008-09-19 2020-02-18 Dexcom, Inc. Particle-containing membrane and particulate electrode for analyte sensors
US10980461B2 (en) 2008-11-07 2021-04-20 Dexcom, Inc. Advanced analyte sensor calibration and error detection
EP3536241A1 (en) 2011-04-08 2019-09-11 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
EP4233718A2 (en) 2011-04-08 2023-08-30 DexCom, Inc. Systems and methods for processing and transmitting sensor data
EP3092949A1 (en) 2011-09-23 2016-11-16 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
EP3888551A1 (en) 2011-09-23 2021-10-06 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
EP3505065A1 (en) 2011-09-23 2019-07-03 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
EP3505064A1 (en) 2011-09-23 2019-07-03 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
EP4275598A2 (en) 2012-04-04 2023-11-15 DexCom, Inc. Applicator and method for applying a transcutaneous analyte sensor
WO2013152090A2 (en) 2012-04-04 2013-10-10 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
EP3975192A1 (en) 2012-06-05 2022-03-30 Dexcom, Inc. Systems and methods for processing analyte data and generating reports
WO2013184566A2 (en) 2012-06-05 2013-12-12 Dexcom, Inc. Systems and methods for processing analyte data and generating reports
US11145410B2 (en) 2012-06-05 2021-10-12 Dexcom, Inc. Dynamic report building
EP4018929A1 (en) 2012-06-29 2022-06-29 Dexcom, Inc. Method and system for processing data from a continuous glucose sensor
WO2014004460A1 (en) 2012-06-29 2014-01-03 Dexcom, Inc. Use of sensor redundancy to detect sensor failures
US11737692B2 (en) 2012-06-29 2023-08-29 Dexcom, Inc. Implantable sensor devices, systems, and methods
US11892426B2 (en) 2012-06-29 2024-02-06 Dexcom, Inc. Devices, systems, and methods to compensate for effects of temperature on implantable sensors
EP3915465A2 (en) 2012-06-29 2021-12-01 Dexcom, Inc. Use of sensor redundancy to detect sensor failures
EP4080517A1 (en) 2012-07-09 2022-10-26 Dexcom, Inc. Systems and methods for leveraging smartphone features in continuous glucose monitoring
EP4075441A1 (en) 2012-07-09 2022-10-19 Dexcom, Inc. Systems and methods for leveraging smartphone features in continuous glucose monitoring
WO2014011488A2 (en) 2012-07-09 2014-01-16 Dexcom, Inc. Systems and methods for leveraging smartphone features in continuous glucose monitoring
EP3767633A1 (en) 2012-07-09 2021-01-20 Dexcom, Inc. Systems and methods for leveraging smartphone features in continuous glucose monitoring
US11179079B2 (en) 2012-09-28 2021-11-23 Dexcom, Inc. Zwitterion surface modifications for continuous sensors
US11864891B2 (en) 2012-09-28 2024-01-09 Dexcom, Inc. Zwitterion surface modifications for continuous sensors
WO2014052080A1 (en) 2012-09-28 2014-04-03 Dexcom, Inc. Zwitterion surface modifications for continuous sensors
EP3782550A1 (en) 2012-09-28 2021-02-24 Dexcom, Inc. Zwitterion surface modifications for continuous sensors
EP4231309A2 (en) 2012-11-07 2023-08-23 DexCom, Inc. Systems and methods for managing glycemic variability
EP3654348A1 (en) 2012-11-07 2020-05-20 Dexcom, Inc. Systems and methods for managing glycemic variability
US10860687B2 (en) 2012-12-31 2020-12-08 Dexcom, Inc. Remote monitoring of analyte measurements
US11744463B2 (en) 2012-12-31 2023-09-05 Dexcom, Inc. Remote monitoring of analyte measurements
US10993617B2 (en) 2012-12-31 2021-05-04 Dexcom, Inc. Remote monitoring of analyte measurements
US10856736B2 (en) 2012-12-31 2020-12-08 Dexcom, Inc. Remote monitoring of analyte measurements
US11109757B2 (en) 2012-12-31 2021-09-07 Dexcom, Inc. Remote monitoring of analyte measurements
US11213204B2 (en) 2012-12-31 2022-01-04 Dexcom, Inc. Remote monitoring of analyte measurements
US11382508B2 (en) 2012-12-31 2022-07-12 Dexcom, Inc. Remote monitoring of analyte measurements
US10869599B2 (en) 2012-12-31 2020-12-22 Dexcom, Inc. Remote monitoring of analyte measurements
US11850020B2 (en) 2012-12-31 2023-12-26 Dexcom, Inc. Remote monitoring of analyte measurements
US11160452B2 (en) 2012-12-31 2021-11-02 Dexcom, Inc. Remote monitoring of analyte measurements
EP3806103A1 (en) 2013-03-14 2021-04-14 Dexcom, Inc. Advanced calibration for analyte sensors
US11677443B1 (en) 2013-03-14 2023-06-13 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
EP3401818A1 (en) 2013-03-14 2018-11-14 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
US11491001B2 (en) 2013-03-14 2022-11-08 Cell and Molecular Tissue Engineering, LLC Implantable devices coated with extracellular matrix
EP4220654A1 (en) 2013-03-14 2023-08-02 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
US10130288B2 (en) 2013-03-14 2018-11-20 Cell and Molecular Tissue Engineering, LLC Coated sensors, and corresponding systems and methods
WO2014158405A2 (en) 2013-03-14 2014-10-02 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
EP4235684A1 (en) 2013-03-14 2023-08-30 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
WO2014158327A2 (en) 2013-03-14 2014-10-02 Dexcom, Inc. Advanced calibration for analyte sensors
US10985804B2 (en) 2013-03-14 2021-04-20 Dexcom, Inc. Systems and methods for processing and transmitting sensor data
US9717583B2 (en) 2014-03-13 2017-08-01 Cell and Molecular Tissue Engineering, LLC Sensors, cannulas, collars and coated surgical mesh, and corresponding systems and methods
WO2015156966A1 (en) 2014-04-10 2015-10-15 Dexcom, Inc. Sensors for continuous analyte monitoring, and related methods
EP4257044A2 (en) 2014-04-10 2023-10-11 DexCom, Inc. Sensor for continuous analyte monitoring
WO2016085556A1 (en) * 2014-09-12 2016-06-02 Cell and Molecular Tissue Engineering, LLC Coated implants, and corresponding systems and methods
EP4046571A1 (en) 2015-10-21 2022-08-24 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
US11399721B2 (en) 2015-12-28 2022-08-02 Dexcom, Inc. Systems and methods for remote and host monitoring communications
US10932672B2 (en) 2015-12-28 2021-03-02 Dexcom, Inc. Systems and methods for remote and host monitoring communications
EP4324921A2 (en) 2015-12-30 2024-02-21 Dexcom, Inc. Biointerface layer for analyte sensors
EP4253536A2 (en) 2015-12-30 2023-10-04 DexCom, Inc. Diffusion resistance layer for analyte sensors
EP4292528A1 (en) 2015-12-30 2023-12-20 Dexcom, Inc. Membrane layers for analyte sensors
EP3895614A1 (en) 2015-12-30 2021-10-20 Dexcom, Inc. Enzyme immobilized adhesive layer for analyte sensors
US11112377B2 (en) 2015-12-30 2021-09-07 Dexcom, Inc. Enzyme immobilized adhesive layer for analyte sensors
US10980453B2 (en) 2016-03-31 2021-04-20 Dexcom, Inc. Systems and methods for display device and sensor electronics unit communication
US10980451B2 (en) 2016-03-31 2021-04-20 Dexcom, Inc. Systems and methods for display device and sensor electronics unit communication
US10568552B2 (en) 2016-03-31 2020-02-25 Dexcom, Inc. Systems and methods for display device and sensor electronics unit communication
US10881335B2 (en) 2016-03-31 2021-01-05 Dexcom, Inc. Systems and methods for display device and sensor electronics unit communication
US10561349B2 (en) 2016-03-31 2020-02-18 Dexcom, Inc. Systems and methods for display device and sensor electronics unit communication
US10980450B2 (en) 2016-03-31 2021-04-20 Dexcom, Inc. Systems and methods for display device and sensor electronics unit communication
US10799157B2 (en) 2016-03-31 2020-10-13 Dexcom, Inc. Systems and methods for display device and sensor electronics unit communication
US11395631B2 (en) 2017-06-23 2022-07-26 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
US11311241B2 (en) 2017-06-23 2022-04-26 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
EP3928688A1 (en) 2017-06-23 2021-12-29 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
EP3925522A1 (en) 2017-06-23 2021-12-22 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
EP4008240A1 (en) 2017-06-23 2022-06-08 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
US11504063B2 (en) 2017-06-23 2022-11-22 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
US11510625B2 (en) 2017-06-23 2022-11-29 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and associated methods
EP4111949A1 (en) 2017-06-23 2023-01-04 Dexcom, Inc. Transcutaneous analyte sensors, applicators therefor, and needle hub comprising anti-rotation feature
US11350862B2 (en) 2017-10-24 2022-06-07 Dexcom, Inc. Pre-connected analyte sensors
US11331022B2 (en) 2017-10-24 2022-05-17 Dexcom, Inc. Pre-connected analyte sensors
US11382540B2 (en) 2017-10-24 2022-07-12 Dexcom, Inc. Pre-connected analyte sensors
US11706876B2 (en) 2017-10-24 2023-07-18 Dexcom, Inc. Pre-connected analyte sensors
US11918354B2 (en) 2019-12-31 2024-03-05 Dexcom, Inc. Particle-containing membrane and particulate electrode for analyte sensors

Also Published As

Publication number Publication date
US8050731B2 (en) 2011-11-01
US20100119693A1 (en) 2010-05-13
US20060086624A1 (en) 2006-04-27
US8865249B2 (en) 2014-10-21
JP2005531755A (en) 2005-10-20
EP1506307A1 (en) 2005-02-16
US20180014765A1 (en) 2018-01-18
US9179869B2 (en) 2015-11-10
US20130030273A1 (en) 2013-01-31
US10154807B2 (en) 2018-12-18
US7226978B2 (en) 2007-06-05
US9801574B2 (en) 2017-10-31
US8053018B2 (en) 2011-11-08
WO2003100083A1 (en) 2003-12-04
US20190083018A1 (en) 2019-03-21
JP4317519B2 (en) 2009-08-19
US20120040101A1 (en) 2012-02-16
US20160022186A1 (en) 2016-01-28
AU2003229330A1 (en) 2003-12-12
US20140378798A1 (en) 2014-12-25
US20030217966A1 (en) 2003-11-27

Similar Documents

Publication Publication Date Title
US10154807B2 (en) Techniques to improve polyurethane membranes for implantable glucose sensors
US6642015B2 (en) Hydrophilic polymeric material for coating biosensors
US5777060A (en) Silicon-containing biocompatible membranes
AU658450B2 (en) Hydrophilic polyurethane membranes for electrochemical glucose sensors
JP4763777B2 (en) Enzyme sensor comprising a cover membrane layer coated with a hydrophilic polymer
US8509871B2 (en) Sensor head for use with implantable devices
WO1992013271A1 (en) Implantable biological fluid measuring device
WO2006018425A2 (en) Multiphase biocompatible semi-permeable membrane for biosensors
CN102762740A (en) Analyte sensors comprising blended membrane compositions and methods for making and using them
EP0870191A1 (en) Silicon-containing biocompatible membranes
WO2004060297A2 (en) Hydrophilic cross-linking agents for use in enzymatic sensors
JP4098364B2 (en) Silicon-containing biocompatible membrane
CA2238005C (en) Silicon-containing biocompatible membranes
Akmal et al. An overview of medical polymers and diagnostic reagents
JP2000500691A (en) Silicon-containing biocompatible membrane

Legal Events

Date Code Title Description
AS Assignment

Owner name: DEXCOM, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:TAPSAK, MARK A.;RHODES, RATHBUN K.;SHULTS, MARK C.;AND OTHERS;REEL/FRAME:017244/0872;SIGNING DATES FROM 20020516 TO 20020521

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION