+

WO2000059373A1 - Dispositif d'analyse permettant de determiner les caracteristiques d'un fluide en continu - Google Patents

Dispositif d'analyse permettant de determiner les caracteristiques d'un fluide en continu Download PDF

Info

Publication number
WO2000059373A1
WO2000059373A1 PCT/US2000/009393 US0009393W WO0059373A1 WO 2000059373 A1 WO2000059373 A1 WO 2000059373A1 US 0009393 W US0009393 W US 0009393W WO 0059373 A1 WO0059373 A1 WO 0059373A1
Authority
WO
WIPO (PCT)
Prior art keywords
assay device
fluid
well
reactant
working electrode
Prior art date
Application number
PCT/US2000/009393
Other languages
English (en)
Other versions
WO2000059373A9 (fr
Inventor
Krishna S. Kumar
Joseph Papp
J. David Farquhar
Lance Taylor
Alan M. Smith
Mark S. Vreeke
Michael R. Hatch
Jarad Schiffer
Mark L. Faupel
James Connolly
Original Assignee
Spectrx, 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 Spectrx, Inc. filed Critical Spectrx, Inc.
Priority to CA002366753A priority Critical patent/CA2366753A1/fr
Priority to EP00921911A priority patent/EP1164925A1/fr
Priority to JP2000608941A priority patent/JP2002541441A/ja
Priority to AU42169/00A priority patent/AU4216900A/en
Priority to BR0009581-8A priority patent/BR0009581A/pt
Publication of WO2000059373A1 publication Critical patent/WO2000059373A1/fr
Publication of WO2000059373A9 publication Critical patent/WO2000059373A9/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1486—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means using enzyme electrodes, e.g. with immobilised oxidase
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1495—Calibrating or testing of in-vivo probes

Definitions

  • the present invention relates in general to analyte detection systems and methods. More specifically, this invention relates to an assay device that detects the presence, amount or other characteristic of an analyte of interest such as a glucose level within a fluid collected from a tissue on a continuous/continual basis.
  • an analyte of interest such as a glucose level within a fluid collected from a tissue on a continuous/continual basis.
  • U. S. Patent No. 5,961,451 to Reber et al. This patent sets forth a system which monitors the glucose level in the patient's interstitial fluid via an electrochemical assay device. However, this system is for one-time use only. The assay device must be replaced after every use.
  • U. S Patent No. 5,391,250 to Cheney II et al. and U. S. Patent No. 5,437,999 to Diebold et al. teach methods for fabricating electrochemical devices for one-time use biological applications.
  • the present invention relates to an assay device for detecting an analyte in a fluid, comprising: a) an inlet port to receive fluid; b) a well in fluid communication with the inlet port; c) an outlet port in fluid communication with the well to discharge fluid; d) at least one first working electrode and at least one reference electrode disposed within the well; e) a quantity of reactant that reacts with the analyte to form a reaction product, wherein the reaction product is in fluid communication with the at least one first working electrode; and f) at least one membrane disposed over or around the reactant to regulate contact of the analyte in the fluid with the reactant.
  • the membrane serves to extend the useful life of the assay device by slowing consumption of the reactant. As a result, the assay device is well suited for continuous monitoring applications.
  • the present invention relates to an assay device for detecting and enabling measurement of an analyte in a fluid
  • an assay device for detecting and enabling measurement of an analyte in a fluid
  • Figure 1 is a cross-section view of a preferred embodiment of the assay device according to the present invention.
  • Figure 2 is a cross-section view of an alternative embodiment of the assay device.
  • Figure 3 is a cross-section view of an another alternative embodiment of the assay device.
  • Figure 4 depicts an exploded view of still another embodiment of an assay device according to the present invention.
  • analyte shall mean the component that is being detected or measured in an analysis.
  • the analyte may be any chemical or biological material or compound suitable for passage through a biological membrane technology known in the art, of which an individual might want to know the concentration or activity inside the body.
  • Glucose is a specific example of an analyte because it is a sugar suitable for passage through the skin, and individuals, for example those having diabetes, might want to know their blood glucose levels.
  • Other examples of analytes include, but are not limited to, such compounds as sodium, potassium, billirubin, urea, ammonia, calcium, lead, iron, lithium, salicylates, pharmaceutical compounds, and the like.
  • Ranges may be expressed herein as from “about” or “approximately” one particular value and/or to “about” or “approximately” another particular value. When such a range is expressed, another embodiment comprises from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent "about,” it will be understood that the particular value forms another embodiment.
  • the present invention is directed at an assay device for detecting and enabling measurement of an analyte in a fluid.
  • the assay device contains: a) an inlet port to receive fluid; b) a well in fluid communication with the inlet port; c) an outlet port in fluid communication with the well, wherein the outlet port is designed to allow discharge of the fluid; d) at least one first working electrode and at least one reference electrode disposed within the well; e) a quantity of reactant that reacts with the analyte to form a reaction product, wherein the reaction product is in fluid communication with the at least one first working electrode; and f) at least one membrane disposed over or around the reactant to regulate contact of the analyte in the fluid with the reactant.
  • the present invention is directed to an assay device containing: a) an inlet port to receive fluid; b) a well in fluid communication with the inlet port; c) an outlet port in fluid communication with the well, wherein the outlet port is designed to allow discharge of the fluid; d) at least one first working electrode and at least one reference electrode disposed within the well; e) a quantity of reactant that reacts with the analyte to form a reaction product, wherein the reaction product is in fluid communication with the at least one first working electrode; and f) calibration port that is in fluid communication with the well.
  • the assay device according to the present invention is suitable for use in a continuous/continual analyte monitoring system, such as that disclosed in International Application No. PCT/US99/16378, entitled “System and Method for Continuous Analyte Monitoring,” filed July 20, 1999, which is incorporated herein by reference.
  • the assay device 1000 comprises a bottom layer 100 that is in fluid communication with a channel- forming adhesive layer 200 via an inlet port 910.
  • the channel-forming adhesive layer 200 has a layer of adhesive with a channel cut into it to form a well 250.
  • Within the well 250 are the membrane 300 and electrodes 400.
  • electrode 410 is a working electrode
  • electrode 420 is a working electrode
  • electrode 430 is a reference electrode
  • electrode 440 is a counter-electrode. At least one of the working electrodes 420 is coated with a reactant 500.
  • the electrodes 400 are disposed on or in a support base 600.
  • the support base 600 is adjacent to an adhesive layer 700.
  • An outlet port 920 extends through the support base layer 600, the adhesive layer 700, and a top layer 800.
  • the bottom layer 100 provides structural support to the assay device 1000 and serves as the interface between the fluid source and the assay device 1000.
  • Any suitable material, in any thickness or shape may be used for the bottom layer 100.
  • Example suitable materials include acrylic, polyester, plastic, ceramic, polycarbonate and polyvinylchloride.
  • the inlet port 910 which provides fluid communication between the bottom layer 100, the channel-forming adhesive layer 200, and the well 250, may be in any position and in any dimension/shape to allow sufficient flow to the electrodes 400.
  • the inlet port 910 is suitable for alignment with holes/porations in a tissue from which fluid is to be drawn, such as interstitial fluid.
  • An example of a mechanism to facilitate alignment of the assay device 1000 with the holes/porations in the tissue is disclosed in U.S. Provisional Application Serial No. 60/140,257 filed June 18, 1999 entitled “System and Method for Alignment of Micropores for Efficient Fluid Extraction and Substance Delivery,” which is incorporated herein by reference.
  • the channel-forming adhesive layer 200 forms the well 250 to limit the volume of fluid within the assay device 1000.
  • Suitable materials for the channel- forming adhesive layer 200 are compatible with the fluid of interest, provide adhesive support to the assay device 1000, and are thick enough to provide a well 250 from a channel cut into the channel-forming adhesive layer 200.
  • the fluid of interest is blood or interstitial fluid, thereby requiring the channel- forming adhesive layer 200 to be constructed from adhesive-like materials that are not water-soluble.
  • the electrodes 400 are disposed on or in a support base 600 using screen- printing, pad printing, sputter coating, photolithography or other suitable techniques, using known inks and dielectrics.
  • the support base 600 may be of any thickness effective to provide support and bind the electrodes 400.
  • One preferred embodiment includes a support base 600 of 10 mil thick transparent polyester.
  • Other suitable materials may be used including ceramic, polycarbonate, and polyvinylchloride.
  • an adhesive layer 700 and a top layer 800 provide additional support to the assay device 1000.
  • the adhesive layer 700 binds the support base 600 to the top layer 800.
  • the material of construction and dimension of the adhesive layer 700 is not critical to the present invention, thereby allowing any effective adhesive to be used.
  • the top layer 800 like the bottom layer 100, provides structural support to the assay device 1000.
  • the top layer 800 is constructed of the same material or compatible material as the bottom layer 100.
  • An outlet port 920 allows discharge of the fluid from the well 250 through the support base 600, adhesive layer 700, and the top layer 800. It may be in any position and in any dimension/shape to allow sufficient flow to the electrodes 400.
  • the outlet port 920 also is suitable for connection to a supply of vacuum sufficient to draw fluid through the well 250. In one preferred embodiment, the vacuum is sufficient to produce fluid from the skin at a site of where small holes/porations have been made in the tissue.
  • the well 250 serves to expose the membrane 300 and electrodes 400 to the fluid that is monitored. Therefore, the well 250 is preferably of a dimension that the membrane 300 and the electrodes 400 do not obstruct the flow of fluid.
  • a reactant 500 reacts with the analyte to form a reaction product.
  • the reaction product is in fluid communication with one or both of the working electrodes 410 and 420 whereby electrons are created.
  • the reactant 500 may react with glucose, which may in turn form hydrogen peroxide.
  • oxygen gas, hydrogen ions and electrons are produced.
  • Each working electrode 410 and 420 may be made from a variety of materials such as carbon and metals such as gold or silver.
  • each working electrode 410 and 420 is made from catalytic metals such as platinum, palladium, chromium, ruthenium, rubidium, or mixtures thereof.
  • the working electrodes 410 and 420 contain platinum.
  • At least one working electrode and at least one reference electrode are necessary. However, more than one working electrode and one or more counter-electrodes may also be present.
  • the working electrode 410 does not contain the reactant and therefore it produces an electrical signal that is indicative of the fluid without the analyte. This allows reduction or elimination of the signal due to various interferent compounds by subtracting the electrical signal of the working electrode 410 from the electrical signal of the working electrode 420.
  • one working electrode may be used if the levels of interference are not significant or if an interference blocking layer is included.
  • This interference blocking layer could be positioned anywhere between the fluid to be analyzed and the working electrodes 410 and 420.
  • the interference blocking layer is placed directly over the working electrodes 410 and 420.
  • the interference blocking layer is placed adjacent to the membrane 300.
  • Suitable interference blocking layers include NAFIONTM and cellulose acetate.
  • the reference electrode 430 establishes a potential relative to the fluid.
  • the reference electrode 430 contains silver/silver-chloride.
  • the counter- electrode 440 which is optional, serves to ground the current generated by the working electrodes 410 and 420.
  • the counter-electrode 440 contains substantially the same materials as the working electrodes 410 and 420.
  • the assay device 1000 may contain more than one working electrode, more than one reference electrode and more than one counter-electrode, as is well known in the art.
  • the active surface of the electrodes 400 may be any shape and dimension to effectively operate. Particularly, the surface area of the any of the electrodes 400 can be varied as long as there is sufficient sensitivity to measuring the current. Preferably, the electrodes 400 have active surface areas between 0.1 mm 2 and 10 mm 2 . Most preferably, the electrodes 400 have a surface area of lmm 2 .
  • the working electrodes 410 and 420 may be pre-conditioned by running at a specific voltage, such as +1.6 V relative to the reference electrode 430 for a suitable amount of time, such as 30 minutes, in a buffer system. This conditions the surface of the working electrodes 410 and 420 and increases their sensitivity to the reaction product generated by the reactant 500. Alternately, the working electrodes 410 and 420 could be conditioned for shorter times at higher voltages.
  • the working potential will depend on the composition and shape of catalytic surface area. As such, the working potential can vary from 200 mV to 2 V. Such potential may be supplied via a monitoring unit coupled to the assay device wherein the monitoring unit utilizes an amperometric or coulometric measurement technique, known in the art.
  • the working potential is generated either by holding the working electrodes 410 and 420 at a positive potential or by holding the counter-electrode 440 at a negative potential.
  • the working electrodes 410 and 420 may be held at +800 mV and the reference electrode 430 and counter-electrode 440 at 0 mV, or the working electrodes 410 and 420 may be held at 0 mV and the reference electrode 430 and counter- electrode 440 at -800 mV.
  • the electrodes may be connected to leads that in turn are connected to a monitoring unit ( Figure 4), patient worn or otherwise, via traces of graphite or silver/silver-chloride.
  • traces may be applied via any method that provides a sufficient resolution such as ink-jet printing or pad printing.
  • the printed traces could be replaced with traditional connection techniques.
  • a quantity of reactant 500 that reacts with the analyte to form a reaction product is disposed proximate to the at least one first working electrode such that when the analyte contacts the reactant 500, the reaction product is in fluid communication with the working electrode.
  • the quantity of reactant 500 covers a portion of the first working electrode (working electrode 420 shown in Figure 1).
  • the quantity of reactant 500 may also be disposed on or in at least one working electrode.
  • the reactant 500 is selected to react with a specific analyte.
  • the quantity of reactant 500 is suitable to react with glucose.
  • suitable reactants for the analyte glucose include glucose oxidase enzyme ("GOX"), glucose dehydrogenase (“GDH”), or mixtures thereof.
  • the glucose in the fluid makes contact with the reactant(s) to produce reaction products, which in the case of GOX, are gluconolactone and hydrogen peroxide.
  • the hydrogen peroxide diffuses to the working electrode 420 and reacts with the catalytic metal to produce electrons as described above.
  • the reactants may include a mediator as an electron receptor instead of using oxygen.
  • the mediator reacts with the working electrode 420 to produce electrons.
  • Mediators that are commonly used are ferrocene, ferrocyamide and their derivatives.
  • the reactant 500 is prepared by mixing 8 mg/mL GOX with 60 mg/mL bovine serum albumen ("BSA”) that is dissolved in phosphate buffered saline (“PBS”) that contains 10% glycerol and 0.01% NaN 3 .
  • BSA bovine serum albumen
  • PBS phosphate buffered saline
  • 20 ⁇ L of 25% glutaraldehyde is added to the mixture immediately before application.
  • a l ⁇ L drop of this mixture is placed onto one of the working electrodes. The mixture is then allowed to solidify and cure at room temperature for approximately eight to sixteen hours.
  • the BSA serves as a carrier for the GOX due to its multiple cross-linking sites. As such, it can be replaced with any material that has multiple surface amine groups.
  • the combination of BSA and glutaraldehyde as a cross linking system can be replaced with a system that will immoblize the active enzyme (in this case, GOX or GDH) without inhibiting its activity. Suitable replacements include other cross-linkers, polymer films, avidin-biotin linkages, antibody linkages, and covalent attachment to colloidal gold or agarose beads.
  • the PBS acts to maintain the reactant in a neutral pH range (such as a pH of about 6.5 to about 7.5).
  • a neutral pH range such as a pH of about 6.5 to about 7.5.
  • Any suitable buffer may be used.
  • Example buffers include phosphate, citrate, Tris-HCl, MOPS, HEPES, MES, Bis-Tris, BES, ADA, ACES, MDPSO, Bis-Tris Propane, and TES.
  • the glycerol serves to prevent the reactant 500 from becoming dehydrated which reduces the wetting time for later use.
  • any suitable additive may be used.
  • the NaN 3 acts as an anti-bacterial agent.
  • the NaN 3 could be replaced by any anti-microbial agent including antibiotics and detergents.
  • the glutaraldehyde is a cross-linking agent that links the GOX and BSA into a matrix that will not dissolve or move from the electrode surface.
  • the glycerol could be present in an amount of 5% to 50%o (by weight).
  • the glycerol can be replaced or supplemented by any hygroscopic preservative or wetting agents including mild detergents such as TWEEN-20TM, SPANTM, TRITONTM, BRIJTM, MYRJTM and PLURONICSTM familes of detergents .
  • any of the components to the reactant 500 and the overall amount of reactant 500 are not critical to the present invention as long as the amount is effective. These proportions and overall amount of reactant 500 are limited by the preference of having an excess of reactant 500 as well as maintaining the reactant' s solubility in the available volume. Preferably, the concentration of the reactant 500 is a minimum of 1 mg/mL.
  • the reactant 500 may be applied to a working electrode with any method that allows for volume and position control capable with techniques such as screen printing, ink-jet printing, air brush, and pad printing.
  • the reactant 500 is preferably applied without glutaraldehyde, and then, the glutaraldehyde is placed down. This avoids fouling the nozzle with solidifying material.
  • the reactant 500 is dried and cured with the times of each varying based upon the amount and thickness of reactant layer(s) and the composition. Suitable drying conditions include temperatures up to 150°C, controlled humidity, and cure times of 15 minutes to 24 hours.
  • the GOX enzyme will saturate at concentrations of approximately 3 mM glucose. In order to detect higher levels of glucose, the concentration reaching the reactant 500 must be held to a fraction of the total concentration.
  • a membrane 300 is disposed over or around the reactant 500. In one preferred embodiment, the membrane 300 is disposed over or around all of the electrodes 400 as shown in Figure 3 In another preferred embodiment, the membrane 300 is disposed over or around the working electrodes 410 and 420 as shown in Figure 2. Alternatively, the membrane 300 is disposed over or around each electrode 400 or each working electrode 410 and 420 as shown in Figures 1.
  • the membrane 300 preferably is a diffusion-limiting membrane that extends the linear range and the lifetime of the assay device 1000 system and makes it useful in a continuous/continual monitoring system.
  • the membrane 300 has pores which regulate diffusion of an analyte therethrough. Therefore, the membrane 300 may be sized to limit the rate at which the analyte or an interferent makes contact with the reactant 500, thereby increasing the linear range of the assay device 1000.
  • the membrane 300 may have low porosity to reduce glucose flux.
  • the membrane 300 limits the amount of analyte that is present at the electrodes at any one time, allowing the electrodes 400 to operate continuously over long periods of time without depleting the reactant.
  • a monitoring unit coupled to the at least one working electrode may continuously draw fluid through the assay device and detect the presence or level of an analyte in excess of 24 hours, more preferably in excess of 48 hours, and still more preferably in excess of 70 hours.
  • One preferred membrane 300 is a 0.01 ⁇ m pore diameter polycarbonate ("PC") track-etch member 6 ⁇ m thick.
  • PC polycarbonate
  • Other suitable membranes that effectively produce a diffusion rate include dialysis membranes, polyurethane membranes, or polyvinylchloride membranes. Castable membranes such as NAFIONTM, cellulose acetate, silastics and alkoxy silanes are also effective for this use. Additionally, multiple membranes may be used.
  • the membrane 300 may be secured by a layer of cross-linked BSA in the same buffer as the reactant 500.
  • the cross-linked BSA consists of 60 mg/mL BSA dissolved in PBS containing 10%o glycerol and 0.01% NaN3.
  • 20 ⁇ L/mL of 25% glutaraldehyde may be added immediately before use.
  • any effective amount of this layer of cross-linked BSA may be used.
  • a 2 ⁇ L drop of the cross-linked BSA is placed on the reactant covered electrode.
  • a 5 mm diameter circle of the 0.01 ⁇ m PC membrane is placed over the drop of cross-linked BSA or other suitable, large polyamine.
  • the membrane 300 is gently pressed into place under a sheet of parafilm. It is allowed to cure for 16 hours at room temperature under the parafilm, and then the parafilm is removed.
  • the membrane 300 may be disposed over or around the reactant 500 by any suitable method including lamination, gluing, pressing, rolling and stretching. Any such method should not be destroyed by the fluid to be collected and analyzed. However, if an additional component is added, such as glue or other adhesion material, the additional component should be permeable in the fluid, such as Nafion is permeable in an aqueous-based fluid.
  • suitable adhesives include epoxies, UV curable adhesives, pressure sensitive adhesives and hydrogels such as HEMA.
  • the assay device 1000 is positioned on a tissue site overlying one or more openings made in the tissue.
  • the openings in the tissue may be made by a variety of means, such as those disclosed in commonly assigned U.S. Patent No. 5,885,211.
  • Fluid enters the assay device 1000 of Figure 1 through the inlet port 910. Under application of vacuum at the outlet port 920, the fluid travels through the well 250 and contacts the membrane 300.
  • the membrane 300 is permeable to the analyte in the fluid and thereby allows the analyte to contact the electrodes 400 and the reactant 500.
  • the analyte reacts with the reactant 500 to generate a reaction product.
  • the reaction product contacts the working electrode 420 and creates electrons, thereby generating a current flow.
  • the fluid continues through the outlet port 920 whereupon it exits the assay device 1000.
  • Current flow across the working electrode(s) is measured, and from this a measurement of the analyte is obtained.
  • the assay device 1000 may be used in conjunction with amperometric and coulometric measuring techniques.
  • the current (charge/second) is measured at the applied voltage. This can be measured continuously, which is a preferred method in a flowing system.
  • the total charge accumulated over a period of time is measured after a voltage is applied.
  • the fluid is allowed to react with the reactant over a fixed period of time, thereby generating a reaction product. Then a voltage is applied and the current, which is measured over a fixed period of time, is integrated (added) to calculate the total amount of charge produced by the reaction product.
  • This alternative method has the advantage of generating larger signals and reducing the impact of electroactive interfering substances.
  • the membrane 300 preserves the life of the reactant 500 by helping to hold the reactant 500 in place and to thereby reduce the risk of rapid dissolution of the reactant 500 in the fluid. Also, by restricting the amount of analyte and interferents to the reactant 500, the membrane 300 helps ensure that the reactant 500 is in excess than what is needed to fully engage the analyte. In this way, as the reactant 500 degrades over time, it may remain in excess and deterioration in performance will be minimized.
  • a variation of the assay device 1000 is shown in which a well 250 opens into an outlet port 920.
  • the outlet port 920 does not provide fluid communication through the support base 600, the adhesive layer 700, and the top layer 800. However, the outlet port 920 is suitable for connection to a supply of vacuum sufficient to draw fluid through the well 250.
  • the outlet port 920 may be filled with wiring and drain tubing, and then epoxy sealed.
  • Figure 3 shows another alternative preferred embodiment of the assay device 1000.
  • the well 250 is coupled to the outlet port 920.
  • Figure 3 shows an assay device that comprises only a support base 600 and bottom layer 100.
  • the bottom layer 100 provides the well 250 to expose the membrane 300 and electrodes 400 to the fluid.
  • Figure 4 shows another embodiment of an assay device 1000 according to the present invention.
  • This embodiment includes a bottom layer 100, a channel- forming adhesive layer 200, a support base 600, an adhesive layer 700, and a top layer 800.
  • Figure 4 also includes an inlet port 910, a well 250, an outlet port 920, a calibration port 950, and drain tubing 940.
  • this embodiment includes at least one working electrode, a reference electrode, and a reactant proximate to the working electrode as shown in Figures 1-3.
  • This embodiment may optionally include at least one membrane, as shown in Figure 1.
  • the electrodes are connected to a monitoring unit 970 via leads 960.
  • the monitoring unit 970 is also connected to assay device 1000 via the drain tubing 940.
  • the drain tubing 940 provides vacuum to the assay device 1000.
  • the calibration port 950 is suitable for connection to a reservoir 980 containing calibration fluid.
  • the calibration port 950 may include a membrane 990 permeable to the calibration fluid.
  • the calibration fluid consists of water and the analyte to be detected.
  • Other compounds may also be present, such as surfactants, which ensure smoother flow by reducing surface tension, such as SDS, or any of the detergents herein described.
  • preservatives such as azide, EDTA, or any antibacterial or appropriate biocide that will not degrade of interfere with the reactant's performance may be added to the calibration fluid.
  • the calibration fluid may include thickeners, such as polymers and proteins, to simulate the flow characteristics of the analyte-containing fluid that is being measured.
  • the reservoir 980 is in fluid communication with the well 250 such that the calibration fluid flushes the well 250 to contact the electrodes with the calibration fluid.
  • the calibration fluid is removed from the well 250 through the outlet port 920 under application of vacuum.
  • the reservoir 980 may release the calibration fluid into the well 250 using any effective mechanism.
  • the reservoir 980 comprises a bag-like member that opens and releases the calibration fluid into the well 250 in response to application of vacuum applied at the outlet port 920.
  • the reservoir 980 may be formed of a material that when mechanically punctured releases the calibration fluid into the well 250.
  • the membrane 990 is a self-sealing membrane that is rupturable to allow introduction of the calibration fluid such as by a syringe containing calibration fluid to deliver the calibration fluid into the well 250.
  • the calibration fluid is delivered into the well 250 while vacuum is applied at the outlet port 920.
  • the calibration fluid is introduced into the well 250 via a valve that operates as a one-way valve or is controlled external to the assay device 1000.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Biomedical Technology (AREA)
  • Medical Informatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Optics & Photonics (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

Cette invention concerne un dispositif d'essai permettant de détecter la présence d'un analysat dans un liquide et de procéder à des mesures sur ledit analysat. Ce dispositif d'analyse comprend les éléments suivants: a) orifice d'admission du liquide; b) puits en communication fluidique avec l'orifice d'admission; c) orifice de sortie en communication fluidique avec le puits dans lequel le liquide peut être refoulé; d) au moins une première électrode de travail et au moins une électrode de référence disposées dans le puits; e) un volume de réactif qui réagit avec l'analysat pour former un produit de réaction, lequel produit de réaction est en communication fluidique avec la première électrode de travail; et f) au moins une membrane disposée sur ou autour du réactif pour réguler le contact de ce dernier avec l'analysat présent dans le fluide.
PCT/US2000/009393 1999-04-07 2000-04-07 Dispositif d'analyse permettant de determiner les caracteristiques d'un fluide en continu WO2000059373A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
CA002366753A CA2366753A1 (fr) 1999-04-07 2000-04-07 Dispositif d'analyse permettant de determiner les caracteristiques d'un fluide en continu
EP00921911A EP1164925A1 (fr) 1999-04-07 2000-04-07 Dispositif d'analyse permettant de determiner les caracteristiques d'un fluide en continu
JP2000608941A JP2002541441A (ja) 1999-04-07 2000-04-07 流体の特性を連続的に測定する分析デバイス
AU42169/00A AU4216900A (en) 1999-04-07 2000-04-07 Assay device for measuring characteristics of a fluid on a continual basis
BR0009581-8A BR0009581A (pt) 1999-04-07 2000-04-07 Dispositivos de ensaio para detectar, e possibilitar a medição de, um analito em um fluido, e, sistema de monitoração

Applications Claiming Priority (10)

Application Number Priority Date Filing Date Title
US12819899P 1999-04-07 1999-04-07
US60/128,198 1999-04-07
US13997599P 1999-06-18 1999-06-18
US13997699P 1999-06-18 1999-06-18
US60/139,975 1999-06-18
US60/139,976 1999-06-18
US16580999P 1999-11-16 1999-11-16
US60/165,809 1999-11-16
US18269800P 2000-02-15 2000-02-15
US60/182,698 2000-02-15

Publications (2)

Publication Number Publication Date
WO2000059373A1 true WO2000059373A1 (fr) 2000-10-12
WO2000059373A9 WO2000059373A9 (fr) 2002-02-07

Family

ID=27537800

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/009393 WO2000059373A1 (fr) 1999-04-07 2000-04-07 Dispositif d'analyse permettant de determiner les caracteristiques d'un fluide en continu

Country Status (6)

Country Link
EP (1) EP1164925A1 (fr)
JP (1) JP2002541441A (fr)
AU (1) AU4216900A (fr)
BR (1) BR0009581A (fr)
CA (1) CA2366753A1 (fr)
WO (1) WO2000059373A1 (fr)

Cited By (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003011131A3 (fr) * 2001-07-27 2003-08-21 Dexcom Inc Tete d'analyse permettant de controler le glucose pour dispositifs implantables
US6790179B2 (en) 2001-08-01 2004-09-14 Johnson & Johnson Consumer Companies, Inc. Method of examining and diagnosing skin health
US6840910B2 (en) 2001-08-01 2005-01-11 Johnson & Johnson Consumer Companies, Inc. Method of distributing skin care products
US6855117B2 (en) 2001-08-01 2005-02-15 Johnson & Johnson Consumer Companies, Inc. Method of treating the skin of a subject
WO2008042918A3 (fr) * 2006-10-04 2008-09-04 Dexcom Inc Système d'électrode double pour capteur de substances à analyser en continu
EP2228004A1 (fr) * 2009-03-09 2010-09-15 Achilleas Tsoukalis Biocapteur implantable avec étalonnage automatique
EP2239567A3 (fr) * 2003-12-05 2010-11-17 DexCom, Inc. Techniques d'étalonnage pour capteur d'analytes en continu
US8277713B2 (en) 2004-05-03 2012-10-02 Dexcom, Inc. Implantable analyte sensor
US9042953B2 (en) 1998-04-30 2015-05-26 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9044199B2 (en) 2004-07-13 2015-06-02 Dexcom, Inc. Transcutaneous analyte sensor
US9055901B2 (en) 2004-07-13 2015-06-16 Dexcom, Inc. Transcutaneous analyte sensor
US9066697B2 (en) 1998-04-30 2015-06-30 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
US9078607B2 (en) 2005-11-01 2015-07-14 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9078608B2 (en) 2005-03-10 2015-07-14 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
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
US9610034B2 (en) 2001-01-02 2017-04-04 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9649069B2 (en) 2003-08-22 2017-05-16 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
US9668682B2 (en) 2007-09-13 2017-06-06 Dexcom, Inc. Transcutaneous analyte sensor
US9668677B2 (en) 2004-07-13 2017-06-06 Dexcom, Inc. Analyte sensor
US9693721B2 (en) 2008-03-28 2017-07-04 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US9717449B2 (en) 2007-10-25 2017-08-01 Dexcom, Inc. Systems and methods for processing sensor data
US9741139B2 (en) 2007-06-08 2017-08-22 Dexcom, Inc. Integrated medicament delivery device for use with continuous analyte sensor
US9750441B2 (en) 2003-12-09 2017-09-05 Dexcom, Inc. Signal processing for continuous analyte sensor
US9757061B2 (en) 2006-01-17 2017-09-12 Dexcom, Inc. Low oxygen in vivo analyte sensor
US9775543B2 (en) 2004-07-13 2017-10-03 Dexcom, Inc. Transcutaneous analyte sensor
US9801574B2 (en) 2002-05-22 2017-10-31 Dexcom, Inc. Techniques to improve polyurethane membranes for implantable glucose sensors
US9833143B2 (en) 2004-05-03 2017-12-05 Dexcom, Inc. Transcutaneous analyte sensor
US9839395B2 (en) 2007-12-17 2017-12-12 Dexcom, Inc. Systems and methods for processing sensor data
US9895089B2 (en) 2003-08-01 2018-02-20 Dexcom, Inc. System and methods for processing analyte sensor data
US9937293B2 (en) 2004-02-26 2018-04-10 Dexcom, Inc. Integrated delivery device for continuous glucose sensor
US9962091B2 (en) 2002-12-31 2018-05-08 Abbott Diabetes Care Inc. Continuous glucose monitoring system and methods of use
US9986942B2 (en) 2004-07-13 2018-06-05 Dexcom, Inc. Analyte sensor
US9993186B2 (en) 2003-07-25 2018-06-12 Dexcom, Inc. Oxygen enhancing membrane systems for implantable devices
US10028683B2 (en) 2008-09-19 2018-07-24 Dexcom, Inc. Particle-containing membrane and particulate electrode for analyte sensors
US10039480B2 (en) 2001-07-27 2018-08-07 Dexcom, Inc. Membrane for use with implantable devices
US10052055B2 (en) 2003-08-01 2018-08-21 Dexcom, Inc. Analyte sensor
US10052051B2 (en) 2002-05-22 2018-08-21 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US10136844B2 (en) 2006-10-04 2018-11-27 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US10201301B2 (en) 2005-11-01 2019-02-12 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US10278580B2 (en) 2004-02-26 2019-05-07 Dexcom, Inc. Integrated medicament delivery device for use with continuous analyte sensor
US10300507B2 (en) 2005-05-05 2019-05-28 Dexcom, Inc. Cellulosic-based resistance domain for an analyte sensor
US10349873B2 (en) 2006-10-04 2019-07-16 Dexcom, Inc. Analyte sensor
US10478108B2 (en) 1998-04-30 2019-11-19 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US10537678B2 (en) 2009-03-27 2020-01-21 Dexcom, Inc. Methods and systems for promoting glucose management
US10602968B2 (en) 2008-03-25 2020-03-31 Dexcom, Inc. Analyte sensor
US10653835B2 (en) 2007-10-09 2020-05-19 Dexcom, Inc. Integrated insulin delivery system with continuous glucose sensor
US10667733B2 (en) 2009-09-30 2020-06-02 Dexcom, Inc. Transcutaneous analyte sensor
US10980461B2 (en) 2008-11-07 2021-04-20 Dexcom, Inc. Advanced analyte sensor calibration and error detection
US11000215B1 (en) 2003-12-05 2021-05-11 Dexcom, Inc. Analyte sensor
US11102306B2 (en) 2008-02-21 2021-08-24 Dexcom, Inc. Systems and methods for processing, transmitting and displaying sensor data
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
US11371957B2 (en) 2017-06-30 2022-06-28 Abbott Diabetes Care Inc. Method and apparatus for analyte detection using an electrochemical biosensor
US11382539B2 (en) 2006-10-04 2022-07-12 Dexcom, Inc. Analyte sensor
US11432772B2 (en) 2006-08-02 2022-09-06 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
US11559260B2 (en) 2003-08-22 2023-01-24 Dexcom, Inc. Systems and methods for processing analyte sensor data
US11564602B2 (en) 2003-11-19 2023-01-31 Dexcom, Inc. Integrated receiver for continuous analyte sensor
US11633133B2 (en) 2003-12-05 2023-04-25 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US11730407B2 (en) 2008-03-28 2023-08-22 Dexcom, Inc. Polymer membranes for continuous analyte sensors

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9155496B2 (en) 1997-03-04 2015-10-13 Dexcom, Inc. Low oxygen in vivo analyte sensor
US7192450B2 (en) 2003-05-21 2007-03-20 Dexcom, Inc. Porous membranes for use with implantable devices
US8346337B2 (en) 1998-04-30 2013-01-01 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9282925B2 (en) 2002-02-12 2016-03-15 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
US7134999B2 (en) 2003-04-04 2006-11-14 Dexcom, Inc. Optimized sensor geometry for an implantable glucose sensor
US8275437B2 (en) 2003-08-01 2012-09-25 Dexcom, Inc. Transcutaneous analyte sensor
US6931327B2 (en) 2003-08-01 2005-08-16 Dexcom, Inc. System and methods for processing analyte sensor data
US7774145B2 (en) 2003-08-01 2010-08-10 Dexcom, Inc. Transcutaneous analyte sensor
US9135402B2 (en) 2007-12-17 2015-09-15 Dexcom, Inc. Systems and methods for processing sensor data
US8845536B2 (en) 2003-08-01 2014-09-30 Dexcom, Inc. Transcutaneous analyte sensor
US8886273B2 (en) 2003-08-01 2014-11-11 Dexcom, Inc. Analyte sensor
ES2646312T3 (es) 2003-12-08 2017-12-13 Dexcom, Inc. Sistemas y métodos para mejorar sensores de analito electromecánicos
US7637868B2 (en) 2004-01-12 2009-12-29 Dexcom, Inc. Composite material for implantable device
US8886272B2 (en) 2004-07-13 2014-11-11 Dexcom, Inc. Analyte sensor
JP4846459B2 (ja) * 2006-06-13 2011-12-28 東亜ディーケーケー株式会社 ガス分析ユニット、ガス分析計、及びガス分析方法。
JP2009098027A (ja) * 2007-10-17 2009-05-07 Eiwa Corp マルチ・チャンネルフロー二重電極測定装置
US8268604B2 (en) * 2007-12-20 2012-09-18 Abbott Point Of Care Inc. Compositions for forming immobilized biological layers for sensing
US8682408B2 (en) 2008-03-28 2014-03-25 Dexcom, Inc. Polymer membranes for continuous analyte sensors

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0453283A1 (fr) * 1990-04-19 1991-10-23 Teknekron Sensor Development Corporation Capteur integral interstitiel pour fluide
WO1998030891A1 (fr) * 1997-01-06 1998-07-16 Implanted Biosystems, Inc. Detecteur implantable a electrode auxiliaire

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0453283A1 (fr) * 1990-04-19 1991-10-23 Teknekron Sensor Development Corporation Capteur integral interstitiel pour fluide
WO1998030891A1 (fr) * 1997-01-06 1998-07-16 Implanted Biosystems, Inc. Detecteur implantable a electrode auxiliaire

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HINTSCHE R ET AL: "CHEMICAL MICROSENSOR SYSTEMS FOR MEDICAL APPLICATIONS IN CATHETERS", SENSORS AND ACTUATORS B,CH,ELSEVIER SEQUOIA S.A., LAUSANNE, vol. B27, no. 1/03, PART 02, 1 June 1995 (1995-06-01), pages 471 - 473, XP000516364, ISSN: 0925-4005 *
STEINKUHL R ET AL: "MICRODIALYSIS SYSTEM FOR CONTINUOUS GLUCOSE MONITORING", SENSORS AND ACTUATORS B,CH,ELSEVIER SEQUOIA S.A., LAUSANNE, vol. B33, no. 1/03, 1 July 1996 (1996-07-01), pages 19 - 24, XP000632919, ISSN: 0925-4005 *

Cited By (175)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9931067B2 (en) 1997-03-04 2018-04-03 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
US9339223B2 (en) 1997-03-04 2016-05-17 Dexcom, Inc. Device and method for determining analyte levels
US9066695B2 (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
US10478108B2 (en) 1998-04-30 2019-11-19 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
US9066694B2 (en) 1998-04-30 2015-06-30 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
US10039480B2 (en) 2001-07-27 2018-08-07 Dexcom, Inc. Membrane for use with implantable devices
EP1669022A3 (fr) * 2001-07-27 2006-06-21 DexCom, Inc. Tête d'analyse pour dispositifs implantables
WO2003011131A3 (fr) * 2001-07-27 2003-08-21 Dexcom Inc Tete d'analyse permettant de controler le glucose pour dispositifs implantables
US9804114B2 (en) 2001-07-27 2017-10-31 Dexcom, Inc. Sensor head for use with implantable devices
US6790179B2 (en) 2001-08-01 2004-09-14 Johnson & Johnson Consumer Companies, Inc. Method of examining and diagnosing skin health
US6855117B2 (en) 2001-08-01 2005-02-15 Johnson & Johnson Consumer Companies, Inc. Method of treating the skin of a subject
US6840910B2 (en) 2001-08-01 2005-01-11 Johnson & Johnson Consumer Companies, Inc. Method of distributing skin care products
US10052051B2 (en) 2002-05-22 2018-08-21 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US9801574B2 (en) 2002-05-22 2017-10-31 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
US11020026B2 (en) 2002-05-22 2021-06-01 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US9962091B2 (en) 2002-12-31 2018-05-08 Abbott Diabetes Care Inc. Continuous glucose monitoring system and methods of use
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
US9895089B2 (en) 2003-08-01 2018-02-20 Dexcom, Inc. System and methods for processing analyte sensor data
US10786185B2 (en) 2003-08-01 2020-09-29 Dexcom, Inc. System and methods for processing analyte sensor data
US10052055B2 (en) 2003-08-01 2018-08-21 Dexcom, Inc. Analyte sensor
US11589823B2 (en) 2003-08-22 2023-02-28 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
US9724045B1 (en) 2003-08-22 2017-08-08 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
US9649069B2 (en) 2003-08-22 2017-05-16 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
US11559260B2 (en) 2003-08-22 2023-01-24 Dexcom, Inc. Systems and methods for processing analyte sensor data
US9750460B2 (en) 2003-08-22 2017-09-05 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
US11564602B2 (en) 2003-11-19 2023-01-31 Dexcom, Inc. Integrated receiver for continuous analyte sensor
EP2239567B1 (fr) 2003-12-05 2015-09-02 DexCom, Inc. Techniques d'étalonnage pour capteur d'analytes en continu
EP2239567A3 (fr) * 2003-12-05 2010-11-17 DexCom, Inc. Techniques d'étalonnage pour capteur d'analytes en continu
EP2256493A1 (fr) * 2003-12-05 2010-12-01 DexCom, Inc. Techniques d'étalonnage pour capteur d'analytes en continu
US11000215B1 (en) 2003-12-05 2021-05-11 Dexcom, Inc. Analyte sensor
US10188333B2 (en) 2003-12-05 2019-01-29 Dexcom, Inc. Calibration techniques for a continuous analyte sensor
US11020031B1 (en) 2003-12-05 2021-06-01 Dexcom, Inc. Analyte sensor
US10299712B2 (en) 2003-12-05 2019-05-28 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US11633133B2 (en) 2003-12-05 2023-04-25 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US9750441B2 (en) 2003-12-09 2017-09-05 Dexcom, Inc. Signal processing for continuous analyte sensor
US11638541B2 (en) 2003-12-09 2023-05-02 Dexconi, Inc. Signal processing for continuous analyte sensor
US10278580B2 (en) 2004-02-26 2019-05-07 Dexcom, Inc. Integrated medicament delivery device for use with continuous analyte sensor
US10966609B2 (en) 2004-02-26 2021-04-06 Dexcom, Inc. Integrated medicament delivery device for use with continuous analyte sensor
US12102410B2 (en) 2004-02-26 2024-10-01 Dexcom, Inc Integrated medicament delivery device for use with continuous analyte sensor
US11246990B2 (en) 2004-02-26 2022-02-15 Dexcom, Inc. Integrated delivery device for continuous glucose sensor
US10835672B2 (en) 2004-02-26 2020-11-17 Dexcom, Inc. Integrated insulin delivery system with continuous glucose sensor
US9937293B2 (en) 2004-02-26 2018-04-10 Dexcom, Inc. Integrated delivery device for continuous glucose sensor
US12115357B2 (en) 2004-02-26 2024-10-15 Dexcom, Inc. Integrated delivery device for continuous glucose sensor
US12226617B2 (en) 2004-02-26 2025-02-18 Dexcom, Inc. Integrated delivery device for continuous glucose sensor
US9833143B2 (en) 2004-05-03 2017-12-05 Dexcom, Inc. Transcutaneous analyte sensor
US10327638B2 (en) 2004-05-03 2019-06-25 Dexcom, Inc. Transcutaneous analyte sensor
US8277713B2 (en) 2004-05-03 2012-10-02 Dexcom, Inc. Implantable analyte sensor
US11026605B1 (en) 2004-07-13 2021-06-08 Dexcom, Inc. Analyte sensor
US10709363B2 (en) 2004-07-13 2020-07-14 Dexcom, Inc. Analyte sensor
US11883164B2 (en) 2004-07-13 2024-01-30 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US9044199B2 (en) 2004-07-13 2015-06-02 Dexcom, Inc. Transcutaneous analyte sensor
US9986942B2 (en) 2004-07-13 2018-06-05 Dexcom, Inc. Analyte sensor
US9055901B2 (en) 2004-07-13 2015-06-16 Dexcom, Inc. Transcutaneous analyte sensor
US9060742B2 (en) 2004-07-13 2015-06-23 Dexcom, Inc. Transcutaneous analyte sensor
US9078626B2 (en) 2004-07-13 2015-07-14 Dexcom, Inc. Transcutaneous analyte sensor
US11064917B2 (en) 2004-07-13 2021-07-20 Dexcom, Inc. Analyte sensor
US11045120B2 (en) 2004-07-13 2021-06-29 Dexcom, Inc. Analyte sensor
US9603557B2 (en) 2004-07-13 2017-03-28 Dexcom, Inc. Transcutaneous analyte sensor
US9833176B2 (en) 2004-07-13 2017-12-05 Dexcom, Inc. Transcutaneous analyte sensor
US9610031B2 (en) 2004-07-13 2017-04-04 Dexcom, Inc. Transcutaneous analyte sensor
US10993642B2 (en) 2004-07-13 2021-05-04 Dexcom, Inc. Analyte sensor
US10993641B2 (en) 2004-07-13 2021-05-04 Dexcom, Inc. Analyte sensor
US9814414B2 (en) 2004-07-13 2017-11-14 Dexcom, Inc. Transcutaneous analyte sensor
US9801572B2 (en) 2004-07-13 2017-10-31 Dexcom, Inc. Transcutaneous analyte sensor
US10980452B2 (en) 2004-07-13 2021-04-20 Dexcom, Inc. Analyte sensor
US10314525B2 (en) 2004-07-13 2019-06-11 Dexcom, Inc. Analyte sensor
US9775543B2 (en) 2004-07-13 2017-10-03 Dexcom, Inc. Transcutaneous analyte sensor
US9668677B2 (en) 2004-07-13 2017-06-06 Dexcom, Inc. Analyte sensor
US10932700B2 (en) 2004-07-13 2021-03-02 Dexcom, Inc. Analyte sensor
US10918314B2 (en) 2004-07-13 2021-02-16 Dexcom, Inc. Analyte sensor
US10918315B2 (en) 2004-07-13 2021-02-16 Dexcom, Inc. Analyte sensor
US10524703B2 (en) 2004-07-13 2020-01-07 Dexcom, Inc. Transcutaneous analyte sensor
US10918313B2 (en) 2004-07-13 2021-02-16 Dexcom, Inc. Analyte sensor
US10827956B2 (en) 2004-07-13 2020-11-10 Dexcom, Inc. Analyte sensor
US10813576B2 (en) 2004-07-13 2020-10-27 Dexcom, Inc. Analyte sensor
US10799158B2 (en) 2004-07-13 2020-10-13 Dexcom, Inc. Analyte sensor
US10799159B2 (en) 2004-07-13 2020-10-13 Dexcom, Inc. Analyte sensor
US10722152B2 (en) 2004-07-13 2020-07-28 Dexcom, Inc. Analyte sensor
US10022078B2 (en) 2004-07-13 2018-07-17 Dexcom, Inc. Analyte sensor
US10709362B2 (en) 2004-07-13 2020-07-14 Dexcom, Inc. Analyte sensor
US10610102B2 (en) 2005-03-10 2020-04-07 Dexcom, Inc. Transcutaneous analyte sensor
US10716498B2 (en) 2005-03-10 2020-07-21 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
US10624539B2 (en) 2005-03-10 2020-04-21 Dexcom, Inc. Transcutaneous analyte sensor
US10898114B2 (en) 2005-03-10 2021-01-26 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
US9918668B2 (en) 2005-03-10 2018-03-20 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
US10610136B2 (en) 2005-03-10 2020-04-07 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
US11051726B2 (en) 2005-03-10 2021-07-06 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
US10610137B2 (en) 2005-03-10 2020-04-07 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
US10925524B2 (en) 2005-03-10 2021-02-23 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
US10918316B2 (en) 2005-03-10 2021-02-16 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US9078608B2 (en) 2005-03-10 2015-07-14 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US10918317B2 (en) 2005-03-10 2021-02-16 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
US10813577B2 (en) 2005-06-21 2020-10-27 Dexcom, Inc. Analyte sensor
US10610103B2 (en) 2005-06-21 2020-04-07 Dexcom, Inc. Transcutaneous analyte sensor
US10709332B2 (en) 2005-06-21 2020-07-14 Dexcom, Inc. Transcutaneous analyte sensor
US11272867B2 (en) 2005-11-01 2022-03-15 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
US10231654B2 (en) 2005-11-01 2019-03-19 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
US11911151B1 (en) 2005-11-01 2024-02-27 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
US11363975B2 (en) 2005-11-01 2022-06-21 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
US10201301B2 (en) 2005-11-01 2019-02-12 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9757061B2 (en) 2006-01-17 2017-09-12 Dexcom, Inc. Low oxygen in vivo analyte sensor
US11596332B2 (en) 2006-01-17 2023-03-07 Dexcom, Inc. Low oxygen in vivo analyte sensor
US10265000B2 (en) 2006-01-17 2019-04-23 Dexcom, Inc. Low oxygen in vivo analyte sensor
US11191458B2 (en) 2006-01-17 2021-12-07 Dexcom, Inc. Low oxygen in vivo analyte sensor
US11432772B2 (en) 2006-08-02 2022-09-06 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
US10136844B2 (en) 2006-10-04 2018-11-27 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US11382539B2 (en) 2006-10-04 2022-07-12 Dexcom, Inc. Analyte sensor
US10349873B2 (en) 2006-10-04 2019-07-16 Dexcom, Inc. Analyte sensor
US11399745B2 (en) 2006-10-04 2022-08-02 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
WO2008042918A3 (fr) * 2006-10-04 2008-09-04 Dexcom Inc Système d'électrode double pour capteur de substances à analyser en continu
US10403012B2 (en) 2007-06-08 2019-09-03 Dexcom, Inc. Integrated medicament delivery device for use with continuous analyte sensor
US9741139B2 (en) 2007-06-08 2017-08-22 Dexcom, Inc. Integrated medicament delivery device for use with continuous analyte sensor
US11373347B2 (en) 2007-06-08 2022-06-28 Dexcom, Inc. Integrated medicament delivery device for use with continuous analyte sensor
US9668682B2 (en) 2007-09-13 2017-06-06 Dexcom, Inc. Transcutaneous analyte sensor
US11672422B2 (en) 2007-09-13 2023-06-13 Dexcom, Inc. Transcutaneous analyte sensor
US12016648B2 (en) 2007-09-13 2024-06-25 Dexcom, Inc. Transcutaneous analyte sensor
US11160926B1 (en) 2007-10-09 2021-11-02 Dexcom, Inc. Pre-connected analyte sensors
US11744943B2 (en) 2007-10-09 2023-09-05 Dexcom, Inc. Integrated insulin delivery system with continuous glucose sensor
US10653835B2 (en) 2007-10-09 2020-05-19 Dexcom, Inc. Integrated insulin delivery system with continuous glucose sensor
US12246166B2 (en) 2007-10-09 2025-03-11 Dexcom, Inc. Integrated insulin delivery system with continuous glucose sensor
US9717449B2 (en) 2007-10-25 2017-08-01 Dexcom, Inc. Systems and methods for processing sensor data
US10182751B2 (en) 2007-10-25 2019-01-22 Dexcom, Inc. Systems and methods for processing sensor data
US11272869B2 (en) 2007-10-25 2022-03-15 Dexcom, Inc. Systems and methods for processing sensor data
US9839395B2 (en) 2007-12-17 2017-12-12 Dexcom, Inc. Systems and methods for processing sensor data
US11342058B2 (en) 2007-12-17 2022-05-24 Dexcom, Inc. Systems and methods for processing sensor data
US10827980B2 (en) 2007-12-17 2020-11-10 Dexcom, Inc. Systems and methods for processing sensor data
US9901307B2 (en) 2007-12-17 2018-02-27 Dexcom, Inc. Systems and methods for processing sensor data
US12165757B2 (en) 2007-12-17 2024-12-10 Dexcom, Inc. Systems and methods for processing sensor data
US10506982B2 (en) 2007-12-17 2019-12-17 Dexcom, Inc. Systems and methods for processing sensor data
US11102306B2 (en) 2008-02-21 2021-08-24 Dexcom, Inc. Systems and methods for processing, transmitting and displaying sensor data
US10602968B2 (en) 2008-03-25 2020-03-31 Dexcom, Inc. Analyte sensor
US11896374B2 (en) 2008-03-25 2024-02-13 Dexcom, Inc. Analyte sensor
US11147483B2 (en) 2008-03-28 2021-10-19 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US11730407B2 (en) 2008-03-28 2023-08-22 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US10143410B2 (en) 2008-03-28 2018-12-04 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US9693721B2 (en) 2008-03-28 2017-07-04 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US11918354B2 (en) 2008-09-19 2024-03-05 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
US10561352B2 (en) 2008-09-19 2020-02-18 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
US10980461B2 (en) 2008-11-07 2021-04-20 Dexcom, Inc. Advanced analyte sensor calibration and error detection
US8548552B2 (en) 2009-03-09 2013-10-01 Achilleas Tsoukalis Implantable biosensor with automatic calibration
GR1007310B (el) * 2009-03-09 2011-06-10 Αχιλλεας Τσουκαλης Εμφυτευσιμος βιοαισθητηρας με αυτοματη βαθμονομηση
EP2228004A1 (fr) * 2009-03-09 2010-09-15 Achilleas Tsoukalis Biocapteur implantable avec étalonnage automatique
US10537678B2 (en) 2009-03-27 2020-01-21 Dexcom, Inc. Methods and systems for promoting glucose management
US10610642B2 (en) 2009-03-27 2020-04-07 Dexcom, Inc. Methods and systems for promoting glucose management
US10675405B2 (en) 2009-03-27 2020-06-09 Dexcom, Inc. Methods and systems for simulating glucose response to simulated actions
US10835161B2 (en) 2009-09-30 2020-11-17 Dexcom, Inc. Transcutaneous analyte sensor
US10667733B2 (en) 2009-09-30 2020-06-02 Dexcom, Inc. Transcutaneous analyte sensor
US11937927B2 (en) 2009-09-30 2024-03-26 Dexcom, Inc. Transcutaneous analyte sensor
US11371957B2 (en) 2017-06-30 2022-06-28 Abbott Diabetes Care Inc. Method and apparatus for analyte detection using an electrochemical biosensor
US11382540B2 (en) 2017-10-24 2022-07-12 Dexcom, Inc. Pre-connected analyte sensors
US11943876B2 (en) 2017-10-24 2024-03-26 Dexcom, Inc. Pre-connected analyte sensors
US12150250B2 (en) 2017-10-24 2024-11-19 Dexcom, Inc. Pre-connected analyte sensors
US11706876B2 (en) 2017-10-24 2023-07-18 Dexcom, Inc. Pre-connected analyte sensors
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

Also Published As

Publication number Publication date
AU4216900A (en) 2000-10-23
BR0009581A (pt) 2002-02-05
JP2002541441A (ja) 2002-12-03
CA2366753A1 (fr) 2000-10-12
WO2000059373A9 (fr) 2002-02-07
EP1164925A1 (fr) 2002-01-02

Similar Documents

Publication Publication Date Title
EP1164925A1 (fr) Dispositif d'analyse permettant de determiner les caracteristiques d'un fluide en continu
CA2474912C (fr) Bande biocapteur electrochimique pour analyse d'echantillons liquides
US6033866A (en) Highly sensitive amperometric bi-mediator-based glucose biosensor
JP3947356B2 (ja) 微小球含有センサー
EP1182456B1 (fr) Biodétecteurs avec des membranes chromatographiques poreuses
Mădăraş et al. Microfabricated amperometric creatine and creatinine biosensors
Kurita et al. Microfluidic device integrated with pre-reactor and dual enzyme-modified microelectrodes for monitoring in vivo glucose and lactate
JPH0617889B2 (ja) 生物化学センサ
MXPA01013204A (es) Sensor electroquimico para analisis de muestras de liquido.
Tang et al. Composite liquid membrane for enzyme electrode construction
WO2019176339A1 (fr) Matériau de film protecteur pour sonde de biocapteur
US7648624B2 (en) Oxygen sensor
MXPA01010156A (es) Dispositivo de prueba para medir caracteristicas de un fluido en una base continua
Eggenstein et al. Potentiometric biosensor in double matrix membrane technology
Yamada et al. Wristwatch Biosensor for Sweat Lactic Acid Monitoring
JPH0345336B2 (fr)
JP3902156B2 (ja) オンラインカテコールアミンセンシングデバイス
JP2006126092A (ja) 薄層流路および透析膜を有する微小バイオセンサ
JPH0676984B2 (ja) バイオセンサ
JP4517498B2 (ja) バイオセンサ
JPH045943B2 (fr)
JPH0640089B2 (ja) バイオセンサ
JPS612059A (ja) 生理活性物質固定電極
JP2001208720A (ja) 酸素センサ
JPH01134243A (ja) バイオセンサ

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
ENP Entry into the national phase

Ref document number: 2366753

Country of ref document: CA

Ref country code: CA

Ref document number: 2366753

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: PA/a/2001/010156

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 2000921911

Country of ref document: EP

ENP Entry into the national phase

Ref country code: JP

Ref document number: 2000 608941

Kind code of ref document: A

Format of ref document f/p: F

WWP Wipo information: published in national office

Ref document number: 2000921911

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 09937863

Country of ref document: US

AK Designated states

Kind code of ref document: C2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: C2

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

COP Corrected version of pamphlet

Free format text: PAGES 1/4-4/4, DRAWINGS, REPLACED BY NEW PAGES 1/4-4/4; DUE TO LATE TRANSMITTAL BY THE RECEIVING OFFICE

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWW Wipo information: withdrawn in national office

Ref document number: 2000921911

Country of ref document: EP

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载