WO2005045413A1 - A method of reducing interferences in an electrochemical sensor using two different applied potentials - Google Patents

A method of reducing interferences in an electrochemical sensor using two different applied potentials Download PDF

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Publication number
WO2005045413A1
WO2005045413A1 PCT/GB2004/004588 GB2004004588W WO2005045413A1 WO 2005045413 A1 WO2005045413 A1 WO 2005045413A1 GB 2004004588 W GB2004004588 W GB 2004004588W WO 2005045413 A1 WO2005045413 A1 WO 2005045413A1
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Prior art keywords
current
working electrode
potential
glucose
analyte
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PCT/GB2004/004588
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French (fr)
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Oliver William Hardwicke Davies
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Lifescan Scotland Limited
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Priority to DE602004021835T priority Critical patent/DE602004021835D1/en
Priority to JP2006537429A priority patent/JP4694498B2/en
Priority to AU2004288008A priority patent/AU2004288008B2/en
Priority to AT04791625T priority patent/ATE435419T1/en
Priority to CA2543797A priority patent/CA2543797C/en
Priority to EP04791625A priority patent/EP1678490B1/en
Application filed by Lifescan Scotland Limited filed Critical Lifescan Scotland Limited
Priority to DK04791625T priority patent/DK1678490T3/en
Priority to PL04791625T priority patent/PL1678490T3/en
Priority to KR1020067010291A priority patent/KR101201245B1/en
Publication of WO2005045413A1 publication Critical patent/WO2005045413A1/en
Priority to IL175321A priority patent/IL175321A0/en
Priority to HK06112291.5A priority patent/HK1091898A1/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING 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
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001—Enzyme electrodes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/49—Systems involving the determination of the current at a single specific value, or small range of values, of applied voltage for producing selective measurement of one or more particular ionic species
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1486—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using enzyme electrodes, e.g. with immobilised oxidase
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150007—Details
    • A61B5/150015—Source of blood
    • A61B5/150022—Source of blood for capillary blood or interstitial fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150007—Details
    • A61B5/150206—Construction or design features not otherwise provided for; manufacturing or production; packages; sterilisation of piercing element, piercing device or sampling device
    • A61B5/150274—Manufacture or production processes or steps for blood sampling devices
    • A61B5/150282—Manufacture or production processes or steps for blood sampling devices for piercing elements, e.g. blade, lancet, canula, needle
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150007—Details
    • A61B5/150358—Strips for collecting blood, e.g. absorbent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150007—Details
    • A61B5/150374—Details of piercing elements or protective means for preventing accidental injuries by such piercing elements
    • A61B5/150381—Design of piercing elements
    • A61B5/150412—Pointed piercing elements, e.g. needles, lancets for piercing the skin
    • A61B5/150435—Specific design of proximal end
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150007—Details
    • A61B5/150374—Details of piercing elements or protective means for preventing accidental injuries by such piercing elements
    • A61B5/150381—Design of piercing elements
    • A61B5/150503—Single-ended needles
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING 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
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001—Enzyme electrodes
    • C12Q1/005—Enzyme electrodes involving specific analytes or enzymes
    • C12Q1/006—Enzyme electrodes involving specific analytes or enzymes for glucose
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28—Electrolytic cell components
    • G01N27/30—Electrodes, e.g. test electrodes; Half-cells
    • G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
    • G01N27/3271—Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood
    • G01N27/3274—Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A90/00—Technologies having an indirect contribution to adaptation to climate change
    • Y02A90/10—Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Definitions

  • Electrochemical glucose test strips such as those used in the OneTouch ® Ultra ® whole blood testing kit, which is available from LifeScan, Inc., are designed to measure the concentration of glucose in a blood sample from patients with diabetes.
  • the measurement of glucose is based upon the specific oxidation of glucose by the flavo-enzyme glucose oxidase. During this reaction, the enzyme becomes reduced. The enzyme is re-oxidised by reaction with the mediator ferricyanide, which is itself reduced during the course or the reaction.
  • a redox mediator such as ferricyanide is a compound that exchanges electrons between a redox enzyme such as glucose oxidase and an electrode.
  • glucose current As the concentration of glucose in the sample increases, the amount of reduced mediator formed also increases, hence, there is a direct relationship between current resulting from the re-oxidation of reduced mediator and glucose concentration.
  • the transfer of " electrons across the electrical interface results in a flow of current (2 moles of electrons for every mole of glucose that is oxidized).
  • the current resulting from the introduction of glucose may, therefore, be referred to as the glucose current.
  • meters Because it can be very important to know the concentration of glucose in blood, particularly in people with Diabetes, meters have been developed using the principals set forth above to enable the average person to sample and test their blood to determine the glucose concentration at any given time.
  • the Glucose Current generated is monitored by the meter and converted into a reading of glucose concentration using a preset algorithm that relates current to glucose concentration via a simple mathematical formula.
  • the meters work in conjunction with a disposable strip that includes a sample chamber and at least two electrodes disposed within the sample chamber in addition to the enzyme (e.g. glucose oxidase) and mediator (e.g. ferricyanide).
  • the user pricks their finger or other convenient site to induce bleeding and introduces a blood sample to the sample chamber, thus starting the chemical reaction set forth above.
  • the function of the meter is two fold. Firstly, it provides a polarizing voltage (approximately 0.4 V in the case of OneTouch ® Ultra that polarizes the electrical interface and allows current flow at the carbon working electrode surface. Secondly, it measures the current that flows in the external circuit between the anode (working electrode) and the cathode (reference electrode).
  • the meter may, therefore be considered to be a simple electrochemical system that operates in two-electrode mode although, in practice, third and, even fourth electrodes may be used to facilitate the measurement of glucose and/or perform other functions in the meter.
  • the equation set forth above is considered to be a sufficient approximation of the chemical reaction taking place on the test strip and the meter reading a sufficiently accurate representation of the glucose content of the blood sample.
  • it maybe advantageous to improve the accuracy of the measurement For example, where a portion of the current measured at the electrode results from the presence of other chemicals or compounds in the sample. Where such additional chemicals or compounds are present, they may be referred to as interfering compounds and the resulting additional current may be referred to as Interfering Currents
  • Examples of potentially interfering chemicals include ascorbate, urate and acetaminophen (TylenolTM or Paracetamol).
  • One mechanism for generating Interfering Currents in an electrochemical meter for measuring the concentration of an analyte in a physiological fluid involves the oxidation of one or more interfering compounds by reduction of the enzyme (e.g. glucose oxidase).
  • a further mechanism for generating Interfering Currents in such a meter involves the oxidation of one or more interfering compounds by reduction of the mediator (e.g. ferricyanide).
  • a further mechanism for generating Interfering Currents in such a meter involves the oxidation of one or more interfering compounds at the working electrode.
  • the total current measured at the working electrode is the superposition of the current generated by oxidation of the analyte and the current generated by oxidation of interfering compounds.
  • Oxidation of interfering compounds may be a result of interaction with the enzyme, the mediator or may occur directly at the working electrode.
  • potentially interfering compounds can be oxidized at the electrode surface and/or by a redox mediator.
  • This oxidation of the interfering compound in a glucose measurement system causes the measured oxidation current to be dependent on both the glucose and the interfering compound. Therefore, if the concentration of interfering compound oxidizes as efficiently as glucose and/or the interfering compound concentration is significantly high relative to the glucose concentration, it may impact the measured glucose concentration.
  • analyte e.g. glucose
  • interfering compounds is especially problematic when the standard potential (i.e.
  • the potential at which a compound is oxidized) of the interfering compound is similar in magnitude to the standard potential of the redox mediator , resulting in a significant portion of the interference Current being generated by oxidation of the interfering compounds at the working electrode.
  • Electrical current resulting from the oxidation of interfering compounds at the working electrode may be referred to as direct interference current. It would, therefore, be advantageous to reduce or minimize the effect of the direct interference current on the measurement of analyte concentration.
  • Previous methods of reducing or eliminating direct interference current include designing test strips that prevent the interfering compounds from reaching the working electrode, thus reducing or eliminating the direct interference current attributable to the excluded compounds.
  • One strategy for reducing the effects of interfering compounds that generate Direct interference current is to place a negatively charged membrane on top of the working electrode.
  • a sulfonated fluoropolymer such as NAFIONTM may be placed over the working electrode to repel all negatively charged chemicals.
  • many interfering compounds including ascorbate and urate, have a negative charge, and thus, are excluded from being oxidized at the working electrode when the surface of the working electrode is covered by a negatively charged membrane.
  • some interfering compounds, such as acetaminophen are not negatively charged, and thus, can pass through the negatively charged membrane, the use of a negatively charged membrane will not eliminate the Direct interference current.
  • Another disadvantage of covering the working electrode with a negatively charged membrane is that commonly used redox mediators, such as ferricyanide, are negatively charged and cannot pass through the membrane to exchange electrons with the electrode.
  • a further disadvantage of using a negatively charged membrane over the working electrode is the potential to slow the diffusion of the reduced mediator to the working electrode, thus increasing the test time.
  • a further disadvantage of using a negatively charged membrane over the working electrode is the increased complexity and expense of manufacturing the test strips with a negatively charged membrane.
  • Another strategy that can be used to decrease the effects of Direct Interfering Currents is to position a size selective membrane on top of the working electrode.
  • a 100 Dalton size exclusion membrane such as cellulose acetate maybe placed over the working electrode to exclude compounds having a molecular weight greater than 100 Daltons.
  • the redox enzyme such as glucose oxidase is positioned over the size exclusion membrane.
  • Glucose oxidase generates hydrogen peroxide, in the presence of glucose and oxygen, in an amount proportional to the glucose concentration. It should be noted that glucose and most redox mediators have a molecular weight greater than 100 Daltons, and thus, cannot pass through the size selective membrane.
  • Hydrogen peroxide however, has a molecular weight of 34 Daltons, and thus, can pass through the size selective membrane.
  • most interfering compounds have a molecular weight greater than 100 Daltons, and thus, are excluded from being oxidized at the electrode surface. Since some interfering compounds have smaller molecular weights, and thus, can pass through the size selective membrane, the use of a size selective membrane will not eliminate the Direct interference current.
  • a further disadvantage of using a size selective membrane over the working electrode is the increased complexity and expense of manufacturing the test strips with a size selective membrane.
  • a redox mediator with a low redox potential for example, a redox potential of between about - 300mV to + 100 mV (vs a saturated calomel electrode).
  • a redox potential for example, a redox potential of between about - 300mV to + 100 mV (vs a saturated calomel electrode).
  • redox mediators having a relatively low redox potential include osmium bipyridyl complexes, ferrocene derivatives, and quinone derivatives.
  • redox mediators having a relatively low potential are often difficult to synthesize, relatively unstable and relatively insoluble.
  • Another strategy that can be used to decrease the effects of interfering compounds is to use a dummy electrode in conjunction with the working electrode.
  • the current measured at the dummy electrode may then be subtracted from the current measured at the working electrode in order to compensate for the effect of the interfering compounds. If the dummy electrode is bare (i.e. not covered by an enzyme or mediator), then the current measured at the dummy electrode will be proportional to the Direct interference current and subtracting the current measured at the dummy electrode from the current measured at the working electrode will reduce or eliminate the effect of the direct oxidation of interfering compounds at the working electrode.
  • the current measured at the dummy electrode will be a combination of Direct interference current and interference current resulting from reduction of the redox mediator by an interfering compound.
  • subtracting the current measured at the dummy electrode coated with a redox mediator from the current measured at the working electrode will reduce or eliminate the effect of the direct oxidation of interfering compounds and the effect of interference resulting from reduction of the redox mediator by an interfering compound at the working electrode.
  • the dummy electrode may also be coated with an inert protein or deactivated redox enzyme in order to simulate the effect of the redox mediator and enzyme on diffusion.
  • test strips have a small sample chamber so that people with diabetes do not have to express a large blood sample, it may not be advantageous to include an extra electrode which incrementally increases the sample chamber volume where the extra electrode is not used to measure the analyte (e.g. glucose). Further, it may be difficult to directly correlate the current measured at the dummy electrode to interference currents at the working electrode.
  • the dummy electrode may be coated with a material or materials (e.g. redox mediator) which differ from the materials used to cover the working electrode (e.g. redox mediator and enzyme), test strips which use dummy electrodes as a method of reducing or eliminating the effect of interfering compounds in a multiple working electrode system may increase the cost and complexity of manufacturing the test strip.
  • test strip designs which utilize multiple working electrodes to measure analyte, such as the system used in the OneTouch ® Ultra ® glucose measurement system are advantageous because the use of two working electrodes. In such systems, it would, therefore, be advantageous to develop a method of reducing or eliminating the effect of interfering compounds. More particularly, it would be advantageous to develop a method of reducing or eliminating the effect of interfering compounds without utilizing a dummy electrode, an intermediate membrane or a redox mediator with a low redox potential.
  • the present invention is directed to a method of reducing the effects of interfering compounds in the measurement of analytes and more particularly to a method of reducing the effects of interfering compounds in a system wherein the test strip utilizes two or more working electrodes.
  • a first potential is applied to a first working electrode and a second potential, having the same polarity but a greater magnitude than the first potential, is applied to a second working electrode.
  • the magnitude of the second potential may also be less than the first potential for an embodiment where a reduction current is used to measure the analyte concentration.
  • the first working electrode and second working electrode may be covered with an enzyme reagent and redox mediator that are analyte specific.
  • the first potential applied to the first working electrode is selected such that it is sufficient to oxidize reduced redox mediator in a diffusion limited manner while the second potential is selected to have a magnitude (i.e. absolute value) greater than the magnitude of the first potential, resulting in a more efficient oxidation of at the second working electrode.
  • the current measured at the first working electrode includes an analyte current and interfering compound current while the current measured at the second working electrode includes an analyte overpotential current and an interfering compound overpotential current.
  • analyte current and the analyte overpotential current both refer to a current that corresponds to the analyte concentration and that the current is a result of a reduced mediator oxidation.
  • the relationship between the currents at the first working electrode and second working electrode may be defined by the following equation,
  • A is the analyte current at the first working electrode
  • Wj is the current measured at the first working electrode
  • W 2 is the current measured at the second working electrode
  • X is an analyte dependent voltage effect factor
  • 7 is an interfering compound dependent voltage effect factor.
  • the concentration of glucose in a sample placed on a test strip can be calculated by placing the sample on a test strip having a first working electrode and second working electrode and a reference electrode, at least the first working electrode and second working electrodes being coated with chemical compounds (e.g. an enzyme and a redox mediator) adapted to facilitate the oxidation of glucose and the transfer of electrons from the oxidized glucose to the first working electrode and the second working electrode when a potential is applied between the first working electrode and the reference electrode, and the second working electrode and the reference electrode.
  • chemical compounds e.g. an enzyme and a redox mediator
  • a first potential is applied between the first working electrode and the reference electrode, the first potential being selected to have a magnitude sufficient to ensure that the magnitude of the current generated by oxidation of the glucose in the sample is limited only by factors other than applied voltage (e.g. diffusion).
  • a second potential is applied between the second working electrode and the reference electrode, the second potential being greater in magnitude than the first potential and, in one embodiment of the present invention, the second potential being selected to increase the oxidation of interfering compounds at the second working electrode.
  • the following equation may be used to reduce the effect of oxidation current resulting from the presence of interfering compounds on the current used to calculate the concentration of glucose in the sample.
  • the glucose concentration may be derived using a calculated current A G where:
  • a JG is a glucose current
  • Wj is the current measured at the first working electrode
  • W 2 is the current measured at the second working electrode
  • X ⁇ is a glucose dependent voltage effect factor
  • Y is an interfering compound dependent voltage effect factor
  • Figure 1 is an exploded perspective view of a test strip embodiment for use in the present invention.
  • Figure 2 is a schematic view of a meter and strip for use in the present invention.
  • Figure 3 is a hydrodynamic voltammogram illustrating the dependence of applied voltage with measured current.
  • the present invention is particularly adapted to the measurement of glucose concentration in blood, it will be apparent to those of skill in the art that the method described herein may be adapted to improve the selectivity of other systems used for the electrochemical measurement of analytes in physiological fluids.
  • systems that may be adapted to improve selectivity using the method according to the present invention include electrochemical sensors used to measure the concentration of lactate, lactate, alcohol, cholesterol, amino acids, choline, and fructosamine in physiological fluids.
  • physiological fluids that may contain such analytes include blood, plasma, serum, urine, and interstitial fluid.
  • the present invention is directed to a method for improving the selectivity of an electrochemical measuring system that is particularly adapted for use in a blood glucose measurement system. More particularly, the present invention is directed to a method for improving the selectivity of a blood glucose measurement system by partially or wholly correcting for the effect of the direct interference current. Selectivity in such systems being a measure of the ability of the system to accurately measure the glucose concentration in a sample of physiological fluid which includes one or more compounds which create an interfering current.
  • the measured current may be a function of the oxidation of interfering compounds commonly found in physiological fluids such as, for example, acetaminophen (TylenolTM or Paracetamol), ascorbic acid, bilirubin, dopamine, gentisic acid, glutathione, levodopa, methyldopa, tolazimide, tolbutamide and uric acid.
  • interfering compounds may be oxidized by, for example, reacting chemically with the redox mediator or by oxidizing at the elecfrode surface.
  • the present invention describes a method of removing some or all of the effect of interfering compounds by quantifying the proportion of the overall oxidation current generated by the interfering compounds and subtracting that quantity from the overall oxidation current.
  • a test strip that includes first working electrode and second working electrode, two different potentials are applied and the oxidation current generated at each of the working electrodes is measure used to estimate the respective oxidation current proportions for both the glucose and interfering compounds.
  • a test strip which includes a sample chamber containing a first working electrode, a second working electrode, and a reference electrode.
  • the first working electrode, the second working electrode and the reference elecfrodes are covered by glucose oxidase (the enzyme) and a Ferricyanide (the redox mediator).
  • glucose oxidase the enzyme
  • Ferricyanide the redox mediator
  • test strip An example of a test strip that may be suitable for use in a method according to the present invention is the OneTouch ® Ultra ® test strip sold by LifeScan, Inc. of Milpitas, California. Other suitable strips are described in international publication WO 01/67099A1 and WO 01/73124A2.
  • a first potential is applied to a first working electrode and a second potential is applied to the second working electrode.
  • the first potential is selected to be in a range in which the glucose current response is relatively insensitive to the applied potential and thus the magnitude of the glucose current at the first working electrode is limited by the amount of reduced redox mediator diffusing to the first working electrode.
  • glucose is not directly oxidized at a working electrode, but instead is indirectly oxidized through using a redox enzyme and a redox mediator.
  • the glucose current refers to an oxidation of reduced redox mediator that correlates to the gluocose concentration.
  • the first potential may range from about 0 millivolts to about 500 millivolts, and more preferably from about 385 millivolts to about 415 millivolts, and yet even more preferably may range from about 395 to 405 mV.
  • a second potential is applied to a second working electrode such that the second potential is greater than the first potential. Where the applied potential is greater than the potential needed to oxidize the glucose.
  • the second potential may range from about 50 millivolts to about 1000 millivolts, and more preferably from about 420 millivolts to about 1000 millivolts.
  • the glucose current at the second working electrode should be substantially equal to the glucose current at the first working electrode, even though the potential at the second working electrode is greater than the potential at the first electrode.
  • any additional current measured at the second working electrode may be attributed to the oxidation of interfering compounds.
  • the higher potential at the second working electrode should cause a glucose overpotenital current to be measured at the second working electrode which is equal or substantially equal in magnitude to the glucose current at the first working electrode because the first potential and second potential are in a limiting glucose current range which is insensitive to changes in applied potential.
  • IR drop i.e. uncompensated resistance
  • a higher applied potential causes an increase in the measured current magnitude.
  • IR drops may be the nominal resistance of the first working electrode, second working electrode, the reference electrode, the physiological fluid between the working electrode and the reference electrode.
  • the application of a higher potential results in the formation of a larger ionic double layer which forms at the electrode/liquid interface, increasing the ionic capacitance and the resulting current at either the firstworking electrode or second working electrode.
  • glucose current at the second working electrode may also be referred to as a glucose overpotential current.
  • the voltage effect factor XQ for glucose may be expected to be between about 0.95 any about 1.1.
  • higher potentials do not have a significant impact on the glucose oxidation current because the redox mediator (ferrocyanide) has fast electron transfer kinetics and reversible electron transfer characteristics with the working electrode. Because the glucose current does not increase with increasing potential after a certain point, the glucose current may be said to be saturated or in a diffusion limited regime.
  • glucose is indirectly measured by oxidizing ferrocyanide at the working electrode and where the ferrocyanide concentration is directly proportional to the glucose concentration.
  • the standard potential (E°) value for a particular electrochemical compound is a measure of that compound's ability to exchange electrons with other chemical compounds.
  • the potential at the first working electrode is selected to be greater than the standard potential (E°) of the redox mediator. Because the first potential is selected such that it is sufficiently greater than the E° value of the redox couple, the oxidation rate does not increase substantially as the applied potential increases. Thus, applying a greater potential at the second working electrode will not increase the oxidation at the second working electrode and any increased current measured at the higher potential electrode must be due to other factors, such as, for example, oxidation of interfering compounds.
  • Figure 3 is a hydrodynamic voltammogram illustrating the dependence of applied voltage with measured current where ferri/ferrocyanide is the redox mediator and carbon is the working electrode. Each data point on the graph represents at least one experiment where a current is measured 5 seconds after applying a voltage across a working electrode and a reference electrode. Figure 3 shows that the current forms an onset of a plateau region at about 400 mV because the applied voltage is sufficiently greater than of the E° value of ferrocyanide. Thus, as illustrated in Figure 3, as the potential reaches approximately 400 mV, the glucose current becomes saturated because the oxidation of ferrocyanide is diffusion limited (i.e. the diffusion of ferrocyanide to the working electrode limits the magnitude of the measured current and is not limited by the electron transfer rate between ferrocyanide and the electrode).
  • an outer sphere electron transfer does not require a chemical reaction before transferring an electron. Therefore, inner sphere electron transfer rates are typically slower than outer sphere electron transfers because they require an additional chemical reaction step.
  • the oxidation of ascorbate to dehydroascorbate is an example of an inner sphere oxidation that requires the liberation of two hydride moieties.
  • the oxidation of ferrocyanide to ferricyanide is an example of an outer sphere electron transfer. Therefore, the current generated by interfering compounds generally increases when testing at a higher potential.
  • Y is an interfering compound dependent voltage effect factor
  • I 2 is the interfering compound overpotential current.
  • the interfering compound voltage effect factor Y is dependent upon a number of factors, including, the particular interfering compound or compounds of concern and the material used for the working electrodes, calculation of a particular interfering compound dependent voltage effect factor for a particular system, test strip, analyte and interfering compound or compounds may require experimentation to optimize the voltage effect factor for those criteria. Alternatively, under certain circumstances, appropriate voltage effect factors may be derived or described mathematically.
  • the interfering compound dependent voltage effect factor 7 could be mathematically described using the Tafel equation for/; and h, / ⁇ 'expj (eq 2 a)
  • Equation 2 (the standard potential of a specific interfering compound) is not important because it is canceled out in the calculation of A ⁇ . Equations 2, 2a, 2b can be combined and rearranged to yield the following equation,
  • Equation 2c provides a mathematical relationship describing the relationship between A ⁇ (i.e. the difference between the first potential and the second potential) and the interfering compound dependent voltage effect factor 7.
  • 7 may range from about 1 to about 100, and more preferably between about 1 and 10.
  • the interfering compound dependent voltage effect factor 7 may be determined experimentally for a specific interfering compound or combination of interfering compounds. It should be noted that the interfering compound dependent voltage effect factor 7 for interfering compounds is usually greater than voltage effect factor X G for glucose.
  • W I A JG + I J (eq 3)
  • Wj is the first current at the first working electrode.
  • the first current includes a superposition of the glucose current A JG and the interfering compound current I .
  • the interfering compound current may be a direct interfering current which has been described hereinabove.
  • W 2 A 2G + (eq 4)
  • the interfering compound overpotential current may be a Direct Interfering compound Current which has been described hereinabove.
  • eq's 1 to 4 which contain 4 unknowns (A JG , A 2 , h, and I 2 )
  • a 2G from eq 1 and I 2 from eq 2 can be substituted into eq 4 to give the following eq 5.
  • eq 3 is multiplied by interfering compound dependent voltage effect factor 7 for interfering compounds to give eq 6.
  • Eq 7 can now be rearranged to solve for the corrected glucose current A JG measured at the first potential as shown in eq 8.
  • X G -Y Eq 8 outputs a corrected glucose current A G which removes the effects of interferences requiring only the current output of the first working electrode and second working electrode (eg Wj and W 2 ), glucose dependent voltage effect factors XQ , and interfering compound dependent voltage effect factor 7 for interfering compounds.
  • a glucose meter containing electronics is electrically interfaced with a glucose test strip to measure the current from Wj and W 2 .
  • XQ and 7 may be programmed into the glucose meter as read only memory.
  • ⁇ and 7 may be transferred to the meter via a calibration code chip.
  • the calibration code chip would have in its memory a particular set of values ⁇ O ⁇ X G and 7 which would be calibrated for a particular lot of test strips. This would account for test strip lot-to-lot variations that may occur in XQ and 7.
  • the corrected glucose current in eq 8 may be used by the meter only when a certain threshold is exceeded. For example, if W 2 is about 10% or greater than Wi, then the meter would use eq 8 to correct for the current output. However, if W 2 is about 10% or less than Wj, the interfering compound concentration is low and thus the meter can simply take an average current value between Wj and W to improve the accuracy and precision of the measurement.
  • a more accurate W approach may be to average Wj with — — where the glucose dependent voltage effect X G W factor X G is taken into account (note — — approximately equals AJ G according to eq 1 and 4 when I 2 is low).
  • the strategy of using eq 8 only under certain situations where it is likely that a significant level of interferences are in the sample mitigates the risk of overcorrecting the measured glucose current. It should be noted that when W 2 is sufficiently greater than Wj by a large amount (e.g. about 100% or more), this is an indicator of having an unusually high concentration of interferences. In such a case, it may be desirable to output an error message instead of a glucose value because a very high level of interfering compounds may cause a breakdown in the accuracy of eq 8.
  • Test strip 600 is an exploded perspective view of test strip 600, which includes six layers disposed upon a base substrate 5. These six layers are a conductive layer 50, an insulation layer 16, a reagent layer 22, an adhesive layer 60, a hydrophilic layer 70, and a top layer 80.
  • Test strip 600 may be manufactured in a series of steps wherein the conductive layer 50, insulation layer 16, reagent layer 22, adhesive layer 60 are deposited on base substrate 5 using, for example, a screen printing process.
  • Hydrophilic layer 70 and top layer 80 may be deposed from a roll stock and laminated onto base substrate 5.
  • the fully assembled test strip forms a sample receiving chamber that can accept a blood sample so that it can be analyzed.
  • Conductive layer 50 includes reference electrode 10, first working electrode 12, second working electrode 14, a first contact 13, a second contact 15, a reference contact 11 , and a strip detection bar 17.
  • Suitable materials which may be used for the conductive layer are Au, Pd, Ir, Pt, Rh, stainless steel, doped tin oxide, carbon, and the like.
  • the material for the conductive layer may be a carbon ink such as those described in US5653918.
  • Insulation layer 16 includes cutout 18 which exposes a portion of reference electrode 10, first working electrode 12, and second working electrode 14 which can be wetted by a liquid sample.
  • insulation layer (16 or 160) may be Ercon E6110-116 Jet Black Insulayer Ink which may be purchased from Ercon, Inc.
  • Reagent layer 22 may be disposed on a portion of conductive layer 50 and insulation layer 16.
  • reagent layer 22 may include chemicals such as a redox enzyme and redox mediator which selectivity react with glucose. During this reaction, a proportional amount of a reduced redox mediator can be generated that then can be measured electrochemically so that a glucose concentration can be calculated.
  • Examples of reagent formulations or inks suitable for use in the present invention can be found in US patents 5,708,247 and 6,046,051; published international applications WOOl/67099 and WOOl/73124, all of which are incorporated by reference herein.
  • Adhesive layer 60 includes first adhesive pad 24, second adhesive pad 26, and third adhesive pad 28.
  • the side edges of first adhesive pad 24 and second adhesive pad 26 located adjacent to reagent layer 22 each define a wall of a sample receiving chamber.
  • the adhesive layer may comprise a water based acrylic copolymer pressure sensitive adhesive which is commercially available from Tape Specialties LTD in Tring, Herts, United Kingdom (part#A6435).
  • Hydrophilic layer 70 includes a distal hydrophilic pad 32 and proximal hydrophilic pad 34.
  • hydrophilic layer 70 be a polyester having one hydrophilic surface such as an anti-fog coating which is commercially available from 3M. It should be noted that both distal hydrophilic film 32 and proximal hydrophilic film 34 are visibly transparent enabling a user to observe a liquid sample filling the sample receiving chamber.
  • Top layer 80 includes a clear portion 36 and opaque portion 38. Top layer 80 is disposed on and adhered to hydrophilic layer 70. As a non-limiting example, top layer 40 may be a polyester. It should be noted that the clear portion 36 substantially overlaps proximal hydrophilic pad 32 which allows a user to visually confirm that the sample receiving chamber is sufficiently filled. Opaque portion 38 helps the user observe a high degree of contrast between a colored fluid such as, for example, blood within the sample receiving chamber and the opaque section of the top film.
  • a colored fluid such as, for example, blood within the sample receiving chamber and the opaque section of the top film.
  • FIG. 2 is a simplified schematic showing a meter 500 interfacing with a test strip 600.
  • Meter 500 has three electrical contacts that form an electrical connection to first working electrode 12, second working electrode 14, and reference electrode 10.
  • connector 101 connects voltage source 103 to first working electrode 12
  • connector 102 connects voltage source 104 to second working electrode 14
  • common connector 100 connects voltage source 103 and 104 to reference elecfrode 10.
  • voltage source 103 in meter 500 applies a first potential E ⁇ between first working electrode 12 and reference electrode 10
  • voltage source 104 applies a second potential E 2 between second working electrode 14 and reference electrode 10.
  • a sample of blood is applied such that first working electrode 12, second working electrode 14, and reference electrode 10 are covered with blood.
  • reagent layer 22 This causes reagent layer 22 to become hydrated which generates ferrocyanide in an amount proportional to the glucose and/or interfering compound concentration present in the sample.
  • meter 500 measures an oxidation current for both first working electrode 12 and second working electrode 14.
  • the first working electrode 12 and second working electrode 14 had the same area. It should be noted that the present invention is not limited to test strips having equal areas. For alternative embodiments to the previously described strips where the areas are different, the current output for each working electrode must be normalized for area. Because the current output is directly proportional to area, the terms within Equation 1 to Equation 8 may be in units of amperes (current) or in amperes per unit area (i.e. current density).

Abstract

The present invention is directed to a method of reducing the effects of interfering compounds in the measurement of analytes and more particularly to a method of reducing the effects of interfering compounds in a system wherein the test strip (600) utilizes two or more working electrodes (12, 14). In the present invention, a first potential (E1) is applied to a first working electrode (12) and a second potential (E2), having the same polarity but a greater magnitude than the first potential (E1), is applied to a second working electrode (14).

Description

A METHOD OF REDUCING INTERFERENCES IN AN ELECTROCHEMICAL SENSOR USING TWO DIFFERENT APPLBED POTENTIALS
BACKGROUND OF INVENTION
[0001] Electrochemical glucose test strips, such as those used in the OneTouch® Ultra® whole blood testing kit, which is available from LifeScan, Inc., are designed to measure the concentration of glucose in a blood sample from patients with diabetes. The measurement of glucose is based upon the specific oxidation of glucose by the flavo-enzyme glucose oxidase. During this reaction, the enzyme becomes reduced. The enzyme is re-oxidised by reaction with the mediator ferricyanide, which is itself reduced during the course or the reaction. These reactions are summarized below.
D-Glucose + GOx{OX) - Gluconic acid + GOx(RED)
GOX(RED) + 2 Fe(CN)6 3 ^ GOx(OX) + 2 Fe(CN)6« -
[0002] When the reaction set forth above is conducted with an applied potential between two electrodes, an electrical current may be created by the electrochemical re-oxidation of the reduced mediator ion (ferrocyanide) at the electrode surface. Thus, since, in an ideal environment, the amount of ferrocyanide created during the chemical reaction described above is directly proportional to the amount of glucose in the sample positioned between the electrodes, the current generated would be proportional to the glucose content of the sample. A redox mediator, such as ferricyanide is a compound that exchanges electrons between a redox enzyme such as glucose oxidase and an electrode. As the concentration of glucose in the sample increases, the amount of reduced mediator formed also increases, hence, there is a direct relationship between current resulting from the re-oxidation of reduced mediator and glucose concentration. In particular, the transfer of" electrons across the electrical interface results in a flow of current (2 moles of electrons for every mole of glucose that is oxidized). The current resulting from the introduction of glucose may, therefore, be referred to as the glucose current.
[0003] Because it can be very important to know the concentration of glucose in blood, particularly in people with Diabetes, meters have been developed using the principals set forth above to enable the average person to sample and test their blood to determine the glucose concentration at any given time. The Glucose Current generated is monitored by the meter and converted into a reading of glucose concentration using a preset algorithm that relates current to glucose concentration via a simple mathematical formula. In general, the meters work in conjunction with a disposable strip that includes a sample chamber and at least two electrodes disposed within the sample chamber in addition to the enzyme (e.g. glucose oxidase) and mediator (e.g. ferricyanide). In use, the user pricks their finger or other convenient site to induce bleeding and introduces a blood sample to the sample chamber, thus starting the chemical reaction set forth above.
[0004] In electrochemical terms, the function of the meter is two fold. Firstly, it provides a polarizing voltage (approximately 0.4 V in the case of OneTouch® Ultra that polarizes the electrical interface and allows current flow at the carbon working electrode surface. Secondly, it measures the current that flows in the external circuit between the anode (working electrode) and the cathode (reference electrode). The meter may, therefore be considered to be a simple electrochemical system that operates in two-electrode mode although, in practice, third and, even fourth electrodes may be used to facilitate the measurement of glucose and/or perform other functions in the meter.
[0005] In most situations, the equation set forth above is considered to be a sufficient approximation of the chemical reaction taking place on the test strip and the meter reading a sufficiently accurate representation of the glucose content of the blood sample. However, under certain circumstances and for certain purposes, it maybe advantageous to improve the accuracy of the measurement. For example, where a portion of the current measured at the electrode results from the presence of other chemicals or compounds in the sample. Where such additional chemicals or compounds are present, they may be referred to as interfering compounds and the resulting additional current may be referred to as Interfering Currents
[0006] Examples of potentially interfering chemicals (i.e. compounds found in physiological fluids such as blood that may generate Interfering Currents in the presence of an electrical field) include ascorbate, urate and acetaminophen (Tylenol™ or Paracetamol). One mechanism for generating Interfering Currents in an electrochemical meter for measuring the concentration of an analyte in a physiological fluid (e.g. a glucose meter) involves the oxidation of one or more interfering compounds by reduction of the enzyme (e.g. glucose oxidase). A further mechanism for generating Interfering Currents in such a meter involves the oxidation of one or more interfering compounds by reduction of the mediator (e.g. ferricyanide). A further mechanism for generating Interfering Currents in such a meter involves the oxidation of one or more interfering compounds at the working electrode. Thus, the total current measured at the working electrode is the superposition of the current generated by oxidation of the analyte and the current generated by oxidation of interfering compounds. Oxidation of interfering compounds may be a result of interaction with the enzyme, the mediator or may occur directly at the working electrode.
[0007] In general, potentially interfering compounds can be oxidized at the electrode surface and/or by a redox mediator. This oxidation of the interfering compound in a glucose measurement system causes the measured oxidation current to be dependent on both the glucose and the interfering compound. Therefore, if the concentration of interfering compound oxidizes as efficiently as glucose and/or the interfering compound concentration is significantly high relative to the glucose concentration, it may impact the measured glucose concentration. [0008] The co-oxidization of analyte (e.g. glucose) with interfering compounds is especially problematic when the standard potential (i.e. the potential at which a compound is oxidized) of the interfering compound is similar in magnitude to the standard potential of the redox mediator , resulting in a significant portion of the interference Current being generated by oxidation of the interfering compounds at the working electrode. Electrical current resulting from the oxidation of interfering compounds at the working electrode may be referred to as direct interference current. It would, therefore, be advantageous to reduce or minimize the effect of the direct interference current on the measurement of analyte concentration. Previous methods of reducing or eliminating direct interference current include designing test strips that prevent the interfering compounds from reaching the working electrode, thus reducing or eliminating the direct interference current attributable to the excluded compounds.
[0009] One strategy for reducing the effects of interfering compounds that generate Direct interference current is to place a negatively charged membrane on top of the working electrode. As one example, a sulfonated fluoropolymer such as NAFION™ may be placed over the working electrode to repel all negatively charged chemicals. In general, many interfering compounds, including ascorbate and urate, have a negative charge, and thus, are excluded from being oxidized at the working electrode when the surface of the working electrode is covered by a negatively charged membrane. However, because some interfering compounds, such as acetaminophen, are not negatively charged, and thus, can pass through the negatively charged membrane, the use of a negatively charged membrane will not eliminate the Direct interference current. Another disadvantage of covering the working electrode with a negatively charged membrane is that commonly used redox mediators, such as ferricyanide, are negatively charged and cannot pass through the membrane to exchange electrons with the electrode. A further disadvantage of using a negatively charged membrane over the working electrode is the potential to slow the diffusion of the reduced mediator to the working electrode, thus increasing the test time. A further disadvantage of using a negatively charged membrane over the working electrode is the increased complexity and expense of manufacturing the test strips with a negatively charged membrane.
[00010] Another strategy that can be used to decrease the effects of Direct Interfering Currents is to position a size selective membrane on top of the working electrode. As one example, a 100 Dalton size exclusion membrane such as cellulose acetate maybe placed over the working electrode to exclude compounds having a molecular weight greater than 100 Daltons. In this embodiment, the redox enzyme such as glucose oxidase is positioned over the size exclusion membrane. Glucose oxidase generates hydrogen peroxide, in the presence of glucose and oxygen, in an amount proportional to the glucose concentration. It should be noted that glucose and most redox mediators have a molecular weight greater than 100 Daltons, and thus, cannot pass through the size selective membrane. Hydrogen peroxide, however, has a molecular weight of 34 Daltons, and thus, can pass through the size selective membrane. In general, most interfering compounds have a molecular weight greater than 100 Daltons, and thus, are excluded from being oxidized at the electrode surface. Since some interfering compounds have smaller molecular weights, and thus, can pass through the size selective membrane, the use of a size selective membrane will not eliminate the Direct interference current. A further disadvantage of using a size selective membrane over the working electrode is the increased complexity and expense of manufacturing the test strips with a size selective membrane.
[00011] Another strategy that can be used to decrease the effects of Direct interference current is to use a redox mediator with a low redox potential, for example, a redox potential of between about - 300mV to + 100 mV (vs a saturated calomel electrode). This allows the applied potential to the working electrode to be relatively low which, in turn, decreases the rate at which interfering compounds are oxidized by the working electrode. Examples of redox mediators having a relatively low redox potential include osmium bipyridyl complexes, ferrocene derivatives, and quinone derivatives. However, redox mediators having a relatively low potential are often difficult to synthesize, relatively unstable and relatively insoluble. Another strategy that can be used to decrease the effects of interfering compounds is to use a dummy electrode in conjunction with the working electrode. The current measured at the dummy electrode may then be subtracted from the current measured at the working electrode in order to compensate for the effect of the interfering compounds. If the dummy electrode is bare (i.e. not covered by an enzyme or mediator), then the current measured at the dummy electrode will be proportional to the Direct interference current and subtracting the current measured at the dummy electrode from the current measured at the working electrode will reduce or eliminate the effect of the direct oxidation of interfering compounds at the working electrode. If the dummy electrode is coated with a redox mediator then the current measured at the dummy electrode will be a combination of Direct interference current and interference current resulting from reduction of the redox mediator by an interfering compound. Thus, subtracting the current measured at the dummy electrode coated with a redox mediator from the current measured at the working electrode will reduce or eliminate the effect of the direct oxidation of interfering compounds and the effect of interference resulting from reduction of the redox mediator by an interfering compound at the working electrode. In some instances the dummy electrode may also be coated with an inert protein or deactivated redox enzyme in order to simulate the effect of the redox mediator and enzyme on diffusion. Because it is preferable that test strips have a small sample chamber so that people with diabetes do not have to express a large blood sample, it may not be advantageous to include an extra electrode which incrementally increases the sample chamber volume where the extra electrode is not used to measure the analyte (e.g. glucose). Further, it may be difficult to directly correlate the current measured at the dummy electrode to interference currents at the working electrode. Finally, since the dummy electrode may be coated with a material or materials (e.g. redox mediator) which differ from the materials used to cover the working electrode (e.g. redox mediator and enzyme), test strips which use dummy electrodes as a method of reducing or eliminating the effect of interfering compounds in a multiple working electrode system may increase the cost and complexity of manufacturing the test strip.
[00013] Certain test strip designs which utilize multiple working electrodes to measure analyte, such as the system used in the OneTouch® Ultra® glucose measurement system are advantageous because the use of two working electrodes. In such systems, it would, therefore, be advantageous to develop a method of reducing or eliminating the effect of interfering compounds. More particularly, it would be advantageous to develop a method of reducing or eliminating the effect of interfering compounds without utilizing a dummy electrode, an intermediate membrane or a redox mediator with a low redox potential.
SUMMARY OF INVENTION
[00014] The present invention is directed to a method of reducing the effects of interfering compounds in the measurement of analytes and more particularly to a method of reducing the effects of interfering compounds in a system wherein the test strip utilizes two or more working electrodes. In one embodiment of the present invention, a first potential is applied to a first working electrode and a second potential, having the same polarity but a greater magnitude than the first potential, is applied to a second working electrode. The magnitude of the second potential may also be less than the first potential for an embodiment where a reduction current is used to measure the analyte concentration. In one embodiment, the first working electrode and second working electrode may be covered with an enzyme reagent and redox mediator that are analyte specific. The first potential applied to the first working electrode is selected such that it is sufficient to oxidize reduced redox mediator in a diffusion limited manner while the second potential is selected to have a magnitude (i.e. absolute value) greater than the magnitude of the first potential, resulting in a more efficient oxidation of at the second working electrode. In this embodiment of the invention, the current measured at the first working electrode includes an analyte current and interfering compound current while the current measured at the second working electrode includes an analyte overpotential current and an interfering compound overpotential current. It should be noted that the analyte current and the analyte overpotential current both refer to a current that corresponds to the analyte concentration and that the current is a result of a reduced mediator oxidation. In an embodiment of this invention, the relationship between the currents at the first working electrode and second working electrode may be defined by the following equation,
Wι -YW X -Y
where A is the analyte current at the first working electrode, Wj is the current measured at the first working electrode, W2 is the current measured at the second working electrode, X is an analyte dependent voltage effect factor and 7 is an interfering compound dependent voltage effect factor. Using the equation set forth above, in a method according to the present invention, it is possible to reduce the effect of oxidation currents resulting from the presence of interfering compounds and calculate a corrected current value that is more representative of the concentration of analyte in the sample being measured. In one embodiment of the present invention, the concentration of glucose in a sample placed on a test strip can be calculated by placing the sample on a test strip having a first working electrode and second working electrode and a reference electrode, at least the first working electrode and second working electrodes being coated with chemical compounds (e.g. an enzyme and a redox mediator) adapted to facilitate the oxidation of glucose and the transfer of electrons from the oxidized glucose to the first working electrode and the second working electrode when a potential is applied between the first working electrode and the reference electrode, and the second working electrode and the reference electrode. In accordance with the present invention, a first potential is applied between the first working electrode and the reference electrode, the first potential being selected to have a magnitude sufficient to ensure that the magnitude of the current generated by oxidation of the glucose in the sample is limited only by factors other than applied voltage (e.g. diffusion). In accordance with the present invention, a second potential is applied between the second working electrode and the reference electrode, the second potential being greater in magnitude than the first potential and, in one embodiment of the present invention, the second potential being selected to increase the oxidation of interfering compounds at the second working electrode. In a further embodiment of the present invention, the following equation may be used to reduce the effect of oxidation current resulting from the presence of interfering compounds on the current used to calculate the concentration of glucose in the sample. In particular, the glucose concentration may be derived using a calculated current A G where:
W2 -YWλ \G XG -Y
where AJG is a glucose current, Wj is the current measured at the first working electrode, W2 is the current measured at the second working electrode, Xβ is a glucose dependent voltage effect factor and Y is an interfering compound dependent voltage effect factor.
BRIEF DESCRIPTION OF THE DRAWINGS The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
Figure 1 is an exploded perspective view of a test strip embodiment for use in the present invention.
Figure 2 is a schematic view of a meter and strip for use in the present invention.
Figure 3 is a hydrodynamic voltammogram illustrating the dependence of applied voltage with measured current.
DETAILED DESCRIPTION OF THE INVENTION While the present invention is particularly adapted to the measurement of glucose concentration in blood, it will be apparent to those of skill in the art that the method described herein may be adapted to improve the selectivity of other systems used for the electrochemical measurement of analytes in physiological fluids. Examples of systems that may be adapted to improve selectivity using the method according to the present invention include electrochemical sensors used to measure the concentration of lactate, lactate, alcohol, cholesterol, amino acids, choline, and fructosamine in physiological fluids. Examples of physiological fluids that may contain such analytes include blood, plasma, serum, urine, and interstitial fluid. It will further be understood that, while the method of the present invention is described in an electrochemical system where the measured current is produced by oxidation, the invention would be equally applicable to a system wherein the measured current is produced by reduction. [00017] The present invention is directed to a method for improving the selectivity of an electrochemical measuring system that is particularly adapted for use in a blood glucose measurement system. More particularly, the present invention is directed to a method for improving the selectivity of a blood glucose measurement system by partially or wholly correcting for the effect of the direct interference current. Selectivity in such systems being a measure of the ability of the system to accurately measure the glucose concentration in a sample of physiological fluid which includes one or more compounds which create an interfering current. Improvement of selectivity thus reduces the current generated at the working electrode by the presence of interfering compounds (i.e. compounds other than glucose which oxidize to generate interfering current) and makes the measured current more representative of the glucose concentration. In particular, the measured current may be a function of the oxidation of interfering compounds commonly found in physiological fluids such as, for example, acetaminophen (Tylenol™ or Paracetamol), ascorbic acid, bilirubin, dopamine, gentisic acid, glutathione, levodopa, methyldopa, tolazimide, tolbutamide and uric acid. Such interfering compounds may be oxidized by, for example, reacting chemically with the redox mediator or by oxidizing at the elecfrode surface.
[00018] In a perfectly selective system, there would be no oxidation current generated by any interfering compound and the entire oxidation current would be generated by oxidation of glucose. However, if oxidation of interfering compounds and the resulting oxidation current cannot be avoided the present invention describes a method of removing some or all of the effect of interfering compounds by quantifying the proportion of the overall oxidation current generated by the interfering compounds and subtracting that quantity from the overall oxidation current. In particular, in a method according to the present invention, using a test strip that includes first working electrode and second working electrode, two different potentials are applied and the oxidation current generated at each of the working electrodes is measure used to estimate the respective oxidation current proportions for both the glucose and interfering compounds. [00019] In one embodiment of a method according to the present invention, a test strip is used which includes a sample chamber containing a first working electrode, a second working electrode, and a reference electrode. The first working electrode, the second working electrode and the reference elecfrodes are covered by glucose oxidase (the enzyme) and a Ferricyanide (the redox mediator). When a sample of blood (the physiological fluid) is placed in the sample chamber, the glucose oxidase is reduced by glucose in the blood sample generating gluconic acid. The gluconic acid is then oxidized by reduction of the Ferricyanide to Ferrocyanide, yielding a reduced redox mediator with a concentration proportional to the glucose concentration. An example of a test strip that may be suitable for use in a method according to the present invention is the OneTouch® Ultra® test strip sold by LifeScan, Inc. of Milpitas, California. Other suitable strips are described in international publication WO 01/67099A1 and WO 01/73124A2.
[00020] In one embodiment of a method according to the present invention a first potential is applied to a first working electrode and a second potential is applied to the second working electrode. In this embodiment, the first potential is selected to be in a range in which the glucose current response is relatively insensitive to the applied potential and thus the magnitude of the glucose current at the first working electrode is limited by the amount of reduced redox mediator diffusing to the first working electrode. It should be noted that glucose is not directly oxidized at a working electrode, but instead is indirectly oxidized through using a redox enzyme and a redox mediator. In the description of the present invention, the glucose current refers to an oxidation of reduced redox mediator that correlates to the gluocose concentration. In an embodiment of the present invention where ferri/ferrocyanide is the redox mediator and carbon is the working electrode, the first potential may range from about 0 millivolts to about 500 millivolts, and more preferably from about 385 millivolts to about 415 millivolts, and yet even more preferably may range from about 395 to 405 mV. A second potential is applied to a second working electrode such that the second potential is greater than the first potential. Where the applied potential is greater than the potential needed to oxidize the glucose. In an embodiment of the present invention where ferri/ferrocyanide is the redox mediator and carbon is the working electrode, the second potential may range from about 50 millivolts to about 1000 millivolts, and more preferably from about 420 millivolts to about 1000 millivolts.
[00021] Because the glucose current does not increase or increases only minimally with increasing potential, the glucose current at the second working electrode should be substantially equal to the glucose current at the first working electrode, even though the potential at the second working electrode is greater than the potential at the first electrode. Thus, any additional current measured at the second working electrode may be attributed to the oxidation of interfering compounds. In other words, the higher potential at the second working electrode should cause a glucose overpotenital current to be measured at the second working electrode which is equal or substantially equal in magnitude to the glucose current at the first working electrode because the first potential and second potential are in a limiting glucose current range which is insensitive to changes in applied potential. However, in practice, other parameters may have an impact on the measured current, for example, where a higher potential is applied to the second working electrode, there is often a slight increase in the overall current at the second working electrode as a result of an IR drop or capacitive effects. When an IR drop (i.e. uncompensated resistance) is present in the system, a higher applied potential causes an increase in the measured current magnitude. Examples of IR drops may be the nominal resistance of the first working electrode, second working electrode, the reference electrode, the physiological fluid between the working electrode and the reference electrode. In addition, the application of a higher potential results in the formation of a larger ionic double layer which forms at the electrode/liquid interface, increasing the ionic capacitance and the resulting current at either the firstworking electrode or second working electrode.
[00022] In order to determine the actual relationship between the glucose current measured at the first working electrode and the second working electrode, it is necessary to develop a suitable equation. It should be noted that the glucose current at the second working electrode may also be referred to as a glucose overpotential current. A directly proportional relationship between the glucose current and the glucose overpotential current may be described by the following equation. XGX AJG = A2G (eq l) where XQ is a glucose dependent voltage effect factor, AJG is the glucose current at the first working electrode and ^σ is the glucose current at the second working electrode.
[00023] In an embodiment of the present invention, where ferri/ferrocyanide is the redox mediator and carbon is the working electrode, the voltage effect factor XQ for glucose may be expected to be between about 0.95 any about 1.1. In this embodiment of the invention, higher potentials do not have a significant impact on the glucose oxidation current because the redox mediator (ferrocyanide) has fast electron transfer kinetics and reversible electron transfer characteristics with the working electrode. Because the glucose current does not increase with increasing potential after a certain point, the glucose current may be said to be saturated or in a diffusion limited regime.
[00024] In the embodiment of the present invention described above, glucose is indirectly measured by oxidizing ferrocyanide at the working electrode and where the ferrocyanide concentration is directly proportional to the glucose concentration. The standard potential (E°) value for a particular electrochemical compound is a measure of that compound's ability to exchange electrons with other chemical compounds. In the method according to the present invention, the potential at the first working electrode is selected to be greater than the standard potential (E°) of the redox mediator. Because the first potential is selected such that it is sufficiently greater than the E° value of the redox couple, the oxidation rate does not increase substantially as the applied potential increases. Thus, applying a greater potential at the second working electrode will not increase the oxidation at the second working electrode and any increased current measured at the higher potential electrode must be due to other factors, such as, for example, oxidation of interfering compounds.
[00025] Figure 3 is a hydrodynamic voltammogram illustrating the dependence of applied voltage with measured current where ferri/ferrocyanide is the redox mediator and carbon is the working electrode. Each data point on the graph represents at least one experiment where a current is measured 5 seconds after applying a voltage across a working electrode and a reference electrode. Figure 3 shows that the current forms an onset of a plateau region at about 400 mV because the applied voltage is sufficiently greater than of the E° value of ferrocyanide. Thus, as illustrated in Figure 3, as the potential reaches approximately 400 mV, the glucose current becomes saturated because the oxidation of ferrocyanide is diffusion limited (i.e. the diffusion of ferrocyanide to the working electrode limits the magnitude of the measured current and is not limited by the electron transfer rate between ferrocyanide and the electrode).
[00026] In general, current generated by the oxidation of interfering compounds is not saturated by increases in applied voltage and shows a much stronger dependence on applied potential than current generated by oxidation of ferrocyanide (the ferrocyanide having been generated from the interaction of glucose with the enzyme and the enzyme with ferrocyanide. Typically, interfering compounds have slower electron transfer kinetics than redox mediators (i.e. ferrocyanide). This difference is ascribed to the fact that most interfering compounds undergo an inner sphere electron transfer pathway as opposed to the faster outer sphere electron transfer pathway of ferrocyanide. A typical inner sphere electron transfer requires a chemical reaction to occur, such as a hydride transfer, before transferring an electron. In contrast, an outer sphere electron transfer does not require a chemical reaction before transferring an electron. Therefore, inner sphere electron transfer rates are typically slower than outer sphere electron transfers because they require an additional chemical reaction step. The oxidation of ascorbate to dehydroascorbate is an example of an inner sphere oxidation that requires the liberation of two hydride moieties. The oxidation of ferrocyanide to ferricyanide is an example of an outer sphere electron transfer. Therefore, the current generated by interfering compounds generally increases when testing at a higher potential.
[00027] A relationship between an interfering compound current at the first working electrode and an interfering compound overpotential current at the second working electrode can be described by the following equation, Yx Iι = I2 (eq 2)
where Y is an interfering compound dependent voltage effect factor, is the interfering compound current, and I2 is the interfering compound overpotential current. Because the interfering compound voltage effect factor Y is dependent upon a number of factors, including, the particular interfering compound or compounds of concern and the material used for the working electrodes, calculation of a particular interfering compound dependent voltage effect factor for a particular system, test strip, analyte and interfering compound or compounds may require experimentation to optimize the voltage effect factor for those criteria. Alternatively, under certain circumstances, appropriate voltage effect factors may be derived or described mathematically.
In an embodiment of the present invention where ferri/ferrocyanide is the redox mediator and carbon is the working electrode, the interfering compound dependent voltage effect factor 7 could be mathematically described using the Tafel equation for/; and h, /^ 'expj (eq 2a)
I2 = α'exp (eq 2b) \ b' j
where 77, =E] - E°, η2 =E2 - E°, b' is a constant depending of the specific elecfroactive interfering compound, E] is the first potential, and E is the second potential. The value of E° (the standard potential of a specific interfering compound) is not important because it is canceled out in the calculation of Aη . Equations 2, 2a, 2b can be combined and rearranged to yield the following equation,
Figure imgf000018_0001
where Δ^E} - E . Equation 2c provides a mathematical relationship describing the relationship between Aη (i.e. the difference between the first potential and the second potential) and the interfering compound dependent voltage effect factor 7. In an embodiment of the present invention, 7 may range from about 1 to about 100, and more preferably between about 1 and 10. In an embodiment of this invention, the interfering compound dependent voltage effect factor 7 may be determined experimentally for a specific interfering compound or combination of interfering compounds. It should be noted that the interfering compound dependent voltage effect factor 7 for interfering compounds is usually greater than voltage effect factor XG for glucose. As the following sections will describe, the mathematical relationship of a) the interfering compound current // and the interfering compound overpotential current I ; and b) the glucose current AJ and the glucose overpotential current A2G will allow a glucose algorithm to be proposed which will reduce the effects of interfering compounds for measuring glucose. In an embodiment of the present invention, an algorithm was developed to calculate a corrected glucose current (i.e. AJG and A2 ) which is independent of interferences. After dosing a sample onto a test strip, a first potential is applied to the first working electrode and a second potential is applied to the second working electrode. At the first working electrode, a first current is measured which can be described by the following equation,
WI = AJG + IJ (eq 3) where Wj is the first current at the first working electrode. In other words, the first current includes a superposition of the glucose current AJG and the interfering compound current I . More specifically, the interfering compound current may be a direct interfering current which has been described hereinabove. At the second working electrode, a second current is measured at the second potential or overpotential which can be described by the following equation, W2 =A2G + (eq 4)
where W2 is the second current at the second working electrode, A2G is the glucose overpotential current measured at the second potential, and I2 is the interfering compound overpotential current measured at the second potential. More specifically, the interfering compound overpotential current may be a Direct Interfering compound Current which has been described hereinabove. Using the previously described 4 equations (eq's 1 to 4) which contain 4 unknowns (AJG, A2 , h, and I2), it is now possible to calculate a corrected glucose current equation which is independent of interfering compounds. As the first step in the derivation, A2G from eq 1 and I2 from eq 2 can be substituted into eq 4 to give the following eq 5.
W2 =XGAJG + YIJ (eq 5)
Next, eq 3 is multiplied by interfering compound dependent voltage effect factor 7 for interfering compounds to give eq 6.
Figure imgf000020_0001
Eq 5 can now be subtracted from eq 6 to give the following form shown in eq 7
W2 - YWj = XGA1G - YAJG (eq 7)
Eq 7 can now be rearranged to solve for the corrected glucose current A JG measured at the first potential as shown in eq 8.
W2 -YWl alG (eq 8) XG -Y Eq 8 outputs a corrected glucose current A G which removes the effects of interferences requiring only the current output of the first working electrode and second working electrode (eg Wj and W2), glucose dependent voltage effect factors XQ , and interfering compound dependent voltage effect factor 7 for interfering compounds.
[00030] A glucose meter containing electronics is electrically interfaced with a glucose test strip to measure the current from Wj and W2. In one embodiment of the present invention, XQ and 7 may be programmed into the glucose meter as read only memory. In another embodiment of the present invention,^ and 7 may be transferred to the meter via a calibration code chip. The calibration code chip would have in its memory a particular set of values ΪOΪXG and 7 which would be calibrated for a particular lot of test strips. This would account for test strip lot-to-lot variations that may occur in XQ and 7.
[00031] In another embodiment of the present invention, the corrected glucose current in eq 8 may be used by the meter only when a certain threshold is exceeded. For example, if W2 is about 10% or greater than Wi, then the meter would use eq 8 to correct for the current output. However, if W2 is about 10% or less than Wj, the interfering compound concentration is low and thus the meter can simply take an average current value between Wj and W to improve the accuracy and precision of the measurement. Instead of simply averaging the current of Wj and W2, a more accurate W approach may be to average Wj with — — where the glucose dependent voltage effect XG W factor XG is taken into account (note — — approximately equals AJG according to eq 1 and 4 when I2 is low). The strategy of using eq 8 only under certain situations where it is likely that a significant level of interferences are in the sample mitigates the risk of overcorrecting the measured glucose current. It should be noted that when W2 is sufficiently greater than Wj by a large amount (e.g. about 100% or more), this is an indicator of having an unusually high concentration of interferences. In such a case, it may be desirable to output an error message instead of a glucose value because a very high level of interfering compounds may cause a breakdown in the accuracy of eq 8.
[00032] The following sections will describe a possible test strip embodiment which may be used with the proposed algorithm of the present invention as shown in eq 8. Figure 1 is an exploded perspective view of test strip 600, which includes six layers disposed upon a base substrate 5. These six layers are a conductive layer 50, an insulation layer 16, a reagent layer 22, an adhesive layer 60, a hydrophilic layer 70, and a top layer 80. Test strip 600 may be manufactured in a series of steps wherein the conductive layer 50, insulation layer 16, reagent layer 22, adhesive layer 60 are deposited on base substrate 5 using, for example, a screen printing process. Hydrophilic layer 70 and top layer 80 may be deposed from a roll stock and laminated onto base substrate 5. The fully assembled test strip forms a sample receiving chamber that can accept a blood sample so that it can be analyzed.
[00033] Conductive layer 50 includes reference electrode 10, first working electrode 12, second working electrode 14, a first contact 13, a second contact 15, a reference contact 11 , and a strip detection bar 17. Suitable materials which may be used for the conductive layer are Au, Pd, Ir, Pt, Rh, stainless steel, doped tin oxide, carbon, and the like. Preferably, the material for the conductive layer may be a carbon ink such as those described in US5653918.
[00034] Insulation layer 16 includes cutout 18 which exposes a portion of reference electrode 10, first working electrode 12, and second working electrode 14 which can be wetted by a liquid sample. As a non-limiting example, insulation layer (16 or 160) may be Ercon E6110-116 Jet Black Insulayer Ink which may be purchased from Ercon, Inc.
[00035] Reagent layer 22 may be disposed on a portion of conductive layer 50 and insulation layer 16. In an embodiment of the present invention, reagent layer 22 may include chemicals such as a redox enzyme and redox mediator which selectivity react with glucose. During this reaction, a proportional amount of a reduced redox mediator can be generated that then can be measured electrochemically so that a glucose concentration can be calculated. Examples of reagent formulations or inks suitable for use in the present invention can be found in US patents 5,708,247 and 6,046,051; published international applications WOOl/67099 and WOOl/73124, all of which are incorporated by reference herein.
[00036] Adhesive layer 60 includes first adhesive pad 24, second adhesive pad 26, and third adhesive pad 28. The side edges of first adhesive pad 24 and second adhesive pad 26 located adjacent to reagent layer 22 each define a wall of a sample receiving chamber. In an embodiment of the present invention, the adhesive layer may comprise a water based acrylic copolymer pressure sensitive adhesive which is commercially available from Tape Specialties LTD in Tring, Herts, United Kingdom (part#A6435).
[00037] Hydrophilic layer 70 includes a distal hydrophilic pad 32 and proximal hydrophilic pad 34. As a non-limiting example, hydrophilic layer 70 be a polyester having one hydrophilic surface such as an anti-fog coating which is commercially available from 3M. It should be noted that both distal hydrophilic film 32 and proximal hydrophilic film 34 are visibly transparent enabling a user to observe a liquid sample filling the sample receiving chamber.
[00038] Top layer 80 includes a clear portion 36 and opaque portion 38. Top layer 80 is disposed on and adhered to hydrophilic layer 70. As a non-limiting example, top layer 40 may be a polyester. It should be noted that the clear portion 36 substantially overlaps proximal hydrophilic pad 32 which allows a user to visually confirm that the sample receiving chamber is sufficiently filled. Opaque portion 38 helps the user observe a high degree of contrast between a colored fluid such as, for example, blood within the sample receiving chamber and the opaque section of the top film.
[00039] Figure 2 is a simplified schematic showing a meter 500 interfacing with a test strip 600. Meter 500 has three electrical contacts that form an electrical connection to first working electrode 12, second working electrode 14, and reference electrode 10. In particular connector 101 connects voltage source 103 to first working electrode 12, connector 102 connects voltage source 104 to second working electrode 14 and common connector 100 connects voltage source 103 and 104 to reference elecfrode 10. When performing a test, voltage source 103 in meter 500 applies a first potential EΪ between first working electrode 12 and reference electrode 10 and voltage source 104 applies a second potential E2 between second working electrode 14 and reference electrode 10. A sample of blood is applied such that first working electrode 12, second working electrode 14, and reference electrode 10 are covered with blood. This causes reagent layer 22 to become hydrated which generates ferrocyanide in an amount proportional to the glucose and/or interfering compound concentration present in the sample. After about 5 seconds from the sample application, meter 500 measures an oxidation current for both first working electrode 12 and second working electrode 14.
[00040] In the previously described first and second test strip embodiments, the first working electrode 12 and second working electrode 14 had the same area. It should be noted that the present invention is not limited to test strips having equal areas. For alternative embodiments to the previously described strips where the areas are different, the current output for each working electrode must be normalized for area. Because the current output is directly proportional to area, the terms within Equation 1 to Equation 8 may be in units of amperes (current) or in amperes per unit area (i.e. current density).
[00041] It will be recognized that equivalent structures may be substituted for the structures illustrated and described herein and that the described embodiment of the invention is not the only structure that may be employed to implement the claimed invention. In addition, it should be understood that every structure described above has a function and such structure can be referred to as a means for performing that function. While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to hose skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

WHAT IS CLAIMED IS:
1. A method of reducing interferences in an electrochemical sensor comprising: applying a first potential to a first working electrode; applying a second potential to a second working electrode, wherein said second potential is greater than the absolute value of said first potential; measuring a first current, at said first working electrode, which comprises an analyte current and an interfering compound current; measuring a second current, at said second working electrode, which comprises an analyte overpotential current and an interfering compound overpotential current, wherein said analyte overpotential current has a first directly proportional relationship to said analyte current and, wherein said interfering compound overpotential current has a second directly proportional relationship to said interfering compound current; and calculating a corrected current value representative of an analyte concentration using an equation which is a function of said first current, said second current, said first directly proportional relationship, and said second directly proportional relationship.
2. The method of claim 1, wherein said equation is
W, - YW, 4 = X-Y where A is said analyte current, Wj is said first current, W2 is said second current, X is an analyte voltage effect factor, and 7 is an interfering compound voltage effect factor.
3. The method of claim 1, wherein said analyte is glucose.
4. The method of claim 1, wherein said first potential is between about 385 millivolts and about 415 millivolts for said electrochemical sensor which comprises a carbon working electrode and a ferrocyanide redox mediator.
5. The method of claim 1, wherein said second potential is between about 420 millivolts and about 1000 millivolts for said electrochemical sensor which comprises a carbon working electrode and a ferrocyanide redox mediator.
6. The method of claim 1, wherein said interfering compound current results from the oxidation of at least one chemical chosen from the group consisting of acetaminophen, ascorbic acid, bilirubin, dopamine, gentisic acid, glutathione, levodopa, methyldopa, tolazimide, tolbutamide, and uric acid.
7. The method of claim 1, wherein said first directly proportional relationship is
Figure imgf000027_0001
where X is said analyte voltage effect factor, A is said analyte current, and A2 is said analyte overpotential current.
8. The method of claim 1, wherein said first directly proportional relationship is
Yx = where 7 is said interfering compound voltage effect factor, I is said interfering compound current, and I2 is said interfering compound overpotential current.
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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8211292B2 (en) 2005-08-05 2012-07-03 Bayer Healthcare Llc Method for distinguishing electrochemical sensors
CN112294325A (en) * 2019-08-02 2021-02-02 华广生技股份有限公司 Miniature biosensor and method for reducing measurement interference
EP3771413A1 (en) * 2019-08-02 2021-02-03 Bionime Corporation Method for manufacturing implantable micro-biosensor
US11950902B2 (en) 2020-07-31 2024-04-09 Bionime Corporation Micro biosensor and method for reducing measurement interference using the same

Families Citing this family (241)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE227844T1 (en) 1997-02-06 2002-11-15 Therasense Inc SMALL VOLUME SENSOR FOR IN-VITRO DETERMINATION
US9155496B2 (en) 1997-03-04 2015-10-13 Dexcom, Inc. Low oxygen in vivo analyte sensor
US7899511B2 (en) 2004-07-13 2011-03-01 Dexcom, Inc. Low oxygen in vivo analyte sensor
US6862465B2 (en) 1997-03-04 2005-03-01 Dexcom, Inc. Device and method for determining analyte levels
US8527026B2 (en) 1997-03-04 2013-09-03 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
US6036924A (en) 1997-12-04 2000-03-14 Hewlett-Packard Company Cassette of lancet cartridges for sampling blood
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
US8974386B2 (en) 1998-04-30 2015-03-10 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US6949816B2 (en) 2003-04-21 2005-09-27 Motorola, Inc. Semiconductor component having first surface area for electrically coupling to a semiconductor chip and second surface area for electrically coupling to a substrate, and method of manufacturing same
US8346337B2 (en) 1998-04-30 2013-01-01 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
US8480580B2 (en) 1998-04-30 2013-07-09 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8688188B2 (en) 1998-04-30 2014-04-01 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US6175752B1 (en) 1998-04-30 2001-01-16 Therasense, Inc. Analyte monitoring device and methods of use
US8465425B2 (en) 1998-04-30 2013-06-18 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
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
US6560471B1 (en) 2001-01-02 2003-05-06 Therasense, Inc. Analyte monitoring device and methods of use
US7310543B2 (en) * 2001-03-26 2007-12-18 Kumetrix, Inc. Silicon microprobe with integrated biosensor
US7344507B2 (en) 2002-04-19 2008-03-18 Pelikan Technologies, Inc. Method and apparatus for lancet actuation
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
US7981056B2 (en) 2002-04-19 2011-07-19 Pelikan Technologies, Inc. Methods and apparatus for lancet actuation
US8337419B2 (en) 2002-04-19 2012-12-25 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US7033371B2 (en) 2001-06-12 2006-04-25 Pelikan Technologies, Inc. Electric lancet actuator
DE60234597D1 (en) 2001-06-12 2010-01-14 Pelikan Technologies Inc DEVICE AND METHOD FOR REMOVING BLOOD SAMPLES
CA2448902C (en) 2001-06-12 2010-09-07 Pelikan Technologies, Inc. Self optimizing lancing device with adaptation means to temporal variations in cutaneous properties
US7749174B2 (en) 2001-06-12 2010-07-06 Pelikan Technologies, Inc. Method and apparatus for lancet launching device intergrated onto a blood-sampling cartridge
US7699791B2 (en) 2001-06-12 2010-04-20 Pelikan Technologies, Inc. Method and apparatus for improving success rate of blood yield from a fingerstick
US7041068B2 (en) 2001-06-12 2006-05-09 Pelikan Technologies, Inc. Sampling module device and method
US9427532B2 (en) 2001-06-12 2016-08-30 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
DE10134650B4 (en) * 2001-07-20 2009-12-03 Roche Diagnostics Gmbh System for taking small amounts of body fluid
US20030032874A1 (en) 2001-07-27 2003-02-13 Dexcom, Inc. Sensor head for use with implantable devices
US8010174B2 (en) 2003-08-22 2011-08-30 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
US10022078B2 (en) 2004-07-13 2018-07-17 Dexcom, Inc. Analyte sensor
US8260393B2 (en) 2003-07-25 2012-09-04 Dexcom, Inc. Systems and methods for replacing signal data 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
US7613491B2 (en) 2002-05-22 2009-11-03 Dexcom, Inc. Silicone based membranes for use in implantable glucose sensors
US9282925B2 (en) 2002-02-12 2016-03-15 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
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
US8221334B2 (en) 2002-04-19 2012-07-17 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7331931B2 (en) 2002-04-19 2008-02-19 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8702624B2 (en) 2006-09-29 2014-04-22 Sanofi-Aventis Deutschland Gmbh Analyte measurement device with a single shot actuator
US7491178B2 (en) 2002-04-19 2009-02-17 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8579831B2 (en) 2002-04-19 2013-11-12 Sanofi-Aventis Deutschland Gmbh 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
US9795334B2 (en) 2002-04-19 2017-10-24 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
US7901362B2 (en) 2002-04-19 2011-03-08 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7297122B2 (en) 2002-04-19 2007-11-20 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7892183B2 (en) 2002-04-19 2011-02-22 Pelikan Technologies, Inc. Method and apparatus for body fluid sampling and analyte sensing
US7976476B2 (en) 2002-04-19 2011-07-12 Pelikan Technologies, Inc. Device and method for variable speed lancet
US7291117B2 (en) 2002-04-19 2007-11-06 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7229458B2 (en) 2002-04-19 2007-06-12 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US9314194B2 (en) 2002-04-19 2016-04-19 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US7371247B2 (en) 2002-04-19 2008-05-13 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
US7717863B2 (en) 2002-04-19 2010-05-18 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US9248267B2 (en) 2002-04-19 2016-02-02 Sanofi-Aventis Deustchland Gmbh Tissue penetration device
US8784335B2 (en) 2002-04-19 2014-07-22 Sanofi-Aventis Deutschland Gmbh Body fluid sampling device with a capacitive sensor
US7232451B2 (en) 2002-04-19 2007-06-19 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7674232B2 (en) 2002-04-19 2010-03-09 Pelikan 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
US7226461B2 (en) 2002-04-19 2007-06-05 Pelikan Technologies, Inc. Method and apparatus for a multi-use body fluid sampling device with sterility barrier release
US7767068B2 (en) 2002-12-02 2010-08-03 Epocal Inc. Heterogeneous membrane electrodes
US7842234B2 (en) 2002-12-02 2010-11-30 Epocal Inc. Diagnostic devices incorporating fluidics and methods of manufacture
US7815579B2 (en) 2005-03-02 2010-10-19 Roche Diagnostics Operations, Inc. Dynamic integrated lancing test strip with sterility cover
US8052926B2 (en) * 2002-12-27 2011-11-08 Roche Diagnostics Operations, Inc. Method for manufacturing a sterilized lancet integrated biosensor
US8574895B2 (en) 2002-12-30 2013-11-05 Sanofi-Aventis Deutschland Gmbh Method and apparatus using optical techniques to measure analyte levels
US7134999B2 (en) 2003-04-04 2006-11-14 Dexcom, Inc. Optimized sensor geometry for an implantable glucose sensor
ES2347248T3 (en) 2003-05-30 2010-10-27 Pelikan Technologies Inc. PROCEDURE AND APPLIANCE FOR FLUID INJECTION.
WO2004107964A2 (en) 2003-06-06 2004-12-16 Pelikan Technologies, Inc. Blood harvesting device with electronic control
WO2006001797A1 (en) 2004-06-14 2006-01-05 Pelikan Technologies, Inc. Low pain penetrating
EP1648298A4 (en) 2003-07-25 2010-01-13 Dexcom Inc Oxygen enhancing membrane systems for implantable devices
US7424318B2 (en) * 2003-12-05 2008-09-09 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US8282549B2 (en) 2003-12-09 2012-10-09 Dexcom, Inc. Signal processing for continuous analyte sensor
WO2007120442A2 (en) 2003-07-25 2007-10-25 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US7467003B2 (en) * 2003-12-05 2008-12-16 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US8423113B2 (en) 2003-07-25 2013-04-16 Dexcom, Inc. Systems and methods for processing sensor data
US7460898B2 (en) * 2003-12-05 2008-12-02 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US7366556B2 (en) * 2003-12-05 2008-04-29 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
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
US8886273B2 (en) 2003-08-01 2014-11-11 Dexcom, Inc. Analyte sensor
US7494465B2 (en) 2004-07-13 2009-02-24 Dexcom, Inc. Transcutaneous analyte sensor
US7774145B2 (en) 2003-08-01 2010-08-10 Dexcom, Inc. Transcutaneous analyte sensor
US7519408B2 (en) 2003-11-19 2009-04-14 Dexcom, Inc. Integrated receiver for continuous analyte sensor
US7276029B2 (en) 2003-08-01 2007-10-02 Dexcom, Inc. System and methods for processing analyte sensor data
US20100168657A1 (en) 2003-08-01 2010-07-01 Dexcom, Inc. System and methods for processing analyte sensor data
US8160669B2 (en) 2003-08-01 2012-04-17 Dexcom, Inc. Transcutaneous analyte sensor
US8845536B2 (en) 2003-08-01 2014-09-30 Dexcom, Inc. Transcutaneous analyte sensor
US20190357827A1 (en) 2003-08-01 2019-11-28 Dexcom, Inc. Analyte sensor
US8761856B2 (en) 2003-08-01 2014-06-24 Dexcom, Inc. System and methods for processing analyte sensor data
US7933639B2 (en) 2003-08-01 2011-04-26 Dexcom, Inc. System and methods for processing analyte sensor data
US9135402B2 (en) * 2007-12-17 2015-09-15 Dexcom, Inc. Systems and methods for processing sensor data
US20140121989A1 (en) 2003-08-22 2014-05-01 Dexcom, Inc. Systems and methods for processing analyte sensor data
US7920906B2 (en) 2005-03-10 2011-04-05 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
WO2005033659A2 (en) 2003-09-29 2005-04-14 Pelikan Technologies, Inc. Method and apparatus for an improved sample capture device
US9351680B2 (en) 2003-10-14 2016-05-31 Sanofi-Aventis Deutschland Gmbh Method and apparatus for a variable user interface
US7655119B2 (en) * 2003-10-31 2010-02-02 Lifescan Scotland Limited Meter for use in an improved method of reducing interferences in an electrochemical sensor using two different applied potentials
EP1678489B1 (en) * 2003-10-31 2007-04-25 Lifescan Scotland Ltd Method of reducing the effect of direct interference current in an electrochemical test strip
US9247900B2 (en) 2004-07-13 2016-02-02 Dexcom, Inc. Analyte sensor
CN100472210C (en) * 2003-12-04 2009-03-25 松下电器产业株式会社 Blood component measuring method, sensor used therefor, and measuring instrument
US8774886B2 (en) 2006-10-04 2014-07-08 Dexcom, Inc. Analyte sensor
EP2239567B1 (en) 2003-12-05 2015-09-02 DexCom, Inc. Calibration techniques for a continuous analyte sensor
US8364231B2 (en) 2006-10-04 2013-01-29 Dexcom, Inc. Analyte sensor
US8423114B2 (en) 2006-10-04 2013-04-16 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US20100185071A1 (en) * 2003-12-05 2010-07-22 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US8287453B2 (en) 2003-12-05 2012-10-16 Dexcom, Inc. Analyte sensor
US11633133B2 (en) 2003-12-05 2023-04-25 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
EP1706026B1 (en) 2003-12-31 2017-03-01 Sanofi-Aventis Deutschland GmbH Method and apparatus for improving fluidic flow and sample capture
US7822454B1 (en) 2005-01-03 2010-10-26 Pelikan Technologies, Inc. Fluid sampling device with improved analyte detecting member configuration
US8808228B2 (en) 2004-02-26 2014-08-19 Dexcom, Inc. Integrated medicament delivery device for use with continuous analyte sensor
US20050245799A1 (en) * 2004-05-03 2005-11-03 Dexcom, Inc. Implantable analyte sensor
US8277713B2 (en) 2004-05-03 2012-10-02 Dexcom, Inc. Implantable analyte sensor
US8792955B2 (en) 2004-05-03 2014-07-29 Dexcom, Inc. Transcutaneous analyte sensor
US8828203B2 (en) 2004-05-20 2014-09-09 Sanofi-Aventis Deutschland Gmbh Printable hydrogels for biosensors
US9775553B2 (en) 2004-06-03 2017-10-03 Sanofi-Aventis Deutschland Gmbh Method and apparatus for a fluid sampling device
US9820684B2 (en) 2004-06-03 2017-11-21 Sanofi-Aventis Deutschland Gmbh Method and apparatus for a fluid sampling device
US7783333B2 (en) 2004-07-13 2010-08-24 Dexcom, Inc. Transcutaneous medical device with variable stiffness
US20060020192A1 (en) 2004-07-13 2006-01-26 Dexcom, Inc. Transcutaneous analyte sensor
US7640048B2 (en) 2004-07-13 2009-12-29 Dexcom, Inc. Analyte sensor
US20080242961A1 (en) * 2004-07-13 2008-10-02 Dexcom, Inc. Transcutaneous analyte sensor
US8452368B2 (en) 2004-07-13 2013-05-28 Dexcom, Inc. Transcutaneous analyte sensor
US8565848B2 (en) 2004-07-13 2013-10-22 Dexcom, Inc. Transcutaneous analyte sensor
US8652831B2 (en) 2004-12-30 2014-02-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for analyte measurement test time
EP1835848A4 (en) * 2004-12-30 2009-07-29 Pelikan Technologies Inc Method and apparatus for analyte measurement test time
US7935063B2 (en) * 2005-03-02 2011-05-03 Roche Diagnostics Operations, Inc. System and method for breaking a sterility seal to engage a lancet
EP1859048B1 (en) * 2005-03-04 2014-06-18 Bayer HealthCare LLC Stabilizing the activity of pqq-dependent glucose dehydrogenase in electrochemical biosensors
US20090076360A1 (en) 2007-09-13 2009-03-19 Dexcom, Inc. Transcutaneous analyte sensor
US8133178B2 (en) 2006-02-22 2012-03-13 Dexcom, Inc. Analyte sensor
US8744546B2 (en) 2005-05-05 2014-06-03 Dexcom, Inc. Cellulosic-based resistance domain for an analyte sensor
WO2007022485A2 (en) * 2005-08-19 2007-02-22 Becton, Dickinson And Company Sterilization of biosensors
WO2007028271A2 (en) * 2005-09-09 2007-03-15 F. Hoffmann-La Roche Ag A system, tools, devices and a program for diabetes care
US20090134043A1 (en) * 2005-11-10 2009-05-28 Kevin Ward Non-biofouling, universal redox electrode and measurement system
CA2635667A1 (en) * 2005-12-27 2007-07-05 Bayer Healthcare Llc Process of making electrodes for test sensors
US9757061B2 (en) 2006-01-17 2017-09-12 Dexcom, Inc. Low oxygen in vivo analyte sensor
EP1991110B1 (en) 2006-03-09 2018-11-07 DexCom, Inc. Systems and methods for processing analyte sensor data
US8163162B2 (en) * 2006-03-31 2012-04-24 Lifescan, Inc. Methods and apparatus for analyzing a sample in the presence of interferents
WO2007120381A2 (en) 2006-04-14 2007-10-25 Dexcom, Inc. Analyte sensor
US7909983B2 (en) * 2006-05-04 2011-03-22 Nipro Diagnostics, Inc. System and methods for automatically recognizing a control solution
BRPI0711337A2 (en) * 2006-05-08 2011-08-30 Bayer Healthcare Llc electrochemical test sensor with reduced sample volume
US7920907B2 (en) 2006-06-07 2011-04-05 Abbott Diabetes Care Inc. Analyte monitoring system and method
DE102006043718B4 (en) * 2006-09-18 2014-12-31 Alexander Adlassnig Determination of hydrogen peroxide concentrations
AU2007303239A1 (en) 2006-10-04 2008-04-10 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US7831287B2 (en) 2006-10-04 2010-11-09 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
ATE534901T1 (en) * 2006-10-05 2011-12-15 Lifescan Scotland Ltd ELECTROCHEMICAL METHODS AND DEVICES FOR USE IN MEASURING ANALYTE CONCENTRATIONS WITH CORRECTED HEMATOCRIT
US9046480B2 (en) 2006-10-05 2015-06-02 Lifescan Scotland Limited Method for determining hematocrit corrected analyte concentrations
ES2544353T3 (en) 2006-10-05 2015-08-28 Lifescan Scotland Ltd Methods to determine an analyte concentration using signal processing algorithms
WO2008040998A2 (en) 2006-10-05 2008-04-10 Lifescan Scotland Limited Systems and methods for determining a substantially hematocrit independent analyte concentration
GB0621352D0 (en) * 2006-10-27 2006-12-06 Suresensors Measurement device
TW200823456A (en) * 2006-11-24 2008-06-01 Health & Life Co Ltd Biosensor
KR100909620B1 (en) * 2007-04-20 2009-07-27 주식회사 영텍 Calibration device
US8236166B2 (en) * 2007-04-27 2012-08-07 Abbott Diabetes Care Inc. No calibration analyte sensors and methods
US8709709B2 (en) 2007-05-18 2014-04-29 Luoxis Diagnostics, Inc. Measurement and uses of oxidative status
US9063070B2 (en) * 2007-05-18 2015-06-23 Luoxis Diagnostics, Inc. Measurement and uses of oxidative status
EP2152350A4 (en) 2007-06-08 2013-03-27 Dexcom Inc Integrated medicament delivery device for use with continuous analyte sensor
TWI336782B (en) * 2007-07-05 2011-02-01 Apex Biotechnology Corp Composite modified electrode trip
WO2009015292A1 (en) * 2007-07-26 2009-01-29 Agamatrix, Inc. Electrochemical test strips
EP4098177A1 (en) 2007-10-09 2022-12-07 DexCom, Inc. Integrated insulin delivery system with continuous glucose sensor
US8417312B2 (en) 2007-10-25 2013-04-09 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
USD612279S1 (en) 2008-01-18 2010-03-23 Lifescan Scotland Limited User interface in an analyte meter
CA2715628A1 (en) 2008-02-21 2009-08-27 Dexcom, Inc. Systems and methods for processing, transmitting and displaying sensor data
IL197532A0 (en) 2008-03-21 2009-12-24 Lifescan Scotland Ltd Analyte testing method and system
US8396528B2 (en) 2008-03-25 2013-03-12 Dexcom, Inc. Analyte sensor
JP5032654B2 (en) * 2008-03-27 2012-09-26 パナソニック株式会社 Measuring device, measuring system, and concentration measuring method
US20090247856A1 (en) * 2008-03-28 2009-10-01 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US8583204B2 (en) 2008-03-28 2013-11-12 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US8682408B2 (en) 2008-03-28 2014-03-25 Dexcom, Inc. Polymer membranes for continuous analyte sensors
US11730407B2 (en) 2008-03-28 2023-08-22 Dexcom, Inc. Polymer membranes for continuous analyte sensors
WO2009126900A1 (en) 2008-04-11 2009-10-15 Pelikan Technologies, Inc. Method and apparatus for analyte detecting device
USD611151S1 (en) 2008-06-10 2010-03-02 Lifescan Scotland, Ltd. Test meter
USD611372S1 (en) 2008-09-19 2010-03-09 Lifescan Scotland Limited Analyte test meter
EP2326944B1 (en) 2008-09-19 2020-08-19 Dexcom, Inc. Particle-containing membrane and particulate electrode for analyte sensors
US8956308B2 (en) 2008-09-29 2015-02-17 Bayer Healthcare Llc Integrated-testing system
US8012428B2 (en) * 2008-10-30 2011-09-06 Lifescan Scotland, Ltd. Analytical test strip with minimal fill-error sample viewing window
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
KR100918027B1 (en) * 2009-02-19 2009-09-18 주식회사 올메디쿠스 Bio-sensor provided with code electrode, method for manufacturing the same, and method for taking sensor information from the same
EP2410910A4 (en) 2009-03-27 2014-10-15 Dexcom Inc Methods and systems for promoting glucose management
US20110048972A1 (en) * 2009-08-31 2011-03-03 Lifescan Scotland Limited Multi-analyte test strip with shared counter/reference electrode and inline electrode configuration
CN102498391B (en) * 2009-08-31 2014-03-19 松下电器产业株式会社 Sensor and concentration measurement method
KR101109857B1 (en) * 2009-09-29 2012-02-14 광운대학교 산학협력단 Electrochemical Biosensor Using Double Pulse Excitation
IL209760A (en) * 2009-12-11 2015-05-31 Lifescan Scotland Ltd Fill sufficiency method and system
GB201005357D0 (en) 2010-03-30 2010-05-12 Menai Medical Technologies Ltd Sampling plate
GB201005359D0 (en) 2010-03-30 2010-05-12 Menai Medical Technologies Ltd Sampling plate
US20120238841A1 (en) * 2010-04-15 2012-09-20 Mark Castle Sample capture in one step for test strips
US8965476B2 (en) 2010-04-16 2015-02-24 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
JP5925285B2 (en) * 2010-04-22 2016-05-25 アークレイ株式会社 Biosensor
JP5753720B2 (en) * 2010-04-22 2015-07-22 アークレイ株式会社 Biosensor
GB201007711D0 (en) * 2010-05-07 2010-06-23 Pa Consulting Services Devices and methods for testing analytes
US8940141B2 (en) * 2010-05-19 2015-01-27 Lifescan Scotland Limited Analytical test strip with an electrode having electrochemically active and inert areas of a predetermined size and distribution
US20110290668A1 (en) * 2010-05-27 2011-12-01 Lifescan Scotland Limited Analytical test strip with crossroads exposed electrode configuration
WO2012017306A2 (en) 2010-08-06 2012-02-09 Schlumberger Technology B.V. Electrochemical sensor
US20120048746A1 (en) * 2010-08-30 2012-03-01 Cilag Gmbh International Analyte test strip with electrically distinguishable divided electrode
CN103096793B (en) * 2010-09-13 2015-05-27 生命扫描苏格兰有限公司 Analyte measurement method and system with hematocrit compensation
CN103718039B (en) * 2010-12-31 2016-08-10 西拉格国际有限责任公司 The system and method measured for high accuracy analyte
JP5834319B2 (en) 2011-02-28 2015-12-16 アイトゥ バイオサイエンス インコーポレイテッドＡｙｔｕ ＢｉｏＳｃｉｅｎｃｅ，Ｉｎｃ． Apparatus for measuring redox potential
WO2012133633A1 (en) * 2011-03-29 2012-10-04 株式会社テクノメデイカ Disposable lysine sensor
WO2012142502A2 (en) 2011-04-15 2012-10-18 Dexcom Inc. Advanced analyte sensor calibration and error detection
TWI427291B (en) * 2011-07-06 2014-02-21 Bionime Corp Method for operating a measurement of a sample on an electrochemical test strip
US8936199B2 (en) 2012-04-13 2015-01-20 Blackberry Limited UICC apparatus and related methods
USD703208S1 (en) * 2012-04-13 2014-04-22 Blackberry Limited UICC apparatus
CA2869151C (en) 2012-04-19 2020-02-18 Luoxis Diagnostics, Inc. Multiple layer gel
USD701864S1 (en) * 2012-04-23 2014-04-01 Blackberry Limited UICC apparatus
JP2013242171A (en) * 2012-05-18 2013-12-05 Tanita Corp Concentration measuring apparatus
TWI513978B (en) 2012-06-08 2015-12-21 Hmd Biomedical Inc Test strip, detecting device and detection method
US20130341207A1 (en) * 2012-06-21 2013-12-26 Lifescan Scotland Limited Analytical test strip with capillary sample-receiving chambers separated by stop junctions
US9128038B2 (en) * 2012-06-21 2015-09-08 Lifescan Scotland Limited Analytical test strip with capillary sample-receiving chambers separated by a physical barrier island
US8877023B2 (en) * 2012-06-21 2014-11-04 Lifescan Scotland Limited Electrochemical-based analytical test strip with intersecting sample-receiving chambers
GB2505694B (en) * 2012-09-07 2017-03-22 Lifescan Scotland Ltd Electrochemical-based analytical test strip with bare interferent electrodes
CN104737014B (en) 2012-10-23 2018-03-27 艾图生物科学股份有限公司 Measure and use the method and system of the oxidation-reduction potential of biological sample
US9244036B2 (en) 2012-11-16 2016-01-26 Cilag Gmbh International System and method for determination of a concentration of at least one interfering substance and correction of glucose concentration based on the concentration of the interfering substance
TWI493186B (en) * 2013-02-08 2015-07-21 Hmd Biomedical Inc Test strip, detecting device and detection method
US8858884B2 (en) 2013-03-15 2014-10-14 American Sterilizer Company Coupled enzyme-based method for electronic monitoring of biological indicator
US9121050B2 (en) 2013-03-15 2015-09-01 American Sterilizer Company Non-enzyme based detection method for electronic monitoring of biological indicator
JP5813171B2 (en) 2013-05-02 2015-11-17 アークレイ株式会社 Analytical tool, manufacturing method thereof, and measuring device using the same
GB2514846B (en) * 2013-06-07 2015-09-30 Lifescan Scotland Ltd Electrochemical-based analytical test strip with a soluble electrochemically-active coating opposite a bare electrode
GB2518165B (en) * 2013-09-11 2016-04-27 Cilag Gmbh Int Electrochemical-based analytical test strip with ultra-thin discontinuous metal layer
US20150068893A1 (en) * 2013-09-12 2015-03-12 Joinsoon Medical Technology Co., Ltd. Biosensor test strip for biosensor test device
JP6404681B2 (en) * 2013-11-08 2018-10-10 アークレイ株式会社 Measuring apparatus and measuring method
US20150176049A1 (en) 2013-12-23 2015-06-25 Cilag Gmbh International Determining usability of analytical test strip
CN106574929B (en) 2014-07-25 2019-08-09 贝克顿·迪金森公司 Analyte testing item test and for its implement test-strips and kit
CN111848578B (en) 2014-08-22 2023-10-31 豪夫迈·罗氏有限公司 redox indicator
JP6639479B2 (en) 2014-08-25 2020-02-05 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ Interference-compensated two-electrode test strip
GB201419472D0 (en) 2014-10-31 2014-12-17 Inside Biometrics Ltd Method of using and electrochemical device
CA2972468A1 (en) * 2014-12-31 2016-07-07 Trividia Health, Inc. Glucose test strip with interference correction
US11828660B2 (en) * 2015-05-10 2023-11-28 Jp Laboratories, Inc. UV cured indicating devices
EP3220137B1 (en) 2016-03-14 2019-01-23 Roche Diabetes Care GmbH Method for detecting an interferent contribution in a biosensor
EP3559664B1 (en) * 2016-12-23 2020-12-09 Radiometer Medical ApS Multiple-use sensor assembly for body fluids
CA3065339A1 (en) * 2017-06-30 2019-01-03 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
US11331022B2 (en) 2017-10-24 2022-05-17 Dexcom, Inc. Pre-connected analyte sensors
US10330628B2 (en) 2017-11-21 2019-06-25 Uxn Co., Ltd. Glucose-sensing electrode and device with nanoporous layer
EP3724649A1 (en) * 2017-12-15 2020-10-21 UXN Co. Ltd. Colloid with a nanoporous structure and device and system for non-enzymatic glucose-sensing
CN109270145B (en) 2018-11-20 2021-09-17 三诺生物传感股份有限公司 Method for testing electrochemical test strip with double electrodes
CN110082418B (en) * 2019-05-27 2021-10-15 三诺生物传感股份有限公司 Uric acid electrochemical measurement method
CN112067604B (en) * 2019-08-01 2023-01-10 杭州博拓生物科技股份有限公司 Detection device
ES2915406B2 (en) * 2020-12-21 2024-03-14 Bioquochem S L METHOD FOR MEASURING A CONCENTRATION OF AN ANALYTICAL COMPOUND OR AN ENZYMATIC ACTIVITY IN A COMPLEX SAMPLE BY SELECTIVELY QUANTIFYING HYDROGEN PEROXIDE
US20230314340A1 (en) * 2022-03-29 2023-10-05 Medtronic, Inc. Noise reduction for sensor apparatus

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4431004A (en) * 1981-10-27 1984-02-14 Bessman Samuel P Implantable glucose sensor
US4655880A (en) * 1983-08-01 1987-04-07 Case Western Reserve University Apparatus and method for sensing species, substances and substrates using oxidase
WO1989002593A1 (en) * 1987-08-28 1989-03-23 Harman John N Iii Noise reduction technique for electrochemical cells
US5298146A (en) * 1991-11-08 1994-03-29 Bayer Aktiengesellschaft Device for the simultaneous detection of dissimilar gas components
US5830343A (en) * 1994-07-11 1998-11-03 Fraunhofer-Gesellschaft Zur Foerderung Der Angewandten Forschung E.V. Electrochemical analysis process

Family Cites Families (65)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US565062A (en) * 1896-08-04 Samuel l
US4233031A (en) * 1978-12-11 1980-11-11 Environmental Sciences Associates, Inc. Electrochemical testing system and method
JPS613048A (en) * 1984-06-18 1986-01-09 Matsushita Electric Works Ltd Measurement using biosensor
DE68924026T3 (en) * 1988-03-31 2008-01-10 Matsushita Electric Industrial Co., Ltd., Kadoma BIOSENSOR AND ITS MANUFACTURE.
FR2661548B1 (en) * 1990-04-30 1992-07-17 Telemecanique LOCKING INVERTER CONTACTOR APPARATUS.
JPH04240558A (en) * 1991-01-25 1992-08-27 Sumitomo Metal Ind Ltd Enzyme electrode
JP2960265B2 (en) * 1991-10-18 1999-10-06 松下電器産業株式会社 Biosensor and measurement method using the same
JP2658769B2 (en) * 1991-10-21 1997-09-30 松下電器産業株式会社 Biosensor
JP3135959B2 (en) * 1991-12-12 2001-02-19 アークレイ株式会社 Biosensor and separation and quantification method using the same
ZA938555B (en) * 1992-11-23 1994-08-02 Lilly Co Eli Technique to improve the performance of electrochemical sensors
US5592551A (en) * 1992-12-01 1997-01-07 Scientific-Atlanta, Inc. Method and apparatus for providing interactive electronic programming guide
US5582697A (en) * 1995-03-17 1996-12-10 Matsushita Electric Industrial Co., Ltd. Biosensor, and a method and a device for quantifying a substrate in a sample liquid using the same
US5650062A (en) * 1995-03-17 1997-07-22 Matsushita Electric Industrial Co., Ltd. Biosensor, and a method and a device for quantifying a substrate in a sample liquid using the same
JPH09129236A (en) * 1995-08-25 1997-05-16 Furukawa Battery Co Ltd:The Negative active material for lithium secondary battery and lithium secondary battery
US5628890A (en) 1995-09-27 1997-05-13 Medisense, Inc. Electrochemical sensor
US5650052A (en) * 1995-10-04 1997-07-22 Edelstein; Sergio Variable cell size collimator
US5653918A (en) * 1996-01-11 1997-08-05 E. I. Du Pont De Nemours And Company Flexible thick film conductor composition
US5708247A (en) * 1996-02-14 1998-01-13 Selfcare, Inc. Disposable glucose test strips, and methods and compositions for making same
DE19781229C2 (en) * 1996-06-17 2002-02-28 Mercury Diagnostics Inc Electrochemical test device and method for its production
KR100193716B1 (en) * 1996-10-16 1999-06-15 윤종용 Ink-jet printing method and apparatus using dielectrophoretic force by electric field density difference
JP3460183B2 (en) * 1996-12-24 2003-10-27 松下電器産業株式会社 Biosensor
US5943263A (en) * 1997-01-08 1999-08-24 Micron Technology, Inc. Apparatus and method for programming voltage protection in a non-volatile memory system
ATE227844T1 (en) * 1997-02-06 2002-11-15 Therasense Inc SMALL VOLUME SENSOR FOR IN-VITRO DETERMINATION
BR7700267U (en) * 1997-03-20 1998-11-03 Wahler Metalurgica Ltda Integrated thermostat
US6139718A (en) 1997-03-25 2000-10-31 Cygnus, Inc. Electrode with improved signal to noise ratio
US6046051A (en) 1997-06-27 2000-04-04 Hemosense, Inc. Method and device for measuring blood coagulation or lysis by viscosity changes
JP3859239B2 (en) * 1997-07-22 2006-12-20 アークレイ株式会社 Concentration measuring device, test piece for the concentration measuring device, biosensor system, and terminal forming method for the test piece
EP1009851A1 (en) 1997-09-05 2000-06-21 Abbott Laboratories Electrochemical sensor having equalized electrode areas
JP3267907B2 (en) * 1997-09-29 2002-03-25 松下電器産業株式会社 Biosensor and Substrate Quantification Method Using It
US6001239A (en) * 1998-09-30 1999-12-14 Mercury Diagnostics, Inc. Membrane based electrochemical test device and related methods
JP3267933B2 (en) * 1998-01-27 2002-03-25 松下電器産業株式会社 Substrate quantification method
US6340428B1 (en) * 1998-04-02 2002-01-22 Matsushita Electric Industrial Co., Inc. Device and method for determining the concentration of a substrate
GB2337122B (en) * 1998-05-08 2002-11-13 Medisense Inc Test strip
JP3267936B2 (en) * 1998-08-26 2002-03-25 松下電器産業株式会社 Biosensor
WO2000013099A1 (en) 1998-08-31 2000-03-09 Cubus Corporation Computer product for networking a document development system using message headers associated with message files
US6338790B1 (en) * 1998-10-08 2002-01-15 Therasense, Inc. Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
JP3462401B2 (en) * 1998-10-15 2003-11-05 日本電信電話株式会社 Electrochemical detector
JP5073129B2 (en) * 1999-03-31 2012-11-14 株式会社日本触媒 (Meth) acrylic acid purification method
US6258229B1 (en) 1999-06-02 2001-07-10 Handani Winarta Disposable sub-microliter volume sensor and method of making
US6287451B1 (en) * 1999-06-02 2001-09-11 Handani Winarta Disposable sensor and method of making
GB2351153B (en) * 1999-06-18 2003-03-26 Abbott Lab Electrochemical sensor for analysis of liquid samples
US6616819B1 (en) * 1999-11-04 2003-09-09 Therasense, Inc. Small volume in vitro analyte sensor and methods
EP2889611B1 (en) * 1999-11-15 2019-09-04 PHC Holdings Corporation Biosensor and measurement apparatus.
JP3982133B2 (en) * 2000-01-25 2007-09-26 松下電器産業株式会社 Measuring device using biosensor and biosensor and dedicated standard solution used therefor
GB0005564D0 (en) 2000-03-08 2000-05-03 Inverness Medical Ltd Measurjement of substances in liquid
US20020092612A1 (en) * 2000-03-28 2002-07-18 Davies Oliver William Hardwicke Rapid response glucose sensor
PT1269173E (en) 2000-03-28 2005-10-31 Diabetes Diagnostics Inc QUICK RESPONSE GLUCOSE SENSOR
JP2002055076A (en) * 2000-09-08 2002-02-20 Nec Corp Electrochemical sensor
GB0030929D0 (en) 2000-12-19 2001-01-31 Inverness Medical Ltd Analyte measurement
WO2002057768A1 (en) * 2001-01-17 2002-07-25 Arkray, Inc. Quantitative analyzing method and quantitative analyzer using sensor
US6572745B2 (en) * 2001-03-23 2003-06-03 Virotek, L.L.C. Electrochemical sensor and method thereof
US20060030028A1 (en) * 2001-06-14 2006-02-09 Takahiro Nakaminami Biosensor
DE10158420A1 (en) 2001-11-29 2003-06-12 Basf Ag Adhesive containing glycidyl (meth) acrylate
US6837976B2 (en) * 2002-04-19 2005-01-04 Nova Biomedical Corporation Disposable sensor with enhanced sample port inlet
DE10218828A1 (en) 2002-04-26 2003-11-06 Siemens Ag Mobile RF device with transmission power limitation, can be set to maximum transmission power via mobilephone menu with user personally selecting maximum acceptable radiative loading level
US20030143113A2 (en) * 2002-05-09 2003-07-31 Lifescan, Inc. Physiological sample collection devices and methods of using the same
KR100485671B1 (en) * 2002-09-30 2005-04-27 주식회사 인포피아 A measuring instrument for biosensor
ATE441106T1 (en) 2002-10-30 2009-09-15 Lifescan Scotland Ltd PRETREATMENT OF A SUBSTRATE IN A CONTINUOUS MANUFACTURING PROCESS FOR ELECTROCHEMICAL SENSORS
US20040120848A1 (en) * 2002-12-20 2004-06-24 Maria Teodorczyk Method for manufacturing a sterilized and calibrated biosensor-based medical device
US20040149578A1 (en) 2003-01-30 2004-08-05 Chun-Mu Huang Method for manufacturing electrochemical sensor and structure thereof
US7132041B2 (en) * 2003-02-11 2006-11-07 Bayer Healthcare Llc Methods of determining the concentration of an analyte in a fluid test sample
US7462265B2 (en) * 2003-06-06 2008-12-09 Lifescan, Inc. Reduced volume electrochemical sensor
EP1678489B1 (en) * 2003-10-31 2007-04-25 Lifescan Scotland Ltd Method of reducing the effect of direct interference current in an electrochemical test strip
US7655119B2 (en) * 2003-10-31 2010-02-02 Lifescan Scotland Limited Meter for use in an improved method of reducing interferences in an electrochemical sensor using two different applied potentials
US7875461B2 (en) * 2007-07-24 2011-01-25 Lifescan Scotland Limited Test strip and connector

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4431004A (en) * 1981-10-27 1984-02-14 Bessman Samuel P Implantable glucose sensor
US4655880A (en) * 1983-08-01 1987-04-07 Case Western Reserve University Apparatus and method for sensing species, substances and substrates using oxidase
WO1989002593A1 (en) * 1987-08-28 1989-03-23 Harman John N Iii Noise reduction technique for electrochemical cells
US5298146A (en) * 1991-11-08 1994-03-29 Bayer Aktiengesellschaft Device for the simultaneous detection of dissimilar gas components
US5830343A (en) * 1994-07-11 1998-11-03 Fraunhofer-Gesellschaft Zur Foerderung Der Angewandten Forschung E.V. Electrochemical analysis process

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8211292B2 (en) 2005-08-05 2012-07-03 Bayer Healthcare Llc Method for distinguishing electrochemical sensors
US8480868B2 (en) 2005-08-05 2013-07-09 Bayer Healthcare Llc Method for distinguishing electrochemical sensors
CN112294325A (en) * 2019-08-02 2021-02-02 华广生技股份有限公司 Miniature biosensor and method for reducing measurement interference
CN112294324A (en) * 2019-08-02 2021-02-02 华广生技股份有限公司 Method for reducing interference of miniature biosensor measurement
EP3771415A1 (en) * 2019-08-02 2021-02-03 Bionime Corporation Implantable micro-biosensor and method for manufacturing the same
EP3771410A1 (en) * 2019-08-02 2021-02-03 Bionime Corporation Micro biosensor and method for reducing measurement interference using the same
EP3771411A1 (en) * 2019-08-02 2021-02-03 Bionime Corporation Method for reducing measurement interference of micro biosensor
EP3771413A1 (en) * 2019-08-02 2021-02-03 Bionime Corporation Method for manufacturing implantable micro-biosensor
US11950902B2 (en) 2020-07-31 2024-04-09 Bionime Corporation Micro biosensor and method for reducing measurement interference using the same

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