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US5972199A Expired / Lapsed US ⏱️ 0.0 years remaining

Electrochemical analyte sensors using thermostable peroxidase

Assignee: Abbott Diabetes Care Inc
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Filing: 1997-02-11
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Granted: 1999-10-26
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Expires: 2017-02-11
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Abstract

Abstract A sensor for the detection and measurement of an analyte in a biofluid. The sensor includes two enzymes. One type of sensor measures the concentration of hydrogen peroxide using a thermostable peroxidase enzyme that is immobilized in a redox hydrogel to form a sensing layer on a working electrode. This sensor also includes a hydrogen peroxide-generating second enzyme which is insulated from the redox hydrogel and electrode. This second enzyme generates hydrogen peroxide in response to the presence of an analyte or analyte-generated compound. The second enzyme may be insulated from the electrode by placement of an electrically insulating layer between the sensing layer and the second enzyme layer.

Inventors

  • 👤 Adam Heller
  • 👤 Mark S. Vreeke

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-23 13:28
CPC Classifications
C; C12; C12Q; C12Q1/00; C12Q1/68; C12Q1/6813; C12Q1/6816; C12Q1/6825; C12Q1/001; C12Q1/005; Y; Y10; Y10S; Y10S435/00; Y10S435/817

Claims Analysis

Total Claims: 34
Claim 1
Independent Claim 93 words
An electrochemical sensor, comprising: (a) an electrode; (b) a hydrogen peroxide sensing layer on the electrode, comprising a thermostable peroxidase and non-leachable redox centers for transferring electrons between the electrode and the peroxidase; and (c) a second enzyme capable of catalyzing the production of hydrogen peroxide in the presence of an analyte, the second enzyme being disposed on the electrode proximate the sensing layer but electrically insulated from the sensing layer; wherein the sensor is capable of operation at 37° C. with less than 2% loss of sensitivity per hour of continuous operation.
Claim 2
Dependent Claim 93 words
An electrochemical sensor, comprising: (a) an electrode; (b) a hydrogen peroxide sensing layer on the electrode, comprising a thermostable peroxidase and non-leachable redox centers for transferring electrons between the electrode and the peroxidase; and (c) a second enzyme capable of catalyzing the production of hydrogen peroxide in the presence of an analyte, the second enzyme being disposed on the electrode proximate the sensing layer but electrically insulated from the sensing layer; wherein the sensor is capable of operation at 37° C. with less than 2% loss of sensitivity per hour of continuous operation.
Claim 3
Dependent Claim 12 words
The sensor of claim 1, wherein the thermostable peroxidase is soybean peroxidase.
Claim 4
Dependent Claim 15 words
The sensor of claim 1, wherein the non-leachable redox centers are bound to a polymer.
Claim 5
Dependent Claim 28 words
The sensor of claim 3, wherein the polymer is crosslinked and swells in contact with an aqueous solution the polymer's weight or volume increasing by at least 20%.
Claim 6
Dependent Claim 14 words
The sensor of claim 1, wherein the non-leachable redox centers comprise an osmium cation.
Claim 7
Dependent Claim 15 words
The sensor of claim 5, wherein the osmium cations are coordinatively bound to a polymer.
Claim 8
Dependent Claim 21 words
The sensor of claim 1, wherein the sensor further comprises a biocompatible layer disposed over the sensing layer and the electrode.
Claim 9
Dependent Claim 23 words
The sensor of claim 1, wherein the second enzyme is insulated from the sensing layer by the intrinsic protein structure of the enzyme.
Claim 10
Dependent Claim 22 words
The sensor of claim 1, wherein the second enzyme is insulated from the sensing layer by a hydrogen peroxide-permeable membrane or polymer.
Claim 11
Dependent Claim 88 words
An electrochemical analyte sensor comprising: (a) an electrode; (b) a first layer placed on the electrode and comprising a thermostable peroxidase immobilized on the electrode with a redox polymer; (c) a second layer placed on the first layer and comprising a film of cellulose acetate; (d) a third layer placed on the second layer and comprising an oxidase which catalyzes the production of hydrogen peroxide in the presence of an analyte; and (e) a fourth layer placed on the third layer and comprising a film of cellulose acetate.
Claim 12
Dependent Claim 88 words
An electrochemical analyte sensor comprising: (a) an electrode; (b) a first layer placed on the electrode and comprising a thermostable peroxidase immobilized on the electrode with a redox polymer; (c) a second layer placed on the first layer and comprising a film of cellulose acetate; (d) a third layer placed on the second layer and comprising an oxidase which catalyzes the production of hydrogen peroxide in the presence of an analyte; and (e) a fourth layer placed on the third layer and comprising a film of cellulose acetate.
Claim 13
Dependent Claim 49 words
An electrochemical hydrogen peroxide sensor comprising: (a) a non-corroding electrode; and (b) a thermostable peroxidase immobilized on and electrically connected to the non-corroding electrode; the sensor having no leachable components, and capable of operation at 37° C. with less than 2% loss of sensitivity per hour of continuous operation.
Claim 14
Dependent Claim 49 words
An electrochemical hydrogen peroxide sensor comprising: (a) a non-corroding electrode; and (b) a thermostable peroxidase immobilized on and electrically connected to the non-corroding electrode; the sensor having no leachable components, and capable of operation at 37° C. with less than 2% loss of sensitivity per hour of continuous operation.
Claim 15
Dependent Claim 12 words
The sensor of claim 11, wherein the thermostable peroxidase is soybean peroxidase.
Claim 16
Dependent Claim 25 words
The sensor of claim 11, further comprising non-leachable redox centers disposed on the electrode to electrically connect the thermostable peroxidase connected to the non-corroding electrode.
Claim 17
Dependent Claim 15 words
The sensor of claim 13, wherein the non-leachable redox centers are bound to a polymer.
Claim 18
Dependent Claim 14 words
The sensor of claim 13, wherein the non-leachable redox centers comprise an osmium cation.
Claim 19
Dependent Claim 15 words
The sensor of claim 15, wherein the osmium cations are coordinatively bound to a polymer.
Claim 20
Dependent Claim 18 words
The sensor of claim 11, further comprising a biocompatible layer disposed over the thermostable peroxidase said the electrode.
Claim 21
Dependent Claim 24 words
The sensor of claim 11, further comprising a second enzyme capable of catalyzing the production of hydrogen peroxide in the presence of an analyte.
Claim 22
Dependent Claim 20 words
The sensor of claim 18, wherein the second enzyme is disposed on the electrode but electrically insulated from the electrode.
Claim 23
Dependent Claim 22 words
The sensor of claim 19, wherein the second enzyme is insulated from the electrode by the intrinsic protein structure of the enzyme.
Claim 24
Dependent Claim 21 words
The sensor of claim 19, wherein the second enzyme is insulated from the electrode by a hydrogen peroxide-permeable membrane or polymer.
Claim 25
Dependent Claim 27 words
The sensor of claim 11, wherein the sensor is capable of operation at 50° C. with less than 5% loss of sensitivity per hour of continuous operation.
Claim 26
Dependent Claim 27 words
The sensor of claim 11, wherein the sensor is capable of operation at 50° C. with less than 2% loss of sensitivity per hour of continuous operation.
Claim 27
Dependent Claim 14 words
The sensor of claim 11, wherein the sensor is adapted for in vivo use.
Claim 28
Dependent Claim 24 words
The sensor of claim wherein the sensor is capable of operation at 37° C. for five days with less than 10% drop of sensitivity.
Claim 29
Dependent Claim 33 words
The sensor of claim 11, wherein the sensor is capable of operation at 37° C. with less than 2% loss of sensitivity per hour of continuous operation with intermittent measurements of analyte concentration.
Claim 30
Dependent Claim 13 words
The sensor of claim 11, wherein the sensor is adapted for subcutaneous implantation.
Claim 31
Independent Claim 89 words
A method for the electrochemical analysis of hydrogen peroxide, th method comprising the steps of: (a) generating an electrical signal at a non-corroding electrode of an electrochemical sensor in the presence of hydrogen peroxide, the electrochemical sensor comprising a thermostable peroxidase coimmobilized with a non-leachable redox compound on the non-corroding electrode, the electrochemical sensor being capable of operation at 37° C. with less than 2% less of sensitivity per hour of continuous operation; and (b) correlating the generated electrical signal with the presence of hydrogen peroxide in the sample.
Claim 32
Independent Claim 89 words
A method for the electrochemical analysis of hydrogen peroxide, th method comprising the steps of: (a) generating an electrical signal at a non-corroding electrode of an electrochemical sensor in the presence of hydrogen peroxide, the electrochemical sensor comprising a thermostable peroxidase coimmobilized with a non-leachable redox compound on the non-corroding electrode, the electrochemical sensor being capable of operation at 37° C. with less than 2% less of sensitivity per hour of continuous operation; and (b) correlating the generated electrical signal with the presence of hydrogen peroxide in the sample.
Claim 33
Independent Claim 122 words
A method for continuous measurement of an analyte, comprising the steps of: (a) placing a sensor on or in a body fluid or tissue, the sensor comprising a thermostable peroxidase coimmobilized with a non-leachable redox compound onto a non-corroding electrode and a second enzyme immobilized on the electrode, the thermostable peroxidase being electrically connected to the non-corroding electrode, the second enzyme catalyzing a reaction which generates hydrogen peroxide in the presence of a specified analyte, the sensor being capable of operation at temperatures of 37° C. or higher with less than 2% loss of sensitivity per hour of continuous operation; and (b) correlating an electrical signal generated by the electrode with an amount of analyte present in the body fluid or tissue.
Claim 34
Independent Claim 122 words
A method for continuous measurement of an analyte, comprising the steps of: (a) placing a sensor on or in a body fluid or tissue, the sensor comprising a thermostable peroxidase coimmobilized with a non-leachable redox compound onto a non-corroding electrode and a second enzyme immobilized on the electrode, the thermostable peroxidase being electrically connected to the non-corroding electrode, the second enzyme catalyzing a reaction which generates hydrogen peroxide in the presence of a specified analyte, the sensor being capable of operation at temperatures of 37° C. or higher with less than 2% loss of sensitivity per hour of continuous operation; and (b) correlating an electrical signal generated by the electrode with an amount of analyte present in the body fluid or tissue.

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Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 2002-10-25 2003-04-26 2003-10-26 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 2006-10-25 2007-04-26 2007-10-26 $3760.00 Window Closed / Lapsed
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