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EP0125137A2 Expired / Lapsed EP ⏱️ 0.0 years remaining

Measurement of enzyme-catalysed reactions

Assignee: Medisense Inc
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Filing: 1984-05-08
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Granted: —
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Expires: 2004-05-08
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Abstract

Abstract This invention related to equipment and methods for detecting the presence of, measuring the amount of, and/or monitoring the level of, one or more selected components in a liquid mixture, employing an electrode sensing system. We have discovered that a class of mediating compounds has extremely useful properties for mediating the transfer of charge between enzyme-catalysed reactions and electrode surfaces (15) in electrode sensing systems. Specifically, the specification discloses as electrode sensor mediators, organometallic compounds composed of at least two organic rings, each of which has at least two double bonds in a conjugated relationship; a metal atom is in electron-sharing contact with those rings. An enzyme capable of catalyzing a reaction at a rate representative of the selected compound concentration is in contact with an assay mixture, and the mediator compound transfers charge between the enzyme and the conductive surface of the electrode at a rate representative of the enzyme catalyzed reaction rate.

Inventors

  • 👤 Irving John Higgins
  • 👤 Hugh Allen Oliver Hill
  • 👤 Elliot Verne Plotkin

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-11-01 06:46
CPC Classifications
A; A61; A61B; A61B5/00; A61B5/145; A61B5/1468; A61B5/1486; A61B5/14865; A61B5/68; A61B5/6846; A61B5/6847; A61B5/6848; C; C12; C12Q; C12Q1/00; C12Q1/001; C12Q1/004; Y; Y10; Y10S; Y10S435/00; Y10S435/817

Claims Analysis

Total Claims: 35
Claim 1
Independent Claim 107 words
l.An electrode sensor system for sensing the presence of at least one selected component of a mixture of components said sensor system comprising:- at least two electrically conducting means insulated from each other, each of which is in electrical contact with said mixture via an electrically conductive surface, a mediator compound which transfers electrons between said enzyme and one said conductive surface when said enzyme is catalytically active, said mediator being an organometallic compound which comprises at least two organic rings, each of which is characterised by at least two double bonds that are conjugated and a metal atom in electron-sharing contact with each of said rings.
Claim 2
Dependent Claim 15 words
The system of claim 1 wherein said mediator is confined at said electrically conducting surface.
Claim 3
Dependent Claim 15 words
The system of claim 1 wherein said enzyme is confined at said electrically conducting surface.
Claim 4
Dependent Claim 16 words
The system of claim 1 wherein said selected component is a substrate for said enzyme-catalyzed reaction.
Claim 5
Dependent Claim 13 words
The system of claim 1 wherein said mediator compound is a ferrocene-type compound.
Claim 6
Dependent Claim 39 words
The system of claim 5 wherein said ferrocene-type compound is selected from the group consisting of ferrocene; chloroferrocene; methyl-trimethylaminoferrocene ; 1,1-dimethylferrocene; 1,1 -dicarboxyferrocene; carboxyferrocene; vinylferrocene; trimethylaminoferrocene; 1,1 dimethylferrocene; polyvinylferrocene; ferrocene monocarboxylic acid; hydroxyethylferrocene; acetoferrocene; and 1, 1 bishydroxymethyl ferrocene.
Claim 7
Dependent Claim 13 words
The system of claim 1 wherein said enzyme is a non-oxygen specific flavo-protein.
Claim 8
Dependent Claim 54 words
The system of claim 7 wherein said flavo-protein is selected from the group consisting of methanol oxidase, pyruvate oxidase (EC 1.2.3.3.), xanthine oxidase (EC 1.2.3.2.), sarcosine oxidase (EC 1.5.3.1), lipoamide dehydrogenase (EC 1.6.3.4.), glutathione reductase (EC 1.6.4.2.), carbonmonoxide oxido-reductase, glucose oxidase, glycollate oxidase (EC 1.1.3.1.) L-amino acid oxidase (EC 1.4.3.2.) and lactose oxidase .
Claim 9
Dependent Claim 11 words
The system of claim 1 wherein said enzyme is a quino-protein.
Claim 10
Dependent Claim 22 words
The system of claim 9 wherein said quino-protein is selected from the group consisting of glucose dehydrogenase alcohol dehydrogenase and methanol dehydrogenase.
Claim 11
Dependent Claim 11 words
The system of claim 1 wherein aid metal atom is iron.
Claim 12
Dependent Claim 11 words
The system of claim 1 wherein said metal iron is ruthenium.
Claim 13
Dependent Claim 12 words
The system of claim 1 wherein said mediator compound is a ruthocene.
Claim 14
Dependent Claim 10 words
The system of claim 1 wherein said metal is chromium.
Claim 15
Dependent Claim 12 words
The system of claim 14 wherein said mediator compound is dibenzene chromium.
Claim 16
Dependent Claim 23 words
A sensor as claimed in claim 1 in which the enzyme catalyses a reaction of glucose whereby there is provided a glucose sensor.
Claim 17
Dependent Claim 15 words
A sensor as claimed in claim 16 in which the enzyme is a glucose oxidase.
Claim 18
Dependent Claim 16 words
A sensor as claimed in claim 16 in which the enzyme is a bacterial glucose dehydrogenase.
Claim 19
Dependent Claim 18 words
A sensor as claimed in claim 18 in which the glucose dehydrogenase is that separated from Acinetobacter calcoaceticus.
Claim 20
Dependent Claim 25 words
A sensor as claimed in claim 1 in which the electrode is made of a material chosen from silver, carbon particle paste and solid carbon.
Claim 21
Dependent Claim 66 words
The sensor of claim 1 for use in a liquid mixture including glucose, to be responsive to the presence of glucose, the one said conductive means comprising an electrode composed of carbon, a layer of a ferrocene-type compound at an external surface thereof as an electron-transferring mediator compound, and an enzyme chosen fron glucose oxidase and bacterial glucose dehydrogenase located upon the layer of mediator compound.
Claim 22
Dependent Claim 26 words
A sensor as claimed in claimed in claim 21 in which the ferrocene-type compound is deposited on the surface from a readily evaporable organic solvent therefor.
Claim 23
Dependent Claim 27 words
A sensor as claimed in claim 21 in which the ferrocene-type compound is in polymeric form and produced at the surface by polymerisation of the corresponding monomer.
Claim 24
Dependent Claim 21 words
A sensor as claimed in claim 22 in which the ferrocene-type compound is bonded to the carbon electrode by carbo-diimide cross-linking.
Claim 25
Dependent Claim 21 words
A sensor as claimed in claim 21 in which the enzyme is a glucose oxidase immobilised on the mediator by DCC.
Claim 26
Dependent Claim 25 words
A sensor as claimed in claim 21 in which the enzyme is a bacterial glucose dehydrogenase deposited on the mediator layer from an evaporatable solution.
Claim 27
Dependent Claim 28 words
A sensor as claimed in claim 21 in which the enzyme is a bacterial glucose dehydrogenase held in a gelatine layer at the surface of the mediator layer.
Claim 28
Dependent Claim 18 words
A sensor as claimed in claim 21 having an outermost protective membrane permeable to water and glucose molecules.
Claim 29
Dependent Claim 22 words
The sensor system of claim 28 in which the protective membrane is a layer of cellulose acetate deposited from a solution thereof.
Claim 30
Dependent Claim 17 words
' The sensor system of claim 1 with implantation means suitable for implantation in a human subject.
Claim 31
Dependent Claim 19 words
A sensor system of claim 1 wherein said mediator compound transfers electrons from said enzyme to said conductive surface.
Claim 32
Dependent Claim 13 words
The system of claim 1 in which the enzyme is a haem-containing enzyme.
Claim 33
Dependent Claim 26 words
The system of claim 32 in which the haem-containing enzyme is chosen from the group consisting of lactate dehydrogenase yeast cytochrome C peroxidase and horseradish peroxidase.
Claim 34
Dependent Claim 12 words
The system of claim 1 in which the enzyme is a cuproprotein.
Claim 35
Dependent Claim 12 words
The system of claim 34 in which the cuproprotein is galactose oxidase.

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