Sensor for components of a liquid mixture

• US 4,545,382 A
• Filed: 10/22/1982
• Issued: 10/08/1985
• Est. Priority Date: 10/23/1981
• Status: Expired due to Term

• Current Assignee: Medisense Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Generics International Incorporated (Endo International PLC)
• Inventors: Plotkin, Elliot V., Higgins, Irving J., Hill, Hugh A. O.
• Primary Examiner(s): Cohen, Lee S.
• Application Number:
  US06/436,106
• Time in Patent Office: 1,082 Days
• Field of Search: 128/635, 204/403, 204/415
• US Class Current: 600/347
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: G01N 27/3271 Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001
• CPC Class Codes: Y10S 435/817 Enzyme or microbe electrode

Abstract

A sensor electrode to detect one or more components in a liquid mixture comprises an electrically conductive material having at least an an external surface, the combination of an enzyme catalytic for a reaction of the desired component, and a mediator compound which transfers electrons from the enzyme to the electrode when such catalytic activity takes place. It can be used as an in vivo glucose sensor either with a silver electrode coated with e.g. glucose oxidase and a polyviologen as the mediators, or with a particulate carbon electrode, glucose oxidase and chloranil or fluoranil as mediator. Another system is to use bacterial glucose dehydrogenase or glucose oxidase as the enzyme and/or ferrocene or a ferrocene derivative as the mediators compound to give electrodes with improved linearity, speed of response and insensitivity to oxygen.

Claims

1. A sensor electrode for use in a liquid mixture of components, said electrode being responsive to the presence of at least one selected component of said mixture capable of undergoing an enzyme-catalysed reaction, the electrode being composed of electrically conductive material and comprising, at least at an external surface thereof, the combination of an enzyme and a mediator comprising a ferrocene which transfer electrons between the enzyme and the conductive material of the electrode when the enzyme is catalytically active to provide a current representative of said activity.

2. A sensor electrode as claimed in claim 1 in which the enzyme catalyses a reaction of glucose whereby there is provided a glucose sensor.

3. A sensor electrode as claimed in claim 2 in which the enzyme is a glucose oxidase.

4. A sensor electrode as claimed in claim 2 in which the enzyme is a bacterial glucose dehydrogenase.

5. A sensor electrode as claimed in claim 4 in which the glucose dehydrogenase is that separated from Acinetobacter calcoaceticus.

6. A sensor electrode as claimed in any of claims 1 to 5 in which the mediator is chosen from ferrocene, 1,1'"'"'-ferrocenedicarboxylic acid, dimethyl ferrocene, and polyvinyl ferrocene.

7. A sensor electrode as claimed in any of claims 1 to 5 in which the electrode is made of a material chosen from silver, carbon particle paste and solid carbon.

8. A sensor electrode as claimed in claim 7 wherein said electrode comprises solid carbon, a layer of ferrocene at an external surface thereof, and an enzyme located upon said ferrocene layer.

9. A sensor electrode as claimed in claim 8 in which the ferrocene is deposited on the surface from a readily evaporatable organic solvent therefor.

10. A sensor electrode as claimed in claim 9 in which the ferrocene is bonded to the solid carbon by carbo-diimide cross-linking.

11. A sensor electrode as claimed in claim 8 in which the ferrocene is in polymeric form and produced at the surface by polymerisation of the corresponding monomer.

12. A sensor electrode as claimed in claim 8 having an outermost protective membrane permeable to water and glucose molecules, said membrane covering said enzyme located upon said ferrocene layer.

13. A sensor electrode as claimed in claim 12 in which the protective membrane is a layer of cellulose acetate deposited from a solution thereof.

14. A sensor electrode for use in a liquid mixture including glucose, to provide a current representative of the presence of glucose therein, the electrode consisting essentially of solid carbon, a layer of ferrocene-type compound at an external surface thereof as an electron-transferring mediator, and an enzyme which is glucose oxidase or bacterial glucose dehydrogenase located upon said mediator layer.

15. A sensor electrode as claimed in claim 14 in which the enzyme is a glucose oxidase immobilised on the mediator by DCC.

16. A sensor electrode as claimed in claim 14 in which the enzyme is a bacterial glucose dehydrogenase deposited on the mediator layer from an evaporatable solution.

17. A sensor electrode as claimed in claim 14 in which the enzyme is a bacterial glucose dehydrogenase held in a gelatine layer at the surface of the mediator layer.

18. A sensor suitable for implantation comprising a sensor electrode and means for implantation of said sensor electrode in a human subject, said sensor electrode being responsive to the presence in said subject of at least one selected component capable of undergoing an enzyme-catalyzed reaction, said electrode being composed of electrically conductive material and comprising, at least at an external surface thereof, the combination of an enzyme, and a mediator comprising a ferrocene which transfers electrons between the enzyme and the conductive material of the electrode when the enzyme is catalytically active to provide a current representative of said activity.

19. The sensor of claim 18 in which the implantation means is a needle-like probe carrying said sensor electrode thereon.