Electrode system for measuring an analyte concentration under in-vivo conditions

• US 9,394,563 B2
• Filed: 03/08/2011
• Issued: 07/19/2016
• Est. Priority Date: 09/11/2008
• Status: Active Grant

• Current Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Original Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Inventors: Quarder, Ortrud, Staib, Arnulf, Mischler, Reinhold, Rieger, Ewald, Gillen, Ralph, Kamecke, Ulrike
• Primary Examiner(s): Kahelin, Michael
• Assistant Examiner(s): Alter, Mitchell E
• Application Number:
  US13/042,773
• Publication Number:
  US 20110196216A1
• Time in Patent Office: 1,960 Days
• Field of Search: 600345-372
• US Class Current: 1/1
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/7207 of noise induced by motion artifacts
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

An electrode system for measuring the concentration of an analyte under in-vivo conditions comprises a counter-electrode having an electrical conductor, a working electrode having an electrical conductor on which an enzyme layer containing immobilized enzyme molecules for catalytic conversion of the analyte is arranged, and a diffusion barrier that slows the diffusion of the analyte from body fluid surrounding the electrode system to enzyme molecules. The enzyme layer is in the form of multiple fields that are arranged on the conductor of the working electrode at a distance from each other.

Claims

1. Electrode system for measuring a concentration of an analyte under in-vivo conditions, the system comprising:

a substrate;

a counter-electrode having an electrical conductor arranged on the substrate;

a working electrode having an electrical conductor arranged on the substrate on which an enzyme layer containing immobilized enzyme molecules for catalytic conversion of the analyte is arranged, wherein the enzyme layer is in the form of multiple fields arranged in a row or in a series at a pre-determined distance from one another on the electrical conductor of the working electrode so that the multiple fields are separate from each other; and

a diffusion barrier that slows diffusion of the analyte from body fluid surrounding the electrode system to the enzyme molecules.

2. Electrode system according to claim 1, wherein between the fields of the enzyme layer, the electrical conductor of the working electrode is covered by an insulation layer.

3. Electrode system according to claim 1, wherein at least two of the fields of the enzyme layer are at least 5 mm distant from each other.

4. Electrode system according to claim 1, wherein a distance of at least 0.3 mm exists between neighboring fields of the enzyme layer.

5. Electrode system according to claim 1, wherein the fields of the enzyme layer each extend less than 2 mm in two directions that are perpendicular to each other.

6. Electrode system according to claim 1, wherein the diffusion barrier is in the form of a layer covering the enzyme layer.

7. Electrode system according to claim 6, wherein the diffusion barrier is made of a mixture of at least two different acrylates.

8. Electrode system according to claim 7, wherein at least one of the acrylates is a copolymer.

9. Electrode system according to claim 1, wherein the enzyme interacts with a catalytic redox mediator that is contained in the enzyme layer and reduces or prevents an oxygen dependence of the catalytic conversion of the analyte.

10. Electrode system according to claim 9, wherein the catalytic redox mediator converts hydrogen peroxide.

11. Electrode system according to claim 9, wherein the catalytic redox mediator effects a direct electron transfer.

12. Electrode system according to claim 1, wherein the enzyme layer is covered by a spacer.

13. Electrode system according to claim 12, wherein the spacer covers the working electrode and the counter-electrode in the form of a continuous layer.

14. Electrode system according to claim 1, wherein the electrical conductor of the working electrode narrows between the enzyme layer fields and the electrical conductor of the counter-electrode has a contour that follows the course of the electrical conductor of the working electrode.

18. Electrode system according to claim 1, wherein at least two of the fields of the enzyme layer are at least 3 mm distant from each other.

19. Electrode system according to claim 1, wherein the enzyme layer is applied non-continuously on the working electrode surface so that the multiple fields of the enzyme layer are separated from one another with an electrical insulating layer on the electrical conductor of the working electrode.

21. Electrode system according to claim 1, wherein the working electrode has at least 5 fields of the enzyme layer.

15. Sensor comprising:

an electrode system comprising;

a counter-electrode having an electrical conductor;

a working electrode having an electrical conductor on which an enzyme layer containing immobilized enzyme molecules for catalytic conversion of the analyte is arranged, wherein the enzyme layer is in the form of multiple fields that are arranged in a row or in a series at a pre-determined distance from each other on the electrical conductor of the working electrode so that the multiple fields are separate from each other, and wherein at least two non-neighboring fields of the enzyme layer are at least 3 mm distant from each other; and

a diffusion barrier that slows diffusion of the analyte from body fluid surrounding the electrode system to the enzyme molecules;

a potentiostat connected to the electrode system; and

an amplifier for amplification of measuring signals of the electrode system.

16. Sensor according to claim 15, wherein the electrodes of the electrode system are arranged on a substrate that carries the potentiostat or are attached on a circuit board that carries the potentiostat.

17. Sensor according to claim 15, wherein the electrical conductor of the working electrode narrows between the enzyme layer fields and the electrical conductor of the counter-electrode has a contour that follows the course of the electrical conductor of the working electrode.

20. Sensor according to claim 15, wherein the enzyme layer is applied non-continuously on the working electrode surface so that the multiple fields of the enzyme layer are separated from one another with an electrical insulating layer on the electrical conductor of the working electrode.

22. Sensor according to claim 15, wherein the pre-determined distance between neighboring fields of the enzyme layer is at least 0.3 mm.

23. Sensor according to claim 15, wherein the working electrode has at least 5 fields of the enzyme layer.

24. Electrode system for measuring a concentration of an analyte under in-vivo conditions, the system comprising:

a substrate;

a counter-electrode having an electrical conductor arranged on the substrate;

a working electrode having an electrical conductor arranged on the substrate;

an enzyme layer containing immobilized enzyme molecules for catalytic conversion of the analyte, wherein the enzyme layer is in the form of multiple fields that are arranged in a row or in a series at a pre-determined distance from each other on the electrical conductor of the working electrode so that the multiple fields are separate from each other, and wherein the enzyme interacts with a catalytic redox mediator that is contained in the enzyme layer and reduces or prevents an oxygen dependence of the catalytic conversion of the analyte, and

a diffusion barrier that slows diffusion of the analyte from body fluid surrounding the electrode system to the enzyme molecules.

25. Electrode system according to claim 24, wherein at least two non-neighboring fields of the enzyme layer are at least 3 mm distant from each other.

26. Electrode system according to claim 24, wherein the pre-determined distance between neighboring fields of the enzyme layer is at least 0.3 mm.

27. Electrode system according to claim 24, wherein the working electrode has at least 5 fields of the enzyme layer.