AMPEROMETRIC SENSOR AND METHOD FOR ITS MANUFACTURING

• US 20090099433A1
• Filed: 12/19/2008
• Published: 04/16/2009
• Est. Priority Date: 06/19/2006
• Status: Active Grant

• Current Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Original Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Inventors: Staib, Arnulf, Hajnsek, Martin, Jernigan, Walter, Mischler, Reinhold, Buck, Harvey
• Granted Patent: US 8,527,024 B2
• Time in Patent Office: Days
• US Class Current: 600/345
• 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: C12Q 1/001 Enzyme electrodes

Abstract

An in vivo amperometric sensor is provided for measuring the concentration of an analyte in a body fluid. The sensor comprises a counter electrode and a working electrode, and the working electrode comprises a sensing layer which is generally water permeable and arranged on a support member adjacent to a contact pad. The sensing layer comprises an immobilized enzyme capable of acting catalytically in the presence of the analyte to cause an electrical signal. The sensing layer has an upper surface facing the body fluid and a lower surface facing away from the body fluid, and the immobilized enzyme is distributed within the sensing layer in such a way that the enzyme concentration in the middle between the upper and lower surfaces is at least as high as on the upper surface of the sensing layer.

Claims

1. An amperometric sensor configured for implantation into the living body of a human or animal to measure the concentration of an analyte in a body fluid, said sensor comprising a counter electrode and a working electrode, said working electrode comprising a sensing layer which is generally permeable for water and arranged on a support member adjacent to a contact pad, said sensing layer comprising an immobilized enzyme capable of acting catalytically in the presence of the analyte to cause an electrical signal, the sensing layer having an upper surface facing the body fluid and a lower surface facing away from the body fluid, wherein the immobilized enzyme is distributed in the sensing layer in such a way that the enzyme concentration in the middle between the upper and lower surfaces is at least as high as on the upper surface of the sensing layer.

2. The sensor according to claim 1, wherein the sensing layer has an effective diffusion coefficient D_eff, which characterizes the diffusion of the analyte in the sensing layer and is about 10-times to about 1000-times lower than the diffusion coefficient D of the analyte in water.

3. The sensor according to claim 1, wherein the enzyme comprises a cross-linked enzyme.

4. The sensor according to claim 3, wherein the cross-linked enzyme forms a complex with a hydrophilic partner, and wherein the cross-linked enzyme is an enzyme in which the enzyme molecules form a cross-linked complex with a hydrophilic partner.

5. The sensor according to claim 3, wherein the cross-linked enzyme has an average chain length of about three to about enzyme molecules.

6. The sensor according to claim 5, wherein the average chain length is about 4 to about 8 enzyme molecules.

7. The sensor according to claim 1, wherein the sensing layer is covered by a diffusion barrier which hinders diffusion of analyte molecules to such an extent that after implantation into the living body of a human or an animal the analyte concentration at the upper surface of the sensing layer is at most about ten times lower than in the body fluid surrounding the implanted sensor and wherein the diffusion barrier comprises an electrically conductive enzyme-free layer comprising carbon particles and a polymeric binder.

8. The sensor according to claim 7, wherein after implantation into the living body of a human or an animal the analyte concentration at the upper surface of the sensing layer is at most about five times lower than in the body fluid surrounding the implanted sensor.

9. The sensor according to claim 1, wherein the sensing layer contains porous particles.

10. The sensor according to claim 9, wherein the porous particles comprise one or both of silica and carbon nanotubes.

11. The sensor according to claim 9, wherein the porous particles increase both the porosity and the electrical conductivity of the sensing layer.

12. The sensor according to claim 9, wherein the porous particles measure on average between at least about 1 μ

m and about 5 μ

m.

13. The sensor according to claim 1, wherein the sensing layer is adapted and arranged in such a way that in operation after implantation the analyte concentration in the sensing layer is highest at the upper surface, decreases with increasing distance from the upper surface, and is zero at the lower surface which is the furthest point from the analyte-containing body fluid.

14. The sensor according to claim 1, wherein the contact pad of the working electrode is an electrically conductive film.

15. The sensor according to claim 14, wherein the electrically conductive film comprises a metallic film or a polymer film.

16. The sensor according to claim 1, wherein the working electrode is arranged on a support member made of a plastic material.

17. The sensor according to claim 1, wherein the sensing layer has a thickness of between at least about 5 μ

m and about 100 μ

m.

18. The sensor according to claim 1, wherein the sensing layer has a thickness of between at least about 20 μ

m and about 70 μ

m.

19. The sensor according to claim 1, wherein the sensing layer comprises carbon particles and a polymeric binder.

20. The sensor according to claim 1, wherein the sensing layer is covered by a diffusion barrier which hinders diffusion of analyte molecules to such an extent that after implantation into the living body of a human or an animal the analyte concentration at the upper surface of the sensing layer is at most about ten times lower than in the body fluid surrounding the implanted sensor.

21. The sensor according to claim 20, wherein the sensing layer is covered by a diffusion barrier which hinders diffusion of analyte molecules to such an extent that after implantation into the living body of a human or an animal the analyte concentration at the upper surface of the sensing layer is at most about five times lower than in the body fluid surrounding the implanted sensor.

22. The sensor according to claim 20, wherein the diffusion barrier comprises a dialysis layer.

23. The sensor according to claim 20, wherein the diffusion barrier comprises a polymer layer made of a polymer having a zwitterionic structure.

24. The sensor according to claim 1, wherein the sensing layer includes lateral surfaces which are generally impervious for the body fluid.

25. The sensor according to claim 1, wherein the sensing layer is electrically conductive.

26. The sensor according to claim 25, wherein the sensing layer has an electrical conductivity of at least about 1 Ω

<sup>−

1</sup> cm<sup>−

1</sup>.

27. The sensor according to claim 1, wherein the enzyme comprises an oxidase.

28. The sensor according to claim 1, wherein the enzyme comprises a dehydrogenase.

29. The sensor according to claim 1, wherein the enzyme is distributed generally equally throughout the sensing layer.

30. The sensor according to claim 29, wherein the sensing layer has an enzyme loading parameter α

which is between about 10 to about 200 times smaller than the effective diffusion coefficient D_eff.

31. The sensor according to claim 1, wherein said sensing layer is arranged on the contact pad and the sensing layer has a lower surface facing the contact pad and an upper surface facing away from the contact pad.

32. A method for manufacturing an amperometric sensor configured for implantation into the living body of a human or animal to measure the concentration of an analyte in a body fluid, said method comprising the following steps:

mixing carbon particles, enzyme and a polymeric binder to create a paste;

applying said paste adjacent to a contact pad on a support member of said sensor, hardening that paste into a porous sensing layer.