Electrochemical cell sensor for continuous short-term use in tissues and blood

• US 4,671,288 A
• Filed: 06/13/1985
• Issued: 06/09/1987
• Est. Priority Date: 06/13/1985
• Status: Expired due to Term

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Gough, David A.
• Primary Examiner(s): Cohen, Lee S.
• Application Number:
  US06/744,249
• Time in Patent Office: 726 Days
• Field of Search: 128/635, 204/403, 204/415
• US Class Current: 600/347
• 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 1/005 involving specific analytes or enzymes including groups of enzymes, e.g. oxydases; C12Q1/004 takes precedence
• CPC Class Codes: Y10S 977/905 Specially adapted for travel through blood circulatory system

Abstract

An electrochemical cell sensor for monitoring oxidizable enzyme substrates in biological fluids situated in a housing and suitable for implantation in the body, including at least one oxygen or hydrogen peroxide sensing electrode containing a suitable oxidase enzyme, a reference electrode, and a counter electrode all in communication with biological fluids through one or more openings in the walls of the housing.

Claims

1. An electrochemical cell sensor capable of being implanted into an animal body comprising:

a housing with an opening or openings in the wall of said housing;

said housing comprising a hollow needle composed of platinum or stainless steel, and said housing and said opening or openings covered with a layer of porous biocompatible material;

electrode means situated in said housing and in fluid communication via said opening or openings with fluids present in said animal body and responsive to enzyme substrates or products present in said fluid; and

a means for relating said response of said electrode means to the concentration of said enzyme substrates or products present in said fluids.

2. An electrochemical cell sensor as defined in claim 1 wherein said electrode means is comprised of four (4) electrodes:

an enzyme substrate or product dependent sensing electrode composed of a noble metal and in communication with an oxidase enzyme,

an enzyme substrate independent oxygen-sensing electrode composed of a nobel metal,

a reference electrode composed of silver/silver chloride, and

a common counter electrode, said common counter electrode being said housing.

3. An electrochemical cell sensor as defined in claim 2 wherein said 4 electrodes are insulated.

4. An electrochemical cell sensor as defined in claim 3 wherein said oxidase enzyme is drawn from the group consisting of glucose oxidase, lactate oxidase, uricase, or alcohol oxidase.

5. An electrochemical cell sensor as defined in claim 4 wherein said enzyme substrates are drawn from the group consisting of glucose, lactate, uric acid, ethanol, or oxygen.

6. An electrochemical cell sensor as defined in claim 5 wherein said means of relating said response of said electrode means to the concentration of said enzyme substrates or products in said fluids is by an apparatus that measures the adjusted current output differential of said electrode means.

7. An electrochemical cell sensor as defined in claim 6 wherein said means for relating said response of said electrode means to the concentration of said enzyme substrates or products in said fluids is by an apparatus that measures the adjusted current of the substrate or product sensing electrode and indicates said concentration of said enzyme substrates or products when the concentration of oxygen is sufficiently high as indicated by said enzyme substrate independent oxygen sensing electrode.

8. An electrochemical cell sensor capable of being implanted in an animal body comprising an electrically conductive hollow needle housing with one or more openings in the walls of said electrically conductive hollow needle housing;

an electrode means situated in said housing and in fluid communication via said opening or openings with fluids present in said animal body and responsive to enzyme substrates or products in said fluids, said electrode means comprising four (4) electrodes,

an enzyme substrate or product dependent sensing electrode, composed of a noble metal and in communication with an oxidase enzyme, an enzyme substrate independent oxygen-sensing electrode composed of a noble metal, a reference electrode composed of silver/silver chloride and a common counter electrode being said hollow needle housing; and

a

means for differentially regulating the accessibility of said enzyme substrates or products to said electrode means, and a means for relating said response of said electrode means to the concentration of said said enzyme substrates or products present in said fluids.

9. An electrochemical cell sensor as defined in claim 8 wherein said 4 electrodes are insulated.

10. An electrochemical cell sensor as defined in claim 9 wherein said oxidase enzyme is drawn from the group consisting of glucose oxidase, lactate oxidase, uricase, and alcohol oxidase.

11. An electrochemical cell sensor as defined in claim 10 wherein said enzyme substrates are drawn from the group consisting of glucose, lactate, uric acid, ethanol, or oxygen.

12. An electrochemical cell sensor as defined in claim 11 wherein said means for differentially regulating the accessibility of said enzyme substrates or products comprises material with enzyme substrate selective diffusion properties situated over said opening or openings in said walls of said electrochemical cell sensor hollow needle housing.

13. An electrochemical cell sensor as defined in claim 12 wherein said material with enzyme substrate selective diffusion properties is less restrictive of the diffusion of oxygen than of other enzyme substrates.

14. An electrochemical cell sensor as defined in claim 13 wherein said means of relating said response of said electrode means to the concentration of said enzyme substrates or products is by an apparatus that measures the adjusted current output differential of said electrode means.

15. An electrochemical cell sensor as defined in claim 14 wherein said means of relating said response of said electrode means to the concentration of said enzyme substrates or products in said fluids is by an apparatus that measures the adjusted current of the product or substrate sensing electrode and indicates said concentration of said enzyme substrates or products when the concentration of oxygen is sufficiently high as indicated by said enzyme substrate independent oxygen sensing electrode.

16. An electrochemical cell sensor capable of being implanted into an animal body comprising:

a hollow needle housing with one opening in the walls of said housing,

an electrode means situated in said housing and in fluid communication via said opening with fluids present in said animal body and responsive to enzyme substrates present in said fluids,

a means for supplying oxygen to said electrode means, and

a means for relating said response of said electrode means to the concentration of said enzyme substrates in said fluids.

17. An electrochemical cell sensor as defined in claim 16 wherein said hollow needle housing is composed of platinum or stainless steel and said housing and said opening are covered with a layer of porous biocompatible material.

18. An electrochemical cell sensor as defined in claim 17 wherein said electrode means comprises three (3) electrodes:

an enzyme substrate or product dependent sensing electrode composed of a noble metal and in communication with an oxidase enzyme,

a reference electrode composed of silver/silver chloride, and

a common counter electrode being said hollow needle housing.

19. An electrochemical cell sensor as defined in claim 18 wherein said the enzyme substrate or products dependent sensing electrode is polarized cathodically to determine oxygen.

20. An electrochemical cell sensor as defined in claim 18 wherein said enzyme substrate or product dependent sensing electrode is polarized anodically to determine hydrogen peroxide.

21. An electrochemical cell sensor as defined in claim 18 wherein said means for supplying oxygen is a tunnel that provides communication of atmospheric oxygen with said electrode means.

22. An electrochemical cell sensor as defined in claim 21 wherein said electrode means is insulated.

23. An electrochemical cell sensor as defined in claim 22 wherein said oxidase enzyme is drawn from the group consisting of glucose oxidase, lactate oxidase, uricase, or alcohol oxidase.

24. An electrochemical cell sensor as defined in claim 23 wherein said enzyme substrates are drawn from the group consisting of glucose, lactate, uricase, ethanol, or oxygen.