Composite membrane containing a cross-linked enzyme matrix for a biosensor

• US 8,426,192 B2
• Filed: 12/14/2009
• Issued: 04/23/2013
• Est. Priority Date: 05/31/2001
• Status: Active Grant

• Current Assignee: Instrumentation Lab Co (Instrumentation Lab)
• Original Assignee: Instrumentation Lab Co (Instrumentation Lab)
• Inventors: Pamidi, Prasad, Mansouri, Sohrab, Shin, Melanie, Cosofret, Vasile, Xu, Clarke
• Primary Examiner(s): NAFF, DAVID M
• Application Number:
  US12/637,394
• Publication Number:
  US 20100133101A1
• Time in Patent Office: 1,226 Days
• Field of Search: None
• US Class Current: 435/287.1
• CPC Class Codes: C12Q 1/002 Electrode membranes
• CPC Class Codes: C12Q 1/003 Functionalisation
• 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: C25D 9/02 with organic materials
• CPC Class Codes: Y10S 435/817 Enzyme or microbe electrode

Abstract

An electrochemical sensor system and membrane and method thereof for increased accuracy and effective life of electrochemical and enzyme sensors.

Claims

1. A composite membrane for an enzyme sensor, comprising:

an inner membrane layer comprising a restorable polymerizable membrane, the inner membrane layer adapted to function as an interference rejection membrane;

an outer membrane layer comprising polyurethane, and adapted to be disposed adjacent a flow channel during use; and

an enzyme layer disposed between and in contact with the inner and the outer membrane layers, said enzyme layer comprising a matrix comprising;

at least one enzyme selected from the group consisting of creatinase and sarcosine oxidase;

a cross-linking agent; and

an enzyme stabilizer selected from the group consisting of polyethyleneimine, polypropyleneimine, poly(N-vinylimidazole), polyallylamine, polyvinylpyridine, polyvinylpyrrolidone, polylysine, and protamine;

wherein the outer membrane is adapted to control diffusion of an analyte into the enzyme layer.

2. The matrix membrane of claim 1, further comprising creatininase.

3. The composite membrane of claim 1, wherein said enzyme sensor comprises an electrochemical electrode.

4. The composite membrane of claim 1, wherein said cross-linking agent is selected from the group consisting of a dialdehyde, a diisocyanate, and a diepoxide.

5. The composite membrane of claim 4, wherein said cross-linking agent comprises glutaraldehyde.

6. The composite membrane of claim 5, wherein said cross-linking agent comprises about 1-10% glutaraldehyde by weight.

7. The composite membrane of claim 5, wherein said cross-linking agent comprises about 5% glutaraldehyde by weight.

8. The composite membrane of claim 4, wherein said cross-linking agent comprises 1,4-diisocyanatobutane.

9. The composite membrane of claim 4, wherein said cross-linking agent is selected from the group consisting of 1,2,7,8-diepoxyoctane and 1,2,9,10-diepoxydecane.

10. The composite membrane of claim 4, wherein the enzyme layer has a thickness in the range of about 1 micron to about 10 micron.

11. The composite membrane of claim 4, wherein the enzyme layer has a thickness in the range of about 2 micron to about 5 micron.

12. The composite membrane of claim 4, wherein the outer membrane layer comprises a blend of polyurethane having different water uptake levels.

13. The composite membrane of claim 4, wherein the outer membrane layer has a thickness between about 8 microns and about 15 microns.

14. The composite membrane of claim 4, wherein the enzyme stabilizer comprises a weight percent of the enzyme layer that is between about 1% and about 20%.

15. The composite membrane of claim 4, wherein the enzyme stabilizer is polyethyleneimine.

16. The composite membrane of claim 4, wherein the enzyme stabilizer is poly(N-vinylimidazole).

17. The composite membrane of claim 16, wherein the enzyme stabilizer comprises a weight percent of poly(N-vinylimidazole) between about 1% and about 20%.

18. The composite membrane of claim 16, wherein the enzyme stabilizer comprises about 5% poly(N-vinylimidazole) by weight.

19. The composite membrane of claim 4, wherein the restorable polymerization membrane is formed by polymerization of electropolymerizable monomers selected from the group consisting of benzothiophene, phenylenediamines, and phenols.

20. A composite membrane for an enzyme sensor, comprising:

an inner membrane layer comprising a restorable polymerizable membrane, the inner membrane layer adapted to function as an interference rejection membrane;

an outer membrane layer comprising polyurethane, and adapted to be disposed adjacent a flow channel during use; and

an enzyme layer disposed between and in contact with the inner and the outer membrane layers, said enzyme layer comprising a matrix comprising;

creatininase;

creatinase;

sarcosine oxidase;

glutaraldehyde; and

polyethyleneimine,

wherein the outer membrane is adapted to control diffusion of an analyte into the enzyme layer.