Biosensor membranes composed of polymers containing heterocyclic nitrogens

• US 8,147,666 B2
• Filed: 08/20/2009
• Issued: 04/03/2012
• Est. Priority Date: 05/15/2001
• Status: Expired due to Fees

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories)
• Inventors: Mao, Fei, Cho, Hyun
• Primary Examiner(s): Noguerola, Alex
• Application Number:
  US12/544,794
• Publication Number:
  US 20100112613A1
• Time in Patent Office: 957 Days
• Field of Search: 204/403.05, 204/403.06, 427/2.13
• US Class Current: 204/403.05
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• 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 5/6846 specially adapted to be brought in contact with an internal body part, i.e. invasive
• CPC Class Codes: C12Q 1/002 Electrode membranes
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

Novel membranes comprising various polymers containing heterocyclic nitrogen groups are described. These membranes are usefully employed in electrochemical sensors, such as amperometric biosensors. More particularly, these membranes effectively regulate a flux of analyte to a measurement electrode in an electrochemical sensor, thereby improving the functioning of the electrochemical sensor over a significant range of analyte concentrations. Electrochemical sensors equipped with such membranes are also described.

Claims

1. A crosslinked membrane structure, comprising:

a sensing layer composition comprising a first polymer, an analyte responsive enzyme and a mediator; and

a flux limiting membrane composition comprising a second polymer deposited over at least a portion of the sensing layer, wherein the flux limiting membrane composition comprises a crosslinker, and wherein the second polymer comprises the formula;

2. The membrane structure of claim 1, wherein the first polymer comprises heterocyclic nitrogen containing groups.

3. The membrane structure of claim 2, wherein the heterocyclic nitrogen containing group is a pyridine group, a imidazole group, a oxazole group, a thiazole group, or a pyrazole group.

4. The membrane structure of claim 1, wherein the crosslinked membrane structure is formed in situ.

5. The membrane structure of claim 1, wherein the crosslinked membrane structure is positioned on an electrode substrate.

6. The membrane structure of claim 1, wherein the second polymer comprises heterocyclic nitrogen containing groups.

7. The membrane structure of claim 6, wherein the heterocyclic nitrogen containing group is a pyridine group, a imidazole group, a oxazole group, a thiazole group, or a pyrazole group.

8. The membrane structure of claim 1, wherein the first polymer comprises heterocyclic nitrogen containing groups and the second polymer comprises heterocyclic nitrogen containing groups,

wherein the crosslinker provides for intermolecular crosslinking between heterocyclic nitrogen containing groups.

9. The membrane structure of claim 1, wherein the analyte response enzyme is a glucose responsive enzyme.

10. The membrane structure of claim 1, wherein the mediator comprises an osmium mediator complex.

11. The membrane structure of claim 1, wherein the flux limiting membrane is sufficient to limit a flux of glucose or lactate thereacross.

12. The membrane structure of claim 1, wherein the crosslinker is a deriviative of poly(ethylene glycol) or poly(propylene glycol).

13. The membrane structure of claim 1, wherein a weight ratio of polymer to the crosslinker is from about 4:

1 to about 32;

1.

14. The membrane structure of claim 1, wherein a weight ratio of polymer to the crosslinker is from about 8:

1 to about 16;

1.

15. The membrane structure of claim 1, wherein A is negatively charged.

16. The membrane structure of claim 1, wherein A is a sulfonate group, a carboxylate group, or a phosphate group.

17. The membrane structure of claim 1, wherein A is a sulfopropyl group, a sulfobutyl group, a carboxypropyl group, or a carboxypentyl group.

18. The membrane structure of claim 1, wherein A is of the formula L-G, where L is a C2-C12 linear or branched alkyl linker and G is a negatively charged carboxy or sulfonate.

19. The membrane structure of claim 18, wherein L is substituted with an aryl, alkoxy, alkenyl, alkynyl, —

F, —

Cl, —

OH, aldehyde, ketone, ester, or amide.

20. The membrane structure of claim 1, wherein D is styrene or C1-C18 alkyl methacrylate.

21. The membrane structure of claim 1, wherein an average molecular weight of the second polymer is above about 50,000.

22. The membrane structure of claim 1, wherein an average molecular weight of the second polymer is from about 50,000 to about 200,000.

23. The membrane structure of claim 1, wherein the analyte responsive enzyme is a glucose responsive enzyme or a lactate responsive enzyme.

24. A method of forming a crosslinked membrane structure in situ on an electrode, comprising:

depositing a sensing layer solution comprising an analyte responsive enzyme and a first polymer comprising mediator complexes on an electrode substrate;

depositing over at least a portion of the sensing layer solution a flux limiting membrane composition comprising a crosslinker and a second polymer, wherein the second polymer comprises the formula;

25. The method of claim 24, wherein the depositing is by dip-coating the electrode.

26. The method of claim 24, wherein the depositing is by depositing at least a drop of solution on the electrode.

27. The method of claim 24, wherein the first polymer comprises heterocyclic nitrogen containing groups.

28. The method of claim 27, wherein the heterocyclic nitrogen containing group is a pyridine group, a imidazole group, a oxazole group, a thiazole group, or a pyrazole group.

29. The method of claim 24, wherein the second polymer comprises heterocyclic nitrogen containing groups.

30. The method of claim 29, wherein the heterocyclic nitrogen containing group is a pyridine group, a imidazole group, a oxazole group, a thiazole group, or a pyrazole group.

31. The method of claim 24, wherein the first polymer comprises heterocyclic nitrogen containing groups and the second polymer comprises heterocyclic nitrogen containing groups,

wherein the crosslinker provides for intermolecular crosslinking between heterocyclic nitrogen containing groups.

32. The method of claim 24, wherein the analyte response enzyme is a glucose responsive enzyme.

33. The method of claim 24, wherein the mediator complexes comprise osmium mediator complexes.

34. The method of claim 24, wherein the flux limiting membrane is sufficient to limit a flux of glucose or lactate thereacross.

35. The method of claim 24, wherein the crosslinker is a deriviative of poly(ethylene glycol) or poly(propylene glycol).

36. The method of claim 24, wherein a weight ratio of polymer to the crosslinker is from about 4:

1 to about 32;

1.

37. The method of claim 24, wherein a weight ratio of polymer to the crosslinker is from about 8:

1 to about 16;

1.

38. The method of claim 24, wherein A is negatively charged.

39. The method of claim 24, wherein A is a sulfonate group, a carboxylate group, or a phosphate group.

40. The method of claim 24, wherein A is a sulfopropyl group, a sulfobutyl group, a carboxypropyl group, or a carboxypentyl group.

41. The method of claim 24, wherein A is of the formula L-G, where L is a C2-C12 linear or branched alkyl linker and G is a negatively charged carboxy or sulfonate.

42. The method of claim 41, wherein L is substituted with an aryl, alkoxy, alkenyl, alkynyl, —

F, —

Cl, —

OH, aldehyde, ketone, ester, or amide.

43. The method of claim 24, wherein D is styrene or C1-C18 alkyl methacrylate.

44. The method of claim 24, wherein an average molecular weight of the second polymer is above about 50,000.

45. The method of claim 24, wherein an average molecular weight of the second polymer is from about 50,000 to about 200,000.

46. The method of claim 24, wherein the analyte responsive enzyme is a glucose responsive enzyme or a lactate responsive enzyme.