BIOSENSOR COATING COMPOSITION AND METHODS THEREOF

• US 20090255811A1
• Filed: 04/14/2008
• Published: 10/15/2009
• Est. Priority Date: 04/14/2008
• Status: Active Grant

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Inventors: Karinka, Shridhara Alva, Forrow, Nigel John
• Granted Patent: US 8,262,874 B2
• Time in Patent Office: Days
• US Class Current: 204/403.140
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

The disclosure provides for reagent compositions for biosensors comprising release polymers, methods of making such biosensors and films of reagent compositions comprising release polymers. The reagent compositions comprise a release polymer and an effective analyte detecting amount of an enzyme an enzyme cofactor and a redox compound capable of acting in a biosensor as (i) a redox mediator associated with a working electrode (ii) a redox couple associated with a reference electrode or (iii) the redox mediator associated with the working electrode and the redox couple for the reference electrode.

Claims

1. A reagent composition comprising:

a release polymer and an effective analyte detecting amount of;

an enzyme;

an enzyme cofactor; and

a redox compound capable of acting in a biosensor as

(i) a redox mediator associated with a working electrode;

(ii) a redox couple associated with a reference electrode;

or

(iii) the redox mediator associated with the working electrode and the redox couple for the reference electrode.

2. The composition of claim 1 wherein the reagent composition covers at least a portion of the working electrode, at least a portion of the reference electrode or both at least a portion of the working electrode and at least a portion of the reference electrode.

3. The composition of claim 1 wherein the rheology of the reagent composition is substantially Newtonian and is in the range from about 0.5 mPa s to about 25 mPa s.

4. The composition of claim 1 wherein the release polymer has dispersed within it an effective amount of:

an enzyme;

an enzyme cofactor; and

a redox compound capable of acting in a biosensor as

(i) a redox mediator for a working electrode;

(ii) a redox couple for a reference electrode;

or

(iii) a redox mediator for a working electrode and the redox couple for a reference electrode.

5. The composition of claim 1 further comprising a trigger electrode.

6. The composition of claim 5 wherein the reagent composition covers at least a portion of the trigger electrode.

7. The composition of claim 1 wherein the release polymer is a fast release polymer.

8. The composition of claim 7 wherein the fast release polymer is polyvinyl alcohol-polyethylene glycol graft copolymer.

9. The composition of claim 8 wherein the number average molecular weight (M_n) of the fast release polyvinyl alcohol-polyethylene glycol graft copolymer is from about 30,000 to about 60,000.

10. The composition of claim 1 wherein the release polymer is a sustained release polymer.

11. The composition of claim 10 wherein the sustained release polymer is polyvinyl acetate.

12. The composition of claim 11 wherein the polyvinyl acetate is in aqueous media.

13. The composition of claim 11 wherein the number average molecular weight (M_n) of the polyvinyl acetate is from about 10,000 to about 2,000,000.

14. The composition of claim 1 wherein the release polymer is an acrylic polymer.

15. The composition of claim 14 wherein the number average molecular weight (M_n) of the acrylic polymer is from about 50,000 to about 1,500,000.

16. The composition of claim 1 wherein the release polymer comprises polyvinyl alcohol-polyethylene glycol graft copolymer, polyvinyl acetate, acrylic polymer or mixtures thereof.

17. The composition of claim 1 wherein the redox compound is of the formula:

[M(PQ)₃]X₂

wherein;

M is Ni, Mn, Fe, Co, Os, or Ru;

PQ is

and X is a counter anion.

18. The composition of claim 1 wherein:

the sustained release polymer is poly(vinyl acetate);

the enzyme is dehydrogenase; and

the enzyme cofactor comprises NAD sodium salt, NAD(P), NAD, FAD or PQQ.

19. The composition of claim 18 wherein the enzyme is glucose GDH dependent, cholesterol dependent or ketone dependent.

20. The composition of claim 1 wherein:

the sustained release polymer is poly(vinyl acetate);

the enzyme is cholesterol dehydrogenase; and

the enzyme cofactor comprises NAD sodium salt, FAD or PQQ.

21. The composition of claim 1 wherein:

the sustained release polymer is poly(vinyl acetate);

the enzyme is 3-hydroxybutyrate dehydrogenase; and

the enzyme cofactor comprises NAD sodium salt, FAD or PQQ.

22. The composition of claim 18 wherein:

the sustained release polymer is poly(vinyl acetate);

the enzyme is a NAD(P)-dependent dehydrogenase;

the enzyme cofactor is NAD sodium salt; and

the redox compound is [Ni(PQ)₃]Cl₂, [Ni(PQ)₃]Br₂ or mixtures thereof

wherein PQ is

23. The composition of claim 18 wherein:

the redox compound is [M(PQ)₃]X₂

wherein;

M is Fe or Ru;

PQ is

and X is a counter anion.

24. The composition of claim 18 wherein:

the redox compound is [Os(PQ)₃]X₂

wherein;

PQ is

and X is a counter anion.

25. The composition of claim 18 wherein:

the redox compound is independently [Fe(CN)₆]³⁻

(ferricyanide), Ru(NH₃)₆]³⁺ (hexaammine ruthenium(III)), 2,6-dichlorophenol indophenol (DCIP), [Os(dmo)₂ (1-vinyl imidazole)X]X, [Os(dmo)₂ (1-vinyl imidazole)X]X₂, [Os(dmo)₂ (imidazole)X]X, [Os(dmo)₂ (imidazole)X]X₂, [Os(dmo)₂ (1-methylimidazole)X]X₂, [Os(dmo)₂ (methylimidazole)X]X₂

or mixtures thereof,

wherein;

dmo is 4,4′

-dimethoxy-2,2′

-bipyridine, and X is halogen.

26. A method of coating a biosensor comprising:

coating a reagent composition having the formula of claim 1 on at least one electrode on the biosensor substrate providing a coated biosensor; and

drying the coated biosensor to produce an analyte detecting composition film.

27. The method of claim 26 wherein the drying step is selected from air, O₂, CO₂, convection, vacuum, infra-red or combinations thereof.

28. The method of claim 26 wherein the reagent composition is coated using a slot-die coating method.

29. The method of claim 26 wherein the reagent composition is coated using ink jet coating methods, drop coating methods, hand coating methods, squeegee coating methods, spray coating methods, rod coating methods, roll coating methods, dip coating methods, meter rod coating methods, spin coating methods, curtain coating methods, slide coating methods or combination thereof.

30. The method of claim 26 wherein the reagent composition has a viscosity of from about 0.4 mPa s to about 10 mPa s.

31. The method of claim 26 wherein the reagent composition has a viscosity of from about 1.0 mPa s to about 5 mPa s.

32. The method of claim 26 wherein the analyte detecting composition film has an average thickness of from about 2 μ

m to about 7 μ

m.

33. The method of claim 26 wherein the analyte detecting composition film has an average thickness of from about 3 μ

m to about 6 μ

m.

34. The method of claim 26 wherein the analyte detecting composition film produced has a substantially uniform thickness.

35. The method of claim 26 wherein the rheology of the reagent composition is substantially Newtonian.

36. A biosensor comprising:

at least one electrode; and

a reagent composition associated with the at least one electrode, the reagent composition comprising;

a release polymer and an effective analyte detecting amount of;

an enzyme;

an enzyme cofactor; and

a redox compound capable of acting in a biosensor as

(i) a redox mediator for a working electrode;

(ii) a redox couple for a reference electrode;

or

(iii) a redox mediator for a working electrode and the redox couple for a reference electrode.

37. The biosensor of claim 36 wherein the release polymer has dispersed within it an effective amount of

an enzyme;

an enzyme cofactor; and

a redox compound capable of acting in a biosensor as

(i) a redox mediator for a working electrode;

(ii) a redox couple for a reference electrode;

or

(iii) a redox mediator for a working electrode and the redox couple for a reference electrode.

38. The biosensor of claim 36 wherein the release polymer is a polymer that is soluble in water.

39. The biosensor of claim 36 wherein the release polymer is a polymer that is substantially insoluble in water.

40. The biosensor of claim 36 wherein the redox compound comprises:

[M(PQ)₃]X₂

wherein;

M is Ni, Mn, Fe, Co, Os, or Ru;

PQ is

and X is a counter anion.

41. The biosensor of claim 36 wherein the reagent composition further comprises:

the sustained release polymer is poly(vinyl acetate);

the enzyme is a NAD(P)-dependent dehydrogenase;

the enzyme cofactor is NAD sodium salt; and

the redox compound is [Ni(PQ)₃]Cl₂, [Ni(PQ)₃]Br₂ or mixtures thereof;

wherein PQ is

42. The biosensor of claim 36 wherein:

the redox compound is [M(PQ)₃]X₂

wherein;

M is Fe or Ru;

PQ is

and X is a counter anion.

43. The biosensor of claim 36 wherein:

the redox compound is [Os(PQ)₃]X₂

wherein;

PQ is

and X is a counter anion.

44. The biosensor of claim 36 wherein:

the sustained release polymer is poly(vinyl acetate);

the enzyme is dehydrogenase; and

the enzyme cofactor comprises NAD sodium salt, FAD or PQQ.

45. The biosensor of claim 36 wherein:

the release polymer is poly(vinyl acetate);

the enzyme is NAD(P)-dependent dehydrogenase;

the enzyme cofactor is NAD sodium salt; and

the redox mediator is [Ni(PQ)₃]Cl₂, [Ni(PQ)₃]Br₂ or mixtures thereof

wherein PQ is

46. A biosensor film comprising

a release polymer and an effective analyte detecting amount of:

an enzyme;

an enzyme cofactor; and

a redox compound capable of acting in a biosensor as

(i) a redox mediator for a working electrode;

(ii) a redox couple for a reference electrode;

or

(iii) a redox mediator for a working electrode and the redox couple for a reference electrode.

47. The biosensor film of claim 46 wherein the release polymer has dispersed within it an effective amount of:

an enzyme;

an enzyme cofactor; and

a redox compound capable of acting in a biosensor as

(i) a redox mediator for a working electrode;

(ii) a redox couple for a reference electrode;

or

(iii) a redox mediator for a working electrode and the redox couple for a reference electrode.

48. The biosensor film of claim 46 wherein the release polymer is a fast release polymer.

49. The biosensor film of claim 48 wherein the fast release polymer is polyvinyl alcohol-polyethylene glycol graft copolymer.

50. The biosensor film of claim 49 wherein the number average molecular weight (M_n) of the fast release polyvinyl alcohol-polyethylene glycol graft copolymer is from about 30,000 to about 60,000.

51. The biosensor film of claim 46 wherein the release polymer is a sustained release polymer.

52. The biosensor film of claim 51 wherein the sustained release polymer is polyvinyl acetate.

53. The biosensor film of claim 52 wherein the number average molecular weight (M_n) of the polyvinyl acetate is from about 10,000 to about 2,000,000.

54. The biosensor film of claim 46 wherein the release polymer is an acrylic polymer.

55. The biosensor film of claim 54 wherein the number average molecular weight (M_n) of the acrylic polymer is from about 50,000 to about 1,500,000.

56. The biosensor film of claim 46 wherein the release polymer comprises polyvinyl alcohol-polyethylene glycol graft copolymer, polyvinyl acetate, acrylic polymer or mixtures thereof.

57. The biosensor film of claim 46 wherein the redox compound is of the formula:

[M(PQ)₃]X₂

wherein;

M is Ni, Mn, Fe, Co, Os, or Ru;

PQ is

and X is a counter anion.

58. The biosensor film of claim 46 wherein:

the sustained release polymer is poly(vinyl acetate);

the enzyme is dehydrogenase; and

the enzyme cofactor comprises NAD sodium salt, FAD or PQQ.

59. The biosensor film of claim 46 wherein:

the sustained release polymer is poly(vinyl acetate);

the enzyme is a NAD(P)-dependent dehydrogenase;

the enzyme cofactor is NAD sodium salt; and

the redox compound is [Ni(PQ)₃]Cl₂, [Ni(PQ)₃]Br₂ or mixtures thereof

wherein PQ is

60. The biosensor film of claim 46 wherein:

the redox compound is [M(PQ)₃]X₂

wherein;

M is Fe or Ru;

PQ is

and X is a counter anion.

61. The biosensor film of claim 46 wherein:

the redox compound is [Os(PQ)₃]X₂

wherein;

PQ is

and X is a counter anion.

62. The biosensor film of claim 46 further comprising a colorant.

63. The biosensor film of claim 62 wherein the colorant is a flavin mononucleotide (FMN) of the structure:

64. A biosensor film associated with an optical sensor, comprising

a release polymer and an effective analyte detecting amount of:

an enzyme;

an enzyme cofactor; and

a redox compound capable of acting in a biosensor as

(i) a redox mediator;

(ii) a redox couple;

or

(iii) a redox mediator and a redox couple.

65. The optical sensor of claim 64 wherein the redox compound is of the formula:

[M(PQ)₃]X₂

wherein;

M is Ni, Mn, Fe, Co, Os, or Ru;

PQ is

and X is a counter anion.

66. The optical sensor of claim 64 wherein:

the sustained release polymer is poly(vinyl acetate);

the enzyme is dehydrogenase; and

the enzyme cofactor comprises NAD sodium salt, FAD or PQQ.

67. The optical sensor of claim 64 wherein:

the sustained release polymer is poly(vinyl acetate);

the enzyme is a NAD(P)-dependent dehydrogenase;

the enzyme cofactor is NAD sodium salt; and

the redox compound is [Ni(PQ)₃]Cl₂, [Ni(PQ)₃]Br₂ or mixtures thereof wherein PQ is

68. The optical sensor of claim 64 wherein:

the redox compound is [M(PQ)₃]X₂

wherein;

M is Fe or Ru;

PQ is

and X is a counter anion.

69. The optical sensor of claim 64 wherein:

the redox compound is [Os(PQ)₃]X₂

wherein;

PQ is

and X is a counter anion.

70. The optical sensor of claim 64 further comprising a colorant.