Low total salt reagent compositions and systems for biosensors

• US 8,871,069 B2
• Filed: 06/06/2011
• Issued: 10/28/2014
• Est. Priority Date: 12/08/2008
• Status: Active Grant

• Current Assignee: Ascensia Diabetes Care Holdings AG (PHC Holdings Corporation)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Chu, Amy H., Wu, Huan-Ping, Zhu, Boru
• Primary Examiner(s): Ball, J. Christopher
• Application Number:
  US13/154,088
• Publication Number:
  US 20110297540A1
• Time in Patent Office: 1,240 Days
• Field of Search: 20440301-40315
• US Class Current: 204/403.04
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

A biosensor system for determining the concentration of an analyte in a sample is disclosed that includes a reaction means for selectively performing a redox reaction of an analyte, and a measurement means for measuring a rate of the redox reaction of the analyte. The reaction means includes a binder, a buffer salt, a mediator including at most 20% (w/w) of an inorganic, non-transition metal salt, and an enzyme system. The measurement means includes at least two conductors. The measurement means measures an output signal value from the reaction means at a maximum kinetic performance within at most 7 seconds of introducing a sample to the reaction means, where the output signal value is responsive to the concentration of the analyte in the sample, and the measurement means determines at least one ΔS value responsive to at least one error parameter. The measurement means further determines the analyte concentration in the sample from a compensation equation including at least one reference correlation and the at least one ΔS value, where the compensation equation has a R² value of at least 0.5.

Claims

1. A biosensor system, for determining the concentration of an analyte in a sample, comprising:

a reaction means for selectively performing a redox reaction of an analyte,

where the reaction means comprises a binder, a buffer salt, a mediator comprising at most 20% (w/w) of an inorganic, non-transition metal salt, an enzyme system, and a non-ionic, sugar-based surfactant; and

a measurement means for measuring a rate of the redox reaction of the analyte,

where the measurement means comprises at least two conductors;

where the measurement means measures an output signal value from the reaction means at a maximum kinetic performance within at most 7 seconds of introducing a sample to the reaction means, where the output signal value is responsive to the concentration of the analyte in the sample,

the measurement means is capable of determining at least one slope deviation of the correlation between analyte concentrations and output current values determined from one or more error parameters responsive to at least one error parameter, and

the measurement means is capable of determining the analyte concentration in the sample from a compensation equation including at least one reference correlation and the at least one slope deviation of the correlation between analyte concentrations and output current values determined from one or more error parameters;

where the compensation equation has a R² value of at least 0.5.

2. The system of claim 1, where the reaction means comprises a reagent composition having an average reagent composition surface area and comprising:

the binder,

the buffer salt, present in the reagent composition at a concentration of at most 9.54 nmol per mm² of the reagent composition surface area,

the mediator, present in the reagent composition at a concentration of at most 4.76 nmol per mm² of the reagent composition surface area,

the enzyme system, and

the non-ionic surfactant.

3. The system of claim 2, where the reagent composition comprises:

from about 0.14 to about 0.43 μ

g of the binder per mm² of the reagent composition surface area,

from about 2.30 to 9.54 nmol of the buffer salt per mm² of the reagent composition surface area,

from about 1.70 to 4.76 nmol of the mediator per mm² of the reagent composition surface area,

from about 0.07 to about 0.3 Units of the enzyme system per mm² of the reagent composition surface area,

and from about 0.04 to about 0.24 μ

g of the non-ionic surfactant per mm² of the reagent composition surface area.

4. The system of claim 3, where the reagent composition comprises:

from about 3.40 to about 4.77 nmol of the buffer salt per mm² of the reagent composition surface area, and

from about 2.80 to about 4.00 nmol of the mediator per mm² of the reagent composition surface area.

5. The system of claim 2, where the reagent composition further comprises from about 3 to about 16 ng of an anionic surfactant per mm² of the reagent composition surface area.

6. The system of claim 1, where the reaction means comprises:

a reservoir having a reservoir volume,

at least two conductors in the reservoir, where one of the conductors is a working electrode, and

a reagent composition disposed on or near the working electrode;

where the reagent composition comprises;

the binder,

the buffer salt, present in the reagent composition at a concentration of at most 67 nmol per μ

L of the reservoir volume,

the mediator, present in the reagent composition at a concentration of at most 40 nmol per μ

L of the reservoir volume,

the enzyme system, and

the non-ionic surfactant.

7. The system of claim 6, where the reagent composition comprises:

from about 1 to about 3 μ

g of the polymeric binder per μ

L of the reservoir volume,

from about 16 to 67 nmol of the buffer salt per μ

L of the reservoir volume,

from about 12 to 40 nmol of the mediator per μ

L of the reservoir volume,

from about 0.5 to about 1.8 Units of the enzyme system per μ

L of the reservoir volume, and

from about 0.3 to about 1.7 μ

g of the non-ionic surfactant per μ

L of the reservoir volume.

8. The system of claim 7, where the reagent composition comprises:

from about 24 to about 34 nmol of the buffer salt per μ

L of the reservoir volume, and

from about 20 to about 28 nmol of the mediator per μ

L of the reservoir volume.

9. The system of claim 6, where the reagent composition further comprises from about 20 to about 40 ng of an ionic surfactant per μ

L of the reservoir volume.

10. The system of claim 1, where the reaction means comprises:

at least two conductors, where one of the conductors is a working electrode having a working electrode area, and

a reagent composition disposed on or near the working electrode;

where the reagent composition comprises;

the binder,

the buffer salt, present in the reagent composition at a concentration of at most 167 nmol per mm² of the working electrode area,

the mediator, present in the reagent composition at a concentration of at most 100 nmol per mm² of the working electrode area,

the enzyme system,

a non-ionic surfactant, and

from about 10 to about 350 ng of an ionic surfactant per mm² of the working electrode area.

11. The system of claim 10, where the reagent composition comprises:

from about 1 to about 7.5 μ

g of the binder per mm² of the working electrode area,

from about 16 to 167 nmol of the buffer salt per mm² of the working electrode area,

from about 12 to 100 nmol of the mediator per mm² of the working electrode area,

from about 0.5 to about 5 Units of the enzyme system per mm² of the working electrode area, and

from about 0.3 to about 4.3 μ

g of the non-ionic surfactant per mm² of the working electrode area.

12. The system of claim 1, where the reaction means further comprises an ionic surfactant.

13. The system of claim 12, where the ionic surfactant comprises an anionic surfactant.

14. The system of claim 1, where the buffer salt comprises Na₂HPO₄.

15. The system of claim 1, where the mediator comprises at most 10% (w/w) inorganic, non-transition metal salt.

16. The system of claim 1, where the mediator comprises at most 5% (w/w) inorganic, non-transition metal salt.

17. The system of claim 1, where the mediator comprises at most 4% (w/w) inorganic, non-transition metal salt.

18. The system of claim 1, where the measurement means measures an output signal value from the reaction means at a maximum kinetic performance within at most 5 seconds of introducing a sample to the reaction means.

19. The system of claim 1, where the measurement means measures an output signal value from the reaction means at a maximum kinetic performance within at most 3.5 seconds of introducing a sample to the reaction means.

20. A test sensor for determining the concentration of an analyte in a sample, comprising:

at least two conductors, where one of the conductors is a working electrode; and

a reagent composition disposed on or near the working electrode, the reagent composition having an average reagent composition surface area and comprising;

a binder,

a buffer salt at a concentration of at most 9.54 nmol per mm² of the reagent composition surface area,

a mediator at a concentration of at most 4.76 nmol per mm² of the reagent composition surface area, where the mediator comprises at most 20% (w/w) of an inorganic, non-transition metal salt,

an enzyme system, and

a non-ionic surfactant comprising a sugar-based surfactant.

21. The sensor of claim 20, where the reagent composition comprises

from about 0.14 to about 0.43 μ

g of the binder per mm² of the reagent composition surface area,

from about 2.30 to 9.54 nmol of the buffer salt per mm² of the reagent composition surface area,

from about 1.70 to 4.76 nmol of the mediator per mm² of the reagent composition surface area,

from about 0.07 to about 0.3 Units of the enzyme system per mm² of the reagent composition surface area, and

from about 0.04 to about 0.24 μ

g of the non-ionic surfactant per mm² of the reagent composition surface area.

22. The sensor of claim 21, where the reagent composition comprises

from about 3.40 to about 4.77 nmol of the buffer salt per mm² of the reagent composition surface area, and

from about 2.80 to about 4.00 nmol of the mediator per mm² of the reagent composition surface area.

23. The sensor of claim 20, where the buffer salt comprises Na₂HPO₄.

24. The sensor of claim 20, where the mediator comprises at most 5% (w/w) inorganic, non-transition metal salt.

25. A test sensor for determining the concentration of an analyte in a sample, comprising:

a reservoir having a reservoir volume,

at least two conductors in the reservoir, where one of the conductors is a working electrode, and

a reagent composition disposed on or near the working electrode;

where the reagent composition comprises;

a binder,

a buffer salt at a concentration of at most 67 nmol per μ

L of the reservoir volume,

a mediator at a concentration of at most 40 nmol per μ

L of the reservoir volume, where the mediator comprises at most 20% (w/w) of an inorganic, non-transition metal salt,

an enzyme system, and

a non-ionic surfactant comprising a sugar-based surfactant.

26. The sensor of claim 25, where the reagent composition comprises

from about 1 to about 3 μ

g of the binder per μ

L of the reservoir volume,

from about 16 to 67 nmol of the buffer salt per μ

L of the reservoir volume,

from about 12 to 40 nmol of the mediator per μ

L of the reservoir volume,

from about 0.5 to about 1.8 Units of the enzyme system per μ

L of the reservoir volume, and

from about 0.3 to about 1.7 μ

g of the non-ionic surfactant per μ

L of the reservoir volume.

27. The sensor of claim 26, where the reagent composition comprises

from about 24 to about 34 nmol of the buffer salt per μ

L of the reservoir volume, and

from about 20 to about 28 nmol of the mediator per μ

L of the reservoir volume.

28. The sensor of claim 25, where the buffer salt comprises Na₂HPO₄.

29. The sensor of claim 25, where the mediator comprises at most 5% (w/w) inorganic, non-transition metal salt.

30. A test sensor for determining the concentration of an analyte in a sample, comprising:

at least two conductors, where one of the conductors is a working electrode having a working electrode area; and

a reagent composition disposed on or near the working electrode, the reagent composition comprising;

a binder,

a buffer salt at a concentration of at most 167 nmol per mm² of the working electrode area,

a mediator at a concentration of at most 100 nmol per mm² of the working electrode area, where the mediator comprises at most 20% (w/w) of an inorganic, non-transition metal salt,

an enzyme system, and

a non-ionic surfactant comprising a sugar-based surfactant.

31. The sensor of claim 30, comprising

from about 1 to about 7.5 μ

g of the binder per mm² of the working electrode area,

from about 16 to 167 nmol of the buffer salt per mm² of the working electrode area,

from about 12 to 100 nmol of the mediator per mm² of the working electrode area,

from about 0.5 to about 5 Units of the enzyme system per mm² of the working electrode area, and

from about 0.3 to about 4.3 μ

g of the non-ionic surfactant per mm² of the working electrode area.

32. The sensor of claim 31, comprising

from about 24 to about 84 nmol of the buffer salt per mm² of the working electrode area, and

from about 20 to about 70 nmol of the mediator per mm² of the working electrode area.

33. The sensor of claim 30, where the buffer salt comprises Na₂HPO₄.

34. The sensor of claim 30, where the mediator comprises at most 5% (w/w) inorganic, non-transition metal salt.

35. A test sensor for determining the concentration of an analyte in a sample, comprising:

at least two conductors, where one of the conductors is a working electrode; and

a reagent composition disposed on or near the working electrode, the reagent composition having an average reagent composition surface area and comprising;

a binder,

a buffer salt at a concentration of at most 9.54 nmol per mm² of the reagent composition surface area,

a mediator at a concentration of at most 4.76 nmol per mm² of the reagent composition surface area, where the mediator comprises at most 20% (w/w) of an inorganic, non-transition metal salt,

an enzyme system,

a non-ionic surfactant, and

an ionic surfactant.

36. The sensor of claim 35, where the ionic surfactant comprises an anionic surfactant.

37. The sensor of claim 36, where the reagent composition comprises from about 3 to about 16 ng of the anionic surfactant per mm2 of the reagent composition surface area.

38. A test sensor for determining the concentration of an analyte in a sample, comprising:

a reservoir having a reservoir volume,

at least two conductors in the reservoir, where one of the conductors is a working electrode, and

a reagent composition disposed on or near the working electrode;

where the reagent composition comprises;

a binder,

a buffer salt at a concentration of at most 67 nmol per μ

L of the reservoir volume,

a mediator at a concentration of at most 40 nmol per μ

L of the reservoir volume, where the mediator comprises at most 20% (w/w) of an inorganic, non-transition metal salt,

an enzyme system,

a non-ionic surfactant, and

an ionic surfactant.

39. The sensor of claim 38, where the ionic surfactant comprises an anionic surfactant.

40. The sensor of claim 39, where the reagent composition comprises from about 20 to about 40 ng of the ionic surfactant per μ

L of the reservoir volume.

41. A test sensor for determining the concentration of an analyte in a sample, comprising:

at least two conductors, where one of the conductors is a working electrode having a working electrode area; and

a reagent composition disposed on or near the working electrode, the reagent composition comprising;

a binder,

a buffer salt at a concentration of at most 167 nmol per mm² of the working electrode area,

a mediator at a concentration of at most 100 nmol per mm² of the working electrode area, where the mediator comprises at most 20% (w/w) of an inorganic, non-transition metal salt,

an enzyme system,

a non-ionic surfactant, and

an ionic surfactant.

42. The sensor of claim 41, where the ionic surfactant comprises an anionic surfactant.

43. The sensor of claim 42, where the reagent composition comprises from about 10 to about 350 ng of the ionic surfactant per mm² of the working electrode area.