Disposable oxygen sensor and method for correcting oxygen effect on oxidase-based analytical devices

• US 7,611,621 B2
• Filed: 06/13/2005
• Issued: 11/03/2009
• Est. Priority Date: 06/13/2005
• Status: Active Grant

• Current Assignee: Nova Biomedical Corporation (Nova Chemicals)
• Original Assignee: Nova Biomedical Corporation (Nova Chemicals)
• Inventors: Young, Chung Chang, Cai, Xiaohua, Alesi, Kara
• Primary Examiner(s): Olsen; Kaj K
• Assistant Examiner(s): CARLSON, KOURTNEY SALZMAN
• Application Number:
  US11/160,193
• Publication Number:
  US 20060278537A1
• Time in Patent Office: 1,604 Days
• Field of Search: 20440304-40315, 205/777.5, 205/792, 205/782, 600/347, 435/4, 435/14, 435/25, 435/28
• US Class Current: 205/777.5
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• 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: C12Q 1/006 for glucose
• CPC Class Codes: G01N 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771

Abstract

A system and method for correcting the oxygen effect on oxidase-based analyte sensors includes an oxygen sensor with a working electrode, a reagent matrix disposed on at least the working electrode that contains a reduced form of a redox mediator, an oxidase and a peroxidase, an oxidase-based analyte sensor, a means for determining the oxygen concentration in a portion of a fluid sample using the oxygen sensor, means for determining an analyte concentration in another portion of the fluid sample using the oxidase-based analyte sensor, and means for using the oxygen concentration in the fluid sample to determine a corrected analyte concentration in the fluid sample.

Claims

1. A method of correcting the oxygen effect on oxidase-based analyte sensors comprising:

determining an oxygen concentration of a fluid sample using an oxygen sensor comprising a working electrode, a reference electrode and a reagent matrix disposed on at least said working electrode wherein said reagent matrix contains a reduced form of a redox mediator, an oxidase and a peroxidase and wherein said oxygen sensor has a known correlation between oxygen concentration and analyte concentration expressed as a function of the response of said oxygen sensor to both oxygen and an analyte wherein said analyte is a substrate of said oxidase;

using an oxidased-based analyte sensor wherein the correlation between oxygen concentration and oxygen effect on said oxidase-based analyte sensor is known and wherein an oxidase in said oxidased-based sensor is a substrate of said oxidase in said oxygen sensor;

determining an analyte concentration of said fluid sample using said oxidase-based analyte sensor; and

calculating a corrected analyte concentration in said fluid sample using said determined oxygen concentration.

2. The method of claim 1 wherein said oxygen concentration determining step further includes applying a potential between said reference electrode and said working electrode, measuring a first current generated between said working electrode and said reference electrode, and correlating said first current to a concentration of oxygen in said fluid sample using said function.

3. The method of claim 2 wherein said oxygen concentration determining step further includes deriving said function as an oxygen empirical equation used for determining said oxygen concentration based on the configuration of said oxygen sensor.

4. The method of claim 3 wherein said oxygen empirical equation is represented by the formula

pO₂=ai²+bi+k₁

where a and b are empirical constants at a given glucose concentration determined by the configuration of said oxygen sensor, k₁ is an empirical constant based on electrode configuration, and i is the current measured by said oxygen sensor.

5. The method of claim 1 wherein said calculating step further includes determining a correction factor for said analyte to be added to said determined analyte concentration.

6. The method of claim 5 wherein said correction factor further includes determining an analyte empirical equation used for determining said correction factor of said analyte concentration based on the configuration of said oxidase-based analyte sensor.

7. The method of claim 6 wherein said analyte empirical equation is represented by the formula

Δ

C=(−

2×

10<sup>−

06</sup>C²+3×

10<sup>−

05</sup>C−

k₆)pO₂+k₇

where C is said determined analyte concentration before correction, pO₂ is said determined oxygen concentration, and k₆ and k₇ are empirical constants based on electrode configuration.

8. A system for correcting the oxygen effect on oxidase-based analyte sensors, said system comprising:

an oxygen sensor comprising a working electrode, a reference electrode and a reagent matrix disposed on at least said working electrode wherein said reagent matrix contains a reduced form of a redox mediator, an oxidase and a peroxidase wherein said oxygen sensor has a known correlation between oxygen concentration and analyte concentration expressed as a function of the response of said oxygen sensor to both oxygen and an analyte wherein said analyte is a substrate of said oxidase;

an oxidase-based analyte sensor for measuring an analyte in a portion of a fluid sample wherein said analyte is a substrate of said oxidase in said oxygen sensor and wherein the correlation between oxygen concentration and oxygen effect on said oxidase-based analyte sensor is known;

means for electronically determining an oxygen concentration in a portion of said fluid sample using said oxygen sensor;

means for electronically determining an analyte concentration in another portion of said fluid sample using said oxidase-based analyte sensor; and

means for using said determined oxygen concentration in said fluid sample to determine a corrected value of said analyte concentration in said fluid sample.

9. The system of claim 8 wherein said reagent matrix of said oxygen sensor further includes one or more of a material selected from the group consisting of a surfactant, a polymer binder, an inactive bulking agent, and an antioxidant.

10. The system of claim 8 wherein said reduced form of said redox mediator is capable of being oxidized by hydrogen peroxide.

11. The system of claim 10 wherein said reduced form of said redox mediator is selected from the group consisting of potassium ferrocyanide, [Fe(phen)₃]²⁺, [Fe(bpy)₃]²⁺, [Co(NH₃)]²⁺, [Co(phen)₃]²⁺, [Co(bpy)₃]²⁺, [Os(bpy)₂Cl]⁺, [Os(phen)₂Cl]⁺, [Ru(bpy)₂]²⁺, [Rh(bpy)₂]²⁺, cobalt phthalocyanine, ferrocenes, methylene blue, methylene green, 7,7,8,8-tetracyanoquinodimethane, tetrathiafulvalene, toluidine blue, meldola blue, N-methylphenazine methosulfate, phenyldiamines, 3,3′

,5,5′

-tetramethylbenzidine, pyrogallol, and benzoquinone wherein phen is 1,10-phenanthroline and bpy is 2,2′

-bipyridine.

12. The system of claim 8 wherein said oxidase of said oxygen sensor is capable of producing hydrogen peroxide.

13. The system of claim 12 wherein said oxidase of said oxygen sensor is selected from the group consisting of glucose oxidase, acyl-CoA oxidase, N-acylhexosamine oxidase, D-amino acid oxidase, cholesterol oxidase, fructosyl-peptide oxidase, glutamate oxidase, L-α

-glycerophosphate oxidase, lactate oxidase, putrescine oxidase, pyranose oxidase, pyruvate oxidase, sarcosine oxidase, uricase, and xanthine oxidase.

14. The system of claim 8 wherein said peroxidase of said oxygen sensor is selected from the group consisting of soybean peroxidase and horseradish root peroxidase.

15. The system of claim 8 wherein said means for determining said oxygen concentration includes an oxygen empirical equation based on empirical data obtained with the configuration of said oxygen sensor.

16. The system of claim 15 wherein said oxygen empirical equation is represented by the formula

pO₂=ai²+bi+k₁

where a and b are empirical constants at a given glucose concentration in milligrams per deciliter determined by the configuration of said oxygen sensor, k₁ is an empirical constant based on electrode configuration, and i is the current in nanoamps measured by said oxygen sensor.

17. The system of claim 8 wherein said means for using said oxygen concentration to determine a corrected analyte concentration further includes an analyte empirical equation to determine a correction factor based on empirical data obtained with the configuration of said oxidased-based analyte sensor.

18. The system of claim 17 wherein said analyte empirical equation is represented by the formula

Δ

C=(−

2×

10<sup>−

06</sup>C²+3×

10<sup>−

05</sup>C−

k₆)pO₂+k₇

where C is said determined analyte concentration before correction, pO₂ is said determined oxygen concentration, and k₆ and k₇ are empirical constants based on electrode configuration.

19. The system of claim 9 wherein said polymer binder is selected from the group consisting of polyvinylpyrrolidone, polyethylene oxide, poly(vinyl alcohol), poly(ethylene glycol), poly(propylene glycol), polysulfone, carboxy methyl cellulose, hydroxypropyl cellulose, methyl cellulose, poly(2-ethyl-2oxazoline).

20. The system of claim 9 wherein said polymer binder is a mixture of polyethylene oxide and methyl cellulose.

21. The system of claim 9 wherein said surfactant is selected from the group consisting of anionic, cationic, non-ionic, and zwitterionic detergents.

22. The system of claim 9 wherein said surfactant is selected from the group consisting of Triton X-100, Tween 20, sodium cholate hydrate, hexadecylpyridinium cholide monohydrate, and CHAPs.

23. The system of claim 9 wherein said inactive bulking agent is a sugar.

24. The system of claim 23 wherein said sugar is selected from the group consisting of trehalose, galactose, suctose, lactose, mannitol, mannose, fructose, sucrose, lactose, lactitol, sorbitol, xylitol, and maltose.

25. The system of claim 9 wherein said antioxidant is selected from the group consisting of reductants and oxygen scavengers.

26. The system of claim 9 wherein said antioxidant is selected from the group consisting of sodium sulfite, sodium hydrosulfite, hydrazine, hydroquinone, carbohydrazide, N, N-Diethylhydroxylamine, methylethylketoxime, diethylthreitol, erythorbic acid, and ascorbic acid.

27. A combination for correcting the oxygen effect on oxidase-based analyte sensors, the combination comprising:

a disposable sensor strip comprising;

an oxygen electrode with an oxygen reagent matrix disposed thereon, said oxygen reagent matrix includes a reduced form of a redox mediator, an oxidase and a peroxidase wherein said oxygen sensor has a known correlation between oxygen concentration and analyte concentration expressed as a function of the response of said oxygen sensor to both oxygen and an analyte wherein said analyte is a substrate of said oxidase;

an oxidase-based analyte electrode with an oxidase-based reagent matrix thereon, said oxidase-based reagent matrix includes an oxidized form of a redox mediator and an enzyme capable of catalyzing a reaction involving a substrate for said oxidase of said oxygen electrode and wherein the correlation between oxygen concentration and oxygen effect on said oxidase-based analyte sensor is known;

a reference electrode; and

a sample chamber containing said oxygen electrode, said oxidase-based analyte electrode and said reference electrode; and

meter means for electronically coupling said oxygen electrode and said reference electrode to measure an oxygen concentration in a sample fluid, for electronically coupling said oxidased-based analyte electrode to said reference electrode to measure an analyte concentration in said sample fluid, and for electronically calculating a corrected analyte concentration in said fluid sample using said measured oxygen concentration.

28. The combination of claim 27 wherein said oxygen reagent matrix of said oxygen sensor further includes one or more of a material selected from the group consisting of a surfactant, a polymer binder, an inactive bulking agent, and an antioxidant.

29. The combination of claim 27 wherein said reduced form of said redox mediator is capable of being oxidized by hydrogen peroxide.

30. The combination of claim 29 wherein said reduced form of said redox mediator is selected from the group consisting of potassium ferrocyanide, [Fe(phen)₃]²⁺, [Fe(bpy)₃]²⁺, [Co(NH₃)]²⁺, [Co(phen)₃]²⁺, [Co(bpy)₃]²⁺, [Os(bpy)₂Cl]⁺, [Os(phen)₂CL]⁺, [Ru(bpy)₂]²⁺, [Rh(bpy)₂]²⁺, cobalt phthalocyanine, ferrocenes, methylene blue, methylene green, 7,7,8,8-tetracyanoquinodimethane, tetrathiafulvalene, toluidine blue, meldola blue, N-methylphenazine methosulfate, phenyldiamines, 3,3′

,5,5′

-tetramethylbenzidine, pyrogallol, and benzoquinone wherein phen is 1,10-phenanthroline and bpy is 2,2′

-bipyridine.

31. The combination of claim 27 wherein said oxidase of said oxygen sensor is capable of producing hydrogen peroxide.

32. The combination of claim 31 wherein said oxidase of said oxygen sensor is selected from the group consisting of glucose oxidase, acyl-CoA oxidase, N-acylhexosamine oxidase, D-amino acid oxidase, cholesterol oxidase, fructosyl-peptide oxidase, glutamate oxidase, L-α

-glycerophosphate oxidase, lactate oxidase, putrescine oxidase, pyranose oxidase, pyruvate oxidase, sarcosine oxidase, uricase, and xanthine oxidase.

33. The combination of claim 27 wherein said peroxidase of said oxygen sensor is selected from the group consisting of soybean peroxidase and horseradish root peroxidase.