System and method for measuring an analyte in a sample

• US 8,603,768 B2
• Filed: 01/06/2009
• Issued: 12/10/2013
• Est. Priority Date: 01/17/2008
• Status: Active Grant

• Current Assignee: Cilag Gmbh International (Johnson & Johnson)
• Original Assignee: Lifescan Incorporated (Duv Holding Corporation)
• Inventors: Chatelier, Ronald C., Hodges, Alastair M., Nandagopalan, Santhanagopalan
• Primary Examiner(s): Ball, J. Christopher
• Application Number:
  US12/349,017
• Publication Number:
  US 20090184004A1
• Time in Patent Office: 1,799 Days
• Field of Search: 205/777.5, 205/778, 205/792, 20440301-40315, 436/70, 435/14, 435/25, 600/347, 600/365
• US Class Current: 435/14
• 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
• CPC Class Codes: G01N 27/4163 checking the operation of, or calibrating, the measuring apparatus G01N27/3274, G01N27/4175 and G01N33/0006 take precedence

Abstract

Methods of determining a corrected analyte concentration in view of some error source are provided herein. The methods can be utilized for the determination of various analytes and/or various sources of error. In one example, the method can be configured to determine a corrected glucose concentration in view of an extreme level of hematocrit found within the sample. In other embodiments, methods are provided for identifying various system errors and/or defects. For example, such errors can include partial-fill or double-fill situations, high track resistance, and/or sample leakage. Systems are also provided for determining a corrected analyte concentration and/or detecting some system error.

Claims

1. A method of calculating an analyte concentration of a sample, comprising:

introducing a sample to an electrochemical cell that includes a first electrode and a second electrode;

applying a first test voltage V₁ for a first time interval T₁ between the first electrode and the second electrode sufficient to at least partially oxidize a reduced mediator at the second electrode;

applying a second test voltage V₂ for a second time interval T₂ between the first electrode and the second electrode sufficient to at least partially oxidize the reduced mediator at the first electrode;

calculating an initial analyte concentration of the sample based on at least one test current value determined during the first time interval T₁ and the second time interval T₂;

calculating an error source of the sample; and

calculating a corrected analyte concentration based on the initial analyte concentration and the error source;

wherein the analyte includes glucose and the error source includes a hematocrit level H of the sample, the calculating steps being calculating an initial glucose concentration G₁ of the sample based on at least one test current value determined during the first time interval T₁ and the second time interval T₂, calculating the hematocrit level H of the sample, and calculating a corrected glucose concentration G₂ based on the initial glucose concentration G₁ and the hematocrit level H.

2. The method of claim 1, wherein the step of calculating the corrected glucose concentration comprises:

calculating a correction value Corr with a first function, the first function utilized if the hematocrit level H is less than a lower predetermined hematocrit level H_L and if the initial glucose concentration G₁ is less than an upper predetermined glucose concentration G_U; and

calculating the corrected glucose concentration G₂ based on the initial glucose concentration G₁, the hematocrit level H, and the correction value Corr.

3. The method of claim 2, wherein the first function is an equation, the equation being

Corr=K₁(H_L−

G₁

where Corr is the correction value, K₁ is a first constant, H_L is the lower predetermined hematocrit level, H is the hematocrit level, and G₁ is the initial glucose concentration.

4. The method of claim 3, wherein the corrected glucose concentration G₂ is determined by the equation G₂=G₁+Corr if the initial glucose concentration G₁ is less than a glucose threshold.

5. The method of claim 3, wherein the corrected glucose concentration G₂ is determined by the equation

6. The method of claim 1, wherein the step of calculating the corrected glucose concentration comprises:

calculating a correction value Corr with a second function, the second function utilized if the hematocrit level H is less than a lower predetermined hematocrit level H_L and if the initial glucose concentration G₁ is greater than the upper predetermined glucose concentration G_U; and

calculating the corrected glucose concentration G₂ based on the initial glucose concentration G₁, the hematocrit level H, and the correction value Corr.

7. The method of claim 6, wherein the second function is an equation, the equation being

Corr=K₂(H_L−

H)(G_max−

G₁)

where Corr is the correction value, K₂ is a second constant, H_L is the lower predetermined hematocrit level, H is the hematocrit level, G_max is a predetermined maximum glucose concentration, and G₁ is the initial glucose concentration.

8. The method of claim 1, wherein the corrected glucose concentration G₂ is determined to be substantially equal to the initial glucose concentration G₁ if the hematocrit level H is greater than an upper predetermined hematocrit level H_U and if the first glucose concentration G₁ is less than a lower predetermined glucose concentration G_L.

9. The method of claim 1, wherein calculating the corrected glucose concentration comprises:

calculating a correction value Corr with a fourth function, the fourth function utilized if the hematocrit level H is greater than an upper predetermined hematocrit level H_U and if the initial glucose concentration G₁ is greater than the lower predetermined glucose concentration G_L; and

calculating the corrected glucose concentration G₂ based on the initial glucose concentration G₁, the hematocrit level H, and the correction value Corr.

10. The method of claim 9, wherein the fourth function is an equation, the equation being

Corr=K₄(H−

H_U)(G₁−

G_L)

where Corr is the correction value, K₄ is a fourth constant, H is the hematocrit level, H_U is the upper predetermined hematocrit level, G₁ is the initial glucose concentration, G_L is the lower predetermined glucose concentration.

11. The method of claim 1, wherein the hematocrit level H is based on at least one test current value determined during the first time interval T₁ and the second time interval T₂.

12. The method of claim 1, wherein the hematocrit level H is calculated using a hematocrit equation, the hematocrit equation being

H=K₅ ln(|i₂|)+K₆ ln(G₁)+K₇

where H is the hematocrit level, K₅ is a fifth constant, i₂ is at least one current value during the second time interval, K₆ is a sixth constant, G₁ is the initial glucose concentration, and K₇ is a seventh constant.

13. The method of claim 1, wherein the second test voltage V₂ is applied immediately after the first test voltage V₁.

14. The method of claim 1, wherein the first test voltage V₁ has a first polarity and the second test voltage V₂ has a second polarity, the first polarity being opposite in sign to the second polarity.

15. The method of claim 1, wherein the first test voltage V₁ ranges from about −

100 mV to about −

600 mV with respect to the second electrode.

16. The method of claim 1, wherein the second test voltage V₂ ranges from about +100 mV to about +600 mV with respect to the second electrode.

17. The method of claim 1, wherein the first electrode and the second electrode have an opposing face arrangement.

20. The method of claim 1, wherein the corrected glucose concentration G₂ is calculated based on a set of equations, the set of equations being based on the hematocrit level H of the sample and the initial glucose concentration G₁ of the sample.

21. The method of claim 20, wherein an equation of the set of equations is selected to calculate the corrected glucose concentration G₂ based on at least one of:

a comparison of the hematocrit level H to one or more predetermined hematocrit levels and a comparison of the initial glucose concentration G₁ to one or more predetermined glucose concentration levels.

18. A system for determining an analyte concentration, comprising:

an electrochemical cell having at least two electrodes and being sized and configured to receive a sample, the electrochemical cell further configured to determine an initial analyte concentration and also configured to generate a pre-determined voltage between the first and second electrodes for a pre-determined amount of time, and further configured to measure at least one resulting current of the sample during the pre-determined time; and

a processor for receiving a set of data from the electrochemical cell, the data including the initial analyte concentration, at least one applied voltage, and at least one resulting current, the processor further configured to utilize this data to determine a corrected analyte concentration,

wherein the analyte includes glucose, the electrochemical cell is further configured to calculate a hematocrit level, and the processor receives the calculated hematocrit level, determines a correction term based on the calculated hematocrit level and the initial glucose concentration, and utilizes the correction term as data used to determine the corrected analyte concentration.

22. The system of claim 18, wherein the processor utilizes a set of equations to determine the correction term, the set of equations being based on the calculated hematocrit level of the sample and the initial glucose concentration of the sample.

23. The system of claim 22, wherein the processor selects an equation of the set of equations to calculate the correction term based on at least one of:

a comparison of the calculated hematocrit level of the sample to one or more predetermined hematocrit levels and a comparison of the initial glucose concentration of the sample to one or more predetermined glucose concentration levels.

19. A device for use in determining a corrected analyte concentration, comprising:

a test strip having a sample reaction chamber configured to receive a sample such that the sample is in communication with at least first and second electrodes; and

a reagent layer disposed on at least one electrode, the reagent layer formed of at least one component configured to react with the sample such that at least two voltages applied to the sample at least two time intervals results in corresponding currents within the sample which are indicative of an initial analyte concentration and a corrected analyte concentration,

wherein the analyte includes glucose and the corrected analyte concentration is calculated based on a calculated hematocrit level of the sample and the initial glucose concentration of the sample.

24. The device of claim 19, wherein the corrected analyte concentration is calculated based on a set of a equations, the set of equations being based on the calculated hematocrit level of the sample and the initial glucose concentration of the sample.

25. The device of claim 24, wherein an equation of the set of equations is selected to calculate the corrected glucose concentration based on at least one of:

a comparison of the calculated hematocrit level of the sample to one or more predetermined hematocrit levels and a comparison of the initial glucose concentration of the sample to one or more predetermined glucose concentration levels.