SYSTEM AND METHOD FOR DETERMINING THE CONCENTRATION OF AN ANALYTE IN A SAMPLE FLUID

• US 20100170807A1
• Filed: 12/30/2009
• Published: 07/08/2010
• Est. Priority Date: 06/20/2003
• Status: Active Grant

• Current Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Original Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Inventors: Buck, Harvey B. JR., Beaty, Terry A., Diebold, Eric R.
• Granted Patent: US 8,148,164 B2
• Time in Patent Office: Days
• US Class Current: 205/792
• 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 33/49 Blood chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80

Abstract

The present disclosure relates to various methods for measuring the amount of an analyte present in a biological fluid using an electrochemical testing process. Various embodiments are disclosed, including the use of AC test signals and the performance of tests having a Total Test Time within about 2.0 seconds or less, and/or having a clinically low Total System Error.

Claims

1. A method for determining a concentration of a medically significant component of a biological fluid in contact with a reagent compound, comprising the steps of:

a) applying a first signal having an AC component to the biological fluid;

b) measuring a first response to the first signal;

c) applying a second signal to the biological fluid, wherein the second signal is a DC signal;

d) measuring a second response to the second signal; and

e) combining the first response with the second response to produce an indication of the concentration of the medically significant component;

wherein said first signal comprises a multi-frequency excitation waveform.

2. The method according to claim 1, wherein the first response comprises admittance data corresponding to each frequency of the multi-frequency excitation waveform, the second response comprises an uncorrected response of the medically significant component predicted with the DC signal, and wherein combining the first response with the second response comprises an algorithmic combination of the admittance data and the uncorrected response to calculate a predicted concentration of the medically significant component in the biological fluid.

3. The method according to claim 2, wherein the medically significant component comprises glucose and the biological fluid comprises blood.

4. The method according to claim 1, wherein combining the first response with the second response comprises the steps of determining an interferent correction from the first response, determining an indicated concentration from the second response, and correcting the indicated concentration using the interferent correction.

5. The method according to claim 4, wherein the medically significant component comprises glucose, the biological fluid comprises blood, and the first response comprises information pertaining substantially only to one or both of hematocrit and temperature.

6. The method according to claim 1, wherein the total time from applying the first signal to measuring the second response is within about 2.0 seconds.

7. The method according to claim 1, wherein the method has a Total System Error of less than about 15%.

8. The method according to claim 1, wherein the multi-frequency excitation waveform comprises at least two frequencies selected from the group consisting of about 1 kHz, about 2 kHz, about 10 kHz and about 20 kHz.

9. The method according to claim 8, wherein measuring the first response comprises measuring one or both of admittance and phase information corresponding to each of the frequencies comprising the multi-frequency excitation waveform generally simultaneously.

10. The method according to claim 9, wherein measuring the second response occurs within about 1000 ms or less after the measuring the first response.

11. A method for determining a concentration of glucose in a whole blood sample, comprising:

a) applying a signal to the sample;

b) measuring a response to the signal; and

c) determining the analyte concentration of the sample using at least the response wherein the determination has a Total Test Time of within about 2.0 seconds or less;

wherein the signal has an AC component comprising a multi-frequency excitation waveform.

12. The method of claim 11, wherein the determination has a Total Test Time of between about 0.5 seconds and about 1.525 seconds, and wherein the method has a Total System Error of less than about 11%.

13. A method for determining a concentration of an analyte of interest in a biological sample, comprising:

a) applying a first signal having a first AC component to the sample;

b) measuring a first response to the first signal;

c) applying a second signal having a second AC component to the sample;

d) measuring a second response to the second signal;

e) applying a third signal having a third AC component to the sample;

measuring a third response to the third signal;

g) applying a fourth DC signal to the sample;

h) measuring a fourth response to the fourth signal; and

e) determining the analyte concentration of the sample using at least the first, second and third responses to correct the fourth response for the effects of at least one interferent within the sample, wherein the determination has a Total Test Time of within about 2.0 seconds or less.

14. The method of claim 13, wherein the determination has a Total Test Time of between about 0.5 seconds and about 1.525 seconds.

15. The method of claim 13, wherein the biological fluid is blood and the analyte of interest is glucose.

16. The method of claim 13, wherein the first, second and third signals each comprise an AC signal having different frequencies, and wherein the fourth signal comprises a DC signal.

17. The method of claim 13, wherein the interferent comprises one or both of hematocrit and temperature.

18. A method for determining a concentration of an analyte of interest in a biological sample, comprising:

a) applying a first signal having a first AC component to the sample;

b) measuring a first response to the first signal, wherein the first signal is applied for no more than about 100 ms before the first response is measured;

c) applying a second signal having a second AC component to the sample;

measuring a second response to the second signal, wherein the second signal is applied for no more than about 100 ms before the second response is measured;

e) applying a third signal having a third AC component to the sample;

f) measuring a third response to the third signal, wherein the third signal is applied for no more than about 100 ms before the third response is measured;

g) applying a fourth signal having a fourth AC component to the sample;

h) measuring a fourth response to the fourth signal, wherein the fourth signal is applied for no more than about 100 ms before the fourth response is measured;

i) applying a fifth DC signal to the sample;

j) measuring a fifth response to the fifth signal; and

k) determining the analyte concentration of the sample using at least the first, second, third and fourth responses to correct the fifth response for the effects of at least one interferent within the sample.

19. The method of claim 18, wherein the determination has a Total Test Time of between about 0.5 seconds and about 2.0 seconds.

20. The method of claim 18, wherein the biological fluid is blood and the analyte of interest is glucose.

21. The method of claim 18, wherein the first, second, third and fourth signals each comprise an AC signal.

22. The method of claim 18, wherein the interferent comprises one or both of hematocrit and temperature.

23. The method of claim 18, wherein the first signal is a 10 kHz AC signal, the second signal is a 20 kHz AC signal, the third signal is a 1 kHz AC signal, and the fourth signal is a 2 kHz AC signal.

24. The method of claim 18, wherein the fifth signal is applied for no more than about 200 ms before the fifth response is measured.

25. The method of claim 18, wherein the method has a Total System Error of between about 7.5% and about 11%.

26. The method of claim 19, wherein the method has a Total System Error of between about 7.5% and about 11%.

27. A method for determining a concentration of an analyte of interest in a biological sample, comprising:

a) applying the sample to a reagent film having a thickness between about 1.6 μ

m and about 5 μ

m;

b) applying a signal to the sample;

c) measuring a response to the signal; and

d) determining the analyte concentration of the sample using at least the response wherein the determination has a Total Test Time of within about 2.0 seconds or less.

28. The method of claim 27, wherein the determination has a Total Test Time of between about 0.6 seconds and about 1.525 seconds.

29. The method of claim 27, wherein the biological fluid is blood and the analyte of interest is glucose.

30. The method of claim 27, wherein the signal is a signal having an AC component.

31. The method of claim 30, wherein the signal is a multi-frequency AC signal.

32. The method of claim 27, further comprising the steps of:

e) applying a second signal to the sample; and

f) measuring a second response to the second signal;

wherein step (d) comprises determining the analyte concentration of the sample using at least the first response to correct the second response for the effects of at least one interferent within the sample.

33. The method of claim 32, wherein the second signal is a DC signal.

34. The method of claim 27, wherein step (a) comprises applying the sample to a reagent film having a thickness between about 1.6 μ

m and about 5 μ

m.

35. A method for determining a concentration of an analyte of interest in a biological sample, comprising:

a) providing an electrochemical biosensor having a reagent coating an electrode system configured for use in an electrochemical analysis, the reagent coating having a thickness less than 4 um;

b) providing a biological sample to the biosensor, the biosensor being configured to permit the sample to contact the reagent coating;

c) electrically detecting a time when the sample contacts the reagent coating;

d) applying a first signal to the sample;

e) measuring a first response to the first signal;

f) applying a second signal to the sample;

g) measuring a second response to the second signal; and

h) determining the analyte concentration of the sample using at least the first and second response;

wherein the first signal comprises an AC component having at least two sequentially applied frequencies, the first response comprising response data for each of the frequencies, the response data comprising correction factor information;

wherein the second signal comprises a DC signal, the second response comprising a current response indicative of the analyte concentration;

wherein the first signal is applied substantially at the time the sample contacts the reagent coating for a first period of time from about 400 ms to about 800 ms;

wherein the second signal is applied substantially immediately after the period for the first signal for a second period of time from about 100 ms to about 2200 ms; and

wherein the determination has a Total Test Time of within about 3.0 seconds or less and a TSE about 9.0% or less.

36. The method of claim 35, wherein the second period of time is from about 100 ms to about 300 ms, the Total Test Time is within about 1.1 seconds or less, and the TSE is about 8.5% or less.

37. The method of claim 35, wherein the AC component comprises 4 sequentially applied frequencies each applied for no more than 200 ms such that the first period of time does not exceed 800 ms, and wherein the second period of time is about 100 ms, the Total Test Time is about 900 ms, and the TSE is about 8.0% or less.