System and method for analyte measurement using AC phase angle measurements

• US 20040157337A1
• Filed: 10/17/2003
• Published: 08/12/2004
• Est. Priority Date: 12/22/1997
• Status: Active Grant

• Current Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Original Assignee: Roche Operations Limited (Roche Holding AG)
• Inventors: Beaty, Terry A., Burke, David W., Svetnik, Vladimir, Kuhn, Lance S.
• Granted Patent: US 7,390,667 B2
• Time in Patent Office: Days
• US Class Current: 436/70
• CPC Class Codes: G01N 27/3273 Devices therefor, e.g. test element readers, circuitry details not specific to biochemical electrodes G01N33/4875
• 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: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/112499 with sample on test slide
• CPC Class Codes: Y10T 436/142222 Hetero-O [e.g., ascorbic acid, etc.]
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/144444 Glucose

Abstract

A method of measuring an analyte in a biological fluid comprises applying an excitation signal having a DC component and an AC component. The AC and DC responses are measured; a corrected DC response is determined using the AC response; and a concentration of the analyte is determined based upon the corrected DC response. Other methods and devices are disclosed.

Claims

1. A method for determining a glucose concentration of a blood sample, comprising the steps of:

a) applying a signal having an AC component to the blood sample;

b) measuring an AC phase angle response to the signal; and

c) determining the glucose concentration using the AC phase angle response.

2. The method of claim 1, wherein step (c) comprises determining an effective phase angle, which is proportional to the glucose concentration, using the AC phase angle response.

3. The method of claim 2, wherein step (c) comprises determining the effective phase angle using

P_eff=(Φ

/Γ

)<sup>−

γ</sup>

Where;

P_eff is the effective phase angle,

Φ

is the AC phase angle response, and

⊖ and

γ

are constants.

4. The method of claim 1, wherein step (a) comprises applying a signal having a frequency of 2 kHz or below.

5. The method of claim 1, wherein step (a) comprises applying a signal having a frequency of 1 kHz or below.

6. The method of claim 1, wherein step (a) comprises applying a signal having a frequency of 200 Hz or below.

7. The method of claim 2, wherein step (c) further comprises determining the glucose concentration using

PRED=(a₀+hct₁H_est+hct₂H_est²+tau₁dT+tau₂dT²)+(a₁P_eff)(1+hct₃H_est+hct₄H_est²)(1+tau₃dT+tau₄dT²)

Where:

PRED is the glucose concentration,

P_eff is the effective phase angle,

a₀, a₁, hct, hct₂, hct₃, hct₄, tau₁, tau₂, tau₃ and tau₄ are constants,

H_est is a hematocrit value of the blood sample, and

dT is the temperature

8. The method of claim 3, wherein step (a) comprises applying a signal having a frequency of 2 kHz or below.

9. The method of claim 1, wherein the signal is an AC signal.

10. The method of claim 1, wherein the AC component of the signal has a frequency not less than 1 Hz and not greater than 20 kHz.

11. A method of determining a glucose concentration of a biological fluid sample, comprising:

(a) applying a signal having an AC component to the sample;

(b) measuring an AC phase angle response to the signal; and

(c) determining the glucose concentration based upon the AC phase angle response and a predetermined correlation between the AC phase angle response and the glucose concentration.

12. The method of claim 11, wherein the biological fluid is blood.

13. The method of claim 12, wherein step (c) comprises determining an effective phase angle, which is proportional to the glucose concentration, using the AC phase angle response.

14. The method of claim 13, wherein step (c) comprises determining the effective phase angle using

P_eff=(Φ

/⊖

)<sup>−

γ</sup>

Where;

P_eff is the effective phase angle,

Φ

is the AC phase angle response, and

⊖ and

γ

are constants.

15. The method of claim 11, wherein step (a) comprises applying a signal having a frequency of 2 kHz or below.

16. The method of claim 11, wherein step (a) comprises applying a signal having a frequency of 1 kHz or below.

17. The method of claim 11, wherein step (a) comprises applying a signal having a frequency of 200 Hz or below.

18. The method of claim 13, wherein step (c) further comprises determining the glucose concentration using

PRED=(a₀+hct₁H_est+hct₂H_est²+tau₁dT+tau₂dT²)+(a₁P_eff)(1+hct₃H_est+hct₄H_est²)(1+tau₃dT+tau₄dT²)

Where:

PRED is the glucose concentration,

P_eff is the effective phase angle,

a₀, a₁, hct, hct₂, hct₃, hct₄, tau₁, tau₂, tau₃ and tau₄ are constants,

H_est is a hematocrit value of the blood sample, and

dT is the temperature

19. The method of claim 14, wherein step (a) comprises applying a signal having a frequency of 2 kHz or below.

20. The method of claim 11, wherein the signal is an AC signal.

21. The method of claim 11, wherein the AC component of the signal has a frequency not less than 1 Hz and not greater than 20 kHz.

22. A method of determining a glucose concentration of a test sample comprising:

(a) applying a signal having an AC component to the sample;

(b) measuring an AC phase angle response to the signal; and

(c) determining the glucose concentration using the first AC phase angle response and a predetermined compensation factor.

23. The method of claim 22, wherein the predetermined compensation factor accounts for a test sample temperature.

24. The method of claim 22, wherein the test sample is blood.

25. The method of claim 24, wherein the predetermined compensation factor accounts for a test sample hematocrit value.

26. The method of claim 24, wherein the predetermined compensation factor accounts for a test sample temperature and a test sample hematocrit value.

27. The method of claim 24, wherein step (c) comprises determining an effective phase angle, which is proportional to the glucose concentration, using the AC phase angle response.

28. The method of claim 27, wherein step (c) comprises determining the effective phase angle using

P_eff=(Φ

/⊖

)<sup>−

γ</sup>

Where;

P_eff is the effective phase angle,

Φ

is the AC phase angle response, and

⊖ and

γ

are constants.

29. The method of claim 22, wherein step (a) comprises applying a signal having a frequency of 2 kHz or below.

30. The method of claim 22, wherein step (a) comprises applying a signal having a frequency of 1 kHz or below.

31. The method of claim 22, wherein step (a) comprises applying a signal having a frequency of 200 Hz or below.

32. The method of claim 27, wherein step (c) further comprises determining the glucose concentration using

PRED=(a₀+hct₁H_est+hct₂H_est²+tau₁dT+tau₂dT²)+(a₁P_eff)(1+hct₃H_est+hct₄H_est²)(1+tau₃dT+tau₄dT²)

Where:

PRED is the glucose concentration,

P_eff is the effective phase angle,

a₀, a₁, hct, hct₂, hct₃, hct₄, tau₁, tau₂, tau₃ and tau₄ are constants,

H_est is a hematocrit value of the blood sample, and

dT is the temperature

33. The method of claim 28, wherein step (a) comprises applying a signal having a frequency of 2 kHz or below.

34. The method of claim 22, wherein the signal is an AC signal.

35. The method of claim 22, wherein the AC component of the signal has a frequency not less than 1 Hz and not greater than 20 kHz.

36. A method for determining a hematocrit value of a blood sample, comprising the steps of:

a) applying at least one signal having an AC component to the blood sample;

b) measuring at least one AC phase angle response to respective ones of the at least one signal; and

c) determining the hematocrit value using the at least one AC phase angle response.

37. The method of claim 36, wherein said at least one signal comprises at least two frequencies.

38. The method of claim 36, wherein said at least one signal comprises at least four frequencies.

39. The method of claim 37, wherein said at least two frequencies are applied at least partially simultaneously.

40. The method of claim 38, wherein said at least four frequencies are applied at least partially simultaneously.

41. The method of claim 36, wherein said at least one signal comprises n signals, and wherein step (c) comprises determining the hematocrit value using

H_est=c₀+c₁Φ

₁ . . . c_nΦ

_n

Where;

H_est is the hematocrit value,

c₀, c₁ . . . c_n are constants, and

Φ

₁ . . . Φ

_n are respective AC phase angle responses to each of the n signals.

42. A method for determining a hematocrit value of a blood sample, comprising the steps of:

(a) applying a first signal having an AC component to the blood sample, the first signal having a first frequency;

(b) measuring a first AC phase angle response to the first signal;

(c) applying a second signal having an AC component to the blood sample, the second signal having a second frequency;

(d) measuring a second AC phase angle response to the second signal; and

(e) determining the hematocrit value based at least in part upon the first phase angle response and the second phase angle response.

43. The method of claim 42, further comprising the steps of:

(f) applying a third signal having an AC component to the blood sample, the third signal having a third frequency;

(g) measuring a third AC phase angle response to the third signal;

(h) applying a fourth signal having an AC component to the blood sample, the fourth signal having a fourth frequency; and

(i) measuring a fourth AC phase angle response to the fourth signal;

(j) wherein the determining the hematocrit value is further based upon the third phase angle response and the fourth phase angle response.

44. The method of claim 42 wherein the first frequency is about 10 kHz and the second frequency is about 20 kHz.

45. The method of claim 43 wherein the third frequency is about 2 kHz and the fourth frequency is about 1 kHz.

46. The method of claim 42, wherein the first frequency and the second frequency are applied at least partially simultaneously.

47. The method of claim 43, wherein the first frequency, the second frequency, the third frequency and the fourth frequency are applied at least partially simultaneously.

48. The method of claim 43, wherein step (j) comprises determining the hematocrit value using

H_est=c₀+c₁Φ

₁+c₂Φ

₂+c₃Φ

₃+c₄Φ

₄

Where;

H_est is the hematocrit value,

c₀, c₁, c₂, c₃, c₄ are constants, and

Φ

₁,Φ

₂,Φ

₃,Φ

₄ are respective AC phase angle responses to the first, second, third and fourth signals.