SYSTEM AND METHOD FOR ANALYTE MEASUREMENT USING A NONLINEAR SAMPLE RESPONSE

• US 20070264721A1
• Filed: 05/09/2007
• Published: 11/15/2007
• Est. Priority Date: 10/17/2003
• Status: Abandoned Application

• Current Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Original Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Inventors: Buck, Harvey
• Application Number:
  US11/746,465
• Publication Number:
  US 20070264721A1
• Time in Patent Office: Days
• US Class Current: 436/150
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 27/3273 Devices therefor, e.g. test element readers, circuitry details not specific to biochemical electrodes G01N33/4875

Abstract

The systems and methods of the present invention utilize a linear component of a non-linear, faradaic current response generated by a biological fluid sample when an AC excitation potential sufficient to produce such a faradaic current response is applied to the sample, in order to calculate the concentration of a medically significant component in the biological fluid sample. The current response is created by the excitation of electrochemical processes within the sample by the applied potential. Typically, the linear component of the current response to an applied AC potential contains phase angle and/or admittance information that may be correlated to the concentration of the medically significant component. Also typically, the fundamental linear component of the current response is utilized in the disclosed systems and methods. Harmonics of the fundamental linear component may also be used. Other methods and devices are disclosed.

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, wherein the AC component has a magnitude sufficient to generate a faradaic current response from the biological fluid;

b) measuring the current response to the AC component;

c) determining a fundamental component of the current response, said fundamental component comprising a frequency at least substantially the same as the frequency of the AC component of the first signal; and

d) determining from the fundamental component an indication of the concentration of the medically significant component.

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

3. The method of claim 1, wherein the current response is at least partially caused by electrochemical processes within the biological fluid

4. The method of claim 1, wherein step (d) comprises determining said indication from a magnitude and phase angle of the fundamental component.

5. The method of claim 1, wherein step (d) comprises determining said indication only from a phase angle of the fundamental component.

6. The method of claim 1, wherein the current response comprises Admittance values.

7. The method of claim 5, wherein step (d) comprises calculating a tangent of the phase angle of the fundamental component.

8. The method of claim 5, wherein the phase angle is calculated relative to a non-zero origin.

9. The method of claim 1, wherein the current response is non-linear, and wherein step (c) comprises calculating a first Fourier component of the current response.

10. The method of claim 9, wherein step (c) comprises calculating a first Fourier component of the current response using a transform selected from the group consisting of a Fast Fourier Transform and a Discrete Fourier Transform.

11. The method of claim 1, wherein the biological fluid is blood.

12. The method of claim 11, wherein the medically significant component is glucose.

13. The method of claim 1, wherein the first signal is sinusoidal.

14. The method of claim 1, wherein the magnitude of the first signal is between about 200 and 550 mV rms.

15. The method of claim 1, wherein the first signal has a frequency of between about 10 and 1000 Hz.

16. The method of claim 1, wherein the first signal has a magnitude of about 300 mV rms and a frequency of about 128 Hz.

17. The method of claim 1, wherein the first signal has a magnitude of about 40 mV rms and a frequency of about 200 Hz.

18. The method of claim 1, wherein the concentration of the medically significant component is determined only from the fundamental component.

19. The method of claim 1, further comprising the step of:

e) before said step (a), detecting that the biological fluid is in contact with the reagent compound, wherein said step (d) occurs within about 4 seconds of said detecting.

20. The method of claim 19, wherein said step (d) occurs within about 2 seconds of said detecting.

21. The method of claim 20, wherein said step (d) occurs within about 1 second of said detecting.

22. The method of claim 1, wherein the first signal further comprises a second AC component having a magnitude insufficient for generating a faradaic current response from the biological fluid, and further comprising the steps of:

e) measuring the current response to the second AC component;

f) determining an interferent correction from the current response to the second AC component; and

g) adjusting the indication of the concentration from the fundamental component using the interferent correction.

23. The method of claim 22, further comprising the step of:

h) before said step (a), detecting that the biological fluid is in contact with the reagent compound, wherein said step (d) and said step (g) occurs within about 4 seconds of said detecting.

24. The method of claim 23, wherein said step (d) and said step (g) occurs within about 2 seconds of said detecting.

25. The method of claim 24, wherein said step (d) and said step (g) occurs within about 1 second of said detecting.

26. The method of claim 22, wherein the first signal further comprises a DC component, and the method further comprising the steps of:

h) measuring the current response to the DC component;

i) determining from the current response to the DC component an indication of the concentration of the medically significant component; and

j) correcting the indication from the DC component using the indication from the fundamental component of the AC component, the corrected indication from the DC component being adjusted using the interferent correction.

27. The method of claim 1, wherein the first signal further comprises a DC component, and the method further comprising the steps of:

e) measuring the current response to the DC component;

f) determining from the current response to the DC component an indication of the concentration of the medically significant component; and

g) correcting the indication from the DC component using the indication from the fundamental component of the AC component.

28. The method of claim 1, wherein said first signal comprises an AC signal having a single frequency.

29. The method of claim 1, wherein said first signal comprises an AC signal and a DC signal.

30. The method of claim 1, wherein said first signal comprises an AC signal having multiple frequencies.

111. The method of claim 27, wherein the AC component and the DC component are applied sequentially.

31. 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 AC signal to the biological fluid, wherein the first AC signal has a magnitude sufficient to generate a faradaic current response from the biological fluid;

b) measuring the current response to the first AC signal;

c) determining a fundamental component of the current response, said fundamental component comprising a frequency at least substantially the same as the frequency of the first signal; and

d) determining from the fundamental component an indication of the concentration of the medically significant component.

32. The method of claim 31, wherein the current response is at least partially caused by electrochemical processes within the biological fluid.

33. The method of claim 31, wherein step (d) comprises determining said indication from a magnitude and phase angle of the fundamental component.

34. The method of claim 31, wherein step (d) comprises determining said indication only from a phase angle of the fundamental component.

35. The method of claim 31, wherein the current response comprises Admittance values.

36. The method of claim 34, wherein step (d) comprises calculating a tangent of the phase angle of the fundamental component.

37. The method of claim 34, wherein the phase angle is calculated relative to a non-zero origin.

38. The method of claim 31, wherein the current response is non-linear, and wherein step (c) comprises calculating a first Fourier component of the current response.

39. The method of claim 38, wherein step (c) comprises calculating a first Fourier component of the current response using a transform selected from the group consisting of a Fast Fourier Transform and a Discrete Fourier Transform.

40. The method of claim 31, wherein the biological fluid is blood.

41. The method of claim 40, wherein the medically significant component is glucose.

42. The method of claim 31, wherein the first AC signal is sinusoidal.

43. The method of claim 31, wherein the magnitude of the first signal is between about 200 and 550 mV rms.

44. The method of claim 31, wherein the first signal has a frequency of between about 10 and 1000 Hz.

45. The method of claim 31, wherein the first signal has a magnitude of about 300 mV rms and a frequency of about 128 Hz.

46. The method of claim 31, wherein the first signal has a magnitude of about 40 mV rms and a frequency of about 200 Hz.

47. The method of claim 31, wherein the concentration of the medically significant component is determined only from the fundamental component.

48. The method of claim 31, further comprising the step of:

e) before said step (a), detecting that the biological fluid is in contact with the reagent compound, wherein said step (d) occurs within about 4 seconds of said detecting.

49. The method of claim 48, wherein said step (d) occurs within about 2 seconds of said detecting.

50. The method of claim 49, wherein said step (d) occurs within about 1 second of said detecting.

51. The method of claim 31, further comprising the steps of:

e) applying a second AC signal to the biological fluid, wherein the second AC signal has a magnitude insufficient for generating a faradaic current response from the biological fluid;

f) measuring the current response to the second AC signal;

g) determining an interferent correction from a phase angle of the current response to the second AC signal; and

h) adjusting the indication of the concentration from the fundamental component using the interferent correction.

52. The method of claim 51, further comprising the step of:

i) before said step (a), detecting that the biological fluid is in contact with the reagent compound, wherein said step (d) and said step (h) occurs within about 4 seconds of said detecting.

53. The method of claim 52, wherein said step (d) and said step (h) occurs within about 2 seconds of said detecting.

54. The method of claim 53, wherein said step (d) and said step (h) occurs within about 1 second of said detecting.

55. The method of claim 51, further comprising the steps of:

i) applying a DC signal to the biological fluid;

j) measuring the current response to the DC signal;

k) determining from the current response to the DC signal an indication of the concentration of the medically significant component; and

l) correcting the indication from the DC signal using the indication from the fundamental component of the first AC signal, the corrected indication from the DC component being adjusted using the interferent correction.

56. The method of claim 31, further comprising the steps of:

e) applying a DC signal to the biological fluid;

f) measuring the current response to the DC signal;

g) determining from the current response to the DC signal an indication of the concentration of the medically significant component; and

h) correcting the indication from the DC signal using the indication from the fundamental component of the AC signal.

57. The method of claim 31, wherein said first AC signal comprises an AC signal having a single frequency.

58. The method of claim 31, wherein said first AC signal comprises an AC signal having multiple frequencies.

112. The method of claim 56, wherein the AC signal and the DC signal are applied sequentially.

59. A method for determining a glucose concentration of a blood sample in contact with a reagent compound, comprising the steps of:

a) applying a first signal having an AC component to the blood sample, wherein the AC component has a magnitude sufficient to generate a faradaic current response from the blood sample;

b) measuring the current response to the AC component;

c) determining a fundamental component of the response, said fundamental component comprising a frequency at least substantially the same as the frequency of the AC component of the first signal; and

d) determining from the fundamental component an indication of the glucose concentration.

60. The method of claim 59, wherein the first signal is an AC signal.

61. The method of claim 59, wherein the current response is at least partially caused by electrochemical processes within the blood sample.

62. The method of claim 59, wherein step (d) comprises determining said indication from a magnitude and phase angle of the fundamental component.

63. The method of claim 59, wherein step (d) comprises determining said indication only from a phase angle of the fundamental component.

64. The method of claim 59, wherein the current response comprises Admittance values.

65. The method of claim 62, wherein step (d) comprises calculating a tangent of the phase angle of the fundamental component.

66. The method of claim 62, wherein the phase angle is calculated relative to a non-zero origin.

67. The method of claim 59, wherein the current response is non-linear, and wherein step (c) comprises calculating a first Fourier component of the current response.

68. The method of claim 67, wherein step (c) comprises calculating a first Fourier component of the current response using a transform selected from the group consisting of a Fast Fourier Transform and a Discrete Fourier Transform.

69. The method of claim 59, wherein the first signal is sinusoidal.

70. The method of claim 59, wherein the magnitude of the first signal is between about 200 and 500 mV rms.

71. The method of claim 59, wherein the first signal has a frequency of between about 100 and 1000 Hz.

72. The method of claim 59, wherein the first signal has a magnitude of about 300 mV rms and a frequency of about 128 Hz.

73. The method of claim 59, wherein the first signal has a magnitude of about 40 mV rms and a frequency of about 200 Hz.

74. The method of claim 59, wherein the glucose concentration is determined only from the fundamental component.

75. The method of claim 59, further comprising the step of:

e) before said applying the first signal, detecting that the blood is in contact with the reagent compound, wherein said step (d) occurs within about 4 seconds of said detecting.

76. The method of claim 75, wherein said step (d) occurs within about 2 seconds of said detecting.

77. The method of claim 76, wherein said step (d) occurs within about 1 second of said detecting.

78. The method of claim 59, wherein the first signal further comprises a second AC component having a magnitude insufficient for generating a faradaic current response from the blood, and the method further comprising the steps of:

e) measuring the current response to the second AC component;

f) determining an interferent correction from a phase angle of the current response to the second AC component; and

g) adjusting the indication of the concentration from the fundamental component using the interferent correction.

79. The method of claim 78, further comprising the step of:

h) before said step (a), detecting that the blood is in contact with the reagent compound, wherein said step (d) and said step (g) occurs within about 4 seconds of said detecting.

80. The method of claim 79, wherein said step (d) and said step (g) occurs within about 2 seconds of said detecting.

81. The method of claim 80, wherein said step (d) and said step (g) occurs within about 1 second of said detecting.

82. The method of claim 78, wherein the first signal further comprises a DC component, and the method further comprising the steps of:

h) measuring the current response to the DC component;

i) determining from the current response to the DC component an indication of the concentration of glucose; and

j) correcting the indication from the DC component using the indication from the fundamental component of the AC component, the corrected indication from the DC component being adjusted using the interferent correction.

83. The method of claim 59, wherein the first signal further comprises a DC component, and the method further comprising the steps of:

e) measuring the current response to the DC component;

f) determining from the current response to the DC component an indication of the concentration of glucose; and

g) correcting the indication from the DC component using the indication from the fundamental component of the AC component.

84. The method of claim 59, wherein said first signal comprises an AC signal having a single frequency.

85. The method of claim 59, wherein said first signal comprises an AC signal having multiple frequencies.

86. The method of claim 59, wherein said first signal comprises and AC signal and a DC signal.

113. The method of claim 82, wherein the AC component, the second AC component and the DC component are applied sequentially.

87. A system for determining a concentration of a medically significant component of a biological fluid, the system comprising:

a biosensor comprising at least two electrically isolated electrodes and a reagent compound proximal to or in contact with at least one of the electrodes;

a measurement device in electrical communication with the electrodes of the biosensor, the device being configured and arranged to conduct a measurement sequence and data evaluation when the biological fluid is brought into contact with the at least two electrodes and the reagent compound to bring the electrodes into electrical communication with each other, the fluid and the reagent compound;

said measurement sequence comprising;

application of a first signal having an AC component to the biological fluid using the at least two electrodes, wherein the AC component has a magnitude sufficient to generate a faradaic current response from the biological fluid;

measurement of the current response to the AC component;

determination of a fundamental component of the current response, said fundamental component comprising a frequency at least substantially the same as the frequency of the AC component of the first signal; and

determination from the fundamental component of an indication of the concentration of the medically significant component.

88. The system of claim 87, wherein the determination of an indication of the concentration comprises determination of said indication from a magnitude and phase angle of the fundamental component.

89. The system of claim 87, wherein the current response comprises Admittance values.

90. The system of claim 87, wherein the determination of an indication of the concentration comprises a calculation of the phase angle of the fundamental component, the phase angle being calculated relative to a non-zero origin.

91. The system of claim 87, wherein the current response is non-linear, and wherein the determination of a fundamental component of the current response comprises calculation of a first Fourier component of the current response.

92. The system of claim 87, wherein the biological fluid is blood.

93. The system of claim 92, wherein the medically significant component is glucose.

94. The system of claim 87, wherein the first signal is sinusoidal.

95. The system of claim 87, wherein the magnitude of the first signal is between about 200 and 550 mV rms.

96. The system of claim 87, wherein the first signal has a frequency of between about 10 and 1000 Hz.

97. The system of claim 87, wherein the first signal has a magnitude of about 300 mV rms and a frequency of about 128 Hz.

98. The system of claim 87, wherein the first signal has a magnitude of about 40 mV rms and a frequency of about 200 Hz.

99. The system of claim 87, wherein the measurement sequence further comprises detection of the biological fluid being in contact with the reagent compound before the application of the first signal, wherein the determination of the indication of concentration occurs within about 4 seconds of the detection.

100. The system of claim 99, wherein the determination of the indication of concentration occurs within about 2 seconds of the detection.

101. The system of claim 100, wherein the determination of the indication of concentration occurs within about 1 second of the detection.

102. The system of claim 87, wherein the first signal further comprises a second AC component having a magnitude insufficient for generating a faradaic current response from the biological fluid, and the measurement sequence further comprises measurement of the current response to the second AC component, determination of an interferent correction from a phase angle of the current response to the second AC component, and an adjustment to the indication of the concentration from the fundamental component using the interferent correction.

103. The system of claim 102, wherein the measurement sequence further comprises detection of the biological fluid being in contact with the reagent compound before the application of the first signal, wherein the determination of the indication of concentration and the adjustment to the indication using the interferent correction occurs within about 4 seconds of the detection.

104. The system of claim 103, wherein the determination of the indication of concentration and the adjustment to the indication using the interferent correction occurs within about 2 seconds of the detection.

105. The system of claim 104, wherein the determination of the indication of concentration and the adjustment to the indication using the interferent correction occurs within about 1 second of the detection.

106. The system of claim 102, wherein the first signal further comprises a DC component, and the measurement sequence further comprises a measurement of the current response to the DC component, a determination from the current response to the DC component of an indication of the concentration of the medically significant component, and a correction to the indication from the DC component using the indication from the fundamental component of the AC component, the corrected indication from the DC component being adjusted using the interferent correction.

107. The system of claim 87, wherein the first signal further comprises a DC component, and the measurement sequence further comprises a measurement of the current response to the DC component, determination from the current response to the DC component of an indication of the concentration of the medically significant component, and a correction to the indication from the DC component using the indication from the fundamental component of the AC component.

108. The system of claim 87, wherein said first signal comprises an AC signal having a single frequency.

109. The system of claim 87, wherein said first signal comprises an AC signal and a DC signal.

110. The system of claim 87, wherein said first signal comprises an AC signal having multiple frequencies.

114. The method of claim 106, wherein the AC component, the second AC component and the DC component are applied sequentially.