Calibration techniques for a continuous analyte sensor

• US 20050143635A1
• Filed: 12/03/2004
• Published: 06/30/2005
• Est. Priority Date: 12/05/2003
• Status: Active Grant

• Current Assignee: DexCom Incorporated
• Original Assignee: DexCom Incorporated
• Inventors: Goode, Paul V. Jr., Kamath, Apurv Ullas, Brauker, James H., Simpson, Peter C.
• Granted Patent: US 7,715,893 B2
• Time in Patent Office: Days
• US Class Current: 600/347
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/7203 for noise prevention, reduction or removal
• CPC Class Codes: A61B 5/742 using visual displays A61B5/339 takes precedence
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing

Abstract

Disclosed herein are systems and methods for calibrating a continuous analyte sensor, such as a continuous glucose sensor. One such system utilizes one or more electrodes to measure an additional analyte. Such measurements may provide a baseline or sensitivity measurement for use in calibrating the sensor. Furthermore, baseline and/or sensitivity measurements may be used to trigger events such as digital filtering of data or suspending display of data.

Claims

1. A method for measuring a sensitivity change of a glucose sensor implanted in a host over a time period, the method comprising:

measuring a first signal in the host by obtaining at least one glucose-related sensor data point, wherein the first signal is measured at a glucose-measuring electrode disposed beneath an enzymatic portion of a membrane system on the sensor; and

measuring a second signal in the host by obtaining at least one non-glucose constant data point, wherein the second signal is measured beneath the membrane system on the sensor; and

monitoring the second signal over a time period, whereby a sensitivity change associated with solute transport through the membrane system is measured.

2. The method of claim 1, wherein the second signal is indicative of a presence or absence of a water-soluble analyte.

3. The method of claim 2, wherein the water-soluble analyte comprises urea.

4. The method of claim 1, wherein the second signal is measured at an oxygen-measuring electrode disposed beneath a non-enzymatic portion of the membrane system.

5. The method of claim 1, wherein the glucose-measuring electrode incrementally measures oxygen, whereby the second signal is measured.

6. The method of claim 1, wherein the second signal is measured at an oxygen sensor disposed beneath the membrane system.

7. The method of claim 1, wherein the sensitivity change is calculated as a glucose-to-oxygen ratio, whereby an oxygen threshold is determined that is indicative of a stability of the glucose sensor.

8. The method of claim 7, further comprising filtering the first signal responsive to the stability of the glucose sensor.

9. The method of claim 7, further comprising displaying a glucose value derived from the first signal, wherein the display is suspended depending on the stability of the glucose sensor.

10. The method of claim 7, further comprising calibrating the first signal, wherein the calibrating step is suspended when the glucose sensor is determined to be stable.

11. The method of claim 1, further comprising calibrating the glucose sensor when the sensitivity change exceeds a preselected value.

12. The method of claim 11, wherein the step of calibrating comprises receiving a reference signal from a reference analyte monitor, the reference signal comprising at least one reference data point.

13. The method of claim 11, wherein the step of calibrating comprises using the sensitivity change to calibrate the glucose sensor.

14. The method of claim 11, wherein the step of calibrating is performed repeatedly at a frequency responsive to the sensitivity change.

15. The method of claim 1, further comprising determining a stability of glucose transport through the membrane system, wherein the stability of glucose transport is determined by measuring the sensitivity change over a time period.

16. The method of claim 15, further comprising a step of prohibiting calibration of the glucose sensor when glucose transport is determined to be unstable.

17. The method of claim 15, further comprising a step of filtering at least one glucose-related sensor data point when glucose transport is determined to be unstable.

18. A system for measuring glucose in a host, the system comprising:

a glucose-measuring electrode configured to generate a first signal comprising at least one glucose-related sensor data point, wherein the glucose-measuring electrode is disposed beneath an enzymatic portion of a membrane system on a glucose sensor; and

a transport-measuring electrode configured to generate a second signal comprising at least one non-glucose constant analyte data point, wherein the transport-measuring electrode is situated beneath the membrane system on the glucose sensor.

19. The system of claim 18, further comprising a processor module configured to monitor the second signal whereby a sensitivity change associated with transport of the non-glucose constant analyte through the membrane system over a time period is measured.

20. The system of claim 19, wherein the transport-measuring electrode is configured to measure oxygen.

21. The system of claim 20, wherein the processor module is configured to determine whether a glucose-to-oxygen ratio exceeds a threshold level, wherein a value is calculated from the first signal and the second signal, wherein the value is indicative of the glucose-to-oxygen ratio.

22. The system of claim 19, wherein the processor module is configured to calibrate the glucose-related sensor data point in response to the sensitivity change.

23. The system of claim 19, wherein the processor module is configured to receive reference data from a reference analyte monitor, the reference data comprising at least one reference data point, wherein the processor module is configured to use the reference data point for calibrating the glucose-related sensor data point.

24. The system of claim 19, wherein the processor module is configured to use the sensitivity change for calibrating the glucose-related sensor data point.

25. The system of claim 19, wherein the processor module is configured to calibrate the glucose-related sensor data point repeatedly at a frequency, wherein the frequency is selected based on the sensitivity change.

26. The system of claim 19, further comprising a stability module configured to determine a stability of glucose transport through the membrane system, wherein the stability of glucose transport is correlated with the sensitivity change.

27. The system of claim 26, wherein the processor module is configured to prohibit calibration of the glucose-related sensor data point when the stability of glucose transport falls below a threshold.

28. The system of claim 26, wherein the processor module is configured to initiate filtering of the glucose-related sensor data point when the stability of glucose transport falls below a threshold.

29. The system of claim 19, wherein the transport-measuring electrode is configured to measure urea.

30. A method for processing data from a glucose sensor in a host, the method comprising:

measuring a first signal associated with glucose and non-glucose related electroactive compounds, wherein the first signal is measured at a first electrode disposed beneath an active enzymatic portion of a membrane system;

measuring a second signal associated with a non-glucose related electroactive compound, wherein the second signal is measured at a second electrode that is disposed beneath a non-enzymatic portion of the membrane system; and

monitoring the second signal over a time period, whereby a change in the non-glucose related electroactive compound in the host is measured.

31. The method of claim 30, further comprising a step of subtracting the second signal from the first signal, whereby a differential signal comprising at least one glucose sensor data point is determined.

32. The method of claim 31, wherein the step of subtracting is performed electronically in the sensor.

33. The method of claim 31, wherein the step of subtracting is performed digitally in the sensor or an associated receiver.

34. The method of claim 31, further comprising calibrating the glucose sensor, wherein the step of calibrating comprises:

receiving reference data from a reference analyte monitor, the reference data comprising at least two reference data points;

providing at least two matched data pairs by matching the reference data to substantially time corresponding sensor data; and

calibrating the glucose sensor using the two or more matched data pairs and the differential signal.

35. The method of claim 30, further comprising a step of calibrating the glucose sensor in response to a change in a non-glucose related electroactive compound over the time period.

36. The method of claim 35, wherein the step of calibrating comprises receiving reference data from a reference analyte monitor, the reference data comprising at least one reference data point.

37. The method of claim 35, wherein the step of calibrating comprises using the change in the non-glucose related electroactive compound over the time period to calibrate the glucose sensor.

38. The method of claim 35, wherein the step of calibrating is performed repeatedly at a frequency, wherein the frequency is selected based on the change in the non-glucose related electroactive compound over the time period.

39. The method of claim 30, further comprising prohibiting calibration of the glucose sensor when the change in the non-glucose related electroactive compound rises above a threshold during the time period.

40. The method of claim 31, further comprising filtering the glucose sensor data point when the change in the non-glucose related electroactive compound rises above a threshold during the time period.

41. The method of claim 31, further comprising measuring a third signal in the host by obtaining at least one non-glucose constant data point, wherein the third signal is measured beneath the membrane system.

42. The method of claim 41, further comprising monitoring the third signal over a time period, whereby a sensitivity change associated with solute transport through the membrane system is measured.

43. The method of claim 41, wherein an oxygen-measuring electrode disposed beneath the non-enzymatic portion of the membrane system measures the third signal.

44. The method of claim 41, wherein the first electrode measures the third signal by incrementally measuring oxygen.

45. The method of claim 41, wherein an oxygen sensor disposed beneath the membrane system measures the third signal.

46. The method of claim 41, wherein an urea-measuring electrode disposed beneath the non-enzymatic portion of the membrane system measures the third signal.

47. The method of claim 41, wherein the first electrode measures the third signal by incrementally measuring urea.

48. The method of claim 41, wherein an urea sensor disposed beneath the membrane system measures the third signal.

49. The method of claim 30, further comprising determining whether a glucose-to-oxygen ratio exceeds a threshold level by calculating a value from the first signal and the second signal, wherein the value is indicative of the glucose-to-oxygen ratio.

50. The method of claim 42, further comprising calibrating the glucose sensor in response to the sensitivity change measured over a time period.

51. The method of claim 49, wherein the step of calibrating comprises receiving reference data from a reference analyte monitor, the reference data comprising at least one reference data point.

52. The method of claim 49, wherein the step of calibrating comprises using the sensitivity change.

53. The method of claim 49, wherein the step of calibrating is performed repeatedly at a frequency, wherein the frequency is selected based on the sensitivity change.

54. The method of claim 42, further comprising determining glucose transport stability through the membrane system, wherein the glucose transport stability corresponds to the sensitivity change over a period of time.

55. The method of claim 54, further comprising prohibiting calibration of the glucose sensor when the glucose transport stability falls below a threshold.

56. The method of claim 54, further comprising filtering the glucose-related sensor data point when the glucose transport stability falls below a threshold.

57. A system for measuring glucose in a host, the system comprising:

a first working electrode configured to generate a first signal associated with a glucose related electroactive compound and a non-glucose related electroactive compound, wherein the first electrode is disposed beneath an active enzymatic portion of a membrane system on a glucose sensor;

a second working electrode configured to generate a second signal associated with the non-glucose related electroactive compound, wherein the second electrode is disposed beneath a non-enzymatic portion of the membrane system on the glucose sensor; and

a processor module configured to monitor the second signal over a time period, whereby a change in the non-glucose related electroactive compound is measured.

58. The system of claim 57, further comprising a subtraction module configured to subtract the second signal from the first signal, whereby a differential signal comprising at least one glucose sensor data point is determined.

59. The system of claim 58, wherein the subtraction module comprises a differential amplifier configured to electronically subtract the second signal from the first signal.

60. The system of claim 57, wherein the subtraction module comprises at least one of hardware and software configured to digitally subtract the second signal from the first signal.

61. The system of claim 57, further comprising a reference electrode, wherein the first working electrode and the second working electrode are operatively associated with the reference electrode.

62. The system of claim 61, further comprising a counter electrode, wherein the first working electrode and the second working electrode are operatively associated with the counter electrode.

63. The system of claim 57, further comprising a first reference electrode and a second reference electrode, wherein the first reference electrode is operatively associated with the first working electrode, and wherein the second reference electrode is operatively associated with the second working electrode.

64. The system of claim 63, further comprising a first counter electrode and a second counter electrode, wherein the first counter electrode is operatively associated with the first working electrode, and wherein the second counter electrode is operatively associated with the second working electrode.

65. The system of claim 58, further comprising a reference input module adapted to obtain reference data from a reference analyte monitor, the reference data comprising at least one reference data point, wherein the processor module is configured to format at least one matched data pair by matching the reference data to substantially time corresponding glucose sensor data and subsequently calibrating the system using at least two matched data pairs and the differential signal.

66. The system of claim 58, wherein the processor module is configured to calibrate the system in response to the change in the non-glucose related electroactive compound in the host over the time period.

67. The system of claim 66, wherein the processor module is configured to request reference data from a reference analyte monitor, the reference data comprising at least one reference data point, wherein the processor module is configured to recalibrate the system using the reference data.

68. The system of claim 66, wherein the processor module is configured to recalibrate the system using the change in the non-glucose related electroactive compound measured over the time period.

69. The system of claim 66, wherein the processor module is configured to repeatedly recalibrate at a frequency, wherein the frequency is selected based on the change in the non-glucose related electroactive compound over the time period.

70. The system of claim 65, wherein the processor module is configured to prohibit calibration of the system when a change in the non-glucose related electroactive compound rises above a threshold during the time period.

71. The system of claim 58, wherein the processor module is configured to filter the glucose sensor data point when the change in the non-glucose related electroactive compound rises above a threshold during the time period.

72. The system of claim 58, further comprising a third electrode configured to generate a third signal, the third signal comprising at least one non-glucose constant analyte data point, wherein the third electrode is disposed beneath the membrane system on the sensor.

73. The system of claim 72, wherein the third electrode is configured to measure oxygen.

74. The system of claim 72, wherein the processor module is configured to determine whether a glucose-to-oxygen ratio exceeds a threshold level, wherein a value indicative of the glucose-to-oxygen ratio is calculated from the first signal and the second signal.

75. The system of claim 72, wherein the processor module is configured to monitor the third signal over a time period, whereby a sensitivity change associated with solute transport through the membrane system is measured.

76. The system of claim 75, wherein the processor module is configured to calibrate the glucose-related sensor data point in response to the sensitivity change.

77. The system of claim 72, wherein the processor module is configured to receive reference data from a reference analyte monitor, the reference data comprising at least one reference data point, wherein the processor module is configured to calibrate the glucose sensor data point using the reference data point.

78. The system of claim 75, wherein the processor module is configured to calibrate the glucose-related sensor data point repeatedly at a frequency, wherein the frequency is selected based on the sensitivity change.

79. The system of claim 75, further comprising a stability module configured to determine a stability of glucose transport through the membrane system, wherein the stability of glucose transport is correlated with the sensitivity change.

80. The system of claim 78, wherein the processor module is configured to prohibit calibration of the glucose-related sensor data point when the stability of glucose transport falls below a threshold.

81. The system of claim 78, wherein the processor module is configured to filter the glucose-related sensor data point when the stability of glucose transport falls below a threshold.

82. The system of claim 72, wherein the third electrode is configured to measure urea.