Advanced analyte sensor calibration and error detection

• US 9,149,220 B2
• Filed: 04/13/2012
• Issued: 10/06/2015
• Est. Priority Date: 04/15/2011
• Status: Active Grant

• Current Assignee: DexCom Incorporated
• Original Assignee: DexCom Incorporated
• Inventors: Bohm, Sebastian, Rong, Daiting, Simpson, Peter C.
• Primary Examiner(s): Previl, Daniel
• Application Number:
  US13/446,977
• Publication Number:
  US 20120262298A1
• Time in Patent Office: 1,271 Days
• Field of Search: 340/604, 340/612, 340/636.11, 34063612-63615, 340/691.6
• US Class Current: 1/1
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• CPC Class Codes: A61B 2560/0276 Determining malfunction
• CPC Class Codes: A61B 2560/04 Constructional details of apparatus
• CPC Class Codes: A61B 2562/085 combined with means for recording calibration data
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• CPC Class Codes: A61B 5/1451 for interstitial fluid
• CPC Class Codes: A61B 5/14517 for sweat
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14535 for measuring haematocrit
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/14542 for measuring blood gases A61B5/14551 takes precedence
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/14735 comprising an immobilised reagent
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• 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 5/15003 for venous or arterial blood
• CPC Class Codes: A61B 5/150992 Blood sampling from a fluid line external to a patient, such as a catheter line, combined with an infusion line; blood sampling from indwelling needle sets, e.g. sealable ports, luer couplings, valves tubing connectors and couplings A61M39/00
• CPC Class Codes: A61B 5/155 : Devices specially adapted for continuous or multiple sampling, e.g. at predetermined intervals devices loaded with multiple lancets simultaneously A61B5/15146
• CPC Class Codes: A61B 5/157 : Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: A61B 5/412 : Detecting or monitoring sepsis
• CPC Class Codes: A61B 5/4839 : combined with drug delivery
• CPC Class Codes: A61B 5/6848 : Needles
• CPC Class Codes: A61B 5/6849 : in combination with a needle set
• CPC Class Codes: A61B 5/6866 : Extracorporeal blood circuits, e.g. dialysis circuits
• CPC Class Codes: A61B 5/7257 : using Fourier transforms
• CPC Class Codes: A61B 5/7267 : involving training the classification device
• CPC Class Codes: A61B 5/7275 : Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor
• CPC Class Codes: A61B 5/743 : Displaying an image simultaneously with additional graphical information, e.g. symbols, charts, function plots
• CPC Class Codes: A61M 2005/14296 : Pharmacokinetic models
• CPC Class Codes: A61M 2230/201 : Glucose concentration
• CPC Class Codes: A61M 5/14 : Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
• CPC Class Codes: A61M 5/16804 : Flow controllers
• CPC Class Codes: A61M 5/1723 : using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: C12Q 1/001 : Enzyme electrodes
• CPC Class Codes: C12Q 1/006 : for glucose
• CPC Class Codes: G01D 18/00 : Testing or calibrating apparatus or arrangements provided for in groups G01D1/00 - G01D15/00
• CPC Class Codes: G01N 27/026 : Dielectric impedance spectroscopy electrochemical impedance spectroscopy for measuring corrosion G01N17/02
• 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
• CPC Class Codes: G16H 10/40 : for data related to laboratory analysis, e.g. patient specimen analysis
• CPC Class Codes: G16H 20/17 : delivered via infusion or injection
• CPC Class Codes: G16H 40/40 : for the management of medical equipment or devices, e.g. scheduling maintenance or upgrades
• CPC Class Codes: G16H 40/63 : for local operation
• CPC Class Codes: H05K 999/00 : dummy group
• CPC Class Codes: H05K 999/99 : dummy group
• CPC Class Codes: Y02A 90/10 : Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

Systems and methods for processing sensor data and self-calibration are provided. In some embodiments, systems and methods are provided which are capable of calibrating a continuous analyte sensor based on an initial sensitivity, and then continuously performing self-calibration without using, or with reduced use of, reference measurements. In certain embodiments, a sensitivity of the analyte sensor is determined by applying an estimative algorithm that is a function of certain parameters. Also described herein are systems and methods for determining a property of an analyte sensor using a stimulus signal. The sensor property can be used to compensate sensor data for sensitivity drift, or determine another property associated with the sensor, such as temperature, sensor membrane damage, moisture ingress in sensor electronics, and scaling factors.

Claims

1. A method for determining whether an analyte sensor system is functioning properly, the method comprising:

applying a stimulus signal to the analyte sensor;

measuring a response to the stimulus signal;

estimating a value of a sensor property based on the signal response;

correlating the sensor property value with a predetermined relationship of the sensor property and a sensor sensitivity profile, the sensor sensitivity profile representative of a predicted change in sensitivity of the analyte sensor over time; and

initiating an error routine if the correlation does not exceed a predetermined correlation threshold.

2. The method of claim 1, wherein correlating includes performing a data association analysis.

3. The method of claim 1, wherein the error routine comprises displaying a message to a user indicating that the analyte sensor is not functioning properly.

4. The method of claim 1, wherein the sensor property is an impedance of the sensor membrane.

5. A sensor system configured to implement the method of claim 1.

6. A method for determining a temperature associated with an analyte sensor, the method comprising:

applying a stimulus signal to the analyte sensor;

measuring a signal response of the signal;

determining a temperature associated with of the analyte sensor, the determining comprising correlating at least one property of the signal response to a predetermined relationship of the sensor property to temperature; and

generating estimated analyte concentration values using the determined temperature and sensor data generated from the analyte sensor,

wherein the generating includes compensating the sensor data using the determined temperature and converting the compensated sensor data to the generated estimated analyte values using a conversion function.

7. The method of claim 6, further comprising measuring a temperature using a second sensor, wherein the determining further comprises using the measured temperature to determine the temperature associated with the analyte sensor.

8. The method of claim 7, wherein the second sensor is a thermistor.

9. A sensor system configured to implement the method of claim 6.

10. A method for determining a temperature associated with an analyte sensor, the method comprising:

applying a stimulus signal to the analyte sensor;

measuring a signal response of the signal;

determining a temperature associated with the analyte sensor, the determining comprising correlating at least one property of the signal response to a predetermined relationship of the sensor property to temperature; and

generating estimated analyte concentration values using the determined temperature and sensor data generated from the analyte sensor,

wherein the generating includes forming or modifying a conversion function using the determined temperature and converting the sensor data to the generated estimated analyte values using the formed or modified conversion function.

11. A method for determining moisture ingress in an electronic sensor system, comprising:

applying a stimulus signal having a particular frequency or a signal comprising a spectrum of frequencies to an analyte sensor;

measuring a response to the stimulus signal;

calculating, using sensor electronics, an impedance based on the measured signal response;

determining, using sensor electronics, whether the impedance satisfies a predetermined criterion corresponding to moisture ingress; and

initiating, using sensor electronics, an error routine if the impedance satisfies the predetermined criterion.

12. The method of claim 11, wherein the error routine includes one or more of triggering an audible alarm and a visual alarm on a display screen to alert a user that the sensor system may not be functioning properly.

13. The method of claim 11, wherein the stimulus signal has a predetermined frequency.

14. The method of claim 11, wherein the stimulus signal comprises a spectrum of frequencies.

15. The method of claim 11, wherein the calculated impedance comprises a magnitude value and a phase value, and wherein the determination comprises comparing the impedance magnitude value to a predefined impedance magnitude threshold and the phase value to a predefined phase threshold.

16. The method of claim 11, wherein the calculated impedance is a complex impedance value.

17. A sensor system configured to implement the method of claim 11.

18. A method for determining membrane damage of an analyte sensor using a sensor system, comprising:

applying a stimulus signal to an analyte sensor;

measuring a response to the stimulus signal;

calculating, using sensor electronics, an impedance based on the signal response;

determining, using the sensor electronics, whether the impedance falls within a predefined level corresponding to membrane damage; and

initiating, using the sensor electronics, an error routine if the impedance exceeds the predefined level.

19. The method of claim 18, wherein the error routine includes triggering one or more of an audible alarm and a visual alarm on a display screen.

20. The method of claim 18, wherein the stimulus signal has a predetermined frequency.

21. The method of claim 18, wherein the stimulus signal comprises a spectrum of frequencies.

22. The method of claim 18, wherein the calculated impedance comprises a magnitude value and a phase value, and wherein the determination comprises comparing the impedance magnitude value to a predefined impedance magnitude threshold and the phase value to a predefined phase threshold.

23. The method of claim 18, wherein the calculated impedance is a complex impedance value.

24. A sensor system configured to implement the method of claim 18.

25. A method for determining reuse of an analyte sensor, comprising,

applying a stimulus signal to an analyte sensor;

measuring a response of the stimulus signal;

calculating an impedance response based on the response;

comparing the calculated impedance to a predetermined threshold; and

initiating a sensor reuse routine if it is determined that the impedance exceeds the threshold.

26. The method of claim 25, wherein the sensor reuse routine includes triggering an audible and/or visual alarm notifying the user of improper sensor reuse.

27. The method of claim 25, wherein the sensor reuse routing includes causing a sensor system to fully or partially shut down and/or cease display of sensor data on a user interface of the sensor system.

28. A sensor system configured to implement the method of claim 25.

29. A method for determining reuse of an analyte sensor, comprising,

applying a stimulus signal to an analyte sensor;

measuring a response of the stimulus signal;

calculating an impedance based on the response;

using a data association function to determine a correlation of the calculated impedance to one or more recorded impedance values; and

initiating a sensor reuse routine if it is determined that the correlation is above a predetermined threshold.

30. The method of claim 29, wherein the sensor reuse routine includes triggering an audible and/or visual alarm notifying the user of improper sensor reuse.

31. The method of claim 29, wherein the sensor reuse routing includes causing a sensor system to fully or partially shut down and/or cease display of sensor data on a user interface of the sensor system.

32. A sensor system configured to implement the method of claim 29.

33. A method for applying an overpotential to an analyte sensor, comprising,

applying a stimulus signal to an analyte sensor;

measuring a response of the stimulus signal;

determining a sensor sensitivity or change in sensor sensitivity based on the response;

applying an over potential to the sensor based on the determined sensitivity or sensitivity change; and

generating continuous analyte data, the generating comprising applying a bias potential to the analyte sensor and measuring a response of the bias potential,

wherein the overpotential is greater than the bias potential.

34. The method of claim 33, wherein the determining further comprises calculating an impedance based on the response and determining the sensitivity or sensitivity change based on the impedance.

35. The method of claim 34, wherein the determining the sensitivity or sensitivity change further comprises correlating the impedance to a predetermined impedance to sensitivity relationship.

36. The method of claim 33, wherein the applying comprises determining or modifying a length of time the over potential is applied to the sensor.

37. The method of claim 33, wherein the applying comprises determining or modifying a magnitude of the over potential applied to the sensor.

38. A sensor system configured to implement the method of claim 33.

39. A method for determining a property of a continuous analyte sensor, the method comprising:

applying a stimulus signal to a first analyte sensor having a first working electrode and a first reference electrode;

measuring a signal response of the stimulus signal using a second analyte sensor having a second working electrode and a second reference electrode;

determining a property of the first sensor by correlating the response to a predetermined relationship; and

generating sensor data by applying a bias voltage to the first working electrode and measuring a response to the bias voltage.

40. The method of claim 39, further comprising calibrating the sensor data using the determined property.

41. The method of claim 39, wherein the determined property is one of an impedance and a temperature.

42. The method of claim 39, further comprising determining sensor membrane damage using the determined property.

43. The method of claim 39, further comprising determining moisture ingress in a sensor system encompassing the first and second analyte sensors using the determined property.

44. A sensor system configured to implement the method of claim 39.

45. A method for determining a scaling used in a continuous analyte sensor system, the method comprising:

applying a first stimulus signal to a first working electrode of an analyte sensor;

measuring a response to the first stimulus signal;

applying a second stimulus signal to a second working electrode of the analyte sensor;

measuring a response to the second stimulus signal;

determining, using sensor electronics, a scaling factor based on the measured responses to the first and second stimulus signals; and

using the scaling factor to generate estimated analyte values based on sensor data generated by the analyte sensor.

46. The method of claim 45, wherein the method is performed periodically.

47. The method of claim 45, wherein the determining comprises calculating a first impedance using the response to the first stimulus signal and calculating a second impedance using the response to the second stimulus signal, and wherein the scaling factor is a ratio of the first impedance and the second impedance.

48. The method of claim 45, wherein the first working electrode has a membrane comprising an enzyme configured to react with the analyte and the second working electrode has a membrane does not have the enzyme.

49. The method of claim 45, wherein determining the scaling factor comprises updating a previous scaling factor based on the measured responses to the first and second stimulus signals.

50. The method of claim 45, wherein scaling factor is an acetaminophen scaling factor, wherein the method further comprises updating a further scaling factor based on the acetaminophen scaling factor, and wherein the further scaling factor applied to the sensor data to generate the estimated analyte values.

51. A sensor system configured to implement the method of claim 45.

52. A method for calibrating an analyte sensor, the method comprising:

applying a predetermined signal to an analyte sensor;

measuring a response to the applied signal;

determining, using sensor electronics, a change in impedance associated with a membrane of the analyte sensor based on the measured response;

calculating a sensitivity change of the analyte sensor based on the determined impedance;

calculating a corrected sensitivity based on the calculated sensitivity change and a previously used sensitivity of the analyte sensor; and

generating estimated analyte values using the corrected sensitivity.

53. The method of claim 52, wherein calculating the sensitivity change comprises applying a non-linear compensation function.

54. The method of claim 53, wherein the non-linear compensation function is expressed as the equation Δ

S=(a*log(t)+b)*Δ

I, where Δ

S is the change in sensitivity, t is a time since calibration of the analyte sensor, Δ

I is the determined change in impedance, and a and b are a predetermined coefficients.

55. The method of claim 54, wherein a and b are determined by prior testing of similar analyte sensors.

56. A sensor system configured to implement the method of claim 52.