Methods and systems for improving the reliability of orthogonally redundant sensors

• US 9,943,256 B2
• Filed: 04/24/2014
• Issued: 04/17/2018
• Est. Priority Date: 12/16/2013
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Varsavsky, Andrea, Li, Xiaolong, Liu, Mike C., Zhong, Yuxiang, Yang, Ning
• Primary Examiner(s): Winakur, Eric
• Assistant Examiner(s): Liu, Chu Chuan (JJ)
• Application Number:
  US14/260,948
• Publication Number:
  US 20150164383A1
• Time in Patent Office: 1,454 Days
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• CPC Class Codes: A61B 2560/0238 Means for recording calibration data
• CPC Class Codes: A61B 2562/06 Arrangements of multiple sensors of different types
• CPC Class Codes: A61B 5/0004 characterised by the type of physiological signal transmitted
• 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 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/14556 by fluorescence A61B5/14555 takes precedence
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/1468 using chemical or electrochemical methods, e.g. by polarographic means A61B5/1486 takes precedence
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/7221 Determining signal validity, reliability or quality A61B5/7207 and A61B5/7217 take precedence
• CPC Class Codes: A61B 5/7278 Artificial waveform generation or derivation, e.g. synthesising signals from measured signals A61B5/327 takes precedence
• CPC Class Codes: A61M 2005/1726 the body parameters being measured at, or proximate to, the infusion site
• CPC Class Codes: A61M 2205/3306 Optical measuring means
• CPC Class Codes: A61M 2205/3584 using modem, internet or bluetooth
• CPC Class Codes: A61M 2205/3592 using telemetric means, e.g. radio or optical transmission
• CPC Class Codes: A61M 2205/50 with microprocessors or computers
• CPC Class Codes: A61M 2205/505 : Touch-screens; Virtual keyboard or keypads; Virtual buttons; Soft keys; Mouse touches
• CPC Class Codes: A61M 2205/52 : with memories providing a history of measured variating parameters of apparatus or patient
• CPC Class Codes: A61M 2230/005 : Parameter used as control input for the apparatus
• CPC Class Codes: A61M 2230/201 : Glucose concentration
• CPC Class Codes: A61M 5/142 : Pressure infusion, e.g. using pumps
• CPC Class Codes: A61M 5/14244 : adapted to be carried by the patient, e.g. portable on the body
• 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 1/006 : for glucose
• CPC Class Codes: G01N 21/00 : Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light G01N3/00 - G01N19/00 take precedence
• CPC Class Codes: G01N 21/59 : Transmissivity G01N21/25 takes precedence
• CPC Class Codes: G01N 21/84 : Systems specially adapted for particular applications
• CPC Class Codes: G01N 2201/127 : Calibration; base line adjustment; drift compensation
• CPC Class Codes: G01N 27/27 : Association of two or more measuring systems or cells, each measuring a different parameter, where the measurement results may be either used independently, the systems or cells being physically associated, or combined to produce a value for a further parameter
• 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 27/4163 : checking the operation of, or calibrating, the measuring apparatus G01N27/3274, G01N27/4175 and G01N33/0006 take precedence
• 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: G01N 33/66 : involving blood sugars, e.g. galactose

Abstract

Methods and systems for sensor calibration and sensor glucose (SG) fusion are used advantageously to improve the accuracy and reliability of orthogonally redundant glucose sensor devices, which may include optical and electrochemical glucose sensors. Calibration for both sensors may be achieved via fixed-offset and/or dynamic regression methodologies, depending, e.g., on sensor stability and Isig-Ratio pair correlation. For SG fusion, respective integrity checks may be performed for SG values from the optical and electrochemical sensors, and the SG values calibrated if the integrity checks are passed. Integrity checks may include checking for sensitivity loss, noise, and drift. If the integrity checks are failed, in-line sensor mapping between the electrochemical and optical sensors may be performed prior to calibration. The electrochemical and optical SG values may be weighted (as a function of the respective sensor'"'"'s overall reliability index (RI)) and the weighted SGs combined to obtain a single, fused SG value.

Claims

1. A continuous glucose monitoring system comprising:

an orthogonally redundant glucose sensor device for determining the concentration of glucose in a body of a user, said sensor device comprising an optical glucose sensor and an electrochemical glucose sensor; and

an external transmitter operatively coupled to said electrochemical and optical glucose sensors and having a housing, wherein the transmitter includes sensor electronics in said housing, said sensor electronics including at least one physical microprocessor that is configured to;

receive a first signal from the electrochemical glucose sensor and a second signal from the optical glucose sensor;

perform a respective integrity check on each of said first and second signals;

determine whether the first signal can be calibrated, and whether the second signal can be calibrated, wherein said determination is made based on whether the first signal and the second signal pass or fail their respective integrity checks;

if it is determined that the first signal can be calibrated, calibrate said first signal to generate an electrochemical sensor glucose (SG) value;

if it is determined that the second signal can be calibrated, calibrate said second signal to generate an optical sensor glucose (SG) value; and

fuse said electrochemical SG value and said optical SG value to calculate a single, fused sensor glucose value for the orthogonally redundant glucose sensor device,

wherein said optical glucose sensor includes a lightguide on a first respective substrate, said electrochemical glucose sensor includes at least one electrode on a second respective substrate, and said first and second respective substrates are integrated into an integrated flex circuit; and

wherein said lightguide is disposed in an interior of said integrated flex circuit and said at least one electrode is disposed on an external surface of said integrated flex circuit.

2. The system of claim 1, wherein said first signal is an electrical current (Isig).

3. The system of claim 1, wherein each said integrity check includes checking for sensitivity loss.

4. The system of claim 1, wherein each said integrity check includes checking for noise.

5. The system of claim 1, wherein each said integrity check includes checking for sensor drift.

6. The system of claim 1, wherein the integrity check for the electrochemical sensor includes checking for sensitivity loss, noise, and sensor drift, and wherein the microprocessor determines that the first signal passes its integrity check, and can be calibrated, if the sensitivity loss, noise, and drift fall within respective calculated limits.

7. The system of claim 6, wherein, if one or more of the sensitivity loss, noise, and drift fall outside of respective calculated limits, the microprocessor determines that the first signal fails its integrity check and cannot be calibrated.

8. The system of claim 7, wherein, if the microprocessor determines that the first signal has failed its integrity check, the microprocessor further determines whether the second signal passes its integrity check and, if the second signal passes its integrity check, uses the second signal to correct said first signal.

9. The system of claim 8, wherein the microprocessor uses the second signal to correct the first signal via in-line sensor mapping to generate a corrected first signal.

10. The system of claim 9, wherein the microprocessor calibrates the corrected first signal to generate said electrochemical SG value.

11. The system of claim 9, wherein the microprocessor performs said in-line sensor mapping by using the relation first_signal_buffer_n=a×

second_signal_buffer_n+b, where a and b are mapping parameters.

12. The system of claim 1, wherein the integrity check for the optical sensor includes checking for sensitivity loss, noise, and sensor drift, and wherein the microprocessor determines that the second signal passes its integrity check, and can be calibrated, if the sensitivity loss, noise, and drift fall within respective calculated limits.

13. The system of claim 12, wherein, if one or more of the sensitivity loss, noise, and drift fall outside of respective calculated limits, the microprocessor determines that the second signal fails its integrity check and cannot be calibrated.

14. The system of claim 13, wherein, if the microprocessor determines that the second signal has failed its integrity check, the microprocessor further determines whether the first signal passes its integrity check and, if the first signal passes its integrity check, uses the first signal to correct said second signal.

15. The system of claim 14, wherein the microprocessor uses the first signal to correct the second signal via in-line sensor mapping to generate a corrected second signal.

16. The system of claim 15, wherein the microprocessor calibrates the corrected second signal to generate said optical SG value.

17. The system of claim 15, wherein the microprocessor performs said in-line sensor mapping by using the relation first_signal_buffer_n=a×

second_signal_buffer_n+b, where a and b are mapping parameters.

18. The system of claim 1, wherein the transmitter wirelessly transmits said single, fused sensor glucose value.

19. The system of claim 1, wherein the transmitter is worn on the user'"'"'s body.

20. The system of claim 1, further including a handheld monitor.

21. The system of claim 20, wherein the handheld monitor includes an integrated blood glucose meter.

22. The system of claim 21, wherein the transmitter wirelessly transmits said single, fused sensor glucose value to the hand-held monitor.

23. The system of claim 1, further including an insulin pump.

24. The system of claim 23, wherein the transmitter wirelessly transmits said single, fused sensor glucose value to the insulin pump.

25. The system of claim 24, wherein said glucose monitoring system is a closed-loop system.

26. The system of claim 1, wherein the optical glucose sensor includes an assay having a glucose receptor, a glucose analog, a first fluorophore, and a reference fluorophore different from said first fluorophore.

27. The system of claim 26, wherein said output signal of the optical glucose sensor is a ratio of the fluorescence signal from the first fluorophore to the fluorescence signal from the reference fluorophore.

28. The system of claim 1, wherein each of the electrochemical and optical sensors has a distal portion and a proximal portion, and wherein respective distal portions of the optical sensor and the electrochemical sensor are co-located within the user'"'"'s body.

29. The system of claim 1, further including an insertion needle, wherein said integrated flex circuit is configured to be carried inside said needle for simultaneous insertion of said optical glucose sensor and said electrochemical glucose sensor into the user'"'"'s body.

30. The system of claim 1, wherein each of said optical and electrochemical glucose sensors has a respective proximal portion that is disposed externally to the user'"'"'s body and a respective distal portion configured for internal placement in the user'"'"'s body.

31. The system of claim 30, wherein said lightguide is an optical fiber having said proximal portion that is disposed externally to the user'"'"'s body and said distal portion configured for internal placement in the user'"'"'s body.

32. The system of claim 31, wherein the optical fiber has a circular cross-section having a diameter of less than 200 μ

m.

33. The system of claim 30, wherein said housing of the external transmitter houses said respective proximal portions of the optical and electrochemical glucose sensors.

34. A program code storage device, comprising:

a non-transitory computer-readable medium; and

non-transitory computer-readable program code, stored on the computer-readable medium, the computer-readable program code having instructions, which when executed cause a microprocessor to;

receive a first signal from an electrochemical glucose sensor and a second signal from an optical glucose sensor of an orthogonally redundant glucose sensor device for determining the concentration of glucose in a body of a user, wherein said optical glucose sensor includes a lightguide on a first respective substrate, said electrochemical glucose sensor includes at least one electrode on a second respective substrate, and said first and second respective substrates are integrated into an integrated flex circuit, and wherein said lightguide is disposed in an interior of said integrated flex circuit and said at least one electrode is disposed on an external surface of said integrated flex circuit;

perform a respective integrity check on each of said first and second signals;

determine whether the first signal can be calibrated, and whether the second signal can be calibrated, wherein said determination is made based on whether the first signal and the second signal pass or fail their respective integrity checks;

if it is determined that the first signal can be calibrated, calibrate said first signal to generate an electrochemical sensor glucose (SG) value;

if it is determined that the second signal can be calibrated, calibrate said second signal to generate an optical sensor glucose (SG) value; and

fuse said electrochemical SG value and said optical SG value to calculate a single, fused sensor glucose value for the orthogonally redundant glucose sensor device.

35. The program code storage device of claim 34, wherein said first signal is an electrical current (Isig).

36. The program code storage device of claim 34, wherein the optical glucose sensor includes an assay fluorophore and a reference fluorophore, wherein the assay fluorophore generates an assay fluorescence signal and the reference fluorophore generates a reference fluorescence signal, and wherein said second signal from the optical glucose sensor is a ratio of the assay fluorescence signal to the reference fluorescence signal.

37. The program code storage device of claim 34, wherein each said integrity check includes checking for sensitivity loss.

38. The program code storage device of claim 34, wherein each said integrity check includes checking for noise.

39. The program code storage device of claim 34, wherein each said integrity check includes checking for sensor drift.

40. The program code storage device of claim 34, wherein the integrity check for the electrochemical sensor includes checking for sensitivity loss, noise, and sensor drift, and wherein the computer-readable program code includes instructions, which when executed cause the microprocessor to determine that the first signal passes its integrity check, and can be calibrated, if the sensitivity loss, noise, and drift fall within respective calculated limits.

41. The program code storage device of claim 40, wherein, if one or more of the sensitivity loss, noise, and drift fall outside of respective calculated limits, it is determined that the first signal fails its integrity check and cannot be calibrated.

42. The program code storage device of claim 41, wherein, if it is determined that the first signal has failed its integrity check, the instructions, when executed, further cause the microprocessor to determine whether the second signal passes its integrity check and, if the second signal passes its integrity check, to use the second signal to correct said first signal.

43. The program code storage device of claim 42, the computer-readable program code including instructions, which when executed cause the microprocessor to use the second signal to correct the first signal via in-line sensor mapping to generate a corrected first signal.

44. The program code storage device of claim 43, the computer-readable program code including instructions, which when executed cause the microprocessor to calibrate the corrected first signal to generate said electrochemical SG value.

45. The program code storage device of claim 43, the computer-readable program code including instructions, which when executed cause the microprocessor to perform said in-line sensor mapping by using the relation first_signal_buffer_n=a×

second_signal_buffer_n+b, where a and b are mapping parameters.

46. The program code storage device of claim 34, wherein the integrity check for the optical sensor includes checking for sensitivity loss, noise, and sensor drift, and wherein the computer-readable program code includes instructions, which when executed cause the microprocessor to determine that the second signal passes its integrity check, and can be calibrated, if the sensitivity loss, noise, and drift fall within respective calculated limits.

47. The program code storage device of claim 46, wherein, if one or more of the sensitivity loss, noise, and drift fall outside of respective calculated limits, it is determined that the second signal fails its integrity check and cannot be calibrated.

48. The program code storage device of claim 47, wherein, if it is determined that the second signal has failed its integrity check, the instructions, when executed, further cause the microprocessor to determine whether the first signal passes its integrity check and, if the first signal passes its integrity check, to use the first signal to correct said second signal.

49. The program code storage device of claim 48, the computer-readable program code including instructions, which when executed cause the microprocessor to use the first signal to correct the second signal via in-line sensor mapping to generate a corrected second signal.

50. The program code storage device of claim 49, the computer-readable program code including instructions, which when executed cause the microprocessor to calibrate the corrected second signal to generate said optical SG value.

51. The program code storage device of claim 49, the computer-readable program code including instructions, which when executed cause the microprocessor to perform said in-line sensor mapping using the relation first_signal_buffer_n=a×

second_signal_buffer_n+b, where a and b are mapping parameters.

52. The program code storage device of claim 34, wherein said integrated flex circuit is configured to be carried inside an insertion needle for simultaneous insertion of said optical glucose sensor and said electrochemical glucose sensor into the user'"'"'s body.

53. The program code storage device of claim 34, wherein each of said optical and electrochemical glucose sensors has a respective proximal portion that is disposed externally to the user'"'"'s body and a respective distal portion configured for internal placement in the user'"'"'s body.

54. The program code storage device of claim 53, wherein said lightguide is an optical fiber having said proximal portion that is disposed externally to the user'"'"'s body and said distal portion configured for internal placement in the user'"'"'s body.

55. The program code storage device of claim 54, wherein the optical fiber has a circular cross-section having a diameter of less than 200 μ

m.