Methods and systems for improving the reliability of orthogonally redundant sensors

• US 9,649,058 B2
• Filed: 04/24/2014
• Issued: 05/16/2017
• Est. Priority Date: 12/16/2013
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Li, Xiaolong, Varsavsky, Andrea, Liu, Mike C., Zhong, Yuxiang, Yang, Ning
• Primary Examiner(s): Winakur, Eric
• Assistant Examiner(s): Fardanesh, Marjan
• Application Number:
  US14/261,011
• Publication Number:
  US 20150164384A1
• Time in Patent Office: 1,118 Days
• Field of Search: None
• 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

a 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;

(a) receive a first signal from the electrochemical glucose sensor and a second signal from the optical glucose sensor, wherein said second signal is obtained at a first point in time;

(b) receive a meter glucose value, said meter glucose value being indicative of the user'"'"'s blood glucose (BG) level and being obtained at a second point in time;

(c) pair said meter glucose value with said second signal;

(d) perform a validity check on the paired meter glucose value and second signal;

(e) calculate a mapped value for the second signal based on the first signal; and

(f) calibrate the mapped value of the second signal based on said first meter glucose value.

2. The system of claim 1, wherein the sensor device is either configured to be implanted or subcutaneously disposed in the body of the user.

3. The system of claim 1, wherein the transmitter is configured to be worn on the user'"'"'s body.

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

5. The system of claim 4, wherein the handheld monitor includes an integrated blood glucose meter.

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

7. The system of claim 6, wherein said glucose monitoring system is a closed-loop system.

8. 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.

9. The system of claim 8, 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.

10. 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 configured to be co-located within the user'"'"'s body.

11. The system of claim 1, wherein the microprocessor is configured to perform said validity check only if the first and second signals are not in an initialization period.

12. The system of claim 11, wherein, in step (e), the microprocessor calculates said mapped value of the second signal based on one or more values for the first signal that were generated after the initialization period and before said first meter glucose value.

13. The system of claim 1, wherein, prior to step (e), the microprocessor calculates a correlation value between said first and second signals.

14. The system of claim 13, wherein the microprocessor is configured to calculate said correlation value by performing linear fitting of the second signal to the first signal, and then calculating the coefficient of determination between the second signal and the first signal.

15. The system of claim 14, wherein, if the correlation value is less than a calculated threshold, then the microprocessor determines that the first and second signals do not correlate well with each other, saves said meter glucose value and second signal to a buffer, and does not perform steps (e) and (f);

if the correlation value is greater than a calculated threshold, then the microprocessor determines that the first and second signals correlate well with each other, and said mapping in step (e) can be performed.

16. The system of claim 15, wherein the buffer is a first-in-first-out (FIFO) buffer, and has a calculated size.

17. The system of claim 15, wherein, to perform said mapping, the microprocessor performs a linear regression calculation on stored values of said first and second signals so as to obtain a first slope value and a first offset value, said stored values being values of said first and second signals that were generated before said first meter glucose value.

18. The system of claim 17, wherein the microprocessor calculates said mapped value for the second signal by using the relation (mapped signal)=(first signal+first offset)*(first slope).

19. The system of claim 18, wherein, in step (f), the microprocessor calibrates the mapped value for the second signal so as to generate an optical sensor glucose value by using the relation (optical sensor glucose value)=(mapped value of second signal+fixed offset)*(second slope), wherein said second slope is calculated based on a paired meter glucose value and second signal value.

20. The system of claim 19, wherein said fixed offset is empirically derived from in vivo or in vitro data.

21. The system of claim 1, wherein, the microprocessor is configured to perform a validity check on said subsequent meter glucose value and its paired second signal, and then save the paired subsequent meter glucose value and second signal to a first-in-first-out (FIFO) buffer.

22. The system of claim 19, further including a hand-held monitor, wherein the transmitter wirelessly transmits said optical sensor glucose value to the hand-held monitor.

23. The system of claim 19, further including an insulin pump, wherein the transmitter wirelessly transmits said optical sensor glucose value to the insulin pump.

24. The system of claim 1, 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 is a ratio of the assay fluorescence signal to the reference fluorescence signal.