Orthogonally Redundant Sensor Systems and Methods

• US 20130060105A1
• Filed: 05/23/2012
• Published: 03/07/2013
• Est. Priority Date: 09/06/2011
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: SHAH, RAJIV, AASMUL, SOREN, KRISTENSEN, JESPER SVENNING, WOLFE, KATHERINE T., BANSAL, ANUBHUTI
• Granted Patent: US 9,642,568 B2
• Time in Patent Office: Days
• US Class Current: 600/316
• CPC Class Codes: A61B 5/0002 Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network A61B5/07 takes precedence; transmission systems for measured values G08C; transmission H04B; transmission of digital information H04L; wireless communication networks H04W
• CPC Class Codes: A61B 5/0004 characterised by the type of physiological signal transmitted
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• 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 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• 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 5/742 using visual displays A61B5/339 takes precedence
• CPC Class Codes: A61M 2230/201 Glucose concentration
• 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: G01N 2021/6441 with two or more labels
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 2021/772 Tip coated light guide
• CPC Class Codes: G01N 2021/7733 Reservoir, liquid reagent
• CPC Class Codes: G01N 2021/775 Indicator and selective membrane
• CPC Class Codes: G01N 2021/7759 Dipstick; Test strip
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved fluorescence
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/7703 : using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B
• CPC Class Codes: G01N 2333/4724 : Lectins
• CPC Class Codes: G01N 33/66 : involving blood sugars, e.g. galactose

Abstract

A continuous glucose monitoring system may include a hand-held monitor, a transmitter, an insulin pump, and an orthogonally redundant glucose sensor, which may comprise an optical glucose sensor and a non-optical glucose sensor. The former may be a fiber optical sensor, including a competitive glucose binding affinity assay with a glucose analog and a fluorophore-labeled glucose receptor, which is interrogated by an optical interrogating system, e.g., a stacked planar integrated optical system. The non-optical sensor may be an electrochemical sensor having a plurality of electrodes distributed along the length thereof. Proximal portions of the optical and electrochemical sensors may be housed inside the transmitter and operationally coupled with instrumentation for, e.g., receiving signals from the sensors, converting to respective glucose values, and communicating the glucose values. The sensors'"'"' distal portions may be inserted into a user'"'"'s body via a single delivery needle and may be co-located inside the user'"'"'s body.

Claims

1. A continuous glucose monitoring system comprising:

an orthogonally redundant glucose sensor, comprising;

an optical glucose sensor having a proximal portion that is disposed externally to a body of a user and a distal portion for internal placement in the user'"'"'s body, wherein the optical glucose sensor includes an assay having a glucose receptor, a glucose analog, and a first fluorophore; and

a non-optical glucose sensor having a proximal portion that is disposed externally to the user'"'"'s body and a distal portion for internal placement in the user'"'"'s body;

a hand-held monitor having a display; and

an external transmitter having a housing that houses the proximal portion of the optical glucose sensor and the proximal portion of the non-optical glucose sensor, wherein the transmitter includes instrumentation in said housing to receive an optical signal from the optical sensor and a non-optical signal from the non-optical sensor and to convert each of said optical and non-optical signals to respective glucose values, and wherein the transmitter wirelessly transmits said respective glucose values.

2. The system of claim 1, wherein the non-optical glucose sensor is an electrochemical glucose sensor.

3. The system of claim 2, wherein the electrochemical glucose sensor includes a plurality of electrodes.

4. The system of claim 3, wherein each of the plurality of electrodes includes said proximal portion that is disposed externally to the user'"'"'s body and said distal portion for internal placement in the user'"'"'s body.

5. The system of claim 4, wherein the distal portion of each of the plurality of electrodes is inserted subcutaneously into the user'"'"'s body.

6. The system of claim 4, wherein the plurality of electrodes are distributed along the length of the electrochemical glucose sensor.

7. The system of claim 6, wherein said plurality of electrodes are working electrodes.

8. The system of claim 1, wherein the optical glucose sensor includes an optical fiber having said proximal portion that is disposed externally to the user'"'"'s body and said distal portion for internal placement in the user'"'"'s body.

9. The system of claim 8, further including a glucose-permeable membrane, wherein the membrane has a closed end, a hollow interior, and an open end that is coupled to the optical fiber'"'"'s distal portion.

10. The system of claim 9, wherein the assay is housed in an assay compartment defined within the membrane'"'"'s hollow interior and between the optical fiber'"'"'s distal portion and the membrane'"'"'s closed end.

11. The system of claim 10, wherein the assay compartment is placed within the user'"'"'s tissue.

12. The system of claim 9, wherein the membrane is biodegradable.

13. The system of claim 8, wherein the proximal portion of the optical fiber is optically coupled to an assay interrogating system.

14. The system of claim 13, wherein the assay interrogating system is an optoelectronic interrogating system.

15. The system of claim 14, wherein the interrogating system includes an illumination source, and wherein said illumination source is a red laser diode.

16. The system of claim 15, wherein said first fluorophore is one of Alexa Fluor 647 (AF647), Alexa Fluor 750 (AF750), and QSY 21.

17. The system of claim 14, wherein the interrogating system is a stacked planar integrated optical system (SPIOS).

18. The system of claim 13, wherein the interrogating system is housed inside said transmitter.

19. The system of claim 8, wherein the optical fiber has a circular cross-section having a diameter of between about 200 μ

m and about 500 μ

m.

20. The system of claim 8, wherein the optical fiber has a circular cross-section having a diameter of less than 200 μ

m.

21. The system of claim 1, wherein the assay further includes a reference fluorophore different from said first fluorophore.

22. The system of claim 21, wherein said reference fluorophore is Alexa Fluor 700 (AF700).

23. The system of claim 21, wherein said reference fluorophore is labeled onto Human Serum Albumin (HSA).

24. The system of claim 1, wherein the glucose receptor is labeled with said first fluorophore, the glucose analog is labeled with a dye, and said first fluorophore and dye form a Fö

rster Resonance Energy Transfer pair.

25. The system of claim 24, wherein the glucose receptor is Mannan Binding Lectin (MBL), and the glucose analog is dextran.

26. The system of claim 25, wherein the first fluorophore is Alexa Fluor 594 (AF594), and the dye is hexamethoxy crystalviolet-1 (HMCV1).

27. The system of claim 24, wherein each of the first fluorophore and the dye is water soluble.

28. The system of claim 1, wherein the respective distal portions of the optical sensor and the non-optical sensor are co-located within the user'"'"'s body.

29. The system of claim 1, wherein the external transmitter is worn on the body of the user.

30. The system of claim 29, wherein the external transmitter is sized so as to have a volume of no more than 15 cm³ and a weight of about 10 g.

31. The system of claim 30, wherein the volume of the external transmitter is about 11 cm³.

32. The system of claim 1, wherein the non-optical glucose sensor includes a plurality of electrodes, each said electrode having a proximal portion that is disposed externally to the user'"'"'s body and a distal portion for internal placement in the user'"'"'s body, and wherein the optical glucose sensor includes an optical fiber having a proximal portion that is disposed externally to the user'"'"'s body and a distal portion for internal placement in the user'"'"'s body.

33. The system of claim 32, wherein the respective distal portions of the plurality of electrodes and the distal portion of the optical fiber are co-located within the user'"'"'s body.

34. The system of claim 1, wherein the optical glucose sensor has at least one failure mode, the non-optical glucose sensor has at least one failure mode, and the at least one failure mode of the optical glucose sensor is different from the at least one failure mode of the non-optical sensor.

35. The system of claim 1, wherein the mean absolute relative difference (MARD) for the system is about 13%.

36. The system of claim 35, wherein the system further has a sensitivity and specificity of at least 95% and a false alert occurrence rate below 10%.

37. The system of claim 1, wherein the handheld monitor includes an integrated blood glucose meter.

38. The system of claim 1, wherein the transmitter wirelessly transmits said respective glucose values to the hand-held monitor.

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

40. The system of claim 39, wherein the transmitter wirelessly transmits said respective glucose values to the insulin pump.

41. The system of claim 40, wherein said glucose monitoring system is a closed-loop system.