Optical systems and methods for ratiometric measurement of blood glucose concentration

• US 8,838,195 B2
• Filed: 02/06/2008
• Issued: 09/16/2014
• Est. Priority Date: 02/06/2007
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Markle, David R., Wessling, Ritchie A., Kolehmainen, Donald J.
• Primary Examiner(s): Winakur, Eric
• Assistant Examiner(s): Fardanesh, Marjan
• Application Number:
  US12/027,158
• Publication Number:
  US 20080188725A1
• Time in Patent Office: 2,414 Days
• Field of Search: 600309-344
• US Class Current: 600/316
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14552 Details of sensors specially adapted therefor
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/7203 for noise prevention, reduction or removal
• 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 21/645 Specially adapted constructive features of fluorimeters

Abstract

Novel optical devices, methods and systems relating to the detection of glucose, and more particularly to real-time glucose monitoring, are disclosed herein. More particularly, various hardware and methodological means are disclosed for ratiometric correction of optical glucose measurements for artifacts of optical systems.

Claims

1. An optical device for determining blood glucose concentration, comprising:

an excitation light source that emits an excitation light signal;

a fiber optic sensor optically coupled to the excitation light source through an optical fiber configured as a spatial filter and comprising an indicator system comprising a fluorophore operably coupled to a glucose binding moiety, wherein upon absorption of at least a portion of the excitation light signal, the indicator system emits an emission light signal having an intensity related to the blood glucose concentration; and

a light sensitive module operably coupled to at least the fiber optic sensor, wherein the light sensitive module detects the emission light signal and at least a second light signal, wherein the second light signal is derived from the excitation light source or an optional reference light source;

wherein the fiber optic sensor is mechanically coupled to the optical fiber configured as the spatial filter.

2. The optical device of claim 1, further comprising a data processing device configured to determine the blood glucose concentration by performing a ratiometric analysis of the emission light signal and the at least second light signal therein substantially compensating for changes in the optical emission signal intensity unrelated to the blood glucose concentration.

3. The optical device of claim 1, further comprising at least one optical module configured to deliver the excitation light signal and the reference light signal to the fiber optic sensor.

4. The optical device of claim 3, wherein the optical module comprises an interference filter.

5. The optical device of claim 1, further comprising a mode mixing scrambler configured to remove high mode light from at least the excitation light signal.

6. The optical device of claim 1, further comprising a second excitation light source that emits a second excitation light signal at a different wavelength than the first excitation light source.

7. The optical device of claim 6, wherein the fluorophore is excited by the first and second excitation light signals and emits a first and second light signal at the same wavelengths.

8. The optical device of claim 1, wherein the light sensitive module comprises a beam splitter configured to receive at least the emission light signal and the excitation light signal from the fiber optic sensor, wherein the beam splitter is configured to reflect a first portion of light and configured to allow a second portion of light to pass through the beam splitter.

9. The optical device of claim 1, wherein the light sensitive module comprises at least a first detector, a second detector, a first amplifier, a second amplifier, and a first analog to digital converter, and a second analog to digital converter.

10. The optical device of claim 1, wherein the light sensitive module comprises a micro spectrometer.

11. The optical device of claim 1, wherein the fiber optic sensor further comprises a second fluorophore, wherein upon absorption of at least a portion of the excitation light signal, the second fluorophore emits a second emission light signal having an intensity insensitive to at least the blood pH and glucose concentration.

12. The optical device of claim 1, wherein the fiber optic sensor further comprises a dye coated surface that emits a second emission light upon excitation by the excitation light signal.

13. A ratiometric method for correcting an optical measurement of blood glucose concentration for optical artifacts unrelated to the blood glucose concentration, comprising:

providing the optical device of claim 1;

deploying the fiber optic sensor;

actuating the excitation light source therein exciting the indicator system, and optionally actuating the optional reference light source;

detecting the emission light signal and the second light signal; and

correcting the blood glucose concentration, comprising;

calculating a ratio of the emission light signal to the second light signal; and

comparing said ratio with a predetermined function that correlates ratios of emission light signals to second light signals with blood glucose concentrations.

14. The device of claim 1, further comprising a reflective surface.

15. The device of claim 14, wherein the reflective surface is configured to reflect the emission light signal and the excitation light signal through the optical device.

16. The device of claim 14, wherein the reflective surface is a mirror.

17. The device of claim 1, wherein the indicator system is housed within a cavity and is immobilized within a hydrogel which is permeable to glucose in the blood vessel.

18. The device of claim 17, wherein the cavity comprises a geometric design.

19. The device of claim 18, wherein the design of the cavity comprises a plurality of holes in the sensor.

20. The device of claim 19, wherein the plurality of holes are positioned perpendicular to a tangent along a length of the sensor, and wherein the plurality of holes are evenly spaced horizontally and evenly rotated around the sides of the sensor.

21. The device of claim 19, wherein the plurality of holes are positioned at an angle to a tangent along a length of the sensor, and wherein the plurality of holes are evenly spaced horizontally and evenly rotated around the sides of the sensor.

22. The device sensor of claim 18, wherein the design of the cavity comprises a groove along a length of the sensor.

23. The device sensor of claim 22, wherein the groove comprises a depth that extends to the center of the sensor.

24. The device sensor of claim 22, wherein the groove spirals around the length of the sensor.

25. The device sensor of claim 18, wherein the design of the cavity comprises a plurality of sections cut from the sensor.

26. The device sensor of claim 25, wherein the sections form a triangular wedge area that extends to the center of the sensor, and wherein the sections are evenly spaced horizontally and evenly rotated around the sides of the sensor.

27. The device of claim 17, wherein the hydrogel is confined by a semi-permeable membrane that allows passage of glucose and blocks passage of the indicator system.

28. The optical device of claim 1, wherein no collimating or focusing lens is used.