Optical microneedle-based spectrometer

• US 8,452,356 B2
• Filed: 05/02/2009
• Issued: 05/28/2013
• Est. Priority Date: 05/02/2008
• Status: Expired due to Fees

• Current Assignee: SRI International, Inc.
• Original Assignee: SRI International, Inc.
• Inventors: Vestel, Michael J., Nashold, Karen M., Stetter, Joseph R., Walter, Diane P., Faris, Gregory W., Schmidt, Roger, Holland, Christopher
• Primary Examiner(s): SZMAL, BRIAN SCOTT
• Application Number:
  US12/434,640
• Publication Number:
  US 20100121163A1
• Time in Patent Office: 1,487 Days
• Field of Search: 600/310, 600/316, 600/581, 604/503, 604/6.04, 604/6.09, 216/2, 216/11, 216/41, 216/56, 216/67, 216/79, 264/154, 264/322, 264/328.1, 264/504, 436/57, 356/450
• US Class Current: 600/310
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/6833 Adhesive patches
• CPC Class Codes: A61B 5/6849 in combination with a needle set

Abstract

Optical microneedles are adapted for near-infrared or mid-infrared in vivo spectroscopic sensing; and provide a MEMS-based spectrometer for continuous lactate and glucose monitoring by means of a near-infrared or mid-infrared optical microneedle array in a transdermal patch.

Claims

1. A method of transdermally analyzing a physiological fluid with a minimally-invasive device for transdermally analyzing a physiological fluid, comprising:

an array of optical microneedles and an optical connector,

wherein the optical microneedles comprise mid infrared light-transmitting microneedles and corresponding light-receiving microneedles, and comprise tips adapted and oriented to penetrate skin and optically probe physiological fluid, and the optical microneedles and the connector are in an optical path configured to pass mid infrared light from a source through the connector, then through and out the tips of the light-transmitting microneedles, to then interact with the physiological fluid before entering the tips of, and passing through the light-receiving microneedles, and then through the connector to a spectrometer detector for optical signal analysis informative of the physiological fluid, the method comprising;

penetrating a skin surface with the microneedle tips;

transmitting light from a light source through the light-transmitting microneedles, through physiological fluid beneath the skin surface, through the light-receiving microneedles and to a detector which can discriminate the wavelength dependent transmission, either by using a wavelength discriminating source or spectrometer at the output end of the instrument; and

analyzing the light incident at the detector as informative of the physiological fluid, and

further comprising the step of adjusting the optical path length by selecting multiple, parallel, or series microneedles with or without different lengths to enhance the signal/noise performance of the microneedles for a given target analyte or interferent.

2. The method of claim 1, which provides multiple wavelength measurements using a spectrometer on either the source or detector side, and comprises a tunable light source or a multiwavelength light source array.

3. The method of claim 1 wherein the tips are sterile.

4. The method of claim 1 wherein the tips are sterilely packaged.

5. The method of claim 1 wherein the array comprises between 2 and 10,000 microneedles.

6. The method of claim 1 wherein the array comprises between 2 and 10,000 microneedles arrayed on and normal to a surface, with the tips distal to the surface.

7. The method of claim 1 wherein the array is a pair of microneedles.

8. The method of claim 1 wherein light-reflectors are embossed or coated on the microneedle tips to direct the light into and out of microneedles.

9. The method of claim 1, wherein the microneedles comprise a material selected from the group consisting of high-density polyethylene (HDPE), ZnSe, diamond, polycrystalline infrared (PIR) fiber, sapphire, and chalcogenide glasses.

10. The method of claim 1, wherein the microneedles comprise a material that is diamond.

11. The method of claim 1, wherein the device is a MEMs-fabricated chip.

12. The method of claim 1, wherein the device further comprises disposable planar and/or MEMS waveguides structures to couple and direct the light to and from the microneedles, source and detector.

13. The method of claim 1, wherein the device is a skin patch.

14. The method of claim 1, wherein the microneedles comprise a material selected from the group consisting of high-density polyethylene (HDPE), ZnSe, diamond, polycrystalline infrared (PIR) fiber, sapphire, and chalcogenide glasses.

15. The method of claim 1, wherein the microneedles comprise a material that is diamond.

16. The method of claim 1, wherein the device is adapted for continuous glucose, alanine, ascorbate, lactate, triacetin, urea or drug monitoring.

17. The method of claim 1 wherein the device is part of a monitoring system comprising the device, the light source and the detector.

18. The method of claim 17 wherein the source is wavelength tunable.

19. The method of claim 17 wherein the source is a tunable laser device rather than a broadband source which then must be scanned at the detector stage.

20. The method of claim 17 wherein the source comprises a quantum cascade laser.

21. The method of claim 17 further comprising quantum cascade lasers, a planar waveguide, partial reflectors to the array of optical microneedles, a miniature MWIR detector, and controlling electronics.

22. The method of claim 17 wherein the light source is broadband or tunable and the detector is wavelength discriminating.

23. The method of claim 17 wherein the system is adapted to multiplex analysis of analytes of the physiological fluid.

24. The method of claim 1, wherein the microneedles have diameters of 1 to 500 μ

m, spacings of 10 to 5000 μ

m, and lengths of 10 to 1000 μ

m.

25. The method of claim 1 wherein the microneedles act as miniature attenuated total reflection waveguides or crystals, creating evanescent waves which interact with the physiological fluid, and the light absorbed by the evanescent waves is discriminated by the detector, which can characterize the absorption as a function of wavelength.

26. The method of claim 1 wherein the microneedles act as a single-mode waveguide wherein either an attached cladding contains the mode or the tissue acts as a cladding to contain the mode.

27. The method of claim 1 wherein retroreflection from the microneedle tips serves to monitor both absorption and/or refractive index in the tissue.

28. The method of claim 1 wherein the microneedles probe absorption in the physiological fluid through the Kramers Kronig relationship using measurements of refractive index with or without absorption measurements.

29. The method of claim 1 wherein the microneedles probe the analyte concentration through changes in refractive index.