Compact apparatus for noninvasive measurement of glucose through near-infrared spectroscopy

• US 20060173254A1
• Filed: 01/03/2006
• Published: 08/03/2006
• Est. Priority Date: 03/08/2002
• Status: Active Grant

• Current Assignee: GLT Acquisition Corporation
• Original Assignee: George M. Acosta, James R. Henderson, Kevin H. Hazen, N. Alan Abul Haj, Stephen L. Monfre, Thomas B. Blank, Timothy L Ruchti
• Inventors: Haj, N. Alan Abul, Henderson, James R., Ruchti, Timothy L., Acosta, George M., Monfre, Stephen L., Hazen, Kevin H., Blank, Thomas B.
• Granted Patent: US 7,787,924 B2
• Time in Patent Office: Days
• US Class Current: 600/316
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• CPC Class Codes: A61B 2560/0233 Optical standards
• CPC Class Codes: A61B 2560/0252 using ambient temperature
• CPC Class Codes: A61B 2560/0412 Low-profile patch shaped housings
• CPC Class Codes: A61B 2560/0443 Modular apparatus
• CPC Class Codes: A61B 2560/0456 Apparatus provided with a docking unit
• CPC Class Codes: A61B 2562/0242 for varying or adjusting the optical path length in the tissue
• CPC Class Codes: A61B 2562/146 for optical coupling
• CPC Class Codes: A61B 2562/227 Sensors with electrical connectors
• CPC Class Codes: A61B 2562/228 Sensors with optical connectors
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes 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 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/6833 Adhesive patches
• CPC Class Codes: A61B 5/7203 for noise prevention, reduction or removal
• CPC Class Codes: A61B 5/7225 Details of analog processing, e.g. isolation amplifier, gain or sensitivity adjustment, filtering, baseline or drift compensation A61B5/30, A61B5/316 take precedence; transformers for specific applications H01F38/00; amplifiers H03F
• CPC Class Codes: A61B 5/726 using Wavelet transforms
• CPC Class Codes: G01N 21/359 using near infrared light
• CPC Class Codes: G01N 21/49 within a body or fluid

Abstract

The invention involves the monitoring of a biological parameter through a compact analyzer. The preferred apparatus is a spectrometer based system that is attached continuously or semi-continuously to a human subject and collects spectral measurements that are used to determine a biological parameter in the sampled tissue. The preferred target analyte is glucose. The preferred analyzer is a near-IR based glucose analyzer for determining the glucose concentration in the body.

Claims

1. An apparatus for noninvasive measurement of glucose through near-infrared spectroscopy, comprising:

a base module comprising a grating and a detector array;

a sample module, securely and removeably interfaced to a sample site, said sample module coupled to said base module, said sample module comprising;

an illumination source;

a first optic located between said illumination source and said sample site, wherein said first optic removes heat; and

a second optic located between said illumination source and said sample site, wherein said second optic contacts an area about said sample site and aids in mechanical stabilization of a collection optic, said collection optic being in close proximity to said sample site, wherein said close proximity reduces specular reflectance; and

a communication bundle for carrying optical and/or electrical signals between said base module and said sample module, and for carrying power to said sample module from said base module.

2. The apparatus of claim 1, said sample module further comprising at least one of:

a low profile sample interface;

a low wattage stabilized source in close proximity to said sampled site;

an excitation collection cavity or optics;

a guide;

a preheated interfacing solution;

means for maintaining a temperature controlled skin sample;

a mechanism for constant pressure and/or displacement of sampled skin tissue; and

a photonic stimulation source.

3. The apparatus of claim 1, said sample module further comprising:

a guide that is securely and removeably attached to said sample site, said guide continuously and/or periodically physically and optically locating said sample module relative to said sample site in a repeatable manner and with minimal disturbance to said sample site.

4. The apparatus of claim 3, further comprising means for:

pretreatment of said sample site sample module

reduction of specular reflectance;

to approach and maintain appropriate sample site temperature variation; and

minimizing sample site hydration changes.

5. The apparatus of claim 1, wherein said sample module collects a diffusely reflected and/or transflected signal from said sample site.

6. The apparatus of claim 1, either of said base module and said sample module further comprise any of:

a wavelength reference standard; and

an intensity reference standard.

7. The apparatus of claim 1, wherein said communication bundle is integrated between said sample module and said base module.

8. The apparatus of claim 1, wherein said sample module and said base module are integrated together into a handheld unit.

9. The apparatus of claim 3, wherein said sample module reversibly couples into said guide for reproducible contact pressure and/or sample location.

10. The apparatus of claim 9, said guide further comprising:

at least one magnet for aiding in positioning a sample module probe to ensure proper penetration of said probe into a guide aperture, and to enable a constant pressure and/or displacement interface of said sample site;

wherein said magnet is optionally electrically activated to facilitate controlled movement into a guide aperture and to allow, through reversal of said magnet poles, withdrawal from said guide aperture without pulling.

11. The apparatus of claim 1, said sample module further comprising:

a heater for maintaining said sample site at a constant temperature.

12. The apparatus of claim 1, wherein said base module either resides on a support surface or is worn by a person.

13. The apparatus of claim 1, wherein said base module is coupled directly to said sample module, with said communication bundle forming an integral part thereof.

14. The apparatus of claim 1, said illumination source comprising:

a tungsten halogen source ranging in power from about 0.05 to 5 Watts.

15. The apparatus of claim 1, said illumination source comprising:

at least one light emitting diode.

16. The apparatus of claim 1, further comprising:

a photodiode; and

a feedback controller for allowing said illumination source to be driven at different levels at different points in time during and prior to data acquisition,

wherein said photodiode is placed before an optional order sorter to detect visible light from said illumination source.

17. The apparatus of claim 1, said illumination source further comprising:

a reflector having any of a parabolic, elliptical, and spherical shape.

18. The apparatus of claim 1, said communication bundle further comprising:

quick connect optics which comprise;

a first collection optic that is fixed into said communication bundle; and

a connector in said communication bundle for accepting a connection to said sample module.

19. The apparatus of claim 1, wherein said communication bundle is readily removed from said sample module, allowing said sample module to remain in close proximity with said sample site.

20. The apparatus of claim 1, wherein said first optic comprises:

a silicon filter for removing light under 1050 nm, wherein a grating is used in the 1150 to 1850 nm region without detection of second or higher order light off of said grating,

wherein said silicon filter is placed before the grating.

21. The apparatus of claim 1, wherein said first optic comprises any of:

a filter that is a silicon longpass optic;

a filter that is coated to block light from 1900 to 2500 nm;

a filter that is antireflection-coated to match refractive indices and increase light throughput;

a filter used in combination with a shortpass filter;

a filter that is coated with a blocker for removing a largest intensity of a black body curve of a typical tungsten halogen source that is not blocked by silicon, wherein said blocking band covers any region from about 1800 to 3000 nm; and

a filter that is used in combination with an RG glass that cuts off at about 2500 nm

to provide a bandpass filter passing light from approximately 1100 to 2500 nm, wherein said filter combination is optionally used in conjunction with a coating layer to provide a bandpass from 1100 to 1900 nm.

22. The apparatus of claim 1, said sample module further comprising:

a Fabry-Perot interferometer.

23. The apparatus of claim 1, said sample module comprising:

a surface defining an aperture for providing optical pathlengths within a sample for indirectly monitoring glucose concentrations within a body, providing acceptable energy delivery to said sample site, and providing appropriate heating/temperature control of said sample site;

wherein variation of said aperture affects a net analyte signal of a sampled tissue.

24. The apparatus of claim 1, further comprising:

a fiber optic collection fiber placed in a center of an illumination area defined by an aperture.

25. The apparatus of claim 1, further comprising:

means for performing an indirect determination of glucose from sample constituents which comprise any of;

fat, protein, and water, wherein said sample constituents are distributed as a function of depth in a sample, wherein a magnitude of an indirect signal varies with said aperture.

26. The apparatus of claim 1, wherein said sample module is semi-permanently attached to said sample site with a replaceable adhesive.

27. The apparatus of claim 24, further comprising:

a removable plug for placement in said aperture to stabilize tissue at said sample site.

28. The apparatus of claim 1, wherein said second optic provides a hydration barrier of said sample site.

29. The apparatus of claim 1, sample module further comprising means for treating said sample site with any of:

photonic stimulation;

ultrasound pretreatment;

mechanical stimulation;

cooling; and

heating.

30. The apparatus of claim 1, said sample module further comprising:

a light emitting diode for providing photonic stimulation to induce capillary blood vessel dilation.

31. The apparatus of claim 1, further comprising:

a coupling fluid dispensed between said sample module and said sample site for coupling incident photons into a tissue sample, wherein said coupling fluid is optionally preheated to minimize changes to a surface temperature of said sample site, and minimize spectral changes observed from said tissue sample, wherein said coupling fluid, if preheated, is preheated using any of illumination source energy, sample site heater energy, and an auxiliary heat source.

32. The apparatus of claim 1, further comprising:

means for automated delivery of a coupling fluid prior to optical sampling.

33. The apparatus of claim 1, further comprising:

means for using any of a signal and an absence of observed intensity at large water absorbance bands about 1450, 1900, and 2500 nm to determine when said sample module is in close proximity with a sample site surface.

34. The apparatus of claim 1, wherein said base module further comprises:

a two-way wireless communication system for transferring data between said sample module and any of said base module and a data collection/processing system.

35. The apparatus of claim 1, further comprising:

means for standardizing a near-infrared wavelength axis based on a comparative analysis of a master spectrum and a slave spectrum of a standardization material.

36. The apparatus of claim 35, wherein said standardization material is any of:

measured external to said base module;

measured continuously and mounted within said base module in a separate light path, wherein an internal wavelength standard is measured simultaneously with said sample;

moved through an actuator into a main optical train at an appropriate time;

wherein a reference spectrum is collected in any of a transmittance mode, reflectance mode, or a diffuse reflectance mode.

37. The apparatus of claim 1, further comprising:

means for measuring a reference spectrum and a wavelength standardization spectrum through spectroscopic measurement of a non-absorbing material and a material with known and immutable spectral absorbance bands.

38. The apparatus of claim 1, said base module further comprising:

means for bias correcting one or more of spectra (X) and glucose concentration data (Y).

39. The apparatus of claim 1, said base module further comprising:

means for calibrating to an individual or a group of individuals based upon a calibration data set comprised of paired data points of processed spectral measurements and reference biological parameter values.

40. The apparatus of claim 39, wherein said reference values comprise at least one of the following:

finger capillary blood glucose concentrations;

alternate site capillary blood glucose concentrations at a site on the body other than the finger;

interstitial glucose concentrations; and

venous blood glucose concentrations.

41. The apparatus of claim 1, wherein said base module is integrally connected to a docking station, wherein said docking station comprises a computer and a glucose management center;

wherein said glucose management center keeps track of events occurring in time comprising any of glucose intake, insulin delivery, and determined glucose concentration.

42. The apparatus of claim 1, said base module further comprising:

means for estimating precision of measurement through a statistical analysis of repeated or successive measurements; and

means for determining when a biological parameter is close to a preset level through a statistical estimate of confidence limits of a future analyte prediction.

43. The apparatus of claim 1, said base module further comprising:

means for determining when a biological parameter is close to a preset level, wherein an alarm is invoked if an associated preset alarm level is within a confidence interval of a future biological parameter prediction.

44. The apparatus of claim 1, further comprising:

means for taking any of continuous and semi-continuous measurements when said sample module is in proximate contact with said sample site.

45. The apparatus of claim 1, said base module further comprising:

means for using time based information and trends to perform functions comprising any of;

estimate of precision, determination of a confidence interval, and prediction of future events.

46. The apparatus of claim 1, further comprising:

a link provided to an insulin delivery system to provide a feedback mechanism for control purposes.

47. The apparatus of claim 1, said sample module further comprising:

a spectrometer system comprising light emitting diodes to provide near-infrared radiation to said sample site over predefined wavelength ranges, wherein each of said light emitting diodes provides near-infrared radiation over a band of wavelengths.

48. The apparatus of claim 47, wherein said LEDs are sequentially energized one at a time and/or in groups to obtain various estimates of diffuse reflectance of various tissue volumes at specific wavelengths or bands of wavelengths.

49. The apparatus of claim 47, wherein said LEDs are pulsed to provide short measurements with high signal-to-noise ratios to provide greater illumination intensity while avoiding photo heating of a sampled tissue volume.