Noninvasive measurement of glucose through the optical properties of tissue

• US 20040068163A1
• Filed: 10/27/2003
• Published: 04/08/2004
• Est. Priority Date: 01/26/2001
• Status: Active Grant

• Current Assignee: GLT Acquisition Corporation
• Original Assignee: Sensys Medical, Inc. (Sensys Medical Limited)
• Inventors: Ruchti, Timothy L., Monfre, Stephen L., Blank, Thomas B., Lorenz, Alexander, Thennadil, Suresh N.
• Granted Patent: US 6,990,364 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 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: G01N 2021/3595 using FTIR
• CPC Class Codes: G01N 21/31 Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry G01N21/72 takes precedence
• CPC Class Codes: G01N 21/33 using ultraviolet light G01N21/39 takes precedence
• CPC Class Codes: G01N 21/359 using near infrared light

Abstract

Methods and apparatus for noninvasive determination of blood analytes, such as glucose, through NIR spectroscopy utilize optical properties of tissue as reflected in key spectroscopic features to improve measurement accuracy and precision. Physiological conditions such as changes in water distribution among tissue compartments lead to complex alterations in the measured absorbance spectrum of skin and reflect a modification in the effective pathlength of light, leading to a biased noninvasive glucose measurement. Changes in the optical properties of tissue are detected by identifying key features responsive to physiological variations. Conditions not conducive to noninvasive measurement of glucose are detected. Noninvasive glucose measurements that are biased by physiological changes in tissue are compensated. In an alternate embodiment, glucose is measured indirectly based on natural physiological response of tissue to glucose concentration. A spectroscopic device capable of such measurements is provided.

Claims

4-1. The method of claim 1, further comprising the step of extracting said features, feature extraction comprising any mathematical transformation that enhances a quality or aspect of a sample measurement for interpretation so that structural properties and physiological state of said tissue sample are concisely represented.

36. An apparatus for noninvasive measurement of a target analyte in a tissue sample comprising:

means for measuring a spectrum of a tissue sample;

means for detecting changes in optical properties of said tissue sample related to physiological changes in said tissue, as manifested by spectral features reflecting said changes; and

either correcting a direct analyte measurement on the basis of said detected changes;

or

measuring said analyte indirectly on the basis of said spectral features.

37. The apparatus of claim 36, wherein said means for measuring a spectrum of a tissue sample comprises a spectrometer system, said spectrometer system comprising:

a source of near infrared (NIR) radiation;

a wavelength selection element;

a means for interfacing with the measurement site on the skin of a subject, wherein radiation is directed toward the measurement site from the source, and a light signal returned from the site is collected;

means for detecting said returned radiation; and

means for digitizing said returned signal.

38. The apparatus of claim 37, wherein said NIR source radiates energy in a range of approximately 700-2500 nm.

39. The apparatus of claim 37, wherein said NIR source comprises any of:

an LED array;

a halogen lamp.

40. The apparatus of claim 37, further comprising a band pass filter to minimize effect of wavelengths radiated from said source that are outside a spectral range of interest.

41. The apparatus of claim 37, wherein said wavelength selection element comprises any of:

a dispersive element;

an interferometer; and

successive illumination of elements of an LED array.

42. The apparatus of claim 41, further comprising a reference wavelength standard, wherein changes in said wavelength selection element caused by environmental changes are compensated by scanning said standard proximate to or simultaneous with interrogation of said tissue.

43. The apparatus of claim 37, wherein said means for interfacing with the measurement site on the skin of a subject comprises:

at least one optical element that directs radiation to and/or from the tissue, said optical element including any of;

a light pipe;

a fiber optic;

a lens system; and

a light directing mirror system.

44. The apparatus of claim 43, said means for interfacing with the measurement site on the skin of a subject further comprising:

a guide to assist in interfacing said optical element and said measurement site.

45. The apparatus of claim 44, said means for interfacing with the measurement site further comprising a subject interface module, said subject interface module including at least an elbow rest and a wrist rest.

46. The apparatus of claim 43, said means for interfacing with the measurement site on the skin of a subject further comprising:

an optical coupling fluid, a portion of said fluid being interposed between said measurement site and said source to minimize specular reflectance from surface of the skin.

47. The apparatus of claim 37, wherein an area irradiated and an area from which returning radiation is collected from are separated by a preselected distance, said distance selected to target a tissue volume conducive to measurement of a property of interest.

48. The apparatus of claim 37, wherein said means for detecting said returned radiation comprises:

single diodes or diode arrays responsive to targeted wavelengths of interest.

49. The apparatus of claim 48, wherein said diodes include InGaAs detectors.

50. The apparatus of claim 48, wherein said diodes are selected such that material junctions in said diodes do not coincide with targeted wavelengths.

51. The apparatus of claim 48, wherein said diodes convert said signal to a voltage.

52. The apparatus of claim 37, said means for digitizing said returned signal comprises an ADC (analog-to-digital converter), wherein said signal, having been converted to a voltage, is digitally sampled for analysis on a microprocessor-based system.

53. The apparatus of claim 52, further comprising a display, wherein a result of said analysis is displayed.

54. The apparatus of claim 36, wherein said means for detecting changes in optical properties of said tissue sample related to physiological changes in said tissue, as manifested by spectral features reflecting said changes;

and

either correcting a direct analyte measurement on the basis of said detected changes;

or

measuring said analyte indirectly on the basis of said spectral features comprises an analyzer, said analyzer including;

means for measuring a spectrum, m of said tissue, said spectrum denoted by a vector m∈

<sup>1×

N</sup> of absorbance values pertaining to a set of N wavelengths, λ

∈

^N spanning near IR region of approximately 700 to 2500 nm.

55. The apparatus of claim 54, said analyzer further comprising:

means for preprocessing said spectrum.

56. The apparatus of claim 55, said analyzer further comprising:

means for extracting said features, comprising any mathematical transformation that enhances a quality or aspect of a sample measurement for interpretation so that structural properties and physiological state of said tissue sample are concisely represented.

57. The apparatus of claim 56, said analyzer further comprising:

a tissue template determined through one or more spectral measurements combined according to a predetermined data selection criterion during each a measurement period, said tissue template subtracted from said spectrum.

58. The apparatus of claim 57, said analyzer further comprising

means for calculating a measurement bias adjustment.

59. The apparatus of claim 58, said analyzer further comprising

means for detecting outliers and conditions detrimental to spectroscopic glucose measurement though selected features.

60. The apparatus of claim 59, said analyzer further comprising:

at least one calibration model, said model determined from a calibration set of exemplary paired data points each consisting of a spectral measurement, x and an associated reference analyte value, y, said calibration set including analyte concentrations that span the expected range of variation and spectral variation representative of future spectral measurements, said model comprising an equation, a set of parameters and corresponding computer code implemented to measure a subject'"'"'s analyte level on the basis of a processed spectral measurement.