Method and apparatus for the non-invasive sensing of glucose in a human subject

• US 9,037,206 B2
• Filed: 03/19/2012
• Issued: 05/19/2015
• Est. Priority Date: 06/14/2005
• Status: Active Grant

• Current Assignee: Dominion Assets LLC
• Original Assignee: Dominion Assets LLC
• Inventors: Grata, Jeremy, Pitsakis, Michael N.
• Primary Examiner(s): Winakur, Eric
• Assistant Examiner(s): Fardanesh, Marjan
• Application Number:
  US13/423,705
• Publication Number:
  US 20120238844A1
• Time in Patent Office: 1,156 Days
• Field of Search: 600309-344
• US Class Current: 600/316
• CPC Class Codes: A61B 2562/0233 Special features of optical sensors or probes classified in A61B5/00
• CPC Class Codes: A61B 5/1112 Global tracking of patients, e.g. by using GPS
• 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 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: G01J 1/46 using a capacitor
• CPC Class Codes: G01J 3/02 Details
• CPC Class Codes: G01J 3/027 Control of working procedures of a spectrometer; Failure detection; Bandwidth calculation
• CPC Class Codes: G01J 3/42 Absorption spectrometry; Double beam spectrometry; Flicker spectrometry; Reflection spectrometry beam switching arrangements G01J3/08
• CPC Class Codes: G01N 21/359 using near infrared light

Abstract

An apparatus for a non-invasive sensing of biological analytes in a sample includes an optics system having at least one radiation source and at least one radiation detector; a measurement system operatively coupled to the optics system; a control/processing system operatively coupled to the measurement system and having an embedded software system; a user interface/peripheral system operatively coupled to the control/processing system for providing user interaction with the control/processing system; and a power supply system operatively coupled to the measurement system, the control/processing system and the user interface system for providing power to each of the systems. The embedded software system of the control/processing system processes signals obtained from the measurement system to determine a concentration of the biological analytes in the sample.

Claims

1. A method of spectrophotometric referencing that utilizes pulse differential spectroscopy applicable to capillary blood diffuse reflectance by:

a) providing an optics system with at least one optical path which emits a plurality of narrow band pulses of near infrared light within a range of from about 1,200 nm to about 1,900 nm, each narrow band having a unique center emission wavelength, and each narrow band activated individually and sequentially during each scan cycle, said scan cycle occurring multiple times per second and continuously for a period equivalent to at least more than one cardiac cycle;

b) repeatedly sampling at least multiple times per second, irrespective of the systolic and diastolic phases of the cardiac cycle, at each unique emission center wavelength within each of the plurality of the narrow bands within the wavelength range at least one path of the optics system through an external, diffusely-reflecting, capillary-bearing sample, wherein the optical path is time-varying as a result of heart pulsation and changes minutely close in time as a minimum and a maximum photon path changes during a heart pulse;

c) synchronously detecting at each unique center emission wavelength of each narrow band, with each cycle of sequentially activating the plurality of narrow bands, a time-dependent diffuse reflectance signal of the optical path through the sample;

d) computing a spectrophotometric absorbance at each unique center wavelength, as a ratio of a maxima to a minima of the time-dependent diffuse reflectance signal; and

e) determining a concentration of biological analytes in a sample using the spectrophotometric absorbance.

2. The method of claim 1, further comprising the step of synchronizing a detected time signal at each unique center emission wavelength of each narrow band for each scan cycle.

3. The method of claim 1, further comprising the steps of:

(i) providing a radiation source having a plurality of narrow band emitters for sequentially emitting a plurality of emission bands over a selected wavelength range in the near infrared, each emission band having the unique center emission wavelength and each emission band activated individually with each scan cycle repeated multiple times per second continuously for a period equivalent to at least two cardiac cycles;

(ii) obtaining a spectral measurement taken during each scan cycle at the unique center emission wavelength of a specified narrow band emitter;

(iii) calculating a ratio between the spectral measurements taken at the time dependent scan cycle of the minimum reflectance and the spectral measurement taken at the time dependent scan cycle of the maximum reflectance, for each unique center wavelength of each narrow band thereby providing a sensed signal of the biological analyte.

4. The method of claim 3, wherein steps (ii)-(iv) are repeated for a subsequent, specified narrow band emitter.

5. The method of claim 3, wherein the spectral measurement taken at a diastolic state provides a signal including a bulk skin signal and a base capillary signal, and the spectral measurement taken at a systolic state provides a signal including a bulk skin signal, a base capillary signal and a perturbed capillary signal.

6. The method of claim 5, further comprising the steps of:

calculating the perturbed capillary signal using the calculated ratio of step (iii); and

associating the perturbed capillary signal with the specified biological analyte.

7. The method of claim 3, wherein the specified narrow band emitter is activated at least 100 times per second.

8. The method of claim 3, wherein the radiation source is a laser diode array, an edge-emitting laser diode array, a surface-emitting laser diode array, a semiconductor laser diode array, an alternate laser diode array or any combination thereof.

9. The method of claim 3, wherein the radiation source is a laser diode array having a plurality of discrete laser diode elements.

10. The method of claim 9, wherein each discrete laser diode element has a unique center emission wavelength, and the center emission wavelengths of the plurality of laser diode elements are spaced between about 1,200 nm and about 1,900 nm.

11. The method of claim 9, wherein each discrete laser diode element is individually addressable and configured to be activated according to a sequence.