Systems and methods for blood glucose and other analyte detection and measurement using collision computing

• US 9,453,794 B2
• Filed: 03/25/2016
• Issued: 09/27/2016
• Est. Priority Date: 09/29/2014
• Status: Active Grant

• Current Assignee: Zyomed Holdings, Inc.
• Original Assignee: Zyomed Corp.
• Inventors: Gulati, Sandeep, Ruchti, Timothy L., Van Antwerp, William, Smith, John L.
• Primary Examiner(s): Kim, Kiho
• Application Number:
  US15/081,430
• Publication Number:
  US 20160231235A1
• Time in Patent Office: 186 Days
• US Class Current: 1/1
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• 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 5/024 Detecting, measuring or recording pulse rate or heart rate A61B5/0205, A61B5/021 take precedence
• CPC Class Codes: A61B 5/02416 using photoplethysmograph signals, e.g. generated by infrared radiation A61B5/14552 takes precedence
• CPC Class Codes: A61B 5/02433 for infrared radiation
• 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: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/7203 for noise prevention, reduction or removal
• CPC Class Codes: A61B 5/7235 Details of waveform analysis A61B5/349 takes precedence
• CPC Class Codes: A61B 5/7253 characterised by using transforms
• CPC Class Codes: A61B 5/7264 Classification of physiological signals or data, e.g. using neural networks, statistical classifiers, expert systems or fuzzy systems neural networks per se G06N3/00; expert systems per se G06N5/00
• CPC Class Codes: A61B 5/7267 involving training the classification device
• CPC Class Codes: G01N 21/3577 for analysing liquids, e.g. polluted water
• CPC Class Codes: G01N 21/359 using near infrared light
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B
• CPC Class Codes: G01N 21/49 within a body or fluid
• CPC Class Codes: G01N 2201/0612 Laser diodes
• CPC Class Codes: G01N 2201/062 LED's
• CPC Class Codes: G01N 2201/067 : Electro-optic, magneto-optic, acousto-optic elements
• CPC Class Codes: G01N 2201/12 : Circuits of general importance; Signal processing
• CPC Class Codes: G01N 2201/129 : Using chemometrical methods
• CPC Class Codes: G01N 33/4833 : of solid biological material, e.g. tissue samples, cell cultures tissue in vivo A61B5/00; cell suspensions G01N33/48735
• CPC Class Codes: G01N 33/49 : Blood chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80
• CPC Class Codes: G16H 50/20 : for computer-aided diagnosis, e.g. based on medical expert systems
• CPC Class Codes: G16H 50/70 : for mining of medical data, e.g. analysing previous cases of other patients

Abstract

In a noninvasive system for detection/measurement of glucose and other analytes in a medium such as tissue, illumination is directed to the medium and corresponding radiation from the medium is collected. Spectral energy changes associated with fragment(s)/feature(s) obtained from the collected radiation are determined using collision computing. Such spectral energy changes generally represent analyte concentration. The illumination is controlled to target a particular volume of the medium and/or such that the spectral energy changes become directionally monotonic with respect to analyte concentration. The illumination parameters include: intensity, wavelength, bandwidth, focal length, and/or duration of illumination, location and/or a size of an illuminated spot on the medium surface, depth at which the illumination can reach below the medium surface, spacing between the illuminated spot and a spot on the medium surface from which radiation is collected, and angle of the illumination relative to the medium surface.

Claims

1. A method for facilitating analysis of a medium, the method comprising the steps of:

directing illumination to a medium;

controlling a parameter of the illumination;

collecting a first radiation fragment from the medium; and

determining, via a collision computer, a first renormalized spectral energy change associated with at least a portion of the first radiation fragment.

2. The method of claim 1, wherein the medium comprises a tissue.

3. The method of claim 1, wherein controlling the parameter comprises selecting a value of the parameter based on, at least in part, a specified target volume within the medium.

4. The method of claim 1, wherein the first renormalized spectral energy change corresponds to a quantity of an analyte present within the medium.

5. The method of claim 1, further comprising:

collecting a second radiation fragment from the medium, at least one of;

(i) a time of collection of the second fragment being different from a time of collection of the first fragment, and (ii) a spatial characteristic of the second fragment being different from a corresponding spatial characteristic of the first fragment; and

determining, via collision computing, a second renormalized spectral energy change associated with at least a portion of the second radiation fragment,

wherein one of;

(a1) the first renormalized spectral energy change comprises a first renormalized spectral energy gain and the second renormalized spectral energy change comprises a second renormalized spectral energy gain; and

(b1) controlling the parameter comprises adjusting the parameter to a value at which the second renormalized spectral energy gain is not less than the first renormalized spectral energy gain; and

(a2) the first renormalized spectral energy change comprises a first renormalized spectral energy loss and the second renormalized spectral energy change comprises a second renormalized spectral energy loss; and

(b2) controlling the parameter comprises adjusting the parameter to a value at which the second renormalized spectral energy loss is not less than the first renormalized spectral energy loss.

6. The method of claim 5, wherein the parameter comprises at least one of:

(i) an amplitude of the illumination, comprising at least one of an intensity of the illumination and a duration of the illumination, (ii) a focal length of the illumination, (iii) a focal point of the illumination, (iv) a location of a target region to be illuminated by the illumination, (v) a size of the target region to be illuminated by the illumination, (vi) an angle of incidence of the illumination upon the medium, and (vii) a spectral characteristic, comprising at least one of a wavelength and a bandwidth, of the illumination.

7. The method of claim 1, wherein controlling the parameter comprises adjusting a focal length of the illumination.

8. The method of claim 7, wherein adjusting the focal length comprises at least one of:

(i) electronic tuning of a photorefractive material, (ii) acoustic tuning of a photorefractive material, (iii) electrical modulation of a dynamic lens, and (iv) radio frequency (RF) modulation of a dynamic lens.

9. The method of claim 1, wherein controlling the parameter comprises adjusting an amplitude of the illumination by adjusting at least one of:

(i) an area of exposed emitter surface, (ii) a shutter aperture size, (iii) a voltage of the illumination source, and (iv) a number of illumination sources that are tuned ON.

10. The method of claim 1, wherein controlling the parameter comprises adjusting a spatial parameter associated with a target of the illumination.

11. The method of claim 10, wherein adjusting the spatial parameter comprises varying a spacing between the illumination target and an area of detection used for collecting the first radiation fragment, varying the spacing comprising at least one of opto-mechanically varying the spacing and electro-optically varying the spacing.

12. The method of claim 10, wherein adjusting the spatial parameter comprises varying an illuminated area of the illumination target, varying the illuminated area comprising at least one of opto-mechanically varying the illuminated area and electro-optically varying the illuminated area by adjusting at least one of a standoff and a focal length of an illumination source.

13. The method of claim 10, wherein adjusting the spatial parameter comprises at least one of opto-mechanically varying a location of the illumination target and electro-optically varying the location of the illumination target.

14. The method of claim 1, wherein controlling the parameter comprises adjusting a duration of the illumination by at least one of:

(i) turning at least one illumination source ON and OFF, and (ii) adjusting a duration for which a shutter remains open.

15. The method of claim 1, wherein controlling the parameter comprises adjusting an angle at which the illumination is incident upon a surface of the medium.

16. The method of claim 1, wherein controlling the parameter comprises adjusting at least one of:

(i) a wavelength of the illumination and (ii) a bandwidth of the illumination.

17. A system for facilitating analysis of a medium, comprising:

an adjustable illumination subsystem for directing illumination to a medium;

a collector for collecting a radiation fragment from the medium; and

a collision computer programmed to compute a first renormalized spectral energy change associated with at least a portion of the radiation fragment.

18. The system of claim 17, wherein the adjustable illumination subsystem is adapted to adjust at least one of:

(i) an amplitude of the illumination, comprising at least one of an intensity of the illumination and a duration of the illumination, (ii) a focal length of the illumination, (iii) a focal point of the illumination, (iv) a location of a target region to be illuminated by the illumination, (v) a size of the target region to be illuminated by the illumination, (vi) an angle of incidence of the illumination upon the medium, and (vii) a spectral characteristic, comprising at least one of a wavelength and a bandwidth, of the illumination.

19. The system of claim 17, wherein the adjustable illumination subsystem comprises a device having an adjustable focus, for adjusting a focal length of the illumination.

20. The method of claim 19, wherein the device comprises at least one of:

(i) electronically tunable photorefractive element, (ii) acoustically tunable photorefractive element, (iii) an electrically modulated dynamic lens, and (iv) a radio frequency (RF) modulated dynamic lens.

21. The system of claim 20, wherein the photorefractive element comprises a phase-conjugate mirror.

22. The system of claim 17, wherein the adjustable illumination subsystem comprises at least one of:

(i) an emitter having an adjustable exposed surface area, (ii) a shutter having an adjustable aperture, at least one of a size of the aperture and a duration for which the aperture is open being adjustable, (iii) an illumination source having adjustable voltage, and (iv) a plurality of illumination sources, at least one of which is selectively switchable ON and OFF, for adjusting an amplitude of the illumination.

23. The system of claim 22, wherein a duration for which at least one of the illumination sources is selectively switched ON is adjustable.

24. The system of claim 17, wherein the adjustable illumination subsystem comprises a translator adapted to spatially adjust at least one of:

(i) a focal point of the illumination relative to a surface of the medium and (ii) a location of a target area of the illumination.

25. The system of claim 24, wherein the translator is adapted to adjust at least one of:

(i) a focal length of the illumination, and (ii) a standoff between a component of the illumination subsystem and the surface of the medium.

26. The system of claim 24, wherein the translator comprises at least one of an opto-mechanical translator and an electro-optical translator.

27. The system of claim 24, wherein the translator comprises at least one of a scanning mirror and a voice coil.

28. The system of claim 17, wherein the adjustable illumination subsystem comprises an optical component for directing the illumination to the medium at a specified angle of incidence upon a surface of the medium.

29. The system of claim 28, wherein the optical component comprises a plurality of optical fibers each being oriented at a different angle relative to a normal axis.

30. The system of claim 17, wherein the adjustable illumination subsystem comprises an illumination source having at least one of:

(i) an adjustable wavelength, and (ii) an adjustable bandwidth.