Non-invasive reagentless glucose determination

• US 8,843,186 B2
• Filed: 11/21/2012
• Issued: 09/23/2014
• Est. Priority Date: 11/21/2012
• Status: Active Grant

• Current Assignee: Folim G. Halaka
• Original Assignee: Folim G. Halaka
• Inventors: Halaka, Folim G.
• Primary Examiner(s): Winakur, Eric
• Assistant Examiner(s): Fardanesh, Marjan
• Application Number:
  US13/683,924
• Publication Number:
  US 20140142400A1
• Time in Patent Office: 671 Days
• Field of Search: 600310-344
• 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 5/0093 Detecting, measuring or recording by applying one single type of energy and measuring its conversion into another type of energy
• CPC Class Codes: A61B 5/05 Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves impedance plethysmography A61B5/0295; measuring movement of the entire body or parts thereof A61B5/11; detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof A61B5/24
• CPC Class Codes: A61B 5/0507 using microwaves or terahertz waves
• 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 5/7257 using Fourier transforms
• CPC Class Codes: B03C 2201/26 for use in medical applications
• CPC Class Codes: B03C 5/005 Dielectrophoresis, i.e. dielectric particles migrating towards the region of highest field strength B03C5/02 takes precedence; electrophoresis B01D57/02
• CPC Class Codes: B03C 5/026 using open-gradient differential dielectric separation, i.e. using electrodes of special shapes for non-uniform field creation, e.g. Fluid Integrated Circuit [FIC]

Abstract

Non-invasive apparatus and method for determining and monitoring glucose concentrations in human subjects. Glucose level is estimated through the effect of glucose on biological cells with glucose dependencies, e.g., red blood cells. The invention is based on the interaction of such cells with oscillating electric field gradients. The response of biological cells depends on factors including shape, size, and electrical charge distribution. The field gradient causes the cells to undergo characteristic motion which is detected by light beam scattering. The autocorrelation of the scattered light is computed, and the Fourier transform (FT) is performed to produce a characteristic velocity spectrum in which the peaks are characteristic of the cell “bio-electrical” states. The glucose level is estimated through measurements of changes of FT with changes in glucose levels after calibration with standard glucose methods.

Claims

1. A non-invasive glucose measuring apparatus comprising:

an elongated housing configured to present an oscillating, non-uniform electric field onto a predetermined part of a human body;

said housing containing first and second electrodes, the first electrode being arcuate;

the second electrode being substantially centered in said arcuate first electrode, wherein said electrodes are configured to generate the non-uniform electric field near the arcuate electrode and the center electrode when the electrodes are connected to an oscillating electrical power source;

a light source

said elongated housing also configured to present a collimated light beam generated by the light source onto said predetermined part and to direct light scattered from said part into a detector;

a processor in communication with said detector, said processor executing a program that produces an autocorrelation related to said scattered light;

said program comparing said autocorrelation, or a function of said autocorrelation, against a predetermined calibration to determine a glucose level.

2. The non-invasive glucose measuring apparatus of claim 1 wherein said light source is a laser.

3. The non-invasive glucose measuring apparatus of claim 1 wherein said detector is a photomultiplier or a photo-diode.

4. The non-invasive glucose measuring apparatus of claim 1 wherein said oscillating, non-uniform electric field is powered by an oscillating power supply.

5. The non-invasive glucose measuring apparatus of claim 4 wherein said oscillating power supply supplies an oscillating voltage of between approximately 1 volt and 1000 volts.

6. The non-invasive glucose measuring apparatus of claim 4 wherein said oscillating power supply supplies a voltage oscillating at a frequency between approximately 0 Hz and 100 GHz.

7. The non-invasive glucose measuring apparatus of claim 1 wherein said light source is a laser;

said detector is a photomultiplier or a photo-diode; and

said oscillating, non-uniform electric field is powered by an oscillating power supply.

8. The non-invasive glucose measuring apparatus of claim 7 wherein said processor, said laser, said detector and said oscillating power supply are separate from said elongated housing, and wherein light is supplied from said laser to said elongated housing and from said elongated housing to said detector by fiber optics, and a voltage is applied from said oscillating power supply to said probe by an electrical conductor to form said non-uniform field.

9. The non-invasive glucose measuring apparatus of claim 1 wherein said program that produces said autocorrelation function uses a correlator device.

10. The non-invasive glucose measuring apparatus of claim 1 wherein said program performs a Fourier Transform on said autocorrelation.

11. The non-invasive glucose measuring apparatus of claim 1 wherein said non-uniform electric field has a gradient between approximately 10 volts/cm² and approximately 10⁹ volts/cm².

12. The non-invasive glucose measuring apparatus of claim 1 wherein said oscillating, non-uniform electric field is sinusoidal.

13. The non-invasive glucose measuring apparatus of claim 1 wherein said predetermined calibration function is constructed by forming a plurality of autocorrelations or functions of autocorrelations with said apparatus at different glucose levels and comparing each to a calibrated glucose level taken close to the same time on the same subject with a validated glucose measuring device.

14. The non-invasive glucose measuring apparatus of claim 1 wherein said non-uniform electric field is formed by a first and second electrode, said first electrode being a ring or partial ring;

said second electrode being located at a point in proximity to a center-point of said ring.

15. The non-invasive glucose measuring apparatus of claim 1 further comprising an electrode producing said non-uniform electric field and wherein a portion of said collimated light beam reflects off of said electrode into said detector to create a heterodyne.

16. A method of in-vivo measurement of a glucose level in a bio fluid using an elongated housing comprising:

exposing a non-uniform, oscillating electric field onto a predetermined part of a human body containing said bio-fluid, said field originating from first and second electrodes in said elongated housing;

wherein the first electrode being arcuate;

the second electrode being substantially centered in said arcuate first electrode, wherein said electrodes are configured to generate a non-uniform electric field near the arcuate electrode and the center electrode;

scattering a light beam from said bio-fluid into a detector;

processing an output from said detector to form an autocorrelation;

computing a mathematical transform of said autocorrelation to produce a velocity spectrum;

comparing at least one peak in said velocity spectrum against a calibration to determine a glucose level in said bio-fluid.

17. The method of claim 16 further comprising:

producing said calibration by measuring glucose levels in test subjects using said probe and comparing said glucose levels with levels measured using a validated glucose meter.

18. A non-invasive glucose elongated housing comprising an electrode arrangement adapted to produce a non-uniform electric field and to present said field onto a target external to the elongated housing;

said elongated housing adapted to provide a collimated light beam onto the target, and to gather scattered light from the target, supplying said scattered light to a detector;

said elongated housing also adapted to reflect a portion of said collimated light beam from said electrode arrangement and to also supply that to the detector;

said housing containing a non-linear electric field generator comprising a first and second electrodes, the first electrode being arcuate;

the second electrode being substantially centered in said arcuate first electrode, wherein said non-linear electric field generator produces a non-uniform electric field near the arcuate electrode and the center electrode when the electrodes are connected to an oscillating electrical power source;

a processor, separate from the elongated housing, in communication with said detector, said processor executing a program that produces an autocorrelation related to said scattered light;

said program comparing said autocorrelation, or a function of said autocorrelation, against a predetermined calibration to determine a glucose level.

19. The non-invasive glucose elongated housing of claim 18 wherein said autocorrelation is transformed into a velocity spectrum.

20. The non-invasive glucose elongated housing of claim 19 wherein at least one peak in said velocity spectrum is compared against a calibration to produce a glucose level estimate.

21. A dielectrophoretic dynamic light scattering probe for measuring a property of a bodily fluid comprising:

an elongated, substantially tubular housing having a proximal and distal end, said housing containing a first and second fiber optic, the first fiber optic adapted to convey a collimated light beam to a location proximate said bodily fluid from the distal end to the proximal end of said probe;

the second fiber optic conveying scattered light from the proximal end to the distal end of said probe;

said housing containing a non-linear electric field generator comprising a first and second electrodes, the first electrode being arcuate;

the second electrode being substantially centered in said arcuate first electrode, wherein said non-linear electric field generator produces a non-uniform electric field near the arcuate electrode and the center electrode when the electrodes are connected to an oscillating electrical power source;

said housing and said non-linear electric field generator adapted to be placed near an extremity of a human patient, wherein the non-linear electric field generator is configured to present said non-linear electric field into the human extremity;

the first fiber optic configured to present said collimated light beam into the human extremity, and said second fiber optic configured to convey scattered light from the human extremity to a detector, said detector electrically coupled to a processor that computes an autocorrelation and determines said property.