METHODS AND SYSTEMS FOR NON-INVASIVE MEASUREMENT OF BLOOD GLUCOSE CONCENTRATION BY TRANSMISSION OF MILLIMETER WAVES THROUGH HUMAN SKIN

• US 20160051171A1
• Filed: 08/25/2015
• Published: 02/25/2016
• Est. Priority Date: 08/25/2014
• Status: Active Grant

• Current Assignee: California Institute of Technology, Huntington Medical Research Institutes
• Original Assignee: California Institute of Technology
• Inventors: PIKOV, Victor, SIEGEL, Peter H.
• Granted Patent: US 11,229,383 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61B 5/01 Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue clinical contact thermometers G01K13/20
• CPC Class Codes: A61B 5/021 Measuring pressure in heart or blood vessels A61B5/0205 takes precedence
• 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 5/4848 Monitoring or testing the effects of treatment, e.g. of medication
• CPC Class Codes: A61B 5/4866 Evaluating metabolism A61B5/083 takes precedence
• CPC Class Codes: A61B 5/7235 Details of waveform analysis A61B5/349 takes precedence

Abstract

A device is described for interrogating human skin using tight coupling between the transmitter and receiver of the millimeter waves (MMWs). Methods are provided to evaluate changes in the amplitude and/or phase of the transmitted MMWs in order to estimate the blood concentration of glucose. Using this device and the related methods, the blood glucose concentration or a change in the blood glucose concentration can be monitored for diagnosing diabetes mellitus and other metabolic disorders of carbohydrate metabolism characterized by either high blood glucose level (hyperglycemia) or low blood glucose level (hypoglycemia), as well as for monitoring (including self-monitoring) a metabolic disorder progression or an efficacy of treatment.

Claims

1. A device comprising:

an electromagnetic wave transmitter, configured to be attached to biological tissue and transmit electromagnetic waves through biological tissue; and

an electromagnetic wave receiver, configured to receive the electromagnetic waves transmitted through the biological tissue.

2. The device of claim 1, wherein the electromagnetic waves are in the microwave or millimeter wavelength range.

3. The device of claim 2, wherein the biological tissue is human skin.

4. The device of claim 3, further comprising an electromagnetic wave analyzer, configured to analyze the electromagnetic waves before or after transmission.

5. The device of claim 4, further comprising a display for displaying results from the electromagnetic wave analyzer.

6. The device of claim 5, wherein the electromagnetic wave transmitter is configured to modulate, and the electromagnetic wave receiver is configured to detect, a magnitude and phase of the electromagnetic waves.

7. The device of claim 6, wherein the electromagnetic wave transmitter comprises an electromagnetic wave source and a waveguide or antenna.

8. The device of claim 7, wherein the electromagnetic wave source is chosen from the group comprising:

a backward-wave oscillator, an orotron, a Gunn diode oscillator, an IMPATT diode, a solid state Gunn diode, a synthesizer with upconverter, an oscillator and discrete amplifier, a MMIC amplifier, a silicon or silicon germanium CMOS oscillator and power amplifier, a YIG tuned oscillator, a dielectric resonator, a vacuum tube oscillator, a clinotron, a gyro-klystron, a gyrotron, a traveling wave tube, a gyro-traveling wave tube, a pulsed magnetron.

9. The device of claim 8, wherein the electromagnetic wave transmitter comprises an antenna, the antenna comprising a polymer substrate.

10. The device of claim 9, wherein the polymer substrate is chosen from the group comprising:

polyimide, LCP, polytetrafluoroethylene, SU-8 photoresist, polyethylene, polypropylene, TPX, polystyrene, parylene.

11. The device of claim 10, wherein the antenna further comprises a metallic pattern.

12. The device of claim 7, wherein the electromagnetic wave transmitter comprises a waveguide, the waveguide chosen from the group comprising:

a 3D open ended hollow structure, 3D open ended dielectrically loaded structures, a conical structure, a pyramidal structure, an ellipsoidal horn structure.

13. The device of claim 7, wherein the waveguide or antenna comprises a planar or 3D waveguide, a coupled radiator, a planar antenna coupled oscillator and amplifier, a wire or planar rectenna, or an RF radiator.

14. The device of claim 7, further comprising at least one sensor chosen from the group comprising:

a thermometer configured to detect a temperature of the human skin, a piezoelectric or ultrasound sensor configured to detect tissue pressure at the human skin.

15. The device of claim 1, wherein the electromagnetic waves are microwaves or millimeter waves.

16. The device of claim 15, wherein the electromagnetic waves have a frequency between 20 and 300 GHz.

17. The device of claim 1, further comprising an electromagnetic beam shaping element between the electromagnetic wave transmitter and the biological tissue.

18. The device of claim 17, wherein the electromagnetic beam shaping element is chosen from the group comprising:

a convex lens, a concave lens, a collimating lens, a spherical minor, a parabolic minor, an elliptical mirror, a conical mirror.

19. The device of claim 1, wherein a distance between the electromagnetic wave transmitter and receiver is less than one wavelength of the electromagnetic wave.

20. The device of claim 1, wherein a distance between the electromagnetic wave transmitter and receiver is between one and two wavelengths of the electromagnetic wave.

21. A method comprising:

applying electromagnetic waves at a frequency in the range of 20 to 300 GHz to biological skin containing blood vessels;

receiving the electromagnetic waves transmitted through the biological skin;

analyzing the received electromagnetic waves for changes in magnitude or phase; and

estimating a chemical concentration or a change in the chemical concentration in blood within the blood vessels, based on the analyzed electromagnetic waves.

22. The method of claim 21, wherein applying electromagnetic waves comprises applying several electromagnetic waves frequencies, amplitudes, and modulation rates.

23. The method of claim 21, wherein applying electromagnetic waves comprises applying the electromagnetic waves in a duty cycled manner.

24. The method of claim 21, wherein the chemical concentration is of blood glucose is estimated based on decreased absorption of electromagnetic waves.

25. The method of claim 24, further comprising diagnosing or monitoring metabolic disorders of carbohydrate metabolism characterized by hyperglycemia or hypoglycemia, based on the blood glucose concentration.

26. The method of claim 25, wherein the metabolic disorder is diabetes mellitus.

27. The method of claim 26, wherein the biological skin is on an ear, neck, arm, or leg.

28. The method of claim 27, wherein applying electromagnetic waves is through an electromagnetic wave transmitter comprising an electromagnetic wave source and a first antenna or waveguide.

29. The method of claim 28, wherein the electromagnetic wave source is chosen from the group comprising:

a backward-wave oscillator, an orotron, a Gunn diode oscillator, an IMPATT diode, a solid state Gunn diode, a synthesizer with upconverter, an oscillator and discrete amplifier, a MMIC amplifier, a silicon or silicon germanium CMOS oscillator and power amplifier, a YIG tuned oscillator, a dielectric resonator, a vacuum tube oscillator, a clinotron, a gyro-klystron, a gyrotron, a traveling wave tube, a gyro-traveling wave tube, a pulsed magnetron.

30. The method of claim 29, wherein the electromagnetic wave transmitter comprises a first antenna, the first antenna comprising a polymer substrate chosen from the group comprising:

polyimide, LCP, polytetrafluoroethylene, SU-8 photoresist, polyethylene, polypropylene, TPX, polystyrene, parylene.

31. The method of claim 29, wherein the electromagnetic wave transmitter comprises a first waveguide, the first waveguide chosen from the group comprising:

a 3D open ended hollow structure, 3D open ended dielectrically loaded structures, a conical structure, a pyramidal structure, an ellipsoidal horn structure.

32. The method of claim 30, wherein the first antenna is fabricated by nanoimprint lithography, optical lithography, electron beam lithography, X-ray lithography, or synchrotron radiation etching.

33. The method of claim 32, wherein the first antenna further comprises a metallic structure, the metallic structure fabricated by electroplating, liftoff, spinning, plasma etching, or sputter deposition.

34. The method of claim 28, wherein applying electromagnetic waves further comprises applying an electromagnetic beam shaping element between the electromagnetic wave transmitter and the biological skin.

35. The method of claim 34, wherein the electromagnetic beam shaping element is chosen from the group comprising:

a convex lens, a concave lens, a collimating lens, a spherical mirror, a parabolic minor, an elliptical mirror, a conical mirror.

36. The method of claim 21, further comprising:

monitoring over at least seven days an individual'"'"'s absorption signature of the electromagnetic waves, based on the estimating;

evaluating normal day-to-day variability for the individual'"'"'s absorption signature, based on the monitoring;

correlating levels of the chemical concentration directly with an absolute value for the individual; and

evaluating changes in the chemical concentration deviating from normal chemical concentration levels, based on the monitoring, evaluating and correlating.

37. The method of claim 36, wherein the absolute value is determined through a blood test.

38. The method of claim 37, wherein the chemical concentration is of glucose.

39. The method of claim 21, wherein applying electromagnetic waves at a frequency in the range of 20 to 300 GHz comprises applying the electromagnetic waves at a plurality of frequencies for each estimating.

40. The method of claim 36, wherein evaluating changes is in response to a change in a diet or activity pattern.

41. The method of claim 28, wherein receiving the electromagnetic waves is through an electromagnetic wave receiver comprising a second antenna or waveguide and a distance between the first antenna or waveguide and the second antenna or waveguide is less than one wavelength of the electromagnetic waves.

42. The method of claim 28, wherein receiving the electromagnetic waves is through an electromagnetic wave receiver comprising a second antenna or waveguide and a distance between the first antenna or waveguide and the second antenna or waveguide is between one and two wavelengths of the electromagnetic waves.