Non-invasive biothermophotonic sensor for blood glucose monitoring

• US 20070213607A1
• Filed: 03/07/2006
• Published: 09/13/2007
• Est. Priority Date: 03/07/2006
• Status: Active Grant

• Current Assignee: Andreas Mandelis, Sergey Telenkov
• Original Assignee: Andreas Mandelis, Sergey Telenkov
• Inventors: Telenkov, Sergey, Mandelis, Andreas
• Granted Patent: US 7,729,734 B2
• Time in Patent Office: Days
• US Class Current: 600/316
• CPC Class Codes: A61B 5/0091 for mammography
• 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 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/7228 Signal modulation applied to the input signal sent to patient or subject; demodulation to recover the physiological signal modulation H03C

Abstract

There is provided a glucose monitoring method and apparatus based on the principle of Wavelength-Modulated Differential Laser Photothermal Radiometry (WM-DPTR). Two intensity modulated laser beams operating in tandem at specific mid-infrared (IR) wavelengths and current-modulated synchronously by two electrical waveforms 180 degrees out-of-phase, are used to interrogate the tissue surface. The laser wavelengths are selected to absorb in the mid infrared range (8.5-10.5 μm) where the glucose spectrum exhibits a discrete absorption band. The differential thermal-wave signal generated by the tissue sample through modulated absorption between two specific wavelengths within the band (for example, the peak at 9.6 and the nearest baseline at 10.5 μm) lead to minute changes in sample temperature and to non-equilibrium blackbody radiation emission. This modulated emission is measured with a broadband infrared detector. The detector is coupled to a lock-in amplifier for signal demodulation. Any glucose concentration increases will be registered as differential photothermal signals above the fully suppressed signal baseline due to increased absorption at the probed peak or near-peak of the band at 9.6 μm at the selected wavelength modulation frequency. The emphasis is on the ability to monitor blood glucose levels in diabetic patients in a non-invasive, non-contacting manner with differential signal generation methods for real-time baseline corrections, a crucial feature toward precise and universal calibration (independent of person-to-person contact, skin, temperature or IR-emission variations) in order to offer accurate absolute glucose concentration readings.

Claims

1. ) A glucose monitoring method based on the principle of Wavelength-Modulated Differential Laser Photothermal Radiometry (WM-DPTR), comprising:

a) irradiating the tissue surface with two specialty low-power (˜

200 mW) radiation emitting sources.

b) modulating the said sources in tandem and synchronously at angular modulation frequency ω

=2π

f with fin the 0.1-10000 Hz range by appropriate modulating means.

c) producing periodic frequency pulses of the irradiating sources (laser beams) in the range covering 0.1 Hz to 10 kHz, especially in the vicinity of (but not confined to) 700 Hz.

d) making the two spatially separated beams at the desired wavelengths co-incident on the sample surface using appropriate optical elements.

e) equalizing the intensities of the two beams and monitoring sub-surface tissue fluid differential absorption at the pre-determined wavelengths in the presence of glucose concentration within the normal human range (90-120 mg/dl) in order to determine the healthy band for normal residual glucose of the emissive infrared signal and/or adjust the said signal to zero to null the differential absorption from the healthy band.

f) generating out-of-phase photothermal-wave signals at both wavelengths leading to minute changes in net sample temperature (<

1K) due to differential absorption.

g) using photothermal-wave superposition (destructive interference) over one modulation period in the tissue leading to net differential blackbody radiation emission.

h) collecting said emission signal with suitable mid-IR collecting optics including solid-angle and reflectivity optimized curved mirrors and specialty fiber-optic delivery systems.

i) detecting said collected signal with a wide-bandwidth (dc-MHz) detector.

j) outfitting the said detector with a narrow bandpass IR filter to block the CO₂ laser emission line range, if so required by possible overlap of the spectral bandwidth of the detector with the source emission range.

k) demodulating the said detector signal by an appropriate demodulating device (lock-in amplifier).

l) recording the said detector signals.

m) processing said recorded signal and correlating it to glucose concentration.

2. ) the method according to claim 1 wherein said irradiating sources are two specialty low-power (˜

200 mW) CO₂ lasers emitting in the vicinity of 9.6 and 10.5 μ

m wavelength, respectively or two specialty low-power (˜

200 mW) halogen lamps with filters in the 9.6 to 10.7μ

range.

3. ) the method according to claim 1 wherein said modulation of the said sources is done by electrical waveforms 180 degrees out-of-phase or by mechanical choppers 180 degrees out-of-phase or by opto-acoustic modulators 180 degrees out-of-phase or by electro-optical modulators 180 degrees out-of-phase.

4. ) the method according to claim 1 wherein said making the two spatially separated beams at the desired wavelengths co-incident on the sample surface with an appropriate beam combiner and mid-1R-transparent optical lens or with optical fibers fitted with a beam combiner and optical lens at the tip.

5. ) the method according to claim 1 wherein said equalizing the intensities of the two beams to obtain the baseline signal is done by using a variable neutral density filter or by adjusting the current amplitude driving one of the lasers.

6. ) the method according to claim 1 wherein said collecting the said emission signal is done with mid-IR collecting optics including solid-angle and reflectivity optimized curved mirrors or with a mid-IR collecting fiber optic system.

7. ) the method according to claim 1 wherein detecting said emission signal is done with a with a broadband HgCdTe (MCT) detector with sensitivity in the (2-12 μ

m) range or with a thermoelectrically cooled or room-temperature solid state HgCdZnTe (MCZT) detector (2-6 μ

m) or with a ZnSe, Ge, or other commercially available or specially designed engineered detector with sensitivity in the (2-12 μ

m) range.

8. ) the method according to claim 1 wherein said demodulating of the said detector signal is done by using a lock-in amplifier or by using a lock-in amplifier card or digital LIA (software) or by using an appropriate data acquisition card and digital LIA software.

9. ) the method according to claim 1 wherein said recording of the said signals is done by a personal computer or other storage and display device.

10. ) the method according to claim 1 wherein said processing of said recorded signal and correlating it to glucose concentration is done by proprietary software.

11. ) A glucose monitoring biothermophotonic apparatus based on the principle of Wavelength-Modulated Differential Laser Photothermal Radiometry (WM-DPTR), comprising:

n) irradiating the tissue surface with two specialty low-power (˜

200 mW) radiation emitting sources.

o) modulating the said sources in tandem and synchronously at angular modulation frequency ω

=2π

f with fin the 0.1-10000 Hz range by appropriate modulating means.

p) producing periodic frequency pulses of the irradiating sources (laser beams) in the range covering 0.1 Hz to 10 kHz, especially in the vicinity of (but not confined to) 700 Hz.

q) making the two spatially separated beams at the desired wavelengths co-incident on the sample surface using appropriate optical elements.

r) equalizing the intensities of the two beams and monitoring sub-surface tissue fluid differential absorption at the pre-determined wavelengths in the presence of glucose concentration within the normal human range (90-120 mg/dl) in order to determine the healthy band for normal residual glucose of the emissive infrared signal and/or adjust the said signal to zero to null the differential absorption from the healthy band.

s) generating out-of-phase photothermal-wave signals at both wavelengths leading to minute changes in net sample temperature (<

1K) due to differential absorption.

t) using photothermal-wave superposition (destructive interference) over one modulation period in the tissue leading to net differential blackbody radiation emission.

u) collecting said emission signal with suitable mid-IR collecting optics including solid-angle and reflectivity optimized curved mirrors and specialty fiber-optic delivery systems.

v) detecting said collected signal with a wide-bandwidth (dc-MHz) detector.

w) outfitting the said detector with a narrow bandpass IR filter to block the CO₂ laser emission line range, if so required by possible overlap of the spectral bandwidth of the detector with the source emission range.

x) demodulating the said detector signal by an appropriate demodulating device (lock-in amplifier).

y) recording the said detector signals.

z) processing said recorded signal and correlating it to glucose concentration.

12. ) the apparatus according to claim 11 wherein said irradiating sources are two specialty low-power (˜

200 mW) CO₂ lasers emitting in the vicinity of 9.6 and 10.5 μ

m wavelength, respectively or two specialty low-power (˜

200 mW) halogen lamps with filters in the 9.6 to 10.7μ

range.

13. ) the apparatus according to claim 11 wherein said modulation of the said sources is done by electrical waveforms 180 degrees out-of-phase or by mechanical choppers 180 degrees out-of-phase or by opto-acoustic modulators 180 degrees out-of-phase or by electro-optical modulators 180 degrees out-of-phase.

14. ) the apparatus according to claim 11 wherein said making the two spatially separated beams at the desired wavelengths co-incident on the sample surface with an appropriate beam combiner and mid-1R-transparent optical lens or with optical fibers fitted with a beam combiner and optical lens at the tip.

15. ) the apparatus according to claim 11 wherein said equalizing the intensities of the two beams to obtain the baseline signal is done by using a variable neutral density filter or by adjusting the current amplitude driving one of the lasers.

16. ) the apparatus according to claim 11 wherein said collecting the said emission signal is done with a mid-IR collecting optics including solid-angle and reflectivity optimized curved mirrors or with a mid-IR collecting fiber optic system.

17. ) the apparatus according to claim 11 wherein detecting said emission signal is done with a with a broadband HgCdTe (MCT) detector with sensitivity in the (2-12 μ

m) range or with a thermoelectrically cooled or room-temperature solid state HgCdZnTe (MCZT) detector (2-6 μ

m) or with a ZnSe, Ge, or other commercially available or specially designed engineered detector with sensitivity in the (2-12 μ

m) range.

18. ) the apparatus according to claim 11 wherein said demodulating of the said detector signal is done by using a lock-in amplifier or by using a lock-in amplifier card or digital LIA (software) or by using an appropriate data acquisition card and digital LIA software.

19. ) the apparatus according to claim 11 wherein said recording of the said signals is done by a personal computer or other storage and display device.

20. ) the apparatus according to claim 11 wherein said processing of said recorded signal and correlating it to glucose concentration is done by proprietary software.