Device for optical monitoring of constituent in tissue or body fluid sample using wavelength modulation spectroscopy, such as for blood glucose levels

• US 7,356,364 B1
• Filed: 01/21/2005
• Issued: 04/08/2008
• Est. Priority Date: 01/23/2004
• Status: Expired due to Fees

• Current Assignee: University of Hawai'i
• Original Assignee: University of Hawai'i
• Inventors: Roeder, John, Schorlemmer, Anita, Ho, Hao Chih, Bullock, Audra M., Ling, Daniel F.
• Primary Examiner(s): Winakur; Eric
• Assistant Examiner(s): Berhanu; Etsub D
• Application Number:
  US11/041,168
• Time in Patent Office: 1,173 Days
• Field of Search: 600/309, 600/310, 600/316, 600/322
• US Class Current: 600/310
• 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 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/6816 Ear lobe
• CPC Class Codes: A61B 5/7239 using differentiation including higher order derivatives

Abstract

A device for monitoring the concentration level of a constituent in tissue or a body fluid sample, such as glucose concentration in blood, has a laser light source which is modulated about a center emission frequency to probe the absorption spectrum of the constituent being monitored, a laser driver circuit for tuning and modulating the laser light, a photodetector for detecting light from the laser light source transmitted through the sample as the modulation frequency of the laser is tuned, and a demodulator for demodulating the transmitted light and detecting variations in magnitude at harmonics of the modulation frequency to assess the concentration level of that constituent. The device utilizes short-wavelength near-infrared laser light to monitor blood glucose levels, and could also be used for drug screening and diagnosis of other medical conditions as well. In one embodiment, the device is used to monitor blood glucose level externally from the body and non-invasively by trans-illumination through a thin layer of skin, without the need for physical penetration of the skin. In another embodiment, the device is used as an intravenous sensor deployed through a catheter, and its output can be used to control an insulin pump to stabilize the patient'"'"'s blood glucose levels.

Claims

1. A device for monitoring the concentration level of a constituent in tissue or a body fluid sample comprising:

(a) a laser light source in which the light is frequency modulated about a center emission frequency selected to probe a characteristic feature in an absorption spectrum of a constituent of the sample to be monitored;

(b) a laser driver circuit, operatively coupled to said laser light source, for controlling the frequency modulation of the laser light and tuning the center emission frequency of the laser light through a desired region of the absorption spectrum of said constituent;

(c) a photodetector for detecting light from the laser light source transmitted through the sample as the modulation emission frequency of the laser is tuned; and

(d) a demodulator for demodulating the transmitted light and detecting variations in magnitude at harmonics of the modulation frequency so as to assess the concentration level of the constituent of the sample.

2. A device according to claim 1, wherein the laser light source is operated to pass the laser light through the sample as the modulation frequency is tuned about the center emission frequency, and light transmission signals are detected at a higher order harmonic to provide information on the absorber constituent of the sample.

3. A device according to claim 1, wherein the transmitted light detected by the photodetector is demodulated for higher order harmonics using phase-sensitive coherent detection.

4. A device according to claim 1, adapted for monitoring concentration of a constituent in bodily fluid non-invasively, wherein the laser light source and photodetector are positioned to provide trans-illumination through a thin layer of skin containing blood vessels.

5. A device according to claim 4, wherein the laser light source and photodetector are positioned on opposite sides of an earlobe or finger webbing to measure blood glucose concentration, without the need for physical penetration of the skin.

6. A device according to claim 1, adapted for monitoring concentration of a constituent in blood intravenously, wherein the laser light is transmitted and detected through an optical fiber in a catheter probe inserted intravenously into a patient'"'"'s blood vessel.

7. A device according to claim 6, adapted for monitoring glucose concentration of blood in blood vessels, wherein the center modulation frequency is selected for monitoring the absorption spectrum of glucose in blood.

8. A device according to claim 7, wherein the transmitted light is spectrally analyzed and processed by a microprocessor to measure the patient'"'"'s blood glucose levels, and used to control an insulin pump to stabilize the patient'"'"'s glucose concentration within a desired range.

9. A device according to claim 1, adapted for monitoring blood glucose concentration, wherein the center modulation frequency of the laser light source is in the short wavelength near-infrared (sw-NIR) spectrum.

10. A device according to claim 1, wherein a Fabry-Perot etalon is used for stabilizing the modulation frequency of the laser light source.

11. A device according to claim 10, wherein the laser driver circuit is tuned and locked to the resonant frequencies of the etalon with feedback from the third harmonic signal of the selected modulation frequency.

12. A device according to claim 10, wherein a spectral signature of light transmission at a second harmonic of the selected modulation frequency is used to characterize the constituent of the sample being monitored.

13. A device according to claim 10, wherein a spectral signature of light transmission at a fourth harmonic of the selected modulation frequency is used to characterize the constituent of the sample being monitored.

14. A method for monitoring the concentration level of a constituent in tissue or a body fluid sample, comprising:

(a) providing a laser light source for light modulated about a center emission frequency selected to probe a characteristic feature in an absorption spectrum of a constituent of the sample to be monitored;

(b) tuning the center emission frequency of the laser light through a desired region of the absorption spectrum of said constituent;

(c) detecting light from the laser light source transmitted through the sample as the modulation emission frequency of the laser light source is tuned; and

(d) demodulating the transmitted light and detecting variations in magnitude at harmonics of the modulation frequency to assess the concentration level of the constituent of the sample being monitored.

15. A method according to claim 14, wherein the laser light source is operated to pass the laser light through the sample as the modulation frequency is tuned about the center emission frequency, and light transmission signals are detected at a higher order harmonic to provide information on the absorber constituent of the sample.

16. A method according to claim 14, wherein the transmitted light is demodulated for higher order harmonics using phase-sensitive coherent detection.

17. A method according to claim 14, used for monitoring concentration of a constituent in bodily fluid non-invasively, by trans-illumination through a thin layer of skin containing blood vessels.

18. A method according to claim 17, wherein the laser light is transmitted through a thin portion of a patient'"'"'s skin, such as an earlobe or finger webbing, without the need for physical penetration of the skin.

19. A method according to claim 14, adapted for monitoring concentration of a constituent in blood intravenously, wherein the laser light is transmitted and detected through an optical fiber inserted through a catheter probe inserted intravenously into a patient'"'"'s blood vessel.

20. A method according to claim 14, adapted for monitoring blood glucose concentration, wherein the center emission frequency of the laser light source is in the sw-NIR spectrum, and a second or fourth harmonic or a ratio of second to fourth harmonic of the modulation frequency is used to characterize the constituent of the sample being monitored.