Non-invasive methods of using spectral information in determining analyte concentrations

• US 20080051645A1
• Filed: 08/21/2007
• Published: 02/28/2008
• Est. Priority Date: 08/22/2006
• Status: Active Grant

• Current Assignee: Bayer Healthcare LLC (Bayer AG)
• Original Assignee: Bayer Healthcare LLC (Bayer AG)
• Inventors: Houlne, Michael, Rebec, Mihailo
• Granted Patent: US 7,603,151 B2
• Time in Patent Office: Days
• US Class Current: 600/316
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• 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

Abstract

A non-invasive method of determining the concentration of an analyte uses Raman or fluorescence spectral information. A high-intensity band of light is applied to one side of skin tissue. The high-intensity light enters the skin tissue and generates a Raman or fluorescence signal. A Raman-generating material or fluorescence-generating material is placed in a location nearest the other side of skin tissue. The Raman-generating or fluorescence-generating material is located generally opposite of the entry of the applied high-intensity light. The Raman or fluorescence signal is collected and the analyte concentration is determined using the collected Raman signal.

Claims

1. A non-invasive method of determining the concentration of an analyte using Raman spectral information, the method comprising the acts of:

applying a high-intensity, narrow band of light to a first side of tissue, the high-intensity light entering the tissue and generating a Raman signal;

placing a Raman-generating material in a location nearest a second side of the tissue, the second side being located generally opposite of the first side;

reflecting the high-intensity light from the Raman-generating material so as to produce additional Raman signal that passes through the tissue towards the first side of the tissue;

reflecting the Raman signal generated from the high-intensity light entering the tissue towards the first side of the tissue via the Raman-generating material;

collecting the Raman signal generated from the high-intensity light entering the tissue and the additional Raman signal generated from the Raman-generating material; and

determining the analyte concentration using information from the collected Raman signals.

2. The method of claim 1, wherein the high-intensity light is applied from a monochromatic light source.

3. The method of claim 2, wherein the high-intensity light is applied from a laser-diode source.

4. The method of claim 1, wherein the analyte is glucose.

5. The method of claim 1, wherein the tissue is skin, the skin tissue is from about 1 to about 5 mm in thickness.

6. The method of claim 1, wherein the Raman signal is collected at a wavelength range of from about 300 to about 5000 nm.

7. The method of claim 6, wherein the Raman signal is collected a wavelength range of from about 830 to about 1030 nm.

8. The method of claim 1, wherein the information from the collected Raman signals assists in determining the level of optical scattering and absorbance of the tissue, the information being used to assist in determining the analyte concentration.

9. The method of claim 1, wherein the information from the collected Raman signals assists in determining the level of optical scattering of the tissue, the information being used to assist in determining the analyte concentration.

10. The method of claim 1, wherein the information from the collected Raman signals assists in determining the level of absorbance of the tissue, the information being used to assist in determining the analyte concentration.

18. The method of claim 1, wherein the information from the collected Raman signals assists in determining the level of absorbance of the tissue, the information being used to assist in determining the analyte concentration.

11. A non-invasive method of diagnosis using Raman spectral information, the method comprising the acts of:

applying a high-intensity, narrow band of light to a first side of tissue, the high-intensity light entering the tissue and generating a Raman signal;

placing a Raman-generating material in a location nearest a second side of the tissue, the second side being located generally opposite of the first side;

reflecting the high-intensity light from the Raman-generating material so as to produce additional Raman signal that passes through the tissue towards the first side of the tissue;

reflecting the Raman signal generated from the high-intensity light entering the tissue towards the first side of the tissue via the Raman-generating material;

collecting the Raman signal generated from the high-intensity light entering the tissue and the additional Raman signal generated from the Raman-generating material; and

using information from the collected Raman signals to perform a general diagnosis.

12. The method of claim 11, wherein performing the general diagnosis includes identifying the presence of a particular analyte.

13. The method of claim 11, wherein performing the general diagnosis includes identifying a particular molecule.

14. The method of claim 11, wherein the Raman signal is collected at a wavelength range of from about 300 to about 5000 nm.

15. The method of claim 14, wherein the Raman signal is collected a wavelength range of from about 830 to about 1030 nm.

16. The method of claim 11, wherein the information from the collected Raman signals assists in determining the level of optical scattering and absorbance of the skin tissue, the information being used to assist in performing the general diagnosis.

17. The method of claim 11, wherein the information from the collected Raman signals assists in determining the level of optical scattering of the tissue, the information being used to assist in performing the general diagnosis.

19. A non-invasive method of determining the concentration of an analyte using Raman spectral information, the method comprising the acts of:

pinching an area of the skin tissue;

placing a Raman-generating material near or around the pinched skin tissue, the Raman-generating material forming at least one opening therethrough;

applying a high-intensity, narrow band of light to the skin tissue through the at least one opening, the high-intensity light entering the skin tissue and generating a Raman signal;

reflecting the high-intensity light and Raman signal that pass through the pinched skin tissue back into the pinched skin tissue via the Raman-generating material;

collecting the Raman signal generated from the high-intensity light entering the skin tissue and the additional Raman signal generated from the Raman-generating material; and

determining the analyte concentration using the collected Raman signals.

20. The method of claim 19, wherein the Raman signal is collected a wavelength range of from about 300 to about 5000 nm.

21. The method of claim 20, wherein the Raman signal is collected a wavelength range of from about 830 to about 1030 nm.

22. A non-invasive method of determining the concentration of an analyte using fluorescence spectral information, the method comprising the acts of:

applying a high-intensity, narrow band of light to a first side of tissue, the high-intensity light entering the tissue and generating a fluorescence signal;

placing a fluorescence-generating material in a location nearest a second side of the tissue, the second side being located generally opposite of the first side;

reflecting the high-intensity light from the fluorescence-generating material so as to produce additional fluorescence signal that passes through the tissue towards the first side of the tissue;

reflecting the fluorescence signal generated from the high-intensity light entering the tissue towards the first side of the tissue via the fluorescence-generating material;

collecting the fluorescence signal generated from the high-intensity light entering the tissue and the additional fluorescence signal generated from the fluorescence-generating material; and

determining the analyte concentration using information from the collected fluorescence signals.

23. A non-invasive method of diagnosis using fluorescence spectral information, the method comprising the acts of:

applying a high-intensity light to a first side of tissue, the high-intensity light entering the tissue and generating a fluorescence signal;

placing a fluorescence-generating material in a location nearest a second side of the tissue, the second side being located generally opposite of the first side;

reflecting the high-intensity light from the fluorescence-generating material so as to produce additional fluorescence signal that passes through the tissue towards the first side of the tissue;

reflecting the fluorescence signal generated from the high-intensity light entering the tissue towards the first side of the tissue via the fluorescence-generating material;

collecting the fluorescence signal generated from the high-intensity light entering the tissue and the additional fluorescence signal generated from the fluorescence-generating material; and

using information from the collected fluorescence signals to perform a general diagnosis.