Method for non-invasive blood analyte measurement with improved optical interface

• US 5,823,951 A
• Filed: 04/18/1997
• Issued: 10/20/1998
• Est. Priority Date: 08/09/1995
• Status: Expired due to Fees

• Current Assignee: Rio Grande Medical Technologies Incorporated
• Original Assignee: Rio Grande Medical Technologies Incorporated
• Inventors: Messerschmidt, Robert G.
• Primary Examiner(s): Bahr, Jennifer
• Assistant Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US08/844,501
• Time in Patent Office: 550 Days
• Field of Search: 128/633, 128/664, 356/39-41, 600/310, 600/322, 600/323, 600/473, 514/744, 514/937, 514/941
• US Class Current: 600/322
• CPC Class Codes: A61B 2562/146 for optical coupling
• 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 5/1495 Calibrating or testing of in-vivo probes

Abstract

A method for non-invasively measuring the concentration of an analyte, particularly blood analyte in blood. The method utilizes spectrographic techniques in conjunction with an improved optical interface between a sensor probe and a skin surface or tissue surface of the body containing the blood to be analyzed. An index-matching medium is disclosed to improve the interface between the sensor probe and skin surface during spectrographic analysis. In a preferred embodiment, the blood analyte concentration in blood is quantified utilizing a partial squares analysis relative to a model incorporating analysis of plural known blood samples.

Claims

1. A method for non-invasive spectroscopic analysis of blood analytes in a tissue through a surface thereof, said method comprising the steps of:

(a) providing a means for irradiating said tissue with infrared energy;

(b) providing an output element, said output element operatively connected to a spectrum analyzer;

(c) providing a hydrophilic index-matching compound, said index-matching compound conforming to said surface of said tissue when applied thereto and having a refractive index closely matched to that of said tissue surface;

(d) disposing a quantity of said compound between said output element and said tissue surface to couple said output clement to said tissue surface and said analytes in said tissue through said index-matching compound;

(e) irradiating said tissue with said infrared energy so that there is differential absorption of said infrared energy in said tissue; and

,

(f) collecting infrared energy exiting said tissue through said output element as coupled to said tissue surface through said index-matching compound and quantifying said infrared energy with said spectrum analyzer.

2. The method of claim 1, wherein said index-matching compound is a liquid.

3. The method of claim 2, wherein said index-matching compound comprises a chlorinated fluorocarbon polymer oil.

4. The method of claim 3, wherein said chlorinated fluorocarbon polymer oil is a polymer of chlorotrifluoroethylene.

5. The method of claim 1, wherein said index-matching compound is a deformable solid.

6. The method of claim 1, wherein said infrared energy has multiple wavelengths in the range between about 1.0 and about 2.5 μ

m.

7. The method of claim 6, wherein said index-matching compound has a refractive index between 1.20 and 1.45.

8. A method for eliminating critical angle loss of diffusely reflected infrared energy at a tissue surface, said loss occurring from total internal reflection of said infrared energy when exiting from said tissue surface in a non-invasive spectroscopic method of measuring blood analytes in a tissue beneath said tissue surface, said method comprising the steps of:

(a) providing a means for irradiating said tissue with infrared energy of multiple wavelengths;

(b) providing an output element, said output element operatively connected to a spectrum analyzer;

(c) providing a hydrophilic index-matching compound, said index matching compound having a refractive index closely matched to that of said tissue surface, and disposing a quantity of said compound between said output element and said tissue surface to couple said output element to said tissue surface and said analytes in said tissue through said index-matching compound;

(d) irradiating said tissue with said multiple wavelengths of infrared energy so that there is differential absorption of at least some of said wavelengths in said tissue; and

,

(e) collecting diffusely reflected infrared energy exiting said tissue through said output element as coupled to said tissue surface through said index-matching compound and quantifying said diffusely reflected infrared energy with said spectrum analyze.

9. The method of claim 8, wherein said infrared energy has multiple wavelengths in the range between about 1.0 and about 2.5 μ

m.

10. The method of claim 9, wherein said index-matching compound has a refractive index between 1.20 and 1.45.

11. The method of claim 8, wherein said index-matching compound comprises a chlorinated fluorocarbon polymer oil.

12. The method of claim 11, wherein said chlorinated fluorocarbon polymer oil is a polymer of chlorotrifluoroethylene.

13. A non-invasive method for measuring the concentration of a blood analyte in human tissue by measuring diffusely reflected infrared energy from said human tissue comprising the steps of:

(a) providing an apparatus for measuring diffusely reflected infrared energy, said apparatus including an energy source emitting infrared energy at multiple wavelengths operatively connected to an input element, said apparatus further including an output element operatively connected to a spectrum analyzer;

(b) providing a hydrophilic index-matching compound and disposing a quantity of said compound between said human tissue and said input element and output element to couple said elements with said analyte-containing tissue through said index-matching compound;

(c) irradiating said tissue through said input element with multiple wavelengths of infrared energy so that there is differential absorption of at least some of said wavelengths; and

,

(d) collecting at least a portion of the non-absorbed infrared energy with said output element, wherein said output element coupled through said index-matching compound prevents loss of diffusely reflected infrared energy by total reflection exiting said tissue, followed by measuring the intensities of said wavelengths of the non-absorbed infrared energy with subsequent calculation of blood analyte concentration.

14. The method of claim 13, wherein said input element and output element are incorporated into a single sensor element.

15. The method of claim 13, wherein said index-matching medium has a refractive index closely matched to that of the tissue being irradiated.

16. The method of claim 15, wherein said index-matching medium has a refractive index between 1.30 and 1.45.

17. The method of claim 13, wherein said step of calculating a concentration of said blood analyte includes comparing said differential absorption to a model including differential absorption data on plural known analyte-containing tissue samples.

18. The method of claim 17, wherein a partial least squares analysis is utilized to compare said differential absorption of said analyte-containing tissue to said model.

19. The method of claim 13, wherein said input element and said output element include optical lenses.

20. A fluid composition for providing an optical interface between a skin surface on a body and a spectrographic sensor element when measuring the absorption of infrared energy by constituents under said skin surface within said body at multiple wavelengths, said fluid composition comprising:

(a) about 80% to about 99% of a mixture of perfluorocarbons and chlorofluorocarbons; and

,

(b) about 1% to about 20% of a hydrophilic additive.

21. The fluid composition of claim 20, wherein said hydrophilic additive is isopropyl alcohol.

22. The fluid composition of claim 20, wherein said mixture of perfluorocarbons and chlorofluorocarbons comprise about 90% chlorotrifluoroethene and about 10% other fluorocarbons.

23. The fluid composition of claim 20 further comprising about 1% to about 10% of cleansing agents, said cleansing agents including at least mineral oil.

24. The fluid composition of claim 20 further comprising about 1% to about 5% of a surfactant, said surfactant including at least sodium dodecyl sulfate.

25. The fluid composition of claim 20 wherein the index of refraction of said fluid is about 1.30 to about 1.40.

26. The fluid composition of claim 20 wherein the index of refraction of said fluid is about 1.38.

27. The fluid composition of claim 26 further comprising an antiseptic additive.

28. A quantitative analysis instrument for non-invasive measurement of a blood analyte in human tissue, said instrument comprising:

(a) a source of at least three wavelengths of infrared energy, said wavelengths being in the range of 500 to 2500 nm;

(b) an input sensor clement for directing said infrared energy into said tissue and an output sensor element for collecting at least a portion of the non-absorbed diffusely reflected infrared energy from said tissue;

(c) said input and output sensors being adapted to permit positioning of a hydrophilic index-matching compound across their surface and between said input and output sensors and the analyte-containing tissue;

(d) at least one detector for measuring a set of intensities of at least a portion of the non-absorbed diffusely reflected infrared energy from said tissue collected by said output sensor element;

(e) electronics for processing said measured set of intensities to estimate the value of said blood analyte; and

(f) means for indicating said estimated value of said blood analyte.

29. The analysis instrument of claim 28, wherein said sensor elements are adapted for use with an index-matching compound such that the thickness of the index-matching compound remains constant during the measurement period.

30. The analysis instrument of claim 28, wherein said sensor elements are adapted for use with an index-matching compound such that the thickness of the index-matching compound is relatively constant from one tissue measurement to the next tissue measurement.