Method for improving non-invasive determination of the concentration of analytes in a biological sample

• US 6,241,663 B1
• Filed: 04/29/1999
• Issued: 06/05/2001
• Est. Priority Date: 05/18/1998
• Status: Expired due to Term

• Current Assignee: Abbott Laboratories
• Original Assignee: Abbott Laboratories
• Inventors: Khalil, Omar S., Jeng, Tzyy-Wen, Hanna, Charles F., Wu, Xiaomao, Yeh, Shu-Jen
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US09/302,207
• Time in Patent Office: 768 Days
• Field of Search: 600/310, 600/322, 600/323, 600/326, 600/334, 600/344, 600/473, 356/39, 356/41, 250/341.1, 250/341.2, 250/341.5, 250/341.6, 250/339.03, 250/339.09
• US Class Current: 600/310
• CPC Class Codes: A61B 2562/0233 Special features of optical sensors or probes classified in A61B5/00
• CPC Class Codes: A61B 2562/0242 for varying or adjusting the optical path length in the tissue
• CPC Class Codes: A61B 2562/043 in a linear array
• 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 5/1491 Heated applicators
• CPC Class Codes: A61B 5/6824 Arm or wrist
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B

Abstract

A method for determining the concentration of an analyte in a biological sample comprising the steps of:

(1) providing an optical measuring instrument that comprises at least one thermally controllable optical measuring element that comes into contact with the surface of the biological sample;

(2) applying an inert, thermally conductive, optically transparent coupling agent to the at least one optical measuring element or to the surface of the biological sample or both so that the coupling agent will be disposed at the interface of the surface of the biological sample and the at least one optical measuring element;

(3) measuring optical properties of the biological sample by means of the optical measuring instrument; and

(4) correlating the optical properties of the biological sample with the concentration of the analyte in the biological sample.

A coupling agent suitable for this invention must have several properties to enable it to help decrease measurement variation, especially drift. One of the most important properties is sufficiently high optical stability that the optical properties of the coupling agent do not change even during prolonged experiments, such as oral glucose tolerance tests. Secondly, the coupling agent should have sufficiently high thermal conductivity to allow fast, efficient heat transfer between the optical probe and the biological sample. Third, the coupling agent should have sufficiently high viscosity to prevent it from migrating from the measurement area. Yet, it should also have sufficiently low viscosity to allow sufficient contact between the optical probe and the biological sample and to permeate into any small pockets between the probe and the biological sample that would otherwise be filled with the air. Fourth, the coupling agent should be inert. Material from the coupling agent should not diffuse into the biological sample and material from the biological sample should not diffuse into the coupling agent.

Claims

1. A method for determining the concentration of analyte in a biological sample comprising the steps of:

(1) providing an optical measuring instrument that comprises at least one thermally controllable optical measuring element that comes into contact with a surface of said biological sample;

(2) applying an inert, thermally conductive, optically transparent coupling agent to said at least one optical measuring element or to said surface of said biological sample or both so that said coupling agent will be disposed at the interface of said surface of said biological sample and said at least one optical measuring element, said coupling agent having sufficiently high optical stability that the optical properties of said coupling agent do not change during optical measurements or during storage, said coupling agent having sufficiently high thermal conductivity to allow rapid, efficient heat transfer between said optical measuring element and said biological sample, said coupling agent having sufficiently high viscosity to prevent it from migrating from said interface, said coupling agent having sufficiently low viscosity to allow sufficient contact between said optical measuring element and said biological sample, said coupling agent having a refractive index higher than that of said biological sample over the temperature range of a measurement;

(3) measuring at least one optical property of said biological sample by means of said at least one optical measuring element; and

(4) correlating the at least one optical property of said biological sample with the concentration of said analyte in said biological sample.

2. The method of claim 1, further including the step of controlling the temperature of said biological sample, whereby said at least one optical property of said biological sample is measured at a given depth from the surface of said biological sample.

3. The method of claim 2, wherein said depth from the surface of said biological sample is less than 3 mm.

4. The method of claim 2, wherein said depth from the surface of said biological sample is less than 2 mm.

5. The method of claim 1, wherein said measuring step is carried out at a plurality of wavelengths.

6. The method of claim 1, wherein said coupling agent is thermally stable at temperatures ranging from 10°

C. to 45°

C.

7. The method of claim 1, wherein said coupling agent is inert to oxygen at temperatures ranging from 10°

C. to 45°

C.

8. The method of claim 1, wherein said coupling agent has a thermal conductivity greater than 1 milliwatt/cm/°

C.

9. The method of claim 1, wherein said coupling agent has sufficient viscosity that it will not migrate from said optical measuring element.

10. The method of claim 9, wherein said coupling agent has a viscosity in the range of from about 10 centipoises to about 100,000 centipoises.

11. The method of claim 1, wherein said coupling agent does not diffuse into said biological sample.

12. A method for measuring the concentration of an analyte in a tissue of a body part comprising the steps of:

(1) providing an optical measuring instrument that comprises at least one thermally controllable optical measuring element that comes into contact with the surface of said tissue;

(2) applying an inert, thermally conductive, optically transparent coupling agent to said at least one optical measuring element or to the surface of said tissue or both so that said coupling agent will be disposed at the interface of said surface of said tissue and said at least one optical measuring element, said coupling agent having sufficiently high optical stability that the optical properties of said coupling agent do not change during optical measurements or during storage, said coupling agent having sufficiently high thermal conductivity to allow rapid, efficient heat transfer between said optical measuring element and said tissue, said coupling agent having sufficiently high viscosity to prevent it from migrating from said interface, said coupling agent having sufficiently low viscosity to allow sufficient contact between said optical measuring element and said tissue, said coupling agent having a refractive index higher than that of said tissue over the temperature range of a measurement;

(3) inducing a change in the concentration of said analyte in said tissue over a defined period of time;

(4) measuring the change in at least one optical property of said tissue by means of said at least one optical measuring element during said defined period of time;

(5) determining the change in the concentration of said analyte in said tissue by means of a reference method that involves taking a sample from said tissue for analysis during said defined period of time;

(6) correlating the change in said at least one optical property of said tissue with the change in the concentration of the analyte in said tissue to derive calibration data; and

(7) using said calibration data to determine the concentration of said analyte in said tissue.

13. The method of claim 12, further including the step of controlling the temperature of said tissue, whereby said at least one optical property of said biological sample is measured at a given depth from the surface of said biological sample.

14. The method of claim 13, wherein said depth from the surface of said tissue is less than 3 mm.

15. The method of claim 13, wherein said depth from the surface of said tissue is less than 2 mm.

16. The method of claim 12, wherein said measuring step is carried out at a plurality of wavelengths.

17. The method of claim 12, wherein said coupling agent is thermally stable at temperatures ranging from 10°

C. to 45°

C.

18. The method of claim 12, wherein said coupling agent is inert to oxygen at temperatures ranging from 10°

C. to 45°

C.

19. The method of claim 12, wherein said coupling agent has a thermal conductivity greater than 1 milliwatt/cm/°

C.

20. The method of claim 12, wherein said coupling agent has sufficient viscosity that it will not migrate from said optical measuring element.

21. The method of claim 20, wherein said coupling agent has a viscosity in the range of from about 10 centipoises to about 100,000 centipoises.

22. The method of claim 12, wherein said coupling agent does not diffuse into said biological sample.