Non-invasive sensor capable of determining optical parameters in a sample having multiple layers

• US 20020084417A1
• Filed: 12/21/2001
• Published: 07/04/2002
• Est. Priority Date: 11/23/1998
• Status: Active Grant

• Current Assignee: Charles F. Hanna, Frits Frans Maria De Mul, Johannes Sake Kanger, Omar S. Khalil, Rene Alexander Bolt, Shu-Jen Yeh, Xiaomao Wu
• Original Assignee: Charles F. Hanna, Frits Frans Maria De Mul, Johannes Sake Kanger, Omar S. Khalil, Rene Alexander Bolt, Shu-Jen Yeh, Xiaomao Wu
• Inventors: Maria de Mul, Frits Frans, Bolt, Rene Alexander, Khalil, Omar S., Hanna, Charles F., Wu, Xiaomao, Yeh, Shu-Jen, Kanger, Johannes Sake
• Granted Patent: US 6,630,673 B2
• Time in Patent Office: Days
• US Class Current: 250/341.8
• 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 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: G01N 21/49 within a body or fluid

Abstract

Apparatus and method for non-invasively measuring at least one optical parameter of a sample, particularly a sample of tissue that comprises a plurality of layers. The at least one parameter can be used to determine the presence or concentration of an analyte of interest in the sample of tissue. The apparatus and method of the present invention (1) measure light that is substantially reflected, scattered, absorbed, or emitted from a shallower layer of the sample of tissue, (2) measure light that is substantially reflected, scattered, absorbed, or emitted from a deeper layer of the sample of tissue, (3) determine at least one optical parameter for each of these layers, and (4) account for the effect of the shallower layer on the at least one optical parameter of the deeper layer. Specifying the sampling depth allows determinations of the optical properties of a specific layer of the sample of the tissue, e.g., dermis, and decreases interference from other layers, e.g., stratum corneum and epidermis, in these determinations.

Claims

1. A method for determining at least one optical parameter of a sample, said sample having a plurality of layers, each of said layers having different properties, said method comprising the steps of:

a) introducing a beam of light into said sample at a light introduction site on a surface of said sample;

b) determining the intensities of light re-emitted from said sample at a plurality of light collection sites on said surface of said sample, at least a first light collection site collecting light re-emitted mainly from a first layer of said sample, at least a second light collection site collecting light re-emitted mainly from a second layer of said sample, said first light collection site being at a first distance from said light introduction site, and said second light collection site being at a second distance from said light introduction site, said first distance being less than said second distance;

c) determining at least one optical parameter of said first layer of said sample; and

d) determining at least one optical parameter of said second layer of said sample, said first layer having an average depth, as measured from said surface of said sample, of smaller magnitude than the average depth of said second layer, as measured from said surface of said sample.

2. The method of claim 1, wherein light is delivered to said light introduction site by means of an optical fiber.

3. The method of claim 1, wherein the effect of interaction of said light with said first layer of said sample upon the measurement of said at least one optical parameter of said second layer of said sample is determined.

4. The method of claim 3, wherein concentration of an analyte in said sample is determined after said at least one optical parameter of said first layer of said sample and said at least one optical parameter of said second layer of said sample are determined.

5. The method of claim 1, wherein said light has at least two wavelengths.

6. The method of claim 1, wherein said light has a wavelength ranging from about 400 nm to about 2500 nm.

7. A method for measuring at least one optical parameter of a sample having a plurality of layers having differing properties, said method comprising the steps of:

a) introducing a beam of light into said sample at a light introduction site;

b) collecting light re-emitted from said sample at a plurality of light collection sites, each of said light collection sites comprising at least two light collecting elements, each of said light collection sites located at a different distance from said light introduction site;

c) determining the intensity of said light re-emitted at a first light collecting element of a light collection site located at a first distance from said light introduction site and the intensity of said light re-emitted at at least a second light collecting element of said light collection site located at said first distance from said light introduction site;

d) determining the absorption coefficient and the scattering coefficient of said sample at a given depth of said sample by means of a mathematical relationship between intensity of said light re-emitted at said first light collecting element of said light collection site located at said first distance from said light introduction site and intensity of said light re-emitted at at least a second light collecting element of said light collection site located at said first distance from said light introduction site;

e) determining the intensity of said light re-emitted at a first light collecting element of a light collection site located at a second distance from said light introduction site and the intensity of said light re-emitted at at least a second light collecting element of said light collection site located at said second distance from said light introduction site, wherein said second distance is greater than said first distance;

f) determining the absorption coefficient and the scattering coefficient of the sample at a greater depth of said sample than that of step d) by means of a mathematical relationship between intensity of said light re-emitted at said first light collecting element of said light collection site located at said second distance from said light introduction site and intensity of said light re-emitted at at least a second light collecting element of said light collection site located at said second distance from said light introduction site.

8. The method of claim 7, wherein said light collecting elements comprise optical fibers.

9. The method of claim 7, wherein said light collecting elements in any light collection site are separated by a distance equal to or less than the average transport mean free path of photons in the sample.

10. The method of claim 9, wherein said light collecting elements in any light collection site are separated by a distance of less than 1 mm.

11. The method of claim 7, wherein the distance between said defined area of said sample and any light collecting element is no more than 6 mm.

13. The apparatus of claim 12, wherein said source of light can be of at least two wavelengths.

14. The apparatus of claim 12, wherein said wavelength of said source of light can range from about 400 nm to about 2500 nm.

15. The apparatus of claim 14, wherein said wavelength of said source of light can range from about 500 nm to about 1500 nm.

16. The apparatus of claim 12, wherein light is directed to said light introduction site by an optical fiber.

18. The apparatus of claim 17, wherein said light collecting elements comprise optical fibers.

19. The apparatus of claim 17, wherein said light collecting elements are disposed in a non-reflecting housing.

20. The apparatus of claim 18, wherein said optical fibers are arranged in a hexagonal close-packed structure.

21. The apparatus of claim 20, wherein some of said close-packed fibers direct re-emitted light to said at least one detector and other of said close-packed fibers direct re-emitted light to a light trap.

22. The apparatus of claim 17, wherein the distance of said defined area of said sample to said groups of light collecting elements and the wavelengths of said source of light are selected to limit the depth of penetration of light in said sample to a depth wherein the temperature is being controlled.

23. The apparatus of claim 17, wherein the distance between said defined area of said sample and any light collecting element is no more than 6 mm.

25. The method of claim 24, wherein light is delivered to said light introduction sites of said sample by means of optical fibers.

26. The method of claim 24, wherein the effect of interaction of said light with said first layer of said sample upon the measurement of said at least one optical parameter of said second layer of said sample is determined.

27. The method of claim 26, wherein concentration of an analyte in said sample is determined after said at least one optical parameter of said first layer of said sample and said at least one optical parameter of said second layer of said sample is determined.

28. The method of claim 24, wherein said light has at least two wavelengths.

29. The method of claim 24, wherein said light has a wavelength ranging from about 400 nm to about 2500 nm.

12. An apparatus for measuring at least one optical parameter of a sample having a plurality of layers having different properties, said apparatus comprising:

a) a source of light;

b) means for introducing light from said source of light into said sample at a light introduction site on a surface of said sample;

c) a plurality of light collecting elements for collecting light re-emitted from said sample at a plurality of light collection sites on said surface of said sample;

d) at least one detector for determining the intensity of light collected at said light collection sites;

e) a means for computing said at least one optical parameter of said sample.

17. An apparatus for measuring at least one optical parameter of a sample having layers having different properties comprising:

a) at least one source of light for introducing light to a defined area on a surface of said sample;

b) at least two groups of light collecting elements, each of said groups of light collecting elements comprising at least two light collecting elements, each of said groups of light collecting elements located at a different distance from said defined area on said surface of said sample;

c) at least one detector for measuring light collected by said light collecting elements; and

d) a signal processor to determine said at least one optical parameter of said sample.

24. A method for determining at least one optical parameter of a sample, said sample having a plurality of layers, each of said layers having different properties, said method comprising the steps of:

a) introducing a plurality of beams of light into said sample at a plurality of light introduction sites on a surface of said sample, a first light introduction site being at a first distance from a light collection site on said surface of said sample, a second light introduction site being at a second distance from said light collection site on said surface of said sample, said first distance being less than said second distance;

b) determining the intensities of light re-emitted from said sample at said light collection site, said light collection site collecting light re-emitted mainly from a first layer of said sample and collecting light re-emitted mainly from a second layer in said sample, said light re-emitted from said first layer being introduced at said first light introduction site, said light re-emitted from said second layer being introduced at said second light introduction site;

c) determining at least one optical parameter of a said first layer of said sample; and

d) determining at least one optical parameter of said second layer of said sample, said first layer having an average depth, as measured from said surface of said sample, of smaller magnitude than the average depth of said second layer, as measured from said surface of said sample.

30. A method for measuring at least one optical parameter of a sample having layers having differing properties, said method comprising the steps of:

a) introducing beams of light into said sample at a plurality of light introduction sites by a plurality of groups of illuminating elements, at least two illuminating elements being at each of said light introduction sites, each of said light introduction sites located at a different distance from a light collection site;

b) collecting light re-emitted from said sample at said light collection site;

c) determining the intensity of said re-emitted light resulting from illumination by a first illuminating element of a light introduction site located at a first distance from said light collection site and the intensity of said re-emitted light resulting from illumination by at least a second illuminating element of said light introduction site located at said first distance from said light collection site;

d) determining the absorption coefficient and the scattering coefficient of said sample at a given depth in said sample by means of a mathematical relationship between intensity of said re-emitted light resulting from illumination by said first illuminating element of said light introduction site located at said first distance from said light collection site and intensity of said re-emitted light resulting from illumination by at least a second illuminating element of said light introduction site located at said first distance from said light collection site;

e) determining the intensity of said re-emitted light resulting from illumination by a first illuminating element of a light introduction site located at a second distance from said light collection site and the intensity of said re-emitted light resulting from illumination by at least a second illuminating element of said light introduction site located at said second distance from said light collection site, wherein said second distance is greater than said first distance;

f) determining the absorption coefficient and the scattering coefficient of said sample at a greater depth of said tissue than that of step d) by means of a mathematical relationship between intensity of said re-emitted light resulting from illumination by said first illuminating element of said light introduction site located at said second distance from said light collection site and intensity of said re-emitted light resulting from illumination by at least a second illuminating element of said light introduction site located at said second distance from said light collection site.

31. The method of claim 30, wherein said illuminating elements comprise optical fibers.

32. The method of claim 30, wherein said illuminating elements in any light introduction site are separated by a distance equal to or less than the mean free path of photons in said sample.

33. The method of claim 32, wherein said illuminating elements in any light introduction site are separated by a distance of less than 1 mm.

34. The method of claim 30, wherein the distance between said defined area of said sample and any light collecting element is no more than 6 mm.

36. The apparatus of claim 35, wherein said at least one source of light can be of at least two wavelengths.

37. The apparatus of claim 35, wherein said wavelength of said at least one source of light can range from about 400 nm to about 2500 nm.

38. The apparatus of claim 37, wherein said wavelength of said at least one source of light can range from about 500 nm to about 1500 nm.

39. The apparatus of claim 35, wherein said plurality of means for introducing light from said at least one source of light into said sample comprises a plurality of optical fibers.

35. An apparatus for measuring at least one optical parameter of a sample, said sample having a plurality of layers having different properties, said apparatus comprising:

a) at least one source of light;

b) a plurality of means for introducing light from said at least one source of light into said sample at a plurality of light introduction sites on a surface of said sample;

c) a light collection site for collecting light re-emitted from said sample;

d) at least one detector for determining the intensity of light collected at said light collection site; and

e) a means for computing said at least one optical parameter of said sample.

40. An apparatus for measuring at least one optical parameter of a sample, said sample having layers having different properties, said apparatus comprising:

a) at least one source of light for introducing light to defined areas on a surface of said sample;

b) at least two groups of illuminating elements, each of said groups of light illuminating elements comprising at least two illuminating elements, each of said groups of illuminating elements located at a different distance from a light collection site on said surface of said sample;

c) at least one detector for determining the intensity of light collected at said light collection site; and

c) a signal processor to determine said at least one optical parameter of said sample.

41. The apparatus of claim 40, wherein said illuminating elements comprise optical fibers.

42. The apparatus of claim 40, wherein said illuminating elements are disposed in a non-reflecting housing.

43. The apparatus of claim 41, wherein said optical fibers are arranged in a hexagonal close-packed structure.

44. The apparatus of claim 43, wherein some of said close-packed fibers direct said light to said at least one illuminating element and other of said close-packed fibers direct said light to a light trap.

45. The apparatus of claim 40, wherein the distance of the illuminating elements to said light collection site and the wavelengths of said at least one source of light are selected to limit the depth of penetration of light in the sample to a depth wherein the temperature is being controlled.

46. The apparatus of claim 40, wherein the distance between said light collection site and any illuminating element is no more than 6 mm.