Optically similar reference samples and related methods for multivariate calibration models used in optical spectroscopy

• US 6,983,176 B2
• Filed: 04/11/2001
• Issued: 01/03/2006
• Est. Priority Date: 04/11/2001
• Status: Expired due to Fees

• Current Assignee: Rio Grande Medical Technologies Incorporated
• Original Assignee: Rio Grande Medical Technologies Incorporated
• Inventors: Rowe, Robert K., Johnson, Robert D., Abbink, Russell E., Haass, Michael J., Strohl, Steven T., Gardner, Craig, Gruner, William, Novak, Matthew J., Nuñez, David, Jones, Howland
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US09/832,608
• Publication Number:
  US 20030023170A1
• Time in Patent Office: 1,728 Days
• Field of Search: 600/310, 600/322, 600/323, 600/331, 600/473, 600/475, 600/476, 600/477, 356/39, 356/42, 356/432, 250/252.1, 250/339.09, 422/82.05, 422/82.09, 436/164, 436/171
• US Class Current: 600/310
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: G01N 21/278 Constitution of standards

Abstract

Systems and methods for establishing and/or maintaining the prediction capability over time of a multivariate calibration model designed for quantitative optical spectroscopic measurement of attributes or analytes in bodily tissues, bodily fluids or other biological samples, which are particularly useful when the spectral absorbance of the attribute or analyte is small relative to the background. The present invention provides an optically similar reference sample to capture the characteristics of instrument and environmental variation and to reduce the effect of such variation on the measurement capability of the model. The optically similar reference is preferably stable over time and is designed such that its optical properties are sufficiently matched to the sample of interest that instrument and environmental variations are captured in the same manner in both the test sample of interest and the optically similar reference sample. The optically similar reference sample may include one or more physical components which are spectroscopically measured in a manner which closely mimics the spectroscopic measurement of the test sample of interest. Spectral similarity may also be achieved by using alternative components with spectral characteristics similar to the components contained in the test sample of interest.

Claims

1. A reference sample for maintaining prediction performance of an optical system used to measure an analyte or attribute in a representative measurement sample, wherein the representative measurement sample comprises a bodily tissue, bodily fluid or other biological sample containing the analyte or attribute and having a dominant absorbing species therein when in vivo, the reference sample comprising the dominant absorbing species contained and disposed such that an optical signal interrogating the reference sample is subjected to diffuse reflection, where the reference sample and the measurement sample absorb light at each of selected wavelengths in a manner to produce similarly shaped spectra over the wavelengths measured, wherein the reference sample has the spectral characteristics of an in vivo sample.

2. A reference sample as in claim 1, wherein the representative measurement sample includes multiple samples from multiple subjects.

3. A reference sample as in claim 2, wherein the reference sample has a spectral similarity ratio, when compared with the representative measurement sample spectra, of 30 or less when evaluated over the selected wavelengths measured.

4. The reference sample of claim 3, wherein the measurement sample is tissue and the selected wavelengths measured is a spectral range of 4,200 cm⁻

1 to 7,200 cm<sup>−

1</sup>.

5. The reference sample of claim 3, wherein the measurement sample is tissue and the selected wavelengths measured is a spectral range of 4,440 cm⁻

1 to 4,800 cm<sup>−

1</sup> and 5,440 cm<sup>−

1</sup> to 6,400 cm<sup>−

1</sup>.

6. The reference sample of claim 3, wherein the measurement sample is tissue, the analyte being measured is glucose and the selected wavelengths measured, in wavenumbers (cm⁻

1), are selected from the group consisting of;

4196, 4227, 4273, 4281, 4304, 4320, 4335, 4366, 4389, 4436, 4451, 4459, 4497, 4528, 4559, 4613, 4690, 4775, 4829, 4860, 4883, 4922, 5014, 5091, 5176, 5230, 5269, 5299, 5315, 5338, 5369, 5392, 5454, 5469, 5477, 5515, 5585, 5623, 5662, 5701, 5731, 5755, 5785, 5809, 5839, 5893, 5924, 5947, 6001, 6094, 6163, 6187, 6287, 6318, 6349, 6449, 6472, 6557, 6595, 6673, 6696, 6935, 6973, 7004, 7043, 7066, 7205, and combinations thereof.

7. A reference sample as in claim 2, wherein the reference sample has a spectral similarity ratio, when compared with the representative measurement sample spectra, of 10 or less when evaluated over the selected wavelengths measured.

8. A reference sample as in claim 2, wherein the reference sample has a spectral similarity ratio, when compared with the representative measurement sample spectra, of 1 or less when evaluated over the selected wavelengths measured.

9. The reference sample of claim 8, wherein the measurement sample is tissue and the selected wavelengths measured is a spectral range of 4,200 cm⁻

1 to 7,200 cm<sup>−

1</sup>.

10. The reference sample of claim 8, wherein the measurement sample is tissue and the selected wavelengths measured is a spectral range of 4,440 cm⁻

1to 4,800 cm<sup>−

1</sup> and 5,440 cm<sup>−

1</sup> to 6,400 cm<sup>−

1</sup>.

11. The reference sample of claim 8, wherein die measurement sample is tissue, the analyte being measured is glucose and the selected wavelengths measured, in wavenumbers (cm⁻

1), are selected from the group consisting of;

4196, 4227, 4273, 4281, 4304, 4320, 4335, 4366, 4389, 4436, 4451, 4459, 4497, 4528, 4559, 4613, 4690, 4775, 4829, 4860, 4383, 4922, 5014, 5091, 5176, 5230, 5269, 5299, 5315, 5338, 5369, 5392, 5454, 5469, 5477, 5515, 5585, 5623, 5662, 5701, 5731, 5755, 5785, 5809, 5839, 5893, 5924, 5947, 6001, 6094, 6163, 6187, 6287, 6318, 6349, 6449, 6472, 6557, 6595, 6673, 6696, 6935, 6973, 7004, 7043, 7066, 7205, and combinations thereof.

12. A reference sample as in claim 2, wherein the reference sample has a regression weighted spectral similarity ratio, when compared to the representative measurement sample spectra, of 30 or less.

13. A reference sample as in claim 2, wherein the reference sample has a regression weighted spectral similarity ratio, when compared to the representative measurement sample spectra, of 10 or less.

14. A reference sample as in claim 2, wherein the reference sample has a regression weighted spectral similarity ratio, when compared to the representative measurement sample spectra, of 1 or less.

15. The reference sample of claim 1, wherein the measurement sample is tissue and the selected wavelengths measured is a spectral range of 4,200 cm⁻

1 to 7,200 cm<sup>−

1</sup>.

16. The reference sample of claim 1, wherein the measurement sample is tissue and the selected wavelengths measured is a spectral range of 4,440 cm⁻

1 to 4,800 cm<sup>−

1</sup> and 5,440 cm<sup>−

1</sup> to 6,400 cm<sup>−

1</sup>.

17. The reference sample of claim 1, wherein the measurement sample is tissue, the analyte being measured is glucose and the selected wavelengths measured, in wavenumbers (cm⁻

1), are selected from the group consisting of;

4196, 4227, 4273, 4281, 4304, 4320, 4335, 4366, 4389, 4436, 4451, 4459, 4497, 4528, 4559, 4613, 4690, 4775, 4829, 4860, 4883, 4922, 5014, 5091, 5176, 5230, 5269, 5299, 5315, 5338, 5369, 5392, 5454, 5469, 5477, 5515, 5585, 5623, 5662, 5701, 5731, 5755, 5785, 5809, 5839, 5893, 5924, 5947, 6001, 6094, 6163, 6187, 6287, 6318, 6349, 6449, 6472, 6557, 6595, 6673, 6696, 6935, 6973, 7004, 7043,7066, 7205, and combinations thereof.

18. A reference sample as in claim 1, wherein the representative measurement sample is from a single subject.

19. A reference sample as in claim 18, wherein the reference sample has a spectral similarity ratio, when compared with the representative measurement sample spectra, of 1500 or less when evaluated over the selected wavelengths measured.

20. The reference sample of claim 19, wherein the measurement sample is tissue and the selected wavelengths measured is a spectral range of 4,200 cm⁻

1 to 7,200 cm<sup>−

1</sup>.

21. The reference sample of claim 19, wherein the measurement sample is tissue and the selected wavelengths measured is a spectral range of 4,440 cm_{31 1} to 4,800 cm⁻

1 and 5,440 cm<sup>−

1</sup> to 6,400 cm<sup>−

1</sup>.

22. The reference sample of claim 19, wherein the measurement sample is tissue, the analyte being measured is glucose and the selected wavelengths measured, in wavenumbers (cm⁻

1), are selected from the group consisting of;

4196, 4227, 4273, 4281, 4304, 4320, 4335, 4366, 4389, 4436, 4451, 4459, 4497, 4528, 4559, 4613, 4690, 4775, 4829, 4860, 4883, 4922, 5014, 5091, 5176, 5230, 5269, 5299, 5315, 5338, 5369, 5392, 5454, 5469, 5477, 5515, 5585, 5623, 5662, 5701, 5731, 5755, 5785, 5809, 5839, 5893, 5924, 5947, 6001, 6094, 6163, 6187, 6287, 6318, 6349, 6449, 6472, 6557, 6595, 6673, 6696, 6935, 6973, 7004, 7043, 7066, 7205, and combinations thereof.

23. A reference sample as in claim 18, wherein the reference sample has a spectral similarity ratio, when compared with the representative measurement sample spectra, of 1000 or less when evaluated over the selected wavelengths measured.

24. The reference sample of claim 23, wherein the measurement sample is tissue and the selected wavelengths measured is a spectral range of 4,200 cm⁻

1 to 7,200 cm<sup>−

1</sup>.

25. The reference sample of claim 23, wherein the measurement sample is tissue and the selected wavelengths measured is a spectral range of 4,440 cm⁻

1 to 4,800 cm<sup>−

1</sup> and 5,440 cm<sup>−

1</sup> to 6,400 cm<sup>−

1</sup>.

26. The reference sample of claim 23, wherein the measurement sample is tissue, the analye being measured is glucose and the selected wavelengths measured, in wavenumbers (cm⁻

1), are selected from the group consisting of;

4196, 4227, 4273, 4281, 4304, 4320, 4335, 4366, 4389, 4436, 4451, 4459, 4497, 4528, 4559, 4613, 4690, 4775, 4829, 4860, 4883, 4922, 5014, 5091, 5176, 5230, 5269, 5299, 5315, 5338, 5369, 5392, 5454, 5469, 5477, 5515, 5585, 5623, 5662, 5701, 5731, 5755, 5785, 5809, 5839, 5893, 5924, 5947, 6001, 6094, 6163, 6187, 6287, 6318, 6349, 6449, 6472, 6557, 6595, 6673, 6696, 6935, 6973, 7004, 7043, 7066, 7205, and combinations thereof.

27. A reference sample as in claim 18, wherein the reference sample has a spectral similarity ratio, when compared with the representative measurement sample spectra, of 1 or less when evaluated over the selected wavelengths measured.

28. The reference sample of claim 27, wherein the measurement sample is tissue and the selected wavelengths measured is a spectral range of 4,200 cm⁻

1 to 7,200 cm<sup>−

1</sup>.

29. The reference sample of claim 27, wherein the measurement sample is tissue and the selected wavelengths measured is a spectral range of 4,440 cm⁻

1 to 4,800 cm<sup>−

1</sup> and 5,440 cm<sup>−

1</sup> to 6,400 cm<sup>−

1</sup>.

30. The reference sample of claim 27 wherein the measurement sample is tissue, the analyte being measured is glucose and the selected wavelengths measured, in wavenumbers (cm⁻

1), are selected from the group consisting of;

4196, 4227, 4273, 4281, 4304, 4320, 4335, 4366, 4389, 4436, 4451, 4459, 4497, 4528, 4559, 4613, 4690, 4775, 4829, 4860, 4883, 4922, 5014, 5091, 5176, 5230, 5269, 5299, 5315, 5338, 5369, 5392, 5454, 5469, 5477, 5515, 5585, 5623, 5662, 5701, 5731, 5755, 5785, 5809, 5839, 5893, 5924, 5947, 6001, 6094, 6163, 6187, 6287, 6318, 6349, 6449, 6472, 6557, 6595, 6673, 6696, 6935, 6973, 7004, 7043, 7066, 7205, and combinations thereof.

31. A reference sample as in claim 18, wherein the reference sample has a regression weighted spectral similarity ratio, when compared to the representative measurement sample spectra, of 4500 or less.

32. A reference sample as in claim 18, wherein the reference sample has a regression weighted spectral similarity ratio, when compared to the representative measurement sample spectra, of 1500 or less.

33. A reference sample as in claim 18, wherein the reference sample has a regression weighted spectral similarity ratio, when compared to the representative measurement sample spectra, of 1 or less.

34. A reference sample for maintaining prediction performance of an optical system used to measure an analyte or attribute in a representative measurement sample, the reference sample including a dominant absorbing species housed in a structure defining a plurality of dispersive optical interfaces, the dominant absorbing species corresponding to a dominant absorbing material present in the representative measurement sample when in vivo, wherein the representative measurement sample comprise a bodily tissue, bodily fluid or other biological sample containing the analyte or attribute, where the reference sample simulates the optical interaction between the measurement sample and the optical system.

35. A reference sample as in claim 34, wherein the reference sample has a spatial similarity, expressed in terms of standard deviation, of 0.079 or less.

36. A reference sample as in claim 34, wherein the reference sample has a spatial similarity, expressed in terms of standard deviation, of 0.052 or less.

37. A reference sample as in claim 34, wherein the reference sample has a spatial similarity, expressed in terms of standard deviation, of approximately 0.0.

38. A reference sample as in claim 34, wherein the reference sample has an angular similarity, expressed in terms of standard deviation, of 0.051 or less.

39. A reference sample as in claim 34, wherein the reference sample has an angular similarity, expressed in terms of standard deviation, of 0.036 or less.

40. A reference sample as in claim 34, wherein the reference sample has an angular similarity, expressed in terms of standard deviation, of approximately 0.0.

41. A reference sample for maintaining prediction performance of an optical system to measure an analyte or attribute in a representative measurement sample, wherein the representative measurement sample comprises a bodily tissue, bodily fluid or other biological sample containing the analyte or attribute as well as a dominant absorbing species present when the representative measurement sample is in vivo, where the reference sample has the same primary optical absorber as the measurement sample, wherein the reference sample has the spectral characteristics of an in vivo sample, the dominant absorbing species being the primary optical absorber, the dominant absorbing species being contained in a housing allowing optical interrogation thereof.

42. A reference sample as in claim 41, wherein the representative measurement sample contains first and second primary constituents, and wherein the reference sample contains the same first and second primary constituents.

43. A reference sample as in claim 42, wherein the second primary constituent comprises protein.

44. A reference sample as in claim 42, wherein the second primary constituent comprises lipid.

45. A reference sample as in claim 42, wherein the second primary constituent comprises a organic polymer.

46. A reference sample as in claim 41, wherein the measurement sample is tissue and the portion of the reference sample that is optically sampled contains less than 80% water by volume.

47. A reference sample for maintaining prediction performance of an optical system used to measure an analyte or attribute in a representative measurement sample, wherein the representative measurement sample comprises a bodily tissue, bodily fluid or other biological sample containing the analyte or attribute, with the reference sample including a structure having one or more optically interactive surfaces and producing a non-stepwise reference spectrum that is optically similar to the representative measurement sample, both the reference sample and the representative measurement sample having a primary optical absorber corresponding to a dominant in vivo optical absorber for the representative measurement sample.

48. A reference sample as in claim 47, wherein the reference sample includes:

an optically transparent layer;

a diffusing layer; and

a constituent layer disposed between the optically transparent layer and the diffusing layer.

49. A reference sample as in claim 48, wherein the representative measurement sample contains a primary constituent, and wherein the constituent layer contains the same primary constituent.

50. A reference sample as in claim 49, wherein the constituent layer contains water.

51. A reference sample as in claim 49, wherein the constituent layer contains protein.

52. A reference sample as in claim 49, wherein the constituent layer contains lipid.

53. A reference sample as in claim 48, wherein the diffusing layer is cone shaped.

54. A reference sample as in claim 48, wherein the optically transparent layer, the constituent layer, and the diffusing layer are cone shaped.

55. A reference sample as in claim 48, wherein the diffusing layer is non-planar.

56. A reference sample as in claim 48, wherein the optically transparent layer is flat.

57. A reference sample as in claim 47, wherein the reference sample includes:

a container that is at least partially optically transparent; and

a scattering solution in the container.

58. A reference sample as in claim 57, wherein the reference sample further includes a stirring mechanism for stirring the scattering solution.

59. A reference sample as in claim 57, wherein the scattering solution comprises reflective beads disposed in a constituent.

60. A reference sample as in claim 47, wherein the reference sample includes:

a first optical splitting layer;

a reflective layer; and

a first constituent layer disposed between the first optical splitting layer and the reflective layer.

61. A reference sample as in claim 60, wherein the representative measurement sample contains a primary constituent, and wherein the first constituent layer contains the same primary constituent.

62. A reference sample as in claim 61, wherein the constituent layer contains water.

63. A reference sample as in claim 60, wherein the reference sample further includes:

a second optical splitting layer; and

a second constituent layer disposed between the first optical splitting layer and the second optical splitting layer.

64. A reference sample as in claim 47, wherein the reference sample includes:

a container that is at least partially optically transparent;

a constituent disposed in the container; and

a spacer disposed in the container.

65. A reference sample as in claim 64, wherein the representative measurement sample contains a primary constituent, and wherein the constituent disposed in the container comprises the same primary constituent.

66. A reference sample as in claim 65, wherein the constituent disposed in the container comprises water.

67. A reference sample as in claim 64, wherein multiple spacers are disposed in the container.

68. A reference sample as in claim 47, wherein the reference sample includes:

an optically transparent layer;

a diffuse reflective layer disposed a distance from the optically transparent layer; and

a constituent layer disposed between the optically transparent layer and the diffuse reflective layer.

69. A reference sample as in claim 68, wherein the representative measurement sample contains a primary constituent, and wherein the constituent layer comprises the same primary constituent.

70. A reference sample as in claim 68, wherein the constituent layer comprises water.

71. A reference layer as in claim 68, wherein the diffuse reflective layer is movable relative to the optically transparent layer to change the distance therebetween.

72. A reference sample as in claim 47, wherein the reference sample includes:

a animal based bodily constituent.

73. A reference sample as in claim 72, wherein the animal based bodily constituent comprises animal bodily tissue.

74. A reference sample as in claim 72, wherein the animal based bodily constituent comprises animal bodily fluid.

75. A reference sample as in claim 47, wherein the reference sample includes:

a gel matrix;

scattering media; and

water.

76. A reference sample as in claim 75, wherein the gel matrix is placed in direct contact with the optical sampling device.

77. A reference sample as in claim 75, wherein the gel matrix is contained in a container that enables optical sampling.

78. A reference sample for maintaining prediction performance or an optical system used to measure an analyte or attribute in a test sample of interest, wherein the test sample comprises a bodily tissue, bodily fluid or other biological sample containing the analyte or attribute, with the reference sample producing a reference sample spectrum that is similar to the test sample spectrum, the reference sample including a transmissive optical interface and an optical sampling compartment, the optical sampling compartment containing water and a diffusely reflective or scattering media and including structure such that an optical signal passing through the transmissive optical interface encounters reflective surfaces at various path lengths from the optical interface.

79. A reference sample as in claim 78, wherein the reference sample spectrum has a spectral similarity ratio, when compared to a representative measurement sample spectra, of 30 or less.

80. A reference sample as in claim 78, wherein the reference sample spectrum has a regression weighted spectral similarity ratio, when compared to a representative measurement sample spectra, of 30 or less.

81. A reference sample as in claim 78, wherein the reference sample has a spatial similarity, expressed in terms of standard deviation, of 0.079 or less.

82. A reference sample as in claim 78, wherein the reference sample has an angular similarity, expressed in terms of standard deviation, of 0.051 or less.

83. A reference device for use with an optical system to maintain prediction performance of the optical system for a constituent of a representative measurement sample, the reference device comprising:

a reference material having a first optical similarity to the representative measurement sample; and

a structure for containing the reference material in a geometric configuration adapted to give the reference device a second optical similarity to the representative measurement sample;

wherein the second optical similarity is greater than the first optical similarity.

84. The reference device of claim 83, wherein the structure includes an optical interface allowing light to enter the reference device and interact with the reference material.

85. The reference device of claim 84, wherein the structure includes a diffusing cone.

86. The reference device of claim 83, wherein the structure provides a geometric configuration such that light entering the reference device may interact with the reference material through several different pathlengths.