Optically similar reference samples

• US 20040082070A1
• Filed: 10/28/2002
• Published: 04/29/2004
• Est. Priority Date: 04/11/2001
• Status: Active Grant

• Current Assignee: Inlight Solutions, Inc.
• Original Assignee: Inlight Solutions, Inc.
• Inventors: Johnson, Robert D., Hull, Edward L., Jones, Howland D. T., Vanslyke, Stephen J., Nunez, David J.
• Granted Patent: US 7,202,091 B2
• Time in Patent Office: Days
• US Class Current: 436/8
• 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: G01J 3/02 Details
• CPC Class Codes: G01J 3/0216 using light concentrators or collectors or condensers
• CPC Class Codes: G01J 3/0218 using optical fibers
• CPC Class Codes: G01J 3/10 Arrangements of light sources specially adapted for spectrometry or colorimetry
• CPC Class Codes: G01N 21/278 Constitution of standards
• CPC Class Codes: G01N 21/4785 Standardising light scatter apparatus; Standards therefor
• CPC Class Codes: G01N 21/49 within a body or fluid
• CPC Class Codes: G01N 2201/1293 resolving multicomponent spectra
• CPC Class Codes: Y10T 436/10 Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing

Abstract

Systems and methods for establishing and/or maintaining the accuracy 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 reduce the effect of instrument or environment variation on the measurement capability of the model. The optically similar reference can be a gel composition having scattering particles suspended therein. The reference gel can be directly applied to a spectroscopic instrument sampler, or can be in a container specifically designed for optimal coupling to a spectroscopic instrument.

Claims

1. A composition comprising:

a. a gelling agent;

b. a scattering agent; and

c. water.

2. A composition as in claim 1, wherein the gelling agent comprises HEC.

3. A composition as in claim 1, wherein the gelling agent comprises PVA.

4. A composition as in claim 1, wherein the gelling agent comprises an initiator and a crosslinking agent that contains a plurality of vinyl groups.

5. A composition as in claim 4, wherein the crosslinking agent comprises N,N′

-methylenebisacrylamide, ethylene glycol dimethacrylate, bisacrylamide, or a combination thereof.

6. A composition as in claim 4, wherein the initiator comprises a peroxide, benzoyl peroxide, a persulfate, ammonium persulfate, azobisisobutyronitrile, a photochemically activated initiator, methylene blue, riboflavin, ammonium persulfate in the presence of TEMED, or a combination thereof.

7. A composition as in claim 4, wherein the gelling agent further comprises a monomer that contains a vinyl group.

8. A composition as in claim 7, wherein the monomer comprises acrylamide, 2-hydroxyethyl methacrylate, poly(ethylene glycol) methacrylate, 1-vinyl-2-pyrrolidinone, or a combination thereof.

9. A composition as in claim 1, further comprising an analyte.

10. A composition as in claim 1, wherein the scattering agent comprises a mesh, a three-dimensional structure, a filaments, a particle, or combinations thereof.

11. A composition as in claim 1, further comprising a protein, a lipid, or a combination thereof.

12. A composition as in claim 1, further comprising a temperature control agent, a pH control agent, an ionic control agent, or a combination thereof.

13. A composition as in claim 1, wherein the scattering agent comprises a first plurality of scattering particles having a first scattering characteristic and a second plurality of scattering particles having a second scattering characteristic, wherein the first scattering characteristic is different than the second scattering characteristic.

14. A composition as in claim 1, wherein the scattering agent comprises particles of at least two different sizes.

15. A composition as in claim 1, wherein the scattering agent comprises particles of at least two different shapes.

16. A composition as in claim 1, wherein the scattering agent comprises particles of at least two different refractive indices.

17. A composition as in claim 1, wherein the scattering agent comprises polystyrene particles.

18. A composition as in claim 1, further comprising a viscosity control agent.

19. A composition as in claim 18, wherein the viscosity control agent comprises sodium lauryl sulfate, ammonium lauryl sulfate, or combinations thereof.

20. A composition as in claim 18, wherein the viscosity control agent comprises sodium lauryl sulfate, ammonium lauryl sulfate, a latex emulsion, a cellulosic water-soluble polymer, a water-soluble resin, a natural gum, a preservative, a surfactant, a defoamer, a plasticizer, an organic solvent, or combinations thereof.

21. A composition as in claim 2 wherein the HEC and the water are present at a ratio of 30 weight % HEC to 70 weight % water.

22. A composition as in claim 3 wherein the PVA and the water are present at a ratio of 30 weight % HEC to 70 weight % water.

23. A composition as in claim 18 wherein the composition comprises:

a. 30,000-40,000 mg/dL gelling agent;

b. 1,000-2,500 mg/dL polystyrene particles;

c. 100-5,000 mg/dL viscosity control agent; and

d. 60,000-85,000 mg/dL water.

24. A composition as in claim 17, wherein the polystyrene particles have a diameter chosen from the group consisting of:

0.2 to 4 μ

m;

0.14 to 0.35 μ

m;

0.3 μ

m;

0.8 to 1 μ

m;

0.9 to 0.95 μ

m;

0.93 μ

m;

5 to 6 μ

m;

4 to 5 μ

m;

5.3 to 5.7 μ

m;

5.5 μ

m;

6 to 7 μ

m;

6.2 to 6.5 μ

m; and

6.3 μ

m.

25. A composition as in claim 17, where the polystyrene particles have a diameter of 0.8 to 1.0 μ

m, and wherein the polystyrene particles are present at a concentration chosen from the group consisting of;

1400 to 1800 mg/dL; and

1600 mg/dL.

26. A composition as in claim 17, wherein the polystyrene particles comprise a first group of polystyrene particles having a first diameter and a second group of polystyrene particles having a second diameter wherein the first diameter is different than the second diameter.

27. A composition as in claim 26, further comprising a third group of polystyrene particles having a third diameter wherein the third diameter is different than the first and the second diameter.

28. A composition as in claim 27, further comprising a fourth group of polystyrene particles having a fourth diameter wherein the fourth diameter is different from the first, second and third diameter.

29. A composition as in claim 28, wherein the first diameter is 0.25 to 0.35 μ

m, the second diameter is 0.9 to 0.95 μ

m, the third diameter is 5.3 to 5.7 μ

m, and the fourth diameter is 6.2 to 6.5 μ

m.

30. A composition as in claim 29, wherein the first diameter is 0.3 μ

m, the second diameter is 0.93 μ

m, the third diameter is 5.5 μ

m and the fourth diameter is 6.3μ

m.

31. A composition as in claim 29, wherein the composition comprises:

a. 150 to 250 mg/dL of the first group of polystyrene beads;

b. 900 to 950 mg/dL of the second group of polystyrene beads;

c. 50 to 350 mg/dL of the third group of polystyrene beads; and

d. 250 to 700 mg/dL of the fourth group of polystyrene beads.

32. A composition as in claim 29, wherein the composition comprises:

a. 170 mg/dL of the first group of polystyrene beads;

b. 940 mg/dL of the second group of polystyrene beads;

c. 310 mg/dL of the third group of polystyrene beads; and

d. 300 mg/dL of the fourth group of polystyrene beads.

33. A composition as in claim 29, wherein the composition comprises:

a. 200 mg/dL of the first group of polystyrene beads;

b. 920 mg/dL of the second group of polystyrene beads;

c. 90 mg/dL of the third group of polystyrene beads; and

d. 640 mg/dL of the fourth group of polystyrene beads.

34. A composition as in claim 31, wherein the composition comprises:

a. 1,300 to 2,300 mg/dL polystyrene beads;

b. 1,000 to 4,000 mg/dL viscosity control agent; and

c. 70,000 to 80,000 mg/dL water.

35. A composition as in claim 32, wherein the composition comprises:

a. 1,700 mg/dL polystyrene beads;

b. 1,000 mg/dL viscosity control agent; and

c. 75,000 mg/dL water.

36. A composition as in claim 32, wherein the composition comprises:

a. 1,850 mg/dL polystyrene beads;

b. 4,000 mg/dL viscosity control agent; and

c. 70,000 mg/dL water.

37. A composition as in claim 25, wherein the composition comprises:

a. 1,400 to 1,800 mg/dL polystyrene beads;

b. 500 to 1,500 mg/dL viscosity control agent; and

c. 75,000 to 80,000 mg/dL water.

38. A composition as in claim 25, wherein the composition comprises:

a. 1,600 mg/dL polystyrene beads;

b. 1000 mg/dL viscosity control agent; and

c. 77,000 mg/dL water.

39. A composition as in claim 1, wherein the composition has spectral absorbance peaks at wavelengths of about 5,200 cm⁻

1 and about 6,900 cm<sup>−

1</sup>.

40. A composition as in claim 34, wherein the composition has a spectral absorbance peak at a wavelength of 5,200 cm⁻

1 and 6,900 cm<sup>−

1</sup>.

41. A composition as in claim 37, wherein the composition has a spectral absorbance peak at a wavelength of 5,200 cm⁻

1 and 6,900 cm<sup>−

1</sup>.

42. A reference gel container comprising:

a. A reference gel container having an outer surface and an inner reference gel surface defining a reference gel cavity;

b. a light guide disposed within the gel reference container extending from the outer surface to the inner reference gel cavity surface; and

c. a reference gel sample disposed within the gel reference cavity;

wherein the reference gel sample possesses bulk light scattering and light absorption properties similar to those of a sample material.

43. The reference gel container of claim 42, wherein the light guide comprises a MgF₂ material.

44. The reference gel container at claim 42, wherein the reference gel container comprises a main body portion defining the reference gel cavity and a light guide holder coupled to main body portion wherein the light guide extends through the light guide holder.

45. The reference gel container of claim 44, further comprising a top plate coupled to the main body potion wherein the reference gel sample is disposed between the top plate and light guide holder.

46. The reference gel container of claim 42, wherein the light guide comprises a low OH-quartz coated with Teflon AF.

47. The reference gel container of claim 42, wherein the reference gel sample comprises:

a. a gelling agent;

b. a plurality of scattering particles; and

c. water.

48. A composition comprising a carrier substance and particles disposed therein such that the composition'"'"'s scattering characteristics at a plurality of wavelengths are substantially similar to those of human tissue.

49. A composition as in claim 48, wherein the scattering characteristics comprise scattering coefficients.

50. A composition as in claim 48, wherein the scattering characteristics comprise scattering phase function.

51. A composition as in claim 48, wherein the scattering characteristics comprise scattering anisotropy.

52. A composition as in claim 48, wherein the human tissue comprises human skin.

53. A composition as in claim 48, wherein the human tissue comprises cervical tissue.

54. A composition as in claim 48, wherein the human tissue comprises mucosal tissue.

55. A method of producing an OSRS material, comprising:

a. Forming a combination of water and a crosslinking agent that contains a plurality of vinyl groups;

then

b. Adding an initiator to the combination.

56. A method as in claim 55, wherein the crosslinking agent comprises N,N′

-methylenebisacrylamide, ethylene glycol dimethacrylate, bisacrylamide, or a combination thereof.

57. A method as in claim 55, wherein the initiator comprises peroxide, benzoyl peroxide, a persulfate, ammonium persulfate, azobisisobutyronitrile, a photochemically activated initiator, methylene blue, riboflavin, ammonium persulfate in the presence of TEMED, or a combination thereof.

58. A method as in claim 55, wherein the combination further comprises a monomer that contains a vinyl group.

60. A method as in claim 55, wherein the combination further comprises an accelerant.

59. A method as in claim 59, wherein the monomer comprises acrylamide, 2-hydroxyethyl methacrylate, poly(ethylene glycol) methacrylate, 1-vinyl-2-pyrrolidinone, or a combination thereof.