Imaging method and apparatus

• US 20050024642A1
• Filed: 05/17/2004
• Published: 02/03/2005
• Est. Priority Date: 07/11/2000
• Status: Active Grant

• Current Assignee: Maven Biotechnologies, LLC
• Original Assignee: Maven Technologies, LLC
• Inventors: Ralin, David, Rassman, William, Lieberman, Robert A., Shapiro, Herbert, Kempen, Lothar U.
• Granted Patent: US 7,193,711 B2
• Time in Patent Office: Days
• US Class Current: 356/369
• CPC Class Codes: G01N 2021/212 Arrangement with total internal reflection
• CPC Class Codes: G01N 21/21 Polarisation-affecting properties G01N21/19 takes precedence
• CPC Class Codes: G01N 21/211 Ellipsometry optical thickness measurement G01B11/06
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/552 Attenuated total reflection
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

An imaging method and apparatus are provided, including a light source emitting a polarized light beam, and an optical assembly including a control layer and/or a light reflection surface. The control layer advantageously allows for control over the properties of a generated evanescent wave to optimize an image of a specimen array within the evanescent wave. The light reflection surface includes coupling means used to couple a receptor/capture agent advantageously allowing for flexible control over receptor specific regions.

Claims

1. An apparatus for imaging, comprising:

a light source emitting a polarized light beam;

an optical assembly including a control layer and a light reflection surface, wherein the light beam is passed through the control layer and reflected by the light reflection surface to provide an evanescent field with controlled height and intensity adjacent the light reflection surface, the light reflection surface being adapted to provide thereon a specimen array such that the specimen array in the evanescent field causes spatially distributed polarization changes in the cross-section of the light beam; and

a detector positioned to detect the spatially distributed polarization changes in the light beam to provide an image of the specimen array.

2. The apparatus as in claim 1, wherein the control layer comprises glass, liquid crystal, and/or semiconductor material.

3. The apparatus as in claim 1, wherein the control layer has a thickness for controlling evanescent field generation.

4. The apparatus as in claim 1, wherein the control layer has a refractive index for controlling evanescent field generation.

5. The apparatus as in claim 1, wherein the control layer has a reflectivity characteristic for controlling evanescent field generation.

6. The apparatus as in claim 1, wherein the light reflection surface includes a metal film to which potential is applied.

7. The apparatus as in claim 6, wherein the metal film is comprised of gold, silver, titanium, and/or chromium.

8. The apparatus as in claim 1, wherein the specimen array includes a two-dimensional array formed of multiple fields comprising biomolecular substances.

9. The apparatus as in claim 8, wherein the biomolecular substances are proteins, peptides, carbohydrates, lipids, and/or polynucleotide sequences.

10. An apparatus for imaging, comprising:

a light source emitting a polarized light beam;

an optical assembly including a light reflection surface, wherein the light beam is reflected by the light reflection surface to provide an evanescent field adjacent the light reflection surface, the light reflection surface including coupling means for providing thereon a specimen array such that the specimen array in the evanescent field causes spatially distributed polarization changes in the cross-section of the light beam; and

a detector positioned to detect the spatially distributed polarization changes in the light beam to provide an image of the specimen array.

11. The apparatus as in claim 10, wherein the light reflection surface is comprised of material selected from the group consisting of semiconductors, metals, and plastics.

12. The apparatus as in claim 10, wherein the light reflection surface is comprised of silane and the coupling means includes a silanizing agent.

13. The apparatus as in claim 10, wherein the light reflection surface is comprised of metal and the coupling means includes a sulfur-containing compound.

14. The apparatus as in claim 13, wherein the metal includes gold, silver, titanium, and/or chromium.

15. The apparatus as in claim 13, wherein the sulfur-containing compound is a thiol.

16. The apparatus as in claim 10, wherein the light reflection surface is comprised of plastic.

17. The apparatus as in claim 10, wherein the coupling means has an affinity for biomolecular substances.

18. The apparatus as in claim 10, wherein the specimen array includes a two-dimensional array formed of multiple fields comprising biomolecular substances.

19. The apparatus as in claim 18, wherein the biomolecular substances are proteins, peptides, carbohydrates, lipids, and/or polynucleotide sequences.

20. A method of imaging, comprising:

passing a polarized light beam into an optical assembly including a control layer and a light reflection surface;

providing an evanescent field with controlled height and intensity adjacent the light reflection surface using the control layer;

providing a specimen array in the evanescent field causing spatially distributed polarization changes in the cross-section of the light beam; and

passing the reflected light beam out of the optical assembly where the spatially distributed polarization changes in the light beam are detected and processed to provide an image of the specimen array.

21. The method of claim 20, wherein an optical property of the control layer is used to control the height and intensity of the evanescent field.

22. The method of claim 21, wherein the optical property of the control layer is selected from the group consisting of thickness, refractive index, and reflectivity characteristic.

23. The method of claim 20, wherein the control layer is comprised of liquid crystal that is used to control optical properties of the control layer.

24. The method of claim 20, wherein the light reflection surface is comprised of a metal.

25. The method of claim 24, further comprising applying a potential to the metal to control the height and intensity of the evanescent field.

26. A method of imaging, comprising:

passing a polarized light beam into an optical assembly including a light reflection surface having coupling means for providing thereon an array of capture agents;

providing an evanescent field adjacent the light reflection surface;

providing molecules of interest such that the array of capture agents coupled with molecules of interest in the evanescent field cause spatially distributed polarization changes in the cross-section of the light beam; and

passing the reflected light beam out of the optical assembly where the spatially distributed polarization changes in the light beam are detected and processed to provide an image of the array of capture agents coupled with the molecules of interest.

27. The method of claim 26, wherein the coupling means is used to couple a capture agent to the light reflection surface.

28. The method of claim 26, wherein the light reflection surface is comprised of glass.

29. The method of claim 28, wherein the coupling means includes a silanizing agent to silanize the light reflection surface.

30. The method of claim 26, wherein the light reflection surface is comprised of metal.

31. The method of claim 30, wherein the coupling means includes a sulphur-containing compound to derivatize or couple capture agents to the light reflection surface.

32. A cassette for use with an imaging apparatus, the cassette comprising:

a light reflection surface including coupling means to allow formation thereon of a specimen array;

a control layer configured to direct a polarized light beam from a light source to the light reflection surface, such that a reflection of the polarized light beam at the light reflection surface generates a controlled evanescent field in the vicinity of the specimen array; and

a flow cell coupled to the light reflection surface, the flow cell including an inlet port and an outlet port for flowing analyte across the specimen array.

33. The cassette as in claim 32, wherein the light source and the control layer are configured for a single reflection of the light beam at the light reflection surface.

34. The cassette as in claim 32, wherein the light reflection surface is comprised of material selected from the group consisting of semiconductors, metals, and plastics.

35. The cassette as in claim 32, wherein the light reflection surface is comprised of silane and the coupling means includes a silanizing agent.

36. The cassette as in claim 32, wherein the light reflection surface is comprised of metal and the coupling means includes a sulfur-containing compound.

37. The cassette as in claim 36, wherein the metal includes gold, silver, titanium, and/or chromium.

38. The cassette as in claim 36, wherein the sulfur-containing compound includes a thiol.

39. The cassette as in claim 32, wherein the light reflection surface is comprised of plastic.

40. The cassette as in claim 32, wherein the coupling means has an affinity for biomolecular substances.

41. The cassette as in claim 32, wherein the control layer comprises glass, liquid crystal, and/or semiconductor material.

42. The cassette as in claim 32, wherein the control layer has a thickness for controlling evanescent field generation.

43. The cassette as in claim 32, wherein the control layer has a refractive index for controlling evanescent field generation.

44. The cassette as in claim 32, wherein the control layer has a reflectivity characteristic for controlling evanescent field generation.

45. The cassette as in claim 32, wherein the light reflection surface includes a metal film to which potential is applied.

46. The cassette as in claim 45, wherein the metal film is comprised of gold, silver, titanium, and/or chromium.

47. The cassette as in claim 32, wherein the specimen array includes a two-dimensional array formed of multiple fields comprising biomolecular substances.

48. The cassette as in claim 47, wherein the biomolecular substances are proteins, peptides, carbohydrates, lipids, and/or polynucleotide sequences.