Optical scanning system

• US 8,187,866 B2
• Filed: 05/17/2011
• Issued: 05/29/2012
• Est. Priority Date: 03/10/2006
• Status: Active Grant

• Current Assignee: LDIP, LLC
• Original Assignee: PLC Diagnostics, Inc.
• Inventors: Duer, Reuven
• Primary Examiner(s): Marcheschi, Michael
• Assistant Examiner(s): Doe, Shanta G
• Application Number:
  US13/109,280
• Publication Number:
  US 20110249260A1
• Time in Patent Office: 378 Days
• Field of Search: 435/6, 4352885-2887, 422/82.08, 422/82.11, 385/12, 385/14
• US Class Current: 435/288.7
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/553 and using surface plasmons fluorescence excitation G01N21/648; enhanced Raman G01N21/658
• CPC Class Codes: G01N 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B

Abstract

An optical scanning system including a switchable light source, a detector, a substrate and a plurality of optical sensing sites, as well s methods and kits for use thereof are provided. The substrate is coupled to and in optical communication with the switchable light source and the detector. Additionally, the substrate includes a plurality of substantially parallel excitation waveguides, and a plurality of substantially parallel collection waveguides, the excitation waveguides and collection waveguides crossing to form a two-dimensional array of intersection regions where an excitation waveguide and a collection waveguide cross and provide optical communication with the intersection region at each crossing. The plurality of optical sensing sites are each in optical communication with an intersection region.

Claims

1. A chip for detecting a biologically active analyte, comprising a substrate wherein the substrate comprises a plurality of substantially parallel excitation waveguides, and a plurality of substantially parallel collection waveguides, the excitation waveguides and collection waveguides crossing to form a two-dimensional array of intersection regions where an excitation waveguide and a collection waveguide cross and provide optical communication with the intersection region at each crossing;

a coupling region at an edge of the substrate in optical communication with each excitation waveguide and configured to couple the excitation waveguides to light traveling parallel to and in the plane of the excitation waveguides from the edge of the substrate; and

a plurality of optical sensing sites each in optical communication with an intersection region.

2. The chip of claim 1, wherein the optical sensing sites comprise a sensor and a sample comprising a biologically active analyte, and wherein a measurable change in a first light wave results when the sensor discriminates or interacts with the biologically active analyte.

3. The chip of claim 1 wherein a first light wave in an excitation waveguide is transduced by a sensor of an optical sensing site in optical communication with the excitation wave guide resulting in a second light wave in a collection waveguide.

4. The chip of claim 2, wherein the sensor is adapted to support an immunoassay.

5. The chip of claim 4, wherein the immunoassay supported is an enzyme-linked immunosorbent assay (ELISA).

6. The chip of claim 4, wherein the immunoassay supported is a fluorescent immunoassay.

7. The chip of claim 2, wherein the sensor is selected from the group consisting of a fluorescence well, an absorption cell, an interferometric sensor, a diffractive sensor and surface plasmon resonance sensor.

8. The chip of claim 1, wherein the biologically active analyte is selected from the group consisting of a nucleic acid, a protein, an antigen, an antibody, a lipid, a polysaccharide, a glycoprotein, a cell, a tissue, a microorganism, a gas, a chemical agent and a pollutant.

9. The chip of claim 8, wherein the nucleic acid is produced via an amplification reaction.

10. The chip of claim 1, wherein the crossing of the excitation waveguides and collection waveguides is substantially perpendicular.

11. The chip of claim 1, wherein the excitation waveguides are single-mode and the collection waveguides are multi-mode.

12. The chip of claim 1, wherein the excitation waveguides and the collection waveguides support single-mode in a first vertical dimension and multi-mode in a second lateral dimension.

13. The chip of claim 1, wherein the excitation waveguides and the collection waveguides are multi-mode.

14. The chip of claim 1, wherein the excitation waveguides and the collection waveguides are single-mode.

15. The chip of claim 1, wherein the excitation waveguide comprises a plurality of branches for drawing a fraction of the light from a first light wave traveling in the excitation waveguide.

16. The chip of claim 15, wherein the excitation waveguide branches are in optical communication with the excitation waveguide.

17. The chip of claim 1, wherein the collection waveguide comprises a plurality of funnels for collecting light from the sensing sites and coupling it to the collection waveguide.

18. The chip of claim 1, wherein the optical sensing sites comprise wells.

19. The chip of claim 1, wherein the optical sensing sites comprise the surface of the substrate above the intersection region of the excitation waveguides and the collection waveguides.

20. The chip of claim 1, wherein the optical sensing sites comprise biochemical interaction sites.

21. The chip of claim 1, wherein the optical sensing sites comprise optical transducers.

22. The chip of claim 21, wherein the optical transducers comprise wells comprising fluorescent compounds, wherein light waves guided by the excitation waveguides excite the fluorescent compound in the wells in the presence of a biologically active analyte, and the collection waveguides collect and guide light emitted from the fluorescent compound in the wells to a detector in optical communication with the collection waveguides.

23. The chip of claim 1, wherein the number of intersection regions is greater than 10.

24. The chip of claim 1, wherein the density of intersection regions is greater than 100 per cm².

25. The chip of claim 1, wherein the density of intersection regions is greater than 2,000 per cm².

26. The chip of claim 1, wherein the chip is in thermal communication with a thermal transfer element.

27. The chip of claim 26, wherein the thermal transfer element is a thermoelectric cooler.

28. The chip of claim 1, wherein each optical sensing site comprises a thermal transfer element in thermal communication with the optical sensing site.

29. The chip of claim 28, wherein the thermal transfer element comprises a thin-film heater.

30. The chip of claim 28, wherein each optical sensing site further comprises a thermistor in thermal communication with the optical sensing site.

31. The chip of claim 1, wherein the substrate further comprises one or more microchannel and one or more reservoirs in fluid communication with one or more optical sensing site.

32. The chip of claim 1, wherein the chip further comprises a fluidics layer coupled to the substrate and comprising one or more microchannel and one or more reservoirs in fluid communication with one or more optical sensing site.

46. The chip of claim 1, wherein the excitation waveguides are configured to couple into the optical sensing site through an evanescent electromagnetic field.

49. The chip of claim 1, further wherein the collection waveguides extend to an edge of the chip for coupling to one or more detectors.

33. A scanning sensing method comprising:

delivering a sample suspected of containing a biologically active analyte to be detected to an optical sensing site of a chip comprising a substrate wherein the substrate comprises a plurality of substantially parallel excitation waveguides, and a plurality of substantially parallel collection waveguides, the excitation waveguides and collection waveguides crossing to form a two-dimensional array of intersection regions where an excitation waveguide and a collection waveguide cross and provide optical communication with the intersection region at each crossing; and

a plurality of optical sensing sites each in optical communication with an intersection region;

providing a first light wave using a switchable light source to one or more of the plurality of substantially parallel excitation waveguides in optical communication with the optical sensing site, wherein the first light wave is transducable by a sensor associated with the optical sensing site to a second light wave carried in one or more of the plurality of substantially parallel collection waveguides in optical communication with the optical sensing site and crossing the excitation waveguides; and

detecting the second light wave using a detector in optical communication with the collection waveguides, wherein a measurable change in the first light waves occurs when the sensor interacts with the biologically active analyte.

34. The method of claim 33, wherein a portion of the sensing sites comprise reference sample material for calibration and/or normalization.

35. The method of claim 33, wherein the biologically active analyte is selected from the group consisting of a nucleic acid, a protein, an antigen, an antibody, a lipid, a polysaccharide, a glycoprotein, a cell, a tissue, a microorganism, a gas, a chemical agent and a pollutant.

36. The method of claim 33, wherein the biologically active analyte is a protein.

37. The method of claim 33, wherein a SNP is detected in the biologically active analyte.

38. The method of claim 33, wherein expression of a gene is detected upon detection of the biologically active analyte.

39. The method of claim 33, wherein the sensor is adapted to support an immunoassay and wherein the sensor interacting with the biologically active analyte comprises an outcome of an immunoassay.

40. The method of claim 39, wherein the immunoassay supported is an enzyme-linked immunosorbent assay (ELISA).

41. The method of claim 39, wherein the immunoassay supported is a fluorescent immunoassay.

42. The method of claim 33, wherein detecting a measurable change in the first lightwave as measured in the second lightwave provides a diagnostic result.

43. The method of claim 33, further comprising conducting a real-time PCR reaction at the optical sensing site.

44. A kit for assaying a sample for a biologically active analyte comprising:

a chip comprising a substrate wherein the substrate comprises a plurality of substantially parallel excitation waveguides, and a plurality of substantially parallel collection waveguides, the excitation waveguides and collection waveguides crossing to form a two-dimensional array of intersection regions where an excitation waveguide and a collection waveguide cross and provide optical communication with the intersection region at each crossing;

a coupling region at an edge of the substrate in optical communication with each excitation waveguide and configured to couple the excitation waveguides to light traveling parallel to and in the plane of the excitation waveguides from the edge of the substrate;

a plurality of optical sensing sites each in optical communication with an intersection region;

packaging; and

instructions for use of the chip in an optical scanning system.

45. The kit of claim 44, wherein the optical sensing sites comprise a sensor adapted to support an immunoassay, and wherein the kit further comprises one or more immunoassay reagents.

47. A chip for detecting a biologically active analyte, comprising a substrate wherein the substrate comprises a plurality of excitation waveguides and a plurality of collection waveguides, the excitation waveguides and collection waveguides arranged in a lateral plane so that the excitation waveguides and collection waveguides cross to form a two-dimensional array of intersection regions where the crossing of each excitation waveguide and collection waveguide provides evanescent optical communication with the intersection region at each crossing, further wherein the excitation waveguides are single-mode in a vertical dimension and multimode in a lateral dimension;

a coupling region at an edge of the substrate in optical communication with each excitation waveguide and configured to couple the excitation waveguides to light traveling parallel to and in the plane of the excitation waveguides from the edge of the substrate; and

a plurality of optical sensing sites each in optical communication with an intersection region.

48. The chip of claim 47, wherein the excitation waveguides are configured to couple into the optical sensing site through an evanescent electromagnetic field.

50. A scanning sensing method comprising:

delivering a sample suspected of containing a biologically active analyte to be detected to an optical sensing site of a chip comprising a substrate wherein the substrate comprises a plurality of excitation waveguides, and a plurality of collection waveguides, the excitation waveguides and collection waveguides crossing to form a two-dimensional array of intersection regions where an excitation waveguide and a collection waveguide cross and provide optical communication with the intersection region at each crossing; and

a plurality of optical sensing sites each in optical communication with an intersection region;

providing a first light from a light source in the plane of the substrate to one or more of the plurality of excitation waveguides in optical communication with the optical sensing site, wherein the first light is transducable by a sensor associated with the optical sensing site to emit light in one or more of the plurality of collection waveguides in optical communication with the optical sensing site and crossing the excitation waveguides; and

detecting the emitted light using a detector in optical communication with the collection waveguides, wherein a measurable change in the first light occurs when the sensor interacts with the biologically active analyte.