Waveguide-based optical scanning systems

• US 9,528,939 B2
• Filed: 09/13/2012
• Issued: 12/27/2016
• Est. Priority Date: 03/10/2006
• Status: Active Grant

• Current Assignee: LDIP, LLC
• Original Assignee: iNDx Lifecare, Inc.
• Inventors: Duer, Reuven
• Primary Examiner(s): Chin, Chris L
• Application Number:
  US13/615,124
• Publication Number:
  US 20130071850A1
• Time in Patent Office: 1,566 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 2021/7709 Distributed reagent, e.g. over length of guide
• CPC Class Codes: G01N 2021/7733 Reservoir, liquid reagent
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 2021/7793 Sensor comprising plural indicators
• CPC Class Codes: G01N 21/0332 with temperature control control of temperature G05D23/00; cryostats F17C3/08
• CPC Class Codes: G01N 21/05 Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 21/553 and using surface plasmons fluorescence excitation G01N21/648; enhanced Raman G01N21/658
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/6454 using an integrated detector array
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 21/76 Chemiluminescence; Bioluminescence
• 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
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

A scanning sensor system, methods of use and kits for detecting a biologically active analyte are provided. The scanning senor system includes a light source, a detector, a substrate comprising a plurality of waveguides and a plurality of optical sensing sites in optical communication with one or more waveguide of the substrate, and at least one adapter configured to couple with the substrate and provide optical communication between the light source, the waveguides of the substrate, and the detector.

Claims

1. A scanning sensing method comprising:

coupling a removable substrate comprising a plurality of in-coupling waveguides, a plurality of out-coupling waveguides and combiners for coupling the in-coupling and out-coupling waveguides, wherein the substrate is coupled in optical communication with an adapter, a light source, and a detector to provide a scanning sensor system, wherein the adapter is coupled to the light source and the detector;

delivering a sample suspected of containing a biologically active analyte to be detected to an optical sensing site of the substrate, wherein the optical sensing site comprises a well;

providing a first light wave using a light source to one or more of the plurality of in-coupling waveguides of the substrate, wherein the in-coupling waveguides are 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 to an out-coupling waveguide; and

detecting the second light wave using the detector, wherein a measurable change in the first light wave as measured in the second light wave occurs when the sensor interacts with the biologically active analyte.

2. The method of claim 1, wherein scanning sensing further comprises switching one or more input light wave from the light source into the substrate to produce the first light wave in one or more of the in-coupling waveguides.

3. The method of claim 1, wherein the light source comprises an optical switch for controlled switching of one or more input light wave, the optical switch can multicast light to a plurality of outputs and into the substrate to controllably produce the first light wave in one or more of the in-coupling waveguides.

4. The method of claim 1, wherein the light source comprises an array of individually controlled light generators for controlled switching of one or more input light wave, to controllably produce the first light wave in one or more of the in-coupling waveguides.

5. The method of claim 1, wherein the incoupling waveguides are in optical communication with a plurality of optical sensing sites and the first wave generates a plurality of second light waves from the plurality of optical sensing sites, the method further comprising simultaneously detecting the plurality of second light waves with the detector wherein the detector comprises a photodetector array.

6. The method of claim 1, wherein, a portion of the sensing sites comprise reference sample material for calibration and/or normalization.

7. The method 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 cell, a tissue, a microorganism, a gas, a chemical agent and a pollutant.

8. The method of claim 1, wherein the biologically active analyte is a protein.

9. The method of claim 1, wherein a SNP is detected in the biologically active analyte.

10. The method of claim 1, wherein a marker for gene expression is detected in the biologically active analyte.

11. The method of claim 1, wherein the sensor comprises an immunoassay reagent that supports an immunoassay and wherein the immunoassay reagent of the sensor interacting with the biologically active analyte comprises an outcome of an immunoassay.

12. The method of claim 11, wherein the immunoassay supported is an enzyme-linked immunosorbent assay (ELISA).

13. The method of claim 11, wherein the immunoassay supported is a fluorescent immunoassay.

14. The method of claim 1, wherein detecting a measurable change in the first lightwave as measured in the second lightwave provides a diagnostic result.

15. The method of claim 1, further comprising conducting a real-time PCR reaction at the optical sensing site.

16. A chip for detecting a biologically active analyte, comprising a substrate wherein the substrate comprises a plurality of in-coupling waveguides coupled to a plurality of out-coupling waveguides by combiners, where the out-coupling waveguides are in optical communication with a plurality of sensing sites.

17. The chip of claim 16, 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.

18. The chip of claim 16 wherein a first light wave in an in-coupling waveguide is transduced by a sensor of an optical sensing site in optical communication with the out-coupling waveguide resulting in a second light wave in a out-coupling waveguide.

19. The chip of claim 17, wherein the sensor comprises an immunoassay reagent that supports an immunoassay.

20. The chip of claim 19, wherein the immunoassay supported is an enzyme-linked immunosorbent assay (ELISA).

21. The chip of claim 19, wherein the immunoassay supported is a fluorescent immunoassay.

22. The chip of claim 17, 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.

23. The chip of claim 16, 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.

24. The chip of claim 23, wherein the nucleic acid is produced via an amplification reaction.

25. The chip of claim 16, wherein the in-coupling waveguides are single-mode and the out-coupling waveguides are multi-mode.

26. The chip of claim 16, wherein the in-coupling waveguides and the out-coupling waveguides support single-mode in a first vertical dimension and multi-mode in a second lateral dimension.

27. The chip of claim 16, wherein the in-coupling waveguides and the out-coupling waveguides are multi-mode.

28. The chip of claim 16, wherein the in-coupling waveguides and the out-coupling waveguides are single-mode.

29. The chip of claim 16, wherein the in-coupling waveguide comprises a plurality of branches for drawing a fraction of the light from a first light wave traveling in the in-coupling waveguide.

30. The chip of claim 29, wherein the in-coupling waveguide branches are in optical communication with the in-coupling waveguide.

31. The chip of claim 16, wherein the out-coupling waveguide comprises a plurality of funnels for collecting light from the sensing sites and coupling it to the out-coupling waveguide.

32. The chip of claim 16, wherein the optical sensing sites comprise wells.

33. The chip of claim 16, wherein the optical sensing sites comprise the surface of the substrate above the out-coupling waveguides.

34. The chip of claim 16, wherein the optical sensing sites comprise biochemical interaction sites.

35. The chip of claim 16, wherein the optical sensing sites comprise optical transducers.

36. The chip of claim 35, wherein the optical transducers comprise wells comprising fluorescent compounds, wherein light waves guided by the in-coupling waveguides excite the fluorescent compound in the wells in the presence of a biologically active analyte, and the out-coupling waveguides collect and guide light emitted from the fluorescent compound or the luminescent compounds in the wells to the detector.

37. The chip of claim 16, wherein the number of sensing wells is greater than 10.

38. The chip of claim 16, wherein the density of sensing wells is greater than 100 per cm².

39. The chip of claim 16, wherein the chip is in thermal communication with a thermal transfer element.

40. The chip of claim 39, wherein the thermal transfer element is a thermoelectric cooler.

41. The chip of claim 16, wherein each optical sensing site comprises a thermal transfer element in thermal communication with the optical sensing site.

42. The chip of claim 41, wherein the thermal transfer element comprises a thin-film heater.

43. The chip of claim 41, wherein each optical sensing site further comprises a thermistor in thermal communication with the optical sensing site.

44. The chip of claim 16, wherein the substrate further comprises one or more microchannel and one or more reservoirs in fluid communication with one or more optical sensing site.

45. The chip of claim 16, 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.