Integrated illumination of optical analytical devices

• US 10,144,963 B2
• Filed: 04/17/2017
• Issued: 12/04/2018
• Est. Priority Date: 02/22/2013
• Status: Active Grant

• Current Assignee: Pacific Bioscience of California Incorporated (L'Oreal SA)
• Original Assignee: Pacific Bioscience of California Incorporated (L'Oreal SA)
• Inventors: Lundquist, Paul, Turner, Stephen
• Primary Examiner(s): WHITE, DENNIS MICHAEL
• Application Number:
  US15/489,655
• Publication Number:
  US 20170219492A1
• Time in Patent Office: 596 Days
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: G01N 2021/7789 Cavity or resonator
• 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 21/6454 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 21/7746 the waveguide coupled to a cavity resonator
• CPC Class Codes: G01N 2201/08 Optical fibres; light guides
• CPC Class Codes: G02B 2006/12147 Coupler
• CPC Class Codes: G02B 6/0229 characterised by nanostructures, i.e. structures of size less than 100 nm, e.g. quantum dots

Abstract

Optical analytical devices and their methods of use are provided. The devices are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The devices include integrated illumination elements and optical waveguides for illumination of the optical reactions. The devices further provide for the efficient coupling of optical excitation energy from the waveguides to the optical reactions. Optical signals emitted from the reactions can thus be measured with high sensitivity and discrimination using features such as spectra, amplitude, and time resolution, or combinations thereof. The devices of the invention are well suited for miniaturization and high throughput.

Claims

1. An analytical device comprising:

a substrate;

an integrated illumination element disposed on the substrate;

a plurality of illumination volumes disposed above the integrated illumination element; and

a plurality of detector elements disposed below the integrated illumination element;

wherein the integrated illumination element comprises a plurality of discrete light sources, and

wherein the plurality of discrete light sources are each disposed directly below an illumination volume, and the plurality of discrete light sources directly illuminate the plurality of illumination volumes from below.

2. The analytical device of claim 1, wherein light emitted from an analyte disposed within at least a first illumination volume is optically coupled to at least a first detector element through at least a first discrete light source.

3. The analytical device of claim 1, wherein the discrete light sources are semiconductor laser diodes, light-emitting diodes, solid-state lasers, or vertical cavity surface-emitting lasers.

4. The analytical device of claim 1, wherein the discrete light sources are diode light sources.

5. The analytical device of claim 4, wherein the diode light sources comprise an electrically pumped p-n junction.

6. The analytical device of claim 1, wherein the illumination volumes are illuminated by light emitted nearly perpendicularly from a top surface of the discrete light sources.

7. The analytical device of claim 6, wherein the light is emitted in a cone shape from the top surface of the discrete light sources.

8. The analytical device of claim 1, wherein the illumination volumes are illuminated by an evanescent field emanating from a top surface of the discrete light sources.

9. The analytical device of claim 1, wherein the discrete light sources are arranged in a strip structure.

10. The analytical device of claim 1, wherein at least a first detector element is disposed directly below a first illumination volume and a first discrete light source.

11. The analytical device of claim 1, further comprising an opaque layer disposed on the integrated illumination element.

12. The analytical device of claim 1, wherein the plurality of illumination volumes are contained in a plurality of nanowells disposed on the substrate, wherein at least a first nanowell is optically coupled to a first discrete light source and to a first detector element.

13. The analytical device of claim 12, further comprising an opaque layer disposed on the integrated illumination element, wherein the plurality of nanowells are disposed in the opaque layer, and wherein the first nanowell is optically coupled to the first discrete light source and to the first detector element through a bottom surface of the first nanowell.

14. The analytical device of claim 12, further comprising a conductor element and an insulator element associated with the first discrete light source, wherein the insulator element is disposed between the conductor element and the opaque layer.

15. The analytical device of claim 1, further comprising an analyte disposed within at least one illumination volume.

16. The analytical device of claim 15, wherein the analyte comprises a biological sample.

17. The analytical device of claim 16, wherein the biological sample comprises a nucleic acid.

18. The analytical device of claim 16, wherein the biological sample comprises a polymerase enzyme.

19. The analytical device of claim 1, wherein the analytical device comprises at least 1,000 illumination volumes.