Integrated illumination of optical analytical devices

• US 10,570,450 B2
• Filed: 12/03/2018
• Issued: 02/25/2020
• 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
• Application Number:
  US16/208,421
• Publication Number:
  US 20190256911A1
• Time in Patent Office: 449 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;

a plurality of illumination volumes; and

a plurality of detector elements;

wherein

the integrated illumination element is disposed in the substrate;

the integrated illumination element comprises an optical resonator within a waveguide;

the optical resonator comprises a laser medium and a first and a second mirror disposed within the waveguide; and

the plurality of illumination volumes are contained in a plurality of nanowells disposed on a surface of the substrate, wherein at least a first nanowell is optically coupled to the waveguide and to one of the detector elements.

2. The analytical device of claim 1, wherein the at least a first nanowell is optically coupled to the waveguide by evanescent illumination emanating from the waveguide.

3. The analytical device of claim 2, wherein the first mirror and the second mirror are 100% reflection mirrors, and wherein the at least a first nanowell is optically coupled to the waveguide at a region directly adjacent to the optical resonator.

4. The analytical device of claim 3, wherein no more than one nanowell or no more than one row of nanowells is coupled to the waveguide.

5. The analytical device of claim 2, wherein the first mirror is a high reflector mirror and the second mirror is a partial reflector mirror.

6. The analytical device of claim 2, wherein the optical resonator amplifies optical energy in the waveguide.

7. The analytical device of claim 2, wherein the at least a first nanowell is optically coupled to the waveguide at a region remote from the optical resonator.

8. The analytical device of claim 7, wherein no more than one nanowell or no more than one row of nanowells is coupled to the waveguide.

9. The analytical device of claim 2, further comprising a second nanowell optically coupled to the waveguide by evanescent illumination emanating from the waveguide, wherein the at least a first nanowell is optically coupled to the waveguide at a region directly adjacent to the optical resonator and the second nanowell is optically coupled to the waveguide at a region remote from the optical resonator.

10. The analytical device of claim 9, wherein no more than one nanowell or no more than one row of nanowells is coupled to the waveguide.

11. The analytical device of claim 1, wherein the integrated illumination element comprises a plurality of optical resonators within a waveguide, each optical resonator comprising a laser medium and a first and a second mirror disposed within the waveguide;

and wherein the at least a first nanowell is optically coupled to the integrated illumination element.

12. The analytical device of claim 11, wherein at least one of the optical resonators amplifies optical energy in the waveguide.

13. The analytical device of claim 12, wherein the at least a first nanowell is optically coupled to the waveguide at a region remote from the optical resonators.

14. The analytical device of claim 1, wherein at least one optical resonator is optically pumped.

15. The analytical device of claim 1, wherein at least one optical resonator is electrically pumped.

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

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

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

19. The analytical device of claim 17, wherein the biological sample comprises a polymerase enzyme.

20. The analytical device of claim 1, wherein the analytical device comprises at least 1,000, at least 10,000, at least 100,000, at least 1,000,000, or at least 10,000,000 illumination volumes.

21. The analytical device of claim 1, wherein at least one detector element of the plurality of detector elements further comprises a spectral diversion element.

22. The analytical device of claim 1, wherein at least one detector element of the plurality of detector elements further comprises a light redirection cone.