Integrated illumination of optical analytical devices
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.
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.