Waveguide substrates and optical systems and methods of use thereof

• US 8,471,230 B2
• Filed: 09/15/2009
• Issued: 06/25/2013
• Est. Priority Date: 09/01/2006
• Status: Active Grant

• Current Assignee: Pacific Bioscience of California Incorporated (L'Oreal SA)
• Original Assignee: Pacific Bioscience of California Incorporated (L'Oreal SA)
• Inventors: Zhong, Cheng Frank, Lundquist, Paul, Foquet, Mathieu, Korlach, Jonas, Bayandorian, Hovig
• Primary Examiner(s): LE, QUE TAN
• Application Number:
  US12/560,308
• Publication Number:
  US 20100065726A1
• Time in Patent Office: 1,379 Days
• Field of Search: 250/221, 250/559.4, 250/573, 250/458.1, 356/317, 356/318, 436518-528, 435/7, 435228-291, 385/12, 385/14
• US Class Current: 250/573
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: G01N 2021/6463 Optics
• CPC Class Codes: G01N 2021/6478 Special lenses
• 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 21/7703 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 2201/06113 Coherent sources; lasers
• CPC Class Codes: G01N 2201/0638 Refractive parts
• CPC Class Codes: G01N 2201/08 Optical fibres; light guides
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

This invention provides substrates for use in various applications, including single-molecule analytical reactions. Methods for propagating optical energy within a substrate are provided. Devices comprising waveguide substrates and dielectric omnidirectional reflectors are provided. Waveguide substrates with improved uniformity of optical energy intensity across one or more waveguides and enhanced waveguide illumination efficiency within an analytic detection region of the arrays are provided.

Claims

1. An analytic device, comprising:

a first substrate comprising a first surface;

two or more waveguides disposed upon or within the first substrate; and

,

an analyte region disposed sufficiently proximal to a core of the at least one of the two or more waveguides to be illuminated by an evanescent field emanating from the core when optical energy is passed through the core, wherein the analyte region comprises a single optically resolvable immobilized complex.

2. The device of claim 1, wherein the two or more waveguides are configured to receive optical energy at a portion of the two or more waveguides comprising a first optical grating, and wherein the first optical grating is disposed within the two or more waveguides such that the grating, normalizes the optical energy intensity among the two or more waveguides.

3. The device of claim 2, comprising a source of a single beam of optical energy and a diffractive optical element for splitting the single beam of optical energy into two or more beams of optical energy.

4. The device of claim 1, wherein the analyte region is disposed within a nanohole.

5. The device of claim 1, wherein the analyte region is disposed within a nanometer-scale aperture that extends into the waveguide.

6. The analytic device of claim 2, further comprising a second optical grating, wherein the first optical grating and the second optical grating form a diffraction grating pair, wherein the diffraction grating pair flanks a portion of the waveguide that is proximal to the analyte region, and wherein the diffraction grating pair intensifies optical energy of at least one desired wavelength within the portion of the waveguide.

7. The analytic device of claim 1 wherein

at least one of the two or more waveguides is a shallow waveguide disposed at a first depth within the first substrate;

and further wherein at least one of the two or more waveguides is a deep waveguide disposed at a second depth within the first substrate, wherein the second depth is greater than the first depth, wherein the shallow waveguide is disposed between the first surface and the deep waveguide, and wherein the shallow waveguide is optically coupled to the deep waveguide; and

further wherein the analyte region is disposed sufficiently proximal to the shallow waveguide, to be illuminated by an evanescent field emanating from a core of the shallow waveguide when optical energy is passed through the shallow waveguide.

8. The analytic device of claim 1, further comprising:

a second substrate comprising;

an originating waveguide disposed upon or within the second substrate;

two or more branch waveguides disposed upon or within the second substrate, wherein the branch waveguides are optically coupled to the originating waveguide, and further wherein the two or more waveguides of the first substrate have a first end configured to be optically coupled to the two or more branch waveguides of the second substrate at an optical coupling location.

9. The device of claim 8, wherein a cross-sectional area at the first end of the two or more waveguides of the first substrate is greater at the optical coupling location than a cross-sectional area of the two or more waveguides of the first substrate at the analyte region.

10. The device of claim 8, wherein the two or more branch waveguides disposed upon or within the second substrate have tapered waveguide cores.

27. The analytic device of claim 1, wherein the two or more waveguides comprise bend that changes a direction of propagation of optical energy within the two or more waveguides.

28. The analytic device of claim 1, wherein the analyte region is within a detection region that comprises a plurality of optically resolvable analyte regions.

11. An analytic device, comprising:

a substrate comprising a first surface and at least a first optical waveguide disposed upon or proximal to the first surface of the substrate;

a reflective or absorptive layer disposed over the first surface of the substrate; and

an analyte region disposed within an aperture extending through the reflective or absorptive layer toward a core of the first optical waveguide, where the analyte region within the aperture is disposed sufficiently proximal to the core of the first optical waveguide to be illuminated by an evanescent field emanating from the core when optical energy is passed through the first optical waveguide, wherein passage of optical energy emanating from the evanescent field or the analyte region is mitigated by the reflective or absorptive layer.

12. The device of claim 11, further comprising a mask layer disposed between the first surface of the substrate and the reflective or absorptive layer, wherein the aperture extends through the mask layer.

13. The device of claim 12, wherein the mask layer comprises a plurality of apertures disposed therethrough, the spacing between the apertures exhibits a random spacing error as compared to apertures that exhibit uniform spacing, such that the random spacing error decreases grating effects associated with uniformly spaced apertures.

14. The device of claim 12, wherein the aperture is a nanometer-scale aperture.

15. The device of claim 14, wherein the aperture extends into the first optical waveguide.

23. The analytic device of claim 11, wherein the aperture penetrates into the first side of the substrate.

24. The analytic device of claim 11, further comprising a detector disposed proximal to the substrate on a side opposite the first side, wherein the reflective or absorptive layer reflects optical energy emanating from the analyte region toward the detector.

25. The analytic device of claim 11, further comprising:

a mask layer disposed upon the first surface of the substrate;

a thin layer disposed between the first surface of the substrate and the mask layer, wherein the thin layer is silane chemistry compatible and further wherein the aperture is a zero-mode waveguide disposed through the mask layer but not through the thin layer or into the substrate, wherein an analyte region within the zero-mode waveguide is sufficiently proximal to the core to be illuminated by an evanescent field emanating from the core when optical energy is passed through the optical waveguide; and

further wherein the reflective or absorptive layer is absent or is not silane chemistry compatible.

26. The analytic device of claim 25, wherein the mask layer comprises Al2O3 and the reflective or absorptive layer is absent.

16. An analytic device, comprising:

a substrate comprising a detection region and at least one optical waveguide that traverses the detection region, wherein the at least one optical waveguide has a first end coupled to an optical energy source and a second end that is not coupled to the optical energy source, and further wherein the optical waveguide is configured to have a higher confinement of optical energy at the second end than at the first end; and

a plurality of analyte regions disposed on a surface of the substrate in the detection region and sufficiently proximal to a core of the optical waveguide to be illuminated by an evanescent field emanating from the core when optical energy is passed through the optical waveguide.

17. The analytic device of claim 16, wherein the core of the optical waveguide is tapered such that there is a gradual decrease in thickness from the first end to the second end.

18. The analytic device of claim 16, wherein the core has a first refractive index at the first end and a second refractive index at the second end, and further wherein the core is configured that there is a gradual increase in refractive index from the first end to the second end.

19. The analytic device of claim 16, wherein the at least one optical waveguide is configured to propagate optical energy of a plurality of wavelengths with comparable electric field intensities.

20. The device of claim 19, wherein the plurality of wavelengths are in the visible spectrum.

21. The device of claim 19, wherein the optical waveguide utilizes different polarizations for each of the plurality of wavelengths.

29. The analytic device of claim 16, further comprising a plurality of nanometer-scale apertures;

a microlens array that collects optical energy signals from the detection region and directs the optical energy signals so collected to a detector; and

the detector.

22. A method for providing uniform illumination to a plurality of analyte regions on a substrate, the method comprising:

a) disposing a waveguide core within a substrate, wherein the waveguide core is configured to gradually decrease a measure of optical confinement of the waveguide core;

b) disposing the plurality of analyte regions along a portion of the substrate proximal to the waveguide core; and

c) coupling excitation illumination into the waveguide core.