Illumination of optical analytical devices

• US 10,578,788 B2
• Filed: 07/09/2018
• Issued: 03/03/2020
• Est. Priority Date: 12/18/2012
• Status: Active Grant

• Current Assignee: Pacific Bioscience of California Incorporated (L'Oreal SA)
• Original Assignee: Pacific Bioscience of California Incorporated (L'Oreal SA)
• Inventors: Grot, Annette, Wang, Shang, Callebaut, Hans, Lundquist, Paul, Turner, Stephen
• Primary Examiner(s): Petkovsek, Daniel
• Application Number:
  US16/030,421
• Publication Number:
  US 20190064421A1
• Time in Patent Office: 603 Days
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 20/00 Nanooptics, e.g. quantum optics or photonic crystals
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: G01N 2021/6441 with two or more labels
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• 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 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• 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
• CPC Class Codes: G02B 23/2461 Illumination
• CPC Class Codes: G02B 6/0016 Grooves, prisms, gratings, scattering particles or rough surfaces
• CPC Class Codes: G02B 6/024 with polarisation maintaining properties
• CPC Class Codes: G02B 6/10 of the optical waveguide type G02B6/02, G02B6/24 take precedence; devices or arrangements for the control of light by electric, magnetic, electro-magnetic or acoustic means G02F1/00; transferring the modulation of modulated light G02F2/00; optical logic elements G02F3/00; optical analogue/digital converters G02F7/00
• CPC Class Codes: G02B 6/12004 Combinations of two or more optical elements
• CPC Class Codes: G02B 6/122 Basic optical elements, e.g. light-guiding paths
• CPC Class Codes: G02F 1/365 in an optical waveguide structure G02F1/377, G02F1/395 take precedence

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 optical waveguides for illumination of the optical reactions. In some embodiments, the devices comprise an optical waveguide comprising a plurality of optical cores and a cladding, a plurality of nanometer-scale apertures disposed on a surface of the device above the optical waveguide, such that optical energy passing through the plurality of optical cores of the optical waveguide illuminates the plurality of nanometer-scale apertures by an evanescent field that emanates from the waveguide, and a plurality of detectors optically coupled to the plurality of nanometer-scale apertures. 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:

an optical waveguide comprising a plurality of optical cores and a cladding;

a plurality of nanometer-scale apertures disposed on a surface of the device above the optical waveguide, such that optical energy passing through the plurality of optical cores of the optical waveguide illuminates the plurality of nanometer-scale apertures by an evanescent field that emanates from the waveguide; and

a plurality of detectors optically coupled to the plurality of nanometer-scale apertures;

wherein at least two optical cores are separated by a spacing of cladding between the at least two optical cores;

wherein at least one nanometer-scale aperture in the plurality of nanometer-scale apertures is jointly illuminated by an evanescent field emanating from the at least two optical cores; and

wherein an optical emission from the at least one nanometer-scale aperture passes through the spacing of cladding between the at least two optical cores to at least one detector.

2. The analytical device of claim 1, further comprising an opaque layer disposed between the optical waveguide and the plurality of optical detectors, wherein the opaque layer comprises a plurality of openings in direct alignment with the nanometer-scale apertures and their optically coupled detectors.

3. The analytical device of claim 1, wherein the device further comprises a plurality of local field enhancement elements, and wherein each local field enhancement element is associated with a nanometer-scale apertures.

4. The analytical device of claim 3, wherein each local field enhancement element comprises a high dielectric material or metal, wherein the high dielectric material has a higher dielectric constant than silicon dioxide, and wherein each local field enhancement element increases optical coupling efficiency between the at least one nanometer-scale aperture and the at least two optical cores.

5. The analytical device element of claim 4, wherein the high dielectric material or metal is arranged in a geometric pattern around the at least one nanometer-scale aperture.

6. The analytical device element of claim 5, wherein the geometric pattern is selected from the group consisting of a circle, a series of concentric circles, a C aperture, a triangle pair, and a diamond.

7. The analytical device of claim 4, wherein the high dielectric material or metal is Al₂O₃, copper, silver, gold, or aluminum.

8. The analytical device element of claim 7, wherein the high dielectric material or metal is Al₂O₃.

9. The analytical device element of claim 7, wherein the high dielectric material or metal is copper.

10. The analytical device element of claim 1, wherein the nanometer-scale apertures are recessed into the cladding.

11. The analytical device of claim 1, wherein the cladding between the plurality of optical cores and the surface of the device has a first thickness that is decreased at locations where the evanescent field illuminates the nanometer-scale apertures.

12. The analytical device of claim 11, wherein the cladding between the plurality of optical cores and the surface of the device has a second thickness of from 150 to 300 nm at locations where the evanescent field does not illuminate the nanometer-scale apertures.

13. The analytical device of claim 12, wherein the second thickness is about 200 nm.

14. The analytical device of claim 1, wherein the analytical device further comprises a plurality of analytes disposed in analyte regions within the plurality of nanometer-scale apertures.

15. The analytical device of claim 14, wherein the plurality of analytes comprise a plurality of biological samples.

16. The analytical device of claim 15, wherein the plurality of biological samples comprise a plurality of nucleic acids.

17. 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 nanometer-scale apertures.