Illumination of optical analytical devices

• US 10,018,764 B2
• Filed: 11/18/2015
• Issued: 07/10/2018
• 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:
  US14/945,186
• Publication Number:
  US 20160154165A1
• Time in Patent Office: 965 Days
• Field of Search: 385 14, 385 30, 385129-132
• 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. 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 an optical core and a cladding;

a metallic layer disposed on a surface of the cladding;

a plurality of nanometer-scale apertures disposed in the metallic layer above the optical waveguide, such that optical energy passing through the optical core of the optical waveguide illuminates the plurality of apertures by an evanescent field that emanates from the waveguide; and

a plurality of local field enhancement elements associated with the plurality of apertures, wherein the local field enhancement elements are arranged in a geometric pattern of high dielectric material or metal surrounding the apertures and positioned below the metallic layer.

2. The analytical device of claim 1, 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.

3. The analytical device of claim 1, wherein the high dielectric material or metal is Al₂O₃, copper, silver, gold, or aluminum.

4. The analytical device of claim 3, wherein the high dielectric material or metal is Al₂O₃.

5. The analytical device of claim 3, wherein the high dielectric material or metal is copper.

6. The analytical device of claim 1, wherein the apertures are recessed into the cladding.

7. The analytical device of claim 1, wherein the cladding between the optical core and the metallic layer has a first thickness that is decreased at locations where the evanescent field illuminates the apertures.

8. The analytical device of claim 7, wherein the cladding between the optical core and the metallic layer has a second thickness of from 150 to 300 nm at locations where the evanescent field does not illuminate the apertures.

9. The analytical device of claim 8, wherein the second thickness is about 200 nm.

10. The analytical device of claim 1, wherein the local field enhancement elements comprise the shape of the nanometer-scale apertures.

11. The analytical device of claim 10, wherein the shape of the nanometer-scale apertures is selected from the group consisting of a C aperture, a triangle pair, and a diamond.

12. 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.

13. The analytical device of claim 12, wherein the plurality of analytes comprise a plurality of biological samples.

14. The analytical device of claim 13, wherein the plurality of biological samples comprise a plurality of nucleic acids.

15. 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.

16. The analytical device of claim 1, wherein the device further comprises a stray-light termination element disposed below the plurality of apertures.

17. An analytical device comprising:

an optical waveguide comprising an optical core and a cladding;

a metallic layer disposed on a surface of the cladding; and

a plurality of nanometer-scale apertures disposed in the metallic layer above the optical waveguide, such that optical energy passing through the optical core of the optical waveguide illuminates the plurality of apertures by an evanescent field that emanates from the waveguide;

wherein the optical core and the metallic layer are separated by a first thickness that is decreased at locations where the evanescent field illuminates the apertures.

18. The analytical device of claim 17, wherein the device further comprises a stray-light termination element disposed below the plurality of apertures.

19. The analytical device of claim 18, further comprising a plurality of local field enhancement elements associated with the plurality of apertures, wherein the local field enhancement elements are arranged in a geometric pattern of high dielectric material or metal surrounding the apertures and positioned below the metallic layer.

20. The analytical device of claim 19, 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.

21. The analytical device of claim 19, wherein the high dielectric material or metal is Al₂O₃, copper, silver, gold, or aluminum.

22. The analytical device of claim 21, wherein the high dielectric material or metal is Al₂O₃.

23. The analytical device of claim 21, wherein the high dielectric material or metal is copper.

24. The analytical device of claim 19, wherein the local field enhancement elements comprise the shape of the nanometer-scale apertures.

25. The analytical device of claim 24, wherein the shape of the nanometer-scale apertures is selected from the group consisting of a C aperture, a triangle pair, and a diamond.

26. The analytical device of claim 18, wherein the optical core and the metallic layer are separated by a second thickness of from 150 to 300 nm at locations where the evanescent field does not illuminate the apertures.

27. The analytical device of claim 26, wherein the second thickness is about 200 nm.

28. The analytical device of claim 18, wherein the analytical device further comprises a plurality of analytes disposed in analyte regions within the plurality of nanometer-scale apertures.

29. The analytical device of claim 28, wherein the plurality of analytes comprise a plurality of biological samples.

30. The analytical device of claim 29, wherein the plurality of biological samples comprise a plurality of nucleic acids.

31. The analytical device of claim 18, 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.