Arrays of integrated analytical devices and methods for production

Patent metadata

Field	Value
Publication number	US-10768362-B2
Application number	US-201916430134-A
Country	US
Kind code	B2
Filing date	Jun 3, 2019
Priority date	Jun 17, 2012
Publication date	Sep 8, 2020
Grant date	Sep 8, 2020

Abstract

Arrays of integrated analytical devices and their methods for production are provided. The arrays 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 integrated devices allow the highly sensitive discrimination of optical signals using features such as spectra, amplitude, and time resolution, or combinations thereof. The arrays and methods of the invention make use of silicon chip fabrication and manufacturing techniques developed for the electronics industry and highly suited for miniaturization and high throughput.

First claim

What is claimed is:

1. An array of integrated analytical devices comprising:
a substrate layer, wherein the substrate layer is a detector layer;
a waveguide module layer disposed above the substrate layer, wherein the waveguide module layer comprises a lower waveguide cladding material, a waveguide core material, and an upper waveguide cladding material; and
a zero-mode waveguide module layer disposed on the waveguide module layer, wherein the zero-mode waveguide module layer comprises a plurality of nanometer-scale apertures penetrating to the waveguide module layer;
wherein at least one analytical device comprises a single detector element in the detector layer, and wherein the single detector element is optically coupled to a single nanometer-scale aperture through the waveguide module layer.

2. The array of claim 1 , wherein the detector layer is a CMOS wafer.

3. The array of claim 1 , wherein the single detector element comprises one pixel.

4. The array of claim 1 , wherein the array does not comprise a color separation layer.

5. The array of claim 1 , wherein the upper waveguide cladding material is SiO 2 .

6. The array of claim 1 , wherein the waveguide core material is Si 3 N 4 .

7. The array of claim 1 , wherein at least one of the plurality of nanometer-scale apertures comprises a fluid sample comprising a fluorescent species.

8. The array of claim 7 , wherein the fluorescent species is a fluorescently labeled nucleotide analog.

9. The array of claim 7 , wherein the fluid sample comprises a plurality of fluorescent species having distinct signal intensities.

10. The array of claim 1 , wherein the plurality of nanometer-scale apertures comprise at least 100 nanometer-scale apertures.

11. The array of claim 1 , wherein the plurality of nanometer-scale apertures have a density of at least 1000 apertures per cm 2 .

12. The array of claim 1 , further comprising a filter module layer disposed between the detector layer and the waveguide module layer.

13. The array of claim 12 , wherein the filter module layer comprises a dielectric filter.

14. The array of claim 12 , wherein the filter module layer comprises an absorptive filter.

15. The array of claim 1 , wherein the plurality of nanometer-scale apertures is formed by etching, and the etching is stopped using an endpoint signal.

16. The array of claim 1 , wherein at least one nanometer-scale aperture fully penetrates the upper waveguide cladding material.

17. The array of claim 16 wherein the at least one nanometer-scale aperture is partially backfilled.

18. The array of claim 17 , wherein the at least one nanometer-scale aperture is partially backfilled using atomic layer deposition or low pressure chemical vapor deposition.

19. The array of claim 1 , further comprising an etch hardmask.

20. An analytical system for the simultaneous measurement of multiple reactions comprising:
the array of integrated analytical devices of claim 1 ; and
an excitation light source.

21. The analytical system of claim 20 , wherein the excitation light source is coupled to the array of integrated analytical devices through an optical coupler integrated in the array.

22. The analytical system of claim 20 , wherein the system comprises a single excitation source.

Assignees

• Pacific Biosciences California Inc

Inventors

• Saxena Ravi
• Ru Michael Tzu
• Orimoto Takashi Whitney
• Grot Annette
• Foquet Mathieu
• Chou Hou-Pu

Classifications

• G01N2021/6467

  Axial flow and illumination · CPC title

• B29L2011/005

  Fresnel lenses · CPC title

• B29D17/007

  Forming the relief pattern on a support larger than the record · CPC title

• G02B6/12004 Primary

  Combinations of two or more optical elements · CPC title

• G01N21/6454

  using an integrated detector array · CPC title