Arrays of integrated analytical devices

• US 10,234,393 B2
• Filed: 02/20/2018
• Issued: 03/19/2019
• Est. Priority Date: 08/27/2014
• 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, Saxena, Ravi, Lundquist, Paul
• Primary Examiner(s): Nguyen, Sang H
• Application Number:
  US15/900,608
• Publication Number:
  US 20180180548A1
• Time in Patent Office: 392 Days
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 2021/6478 Special lenses
• CPC Class Codes: G01N 2021/7756 Sensor type
• CPC Class Codes: G01N 2021/7786 Fluorescence
• 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 21/78 producing a change of colour
• CPC Class Codes: G01N 2201/068 Optics, miscellaneous
• CPC Class Codes: G01N 2201/0873 Using optically integrated constructions
• CPC Class Codes: G02B 2006/12102 Lens
• CPC Class Codes: G02B 2006/12109 Filter
• CPC Class Codes: G02B 27/4238 in optical recording or readout devices optical pick-up devices such as for CD, DVD or BD reader or recorder using diffraction optics G11B7/1353
• CPC Class Codes: G02B 27/4244 in wavelength selecting devices spectrometry G01J
• CPC Class Codes: G02B 5/1895 such optical elements having dioptric power
• CPC Class Codes: G02B 5/201 in the form of arrays
• CPC Class Codes: G02B 5/285 comprising deposited thin solid films G02B5/281 - G02B5/289 take precedence; multilayered film filters for fibre optic multiplexing G02B6/29361
• CPC Class Codes: G02B 6/132 by deposition of thin films
• CPC Class Codes: G02B 6/136 by etching
• CPC Class Codes: H01L 27/14621 : Colour filter arrangements
• CPC Class Codes: H01L 27/14627 : Microlenses
• CPC Class Codes: H01L 27/14685 : Process for coatings or optical elements

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 devices allow the highly sensitive discrimination of optical signals using features such as spectra, amplitude, and time resolution, or combinations thereof. The devices include an integrated diffractive beam shaping element that provides for the spatial separation of light emitted from the optical reactions.

Claims

1. An array of integrated analytical devices, each device comprising:

a nanoscale emission volume;

a detector layer optically coupled to the nanoscale emission volume, wherein the detector layer comprises two sensing regions, each sensing region having an edge adjacent to an edge of another sensing region or a corner adjacent to a corner of another sensing region; and

a diffractive beam shaping element disposed between the nanoscale emission volume and the detector layer;

wherein the nanoscale emission volume is positioned above the adjacent edges or the adjacent corners of the two sensing regions;

wherein light is emitted from the nanoscale emission volume by a plurality of emitters within the emission volume; and

wherein the diffractive beam shaping element spatially separates the light emitted from the nanoscale emission volume and directs the spatially-separated light to the two sensing regions.

2. The array of claim 1, wherein the diffractive beam shaping element is a hybrid lens.

3. The array of claim 1, wherein the diffractive beam shaping element comprises a Fresnel lens.

4. The array of claim 1, further comprising a color filtration layer disposed between the diffractive beam shaping element and the detector layer.

5. The array of claim 4, wherein the color filtration layer comprises a plurality of color filtration elements, each color filtration element optically coupled to one detector layer sensing region and specific for a range of light wavelengths.

6. The array of claim 1, further comprising:

an excitation source optically coupled to the nanoscale emission volume.

7. The array of claim 6, further comprising:

at least one aperture layer disposed between the excitation source and the detector layer.

8. The array of claim 6, further comprising:

a laser rejection filter layer disposed between the excitation source and the detector layer.

9. The array of claim 1, further comprising:

a waveguide excitation source optically coupled to the nanoscale emission volume.

10. The array of claim 9, wherein the nanoscale emission volume is aligned directly above the waveguide excitation source.

11. The array of claim 9, wherein the sensing regions are collinear with respect to the waveguide excitation source.

12. The array of claim 9, wherein the sensing regions are not collinear with respect to the waveguide excitation source.

13. The array of claim 9, wherein the sensing regions are diagonal with respect to the waveguide excitation source.

14. The array of claim 9, wherein the sensing regions are perpendicular with respect to the waveguide excitation source.

15. The array of claim 9, comprising a plurality of waveguide excitation sources, optically coupled to a plurality of nanoscale emission volumes.

16. The array of claim 15, wherein the plurality of waveguide excitation sources are oriented parallel to one another.

17. The array of claim 15, wherein the plurality of nanoscale emission volumes are aligned directly above the plurality of waveguide excitation sources.

18. The array of claim 17, wherein the nanoscale emission volumes are arranged in a regular grid pattern.

19. The array of claim 17, wherein the nanoscale emission volumes are arranged in an offset grid pattern.

20. The array of claim 15, wherein the sensing regions are collinear with respect to the waveguide excitation sources.

21. The array of claim 15, wherein the sensing regions are not collinear with respect to the waveguide excitation sources.

22. The array of claim 21, wherein the sensing regions are diagonal with respect to the waveguide excitation sources.

23. The array of claim 22, wherein the sensing regions associated with a first waveguide excitation source are +45°

diagonal with respect to the first waveguide excitation source and the detector sensing regions associated with an adjacent second waveguide excitation source are −

45°

diagonal with respect to the adjacent second waveguide excitation source.

24. The array of claim 21, wherein the sensing regions are perpendicular with respect to the waveguide excitation sources.

25. The array of claim 1, wherein the detector layer is integral to the device.

26. The array of claim 1, wherein the detector layer is not integral to the device.

27. The array of claim 1, wherein the diffractive beam shaping element collimates the light emitted from the emission volume.

28. The array of claim 1, wherein the sensing regions are rectangular.

29. The array of claim 1, wherein the detector layer is part of a CMOS sensor.

30. The array of claim 1, further comprising an analyte disposed within the nanoscale emission volume.

31. The array of claim 30, wherein the analyte comprises a biological sample.

32. The array of claim 31, wherein the biological sample comprises a nucleic acid.

33. The array of claim 31, wherein the biological sample comprises a polymerase enzyme.

34. The array of claim 1, wherein the array comprises at least 1,000, at least 10,000, at least 100,000, at least 1,000,000, or at least 10,000,000 nanoscale emission volumes.