Methods and systems for analyte detection and analysis

Patent metadata

Field	Value
Publication number	US-11499962-B2
Application number	US-202016862196-A
Country	US
Kind code	B2
Filing date	Apr 29, 2020
Priority date	Nov 17, 2017
Publication date	Nov 15, 2022
Grant date	Nov 15, 2022

Abstract

Provided are systems and methods for analyte detection and analysis. A system can comprise an open substrate configured to rotate. The open substrate can comprise an array of immobilized analytes. A solution comprising a plurality of probes may be directed, via centrifugal force, across the array during rotation of the substrate, to couple at least one of the plurality of probes with at least one of the analytes to form a bound probe. A detector can be configured to detect a signal from the bound probe via continuous rotational area scanning of the substrate.

First claim

What is claimed is:

1. A method for processing a biological analyte, comprising:
(a) generating a thin film adjacent to a substrate having immobilized thereto said biological analyte, wherein said thin film comprises a solution comprising a plurality of probes, wherein said thin film is exposed to a medium comprising a gas, and wherein at least one probe of said plurality of probes couples to said biological analyte; and
(b) detecting one or more signals or signal changes from said biological analyte having said at least one probe coupled thereto.

2. The method of claim 1 , wherein said thin film is engineered to have a predetermined thickness.

3. The method of claim 1 , wherein said thin film has a thickness of at least about 1 micrometer (μm).

4. The method of claim 1 , wherein said thin film has a thickness of between 1 micrometer (μm) and 100 micrometers.

5. The method of claim 1 , wherein said generating in (a) comprises dispensing said solution to said substrate at one or more locations of said substrate.

6. The method of claim 5 , further comprising subjecting said substrate to relative movement with respect to a dispensing unit configured to dispense said solution prior to or during said dispensing of said solution to generate said thin film.

7. The method of claim 6 , wherein said relative movement comprises rotational motion of said substrate.

8. The method of claim 6 , wherein said relative movement comprises non-rotational motion of said substrate.

9. The method of claim 1 , wherein said substrate is substantially planar.

10. The method of claim 1 , wherein said substrate is textured or patterned.

11. The method of claim 1 , wherein said substrate comprises an array of individually addressable locations, and wherein said biological analyte is immobilized to an individually addressable location of said array.

12. The method of claim 11 , wherein said array has immobilized thereto one or more additional biological analytes at different individually addressable locations.

13. The method of claim 1 , wherein said biological analyte is coupled to a bead, which bead is immobilized to said substrate.

14. The method of claim 13 , wherein said bead comprises a plurality of biological analytes, including said biological analyte, attached thereto.

15. The method of claim 14 , wherein said plurality of biological analytes have sequence homology to one another.

16. The method of claim 1 , wherein said biological analyte is immobilized adjacent to said substrate through one or more binders.

17. The method of claim 16 , wherein said substrate comprises at least 100,000 binders, wherein a binder of said at least 100,000 binders immobilizes said biological analyte to said substrate.

18. The method of claim 1 , wherein said biological analyte is a nucleic acid molecule.

19. The method of claim 18 , further comprising, based at least in part on said one or more signals or signal changes, determining a sequence of at least a portion of said nucleic acid molecule.

20. The method of claim 18 , further comprising, based at least in part on said one or more signals or signal changes, identifying a presence of a homopolymer sequence in said nucleic acid molecule.

21. The method of claim 18 , wherein said plurality of probes comprises a plurality of nucleotides or nucleotide analogs, and wherein said at least one probe is at least one nucleotide or nucleotide analog from said plurality of nucleotides or nucleotide analogs.

22. The method of claim 21 , wherein (a) comprises incorporating said at least one nucleotide or nucleotide analog into a growing strand that is complementary to said nucleic acid molecule.

23. The method of claim 18 , wherein said plurality of probes comprises a plurality of oligonucleotide molecules, and wherein said at least one probe is at least one oligonucleotide molecule of said plurality of oligonucleotide molecules.

24. The method of claim 23 , wherein (a) comprises hybridizing said at least one oligonucleotide molecule to said nucleic acid molecule.

25. The method of claim 1 , wherein said detecting in (b) comprises continuously scanning said substrate during relative movement of said substrate with respect to a detection system configured to perform said detecting.

26. The method of claim 1 , wherein said one or more signals comprise one or more optical signals or optical signal changes.

27. The method of claim 1 , further comprising, subsequent to (b), (i) generating an additional thin film adjacent to said substrate, wherein said thin film comprises an additional solution comprising an additional plurality of probes, wherein said additional plurality of probes is different from said plurality of probes, wherein at least one additional probe of said additional plurality of probes couples to said biological analyte, and (ii) detecting one or more additional signals or additional signal changes from said biological analyte having said at least one additional probe coupled thereto, to analyze said biological analyte.

28. The method of claim 27 , wherein said plurality of probes comprises a first plurality of nucleotides or nucleotide analogs of a first canonical base type and wherein said additional plurality of probes comprises a second plurality of nucleotides or nucleotide analogs of a second canonical base type different than said first canonical base type.

29. The method of claim 1 , wherein said plurality of probes comprises a first plurality of nucleotides or nucleotide analogs of a first canonical base type and a second plurality of nucleotides or nucleotide analogs of a second canonical base type different than said first canonical base type.

Assignees

• Ultima Genomics Inc

Inventors

• Barbee Kristopher
• Beckett Nathan
• Pristinski Denis
• Schulte Derek
• Bartov Avishai
• Sullivan Jamie
• Brinza Dumitru
• Lakdawalla Abizar
• Menchen Steven
• Almogy Gilad
• Pratt Mark

Classifications

• G01N1/31 Primary

  Apparatus therefor · CPC title

• G01N2001/387

  mixing by blowing a gas, bubbling · CPC title

• G01N2001/2291

  Movable probes, e.g. swivelling, swinging · CPC title

• G01N1/02

  Devices for withdrawing samples {(sampling of foundation soil E02D1/04; collecting or conveying radioactive samples G01T7/00, e.g. G01T7/02, G01T7/08)} · CPC title

• G01Q10/04

  Fine scanning or positioning · CPC title