Methods and systems for analyte detection and analysis

Patent metadata

Field	Value
Publication number	US-12480938-B2
Application number	US-202418776046-A
Country	US
Kind code	B2
Filing date	Jul 17, 2024
Priority date	Nov 17, 2017
Publication date	Nov 25, 2025
Grant date	Nov 25, 2025

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 plurality of biological analytes, comprising:
(a) rotating a substrate affixed to a chuck about a rotational axis, wherein the substrate comprises a substantially planar surface comprising the plurality of biological analytes immobilized thereto, wherein a fluid outlet and an objective are not in contact with the substrate and are respectively disposed at a first location and a second location above the substantially planar surface of the substrate; (b) dispensing a solution to the substantially planar surface of the substrate, using the fluid outlet at the first location, to contact at least a subset of the plurality of biological analytes, wherein the solution disperses radially outwards from a location of dispense, corresponding to the first location of the fluid outlet, on the substantially planar surface relative to the rotational axis during or subsequent to rotation of the substrate; and (c) imaging the substantially planar surface of the substrate using the objective at the second location to detect one or more signals or signal changes, or lack thereof, from the substrate to process a biological analyte of the plurality of biological analytes.

2 . The method of claim 1 , wherein the substrate is affixed to a vacuum chuck.

3 . The method of claim 1 , wherein the dispensing in (b) generates a layer of the solution over the plurality of biological analytes immobilized to the substantially planar surface of the substrate.

4 . The method of claim 3 , wherein the layer of the solution is engineered to have a predetermined thickness.

5 . The method of claim 1 , wherein the substrate is textured or patterned.

6 . The method of claim 1 , wherein the biological analyte of the plurality of biological analytes is coupled to a bead, which bead is immobilized to the substrate.

7 . The method of claim 6 , wherein multiple additional biological analytes of the plurality of biological analytes are coupled to the bead, and wherein the multiple additional biological analytes and the biological analyte are copies of a template analyte and have sequence homology to one another.

8 . The method of claim 1 , wherein the biological analyte of the plurality of biological analytes comprises a nucleic acid molecule.

9 . The method of claim 8 , wherein the solution comprises a plurality of nucleotides or nucleotide analogs, and wherein the method further comprises, subsequent to (b), incorporating at least one nucleotide or nucleotide analog of the plurality of nucleotides or nucleotide analogs into a growing strand that is hybridized and complementary to the nucleic acid molecule in a primer extension reaction.

10 . The method of claim 9 , wherein the plurality of nucleotides or nucleotide analogs comprises nucleotides or nucleotide analogs of a single canonical base type.

11 . The method of claim 8 , wherein the one or more signals or signal changes, or lack thereof, detected in (c) are processed to sequence at least a portion of the nucleic acid molecule.

12 . The method of claim 1 , wherein the detecting in (c) comprises continuously scanning the substantially planar surface of the substrate during relative movement of the substrate with respect to the objective.

13 . The method of claim 12 , wherein the relative movement comprises rotational movement of the substrate with respect to the objective.

14 . The method of claim 1 , wherein the plurality of biological analytes is immobilized to at least 1,000,000,000 individually addressable locations on the substrate.

15 . The method of claim 1 , wherein a plurality of fluid outlets that are not in contact with the substrate are disposed at additional locations above the substantially planar surface of the substrate, and wherein each of the plurality of fluid outlets dispenses a different type of solution to the substantially planar surface of the substrate.

16 . The method of claim 1 , further comprising moving the substrate during the dispensing of the solution by the fluid outlet in (b), wherein the moving comprises a movement towards or away from the fluid outlet.

17 . The method of claim 1 , further comprising moving the substrate during the imaging in (c), wherein the moving comprises a movement towards or away from the objective.

18 . The method of claim 1 , wherein the substrate is rotated during the dispensing in (b) and during the imaging in (c), and wherein the substrate is rotated at different speeds.

19 . The method of claim 18 , wherein the substrate is rotated at higher angular velocity during the dispensing in (b) than during the imaging in (c).

20 . The method of claim 1 , wherein the objective performs a non-linear scan of the substantially planar surface of the substrate.

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

• G01Q10/04

  Fine scanning or positioning · 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

• G01N2001/2291

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

• G01N35/1002

  Reagent dispensers · CPC title

• G01N35/00069

  whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk · CPC title