Scanning apparatus and methods useful for detection of chemical and biological analytes

• US 10,501,796 B2
• Filed: 09/25/2018
• Issued: 12/10/2019
• Est. Priority Date: 08/15/2017
• Status: Active Grant

• Current Assignee: Pacific Bioscience of California Incorporated (L'Oreal SA)
• Original Assignee: Omniome, Inc.
• Inventors: Buermann, Dale, Erickstad, Michael John, McGinley, Rebecca, Nemiroski, Alex, Rapoport, Harry Scott, Oliphant, Arnold
• Primary Examiner(s): Warden, Jill A
• Application Number:
  US16/141,896
• Publication Number:
  US 20190055598A1
• Time in Patent Office: 441 Days
• Field of Search: 436518, 436823
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/527 for a plurality of reagents
• CPC Class Codes: B01L 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B01L 9/52 Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 2021/0375 Slidable cells
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 21/03 Cuvette constructions
• CPC Class Codes: G01N 21/05 Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 21/13 Moving of cuvettes or solid samples to or from the investigating station handling materials for automatic analysis G01N35/00
• 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 21/645 Specially adapted constructive features of fluorimeters

Abstract

An apparatus can include a vessel, a reference surface, a preload, a scan actuator, and a transmitter. The reference surface can form a structural loop with a detector. The preload can be configured to urge the vessel to contact an area on the reference surface. The scan actuator can be configured to slide the vessel along the reference surface in a scan dimension. The transmitter can be configured to direct signal from the vessel to a detector and/or direct energy from an energy source to the vessel, when the vessel is urged by the preload to contact the reference surface.

Claims

1. A method of scanning a vessel, comprising

(a) providing a detection apparatus that comprises

(i) a vessel that comprises analytes;

(ii) a detector

(iii) a reference surface that forms a structural loop with the detector; and

(iv) a preload;

(b) examining a first subset of the analytes in the vessel while applying the preload to a first portion of the vessel but not a second portion of the vessel, wherein the preload facilitates contact between a first region of the vessel and the reference surface to position the first subset of analytes to occupy an area in an xy plane that is detected by the detector;

(c) translating the vessel along the reference surface; and

(d) examining a second subset of the analytes in the vessel while applying the preload to the second portion of the vessel but not the first portion of the vessel, wherein the preload facilitates contact between a second region of the vessel and the reference surface to position the second subset of the analytes to occupy the area in the xy plane that is detected by the detector.

2. The method of claim 1, wherein the preload is configured to facilitate contact between the vessel and the reference surface while the vessel is examined and while the vessel is translated.

3. The method of claim 1, wherein the preload acts in opposition to pressurized liquid to position the vessel while the vessel is examined.

4. The method of claim 1, wherein the vessel comprises a lumen and a wall, wherein the internal surface of the wall contacts the lumen.

5. The method of claim 4, wherein the analytes are arrayed on the internal surface of the vessel.

6. The method of claim 4, wherein the analytes are within the lumen of the vessel.

7. The method of claim 1, wherein the examining comprises acquiring optical signals produced by the analytes.

8. The method of claim 7, wherein the detection apparatus further comprises an objective that is configured to transmit the optical signals from the vessel to a camera.

9. The method of claim 8, further comprising focusing the objective by changing the relative distance between the objective and the preload in a direction that is orthogonal to the xy plane.

10. The method of claim 1, wherein the translating comprises contacting a rotating gear with perforations on the vessel or on a cartridge that holds the vessel.

11. The method of claim 1, wherein the translating comprises magnetic interactions of a linear actuator with a magnetic or ferromagnetic material on the vessel or on a cartridge that holds the vessel.

12. The method of claim 1, wherein the preload facilitates contact between the vessel and the reference surface during the translating.

13. The method of claim 1, wherein the analytes in the vessel comprise nucleic acids and wherein the scanning of the vessel is carried out in a method of sequencing the nucleic acids.

14. The method of claim 13, wherein the sequencing of the nucleic acids further comprises delivering polymerases and nucleotides to the vessel.

15. The method of claim 14, wherein the polymerases and nucleotides are delivered in a plurality of repeated cycles, wherein the repeated cycles comprise the scanning of the vessel.

16. The method of claim 13, wherein the nucleic acids are labeled with fluorescent labels during the method of sequencing.

17. The method of claim 16, wherein the fluorescent labels are excited via radiation passing through the objective and wherein fluorescent emission from the labels is detected through the objective.

18. The method of claim 1, wherein the examining is carried out using an array of lenses that is configured to transmit optical signals from an array of sites in the vessel to a detector.

19. The method of claim 18, wherein each lens in the array of lenses is configured to observe a single site in an array of sites.

20. The method of claim 1, wherein a computer processing unit implements executable instructions to perform operations (b) through (d).