Optical system and assay chip for probing, detecting and analyzing molecules

• US 10,371,634 B2
• Filed: 01/29/2018
• Issued: 08/06/2019
• Est. Priority Date: 08/08/2014
• Status: Active Grant

• Current Assignee: Quantum-Si Incorporated
• Original Assignee: Quantum-Si Incorporated
• Inventors: Rothberg, Jonathan M., Kabiri, Ali, Sickler, Jason W., Gyarfas, Brett J., Lackey, Jeremy, Schmid, Gerard, Glenn, Paul E., West, Lawrence C., Cipriany, Benjamin, Fife, Keith G.
• Primary Examiner(s): Decenzo, Shawn
• Application Number:
  US15/882,776
• Publication Number:
  US 20180231465A1
• Time in Patent Office: 554 Days
• Field of Search: None
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• CPC Class Codes: G01N 2021/6419 Excitation at two or more wavelengths
• CPC Class Codes: G01N 2021/6421 Measuring at two or more wavelengths
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved 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 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 2201/0446 Multicell plate, sequential
• CPC Class Codes: G01N 2201/062 LED's

Abstract

Apparatus and methods for analyzing single molecule and performing nucleic acid sequencing. An apparatus can include an assay chip that includes multiple pixels with sample wells configured to receive a sample, which, when excited, emits emission energy; at least one element for directing the emission energy in a particular direction; and a light path along which the emission energy travels from the sample well toward a sensor. The apparatus also includes an instrument that interfaces with the assay chip. The instrument includes an excitation light source for exciting the sample in each sample well; a plurality of sensors corresponding the sample wells. Each sensor may detect emission energy from a sample in a respective sample well. The instrument includes at least one optical element that directs the emission energy from each sample well towards a respective sensor of the plurality of sensors.

Claims

1. An instrument configured to interface with an assay chip, the instrument comprising:

an optical housing having an opening;

at least one pulsed excitation light source configured to emit pulses of excitation energy, wherein at least a portion of the pulses of excitation energy is directed towards the opening of the optical housing; and

at least one magnetic alignment component configured to mechanically position the assay chip on the outside of the optical housing relative to the opening such that the assay chip receives at least a portion of the excitation energy exiting the opening when the assay chip interfaces with the instrument.

2. The instrument of claim 1, wherein the at least one magnetic alignment component is configured to mechanically position the assay chip to at least partially overlap with the opening when the assay chip interfaces with the instrument.

3. The instrument of claim 1, wherein the instrument further comprises at least one optical component configured to direct excitation energy emitted by the at least one pulsed excitation light source towards the assay chip when the assay chip interfaces with the instrument.

4. The instrument of claim 1, wherein the instrument further comprises at least one optical component configured to reflect excitation energy emitted by the at least one pulsed excitation light source towards the opening and transmit emission energy from the assay chip.

5. The instrument of claim 1, wherein the instrument further comprises a plurality of sensors, wherein individual sensors of the plurality of sensors are positioned to receive light from a sample well of the assay chip when the assay chip interfaces with the instrument.

6. A system comprising:

an optical housing having an opening;

at least one pulsed excitation light source positioned within the optical housing and configured to emit pulses of excitation energy;

at least one optical component positioned within the optical housing and configured to direct at least a portion of the emitted pulses of excitation energy towards the opening; and

at least one spring-loaded alignment component positioned on a surface of the optical housing.

7. The system of claim 6, wherein the at least one spring-loaded alignment component is configured to mechanically position an assay chip on an outside surface of the optical housing relative to the opening such that the assay chip receives at least a portion of the excitation energy exiting the opening.

8. The system of claim 6, wherein the system further comprises a plurality of sensors positioned within the optical housing.

9. The system of claim 6, wherein the system further comprises a plurality of sensors having individual sensors configured to detect a detection time of incident light.

10. The system of claim 6, wherein the system further comprises a plurality of sensors and at least one optical element configured to direct light towards the plurality of sensors.

11. The system of claim 6, further comprising:

an optical system configured to control a cross-sectional shape of a beam of excitation energy emitted by the at least one pulsed excitation light source.

12. The system of claim 6, further comprising:

an optical system configured to control a polarization of a beam of excitation energy emitted by the at least one pulsed excitation light source.

13. The system of claim 6, further comprising:

an optical system configured to control a pulse length of the pulses of excitation energy emitted by the at least one pulsed excitation light source.

14. The system of claim 6, further comprising:

circuitry configured to generate time-varying electrical signals, wherein the at least one pulsed excitation light source is configured to emit pulses of excitation energy in response to receiving the time-varying electrical signals.

15. The system of claim 6, further comprising:

at least one user interface configured to receive user input indicating a control command for operating the system.

16. The system of claim 6, further comprising:

at least one user interface configured to present an indication of performance of the system.

17. An instrument comprising:

an optical housing having an opening;

at least one pulsed excitation light source positioned within the optical housing and configured to emit pulses of excitation energy, wherein at least a portion of the emitted pulses of excitation energy is directed to exit through the opening; and

at least one pneumatic alignment component positioned on a surface of the optical housing and proximate to the opening.

18. The instrument of claim 17, wherein the at least one pneumatic alignment component is configured to mechanically position an assay chip on an outside surface of the optical housing relative to the opening such that the assay chip receives at least a portion of the excitation energy exiting the opening.

19. The instrument of claim 17, wherein the at least one pneumatic alignment component includes a plurality of pneumatic alignment components positioned around the opening.

20. The instrument of claim 17, wherein the at least one pneumatic alignment component is configured to attach to the optical housing by suction.