Integrated device with external light source for probing detecting and analyzing molecules

• US 10,502,684 B2
• Filed: 03/15/2019
• Issued: 12/10/2019
• 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, West, Lawrence C., Fife, Keith G., Cipriany, Benjamin, Ghasemi, Farshid
• Primary Examiner(s): Ayub, Hina F
• Application Number:
  US16/354,839
• Publication Number:
  US 20190212265A1
• Time in Patent Office: 270 Days
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• 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 2021/6441 with two or more labels
• CPC Class Codes: G01N 2021/6463 Optics
• CPC Class Codes: G01N 2021/6471 Special filters, filter wheel
• 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 21/6454 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 2201/064 Stray light conditioning
• CPC Class Codes: G01N 2201/0696 Pulsed
• CPC Class Codes: G01N 2201/08 Optical fibres; light guides
• CPC Class Codes: G01N 2201/12 Circuits of general importance; Signal processing

Abstract

System and methods for analyzing single molecules and performing nucleic acid sequencing. An integrated device includes multiple pixels with sample wells configured to receive a sample, which when excited, emits radiation. The integrated device includes at least one waveguide configured to propagate excitation energy to the sample wells from a region of the integrated device configured to couple with an excitation energy source. A pixel may also include at least one element for directing the emission energy towards a sensor within the pixel. The system also includes an instrument that interfaces with the integrated device. The instrument may include an excitation energy source for providing excitation energy to the integrated device by coupling to an excitation energy coupling region of the integrated device. One of multiple markers distinguishable by temporal parameters of the emission energy may label the sample and configuration of the sensor within a pixel may allow for detection of a temporal parameter associated with the marker labeling the sample.

Claims

1. An integrated device comprising:

a sample well arranged on a surface of the device and configured to receive a sample;

a waveguide configured to propagate a plurality of pulses of optical excitation energy to the sample well; and

a sensor, positioned to receive light from the sample well, that aggregates into at least two time bins charge carriers of received photons of luminescence emitted by the sample.

2. The integrated device of claim 1 wherein the sensor identifies the sample.

3. The integrated device of claim 1 wherein the sample is a biological sample.

4. The integrated device of claim 3 wherein the biological sample comprises a target nucleic acid molecule.

5. The integrated device of claim 1 wherein the sensor is further configured to generate a signal indicative of an intensity of the emitted luminescence.

6. The integrated device of claim 1 further including a grating coupler, optically coupled to the waveguide.

7. The integrated device of claim 6 further including a first monitoring sensor that assists in aligning to the grating coupler a beam of optical excitation energy through alignment monitoring.

8. The integrated device of claim 7 further including a second monitoring sensor that further assists in aligning to the grating coupler the beam of optical excitation energy through monitoring power of optical excitation energy.

9. The integrated device of claim 1 wherein the sensor includes at least two storage regions that correspond to the at least two time bins.