# US 10,502,684 B2 · Integrated device with external light source for probing detecting and analyzing molecules

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- Number: US 10,502,684 B2
- Document ID: US10502684B2
- Status: Granted
- Kind: B2
- Application number: 16/354,839
- Filed: 2019-03-15
- Published: 2019-07-11
- Granted: 2019-12-10
- Earliest claimed: 2014-08-08
- Assignees: Quantum-Si Incorporated
- Applicants: Quantum-Si Incorporated
- Inventors: Jonathan M. Rothberg; Ali Kabiri; Jason W. Sickler; Brett J. Gyarfas; Jeremy Lackey; Gerard Schmid; Lawrence C. West; Keith G. Fife; Benjamin Cipriany; Farshid Ghasemi
- Web page: https://patentgrep.com/patent/US10502684B2

## CPC

- G01N 21/6408: {with measurement of decay time, time resolved fluorescence}
- C12Q 1/6869: Methods for sequencing
- C12Q 1/6874: involving nucleic acid arrays, e.g. sequencing by hybridisation
- 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)}
- G01N 21/6454: {using an integrated detector array}
- G01N 21/648: {using evanescent coupling or surface plasmon coupling for the excitation of fluorescence}
- G01N 2021/6419: {Excitation at two or more wavelengths}
- G01N 2021/6421: {Measuring at two or more wavelengths}
- G01N 2021/6439: {with indicators, stains, dyes, tags, labels, marks}
- G01N 2021/6441: {with two or more labels}
- G01N 2021/6463: {Optics}
- G01N 2021/6471: {Special filters, filter wheel}
- G01N 2201/064: Stray light conditioning
- G01N 2201/0696: Pulsed
- G01N 2201/08: Optical fibres; light guides
- G01N 2201/12: Circuits of general importance; Signal processing
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## 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

### Claim 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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 3)

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

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 6)

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.

### Claim 8 (depends on 7)

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.

### Claim 9 (depends on 1)

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