# US 2024/0201088 A1 · Optical systems for nucleic acid sequencing and methods thereof

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- Number: US 2024/0201088 A1
- Document ID: US20240201088A1
- Status: Published application
- Kind: A1
- Application number: 18/417,995
- Filed: 2024-01-19
- Published: 2024-06-20
- Earliest claimed: 2021-07-21
- Assignees: Element Biosciences, Inc.
- Applicants: Element Biosciences, Inc.
- Inventors: Arash GHORBANI; Russell HUDYMA; John BAILEY; Michael PREVITE
- Web page: https://patentgrep.com/patent/US20240201088A1

## CPC

- C12Q 1/6874: involving nucleic acid arrays, e.g. sequencing by hybridisation
- C12Q 1/6869: Methods for sequencing
- 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 21/6458: {Fluorescence microscopy (fluorescence microscopes per se G02B21/0076 and G02B21/16)}
- G01N 2021/0346: {Capillary cells; Microcells}
- G01N 2021/052: {Tubular type; cavity type; multireflective}
- 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 2021/6482: {Sample cells, cuvettes}
- 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
- 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)

## Abstract

Fluorescence imaging system designs are described that provide larger fields-of-view, increased spatial resolution, improved modulation transfer and image quality, higher spatial sampling frequency, faster transitions between image capture when repositioning the fields-of-view, improved imaging system duty cycle and a more compact system, and thus enable higher throughput image acquisition and analysis for genomics and other imaging applications at a lower cost.

## Claims

### Claim 1

A method, comprising:
(a) providing a system comprising:
(i) a flow cell comprising a sample,
(ii) a light source,
(iii) a detector comprising a plurality of pixels, and
(iv) a pixel shifter disposed in an optical path from the flow cell to the detector;
(b) illuminating the sample using the light source, wherein the illuminating generates a signal light corresponding to an identity of a portion of the sample;
(c) shifting the signal light across the plurality of pixels using the pixel shifter; and
(d) detecting, using the plurality of pixels, the signal light from the sample to generate data related to the identity of the portion of the sample.

### Claim 2 (depends on 1)

The method of claim 1, wherein the sample is a nucleic acid sample.

### Claim 3 (depends on 2)

The method of claim 2, wherein the portion of the nucleic acid sample comprises a nucleotide or a nucleic acid sequence, and further comprising using the data to identify the nucleotide or the nucleic acid sequence of the nucleic acid sample.

### Claim 4 (depends on 3)

The method of claim 3, wherein the nucleic acid sequence of the nucleic acid sample is determined, at least in part, by:
(i) contacting a labeled molecule to the nucleic acid sample, wherein the labeled molecule binds to the nucleic acid sample,
(ii) illuminating the labeled molecule bound to the nucleic acid sample using the light source, thereby generating light from the labeled molecule,
(iii) detecting, using the plurality of pixels, the light from the labeled molecule to generate the data, wherein the data corresponds to the light from the labeled molecule, and
(iv) processing the data to determine the identity of the portion of the nucleic acid sample bound to the labeled molecule.

### Claim 5 (depends on 4)

The method of claim 4, further comprising (v) removing the labeled molecule from the nucleic acid sample.

### Claim 6 (depends on 5)

The method of claim 5, further comprising (vi) repeating (i)-(v) for an additional labeled molecule that binds to another portion of the nucleic acid sample.

### Claim 7 (depends on 2)

The method of claim 2, further comprising binding one or more labels to the nucleic acid sample, wherein the one or more labels are configured to absorb the light from the light source and emit the signal light.

### Claim 8 (depends on 1)

The method of claim 1, wherein the flow cell comprises a plurality of interior surfaces.

### Claim 9 (depends on 8)

The method of claim 8, wherein the illuminating in (b) comprises illuminating at least two interior surfaces of the plurality of interior surfaces, and the detecting in (d) comprises detecting the signal light from the at least two interior surfaces of the plurality of interior surfaces.

### Claim 10 (depends on 8)

The method of claim 8, wherein the sample is coupled to at least one interior surface of the plurality of interior surfaces.

### Claim 11 (depends on 10)

The method of claim 10, wherein at least a portion of the sample is coupled to each interior surface of the plurality of interior surfaces.

### Claim 12 (depends on 1)

The method of claim 1, further comprising using a plurality of detectors comprising the detector to each detect a portion of the signal light from a plurality of portions of the signal light, wherein each portion of the plurality of portions of the signal light comprises a different wavelength from another portion of the plurality of portions of the signal light.

### Claim 13 (depends on 12)

The method of claim 12, further comprising using a plurality of pixel shifters comprising the pixel shifter to shift the plurality of portions of the signal light over each detector of the plurality of detectors.

### Claim 14 (depends on 12)

The method of claim 12, further comprising using a plurality of focusing elements disposed in an optical path of the signal light to focus the signal light onto the plurality of detectors.

### Claim 15 (depends on 1)

The method of claim 1, further comprising a plurality of light sources comprising the light source, wherein each light source of the plurality of light sources is used to illuminate the sample using a different wavelength of light from another light source of a plurality of light sources.

### Claim 16 (depends on 1)

The method of claim 1, wherein the signal light is a fluorescent signal light.

### Claim 17 (depends on 1)

The method of claim 1, wherein the flow cell comprises a curved surface with the sample coupled thereto.

### Claim 18 (depends on 1)

The method of claim 1, wherein the system has a numerical aperture (NA) of less than about 0.6.

### Claim 19 (depends on 1)

The method of claim 1, wherein the system has a field of view (FOV) of at least about 1 square millimeter (mm2).

### Claim 20 (depends on 1)

The method of claim 1, wherein the detector comprises a charge coupled device (CCD) detector.