# US 2023/0265485 A1 · Nucleic acid analysis device, and nucleic acid analysis method

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- Number: US 2023/0265485 A1
- Document ID: US20230265485A1
- Status: Published application
- Kind: A1
- Application number: 18/168,601
- Filed: 2023-02-14
- Published: 2023-08-24
- Earliest claimed: 2022-02-18
- Assignees: Canon Kabushiki Kaisha
- Applicants: Canon Kabushiki Kaisha
- Inventors: Sota TORII
- Web page: https://patentgrep.com/patent/US20230265485A1

## CPC

- C12Q 1/6806: Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence)
- B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces}
- B01L 3/502784: {specially adapted for droplet or plug flow, e.g. digital microfluidics}
- C12Q 1/68: involving nucleic acids
- 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 21/6452: {Individual samples arranged in a regular 2D-array, e.g. multiwell plates}
- B01L 2200/16: Reagents, handling or storing thereof
- B01L 2300/02: Identification, exchange or storage of information
- B01L 2300/087: Multiple sequential chambers
- G01N 2021/6439: {with indicators, stains, dyes, tags, labels, marks}
- 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
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- 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

Provided is a nucleic acid analysis device with which artifact components are reduced. The nucleic acid analysis device includes a distribution unit, a labeling unit, an information acquisition unit, and an information processing unit. The information processing unit includes an information extraction unit, an artifact component determination unit, a correction unit, and an identifying unit. The artifact component determination unit determines an artifact component from extracted information corresponding to a portion other than a plurality of individual separated compartments. The correction unit uses the artifact component to correct extracted information corresponding to the plurality of individual separated compartments.

## Claims

### Claim 1

A nucleic acid analysis device comprising:
a distribution unit;
a labeling unit;
an information acquisition unit; and
an information processing unit,
wherein the information processing unit includes:
an information extraction unit;
an artifact component determination unit;
a correction unit; and
an identifying unit,
wherein the distribution unit is configured to distribute a sample including nucleic acid and a reagent to a plurality of individual separated compartments to form a set including the plurality of individual separated compartments and a portion other than the plurality of individual separated compartments,
wherein the labeling unit is configured to cause a change in each of the plurality of individual separated compartments to which the sample including target nucleic acid is distributed so that the each of the plurality of individual separated compartments to which the sample including target nucleic acid is distributed and each of the plurality of individual separated compartments to which a sample excluding target nucleic acid is distributed are distinguishable from each other by the identifying unit,
wherein the information acquisition unit is configured to acquire information corresponding to the set,
wherein the information extraction unit is configured to extract, from the acquired information corresponding to the set, each of information corresponding to the plurality of individual separated compartments and information corresponding to the portion other than the plurality of individual separated compartments,
wherein the artifact component determination unit is configured to determine an artifact component from the extracted information corresponding to the portion other than the plurality of individual separated compartments,
wherein the correction unit is configured to use the artifact component to correct the extracted information corresponding to the plurality of individual separated compartments, and
wherein the identifying unit is configured to identify, based on the corrected information corresponding to the plurality of individual separated compartments, each of the plurality of individual separated compartments in which a magnitude of the change exceeds a predetermined threshold.

### Claim 2 (depends on 1)

The nucleic acid analysis device according to claim 1,
wherein the change comprises generation of fluorescence, and
wherein the information corresponding to the set which is acquired by the information acquisition unit includes a fluorescent image of the set.

### Claim 3 (depends on 1)

The nucleic acid analysis device according to claim 1, wherein the information corresponding to the set includes a bright-field image of the set.

### Claim 4 (depends on 1)

The nucleic acid analysis device according to claim 1 wherein the information extraction unit is configured to use a default mask based on a shape of each of the plurality of individual separated compartments in the set.

### Claim 5 (depends on 1)

The nucleic acid analysis device according to claim 1,
wherein the plurality of individual separated compartments comprise wells including the sample including nucleic acid and the reagent that have been distributed, and
wherein the set comprises a well plate including the wells.

### Claim 6 (depends on 5)

The nucleic acid analysis device according to claim 5, wherein the portion other than the plurality of individual separated compartments includes a part of a region other than the wells of the well plate.

### Claim 7 (depends on 1)

The nucleic acid analysis device according to claim 1,
wherein the plurality of individual separated compartments comprise liquid droplets including the sample including nucleic acid and the reagent that have been distributed, and
wherein the set includes the liquid droplets and a dispersion medium.

### Claim 8 (depends on 7)

The nucleic acid analysis device according to claim 7, wherein the portion other than the plurality of individual separated compartments includes a part of the dispersion medium.

### Claim 9 (depends on 1)

The nucleic acid analysis device according to claim 1, wherein the artifact component determination unit is configured to determine the artifact component through estimation involving approximation using a basis function.

### Claim 10 (depends on 9)

The nucleic acid analysis device according to claim 9, wherein the basis function comprises a linear function.

### Claim 11 (depends on 1)

The nucleic acid analysis device according to claim 1, wherein the artifact component determination unit is configured to determine the artifact component through estimation using a regularization term.

### Claim 12 (depends on 1)

The nucleic acid analysis device according to claim 1, wherein the artifact component determination unit is configured to determine the artifact component through estimation involving approximation using a polynomial.

### Claim 13 (depends on 1)

The nucleic acid analysis device according to claim 1, wherein the artifact component determination unit is configured to determine the artifact component through calculation using binning.

### Claim 14 (depends on 2)

The nucleic acid analysis device according to claim 2,
wherein the information and the artifact component each include information on coordinates and a brightness at the coordinates, and
wherein the correction unit is configured to perform one of:
subtracting the brightness of the artifact component from the brightness of the information corresponding to the plurality of individual separated compartments; or
dividing the brightness of the information corresponding to the plurality of individual separated compartments by the brightness of the artifact component.

### Claim 15 (depends on 2)

The nucleic acid analysis device according to claim 2,
wherein the reagent contains an effector protein, crRNA to be bound to the target nucleic acid, and a reporter molecule,
wherein the crRNA is bound to the target nucleic acid to activate the effector protein, and
wherein the labeling unit is configured to modify the reporter molecule by the activated effector protein to generate fluorescence.

### Claim 16

A nucleic acid analysis method comprising:
a distribution step;
a labeling step;
an information acquisition step;
an information extraction step;
an artifact component determination step;
a correction step; and
an identifying step,
wherein the distribution step includes distributing a sample including nucleic acid and a reagent to a plurality of individual separated compartments to form a set including the plurality of individual separated compartments and a portion other than the plurality of individual separated compartments,
wherein the labeling step includes causing a change in each of the plurality of individual separated compartments to which the sample including target nucleic acid is distributed so that the each of the plurality of individual separated compartments to which the sample including target nucleic acid is distributed and each of the plurality of individual separated compartments to which a sample excluding target nucleic acid is distributed are distinguishable from each other in the identifying step,
wherein the information acquisition step includes acquiring information corresponding to the set,
wherein the information extraction step includes extracting, from the acquired information corresponding to the set, each of information corresponding to the plurality of individual separated compartments and information corresponding to the portion other than the plurality of individual separated compartments,
wherein the artifact component determination step includes determining an artifact component from the extracted information corresponding to the portion other than the plurality of individual separated compartments,
wherein the correction step includes using the artifact component to correct the extracted information corresponding to the plurality of individual separated compartments, and
wherein the identifying step includes identifying, based on the corrected information corresponding to the plurality of individual separated compartments, each of the plurality of individual separated compartments in which a magnitude of the change exceeds a predetermined threshold.

### Claim 17 (depends on 16)

A non-transitory storage medium storing a program for causing a computer to execute the nucleic acid analysis method of claim 16.
