IP Library Granted Patent US 12,723,982
Granted Patent B2
US 12,723,982 · App. 18/178,013 · Granted Sep 1, 2026

Cell analysis method and cell analysis system

Inventors: Yuichiro Iwamoto (Tokyo, JP); Akira Terao (Kanagawa, JP); Naomichi Matsuwaki (Tokyo, JP)
Assignee: Canon Kabushiki Kaisha
G01N21/6428B01L3/502761G01N2021/1765G01N2021/6439
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Quick Facts
Patent No.
US 12,723,982
App. No.
18/178,013
Granted
Sep 1, 2026
Kind
B2
Abstract

The cell analysis method includes: a first storage step of storing a first liquid containing a cell in a first tank; a second storage step of storing a second liquid containing a compound in a second tank; a first discharge step of discharging the first liquid to a plurality of portions on a substrate, to thereby form a plurality of first liquid droplets; a second discharge step of discharging the second liquid to the plurality of portions on the substrate in such a manner that the second liquid is allowed to be admixed with the first liquid droplets; a result acquisition step of acquiring results of a reaction between the cell and the compound; and an analysis step of analyzing the results acquired in the result acquisition step to specify a portion in which results satisfying predetermined criteria are obtained among the plurality of portions.

Claims (56)

1 . A cell analysis method comprising:

a first storage step of storing a first liquid containing a cell in a first tank;

a second storage step of storing a second liquid in a second tank, the second liquid containing a compound and being compatible with the first liquid;

a first discharge step of discharging the first liquid to a plurality of portions on a substrate through use of a first discharge portion connected to the first tank so as to allow liquid circulation, the plurality of portions capable of being specified based on addresses, to thereby form a plurality of first liquid droplets;

a second discharge step of discharging, based on the addresses of the plurality of portions to which the first liquid is discharged, the second liquid to the plurality of portions on the substrate through use of a second discharge portion in such a manner that the second liquid is allowed to be admixed with the first liquid droplets, the second discharge portion being connected to the second tank so as to allow liquid circulation;

a result acquisition step of acquiring results of a reaction between the cell and the compound caused by admixture of the first liquid droplets and the second liquid discharged from the second discharge portion;

an analysis step of analyzing the results acquired in the result acquisition step to specify an address of a portion in which results satisfying predetermined criteria are obtained among the plurality of portions; and

a collection step of collecting a coalesced droplet of a first liquid droplet containing the cell and the second liquid by aligning a collection portion with the portion on the substrate specified in the analysis step based on the address.

2 . The cell analysis method according to claim 1 , wherein each of the plurality of portions on the substrate includes a third liquid that is incompatible with both the first liquid and the second liquid,

wherein, in the first discharge step, the first liquid droplets are formed in the third liquid, and

wherein, in the second discharge step, the second liquid is discharged so as to form second liquid droplets in the third liquid where the first liquid droplets and the second liquid discharged from the second discharge portion are allowed to be admixed with each other through the first liquid droplet and the second liquid droplet contacting each other.

3 . The cell analysis method according to claim 1 , wherein the compound contained in the second liquid includes a plurality of kinds of compounds, and

wherein the cell analysis method further comprises an identification step of specifying a kind of the compound derived from the second liquid discharged to the portion specified in the analysis step.

4 . The cell analysis method according to claim 3 , wherein the plurality of kinds of compounds are each modified with a labeling substance so that the kind of the compound is uniquely identified, and

wherein, in the identification step, the kind of the compound is specified based on the labeling substance.

5 . The cell analysis method according to claim 4 , wherein the labeling substance is DNA.

6 . The cell analysis method according to claim 4 , wherein the labeling substance is a fluorescent substance.

7 . The cell analysis method according to claim 1 , wherein, in the second storage step, the second liquid is stored in a plurality of second tanks;

wherein, in the second discharge step, the second liquid is discharged through use of a plurality of second discharge portions connected respectively to the plurality of second tanks that are different from each other so as to allow liquid circulation;

wherein a kind of the compound contained in the second liquid varies among the second liquids stored respectively in the plurality of second tanks, and

wherein, in the second discharge step, whether to discharge the second liquid to each of the plurality of portions on the substrate is controlled regarding each of the plurality of second discharge portions.

8 . The cell analysis method according to claim 1 , wherein the first liquid contains a plurality of kinds of cells.

9 . The cell analysis method according to claim 1 , wherein, in the first storage step, the first liquid is stored in a plurality of first tanks,

wherein, in the first discharge step, the first liquid is discharged through use of a plurality of first discharge portions connected respectively to the plurality of first tanks that are different from each other so as to allow liquid circulation,

wherein a kind of the cell contained in the first liquid varies among the first liquids stored respectively in the plurality of first tanks, and

wherein, in the first discharge step, whether to discharge the first liquid to each of the plurality of portions on the substrate is controlled regarding each of the plurality of first discharge portions.

10 . The cell analysis method according to claim 1 ,

wherein, in the second storage step, the second liquid is stored in a plurality of second tanks,

wherein, in the second discharge step, the second liquid is discharged through use of a plurality of second discharge portions connected respectively to the plurality of second tanks that are different from each other so as to allow liquid circulation;

wherein a kind of the compound contained in the second liquid varies among the second liquids stored respectively in the plurality of second tanks,

wherein, in the second discharge step, whether to discharge the second liquid to each of the plurality of portions on the substrate is controlled regarding each of the plurality of second discharge portions,

wherein, in the first storage step, the first liquid is stored in a plurality of first tanks,

wherein, in the first discharge step, the first liquid is discharged through use of a plurality of the first discharge portions connected respectively to the plurality of first tanks that are different from each other so as to allow liquid circulation,

wherein a kind of the cell contained in the first liquid varies among the first liquids stored respectively in the plurality of first tanks in the first storage step, and

wherein, in the first discharge step, whether to discharge the first liquid to each of the plurality of portions on the substrate is controlled regarding each of the plurality of first discharge portions.

11 . The cell analysis method according to claim 1 , wherein the cell contains a fluorescent dye.

12 . The cell analysis method according to claim 1 , wherein the compound contained in the second liquid is encapsulated in a region surrounded by a liquid that is incompatible with the second liquid.

13 . The cell analysis method according to claim 1 , wherein the compound contained in the second liquid is carried in a porous fine particle.

14 . The cell analysis method according to claim 1 , wherein the compound contained in the second liquid is carried on a surface of a fine particle.

15 . The cell analysis method according to claim 1 , wherein, in the first discharge step, the first discharge portion discharges the first liquid so that the first liquid discharged in one discharge contains one or more cells.

16 . The cell analysis method according to claim 1 , wherein, in the second discharge step, the second discharge portion discharges the second liquid so that the second liquid discharged in one discharge contains one or more molecules of the compound.

17 . The cell analysis method according to claim 1 , wherein the results acquired in the result acquisition step are optical images, and

wherein the analysis of the results in the analysis step is image analysis of the optical images.

18 . The cell analysis method according to claim 1 , wherein the substrate includes a plurality of wells separated from each other by two-dimensional compartments,

wherein the plurality of portions on the substrate are portions in which the plurality of wells are formed, and

wherein the address specifies a specific portion of the well.

19 . The cell analysis method according to claim 1 , wherein the first discharge step and the second discharge step are each a step of discharging a liquid by an inkjet system.

20 . A cell analysis system comprising:

a stage configured to allow a substrate to be set thereon;

a first tank configured to store a first liquid containing a cell;

a second tank configured to store a second liquid that contains a compound and is compatible with the first liquid;

a first discharge portion, which is connected to the first tank so as to allow liquid circulation, and which is configured to discharge the first liquid to a plurality of portions on the substrate, to thereby form a plurality of first liquid droplets, the plurality of portions capable of being specified based on addresses;

a second discharge portion, which is connected to the second tank so as to allow liquid circulation, and which is configured to discharge, based on the addresses of the plurality of portions to which the first liquid is discharged, the second liquid to the plurality of portions on the substrate in such a manner that the second liquid is allowed to be admixed with the first liquid droplets;

a result acquisition portion configured to acquire results of a reaction between the cell and the compound caused by admixture of the first liquid droplets and the second liquid discharged from the second discharge portion; and

an analysis portion configured to analyze the results acquired by the result acquisition portion to specify an address of a portion in which results satisfying predetermined criteria are obtained among the plurality of portions; and

a collection portion configured to collect a coalesced droplet of a first liquid droplet containing the cell and the second liquid by aligning a collection portion with the portion on the substrate specified by the analysis portion based on the address.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 6, 2023
From: IWAMOTO, YUICHIRO; TERAO, AKIRA; MATSUWAKI, NAOMICHI
To: CANON KABUSHIKI KAISHA
Reel/Frame 063236/0876 →
Priority Claims (1)
JP 2022-067941 · Apr 15, 2022 · national
Continuity (1)
Related Publication 20230333016A1 · Oct 19, 2023
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