# US 10,504,223 B2 · Cell image evaluation device, method, and program

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- Number: US 10,504,223 B2
- Document ID: US10504223B2
- Status: Granted
- Kind: B2
- Application number: 15/046,592
- Filed: 2016-02-18
- Published: 2016-06-09
- Granted: 2019-12-10
- Earliest claimed: 2013-08-22
- Assignees: FUJIFILM Corporation
- Applicants: FUJIFILM Corporation
- Inventors: Kenta Matsubara; Tsuyoshi Matsumoto
- Web page: https://patentgrep.com/patent/US10504223B2

## CPC

- G06T 7/0012: {Biomedical image inspection}
- C12M 41/36: {of biomass, e.g. colony counters or by turbidity measurements (electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404)}
- C12M 41/46: {of cellular or enzymatic activity or functionality, e.g. cell viability}
- G02B 21/365: {Control or image processing arrangements for digital or video microscopes (G02B21/361, G02B21/362 take precedence)}
- G06F 18/285: {Selection of pattern recognition techniques, e.g. of classifiers in a multi-classifier system}
- G06V 10/87: {using selection of the recognition techniques, e.g. of a classifier in a multiple classifier system}
- G06V 20/695: {Preprocessing, e.g. image segmentation}
- G01N 2021/4173: {Phase distribution}
- G02B 21/14: affording illumination for phase-contrast observation
- G06T 2207/10056: Microscopic image
- G06T 2207/30024: Cell structures in vitro; Tissue sections in vitro
- G06T: IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
- C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS}
- G02B: OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G06F: ELECTRIC DIGITAL DATA PROCESSING (computer systems based on specific computational models G06N)
- G06V: IMAGE OR VIDEO RECOGNITION OR UNDERSTANDING
- 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

A cell image evaluation device includes an image acquisition unit that acquires a captured image of a cell, a cell evaluation unit that evaluates the cell image, and a maturity information acquisition unit that acquires information related to maturity of the cell. The cell evaluation unit determines a method for evaluating the cell image on the basis of the information related to the maturity.

## Claims

### Claim 1

A cell image evaluation device comprising:
a memory; and
a processor that is connected to the memory and that is configured to:
acquire an observation image of cells captured by an imaging device;
acquire information related to maturity of the cells; and
evaluate undifferentiation and differentiation of the cells using the observation image, according to evaluation criteria of the cells corresponding to the maturity of the cells and a culture condition of the cells,
wherein the information related to maturity is contained in the observation image that is a target for evaluation and the information related to maturity is a period of time from a time of seeding the cells,
wherein, based on the information related to maturity, a combination of types of the evaluation criteria that is used for evaluating a differentiation or an undifferentiation of the observation image is changed, and, based on the information related to maturity, a weight that is respectively added to the plurality of the evaluation criteria that is used for evaluating the observation image is changed, and
wherein, in a case in which the maturity is in an initial stage of seeding, the processor performs a process of extracting a cell colony from the observation image when the culture condition is a colony seeding method of seeding the cells by cell colony and estimates the cell colony from the cells in the observation image when the culture condition is a single cell seeding method of seeding the cells by cell.

### Claim 2 (depends on 1)

The cell image evaluation device according to claim 1, wherein the evaluation criteria include an evaluation criterion based on the uniformity of a distribution of the cells and an evaluation criterion based on a shape of a colony of the cells.

### Claim 3 (depends on 1)

The cell image evaluation device according to claim 1, wherein the processor is further configured to set the weights such that a weight on an outward shape of the cell colony when the maturity is equal to or greater than a predetermined value is greater than a weight on the shape of the cell colony when the maturity is less than the predetermined value.

### Claim 4 (depends on 1)

The cell image evaluation device according to claim 1, wherein, when the maturity is equal to or greater than the predetermined value, the observation image is evaluated, using the uniformity of brightness of the observation image as the evaluation criteria.

### Claim 5 (depends on 1)

The cell image evaluation device according to claim 1, wherein, when the maturity is equal to or greater than the predetermined value, the observation image is evaluated, using the uniformity of a thickness of the cells distributed in the observation image as the evaluation criteria.

### Claim 6 (depends on 1)

The cell image evaluation device according to claim 1, wherein, when the maturity is equal to or greater than the predetermined value, the observation image is evaluated, using the approximation between a combination pattern of a plurality of circles and the cell colony as the evaluation criteria.

### Claim 7 (depends on 1)

The cell image evaluation device according to claim 1, wherein the processor is further configured to change the observation image evaluation method on the basis of culture conditions of the cell.

### Claim 8 (depends on 1)

The cell image evaluation device according to claim 1, wherein, when culture conditions are that a cell different from the cells is used, the processor performs a process of separating an image of the different cell from the cells.

### Claim 9

A cell image evaluation method comprising:
when an observation image of cells is acquired and evaluated, acquiring information related to maturity of the cells, the information related to maturity being contained in the observation image that is a target for evaluation and the information related to maturity is a period of time from a time of seeding the cell; and
determining a method for evaluating undifferentiation and differentiation of the cells using the observation image, according to evaluation criteria of the cells corresponding to the maturity of the cells and a culture condition of the cells,
wherein, based on the information related to maturity, a combination of types of the evaluation criteria that is used for evaluating a differentiation or an undifferentiation of the observation image is changed, and, based on the information related to maturity, a weight that is respectively added to the plurality of the evaluation criteria that is used for evaluating the observation image is changed,
wherein, in a case in which the maturity is in an initial stage of seeding, extracting a cell colony from the observation image when the culture condition is a colony seeding method of seeding the cells by cell colony and estimating the cell colony from the cells in the observation image when the culture condition is a single cell seeding method of seeding the cells by cell.

### Claim 10

A non-transitory computer readable recording medium having a cell image evaluation program stored therein, that causes a computer to perform the following functions:
acquire an observation image of cells;
acquire information related to maturity of the cell; and
evaluate undifferentiation and differentiation of the cells using the observation image, according to evaluation criteria of the cells corresponding to the maturity of the cells and a culture condition of the cells,
wherein the information related to maturity is contained in the observation image that is a target for evaluation and the information related to maturity is a period of time from a time of seeding the cells,
wherein, based on the information related to maturity, a combination of types of the evaluation criteria that is used for evaluating a differentiation or an undifferentiation of the observation image is changed, and, based on the information related to maturity, a weight that is respectively added to the plurality of the evaluation criteria that is used for evaluating the observation image is changed, and
wherein, in a case in which the maturity is in an initial stage of seeding, extracting a cell colony from the observation image when the culture condition is a colony seeding method of seeding the cells by cell colony and estimating the cell colony from the cells in the observation image when the culture condition is a single cell seeding method of seeding the cells by cell.

### Claim 11 (depends on 1)

The cell image evaluation device according to claim 1, wherein based on the information related to maturity, a weight, that is respectively added to the plurality of the evaluation criteria that is used for evaluating the observation image, is changed.