US-12620095-B2 - Cell quality evaluation apparatus, cell quality evaluation method, and program

US12620095B2US 12620095 B2US12620095 B2US 12620095B2US-12620095-B2

Abstract

A cell quality evaluation apparatus performs a process including estimation processing of estimating a quality of cells in the entirety of a cell-culture container by determining feature quantities from a plurality of images and calculating an average value of the feature quantities; derivation processing of deriving an estimation error of the quality estimated in the estimation processing, based on a variation of the feature quantities in the plurality of images and imaging information related to an area of a plurality of imaging regions; and imaging control processing of causing a imaging apparatus to perform re-imaging on at least one re-imaging region different from the plurality of imaging regions in a case where the estimation error is out of an allowable range.

Inventors

Yasushi Shiraishi

Assignees

FUJIFILM CORPORATION

Dates

Publication Date: 20260505
Application Date: 20231211
Priority Date: 20210624

Claims (8)

1 . A cell quality evaluation apparatus that evaluates a quality of cells based on a plurality of images acquired from an imaging apparatus that generates the plurality of images by imaging a plurality of imaging regions selected, by the imaging apparatus, from an entirety of a cell culture region of a cell-culture container for culturing cells, the cell quality evaluation apparatus comprising: at least one processor configured to perform a process including: estimation processing of estimating a quality of cells in the cell-culture container by determining feature quantities from the plurality of images and calculating an average value of the feature quantities, wherein the feature quantities are proportions of a cell-occupied area, areas of cell nuclei, or area ratios between cell nuclei and cytoplasm; derivation processing of deriving an estimation error of the quality estimated in the estimation processing, based on a variation of the feature quantities in the plurality of images and imaging information related to an area of the plurality of imaging regions, wherein the imaging information is a number N representing the total number of the generated plurality of images; and imaging control processing of causing the imaging apparatus to perform re-imaging on at least one re-imaging region of the culture region at a different position than any of the plurality of imaging regions in a case where the estimation error is out of an allowable range.
2 . The cell quality evaluation apparatus according to claim 1 , wherein the estimation error is represented by σ/N 1/2 , where σ denotes a standard deviation that is the variation of the feature quantities.
3 . The cell quality evaluation apparatus according to claim 1 , wherein in the imaging control processing, the re-imaging region is set in the culture region based on the variation of the feature quantities and position information of the plurality of imaging regions.
4 . The cell quality evaluation apparatus according to claim 1 , wherein in the imaging control processing, the re-imaging region is set in the culture region based on a surface shape of the cell-culture container.
5 . The cell quality evaluation apparatus according to claim 1 , wherein the feature quantities are proportions of a cell-occupied area, and in the imaging control processing, the at least one processor further causes the imaging apparatus to set more re-imaging regions in a first region of the culture region than in a second region of the culture region based on determining that the first region has a lower confluence than the second region and a larger estimation error than the second region.
6 . The cell quality evaluation apparatus according to claim 1 , wherein in the derivation processing, the estimation error is derived based on a predetermined table that defines a relationship between the estimation error and a ratio of an area of imaging regions to the entirety of the cell culture region of the cell-culture container.
7 . A cell quality evaluation method for evaluating a quality of cells based on a plurality of images acquired from an imaging apparatus that generates the plurality of images by imaging a plurality of imaging regions selected, by the imaging apparatus, from an entirety of a cell culture region of a cell-culture container for culturing cells, the cell quality evaluation method comprising: performing a process including: estimation processing of estimating a quality of cells in the cell-culture container by determining feature quantities from the plurality of images and calculating an average value of the feature quantities, wherein the feature quantities are proportions of a cell-occupied area, areas of cell nuclei, or area ratios between cell nuclei and cytoplasm; derivation processing of deriving an estimation error of the quality estimated in the estimation processing, based on a variation of the feature quantities in the plurality of images and imaging information related to an area of the plurality of imaging regions, wherein the imaging information is a number N representing the total number of the generated plurality of images; and imaging control processing of causing the imaging apparatus to perform re-imaging on at least one re-imaging region of the culture region at a different position than any of the plurality of imaging regions in a case where the estimation error is out of an allowable range.
8 . A non-transitory computer-readable storage medium storing a program for causing a computer to execute a process for evaluating a quality of cells based on a plurality of images acquired from an imaging apparatus that generates the plurality of images by imaging a plurality of imaging regions selected, by the imaging apparatus, from an entirety of a cell culture region of a cell-culture container for culturing cells, the process comprising: estimation processing of estimating a quality of cells in the cell-culture container by determining feature quantities from the plurality of images and calculating an average value of the feature quantities, wherein the feature quantities are proportions of a cell-occupied area, areas of cell nuclei, or area ratios between cell nuclei and cytoplasm; derivation processing of deriving an estimation error of the quality estimated in the estimation processing, based on a variation of the feature quantities in the plurality of images and imaging information related to an area of the plurality of imaging regions, wherein the imaging information is a number N representing the total number of the generated plurality of images; and imaging control processing of causing the imaging apparatus to perform re-imaging on at least one re-imaging region of the culture region at a different position than any of the plurality of imaging regions in a case where the estimation error is out of an allowable range.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation application of International Application No. PCT/JP2022/021564, filed May 26, 2022, the disclosure of which is incorporated herein by reference in its entirety. Further, this application claims priority from Japanese Patent Application No. 2021-104816, filed on Jun. 24, 2021, the disclosure of which is incorporated herein by reference in its entirety. BACKGROUND 1. Technical Field The technique of the present disclosure relates to a cell quality evaluation apparatus, a cell quality evaluation method, and a program. 2. Description of the Related Art In the fields of regenerative medicine, new drug development, and the like, there is known a technique for evaluating the quality of cells that are being cultured in a cell-culture container, by analyzing captured images obtained by imaging the cell-culture container with an imaging apparatus such as a microscope (for example, see WO2016/098271A). WO2016/098271A discloses calculating a proportion of a cell-occupied area (hereinafter, referred to as confluency) which is a proportion of an area occupied by cells in a cell-culture container on the basis of a plurality of images acquired from a plurality of measurement areas (imaging regions) designated in the cell-culture container. Confluency is one indicator representing the quality of cells that are being cultured. SUMMARY In the case where the quality of cells is estimated on the basis of images acquired from a plurality of imaging regions selected from the entire cell-culture container as described in WO2016/098271A, an estimation error of the quality depends on the number and the size of the imaging regions selected from the entire cell-culture container. To reduce the estimation error of the quality, the entire cell-culture container needs to be imaged by increasing the number of imaging regions selected from the entire cell-culture container or by increasing the area of the imaging regions. Imaging the entire cell-culture container is possible when the cell-culture container has a small volume such as wells in a well plate but is difficult when the cell-culture container has a large volume such as a T-flask. Microscopes capable of imaging the entire large-volume cell-culture container are present. However, such microscopes are large costly apparatuses and thus are difficult for ordinary users to introduce and operate. Accordingly, development of a cell quality evaluation apparatus that allows the quality of cells to be evaluated with a high accuracy even for a large-volume cell-culture container is desired. The technique of the present disclosure aims to provide a cell quality evaluation apparatus, a cell quality evaluation method, and a program that allow the quality of cells to be evaluated with a high accuracy even for a large-volume cell-culture container. A cell quality evaluation apparatus according to the present disclosure is a cell quality evaluation apparatus that evaluates a quality of cells based on a plurality of images acquired from an imaging apparatus that generates the plurality of images by imaging a plurality of imaging regions selected from entirety of a cell-culture container for culturing cells. The cell quality evaluation apparatus includes at least one processor configured to perform a process including estimation processing of estimating a quality of cells in the entirety of the cell-culture container by determining feature quantities from the plurality of images and calculating an average value of the feature quantities; derivation processing of deriving an estimation error of the quality estimated in the estimation processing, based on a variation of the feature quantities in the plurality of images and imaging information related to an area of the plurality of imaging regions; and imaging control processing of causing the imaging apparatus to perform re-imaging on at least one re-imaging region different from the plurality of imaging regions in a case where the estimation error is out of an allowable range. Preferably, the imaging information is a number of images that are the plurality of images, and the estimation error is represented by σ/N1/2, where σ denotes a standard deviation that is the variation of the feature quantities and N denotes the number of images. Preferably, in the imaging control processing, the re-imaging region is set based on the variation of the feature quantities and position information of the plurality of imaging regions. Preferably, in the imaging control processing, the re-imaging region is set based on a surface shape of the cell-culture container. Preferably, the feature quantities are proportions of a cell-occupied area, areas of cell nuclei, or area ratios between cell nuclei and cytoplasm. Preferably, the feature quantities are proportions of a cell-occupied area, and in the imaging control processing, the imaging apparatus is caused to perform re-imaging more in a region