# US 11,441,113 B2 · Cell treatment system > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,441,113 B2 - Document ID: US11441113B2 - Status: Granted - Kind: B2 - Application number: 16/305,378 - Filed: 2017-03-24 - Published: 2020-10-15 - Granted: 2022-09-13 - Earliest claimed: 2016-06-01 - Assignees: Kataoka Corporation - Applicants: Kataoka Corporation - Inventors: Junichi Matsumoto - Web page: https://patentgrep.com/patent/US11441113B2 ## CPC - C12M 35/02: {Electrical or electromagnetic means, e.g. for electroporation or for cell fusion} - C12N 5/00: Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor; (plant reproduction by tissue culture techniques A01H4/00) - C12M 23/20: {Material Coatings (immunocoatings C12M25/00)} - C12M 23/22: {Transparent or translucent parts (glassware for laboratory use B01L3/00)} - C12M 41/36: {of biomass, e.g. colony counters or by turbidity measurements (electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404)} - C12N 13/00: Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves - 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} - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract A cell treatment system includes an analysis unit to calculate the area or size of each of cell aggregates existing on the cell culture vessel based on an image; a display device to show the area or size of each of the cell aggregates on a display; a laser irradiator to emit laser toward the cell culture vessel so as to kill cells existing on the cell culture vessel; an input device to receive an operation input designating cells to be killed with irradiation of the laser or cells to survive without the irradiation of the laser among the cells existing on the cell culture vessel, or an operation input designating a position to be irradiated with the laser or a position not to be irradiated with the laser on the cell culture vessel; and a control unit to control a position irradiated with the laser. ## Claims ### Claim 1 A cell treatment system to kill unwanted cells among cells cultured on a cell culture vessel and nurture desired cell aggregates, the cell treatment system comprising: an imaging device to image all or a Part of the cell culture vessel, wherein a plurality of cell aggregates that each contain a plurality of cells exist on the cell culture vessel; an analyzer programmed to calculate an area or size of one or each of cell aggregates existing on the cell culture vessel based on pixel values from which an image captured by the imaging device is constituted, wherein the analyzer is programmed to make a judgement on whether the area or size of each of the cell aggregates on the cell culture vessel exceeds a proper upper limit or a proper lower limit according to culture time; a display device to show a result of the judgement about each of the cell aggregates existing on the cell culture vessel according to the culture time by the analyzer on a display; a laser irradiator to emit laser toward the cell culture vessel so as to kill cells existing on the cell culture vessel; an input device configured to receive an operation input by a user, the operation input designating cells to be killed with irradiation of the laser or cells to survive without the irradiation of the laser among the cells existing on the cell culture vessel, or the operation input designating a position to be irradiated with the laser or a position not to be irradiated with the laser on the cell culture vessel; and a controller programmed to control a position irradiated with the laser emitted from the laser irradiator toward the cell culture vessel in accordance with the operation input received by the input device. ### Claim 2 (depends on 1) The cell treatment system according to claim 1, wherein the analyzer is programmed to memorize an upper limit or a lower limit on the area or size of a cell aggregate and makes a judgement on whether the area or size of each of the cell aggregates existing on the cell culture vessel exceeds the upper limit or the lower limit. ### Claim 3 (depends on 2) The cell treatment system according to claim 2, wherein the controller controls the laser irradiator such that the laser is emitted so as to kill a cell aggregate which has an area or size smaller than the lower limit among the cell aggregates existing on the cell culture vessel, and cut a cell aggregate which has an area or size larger than the upper limit or reduce the area or size of it among the cell aggregates existing on the cell culture vessel. ### Claim 4 (depends on 2) The cell treatment system according to claim 2, wherein the upper limit and the lower limit of the area or size of the cell aggregate varies depending on the culture time. ### Claim 5 (depends on 2) The cell treatment system according to claim 2, wherein a region on the cell culture vessel where a cell aggregate has an area that is within the upper limit and the lower limit according to culture time comprises a proper range according to a judgement condition. ### Claim 6 (depends on 5) The cell treatment system according to claim 5, wherein the proper range varies as cell culture time passes. ### Claim 7 (depends on 5) The cell treatment system according to claim 5, wherein the analyzer is configured to calculate that each of the cell aggregates is within the proper range based on at least one judgement condition of a plurality of judgement conditions, the judgement conditions comprising; transmittance of the cell aggregate; roundness of the cell aggregate; density of cells of the cell aggregate; and whether the cells comprise target cells or not. ### Claim 8 (depends on 7) The cell treatment system according to claim 7, wherein the roundness of a shape of each of the cell aggregates is calculated, and the analyzer judges that a cell aggregate with the roundness smaller than the lower limit device is to be killed, or to be trimmed so that the cells on a periphery of the cell aggregate are killed and the shape of the cell aggregate approaches a perfect circle. ### Claim 9 (depends on 7) The cell treatment system according to claim 7, wherein the density of cells of each of the cell aggregates is calculated, and the analyzer judges that a cell aggregate with the density smaller than the lower limit or larger than the upper limit in the cell aggregate is to be killed. ### Claim 10 (depends on 2) The cell treatment system according to claim 2, wherein the controller controls the laser irradiator such that the laser is emitted so as to kill a cell aggregate which has the roundness exceeding the lower limit among the cell aggregates existing on the cell culture vessel, and the laser irradiator cuts the cell aggregate which has the roundness exceeding the upper limit or reduce the area or size of it among the cell aggregates existing on the cell culture vessel. ### Claim 11 A cell treatment system to kill unwanted cells among cells cultured on a cell culture vessel and nurture desired cell aggregates, the cell treatment system comprising: an imaging device to image all or a part of the cell culture vessel, wherein a plurality of cell aggregates that each contain a plurality of cells exist on the cell culture vessel; an analyzer programmed to calculate an area or size of one or each of cell aggregates existing on the cell culture vessel based on pixel values from which an image captured by the imaging device is constituted, programmed to memorize an upper limit or a lower limit on the area or size of a cell aggregate according to culture time, and programed to make a judgement on whether the area or size of each of the cell aggregates existing on the cell culture vessel exceeds the upper limit or the lower limit; a laser irradiator to emit laser toward the cell culture vessel so as to kill cells existing on the cell culture vessel; and a controller programmed to control a position irradiated with the laser emitted from the laser irradiator toward the cell culture vessel in accordance with a result of the judgement by the analyzer. ### Claim 12 (depends on 11) The cell treatment system according to claim 11, wherein the controller controls the laser irradiator such that the laser is emitted so as to kill a cell aggregate which has an area or size smaller than the lower limit among the cell aggregates existing on the cell culture vessel, and cut a cell aggregate which has an area or size larger than the upper limit or reduce the area or size of it among the cell aggregates existing on the cell culture vessel. ### Claim 13 (depends on 11) The cell treatment system according to claim 11, wherein the controller performs the laser irradiation on a region in the cell culture vessel where a cell aggregate having an area or size that exceeds the upper limit or the lower limit exists. ### Claim 14 (depends on 11) The cell treatment system according to claim 11, wherein the controller performs the laser irradiation on a region in the cell culture vessel where a cell aggregate having an area that exceeds the upper limit or the lower limit exists. ### Claim 15 (depends on 11) The cell treatment system according to claim 11, wherein the controller performs the laser irradiation on a region in the cell culture vessel where a cell aggregate having a size that exceeds the upper limit or the lower limit exists. ### Claim 16 (depends on 11) The cell treatment system according to claim 11, wherein the upper limit and the lower limit of the area or size of the cell aggregate varies depending on the culture time. ### Claim 17 (depends on 11) The cell treatment system according to claim 11, wherein a region on the cell culture vessel where a cell aggregate has an area that is within the upper limit and the lower limit according to culture time comprises a proper range according to a judgement condition. ### Claim 18 (depends on 17) The cell treatment system according to claim 17, wherein the analyzer is configured to calculate that each of the cell aggregates is within the proper range based on at least one judgement condition of a plurality of judgement conditions, the judgement conditions comprising; transmittance of the cell aggregate; roundness of the cell aggregate; density of cells of the cell aggregate; and whether the cells comprise target cells or not. ### Claim 19 (depends on 18) The cell treatment system according to claim 18, wherein the roundness of a shape of each of the cell aggregates is calculated, and the analyzer judges that a cell aggregate with the roundness smaller than the lower limit device is to be killed, or to be trimmed so that the cells on the periphery of the cell aggregate are killed and the shape of the cell aggregate approaches a perfect circle. ### Claim 20 A cell treatment system to kill unwanted cells among cells cultured on a cell culture vessel and nurture desired cell aggregates, the cell treatment system comprising: an imaging device to image all or a part of the cell culture vessel, wherein a plurality of cell aggregates that each contain a plurality of cells exist on the cell culture vessel; an analyzer programmed to calculate a feature amount of one or each of cell aggregates existing on the cell culture vessel based on pixel values from which an image captured by the imaging device is constituted, wherein the analyzer is programmed to make a judgement on whether the feature amount of each of the cell aggregates on the cell culture vessel exceeds a proper upper limit or a proper lower limit according to culture time, wherein, at least one of: a cell aggregate with a feature amount smaller than the lower limit of the proper range is a bad aggregate in which the cells have not successfully proliferated and which have not grown in accordance with the culture time, or, a cell aggregate with a feature amount larger than the upper limit of the proper range grows excessively fast beyond supposition, although the cells proliferates themselves; a display device to show a result of the judgement about the feature amount of each of the cell aggregates existing on the cell culture vessel according to the culture time by the analyzer on a display; a laser irradiator to emit laser toward the cell culture vessel so as to kill cells existing on the cell culture vessel; an input device configured to receive an operation input by a user, the operation input designating cells to be killed with irradiation of the laser or cells to survive without the irradiation of the laser among the cells existing on the cell culture vessel, or the operation input designating a position to be irradiated with the laser or a position not to be irradiated with the laser on the cell culture vessel; and a controller programmed to control a position irradiated with the laser emitted from the laser irradiator toward the cell culture vessel in accordance with the operation input received by the input device.