Sheet position adjusting device and sheet position adjusting method

The device uses imaging and liquid adjustment to position and reinforce sheet-shaped cell cultures, addressing fragility and deformation issues, ensuring standardized and damage-free handling.

JP2025130119APending Publication Date: 2025-09-08TERUMO KK
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Patent Information

Application Number
JP2024027078
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Filing Date
2024-02-27
Publication Date
2025-09-08

AI Technical Summary

Technical Problem

Sheet-shaped cell cultures are fragile and prone to deformation and breakage during handling and reinforcement, necessitating skilled human techniques for positioning and reinforcement, which lacks standardization.

Method used

A device comprising a culture substrate, imaging unit, liquid volume adjustment units, and control unit to accurately position and reinforce sheet-shaped cell cultures by adjusting liquid volume and applying gelling substances.

Benefits of technology

Enables precise positioning and reinforcement of fragile sheet-shaped cell cultures without deformation or damage, facilitating standardized and effective handling.

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Abstract

To provide a sheet position adjusting device and a sheet position adjusting method that can position a sheet-shaped cell culture in an appropriate position while suppressing deformation and damage to the fragile sheet-shaped cell culture.SOLUTION: A sheet position adjusting device 10 includes: a culture substrate 20 that can accommodate a sheet-shaped cell culture 100; multiple liquid volume adjusting units 40 that supply and / or discharge an immersion liquid 110 to and / or from the culture substrate 20; an imaging unit 30 that can capture images of the sheet-shaped cell culture 100 accommodated in the culture substrate 20; and a control unit 60 that controls the operation of the liquid volume adjusting units 40. The control unit 60 identifies a position of the sheet-shaped cell culture 100 from image information acquired from the imaging unit 30, calculates a direction and an amount of deviation of the position of the sheet-shaped cell culture 100 from a reference position on the culture substrate 20, and determines and operates at least one liquid volume adjusting unit 40 that reduces the amount of deviation, thereby adjusting the position of the sheet-shaped cell culture 100 on the culture substrate 20.SELECTED DRAWING: Figure 2
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Description

[Technical Field]

[0001] The present invention relates to a sheet position adjusting device and a sheet position adjusting method for adjusting the position of a sheet-shaped cell culture. [Background technology]

[0002] In recent years, a treatment has been performed in which cultured cells are formed into a sheet-like culture and then transplanted onto an injured organ (see, for example, Patent Document 1). When the sheet-like cell culture is transplanted onto the surface of an organ, it can survive for a long period of time, using the blood vessels on the surface of the organ as a vascular bed.

[0003] Cells are cultured in a culture substrate together with an immersion fluid. Sheet-shaped cell cultures, which are aggregates of cultured cells, are fragile and prone to deformation and breakage, such as curling. For this reason, sheet-shaped cell cultures are reinforced to maintain their aggregate shape. One known example of such reinforcement is the application of a gelling substance. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2012-39944 Summary of the Invention [Problem to be solved by the invention]

[0005] To reinforce a sheet-shaped cell culture, it is necessary to position the sheet-shaped cell culture near the center of the culture substrate and then remove the immersion solution to facilitate the reinforcement treatment. However, because sheet-shaped cell cultures before reinforcement treatment are very fragile, handling them requires skilled human techniques, and standardization of the procedure using an apparatus is desirable.

[0006] The present invention has been made to solve the above-mentioned problems, and aims to provide a sheet position adjustment device and a sheet position adjustment method that can position a sheet-shaped cell culture in an appropriate position while suppressing deformation and damage to the fragile sheet-shaped cell culture. [Means for solving the problem]

[0007] The above object can be achieved by the invention described in (1) below.

[0008] (1) The sheet position adjustment device of the present invention comprises a culture substrate capable of accommodating a sheet-shaped cell culture together with an immersion liquid, a plurality of liquid volume adjustment units that supply immersion liquid to the culture substrate and / or discharge immersion liquid from the culture substrate, an imaging unit that can image the sheet-shaped cell culture accommodated in the culture substrate, and a control unit that controls the operation of the liquid volume adjustment units, wherein the control unit identifies the position of the sheet-shaped cell culture from image information acquired from the imaging unit, calculates the direction and amount of deviation of the position of the sheet-shaped cell culture from a reference position of the culture substrate, determines and operates at least one liquid volume adjustment unit that reduces the amount of deviation, and adjusts the position of the sheet-shaped cell culture on the culture substrate. [Effects of the Invention]

[0009] The sheet position adjustment device described in (1) above moves the sheet-shaped cell culture, which tends to become dislodged from the surface of the culture substrate and move in the immersion liquid, by supplying and / or discharging the immersion liquid, thereby enabling the sheet-shaped cell culture to be positioned appropriately while suppressing deformation or damage to the fragile sheet-shaped cell culture.

[0010] (2) The sheet position adjusting device described in (1) above may have a reinforcement processing unit that performs a process to reinforce the sheet-shaped cell culture, and the control unit may operate the reinforcement processing unit after adjusting the position of the sheet-shaped cell culture with the liquid volume adjusting unit. In this way, the sheet position adjusting device performs a reinforcement process on the sheet-shaped cell culture arranged at an appropriate position on the culture substrate, and can reinforce the sheet-shaped cell culture to a desired strength.

[0011] (3) In the sheet position adjusting device described in (2) above, the reinforcement processing unit may have a discharge unit that discharges a gelling, viscous, or hardening substance. This allows the sheet position adjusting device to discharge the gelling, viscous, or hardening substance onto the sheet-shaped cell culture placed at an appropriate position on the culture substrate, thereby reinforcing the sheet-shaped cell culture to a desired strength.

[0012] (4) A sheet position adjustment method according to the present invention is a sheet position adjustment method for arranging a sheet-shaped cell culture at an appropriate position on a culture substrate, comprising the steps of: capturing an image of the sheet-shaped cell culture contained in the culture substrate together with an immersion liquid using an imaging unit; identifying the position of the sheet-shaped cell culture from image information acquired from the imaging unit; calculating the direction and amount of deviation of the position of the sheet-shaped cell culture from a reference position on the culture substrate; and selecting and activating at least one liquid volume adjustment unit that reduces the amount of deviation from multiple liquid volume adjustment units that supply immersion liquid to the culture substrate and / or discharge immersion liquid from the culture substrate. This sheet position adjustment method moves the sheet-shaped cell culture, which tends to become detached from the surface of the culture substrate and move in the immersion liquid, by supplying and / or discharging the immersion liquid, thereby enabling the sheet-shaped cell culture to be arranged at an appropriate position while suppressing deformation or damage to the fragile sheet-shaped cell culture.

[0013] (5) The sheet position adjustment method described in (4) above may include a step of operating a reinforcement processing unit that performs a process of reinforcing the sheet-shaped cell culture. In this way, the sheet position adjustment method applies a reinforcement process to the sheet-shaped cell culture arranged at an appropriate position on the culture substrate, thereby reinforcing the sheet-shaped cell culture to a desired strength.

[0014] (6) In the sheet position adjusting method described in (5) above, in the step of operating the reinforcement processing unit, the reinforcement processing unit may eject a substance that gels, increases viscosity, or hardens onto the sheet-shaped cell culture. This allows the sheet position adjusting method to eject a substance that gels, increases viscosity, or hardens onto the sheet-shaped cell culture placed at an appropriate position on the culture substrate, thereby reinforcing the sheet-shaped cell culture to a desired strength. [Brief explanation of the drawings]

[0015] [Figure 1] 1 is a perspective view showing a part of a seat position adjusting device according to an embodiment of the present invention; [Figure 2] 1 is a schematic configuration diagram of a seat position adjusting device according to an embodiment of the present invention; [Figure 3] 10 is a flowchart showing a control flow in a control unit. DETAILED DESCRIPTION OF THE INVENTION

[0016] Hereinafter, embodiments of the present invention will be described with reference to the drawings. Note that dimensions in the drawings may be exaggerated for convenience of explanation and may differ from actual dimensions. Furthermore, in this specification and drawings, components having substantially the same functions are designated by the same reference numerals, and redundant description will be omitted.

[0017] 1 and 2, the sheet position adjustment device 10 according to this embodiment is a device for positioning the sheet-shaped cell culture 100, which is a sheet-shaped aggregate of a plurality of cells cultured on the culture substrate 20 while immersed in an immersion liquid 110, near the center of the culture substrate 20 in order to perform a reinforcement treatment on the sheet-shaped cell culture 100. The sheet-shaped cell culture 100 is in a state where it has been detached from the culture substrate 20.

[0018] The sheet position adjusting device 10 includes a culture substrate 20, an imaging unit 30, a plurality of liquid volume adjusting units 40, a reinforcement processing unit 50, and a control unit 60.

[0019] The culture substrate 20 is a member having a surface that serves as a scaffold for the cells to be cultured, and is a container that accommodates the sheet-shaped cell culture 100 together with the immersion liquid 110. The culture substrate 20 is preferably circular when viewed from above.

[0020] The imaging unit 30 has an image sensor that can capture an image of an area including the sheet-shaped cell culture 100 inside the culture substrate 20 from above the culture substrate 20. The imaging unit 30 is preferably capable of capturing an image of an area including the entire culture substrate 20 so as to capture an image of the sheet-shaped cell culture 100 moving inside the culture substrate 20. The sensor included in the imaging unit 30 is not particularly limited as long as it can capture an image of the sheet-shaped cell culture 100. The imaging unit 30 can transmit captured image data to the control unit 60.

[0021] Each of the liquid volume adjusting units 40 has a supply unit 41 that can supply the immersion liquid 110 and a discharge unit 42 that can discharge the immersion liquid 110. It is preferable that there are two or more liquid volume adjusting units 40 so that the sheet-shaped cell culture 100 in the culture substrate 20 can be moved in any horizontal direction. In the example shown in Fig. 1, the sheet position adjusting device 10 has four liquid volume adjusting units 40 that are evenly arranged in the circumferential direction.

[0022] The supply unit 41 and the discharge unit 42 of each liquid volume adjuster 40 can be operated independently under the control of the control unit 60. The supply unit 41 and the discharge unit 42 have, for example, a supply tube 43 and a discharge tube 44 connected to a pump that can be operated under the control of the control unit 60. The supply tube 43 preferably has a supply port near the bottom surface of the culture substrate 20 so that the immersion liquid 110 can be quietly supplied to the culture substrate 20 without dripping. The discharge tube 44 preferably has a discharge port near the bottom surface of the culture substrate 20 so that the immersion liquid 110 can be discharged to the last drop. The position (height) of the discharge port of the discharge tube 44 is not limited to near the bottom surface of the culture substrate 20 and may be located, for example, near the liquid surface of the immersion liquid 110. When the immersion liquid 110 is manually discharged using a pipette (discharge tube), the position of the pipette can be adjusted as needed, so that the immersion liquid 110 can be discharged using the pipette from a position as close to the liquid surface as possible to minimize water flow. Alternatively, the position of the discharge outlet of the discharge tube 44 may be automatically raised and lowered in accordance with the position of the liquid level of the immersion liquid 110. The control unit 60 may calculate the position of the liquid level from image data, or identify the position of the liquid level from a signal from a separately provided displacement sensor or the like, and control an actuator (e.g., a motor) that raises and lowers the discharge tube 44.

[0023] The reinforcement processing unit 50 is a section where a gelling substance is applied to maintain the shape of the sheet-shaped cell culture 100 remaining on the culture substrate 20 after the immersion liquid 110 has been removed. The reinforcement processing unit 50, for example, separately stores two liquids that gel when mixed, and applies the two liquids to the sheet-shaped cell culture 100 by spraying them from the discharge unit 51 while pressurizing and mixing the two liquids using a pump or the like operable by the control unit 60. The mixed two liquids gel over time, maintaining the shape of the sheet-shaped cell culture 100. The reinforcement processing unit 50 may have two discharge units 51 that discharge the two liquids individually onto the sheet-shaped cell culture 100.

[0024] The substance that gels upon mixing is, for example, a fibrinogen solution and a thrombin solution. When the fibrinogen solution and the thrombin solution are mixed, the fibrinogen becomes fibrin due to the action of thrombin, and gels. Note that gelation also refers to increasing viscosity or hardening, as it increases viscosity and hardness. Alternatively, the substance that gels upon mixing may be a first aqueous solution of NHS-CM dextrin and trehalose hydrate and a second aqueous solution containing sodium carbonate and sodium bicarbonate. Note that, in order to maintain the shape of the sheet-shaped cell culture 100 remaining on the culture substrate 20 after the immersion liquid 110 has been removed, the reinforcement processing unit 50 may supply a substance that increases viscosity or a hardening substance (e.g., an adhesive) rather than applying a gelling substance.

[0025] The control unit 60 receives image data from the imaging unit 30, performs arithmetic processing such as image analysis on the image data, and can identify the position of the sheet-shaped cell culture 100. The control unit 60 can also control and operate the liquid volume adjusting unit 40 and the reinforcement processing unit 50. The control unit 60 is physically configured to include a memory circuit and an arithmetic circuit. The memory circuit can store programs and various parameters. The arithmetic circuit can perform arithmetic processing. The control unit 60 is, for example, a computer.

[0026] The cells to be cultured include, for example, differentiated cells derived from somatic stem cells, adult stem cells, mesenchymal stem cells, ES cells (embryonic stem cells), or iPS cells (induced pluripotent stem cells). Somatic stem cells include, for example, skeletal myoblasts (myoblast cells). Differentiated cells include, for example, cardiomyocytes and fibroblast cells.

[0027] Next, a seat position adjusting method using the seat position adjusting device 10 according to this embodiment will be described with reference to the flowchart shown in FIG.

[0028] First, the control unit 60 operates the liquid volume adjusting unit 40 to supply the immersion liquid 110 from the supply unit 41 in order to detach the sheet-shaped cell culture 100 from the surface of the culture substrate 20 (step S1). As a result, the sheet-shaped cell culture 100 is detached from the surface of the culture substrate 20. The position of the sheet-shaped cell culture 100 detached from the surface of the culture substrate 20 is not particularly limited, but it is usually located near the surface (bottom) of the culture substrate 20. The control unit 60, for example, supplies the immersion liquid 110 to all of the supply units 41 arranged uniformly in the circumferential direction. As a result, the sheet-shaped cell culture 100 can be detached from the culture substrate 20 while suppressing horizontal movement.

[0029] Next, the control unit 60 acquires image information from the imaging unit 30 (step S2). Next, the control unit 60 identifies the position of the sheet-shaped cell culture 100 by image analysis from the acquired image information (step S3). The control unit 60, for example, identifies the outline of the identified sheet-shaped cell culture 100 and identifies the center position (center of gravity position). Next, the control unit 60 calculates the amount of deviation of the center position of the sheet-shaped cell culture 100 from a reference position of the culture substrate 20 (for example, the center position in a horizontal plane) and the direction of the deviation (step S4).

[0030] Next, the control unit 60 determines whether the calculated amount of deviation is less than (or equal to or less than) a preset threshold value (step S5). If the calculated amount of deviation is less than (or equal to or less than) the threshold value, the control unit 60 determines whether the amount of immersion liquid 110 is less than (or equal to or less than) a preset threshold value (step S6). The amount of immersion liquid 110 can be calculated from the amount of immersion liquid 110 previously contained in the culture substrate 20 and the amount of immersion liquid 110 supplied and discharged by the liquid amount adjusting unit 40. Alternatively, the amount of immersion liquid 110 may be calculated by image analysis of image information acquired from the imaging unit 30. Alternatively, the control unit 60 may calculate the amount of immersion liquid 110 by receiving a signal from another sensor (e.g., a weight sensor or a displacement sensor) that can detect the amount of immersion liquid 110. If the amount of immersion liquid 110 is not less than (or equal to or less than) a preset threshold value in step S6, the control unit 60 determines that immersion liquid 110 remains, and uniformly aspirates and removes the immersion liquid 110 from all of the discharge units 42 that are uniformly arranged in the circumferential direction (step S7). This allows the immersion liquid 110 to be removed while suppressing changes in the amount of deviation of the sheet-shaped cell culture 100 from the reference position. After the predetermined amount of immersion liquid 110 has been uniformly removed, the control unit 60 returns to the above-mentioned step S2 and acquires image information from the imaging unit 30 again.

[0031] If the calculated amount of displacement is not less than the threshold value (or not more than the threshold value) in the above-mentioned step S5, the control unit 60 determines the liquid volume adjuster 40 for moving the center position of the sheet-shaped cell culture 100 to the reference position of the culture substrate 20 based on the calculated amount of displacement and direction of displacement (step S8). Subsequently, the control unit 60 operates the determined liquid volume adjuster 40 to move the center position of the sheet-shaped cell culture 100 closer to the reference position of the culture substrate 20 by the flow of the immersion liquid 110 (step S9).

[0032] The supply unit 41 of the liquid volume adjusting unit 40 can move the sheet-shaped cell culture 100 in a direction away from the supply unit 41 by supplying the immersion liquid 110. The discharge unit 42 of the liquid volume adjusting unit 40 can move the sheet-shaped cell culture 100 in a direction toward the discharge unit 42 by discharging the immersion liquid 110. A plurality of supply units 41 are arranged in the circumferential direction to surround the reference position (center position) of the culture substrate 20, and a plurality of discharge units 42 are also arranged in the circumferential direction to surround the center of the culture substrate 20. Therefore, the control unit 60 can move the sheet-shaped cell culture 100 in the desired direction by appropriately selecting the supply units 41 and discharge units 42 to be operated. Note that if the sheet-shaped cell culture 100 is too close to the supply unit 41, the supply of the immersion liquid 110 from the supply unit 41 may cause the sheet-shaped cell culture 100 to roll up or be damaged. Therefore, when the control unit 60 determines that the sheet-shaped cell culture 100 is too close to the supply unit 41 based on the amount of displacement, it may operate the discharge unit 42 located on the opposite side of the too-close supply unit 41 to move the sheet-shaped cell culture 100 away from the too-close supply unit 41. Furthermore, when the control unit 60 determines that the amount of immersion liquid 110 is too small, it may use the supply unit 41 instead of the discharge unit 42 to move the sheet-shaped cell culture 100. Furthermore, the control unit 60 may operate multiple liquid volume adjustment units 40 simultaneously.

[0033] In step S9, after the sheet-shaped cell culture 100 has been moved by the liquid volume adjusting unit 40, the control unit 60 returns to the above-mentioned step S2 and acquires image information from the imaging unit 30 again.

[0034] If the control unit 60 determines in step S6 that the amount of the immersion liquid 110 is less than a preset threshold (or equal to or less than the threshold), it determines that most of the immersion liquid 110 has been discharged, and activates the reinforcement processing unit 50 to discharge the gelling substance in a mist form from the discharge unit 51 (step S10). The gelling substance soaks into the sheet-shaped cell culture 100 and gels over time, completing the reinforcement processing of the sheet-shaped cell culture 100. This completes the sheet position adjustment method.

[0035] As described above, the sheet position adjustment device 10 of this embodiment includes a culture substrate 20 capable of accommodating a sheet-shaped cell culture 100 together with an immersion liquid 110, a plurality of liquid volume adjustment units 40 that supply the immersion liquid 110 to the culture substrate 20 and / or discharge the immersion liquid 110 from the culture substrate 20, an imaging unit 30 that can image the sheet-shaped cell culture 100 accommodated in the culture substrate 20, and a control unit 60 that controls the operation of the liquid volume adjustment units 40. The control unit 60 identifies the position of the sheet-shaped cell culture 100 from the image information acquired from the imaging unit 30, calculates the direction and amount of deviation of the position of the sheet-shaped cell culture 100 from the reference position of the culture substrate 20, and determines and operates at least one liquid volume adjustment unit 40 that reduces the amount of deviation, thereby adjusting the position of the sheet-shaped cell culture 100 on the culture substrate 20. As a result, the sheet position adjustment device 10 moves the sheet-shaped cell culture 100, which tends to become liberated from the surface of the culture substrate 20 and move into the immersion liquid 110, by supplying and / or discharging the immersion liquid 110, thereby enabling the sheet-shaped cell culture 100 to be positioned appropriately while suppressing deformation or damage to the fragile sheet-shaped cell culture 100.

[0036] The sheet position adjusting device 10 has a reinforcement processing unit 50 that performs a process to reinforce the sheet-shaped cell culture 100, and the control unit 60 operates the reinforcement processing unit 50 after adjusting the position of the sheet-shaped cell culture 100 with the liquid volume adjusting unit 40. In this way, the sheet position adjusting device 10 performs a reinforcement process on the sheet-shaped cell culture 100 placed at an appropriate position on the culture substrate 20, and can reinforce the sheet-shaped cell culture 100 to a desired strength.

[0037] The reinforcement processing unit 50 has a discharge unit 51 that discharges a substance that gels, thickens, or hardens. This allows the sheet position adjustment device 10 to discharge the substance that gels, thickens, or hardens onto the sheet-shaped cell culture 100 placed at an appropriate position on the culture substrate 20, thereby reinforcing the sheet-shaped cell culture 100 to a desired strength.

[0038] Furthermore, the sheet position adjustment method in this embodiment is a sheet position adjustment method for arranging a sheet-shaped cell culture 100 at an appropriate position on a culture substrate 20, and is characterized by comprising: step S2 of imaging the sheet-shaped cell culture 100 contained in the culture substrate 20 together with an immersion liquid 110 using an imaging unit 30; step S3 of identifying the position of the sheet-shaped cell culture 100 from the image information acquired from the imaging unit 30; step S4 of calculating the direction and amount of deviation of the position of the sheet-shaped cell culture 100 from the reference position of the culture substrate 20; and steps S8 to S9 of selecting and activating at least one liquid volume adjustment unit 40 that reduces the amount of deviation from multiple liquid volume adjustment units 40 that supply the immersion liquid 110 to the culture substrate 20 and / or discharge the immersion liquid 110 from the culture substrate 20. As a result, the sheet position adjustment method moves the sheet-shaped cell culture 100, which tends to become liberated from the surface of the culture substrate 20 and move into the immersion liquid 110, by supplying and / or discharging the immersion liquid 110, thereby making it possible to position the sheet-shaped cell culture 100 in an appropriate position while suppressing deformation or damage to the fragile sheet-shaped cell culture 100.

[0039] The sheet position adjustment method includes step S10 of operating the reinforcement processing unit 50, which performs a process to reinforce the sheet-shaped cell culture 100. In this way, the sheet position adjustment method performs a reinforcement process on the sheet-shaped cell culture 100 arranged at an appropriate position on the culture substrate 20, and can reinforce the sheet-shaped cell culture 100 to a desired strength.

[0040] In the sheet position adjustment method, in step S10 of operating the reinforcement processing unit 50, the reinforcement processing unit 50 ejects a substance that gels, increases viscosity, or hardens onto the sheet-shaped cell culture 100. In this way, the sheet position adjustment method ejects a substance that gels, increases viscosity, or hardens onto the sheet-shaped cell culture 100 placed at an appropriate position on the culture substrate 20, thereby reinforcing the sheet-shaped cell culture 100 to a desired strength.

[0041] The present invention is not limited to the above-described embodiment, and various modifications may be made by those skilled in the art within the technical spirit of the present invention. For example, the sheet-shaped cell culture 100 does not necessarily need to be reinforced. Furthermore, the supply tube 43 and the discharge tube 44 may be a common tube. [Explanation of symbols]

[0042] 10 Seat position adjustment device 20 Culture substrate 30 Imaging unit 40 Liquid volume adjustment section 41 Supply section 42 Discharge section 43 Supply tube 44 Discharge tube 50 Reinforcement processing section 51 Discharge part 60 Control Unit 100 Sheet-shaped cell cultures 110 Immersion liquid

Claims

1. a culture substrate capable of accommodating a sheet-shaped cell culture together with an immersion liquid; a plurality of liquid volume adjusting units for supplying the immersion liquid to the culture substrate and / or discharging the immersion liquid from the culture substrate; an imaging unit capable of imaging the sheet-shaped cell culture contained in the culture substrate; a control unit that controls the operation of the liquid amount adjusting unit, The control unit Identifying the position of the sheet-shaped cell culture from the image information acquired from the imaging unit; Calculating the direction and amount of deviation of the position of the sheet-shaped cell culture from the reference position of the culture substrate; A sheet position adjustment device, characterized by determining and activating at least one of the liquid volume adjustment units that reduces the amount of deviation, and adjusting the position of the sheet-shaped cell culture on the culture substrate.

2. a reinforcement processing unit that performs a process to reinforce the sheet-shaped cell culture, The sheet position adjusting device according to claim 1 , wherein the control unit operates the reinforcement processing unit after adjusting the position of the sheet-shaped cell culture by the liquid volume adjusting unit.

3. 3. The seat position adjusting device according to claim 2, wherein the reinforcing treatment portion has a discharge portion that discharges a substance that gels, becomes highly viscous, or hardens.

4. A sheet position adjustment method for arranging a sheet-shaped cell culture at an appropriate position on a culture substrate, comprising: capturing an image of the sheet-shaped cell culture contained in the culture substrate together with an immersion liquid by an imaging unit; Identifying the position of the sheet-shaped cell culture from the image information acquired from the imaging unit; calculating a direction and amount of deviation of the position of the sheet-shaped cell culture from a reference position of the culture substrate; A sheet position adjustment method characterized by comprising a step of selecting and activating at least one liquid volume adjustment unit that reduces the amount of deviation from a plurality of liquid volume adjustment units that supply immersion liquid to the culture substrate and / or discharge immersion liquid from the culture substrate.

5. The sheet position adjusting method according to claim 4, further comprising a step of operating a reinforcement processing unit for carrying out a process of reinforcing the sheet-shaped cell culture.

6. The sheet position adjustment method according to claim 5, characterized in that in the step of activating the reinforcement processing unit, a substance that gels, becomes viscous, or hardens is ejected onto the sheet-shaped cell culture by the reinforcement processing unit.

Citation Information

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