Cell culture device

Abstract

We provide cell culture equipment that takes the operator's convenience into consideration. [Solution] The cell culture apparatus 1 comprises a culture vessel 14, a recovery container 18 for an operator to recover some or all of the cells C cultured in the culture vessel 14, a culture circuit 4 configured to perform recovery preparation processing to enable the recovery of the cells by the operator, and a control device 5 that controls the culture circuit 4. The control device 5 is configured to switch between an operating mode between a cell-priority mode that prioritizes the culture status of the cells C and an operator-priority mode that prioritizes the convenience of the operator who recovers the recovery container 18. When the operating mode is operator-priority mode, the control device 5 causes the culture circuit 4 to perform recovery preparation processing at a different timing than when the operating mode is cell-priority mode.

Description

Technical Field

[0001] The present invention relates to a cell culture apparatus.

Background Art

[0002] Patent Document 1 discloses an automatic culture apparatus for culturing cells (hereinafter referred to as cell culture apparatus). The cell culture apparatus is configured to be capable of executing operations for seeding, subculturing, harvesting and the like based on a predetermined schedule without manual intervention. Further, the cell culture apparatus is configured to allow an operator to collect a part of the cells as a sample at the time of subculturing, and to allow the operator to collect all the cells at the time of harvesting. In general, an operator performs work for checking the quality of the collected cells and transferring the collected cells to the next process.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of Invention

Problem to be Solved by the Invention

[0004] Conventionally, it has been considered most preferable that subculturing and harvesting are performed at the timing when the number of proliferating cells becomes optimal. However, in such a concept, the working hours of the operator are not taken into consideration. For this reason, for example, the operator may need to perform work during a time period outside the original working hours, which may increase the burden on the operator.

[0005] An object of the present invention is to provide a cell culture apparatus that takes the convenience of an operator into consideration.

Means for Solving the Problem

[0006] The cell culture apparatus of the first invention comprises a first culture vessel, a recovery vessel for an operator to recover recovery cells which are some or all of the cells cultured in the first culture vessel, a processing unit configured to perform recovery preparation processing to enable the recovery of the recovery cells by the operator, and a control unit that controls the processing unit, wherein the control unit is configured to switch between an operating mode between a cell priority mode which prioritizes the culture status of the cells and an operator priority mode which prioritizes the convenience of the operator who recovers the recovery vessel, and the control unit is characterized in that when the operating mode is the operator priority mode, it causes the processing unit to perform the recovery preparation processing at a different timing than when the operating mode is the cell priority mode.

[0007] In this invention, "cell culture status" refers to, for example, whether the number of cells is optimal (whether the number of cultured cells is close to the median of the appropriate cell number range). "Operator's convenience" refers to the operator's time constraints, for example, the operator's regular working hours. In this invention, when the operating mode is operator-priority mode, the harvesting preparation process can be executed at a time convenient for the operator. Therefore, a cell culture apparatus that takes the operator's convenience into consideration can be provided.

[0008] The cell culture apparatus of the second invention is characterized in that, in the first invention, it comprises an information acquisition unit configured to acquire information regarding the number of cells being cultured in the first culture vessel, and the control unit is configured to allow at least one of a desired processing time, which is the time when it is desired that the recovery preparation process be performed, and an operator-permitted time period, which is the time period during which the operator can perform the work, to be set in advance, and using the information acquired by the information acquisition unit, predicts an appropriate growth time period, which is the time period during which the number of cells falls within a range from a predetermined lower limit to a predetermined upper limit, and when the operating mode is the operator-priority mode, causes the processing unit to perform the recovery preparation process considering the relationship between the appropriate growth time period and the desired processing time and / or the operator-permitted time period.

[0009] The present invention allows for flexible scheduling that takes into account the operator's convenience and the cell culture status. The "time at which the recovery preparation process is performed" in this invention may be set to any time between the start of the recovery preparation process and the completion of the recovery preparation process.

[0010] The cell culture apparatus of the third invention is characterized in that, in the second invention, when the operating mode is the operator priority mode, the control unit controls the processing unit to execute the recovery preparation process at the desired processing time if the desired processing time falls within the appropriate growth period, and controls the processing unit to execute the recovery preparation process at any time that falls within the appropriate growth period if the desired processing time does not fall within the appropriate growth period.

[0011] In this invention, even if the rate of cell proliferation is faster or slower than the ideal rate, the time at which the harvesting preparation process is performed can be brought as close as possible to the desired processing time.

[0012] The cell culture apparatus of the fourth invention is characterized in that, in the third invention, it comprises a second culture vessel for subculturing the cells cultured in the first culture vessel, and a density adjustment unit configured to perform seeding in the first culture vessel and the second culture vessel and to adjust the seeding density of the cells, wherein the control unit controls the density adjustment unit to set the seeding density in the first culture vessel to a predetermined first seeding density, and when the operation mode is the operator priority mode, the processing unit is controlled to perform the harvesting preparation process before the desired processing time, and the density adjustment unit controls the seeding density in the second culture vessel to set the seeding density to a second seeding density lower than the first seeding density.

[0013] Generally, the number of cells in a culture vessel after a predetermined time differs depending on whether the seeding density is high or low. More specifically, the number of cells after a predetermined time is less when the seeding density is low than when the seeding density is high. In this invention, if the preparation for harvesting is performed before the desired processing time, it means that the rate of cell proliferation in the first culture vessel is faster than the ideal rate for the operator. Generally, if the rate of cell proliferation in the first culture vessel is fast, the rate of cell proliferation in the second culture vessel is also expected to be fast. Therefore, if all the cells that can be subcultured are subcultured, the timing of harvesting the cells cultured in the second culture vessel will be even earlier, and there is a risk that the cells will be harvested at a time inconvenient for the operator.

[0014] In this invention, if the rate of cell proliferation in the first culture vessel is fast, the seeding density in the second culture vessel is controlled to be lower than that of the first culture vessel. This delays the time it takes for the cells cultured in the second culture vessel to reach the ideal number. As a result, the timing of harvesting the cells cultured in the second culture vessel can be brought closer to the next desired processing time. Therefore, it is possible to prevent cells from being harvested at an inconvenient time for the operator.

[0015] The cell culture apparatus of the fifth invention is characterized in that, in any of the second to fourth inventions, it comprises an environment adjustment unit configured to adjust the environment relating to the rate of cell proliferation, and the control unit controls the environment adjustment unit such that, when the operating mode is the operator priority mode, the appropriate proliferation time period includes the desired processing time and / or at least a portion of the appropriate proliferation time period overlaps with the operator-allowed time period.

[0016] When the rate of cell proliferation changes, the predicted optimal proliferation time generally changes. In this invention, by actively changing the optimal proliferation time, the timing of the harvesting preparation process can be actively adjusted to suit the operator's convenience.

[0017] The cell culture apparatus of the sixth invention is characterized in that, in any of the second to fifth inventions, the control unit is configured to stop the cell culture when the appropriate growth period does not overlap with the operator-allowable period.

[0018] This invention allows for the early termination of cell cultures that are progressing at a pace that does not match the operator's schedule. This reduces the waste of time caused by continuing cell cultures that are not suitable for the operator's convenience.

[0019] The cell culture apparatus of the seventh invention is characterized in that, in any of the second to sixth inventions, the control unit controls the processing unit to execute the harvesting preparation process at any time that falls within the operator-acceptable time period, when the operating mode is the operator-priority mode and the appropriate growth period does not overlap with the operator-acceptable time period.

[0020] Generally, if cells are harvested outside the optimal growth period, the number and / or quality of the cells will be unsuitable. More specifically, if cells are harvested before the optimal growth period, the number of cells will be too small. If the optimal growth period is exceeded, there is a risk of cell differentiation, for example. However, in fields such as research and development, such cells can sometimes be utilized. In such cases, it is effective to harvest some or all of the cells according to the operator's convenience. [Brief explanation of the drawing]

[0021] [Figure 1] This is a schematic front view of the cell culture apparatus according to this embodiment. [Figure 2] This is a schematic diagram showing the culture circuit. [Figure 3] This is a block diagram showing the electrical configuration of a cell culture device. [Figure 4] (a) to (d) are explanatory diagrams showing the procedure for detaching cells from the bottom of the culture vessel. [Figure 5] (a) and (b) are diagrams showing examples of screens displayed on an output unit. [Figure 6] This is a diagram showing an example of a screen displayed on an output unit. [Figure 7] This is a flowchart showing an outline of the procedure of a cell culture method. [Figure 8] This is a flowchart showing the procedure of subculture or harvesting when the operation mode is the cell priority mode. [Figure 9] (a) to (f) are explanatory diagrams showing the timing of subculture or harvesting. [Figure 10] This is a flowchart showing the procedure of subculture or harvesting when the operation mode is operator priority mode A. [Figure 11] (a) to (f) are explanatory diagrams showing the timing of subculture or harvesting. [Figure 12] This is a flowchart showing the procedure of subculture or harvesting when the operation mode is operator priority mode B. [Figure 13] This is a flowchart showing the procedure of branch processing. [Figure 14] (a) to (f) are explanatory diagrams showing the timing of subculture or harvesting. [Mode for Carrying Out the Invention]

[0022] Next, an embodiment of the present invention will be described. For the convenience of explanation only, the vertical direction on the paper surface of Fig. 1 is defined as the up-down direction (the vertical direction in which gravity acts).

[0023] (Outline of Cell Culture Apparatus) The outline of the cell culture apparatus 1 according to the present embodiment will be described mainly with reference to Fig. 1 and Fig. 2. Fig. 1 is a schematic front view of the cell culture apparatus 1. Fig. 2 is a schematic diagram of the culture circuit 4. The cell culture apparatus 1 is provided with a refrigerator 2 constituting a low-temperature area, an incubator 3 constituting a culture area, a culture circuit 4 (see Fig. 2, which is the processing unit and the density adjustment unit of the present invention), and a control device 5 (see Fig. 1, which is the control unit of the present invention).

[0024] Refrigerator 2 is configured to maintain the temperature of the low-temperature area at approximately 4°C. This allows for the storage of various reagents within Refrigerator 2 while suppressing changes in their components. Refrigerator 2 may also be configured to allow the temperature of the low-temperature area to be adjusted to a temperature other than approximately 4°C. Refrigerator 2 has a door 2a that can be opened and closed.

[0025] Incubator 3 is configured to maintain the temperature of the culture area at approximately 37°C, for example. This allows cells to be cultured within Incubator 3. Incubator 3 may also be configured to adjust the temperature of the culture area to a temperature other than approximately 37°C. Incubator 3 has an openable and closable door 3a. Examples of cells to be cultured include, but are not limited to, mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs).

[0026] Culture circuit 4 is used to perform processes such as cell seeding, culture, subculturing, and harvesting. Culture circuit 4 is configured to move various liquids between multiple containers (described later). These various liquids include the reagents culture medium M (see Figure 4(a)) and detachment solution L (see Figure 4(b)), as well as the cell suspension S (see Figure 4(d)), which is a mixture of the reagents and cells C (see Figure 4(a)). The specific configuration of culture circuit 4 will be described later.

[0027] The control device 5 is, for example, a general-purpose computer device. The control device 5 may be placed inside the incubator 3, for example, but its location is not limited to this. The control device 5 has an input unit 5a, an output unit 5b, and a storage unit 5c (see Figure 3). The input unit 5a has at least one of the following: a known keyboard, mouse, touch panel, etc. The output unit 5b has, for example, a display (not shown). The storage unit 5c has, for example, RAM and / or a hard disk (not shown). The control device 5 is configured to cause the culture circuit 4 to perform cell culture operations according to a predetermined schedule. Other processes that the control device 5 can perform will be described later as needed.

[0028] (Configuration of the culture circuit) The configuration of the culture circuit 4 will be explained with reference to Figure 2. The culture circuit 4 forms, for example, a sealed closed system. The culture circuit 4 is configured to prevent bacteria and other organisms that could harm cells from entering (i.e., to maintain a sterile state). The culture circuit 4 includes, as an example, a culture medium storage container 11, a stripping solution storage container 12, reagent warming containers 13a and 13b, a culture container 14 (the first culture container of the present invention), a subculturing container 15, a culture container 16 (the second culture container of the present invention), a waste liquid container 17, and a recovery container 18. Bottles or bags may be used as these containers, but are not limited to these. The culture circuit 4 also includes, for example, tubes 21, 22, 23, 24, and 25 to which multiple containers are connected. The culture circuit 4 also includes, for example, pumps P1, P2, P3, and P4 configured to move various liquids. Furthermore, the culture circuit 4 includes, for example, openable and closable valves V1, V2, V3a, V3b, V4, V5, V6, V7, and V8, which are provided corresponding to each container. Pumps P1 to P4 and valves V1 to V8 are electrically connected to the control device 5 (see Figure 3).

[0029] The culture medium storage container 11 is a container for storing culture media used for cell culture. The type of culture medium can, for example, be a serum medium containing animal-derived serum (e.g., bovine serum), but is not limited to this. The culture medium storage container 11 is housed inside the refrigerator 2 (see Figure 2). The culture medium storage container 11 is connected, for example, to a branched tube 21. A valve V1 for opening and closing the culture medium storage container 11 is provided near the end of the tube 21 to which the culture medium storage container 11 is connected.

[0030] The delamination solution storage container 12 is a container for storing a delamination solution used to detach cultured cells from the container. Generally, cultured cells adhere to the bottom surface of the container. The delamination solution is a liquid containing, for example, a cell delamination enzyme (such as trypsin, a known enzyme) for detaching cells from the bottom surface of the container, but is not limited to this. The delamination solution storage container 12 is housed inside the refrigerator 2 (see Figure 2). The delamination solution storage container 12 is connected to, for example, a tube 21. A valve V2 for opening and closing the tube 21 is provided near the end to which the delamination solution storage container 12 is connected.

[0031] The reagent warming containers 13a and 13b are containers for warming various reagents (culture medium or stripping solution). The reagents become capable of performing their respective functions when warmed in the reagent warming container 13a or 13b. The reagent warming containers 13a and 13b are housed in the incubator 3 (see Figure 2). The reagent warming containers 13a and 13b are connected, for example, to branched tubes 22. Reagent warming container 13a is used, for example, to warm culture medium. Reagent warming container 13b is used, for example, to warm stripping solution. A valve V3a for opening and closing the tube 22 is provided near the end to which reagent warming container 13a is connected. A valve V3b for opening and closing the tube 22 is also provided near the end to which reagent warming container 13b is connected.

[0032] The culture vessel 14 is a container for culturing cells. The culture vessel 14 is the container in which cells are first seeded when the culture of a predetermined cell type is started. The culture vessel 14 is housed inside the incubator 3 (see Figure 2). The culture vessel 14 is connected, for example, to a branched tube 23. A valve V4 for opening and closing the end of the tube 23 to which the culture vessel 14 is connected is provided near that end.

[0033] The subculturing container 15 is a container used, for example, when subculturing cells cultured in the culture vessel 14. The subculturing container 15 is housed inside the incubator 3 (see Figure 2). The subculturing container 15 is connected to, for example, a tube 25. A valve V5 for opening and closing the tube 25 is provided near the end to which the subculturing container 15 is connected.

[0034] The culture vessel 16 is a container for culturing cells. The culture vessel 16 is generally larger than the culture vessel 14, but is not limited to that size. The culture vessel 16 is used to subculture and further propagate cells cultured in the culture vessel 14. The culture vessel 16 is housed within the incubator 3 (see Figure 2). The culture vessel 16 is connected, for example, to a tube 23. A valve V6 for opening and closing the tube 23 is provided near the end to which the culture vessel 16 is connected.

[0035] The waste liquid container 17 is a container for disposing of used reagents. The waste liquid container 17 is located, for example, in a room temperature area. The waste liquid container 17 is connected, for example, to a branched tube 24. A valve V7 for opening and closing the end of the tube 24 is provided near the end to which the waste liquid container 17 is connected.

[0036] The recovery container 18 is a container used by the operator to recover some or all of the cultured cells. The recovery container 18 is housed, for example, in a refrigerator 2 (see Figure 2). The recovery container 18 is connected, for example, to a tube 24. A valve V8 for opening and closing the end of the tube 24 is provided near the end to which the recovery container 18 is connected.

[0037] Each container is provided with a path (not shown) for releasing air and a filter (not shown) positioned along the path. The path and filter are designed to draw air into the container from which the liquid is discharged and to discharge air from the container into which the liquid is received, when the liquid is moved by one of the pumps P1 to P4.

[0038] Tubes 21-25 are piping components for transferring liquid between containers while maintaining the sterile condition of the culture circuit 4. Tubes 21-25 may, for example, be flexible, but are not limited to this. Tube 21 is connected to pump P1 and communicates with tube 22. Tube 22 is connected to pumps P1, P2, and P4 and communicates with tubes 21, 23, and 25. Tube 23 is connected to pumps P2 and P3 and communicates with tubes 22 and 24. Tube 24 is connected to pump P3 and communicates with tube 23. Tube 25 is connected to pump P4 and communicates with tube 22.

[0039] Pumps P1 to P4 are pumping devices for transferring liquid between containers while maintaining the sterile condition of the culture circuit 4. While known tubular pumps are used as pumps P1 to P4, the type of pumping device is not limited to these. Pump P1 is configured to transfer liquid between a container connected to tube 21 and a container connected to tube 22. Pump P2 is configured to transfer liquid between a container connected to tube 22 or 25 and a container connected to tube 23. Pump P3 is configured to transfer liquid between a container connected to tube 23 and a container connected to tube 24. Pump P4 is configured to transfer liquid between a container connected to tube 22 or 23 and a container connected to tube 25. Pumps P1 to P4 are electrically connected to the control device 5. Pumps P1 to P4 are configured to adjust the amount of liquid transferred by being controlled by the control device 5.

[0040] Furthermore, a vial (not shown) containing seed cells (not shown) to be cultured is connected to the culture circuit 4. The culture circuit 4 is also equipped with an injection device (not shown) configured to extract seed cells from the vial and inject them into the culture vessel 14.

[0041] (Further components) Further components of the cell culture apparatus 1 will be described with reference to Figure 3. Figure 3 is a block diagram showing the electrical configuration of the cell culture apparatus 1. The cell culture apparatus 1 comprises a cell observation unit 31 (information acquisition unit of the present invention), an environment detection unit 32, and an environment adjustment unit 33.

[0042] The cell observation unit 31 is configured to acquire information regarding the number of cells being cultured. This information refers to, for example, the number of cells themselves, or the number of cells per unit volume (i.e., cell density). The cell observation unit 31 includes, for example, a camera (not shown). The camera is positioned, for example, one near the culture vessel 14 and one near the culture vessel 16. The camera is configured, for example, to photograph cells and acquire image data. The cell observation unit 31 is electrically connected to the control device 5. The control device 5 performs image processing based on the image data acquired by the cell observation unit 31 to acquire information regarding the number of cells or the density of cells per unit volume. Alternatively, the cell observation unit 31 may perform image processing and acquire information regarding the number of cells on behalf of the control device 5. Based on the observation results from the cell observation unit 31, the control device 5 predicts the rate of cell proliferation in the culture circuit 4. Note that the cell observation unit 31 is not limited to the above, as long as it is configured to acquire information regarding the number of cells. For example, the cell observation unit 31 may be configured to indirectly obtain information regarding the number of cells by observing metabolites in the culture medium (used culture medium) used in the culture vessel 14 or culture vessel 16.

[0043] The environmental detection unit 32 is for detecting the cell culture environment in the cell culture apparatus 1. The cell culture environment refers to the environment that can affect the cell culture state, such as the temperature inside the incubator 3, the carbon dioxide concentration in the air inside the culture circuit 4, and the pH of the culture medium. The environmental detection unit 32 includes, for example, a thermometer (not shown), a carbon dioxide concentration meter (not shown), and a pH meter (not shown). The environmental detection unit 32 is electrically connected to the control device 5 and is configured to transmit a detection signal to the control device 5. The environmental detection unit 32 may have other components capable of detecting the cell culture environment.

[0044] The environmental adjustment unit 33 is for adjusting the cell culture environment in the cell culture apparatus 1 (more precisely, the environment relating at least to the rate of cell proliferation). The environmental adjustment unit 33 includes, for example, a heater (not shown) located inside the incubator 3, a supply port and valve (not shown) for supplying carbon dioxide into the culture circuit 4, and an exhaust port and valve (not shown) for discharging air from the culture circuit 4. The environmental adjustment unit 33 is electrically connected to the control device 5 and operates according to command signals sent from the control device 5. The environmental adjustment unit 33 may have other components that can adjust the cell culture environment. The control device 5 is configured to adjust the internal and / or external environment of the culture circuit 4 by controlling the environmental adjustment unit 33 based on the observation results from the cell observation unit 31 and the detection results from the environment detection unit 32, which will be described later.

[0045] (Outline of cell culture procedure) Next, we will explain the general procedure for cell culture in cell culture apparatus 1 with reference to Figures 4(a) to (d). Figures 4(a) to (d) are explanatory diagrams showing the procedure for detaching cells C from the bottom surface of culture vessel 14.

[0046] The period from the start of cell culture to subculturing, and the period from subculturing to harvesting, can vary depending on the type of cells being cultured and the target number of cells. Furthermore, harvesting may occur without subculturing, or multiple subculturings may be performed. In this embodiment, the period from the start of culture to subculturing is assumed to be approximately three days. Additionally, subculturing is assumed to be performed once before harvesting. The period from subculturing to harvesting is assumed to be approximately three days.

[0047] In the initial state, all valves V1 to V8 are closed. The control device 5 opens valves located near the source container of the liquid and valves located near the destination container of the liquid, and operates a pump located between the source and destination containers to move the liquid between them. After that, the control device 5 closes these valves and stops the pump from operating. Hereafter, for the sake of simplicity, the above-described control of valve opening and closing and pump control will simply be referred to as "the control device 5 controls the valves and pump." The control device 5 controls each part of the cell culture apparatus 1 to perform the following seeding, subculturing, and harvesting processes.

[0048] First, the control device 5 performs the seeding process. Specifically, the control device 5 first controls valves V1, V3a and pump P1 to transfer a predetermined amount of culture medium M (see Figure 4(a)) from the culture medium storage container 11 to the reagent warming container 13a. After the culture medium M has warmed up, the control device 5 controls valves V3a, V4 and pump P2 to transfer the culture medium M from the reagent warming container 13a to the culture container 14. The control device 5 also controls an injection device (not shown) to transfer seed cells from the vial to the culture container 14. As a result, the seed cells are seeded in the culture container 14 at a predetermined seeding density. Over time, the seed cells are cultured and become cells C (see Figure 4(a)). Cells C adhere to the bottom surface of the culture container 14.

[0049] Approximately three days later, the control device 5 performs the subculturing process of cells C (transferring cells C from culture vessel 14 to culture vessel 16). Specifically, first, the control device 5 controls valves V1, V3a and pump P1 to move fresh culture medium from culture medium storage container 11 to reagent warming container 13a. Next, the control device 5 controls valves V2, V3b and pump P1 to move detachment solution L (see Figure 4(b)) from detachment solution storage container 12 to reagent warming container 13b. Next, the control device 5 controls valves V4, V7 and pump P3 to move used culture medium M from culture vessel 14 to waste liquid container 17 (see Figure 4(a)). Next, the control device 5 controls valves V3b, V4 and pump P2 to move the warmed detachment solution L from reagent warming container 13b to culture vessel 14 (see Figure 4(b)). After a predetermined waiting time has elapsed, the control device 5 controls valves V4, V7 and pump P3 to move the detachment solution L from the culture vessel 14 to the waste liquid container 17 (see Figure 4(c)). The cells C begin to detach from the bottom surface of the culture vessel 14 due to the detachment solution L. Furthermore, the control device 5 controls valves V3a, V4 and pump P2 to move a portion of the preheated culture medium M from the reagent warming container 13a to the culture vessel 14 (see Figure 4(d)). As a result, the cells C detach from the bottom surface of the culture vessel 14 and mix with the culture medium M in the culture vessel 14 to form a cell suspension S (see Figure 4(d)).

[0050] Furthermore, the control device 5 controls valves V3a, V5 and pump P4 to move the culture medium M, which is used to adjust the seeding density during subculturing, from the reagent warming container 13a to the subculturing container 15. The control device 5 also controls valves V4, V5 and pumps P2, P4 to move the amount of cell suspension S required for subculturing from the cell suspension S in the culture container 14 from the culture container 14 to the subculturing container 15. By mixing the new culture medium M and the cell suspension S in the subculturing container 15, a cell suspension (not shown) with the desired seeding density can be obtained. Next, the control device 5 controls valves V5, V6 and pumps P2, P4 to move the cell suspension from the subculturing container 15 to the culture container 16. In this way, subculturing is completed. The control device 5 also controls valves V4, V8 and pump P3 to move the cell suspension remaining in the culture container 14 from the culture container 14 to the recovery container 18. This series of processes, which involves transferring a portion of cells C from the culture vessel 14 to the recovery vessel 18, is included in the recovery preparation process of the present invention. At this time, the culture circuit 4 functions as the processing unit of the present invention. The cell suspension sent to the recovery vessel 18 is recovered by the operator and used, for example, for quality evaluation of cultured cells. The cell suspension recovered by the operator during subculturing is included in the recovery cells of the present invention.

[0051] Approximately three days later, the control device 5 performs the harvesting process for cells C. Specifically, the procedure for detaching cells C from the bottom of the culture vessel 16 is the same as the procedure for processing cells C in the culture vessel 14 described above (see Figures 4(a) to (d)). After that, the culture vessel 16 containing the cell suspension S is recovered by the operator. Further, the cell suspension S may be separated into cells C and other substances by, for example, a centrifuge (not shown). Such a process that makes it possible to recover all of the cells C in the culture vessel 16 at the time of harvest is also included in the recovery preparation process of the present invention. In this case, the culture vessel 16 also corresponds to the recovery container of the present invention. The culture circuit 4 functions as a processing unit of the present invention. The cell suspension S recovered by the operator at the time of harvest is also included in the cells for recovery of the present invention. Alternatively, the cell suspension S may be transferred from the culture vessel 16 to the recovery container. Alternatively, the cell suspension S may be transferred from the culture vessel 16 to another container (not shown), and that other container may be recovered. In this case, that other container corresponds to the recovery container of the present invention.

[0052] Traditionally, it has been considered most preferable to perform subculturing and harvesting at the time when the number of proliferating cells is optimal. However, this approach does not take into account the operator's working hours. As a result, for example, the operator may need to perform work outside of their regular working hours, which could increase their workload. Therefore, in order to provide a cell culture apparatus 1 that takes the operator's convenience into consideration, the control device 5 is configured as follows.

[0053] (Settings that can be configured on the control unit) The settings that can be configured in the control device 5 will be explained with reference to Figures 5(a) to 5(6). Figures 5(a), (b), and 5(6) show examples of screens displayed on the output unit. Here, as an example, we will proceed with the explanation assuming that the input unit 5a has a touch panel and the output unit 5b has a liquid crystal display. However, this is not the only option.

[0054] As shown in Figure 5(a), the control device 5 is configured, for example, to display the menu screen S1 on the output unit 5b. The input unit 5a is configured so that the operator can touch the parts of the menu screen S1 where the "Mode Selection" button and the "Settings" button are displayed. Mode selection refers to the selection of the operating mode of cell culture by the cell culture device 1 (details will be described later). Settings refers to the setting of various culture conditions, which will be described later.

[0055] When the operator touches the "Mode Selection" button on the menu screen S1 (see Figure 5(a)), the control device 5 displays the mode selection screen S2 shown in Figure 5(b) on the output unit 5b. The input unit 5a is configured so that the operator can select, for example, "Cell Priority Mode," "Operator Priority Mode A," and "Operator Priority Mode B" on the mode selection screen S2 (details of each operating mode will be described later). Both Operator Priority Mode A and Operator Priority Mode B are included in the operator priority modes of the present invention.

[0056] For example, the cell-priority mode is selected by default. The operator selects one of the operating modes before starting cell culture. The information of the selected operating mode is then stored in the memory unit 5c. After cell culture has started, the control device 5 executes the operating mode that was previously stored in the memory unit 5c. In this way, the control device 5 is configured to switch between the cell-priority mode and operator-priority mode A or operator-priority mode B.

[0057] When the operator touches the "Settings" button on the menu screen S1 (see Figure 5(a)), the control device 5 displays the setting screen S3 shown in Figure 6 on the output unit 5b. The input unit 5a is configured to allow setting of, for example, "Desired subculturing time," "Desired harvest time," "Lower growth rate," "Upper growth rate," "Operator-acceptable time period," and "Limit time period" on the setting screen S3. These are setting items related to the cell culture schedule. The setting screen S3 may also allow setting of cell culture conditions such as the type of cells to be cultured and the type and amount of culture medium used.

[0058] The desired subculturing time is the time the operator desires for the subculturing process to begin using the cell culture apparatus 1. In Figure 6, the desired subculturing time is set to 13:00. The desired subculturing time is, for example, three days after the start date of cell culture. The desired subculturing time may be directly input by the operator. Alternatively, the desired subculturing time may be indirectly obtained by calculation when the operator sets the cell culture conditions. In this case, the operator may set the cell culture conditions so that the desired subculturing time is 13:00. The desired subculturing time is set to fall within the limit time period described later. The desired subculturing time information is used in both operator priority mode A and operator priority mode B (details will be described later). The desired subculturing time is included in the desired processing time of the present invention.

[0059] The desired harvest time is the time the operator wishes to start harvesting using the cell culture apparatus 1. The desired harvest time can be set in the same way as the method for setting the desired subculturing time described above. The desired harvest time information is also used in both operator priority mode A and operator priority mode B (details will be described later). The desired harvest time is also included in the desired processing time of the present invention.

[0060] The growth rate lower limit is the minimum cell growth rate required at the time of subculturing or harvesting. The cell growth rate is expressed, for example, as a percentage based on the number of seed cells (or seed cell seeding density). If the rate of cell growth is too slow compared to the ideal rate (i.e., if the cells are not growing normally), the required cell growth rate cannot be obtained even after a certain amount of time has passed. Therefore, it is generally necessary to set such a lower limit. In Figure 6, the growth rate lower limit is set to X%. The growth rate lower limit shown in Figure 6 is assumed to be the growth rate lower limit at the time of subculturing. Although not shown in the illustration, the growth rate lower limit at harvesting is also displayed on the setting screen S3. The growth rate lower limit can be input by the operator, for example. The control device 5 is configured to calculate the rate of cell growth during cell culture based on a predetermined calculation formula and to predict the time when the growth rate reaches the growth rate lower limit (hereinafter referred to as the lower limit arrival time). The information on the lower limit arrival time is used in all operating modes.

[0061] The growth rate limit is the upper limit of the cell growth rate at the time of subculturing or harvesting. Generally, if cells proliferate too much, they may differentiate (acquire functions different from the intended function). Therefore, it is generally necessary to set such an upper limit. In Figure 6, the growth rate is set to Y%, which is greater than X%. The growth rate limit shown in Figure 6 is assumed to be the growth rate limit at the time of subculturing. Although not shown in the illustration, the growth rate limit at harvesting is also displayed on the setting screen S3. The growth rate limit can be entered, for example, by the operator. The control device 5 is configured to predict the time when the growth rate reaches the growth rate limit (hereinafter referred to as the time when the limit is reached). The information on the time when the limit is reached is used in all operating modes.

[0062] The operator-permitted time slot is the period during which the operator is available to work. In Figure 6, the operator-permitted time slot is set from 9:00 to 17:00. The operator-permitted time slot can be entered by the operator. The operator-permitted time slot information is used when the operating mode is Operator Priority Mode B (details will be described later).

[0063] The limit time zone is the period during which cells can be subcultured or harvested, taking into account the cell growth rate. The limit time zone is the time zone on the day subculture or harvesting takes place. If the cell growth rate is abnormally fast, subculture or harvesting may occur earlier than the limit time zone. Conversely, if the cell growth rate is abnormally slow, subculture or harvesting may occur later than the limit time zone. In such cases, the cells are not growing normally. The limit time zone is obtained, for example, by calculation when the operator sets the cell culture conditions. This limit time zone information is used in all operating modes.

[0064] (Overview of cell culture methods) Next, an overview of the cell culture method executed by the control device 5 will be explained with reference to the flowchart in Figure 7. First, the control device 5 starts cell culture by seeding cells into the culture vessel 14 as described above (S101). During cell culture, the control device 5 accumulates information on the observation results from the cell observation unit 31. Next, the control device 5 performs subculturing or harvesting based on a schedule corresponding to the operating mode (S102). Details will be described later. Next, the control device 5 decides whether to terminate or continue the cell culture (S103). Termination means completion of harvesting or cessation of cell culture. If the control device 5 decides to terminate the cell culture (S103: Yes), the cell culture ends at that point (S104). If the control device 5 decides to continue the cell culture (S103: No), it returns to S102 and continues to execute the cell culture.

[0065] (Cell priority mode) Next, the subculturing or harvesting procedure when the operating mode is cell-priority mode will be explained with reference to the flowchart in Figure 8 and the explanatory diagrams in Figures 9(a) to (f). The horizontal axis in Figures 9(a) to (f) represents time. Cell-priority mode is an operating mode that prioritizes the cell culture status over the operator's convenience. Cell culture status refers to the situation such as whether the number of cells is optimal or not (for example, whether the number of cultured cells is close to the median of the appropriate cell number range). In cell-priority mode, the timing of subculturing and harvesting is determined according to the cell proliferation rate, as follows.

[0066] First, the control device 5 determines whether the current time is the time to perform the final prediction of the cell proliferation rate before subculturing or harvesting (hereinafter referred to as the final prediction time) (S201). For example, if the number of days from the start of culture to subculturing is three days, the final prediction time is, for example, 8 hours before the initially scheduled subculturing time.

[0067] If the current time is not the final predicted time (S201: No), the control device 5 waits until the final predicted time arrives. If the current time is the final predicted time (S201: Yes), the control device 5 makes the final prediction as follows. First, the control device 5 calculates the cell proliferation rate at the final predicted time (S202). Next, based on the proliferation rate information, the control device 5 predicts the optimal time for subculturing or harvesting, the time to reach the lower limit, and the time to reach the upper limit (S203). The optimal time is the time between the time to reach the lower limit and the time to reach the upper limit. The optimal time is the time when the cell proliferation rate is predicted to be an intermediate value between X% and Y%. Generally, since cells proliferate exponentially, the optimal time is slightly earlier than the time midway between the time to reach the lower limit and the time to reach the upper limit (see Figure 9(a), etc.). The time period between the time to reach the lower limit and the time to reach the upper limit, that is, the time period when the cell proliferation rate falls within the range from the lower limit to the upper limit of the proliferation rate, is the time period when the cell proliferation rate is appropriate (hereinafter, the appropriate proliferation time period). The optimal time and appropriate growth period vary depending on the growth rate of the cultured cells.

[0068] Next, the control device 5 determines whether the appropriate propagation time period overlaps with the limit time period (S204). If there is an overlap (S204: Yes), the control device 5 determines whether the optimal time falls within the limit time period (S205). If the optimal time falls within the limit time period (S205: Yes), the control device 5 starts subculturing (or harvesting) at the optimal time (S206; see Figures 9(a) and (b)). If the optimal time does not fall within the limit time period (S205: No), the control device 5 starts subculturing (or harvesting) at the time that falls within the limit time period and is closest to the optimal time (S207). More specifically, if the optimal time is earlier than the earliest time within the limit time period, the control device 5 starts subculturing (or harvesting) at the earliest time within the limit time period (see Figure 9(c)). If the optimal time is later than the latest time within the limit period, the control device 5 will start subculturing (or harvesting) at the latest time within the limit period (see Figure 9(d)).

[0069] Furthermore, if there is no overlap between the appropriate growth period and the limit period (S204: No), the control device 5 will stop the cell culture (S208; see Figures 9(e) and (f)).

[0070] (Operator priority mode A) Next, the procedure for subculturing or harvesting when the operating mode is Operator Priority Mode A will be explained with reference to the flowchart in Figure 10 and the explanatory diagrams in Figures 11(a) to (f). The horizontal axis in Figures 11(a) to (f) represents time. Operator Priority Mode A is one of the operating modes in which the timing of subculturing and harvesting is determined according to the operator's convenience. Simply put, in Operator Priority Mode A, the desired processing time is taken into consideration instead of the optimal time.

[0071] First, the control device 5 calculates the cell proliferation rate at the final predicted time, similar to when the operating mode is cell-priority mode (S201, S202). Next, the control device 5 predicts the time at which the lower limit and upper limit of the cell proliferation rate are reached (S209). The control device 5 may also predict the optimal time in conjunction with the time at which the lower limit and upper limit are reached. Next, the control device 5 determines whether the appropriate proliferation time period overlaps with the limit time period (S204). If there is an overlap between the appropriate proliferation time period and the limit time period (S204: Yes), the control device 5 determines whether the desired processing time (the desired subculturing time or desired harvest time mentioned above) falls within the appropriate proliferation time period (S210). If the desired processing time falls within the appropriate proliferation time period (S210: Yes), the control device 5 starts subculturing (or harvesting) at the desired processing time (S211. See Figures 11(a) and (b)). If the desired processing time does not fall within the appropriate growth time period (S210: No), the control device 5 starts subculturing (or harvesting) at the time that falls within the appropriate growth time period and is closest to the desired processing time (S212). More specifically, if the desired processing time is earlier than the lower limit arrival time, the control device 5 starts subculturing (or harvesting) at the lower limit arrival time (see Figure 11(c)). If the desired processing time is later than the upper limit arrival time, the control device 5 starts subculturing (or harvesting) at the upper limit arrival time (see Figure 11(d)). In this way, when the operating mode is operator-priority mode A, the harvesting preparation process is executed at a different timing than when the operating mode is cell-priority mode. More specifically, when the operating mode is operator-priority mode A, the harvesting preparation process is executed considering the relationship between the appropriate growth time period and the desired processing time.

[0072] If there is no overlap between the appropriate growth period and the limit period (S204: No), the control device 5 will stop the cell culture (S208. See Figures 11(e) and (f)).

[0073] (Operator priority mode B) Next, the procedure for subculturing or harvesting when the operating mode is Operator Priority Mode B will be explained with reference to the flowcharts in Figures 12 and 13 and the explanatory diagrams in Figures 14(a) to (f). The horizontal axis in Figures 14(a) to (f) represents time. Operator Priority Mode B is one of the operating modes in which the timing of subculturing and harvesting is determined according to the operator's convenience, and it is an operating mode that performs partially different processing from Operator Priority Mode A. Simply put, in Operator Priority Mode B, the desired processing time and the operator's acceptable time period are taken into consideration. Note that in Figures 14(a) to (f), the operator's acceptable time period is simply expressed as "acceptable time period" due to space limitations on the page.

[0074] First, the control device 5 calculates the cell proliferation rate at the final predicted time, similar to when the operating mode is cell-priority mode or operator-priority mode A (S201, S202). Next, the control device 5 predicts the time at which the lower limit and upper limit of the cell proliferation rate are reached (S209). The control device 5 may also predict the optimal time in conjunction with the time at which the lower limit and upper limit are reached. Next, it determines whether the appropriate proliferation time period overlaps with the limit time period (S204). If there is an overlap between the appropriate proliferation time period and the limit time period (S204: Yes), the control device 5 determines whether the appropriate proliferation time period overlaps with the operator-allowed time period (S213).

[0075] If there is an overlap between the appropriate propagation time and the operator-allowable time (S213: Yes), the control device 5 determines whether the desired processing time falls within the appropriate propagation time (S210). If the desired processing time falls within the appropriate propagation time (S210: Yes), the control device 5 starts subculturing (or harvesting) at the desired processing time (S211; see Figures 14(a) and (b)). If the desired processing time does not fall within the appropriate propagation time (S210: No), the control device 5 starts subculturing (or harvesting) at the time that falls within the appropriate propagation time and is closest to the desired processing time (S212). More specifically, if the desired processing time is earlier than the lower limit time, the control device 5 starts subculturing (or harvesting) at the lower limit time (see Figure 14(c)). If the desired processing time is later than the upper limit time, the control device 5 starts subculturing (or harvesting) at the upper limit time (see Figure 14(d)).

[0076] If there is no overlap between the appropriate growth period and the operator-acceptable period (S213: No), the control device 5 executes the branching process (S214) described later. If there is no overlap between the appropriate growth period and the limit period (S204: No), the control device 5 stops the cell culture (S208; not shown in the figure).

[0077] The branching process (S214) will be explained with reference to Figure 13. The control device 5 determines which of the lower limit arrival time and the upper limit arrival time is closer to the desired processing time (S301). If the upper limit arrival time is closer to the desired processing time than the lower limit arrival time (S301: upper limit), the control device 5 starts subculturing (or harvesting) at the earliest time within the operator's allowable time frame (S302; see Figure 14(e)). In this case, cell differentiation may have already occurred at the time of subculturing (or harvesting), but the operator's convenience takes precedence. Even if such cells are subculturished (or harvested), they may still be useful in fields such as research and development.

[0078] If the time to reach the lower limit is closer to the desired processing time than the time to reach the upper limit (S301: lower limit), the control device 5 displays a warning on the output unit 5b, for example (S303). The control device 5 then displays an option on the output unit 5b for the operator to choose whether or not to perform subculturing (or harvesting) at the time to reach the lower limit (S304). If it is selected to perform subculturing (or harvesting) at the time to reach the lower limit (S304: Yes), the control device 5 starts subculturing (or harvesting) at the time to reach the lower limit (S305; see Figure 14(f)). If it is selected not to perform subculturing (or harvesting) at the time to reach the lower limit (S304: No), the control device 5 stops cell culture (S306).

[0079] Thus, even when the operating mode is operator-priority mode B, the recovery preparation process is executed at a different timing than when the operating mode is cell-priority mode. More specifically, when the operating mode is operator-priority mode B, the recovery preparation process is executed considering the relationship between the appropriate growth period, the desired processing time, and the operator-acceptable time period.

[0080] As described above, when the operating mode is operator-priority mode, the recovery preparation process is executed at a different timing than when the operating mode is cell-priority mode. This allows the recovery preparation process to be executed at a time convenient for the operator. Therefore, a cell culture apparatus 1 that takes the operator's convenience into consideration can be provided.

[0081] Furthermore, when the operating mode is set to operator-priority mode, the relationship between the appropriate growth time, the desired processing time, and / or the operator-acceptable time is taken into consideration. This allows for flexible scheduling that takes into account the operator's convenience and the cell culture status.

[0082] Furthermore, if the desired processing time does not fall within the optimal growth period, the preparation for collection will begin at any time that does fall within the optimal growth period. This allows the start time of the preparation for collection to be as close as possible to the desired processing time, regardless of whether the cell growth rate is faster or slower than the ideal rate.

[0083] Furthermore, if the optimal growth period does not overlap with the operator's acceptable time frame, cell culture can be stopped. This allows for the early termination of cell culture that is progressing at a pace that does not match the operator's schedule. Therefore, it is possible to reduce the waste of time caused by continuing cell culture that is not appropriate for the operator's convenience.

[0084] Furthermore, if the optimal growth period does not overlap with the operator-acceptable period, the preparation for cell retrieval can be performed at any time within the operator-acceptable period. If the optimal growth period is exceeded, for example, cell differentiation may occur, but in the field of research and development, such cells may be useful. In such cases, it is effective to retrieve some or all of the cells according to the operator's convenience.

[0085] Next, modified examples of the above embodiments will be described. However, components having the same configuration as the above embodiments will be denoted by the same reference numerals and their descriptions will be omitted as appropriate.

[0086] (1) The control device 5 may be configured to adjust the seeding density during subculturing in at least one of operator priority modes A and B as follows. For example, assume that the timing of subculturing (i.e., when cells are transferred from culture vessel 14 to collection vessel 18) is earlier than the desired subculturing time described above. In this case, the actual growth rate of the cells is faster than the ideal growth rate. The difference between the desired subculturing time and the time when subculturing begins is called the first time lag. In such a case, if seeding to culture vessel 16 is performed at the same seeding density as seeding to culture vessel 14 (first seeding density), the timing at which harvesting can begin will be considerably earlier than the desired harvest time. More specifically, if the difference between the desired harvest time and the time when harvesting begins is called the second time lag, the second time lag will be approximately twice the first time lag. As a result, there is a risk that the preparation for collection will be performed at a time inconvenient for the operator. Therefore, if the control device 5 controls the culture circuit 4 to perform the harvest preparation process before the desired processing time, it may also control the culture circuit 4 to set the seeding density in the culture vessel 16 to a second seeding density, which is lower than the first seeding density. This delays the time it takes for the cells cultured in the culture vessel 16 to reach the ideal number. As a result, the timing of the harvest preparation process for the cells cultured in the culture vessel 16 can be brought closer to the desired harvest time. In other words, by appropriately adjusting the seeding density, the second time lag can be reduced compared to when the seeding density is not adjusted. Therefore, it is possible to prevent cells from being harvested at an inconvenient time for the operator. In this case, the culture circuit 4 functions as a density adjustment unit of the present invention.

[0087] (2) The control device 5 may be configured to control the environmental adjustment unit 33 in at least one of operator priority modes A and B, so as close as possible to a time convenient for the operator when the recovery preparation process begins. More specifically, the control device 5 may control the environmental adjustment unit 33 in at least one of operator priority modes A and B so that the appropriate growth period includes the desired processing time and / or at least a portion of the appropriate growth period overlaps with the operator-acceptable period. In this way, by actively changing the appropriate growth period, the timing of when the recovery preparation process is executed can be actively adjusted to suit the operator's convenience.

[0088] (3) In the embodiments described above, the control device 5 controls the culture circuit 4 to start the recovery preparation process at the desired processing time if the desired processing time falls within the appropriate growth period, when the operating mode is operator priority mode A or B. However, it is not limited to this. For example, the control device 5 may control the culture circuit 4 to complete the recovery preparation process at the desired processing time if the desired processing time falls within the appropriate growth period. Also, in the embodiments described above, the control device 5 controls the culture circuit 4 to start the recovery preparation process at a time as close as possible to the desired processing time if the desired processing time does not fall within the appropriate growth period. However, it is not limited to this. The control device 5 may control the culture circuit 4 to start the recovery preparation process at any time that falls within the appropriate growth period if the desired processing time does not fall within the appropriate growth period.

[0089] (4) In the embodiments described above, the control device 5 performs branching (S214) when the operating mode is operator priority mode B and the appropriate growth period does not overlap with the operator-allowable period (S213: No). However, it is not limited to this. In such cases, the control device 5 may, for example, stop cell culture without performing branching.

[0090] (5) In the embodiments described above, the control device 5 is configured to allow selection of operator priority modes A and B as operator priority modes. However, it is not limited to this. For example, the control device 5 may store only one of the programs for executing operator priority mode A and the program for executing operator priority mode B. Alternatively, the control device 5 may store a program for executing another operator priority mode. In the other operator priority mode, the recovery preparation process may be executed at the following timing, for example. The control device 5 may perform control that does not take into account the desired processing time and takes into account the operator's acceptable time period. As a more specific example, the control device 5 may predict the optimal time described above and execute the recovery preparation process at the optimal time if the optimal time falls within the operator's acceptable time period. The control device 5 may stop cell culture if the optimal time does not fall within the operator's acceptable time period.

[0091] (6) When the operating mode is operator priority mode, the control device 5 may perform the recovery preparation process at a timing other than those described above. For example, the control device 5 may cause the culture circuit 4 to perform the recovery preparation process at a timing different from when the operating mode is cell priority mode, in a manner that does not take into account the relationship between the appropriate growth period and the desired processing time and / or the operator-acceptable period. For example, when the operating mode is operator priority mode, the control device 5 may control the culture circuit 4 so that the recovery preparation process is started or completed at the desired processing time under any circumstances.

[0092] (7) In the embodiments described above, it was assumed that one subculturing was performed between the start of culture and harvesting. However, this is not limited to this. For example, cells cultured in culture vessel 14 may be harvested without subculturing. Alternatively, two or more subculturings may be performed between the start of culture and harvesting. In this case, the culture circuit 4 may be provided with other culture vessels (not shown) in addition to culture vessels 14 and 16. Alternatively, during culture, culture vessels 14 and / or culture vessel 16 may be exchanged with other culture vessels while maintaining a sterile condition. When exchanging the vessels, for example, a known vessel exchange device (not shown) may be used.

[0093] (8) In the embodiments described above, the liquid (reagent or cell suspension) was transported using pumps P1 to P4. However, it is not limited to this. The culture circuit 4 may be configured to transport the liquid in the container using gas supplied under pressure from a gas supply unit (not shown), such as described in Japanese Patent Application Publication No. 2021-40575.

[0094] (9) The pathways formed within the culture circuit 4 are not limited to those described above. The culture circuit 4 may have any pathways as long as it is possible to transfer liquid between multiple containers while maintaining a sterile state.

[0095] (10) In the embodiments described above, multiple reagent heating containers were provided (13a and 13b). Furthermore, multiple containers of the same function may be provided within the culture circuit 4. For example, multiple subculturing containers 15 may be provided. Also, multiple collection containers 18 may be provided. The same applies to other containers. [Explanation of Symbols]

[0096] 1 Cell culture device 4. Culture circuit (processing unit, density adjustment unit) 5. Control device (control unit) 14 Culture container (1st culture container) 16. Culture vessels (second culture vessel, collection vessel) 18 Collection containers 31. Cell Observation Department (Information Acquisition Department) 33 Environment Control Department C cells

Claims

[Claim 1] First culture vessel, A recovery container for the operator to recover some or all of the cells cultured in the first culture vessel, A processing unit configured to perform a recovery preparation process to enable the recovery of the cells by the operator, The system comprises a control unit that controls the processing unit, The control unit, The system is configured to allow switching between a cell-priority mode, which prioritizes the culture status of the cells, and an operator-priority mode, which prioritizes the convenience of the operator who retrieves the collection container. A cell culture apparatus characterized in that, when the operating mode is the operator-priority mode, the processing unit is made to execute the recovery preparation process at a different timing than when the operating mode is the cell-priority mode.

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