JP2023131846A - Automatic cell culture apparatus - Google Patents

Abstract

To provide an automatic cell culture apparatus by which a cultivator mainly assists setting of cell culture conditions.SOLUTION: An automatic cell culture apparatus 1 comprises: a culture part 11; an environment-adjusting part 12; a monitoring part 5; a controller 6 having an input part 6a and a storage part 6c. The storage part 6c stores a plurality of kinds of monitoring items monitored by the monitoring part 5 and a plurality of kinds of control items used by the controller 6 for controlling the culture part 11 and/or the environment-adjusting part 12. The controller 6 allows the storage part 6c to store information of association between monitoring items selected via the input part 6a and at least one kind of control item selected via the input part 6a. Furthermore, the controller 6 determines control information which is information of the control content of at least one control item corresponding to a change of a value of at least one kind of monitoring item corresponding to an input result to the input part 6a, and allows the storage part 6c to store the control information.SELECTED DRAWING: Figure 6

Description

TECHNICAL FIELD The present invention relates to an automatic cell culture device.

The culture device disclosed in Patent Document 1 (hereinafter referred to as an automatic cell culture device) includes a culture section configured to be able to execute a series of processes from the start to the end of cell culture. The automatic cell culture device is equipped with various devices (hereinafter referred to as the monitoring section) for obtaining information on the culture status such as the number of cells, and for operating adjustable parameters such as the temperature of the culture section and the pH of the culture solution (medium). and various devices (hereinafter referred to as the environment control section). The control device provided in the automatic cell culture apparatus is configured to control the environment control section using the monitoring results from the monitoring section.

Further, Patent Document 2 discloses a method for setting up an automatic cell culture device. In this setup method, all cell culture conditions, including culture conditions for mass production of cells, are set or re-set by the manufacturer of the automatic cell culture device, rather than by a culturer affiliated with a company that mass-produces cells. be made (changed). The reason is that cultivators are generally not familiar with automated cell culture equipment, and it is difficult for cultivators to set it up themselves.

JP2019-41656A JP2021-58120A

For example, in the automatic cell culture apparatus described in Patent Document 1, the cell culture conditions described in Patent Document 2 are understood to include conditions for controlling the environment control section using the monitoring result by the monitoring section. Information on how to operate the environment control unit based on what kind of monitoring results can be obtained by a culture person performing manual culture in advance using a manual culture device. However, cultivators generally do not wish to provide such information to others, including manufacturers, from the perspective of protecting know-how. In other words, there is a desire for cultivators to take the initiative in freely setting up automatic cell culture devices. However, since culturers are less familiar with automatic cell culture apparatuses than manufacturers, it is very difficult for culturers to perform advanced tasks such as creating control programs, for example.

An object of the present invention is to help a cultivator take the initiative in setting cell culture conditions in an automatic cell culture apparatus.

The automatic cell culture device of the first invention includes a culture section configured to execute a series of processes from the start to the end of cell culture, and a culture section configured to adjust the culture environment, which is an environment in which cells are cultured. An automatic cell culture apparatus comprising: an environment control section configured to perform a cell culture; and a monitoring section configured to monitor a culture status indicating a state of cell proliferation in the culture section and the culture environment, the monitoring section comprising: a control unit configured to control the culture unit and the environment control unit based on monitoring results, the control unit including an input unit configured to be operated by an operator, and configured to be able to store information. a storage unit, the storage unit stores a plurality of types of monitoring items that can be monitored by the monitoring unit, and the control unit controls the culture unit and/or the environment adjustment unit. A plurality of types of control items are stored, and the control unit stores a selected monitoring item selected from the plurality of types of monitoring items via the input unit, and a plurality of types of monitoring items. storing information on association with a selected control item selected from among the control items via the input unit in the storage unit, and control content of the selected control item in response to a change in the value of the selected monitoring item. The control information that is the information is determined according to the input result to the input section, and the control information is stored in the storage section.

The culture conditions in the present invention refer to the number of cells, cell proliferation rate, and the like. The culture environment in the present invention refers to the temperature of the culture section and its surroundings, the pH of the culture solution (medium), and the like. In the present invention, a cultivator can freely set cell culture conditions to some extent using a simpler method than creating a control program. Therefore, in the automatic cell culture apparatus, the cultivator can take the initiative in helping to set cell culture conditions.

The automatic cell culture apparatus according to a second aspect of the invention, in the first aspect, includes an output section that displays information, and the control section displays information indicating the selected monitoring item and one of the plurality of types of control items. information indicating at least one type of candidate item is displayed on the output unit, and an operation for associating the selected monitoring item with one type of candidate item among the at least one type of candidate item is performed on the input unit. When it is determined that the above-mentioned monitoring item has been carried out, processing for associating the monitoring item with the one type of candidate item is performed, and an operation for canceling the association between the selected monitoring item and the one type of candidate item is performed on the input unit. The present invention is characterized in that, when it is determined that this has been done, a process of canceling the association between the selected monitoring item and the one type of candidate item is performed.

In the present invention, association processing and association cancellation processing can be easily performed by operating the input section based on the display by the output section.

In the automatic cell culture apparatus of a third aspect of the invention, in the first or second aspect, the control section monitors each of the plurality of types of monitoring items according to the input result to the input section. storing monitoring conditions, which are conditions for determining whether or not to carry out monitoring, in the storage unit, and performing monitoring regarding at least some of the plurality of types of monitoring items according to the monitoring conditions during cell culture; It is characterized by switching between the presence and absence of.

In cell culture, current cell culture conditions are not necessarily optimal conditions. In other words, new and better cell culture conditions may be discovered depending on the type of cells to be cultured. The same applies to monitoring conditions. In other words, there is a possibility that the cultivator will newly discover which monitoring item is more appropriate to monitor under which conditions. In such a situation, the present invention, which allows cultivators themselves to easily and flexibly set or change monitoring conditions, is extremely useful.

In the automatic cell culture device according to a fourth aspect of the invention, in any one of the first to third aspects, the storage unit stores one or more candidate formulas that are candidates for threshold formulas for the plurality of types of monitoring items. information, and the control unit generates a threshold value expression indicating a threshold value of one type of monitoring item among the plurality of types of monitoring items, or generates a threshold value expression indicating a threshold value of one type of monitoring item among the plurality of types of monitoring items, in response to an input to the input unit. The method is characterized in that the threshold value formula is selected from candidate formulas and stored in the storage unit in association with the one type of monitoring item.

In the present invention, a cultivator can easily set how the culture unit and/or the environment control unit should be controlled when the value of a monitoring item changes.

A method for setting culture conditions in an automatic cell culture apparatus according to a fifth aspect of the invention includes a culture section configured to execute a series of processes from the start to the end of cell culture, and a culture environment that is an environment in which cells are cultured. An automatic cell culture apparatus comprising: an environment control unit configured to adjust cell growth; and a monitoring unit configured to monitor the culture environment and the culture status indicating the state of cell proliferation in the culture unit. A method for setting culture conditions in an automatic cell culture apparatus, wherein the automatic cell culture apparatus includes a control section that controls the culture section and the environment adjustment section based on monitoring results by the monitoring section. The control unit includes an input unit configured to be operated by an operator, and a storage unit configured to be able to store information, and the storage unit is configured to be operable by an operator. A plurality of types of monitoring items that can be monitored by the control unit and a plurality of types of control items for the control unit to control the culture unit and/or the environment control unit. a monitoring item selection step of performing an operation on the input unit to select one type of selected monitoring item from the plurality of types of monitoring items; and at least one type of control item from the plurality of types of control items. a control item selection step of performing an operation on the input unit to select a selection control item; and an association step of performing an operation of associating the selected monitoring item with the at least one type of selection control item on the input unit. and a control information input step of performing a setting operation on the input unit regarding the control content of the at least one selected control item in response to a change in the value of the selected monitoring item.

In the present invention, in an automatic cell culture apparatus, a culture person can take the initiative in setting cell culture conditions.

FIG. 1 is a schematic front view of a cell culture device according to the present embodiment. FIG. 2 is a block diagram showing the electrical configuration of an automatic cell culture device. FIG. 2 is a schematic diagram showing an example of a culture section. (a) and (b) are diagrams showing screens displayed on the output unit. FIG. 3 is an explanatory diagram showing a new recipe setting screen. (a) and (b) are explanatory diagrams showing association setting screens. (a) and (b) are explanatory diagrams showing monitoring condition setting screens. (a) and (b) are explanatory diagrams showing threshold formula setting screens. (a) and (b) are explanatory diagrams showing control content setting screens. (a) is an explanatory diagram showing information that can be stored in a server, and (b) is an explanatory diagram showing an authority management screen. 2 is a flowchart outlining a procedure for determining and improving cell mass production conditions. It is a flowchart which shows the procedure of new setting of cell culture conditions. FIG. 2 is an explanatory diagram showing information stored in a server.

Next, embodiments of the present invention will be described. For convenience of explanation, the vertical direction on the paper surface of FIG. 1 is defined as the vertical direction (vertical direction in which gravity acts). The left-right direction on the paper surface of FIG. 1 is defined as the left-right direction.

(Outline of automatic cell culture device)
The outline of the automatic cell culture apparatus 1 according to this embodiment will be explained with reference mainly to FIGS. 1 and 2. FIG. 1 is a schematic front view of an automatic cell culture device 1. FIG. FIG. 2 is a block diagram showing the electrical configuration of the automatic cell culture device 1. As shown in FIG. The automatic cell culture device 1 includes a refrigerator 2 (see FIG. 1), an incubator 3 (see FIG. 1), an operation section 4 (see FIG. 2), a monitoring section 5 (see FIG. 2), and a control device 6 (main unit). control unit of the invention).

Refrigerator 2 is for configuring a low temperature area where reagents are stored. The refrigerator 2 is configured to be able to maintain the temperature of the low temperature area at approximately 4°C. Thereby, various reagents can be stored in the refrigerator 2 while suppressing changes in the components of the reagents. The refrigerator 2 may be configured to be able to adjust the temperature of the low temperature area to a temperature other than about 4°C.

The incubator 3 is for configuring a culture area where cells are cultured. The incubator 3 is configured to be able to maintain the temperature of the culture area at about 37° C., for example. The incubator 3 may be configured to be able to adjust the temperature of the culture area to a temperature other than about 37°C. Examples of the types of cells to be cultured include, but are not limited to, mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs).

The operation section 4 is a collection of a plurality of devices operated by the control device 6, which is regarded as one unit. The operation section 4 includes a culture section 11 in which cell culture processing is executed, and an environment adjustment section 12 for adjusting the culture section 11 and the surrounding environment (cell culture environment). The culture section 11 and the environment control section 12 are electrically connected to the control device 6. More details of the culture section 11 and the environment control section 12 will be described later.

The monitoring unit 5 is a unit that is a collection of a plurality of devices for monitoring the growth status of cells and the environment in which the cells are placed. The monitoring unit 5 includes a cell observation unit 13 configured to observe cell proliferation status, etc., and an environment detection unit 14 configured to detect information regarding the environment of the culture unit 11 and its surroundings. . The cell observation section 13 and the environment detection section 14 are electrically connected to the control device 6. More details of the cell observation section 13 and the environment detection section 14 will be described later.

The control device 6 is configured to control the operating section 4 mainly based on the results of monitoring by the monitoring section 5. The control device 6 is, for example, a general computer device. As shown in FIG. 2, the control device 6 includes an input section 6a, an output section 6b, a storage section 6c, and a reading section 6d. The input unit 6a includes, for example, at least one of a known keyboard, mouse, touch panel, and the like. The output unit 6b includes, for example, a display (not shown). The storage unit 6c includes, for example, a RAM and/or a hard disk (not shown). The reading section 6d is used for user authentication. The control device 6 is electrically connected to a server 100 configured to be able to store data. More details of the control device 6 will be described later.

(Cultivation Department)
Next, an example of the culture section 11 will be described with reference to FIG. 3. The culturing unit 11 is for performing processes such as seeding, culturing, passage, and harvesting of cells. The culture unit 11 is configured to be able to execute a series of processes from the start to the end of cell culture. The culture section 11 is configured to move various liquids between a plurality of containers (described later). Various liquids mean various reagents such as a medium for growing cells, and a cell suspension containing a mixture of reagents and cells.

The culture section 11 forms, for example, a sealed closed system. The culture section 11 is configured to prevent entry of bacteria and the like that would harm cells (that is, to maintain a sterile state). The culture section 11 includes, for example, a culture medium storage container 21, a stripping solution storage container 22, reagent heating containers 23 and 24, a culture container 25, a subculture container 26, a culture container 27, and a waste liquid container 28. , and a collection container 29. Bottles or bags are employed as these containers, but are not limited thereto. Furthermore, the culture unit 11 includes, for example, tubes 31, 32, 33, 34, and 35 to which a plurality of containers are connected. Further, the culture unit 11 includes, for example, pumps P1, P2, P3, and P4 configured to move various liquids. Further, the culture section 11 includes, for example, openable/closeable valves V1, V2, V3, V4, V5, V6, V7, V8, and V9 provided corresponding to each container. Pumps P1 to P4 and valves V1 to V9 are electrically connected to control device 6 (see FIG. 2).

The medium storage container 21 is a container for storing a medium used for culturing cells. As the type of medium, for example, a serum medium containing animal-derived serum (eg, bovine serum) can be employed, but the medium is not limited thereto. The culture medium storage container 21 is housed within the refrigerator 2. The medium storage container 21 is connected to a branched tube 31, for example. A valve V1 for opening and closing the culture medium storage container 21 is provided near the end of the tube 31 to which the culture medium storage container 21 is connected.

The stripping solution storage container 22 is a container that stores a stripping solution for stripping cultured cells from the container. Generally, cultured cells adhere to the bottom of the container. The detachment solution is, for example, a liquid containing a cell detachment enzyme (such as known trypsin) for detaching cells from the bottom of the container, but is not limited thereto. The stripping liquid storage container 22 is housed within the refrigerator 2. The stripping liquid storage container 22 is connected to a tube 31, for example. A valve V2 for opening and closing the end of the tube 31 is provided near the end to which the stripping liquid storage container 22 is connected.

The reagent heating containers 23 and 24 are containers for heating various reagents. The various reagents are heated in the reagent heating container 23 or 24 to enable them to perform their respective functions. The reagent heating containers 23 and 24 are housed within the incubator 3. The reagent heating containers 23 and 24 are each connected to a branched tube 32, for example. The reagent heating container 23 is used, for example, to warm the culture medium. The reagent heating container 24 is used, for example, to warm the stripping solution. A valve V3 for opening and closing the end of the tube 32 is provided near the end to which the reagent heating container 23 is connected. A valve V4 for opening and closing the end of the tube 32 is provided near the end to which the reagent heating container 24 is connected.

The culture container 25 is a container for culturing cells. The culture container 25 is a container in which cells are first seeded when culture of a predetermined cell is started. The culture container 25 is housed within the incubator 3. The culture container 25 is connected to a branched tube 33, for example. A valve V5 for opening and closing the end of the tube 33 to which the culture container 25 is connected is provided.

The subculture container 26 is, for example, a container used when subculturing the cells cultured in the culture container 25. The passage container 26 is housed within the incubator 3. The passage container 26 is connected to a tube 35, for example. A valve V6 for opening and closing the end of the tube 35 is provided near the end to which the passage container 26 is connected.

The culture container 27 is a container for culturing cells. The culture container 27 is, for example, larger than the culture container 25, but is not limited thereto. The culture container 27 is used to subculture and further proliferate the cells cultured in the culture container 25. The culture container 27 is housed within the incubator 3. The culture container 27 is connected to a tube 33, for example. A valve V7 for opening and closing the end of the tube 33 to which the culture container 27 is connected is provided.

The waste liquid container 28 is a container for discarding used reagents. The waste liquid container 28 is placed, for example, in a room temperature area. The waste liquid container 28 is connected to a branched tube 34, for example. A valve V8 for opening and closing the end of the tube 34 is provided near the end to which the waste liquid container 28 is connected.

The collection container 29 is a container for an operator (that is, a cultivator who handles the automatic cell culture device 1 and performs cell culture) to collect some or all of the cultured cells. The collection container 29 is housed within the refrigerator 2, for example. The collection container 29 is connected to a tube 34, for example. A valve V9 for opening and closing the end of the tube 34 is provided near the end to which the collection container 29 is connected.

Each container is provided with a path (not shown) for escaping air and a filter (not shown) disposed on the path. The path and filter are for sucking air into the container from which the liquid flows out and expelling air from the container into which the liquid flows when the liquid is moved by any of the pumps P1 to P4. be.

The tubes 31 to 35 are piping members for moving liquid between containers while maintaining the sterile state of the culture section 11. The tubes 31 to 35 preferably have flexibility, for example, but are not limited to this. Tube 31 is connected to pump P1 and communicates with tube 32. Tube 32 is connected to pumps P1, P2 and P4 and communicates with tubes 31, 33 and 35. Tube 33 is connected to pumps P2 and P3 and communicates with tubes 32 and 34. Tube 34 is connected to pump P3 and communicates with tube 33. Tube 35 is connected to pump P4 and communicates with tube 32.

Pumps P1 to P4 are pump devices for moving liquid between containers while maintaining the sterile state of the culture section 11. For example, known tube pumps are employed as the pumps P1 to P4, but the type of pump device is not limited thereto. The pump P1 is configured to be able to transfer liquid between a container connected to the tube 31 and a container connected to the tube 32, for example. The pump P2 is configured to be able to transfer liquid between a container connected to the tube 32 or 35 and a container connected to the tube 33, for example. The pump P3 is configured to be able to transfer between a container connected to the tube 33 and a container connected to the tube 34, for example. The pump P4 is configured to be able to transfer between a container connected to the tube 32 or 33 and a container connected to the tube 35, for example. The pumps P1 to P4 are electrically connected to the control device 6. The pumps P1 to P4 are configured to be able to adjust the amount of liquid to be transferred by being controlled by the control device 6.

Further, a vial (not shown) in which a seed cell (not shown) to be cultured is stored is connected to the culture unit 11. The culture unit 11 is provided with an injection device (not shown) configured to take out seed cells from a vial and inject them into the culture container 25. Instead of a vial, a bag or other container in which seed cells (not shown) are stored may be provided.

(Environmental Control Department)
The environment control unit 12 is configured to control the cell culture environment, as described above. Although not shown, at least a portion of the environment control section 12 is connected to the culture section 11. The environment control section 12 includes, for example, a heater (not shown) disposed in the incubator 3, a supply port and a valve (not shown) for supplying carbon dioxide into the culture section 11, and a supply port and a valve (not shown) for supplying carbon dioxide into the culture section 11. It has an exhaust port and a valve (not shown) for discharging the air. The environment control unit 12 is electrically connected to the control device 6 and operates according to command signals sent from the control device 6. The environment control unit 12 may include other devices that can adjust the cell culture environment.

(Cell Observation Department)
The cell observation unit 13 is configured to be able to acquire information regarding the number of cells being cultured. Information regarding the number of cells means, for example, information on the number of cells themselves or the number of cells per unit volume (that is, cell density). As a higher level concept, the cell observation unit 13 is configured to monitor the culture status indicating the state of cell proliferation in the culture unit 11.

The cell observation unit 13 includes, for example, a camera (not shown). For example, one camera is placed near the culture container 25 and one near the culture container 27. The camera is configured to, for example, photograph cells and obtain image data. The cell observation section 13 is electrically connected to the control device 6. The control device 6 performs image processing based on the image data acquired by the cell observation unit 13, and acquires information on the number of cells or information on the density of cells per unit volume. Alternatively, the cell observation unit 13 may perform image processing and obtain information on the number of cells instead of the control device 6. The control device 6 predicts the pace of proliferation of cells cultured in the culture section 11 based on the observation results by the cell observation section 13 . Note that the cell observation section 13 is not limited to the above-described structure as long as it is configured to be able to acquire information regarding the number of cells. For example, the cell observation unit 13 is configured to be able to indirectly obtain information regarding the number of cells by observing metabolites in the medium (used medium) used in the culture container 25 or 27. It's okay.

(Environmental detection section)
The environment detection unit 14 is for detecting the cell culture environment in the automatic cell culture apparatus 1. The cell culture environment refers to an environment that can affect the cell culture status, such as the temperature inside the incubator 3, the carbon dioxide concentration in the air inside the culture section 11, and the pH of the culture medium. The environment detection unit 14 includes, for example, a thermometer (not shown), a carbon dioxide concentration meter (not shown), and a pH meter (not shown). The environment detection unit 14 is electrically connected to the control device 6 and is configured to transmit a detection signal to the control device 6. The environment detection unit 14 may include other devices capable of detecting the cell culture environment.

(Summary of cell culture procedure)
Next, an outline of the cell culture procedure in the automatic cell culture device 1 will be explained. The period from the start of cell culture until passage is performed, and the period from passage to harvest may vary depending on the type of cells to be cultured and the target cell number. In addition, there are cases where harvesting is performed without subculture, and cases where subculture is performed multiple times. In this embodiment, for convenience of explanation, the period from the start of culture to subculture is referred to as the first period. In addition, subculturing shall be carried out once before harvesting. The period from passage to harvest is the second period.

In the initial state, all valves V1 to V9 are closed. The control device 6 opens a valve disposed near the container from which the liquid is to be transferred and a valve disposed near the container to which the liquid is to be transferred, and opens a valve disposed near the container from which the liquid is to be transferred. Liquid is moved between containers by activating a pump. Thereafter, the control device 6 closes these valves and stops the operation of the pump. Hereinafter, to simplify the explanation, the above-described valve opening/closing control and pump control will be simply referred to as "the control device 6 controls the valves and the pump." The control device 6 controls each part of the automatic cell culture device 1 to execute the following processes of seeding, subculture, and harvesting.

First, the control device 6 executes a seeding process. Specifically, first, the control device 6 controls the valves V1 and V3 and the pump P1 to move a predetermined amount of the culture medium from the culture medium storage container 21 to the reagent heating container 23. After the culture medium is warmed, the controller 6 controls valves V3, V5 and pump P2 to move the culture medium from the reagent heating container 23 to the culture container 25. The control device 6 also controls an injection device (not shown) to move the seed cells from the vial to the culture container 25. Thereby, seed cells are seeded into the culture container 25 at a predetermined seeding density. Over time, the seed cells are cultured and proliferated. The proliferated cells adhere to the bottom surface of the culture container 25.

After the first period has elapsed, the control device 6 performs cell passage processing (transferring cells from the culture container 25 to the culture container 27). Specifically, first, the control device 6 controls the valves V1 and V3 and the pump P1 to move the fresh medium from the medium storage container 21 to the reagent heating container 23. Next, the control device 6 controls the valves V2 and V4 and the pump P1 to move the stripping solution from the stripping solution storage container 22 to the reagent heating container 24. Next, the control device 6 controls the valves V5 and V8 and the pump P3 to move the used culture medium from the culture container 25 to the waste liquid container 28. Next, the control device 6 controls the valves V4 and V5 and the pump P2 to move the warmed stripping solution from the reagent heating container 24 to the culture container 25. After the predetermined standby time has elapsed, the control device 6 controls the valves V5 and V8 and the pump P3 to move the stripping liquid from the culture container 25 to the waste liquid container 28. The cells are about to be detached from the bottom of the culture container 25 by the detachment solution. Further, the control device 6 controls the valves V3 and V5 and the pump P2 to move a portion of the pre-warmed medium from the reagent heating container 23 to the culture container 25. As a result, the cells are peeled off from the bottom surface of the culture container 25 and mixed with the medium in the culture container 25 to form a cell suspension.

Further, the control device 6 controls the valves V3 and V6 and the pump P4 to move the medium for adjusting the seeding density during subculture from the reagent heating container 23 to the subculture container 26. Further, the control device 6 controls valves V5 and V6 and pumps P2 and P4 to remove the amount of cell suspension necessary for passage out of the cell suspension in the culture vessel 25 from the culture vessel 25 for passage. Transfer to container 26. By mixing the new culture medium and the cell suspension in the subculture container 26, a cell suspension having a desired seeding density can be obtained. Next, the control device 6 controls the valves V6 and V7 and the pumps P2 and P4 to move the cell suspension from the subculture container 26 to the culture container 27. Passaging is completed in the above manner. Further, the control device 6 controls the valves V5 and V9 and the pump P3 to move the cell suspension remaining in the culture container 25 from the culture container 25 to the collection container 29. The cell suspension sent to the collection container 29 is collected by an operator and used, for example, to evaluate the quality of cultured cells.

After the second period has elapsed, the control device 6 performs cell harvesting processing. As a specific procedure, the procedure up to peeling the cells from the bottom surface of the culture container 27 is the same as the procedure for processing the cells in the culture container 25 described above. Thereafter, the culture container 27 containing the cell suspension is collected by the operator. Alternatively, the cell suspension may be transferred from the culture container to another container (not shown), and the other container may be collected.

The control device 6 controls the operation section 4 (based on the monitoring result by the monitoring section 5) based on the predetermined cell culture conditions during the period from seeding to harvest described above (that is, from the start to the end of cell culture). The culture section 11 and the environment control section 12) are controlled. This allows the cells to grow in an appropriate environment.

Here, information on how to operate the culture section 11 and the environment control section 12 based on the monitoring results is obtained by the cultivator performing manual culture in advance using a manual culture device. Is possible. However, cultivators generally do not wish to provide such information to others, including the manufacturer of the automatic cell culture device 1, from the viewpoint of protecting know-how and the like. In other words, there is a desire for cultivators to take the initiative in freely setting up the automatic cell culture apparatus 1. However, since the cultivator is not as familiar with the automatic cell culturing apparatus 1 as the manufacturer, it is very difficult for the cultivator to perform advanced tasks such as creating a control program, for example. Therefore, in order to assist the culture person in setting the cell culture conditions, the control device 6 of this embodiment is configured as follows.

(Program for setting cell culture conditions)
The storage unit 6c of the control device 6 stores a program for setting cell culture conditions. In this embodiment, the cell culture conditions refer to a series of control contents of the culture section 11 from seeding to harvesting of predetermined cells, a link between the contents of monitoring by the monitoring section 5 and the contents of control of the operation section 4, etc. means such a set of information. Such a set of information is also referred to as a "recipe" hereinafter. The storage unit 6c is configured to be able to store a plurality of recipes. The plurality of recipes include recipes for mass producing cells.

A program for setting cell culture conditions will be explained with reference to FIGS. 4(a) to 9(b). FIGS. 4A and 4B are diagrams showing screens displayed on the output section 6b. FIG. 5 is an explanatory diagram showing a new recipe setting screen. FIGS. 6A and 6B are explanatory diagrams showing setting screens for associating monitoring items (described later) and control items (described later). FIGS. 7A and 7B are explanatory diagrams showing monitoring condition setting screens. FIGS. 8(a) and 8(b) are explanatory diagrams showing threshold formula setting screens. FIGS. 9A and 9B are explanatory diagrams showing control content setting screens. In this embodiment, for convenience of explanation, the description will proceed assuming that the input section 6a has a touch panel and the output section 6b has a liquid crystal display. However, the configuration of the input section 6a and the configuration of the output section 6b are not limited to this.

As shown in FIG. 4A, the control device 6 is configured to display, for example, a menu screen S1 on the output unit 6b for the operator to make various settings. The input section 6a allows the operator to input the "culture condition setting" button, the "cell culture execution" button, and the "authority management" button on the menu screen S1. is configured so that it can be touched. Setting culture conditions means creating a new recipe or changing a created recipe. Execution of cell culture means the start of execution of cell culture based on a recipe selected in advance from one or more created recipes. Authority management refers to the management of authority information, which will be described later, stored in the server 100 (see FIG. 1).

The control device 6 is configured to display a culture condition setting screen S2 shown in FIG. 4(b) on the output unit 6b when the "culture condition setting" button is touched on the menu screen S1 (see FIG. 4(a)). programmed. More specifically, "the culture condition setting button has been touched" means that a portion of the input section 6a that overlaps the section where the "culture condition setting" button is displayed on the output section 6b in the vertical direction of the screen is touched. It means that. For convenience of explanation, the same shall apply hereinafter.

The control device 6 is configured to allow the operator to touch, for example, a "Create new culture condition" button and a "Change culture condition" button on the culture condition setting screen S2. The control device 6 is also programmed to allow the operator to touch a "back" button to return to the previous screen (for example, the menu screen S1 that was displayed immediately before the culture condition setting screen S2). . Regarding the "back" button, the same applies to other screens described later.

The following will mainly explain how to create a new recipe. The control device 6 is programmed to display a new setting screen S3 shown in FIG. 5 on the output unit 6b when the "Create new culture conditions" button is touched on the culture condition setting screen S2. In the control device 6, the operator selects, for example, "association setting," "monitoring condition setting," "threshold value setting," "control content setting," "monitoring item management," "control item management," and "save" on the new setting screen S3. It has been programmed to be possible.

An overview of each setting shown in FIG. 5 will be explained. “Association setting” means setting an association between an item that can be monitored by the monitoring unit 5 (hereinafter referred to as a monitoring item) and an item that can be executed or adjusted by the operating unit 4 (hereinafter referred to as a control item). In other words, the association setting means setting which control item is to be controlled when the value of which monitoring item changes. “Monitoring condition setting” means setting under what conditions the monitoring unit 5 is to monitor each monitoring item. "Threshold value type setting" means setting how the value of a certain monitoring item changes to perform control related to a control item associated with the monitoring item. “Control content settings” refers to settings for what kind of control is to be performed regarding control items. The control device 6 is programmed so that recipe creation can proceed by the operator performing predetermined operations on screens related to these various settings.

Moreover, "monitoring item management" means managing addition, deletion, etc. of monitoring items. "Control item management" means management such as addition and deletion of control items. “Save” means a process of saving (storing) a new recipe in the storage unit 6c.

Further, the control device 6 is programmed to be able to input a recipe name, for example, on the new setting screen S3. However, the present invention is not limited to this, and the control device 6 may display a screen (not shown) for inputting a recipe name on the output unit 6b, for example, when a "save" button is touched.

Details of each setting shown in FIG. 5 will be explained. First, "association settings" will be explained. The control device 6 is programmed to display the association setting screen S4 shown in FIG. 6(a) on the output unit 6b when the "association setting" button is touched on the new setting screen S3. For example, the control device 6 displays a list of multiple types of monitoring items (hereinafter simply referred to as multiple monitoring items) on the left side of the screen, and displays a list of multiple types of control items on the right side of the screen. The plurality of types of control items displayed on the setting screen S4 correspond to "at least one type of candidate item" of the present invention. Hereinafter, the plurality of types of control items will be simply referred to as a plurality of control items.

The monitoring items include the number of cells, the type and amount of metabolites excreted by the cells, the components of the medium contained in the medium and their amounts, the pH of the medium, the temperature inside the incubator 3, and the temperature in the air inside the culture section 11. Includes carbon dioxide concentration, etc. Please note that these are just examples.

The control items include the types of reagents to be injected into the culture unit 11 ("Reagent M" and "Reagent N" in FIG. 6(a)), the amount of reagents to be injected and their increase/decrease, the timing of replacing the culture medium, etc. It will be done. Please note that these are just examples. In addition, the control items include the output of the heater (not shown) in the incubator 3, the supply amount of carbon dioxide and other gases into the culture section 11, the timing of subculturing, the timing of harvesting, and the like.

The control device 6 is programmed to display, for example, a selection button B1 on the right side of each monitoring item and a selection button B2 on the left side of each control item on the association setting screen S4. That is, for example, a row formed by the plurality of selection buttons B1 and a row formed by the plurality of selection buttons B2 are adjacent to each other in the left-right direction. The positional relationship between the selection button B1 and the selection button B2 is not limited to that described above.

The control device 6 is programmed to make one selection button B1 arbitrarily selected by the operator among the plurality of selection buttons B1 different in color or shape from the other selection buttons B1, for example. For example, when the selection button B1 adjacent to "Number of Cells" in the left-right direction is touched, the control device 6 makes the color of the selection button B1 different from the color of the other selection buttons B1 (see FIG. 6(a)). ). Hereinafter, the currently selected monitoring item related to the selection button B1 will be referred to as a "selected monitoring item."

When any selection button B2 is touched on the association setting screen S4, the control device 6, for example, makes the color of the selection button B2 different from the color of the other selection buttons B2 (see FIG. 6(b)). is programmed to. The control device 6 performs a process of associating the control item (selected control item) related to the selection button B2 with the selected monitoring item. Furthermore, the control device 6 may display, for example, a straight line L connecting the selection button B1 related to the selected monitoring item and the selection button B2 related to the selected control item on the output unit 6b (see FIG. 6(b)).

The control device 6 may be programmed to be able to associate a selected monitoring item with a plurality of control items (that is, a plurality of selected control items). For example, as shown in FIG. 6(b), "cell number" and "passaging timing" may be associated, and "cell number" and "harvesting timing" may be associated. Alternatively, the control device 6 can allow a plurality of monitoring items to be selected at the same time, and can simultaneously display information indicating the association between the plurality of selected monitoring items and one or more control items on the output unit 5b. may be programmed. In other words, the control device 6 may perform a process of associating two monitoring items and one control item, for example.

Further, the control device 6 is programmed to be able to release the association between the selected monitoring item and the selected control item. When the selection button B2 adjacent to a certain selection control item is touched again, the control device 6 performs a process of returning the display of the selection button B2 to its original state and canceling the association between the selection monitoring item and the selection control item. .

The control device 6 may be programmed to be able to associate the same control item with multiple monitoring items. In other words, the control device 6 is programmed so that when any one monitoring item and any one control item are associated, it can associate another monitoring item with that one control item. It's okay.

As described above, the control device 6 selects a selected monitoring item from among a plurality of monitoring items via the input unit 6a, and a selected control item selected from a plurality of control items via the input unit 6a. Processes the association with.

Next, "monitoring condition setting" will be explained. The monitoring conditions are conditions for determining whether or not to monitor each monitoring item. In other words, the monitoring conditions are conditions for switching between execution and non-execution of monitoring regarding each monitoring item. In cell culture, current cell culture conditions are not necessarily optimal conditions. In other words, new and better cell culture conditions may be discovered depending on the type of cells to be cultured. The same applies to monitoring conditions. In other words, there is a possibility that the cultivator will newly discover which monitoring item is more appropriate to monitor under which conditions. "Monitoring condition setting" is a function that allows the cultivator himself/herself to easily and flexibly set or change the monitoring conditions in such a situation.

The control device 6 is programmed to display a monitoring condition setting screen S5 shown in FIG. 7(a) on the output unit 6b when the "monitoring condition setting" button is touched on the new setting screen S3. For example, the control device 6 displays a list of monitoring items on the left side of the screen, and displays a list of monitoring conditions associated with each monitoring item on the right side. For example, on the initial screen shown in FIG. 7(a), the monitoring conditions for all monitoring items are "always on". This means that the monitoring unit 5 constantly monitors all monitoring items from sowing to harvest.

The control device 6 is programmed to change monitoring conditions according to the input results to the input section 6a. More specifically, for example, a plurality of candidates for monitoring conditions are stored in the storage unit 6c. As candidates for monitoring conditions, for example, as shown in FIG. 7(b), "always on", "on every hour", "off during subculture/harvesting", etc. are stored in the storage unit 6c. The candidates stored in the storage unit 6c are not limited to those described above. The control device 6 may be programmed to switch the monitoring conditions in the order of candidates when the output portion of the monitoring conditions adjacent to any one monitoring item is touched on the monitoring condition setting screen S5. Alternatively, the control device 6 may be programmed to display a plurality of candidates for monitoring conditions in the vicinity of the above-mentioned output portion when the output portion is touched. The control device 6 may be programmed so that any one monitoring condition can be selected from among the displayed plurality of candidates.

Next, "threshold value formula setting" will be explained. The threshold value expression is an expression for determining how the value of each monitoring item changes to perform control related to the control item associated with each monitoring item. As will be described later, there are various types of expressions as candidates for the threshold expression.

The control device 6 is programmed to display a threshold value type setting screen S6 shown in FIG. 8(a) on the output unit 6b when the "Threshold value type setting" button is touched on the new setting screen S3. On the threshold formula setting screen S6, for example, the control device 6 displays, in order from the left side of the screen, a list of monitoring items, a list of control items associated with the monitoring items, a list of ideal formulas, a list of upper limits, and a list of lower limits. It is programmed to display the list on the output unit 6b. The ideal expression is an expression that indicates the most preferable change over time in a monitored item. The upper limit and the lower limit are values or formulas set as standards for determining whether or not the control device 6 performs predetermined control. Preferably, the control device 6 is programmed so that at least two types of upper and lower limits can be set for each monitoring item (“upper 1”, “upper 2”, and “lower” in FIG. 8(a)). 1” and “2 below”).

The control device 6 is programmed to store one monitoring item and one ideal formula in association with each other. Further, the control device 6 may, for example, provide two upper limit equations (hereinafter referred to as a first upper limit equation and a second upper limit equation) and two lower limit equations (hereinafter referred to as a first lower limit equation and a second upper limit equation) for one ideal equation. It is programmed to be able to set the lower limit formula). Each of the first upper limit expression, second upper limit expression, first lower limit expression, and second lower limit expression is a threshold expression that indicates the threshold value of the value of the monitoring item (hereinafter, these are referred to as the four threshold expressions. For details, (described later). The control device 6 is programmed to be able to set four threshold expressions associated with each monitoring item. The control device 6 is programmed so that it is not necessary to set all four threshold formulas for each monitoring item. Note that "-" on the initial screen shown in FIG. 8(a) means that the formula is undetermined.

The control device 6 is programmed to be able to set an ideal equation and a threshold equation according to the input result to the input section 6a. More specifically, for example, a plurality of ideal formula candidates are stored in advance in the storage unit 6c. For example, when the display part of the ideal formula related to any one monitoring item (for example, "cell count") is touched on the screen shown in FIG. 8(a), the control device 6 displays the screen shown in FIG. The output unit 6b displays a selection screen for an ideal formula related to the monitoring item as shown in FIG. The vertical axis of the ideal equation indicates the value of the monitored item. The horizontal axis of the ideal equation indicates time. Options for the ideal expression include, for example, a constant, a linear function, and an exponential function (see FIG. 8(b)). Alternatively, although not shown, a polynomial or the like may be included in the ideal expression options. The control device 6 may be programmed to create new ideal options in addition to existing options. A broken line drawn in the displayed graph indicates an ideal formula (see "FI" shown in FIG. 8(b)).

The two-dot chain line located above the dashed line indicating the ideal expression on the screen indicates the first upper limit expression (see "FU1" shown in FIG. 8(b)). When the value of the monitored item exceeds the value obtained based on the first upper limit formula, it is necessary to control the environment control unit 12 to bring the value of the monitored item closer to the ideal formula, for example. The two-dot chain line located below the dashed line indicating the ideal expression on the screen indicates the first lower limit expression (see "FL1" shown in FIG. 8(b)). When the value of the monitored item falls below the value obtained based on the first lower limit equation, it is required to bring the value of the monitored item closer to the ideal equation, for example, by controlling the environment control unit 12. A solid line located above the two-dot chain line indicating the first upper limit expression indicates the second upper limit expression (see "FU2" shown in FIG. 8(b)). When the value of the monitoring item exceeds the value obtained based on the second upper limit formula, for example, it becomes necessary to stop the cell culture. A solid line located below the two-dot chain line indicating the first lower limit expression indicates the second lower limit expression (see "FL2" shown in FIG. 8(b)). When the value of the monitoring item falls below the value obtained based on the second lower limit equation, for example, it becomes necessary to stop the cell culture. The control device 6 is programmed to set an ideal equation, a first upper limit equation, a second upper limit equation, a first lower limit equation, and a second lower limit equation for each monitoring item according to the input to the input unit 6a. There is.

Next, "control content setting" will be explained. The control content in this embodiment means the specific operation content of the operating unit 4 based on the monitoring result by the monitoring unit 5. For example, for reagents, the specific timing and amount of injection are included in the control content. Further, for example, regarding the supply amount of carbon dioxide, a predetermined numerical value or a mathematical expression using as a variable a monitoring item associated with the supply amount of carbon dioxide may correspond to the control content. The control device 6 is programmed so that information on control contents (hereinafter referred to as control information) can be set, for example, as follows.

The control device 6 is programmed to display a control content setting screen S7 shown in FIG. 9(a) on the output unit 6b when the "control content setting" button is touched on the new setting screen S3. On the control content setting screen S7, the control device 6 displays, for example, a list of a plurality of monitoring items and one or more control items associated with each monitoring item. For example, as shown in FIG. 9(a), "medium component A" is displayed as a monitoring item, and "reagent M" and "reagent N" associated with "medium component A" are displayed as control items. There is. Hereinafter, a pair of any one monitoring item and a control item associated with the monitoring item will be referred to as a "related pair."

The control device 6 is programmed, for example, to display a setting screen for control information of a control item associated with the monitoring item when any monitoring item is touched on the control content setting screen S7 ( (See FIG. 9(b)). The control device 6 is programmed to determine (newly set or change) control information according to the input results to the input section 6a. For example, a plurality of candidates for control information may be stored in the storage unit 6c. For example, as shown in FIG. 9(b), the injection timing and amount of reagent M may be set as the control information related to the related pair of "medium component A" and "reagent M." “Turn in when the upper limit is NG” corresponds to the feed timing. “X [ml]” corresponds to the input amount. Note that X here is a constant. Similarly, in the example shown in FIG. 9(b), as the control content regarding the related pair of "medium component A" and "reagent N", when the lower limit of medium component A becomes NG, Y [ml] of reagent is It is set so that N is input.

In addition to the above settings, the control device 6 performs the above-mentioned monitoring item management (addition and deletion of monitoring items, etc.) and control item management (addition and deletion of control items, etc.) according to the input results to the input section 6a. It may be programmed to do so. For example, in this embodiment, the control device 6 is programmed so that "monitoring item management" and "control item management" can be selected on the new setting screen S3 (see FIG. 5). However, the present invention is not limited to this, and "monitoring item management" and "control item management" may be selectable on other screens.

The control device 6 is programmed to store the input recipe name and the contents of the new settings in association with each other in the storage unit 6c when the "Save" button is touched on the new setting screen S3. More specifically, the control device 6 stores information including association information between monitoring items and control items, monitoring condition information, threshold value formula information, and control information in a storage unit in association with the recipe name. Store it in 6c. This makes it possible to newly set culture conditions (that is, create a new recipe).

Further, the control device 6 is programmed to be able to change (update) the contents of the created recipe (see "Culture condition change" in FIG. 4(b)). Further, the control device 6 is programmed to perform cell culture using the created recipe (see "Cell Culture Execution" in FIG. 4(a)). Further, although not shown, the control device 6 may be programmed to be able to rewrite the contents of a predetermined recipe while cell culture is being performed based on the recipe. In other words, the control device 6 is programmed to be able to update association information, monitoring condition information, threshold value formula information, and/or control information, etc. in the recipe while performing cell culture based on the recipe. It's okay if it's done.

(Know-how protection)
Next, a configuration for protecting know-how regarding the automatic cell culture apparatus 1 will be described with reference to FIGS. 10(a) and 10(b). FIG. 10A is an explanatory diagram showing information that can be stored in the server 100. FIG. 10(b) is an explanatory diagram showing the authority management screen S8 (described later). The control device 6 is configured as follows, for example, in order to prevent information regarding cell culture conditions from leaking to the outside and to prevent detailed culture conditions from being unintentionally rewritten or deleted.

As described above, the control device 6 includes the reading section 6d (see FIGS. 1 and 2). The reading section 6d is used for user authentication. The reading unit 6d includes, for example, a known fingerprint recognition sensor (not shown) and/or a camera (not shown).

As an overview, the control device 6 acquires information stored in the server 100 and performs user authentication based on the reading result by the reading section 6d. Then, the control device 6 allows the automatic cell culture device 1 to use and/or update a predetermined recipe based on the information stored in the server 100 and the user authentication result.

The server 100 is configured to be able to store information on permitted recipe names, rights holder IDs, culture device IDs, recipe adjustment history, accessor IDs, and access dates and times. The permitted recipe name is the name of a recipe that can be permitted to be used and/or updated. The right holder ID is the ID of an operator who has the authority to create, use, and update a recipe (hereinafter referred to as "creation, etc."). The culture device ID is individual information of the automatic cell culture device 1 that can be permitted to use and/or update recipes. The recipe adjustment history is a history showing how the created recipe was adjusted. More specifically, the recipe adjustment history is, for example, a history regarding differences between the contents of a certain recipe before updating and the contents of the recipe after updating. "Before updating the recipe" may be the timing immediately after initial setting of the recipe, or may be the timing immediately before updating the recipe. The accesser ID is, for example, the ID of the operator who last operated the control device 6 to access the server 100. The access date and time is the date and time when the server 100 was last accessed. In this embodiment, for convenience of explanation, it is assumed that server 100 authority is previously granted to a predetermined operator (see "U1" in FIG. 10A, hereinafter referred to as operator U1). For convenience of explanation, it is assumed that the storage unit 6c of the control device 6 stores in advance information on the ID of the operator U1 and information for authenticating the operator U1 in association with each other.

The control device 6 is programmed to perform user authentication, for example, when the "Authority Management" button is touched on the menu screen S1 (see FIG. 4(a)). The control device 6 performs user authentication based on the reading result by the reading section 6d, and acquires the ID of the authenticated user. Only when the control device 6 determines that the authenticated user's ID is included in the right holder ID stored in the server 100, the control device 6 displays the authority management screen S8 (FIG. 10(b)) for writing authority information to the server 100. )) is programmed to be displayed on the output section 6b. The control device 6 is programmed to record, change, or delete the information of the permitted recipe name, right holder ID, and culture device ID on the authority management screen S8 according to the input result to the input unit 6a. Further, the control device 6 is programmed to record recipe adjustment history, accessor ID, and access date and time information in the server 100.

(Procedures for determining and improving cell culture conditions)
Next, procedures for determining and improving cell culture conditions in the automatic cell culture apparatus 1 described above will be explained. First, an outline will be explained with reference to the flowchart of FIG. 11. For convenience of explanation, it is assumed that the manual culturers, engineers, and producers described below belong to the same cell culture manufacturer. Cell culture manufacturers are companies that mass produce cells. A manual culturer has the ability to perform manual cell culture. The technician has the ability to create, use and update recipes on the automatic cell culture device 1. The engineer is, for example, the operator U1 mentioned above. Producers have the ability to use and update recipes. The manual cultivator, technician and producer do not necessarily have to be separate people. For example, a technician may have the skills necessary for a manual cultivator. In this case, a technician may perform the work as a manual cultivator. Further, for example, the producer may have the skills necessary for the engineer. In this case, the producer may perform the work as an engineer.

First, a manual cultivator repeatedly performs manual culturing of predetermined cells under various conditions using a culturing apparatus (not shown) configured to allow manual culturing (S101). Hereinafter, for convenience of explanation, the series of treatments from the start of seeding to the completion of harvesting will be referred to as "cell culture treatment." Manual culturists perform a huge number of cell culture processes. Thereby, information necessary for creating a recipe in the automatic cell culture apparatus 1 is accumulated. Note that in order to efficiently vary the conditions, a known method such as experimental design or quality engineering may be used.

Next, based on the information accumulated for recipe creation, the engineer roughly determines the conditions for mass production of the predetermined cells (S102). The engineer operates the control device 6 to newly set a recipe for mass production (hereinafter referred to as mass production recipe) based on the mass production conditions (S103).

Next, the engineer or producer makes fine adjustments to the mass production recipe as necessary while actually performing cell culture processing in the automatic cell culture apparatus 1 (S104). Fine adjustments may be made during the cell culture process (ie, between seeding and harvest). Alternatively, fine adjustment may be performed between cell culture treatments (for example, after the first cell culture treatment and before the second cell culture treatment, etc.).

Next, the producer starts mass production of cells using the finely adjusted mass production recipe (S105). As a result, mass production data is accumulated (S106). Mass production data is various data related to mass production using mass production recipes. For example, the mass production data includes the results of monitoring by the monitoring unit 5, the control details of the operating unit 4, and the quality of cells mass-produced using the mass-production recipe.

Next, for example, an engineer analyzes mass production data (S107). Engineers identify the cell culture process that yields high-quality cells from a huge number of cell culture processes, and determine the reason for the high-quality cells. As an analysis method, for example, a known method such as multivariate analysis or MT method (Mahalanobis Taguchi system) may be used. Furthermore, the engineer further improves the mass production recipe based on the analysis results (S108). In the manner described above, cell culture conditions are determined and improved.

(Culture condition setting method)
Next, the method of newly setting the mass production recipe (namely, the culture condition setting method) described above will be explained with reference to the flowchart of FIG. 12 and FIG. 13. FIG. 13 is an explanatory diagram showing information stored in the server 100. Also, please refer to FIGS. 4 to 9(b) as appropriate.

First, the engineer performs user authentication in the automatic cell culture apparatus 1 (S201). Specifically, for example, after touching (or before touching) the "culture condition setting" button on the menu screen S1, the technician approaches or touches a predetermined part of the body (eyes, fingers, etc.) to the reading section 6d. let After completing user authentication, the technician is allowed to begin creating recipes. The engineer further performs an input operation on the input section 6a while looking at the screen displayed on the output section 6b. For example, the engineer touches a "new culture condition setting" button on the culture condition setting screen S2 (see FIG. 4). As a result, a new setting screen S3 (see FIG. 5) is displayed on the output unit 6b.

Next, the engineer sets the association between the monitoring item and the control item while viewing the association setting screen S4 (S203; see FIGS. 6(a) and 6(b)). Specifically, the engineer performs an operation on the input unit 6a to select one type of monitoring item from among a plurality of types of monitoring items (monitoring item selection step). Further, the engineer performs an operation on the input unit 6a to select at least one type of control item from among the plurality of types of control items (control item selection step). In this embodiment, the selected control item is automatically associated with the one type of monitoring item. That is, the control item selection step also serves as an association step in which the input unit 6a is operated to associate the one type of monitoring item with the at least one type of control item. Note that in this embodiment, when the selected control item is reselected, the association is automatically canceled.

Further, the engineer sets monitoring on/off conditions (the above-mentioned monitoring conditions) regarding the monitoring item while viewing the monitoring condition setting screen S5 (S204; see FIGS. 7(a) and (b)). . Further, the engineer sets the above-mentioned ideal formula and threshold formula while viewing the threshold formula setting screen S6 (S205; see FIGS. 8(a) and 8(b)). Further, the engineer sets control information for each control item while viewing the control content setting screen S7 (S206, control information input step, see FIGS. 9(a) and 9(b)). More specifically, the control information is control content related to each of the above-mentioned related pairs. The engineer may perform the settings from S203 to S206 in this order. Alternatively, the engineer may perform the setting operation while changing the order of steps S203 to S206 as appropriate.

Next, the engineer inputs a recipe name, for example, on the new setting screen S3 (see FIG. 5), and touches the "Save" button. At this time, the control device 6 stores the created recipe in the storage section 6c (S207).

Finally, the engineer sets authority information (S208). Specifically, the engineer touches the "Authority Management" button on the menu screen S1. As a result, the authority management screen S8 (see FIG. 10(b)) is displayed. The engineer inputs the authorized recipe name, right holder ID, and culture device ID into the input section 6a while viewing the authority management screen S8. For example, the engineer inputs a recipe name for a newly created recipe (see "R1" in FIG. 13). As a result, the recipe name is registered in the server 100.

Engineers can freely set authority information to a certain extent. For example, the engineer may register multiple rights holder IDs in the server 100 (see "U1", "U2", and "U3" in FIG. 13). For example, the engineer may register culture device IDs related to a plurality of automatic cell culture devices 1 in the server 100 (see “1A” and “1B” in FIG. 13). However, it is not limited to this. For example, the engineer may associate a plurality of permitted recipe names with a right holder ID and a culture device ID. Only one right holder ID and one culture device ID may be registered.

When the engineer performs an input operation to record authority information, the control device 6 records the recipe adjustment history, accessor ID, and access date and time in the server 100. As a result, necessary information is stored in the server 100 (see FIG. 13).

As described above, cultivators can set cell culture conditions with some degree of freedom using a method that is simpler than creating a control program. Therefore, in the automatic cell culture apparatus 1, the cultivator can take the initiative in helping to set cell culture conditions.

Further, by operating the input unit 6a based on the display by the output unit 6b, it is possible to easily perform association processing and association cancellation processing.

Further, the control device 6 switches whether or not to monitor at least some of the plurality of types of monitoring items according to monitoring conditions during cell culture. In the current situation where cultivators may find more appropriate monitoring conditions, it is extremely useful to allow cultivators themselves to easily and flexibly set or change monitoring conditions.

Further, the control device 6 generates a threshold expression indicating a threshold value of one type of monitoring item among the plurality of types of monitoring items, or selects one or more candidate expressions from among the plurality of types of monitoring items, in response to an input to the input unit 6a. , the threshold value formula is stored in the storage unit 6c in association with one type of monitoring item. Therefore, the cultivator can easily set how the culturing unit 11 and/or the environment control unit 12 should be controlled when the values of the monitored items change.

Next, a modification of the above embodiment will be described. However, components having the same configuration as those in the embodiment described above will be designated by the same reference numerals and the description thereof will be omitted as appropriate.

(1) In the embodiment described above, the control device 6 controls the operation unit 4 based on the relationship between the value of the monitored item and the upper limit expression or the lower limit expression. However, it is not limited to this. The control device 6 may perform feedback control on the operation unit 4 so that the values of the monitored items approach the ideal formula.

(2) In the embodiments described above, the control device 6 was programmed to be able to set two upper limit equations and two lower limit equations corresponding to one ideal equation. However, the number of expressions is not limited to this. For example, only one upper limit expression and one lower limit expression may be settable for one ideal expression. Alternatively, three or more upper limit expressions and three or more lower limit expressions may be set for one ideal expression.

(3) In the embodiments described above, the control device 6 is programmed to be able to set one ideal formula for one monitoring item. However, it is not limited to this. The control device 6 may be programmed, for example, to be able to set a plurality of ideal equations (and upper and lower limits) corresponding to one monitoring item. The control device 6 may be programmed so that the ideal equation to be used can be changed midway depending on conditions such as timing.

(4) In the embodiments described above, the control device 6 switches whether or not to monitor at least some of the plurality of types of monitoring items according to the monitoring conditions during cell culture. However, it is not limited to this. The control device 6 may be programmed to always monitor all monitoring items.

(5) In the embodiments described above, the control device 6 stores recipes. However, it is not limited to this. For example, the server 100 may be configured to store recipes. In this case, the server 100 corresponds to the storage unit of the present invention. Furthermore, the combination of the server 100 and the control device 6 corresponds to the control section of the present invention. Alternatively, a memory card (not shown) configured to be removably attached to the control device 6 may be configured to store the recipe. In this case, a memory card is included in the storage unit of the present invention. Alternatively, the memory card may be configured to be able to store the above-mentioned information regarding the authority instead of the recipe. In this case, the memory card can be used as a medium for multi-factor authentication.

(6) In the embodiments described above, when the selection button B2 is touched on the association setting screen S4, the association or cancellation of the association between the selected monitoring item and the control item related to the selection button B2 is automatically performed. I took it as a thing. However, it is not limited to this. For example, when any selection button B2 is touched, the control device 6 may cause the output unit 6b to display an option as to whether or not to perform the above-mentioned association (or cancellation of the association). Thereafter, the control device 6 may perform the above-mentioned association (or cancellation of the association) according to the input result to the input unit 6a.

(7) In the embodiments described above, one passage was performed between the start of culture and harvest. However, it is not limited to this. For example, the cells cultured in the culture container 25 may be harvested without being passaged. Alternatively, passage may be performed two or more times between the start of culture and harvest. In this case, in addition to the culture containers 25 and 27, other culture containers (not shown) may be provided in advance in the culture section 11. Alternatively, during culture, the culture container 25 and/or culture container 27 may be replaced with another culture container while maintaining a sterile state. For example, a known container exchange device (not shown) may be used during the container exchange operation.

(8) In the embodiments described above, the liquid (reagent or cell suspension) is transferred using pumps P1 to P4. However, it is not limited to this. The culture section 11 is configured to transfer the liquid in the container by using a gas pumped from a gas supply section (not shown) as described in, for example, Japanese Patent Application Publication No. 2021-40575. It's okay.

(9) The paths formed within the culture section 11 are not limited to those described above. The culture section 11 may have any route as long as it can transfer liquid between a plurality of containers while maintaining a sterile state.

(10) In the embodiments described above, a plurality of reagent heating containers are provided. Furthermore, within the culture section 11, a plurality of various containers having the same role may be provided. For example, a plurality of subculture containers 26 may be provided. Further, a plurality of collection containers 29 may be provided. The same applies to other containers.

1 Automatic cell culture device 5 Monitoring section 6 Control device (control section)
6a input section 6b output section 6c storage section 11 culture section 12 environment control section

Claims (5)

a culture unit configured to perform a series of processes from the start to the end of cell culture;
an environment control section configured to control a culture environment in which cells are cultured;
An automatic cell culture device comprising: a culture status indicating the state of cell proliferation in the culture unit; and a monitoring unit configured to monitor the culture environment;
comprising a control unit that controls the culture unit and the environment control unit based on the monitoring result by the monitoring unit,
The control unit includes an input unit configured to be operated by an operator, and a storage unit configured to be able to store information,
The storage unit includes a plurality of types of monitoring items that can be monitored by the monitoring unit, and a plurality of types of control items for the control unit to control the culture unit and/or the environment control unit. , is remembered,
The control unit includes:
association between a selected monitoring item selected from the plurality of types of monitoring items via the input unit and a selected control item selected from the plurality of types of control items via the input unit; storing information in the storage unit, and
determining control information that is information on the control content of the selected control item in response to a change in the value of the selected monitoring item in accordance with an input result to the input unit, and storing the control information in the storage unit. Features of automatic cell culture equipment. Equipped with an output section that displays information,
The control unit includes:
displaying information indicating the selected monitoring item and information indicating at least one type of candidate item among the plurality of types of control items on the output unit;
When it is determined that an operation for associating the selected monitoring item with one type of candidate item among the at least one type of candidate item has been performed on the input unit, the monitoring item and the one type of candidate item are Process the association of
When it is determined that an operation for canceling the association between the selected monitoring item and the one type of candidate item has been performed on the input unit, canceling the association between the selected monitoring item and the one type of candidate item. The automatic cell culture device according to claim 1, wherein the automatic cell culture device performs processing. The control unit causes the storage unit to store monitoring conditions that are conditions for determining whether or not to monitor each of the plurality of types of monitoring items according to the input result to the input unit,
The automatic cell culture apparatus according to claim 1 or 2, wherein during cell culture, execution or non-execution of monitoring related to at least some of the plurality of types of monitoring items is switched depending on the monitoring conditions. . The storage unit stores information on one or more candidate formulas that are candidates for threshold formulas for the plurality of types of monitoring items,
The control unit includes:
In response to an input to the input unit, a threshold expression indicating a threshold of one type of monitoring item among the plurality of types of monitoring items is generated or selected from among the one or more candidate expressions, and the threshold expression is selected from among the one or more candidate expressions. The automatic cell culture device according to any one of claims 1 to 3, characterized in that the information is stored in the storage unit in association with the one type of monitoring item. a culture section configured to perform a series of processes from the start to the end of cell culture; an environment control section configured to adjust the culture environment in which cells are cultured; and the culture section A method for setting culture conditions in an automatic cell culture device, the method comprising: a culture condition indicating the state of cell proliferation in an automatic cell culture device, and a monitoring unit configured to monitor the culture environment. There it is,
The automatic cell culture device includes a control unit that controls the culture unit and the environment control unit based on the monitoring result by the monitoring unit,
The control unit has an input unit configured to be operated by an operator, and a storage unit configured to be able to store information,
The storage unit includes a plurality of types of monitoring items that can be monitored by the monitoring unit, and a plurality of types of control items for the control unit to control the culture unit and/or the environment control unit. , which remembers
a monitoring item selection step of performing an operation on the input unit to select one type of selected monitoring item from the plurality of types of monitoring items;
a control item selection step of performing an operation on the input unit to select at least one type of selection control item from the plurality of types of control items;
an association step of performing an operation of association between the selected monitoring item and the at least one type of selection control item on the input unit;
automatic cell culture, comprising: a control information input step of performing a setting operation on the input unit regarding the control content of the at least one selected control item in response to a change in the value of the selected monitoring item; How to set culture conditions in the device.

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