Ips cell production system and apparatus

Abstract

An iPS cell production system according to an embodiment of the present invention includes: a cartridge provided with a flow path; and a production apparatus for producing iPS cells in the cartridge. The production apparatus has a liquid feeding mechanism, a culture device, and a control device. The liquid feeding mechanism applies, to the flow path in the cartridge, energy for feeding a cell liquid that contains target cells from a donor and a reagent that is used for processing the cell liquid. The culture device controls the culturing environment in the cartridge in order to culture, in the cartridge, iPS cells established in the cartridge through the action, on the target cells, of a reprogramming factor for reprogramming the target cells. The control device controls liquid feeding operation by the liquid feeding mechanism and environment control operation by the culture device in order to produce iPS cells from the target cells.

Description

iPS cell production system and device

[0001] The embodiments disclosed in this specification and drawings relate to an iPS cell production system and apparatus.

[0002] To produce high-quality, inexpensive iPS (Induced Pluripotent Stem Cell) cells, automated control of the iPS cell manufacturing process is required. Producing high-quality iPS cells requires highly skilled manual techniques, but manual methods can lead to variations in quality. Furthermore, quality control requires the involvement of multiple people, which increases labor costs.

[0003] Japan Special Table No. 2023-518207

[0004] One of the problems that the embodiments disclosed in this specification and drawings aim to solve is to produce high-quality iPS cells at low cost. However, the problems that the embodiments disclosed in this specification and drawings aim to solve are not limited to the above problem. Problems corresponding to the effects of each configuration shown in the embodiments described below can also be positioned as other problems.

[0005] An iPS cell production system according to an embodiment includes a cartridge having a flow path and a production device for producing iPS cells within the cartridge. The production device includes a liquid delivery mechanism, a culture device, and a control device. The liquid delivery mechanism applies energy to the flow path within the cartridge to deliver a cell solution containing a donor's target cells and a reagent used to treat the cell solution. The culture device controls the culture environment within the cartridge to culture iPS cells established within the cartridge by the action of a reprogramming factor on the target cells to reprogram the target cells. The control device controls the liquid delivery operation by the liquid delivery mechanism and the environment control operation by the culture device to produce iPS cells from the target cells.

[0006] FIG. 1 is a diagram showing an example of the configuration of an iPS cell production system. FIG. 2 is a perspective view of the exterior of the iPS cell production system. FIG. 3 is a plan view of the exterior of the iPS cell production apparatus. FIG. 4 is a schematic perspective view of the interior of a cartridge. FIG. 5 is a developed view of the flow path configuration of the cartridge. FIG. 6 is a diagram showing an example of the processing procedure of a production process using the iPS cell production system. FIG. 7 is a diagram showing an example of the processing procedure of the culture step (SA7) in the iPS cell production process shown in FIG. 6. FIG. 8 is a plan view showing the arrangement of the cartridge in step SB1. FIG. 9 is a plan view showing the arrangement of the cartridge in step SB3. FIG. 10 is a plan view showing the arrangement of the cartridge in step SB5. FIG. 11 is a perspective view showing the arrangement of the cartridge in step SB5. FIG. 12 is a plan view showing the arrangement of the cartridge in step SB10.

[0007] Hereinafter, the iPS cell production system and device according to this embodiment will be described in detail with reference to the drawings.

[0008] FIG. 1 is a diagram showing an example of the configuration of an iPS cell production system 1. FIG. 2 is a perspective view of the exterior of the iPS cell production system 1. FIG. 3 is a plan view of the exterior of an iPS cell production apparatus 3. The iPS cell production system 1 is an automatically controlled mechanical system that produces iPS cells from a cell solution containing a donor's target cells in a cartridge 2 incorporating a flow path. Blood is used as the cell solution. In this case, the target cells may be any cells contained in peripheral blood mononuclear cells (PBMCs), but as an example, CD34-positive cells are used. Here, an XYZ coordinate system is introduced, with the cartridge 2 as the reference. The X direction is defined as the longitudinal direction of the cartridge 2, the Y direction is defined as the height direction, and the Z direction is defined as the lateral direction. The X, Y, and Z axes are perpendicular to each other.

[0009] As shown in Figures 1, 2, and 3, the iPS cell production system 1 includes a cartridge 2 and an iPS cell production apparatus 3. The cartridge 2 is a disposable container provided with a flow path for producing iPS cells from target cells derived from a donor's sample. The iPS cell production apparatus 3 performs the following steps in the cartridge 2: a blood cell separation step for separating PBMCs from the donor's blood; a reprogramming factor introduction step for introducing reprogramming factors into target cells (e.g., CD34-positive cells) contained in the PBMCs; an iPS cell culture step for culturing iPS cells established by the action of the reprogramming factors on the target cells; and a detachment and recovery step for detaching and recovering iPS cells from the culture container.

[0010] The iPS cell production apparatus 3 is a group of machinery and devices that produce iPS cells from target cells in the cartridge 2. The iPS cell production apparatus 3 has a liquid supply mechanism 31, a culture device (incubator) 33, a valve opening and closing mechanism 35, a cooling device 37, a movement mechanism 39, and a control device 30. The iPS cell production apparatus 3 is connected by wire or wirelessly to the liquid supply mechanism 31, the culture device 33, the valve opening and closing mechanism 35, the cooling device 37, and the movement mechanism 39, and the control device 30, so that signals can be communicated between them.

[0011] The liquid delivery mechanism 31 is a mechanical mechanism that applies energy to deliver various liquids to the flow paths provided within the cartridge 2. As an example, the liquid delivery mechanism 31 applies energy to deliver a cell fluid containing a donor's target cells and a reagent used to process the cell fluid to the flow paths within the cartridge 2. The application of energy delivers the cell fluid, reagents, and the like. Reagents delivered by the liquid delivery mechanism 31 may include, for example, a reagent containing a reprogramming factor for reprogramming peripheral blood mononuclear cells, a culture medium used in the culture process of peripheral blood mononuclear cells or iPS cells, and phosphate-buffered saline (PBS) used in the washing process of peripheral blood mononuclear cells or iPS cells. The energy may be air, magnetic force, electric power, electromagnetic waves, mechanical action, or any other energy. For example, a syringe pump system, a pressure delivery system, or any other system may be used as a liquid delivery system using air. In the following description, the liquid delivery system used by the liquid delivery mechanism 31 is assumed to be a pressure delivery system. In this case, the liquid delivery mechanism 31 is equipped with liquid delivery pads 311 that deliver various liquids into the cartridge 2 by a pressure delivery system. In Figure 2, the liquid delivery mechanism 31 is equipped with two liquid delivery pads 311 that can be driven independently of each other. However, the number of liquid delivery pads 311 equipped in the liquid delivery mechanism 31 may be one or three or more. It is desirable that the number of liquid delivery pads 311 be smaller than the number of ports 21 provided in the cartridge 2.

[0012] The culture device 33 is a mechanical device (incubator) that controls the culture environment within the cartridge 2 in order to culture iPS cells established within the cartridge 2 through the action of reprogramming factors on target cells. The cartridge 2 is provided with a culture vessel for culturing iPS cells. The iPS cells are plate-cultured on the bottom surface (culture surface) of the culture vessel. The culture device 33 controls the temperature, humidity, and / or carbon dioxide gas concentration in the culture vessel 250 as the culture environment. As shown in FIGS. 2 and 3 , the culture device 33 has a storage chamber 331 with an opening 332. The storage chamber 331 is arranged on the movement path P39 of the cartridge 2 so that the cartridge 2 can be inserted through the opening 332.

[0013] The valve opening / closing mechanism 35 is a mechanical mechanism that opens and closes a valve that switches the flow path within the cartridge 2. The valve opening / closing method can be selected appropriately depending on the type of valve of the cartridge 2. While the valve opening / closing method is not particularly limited, a magnetic valve method is used as an example. As will be described in detail later, the magnetic valve is configured by a combination of a first magnet and a magnetic body such as an iron plate, which are arranged on either side of the flow path within the cartridge 2. In this case, the valve opening / closing mechanism 35 has one or more cylinders 351 that extend and retract toward and away from the first magnet. A second magnet (not shown) is attached to the tip of each cylinder 351. The magnetic valve is opened and closed by the extension and retraction of the cylinders 351. In FIG. 3 , the valve opening / closing mechanism 35 is equipped with two cylinders 351 that can be driven independently of each other. However, the valve opening / closing mechanism 35 may be equipped with one or three or more cylinders 351. The cylinder 351 may be supported so as to be movable in the X and Y directions relative to the valve opening and closing mechanism 35, or may be supported so as to be detachable.

[0014] The cooling device 37 is a mechanical device that cools the liquid medium stored in a liquid medium storage container (not shown) provided inside the cartridge 2. Specifically, the cooling device 37 has a device main body that is installed on the floor surface and a cooling element such as a Peltier element that is housed in the device main body. The cooling element is attached to the rear side of the housing of the cartridge 2, and cools the liquid medium stored in the liquid medium storage container that is located near the installation area.

[0015] The movement mechanism 39 is a mechanical mechanism that movably supports the cartridge 2. Specifically, the movement mechanism 39 includes a transport mechanism that supports the cartridge 2 so that it can reciprocate along a movement path P39, and a drive device that drives the transport mechanism. The movement path P39 runs along the longitudinal direction X of the cartridge 2. The transport mechanism includes a ball screw, rack and pinion, LM guide, linear guide, or the like. The drive device includes a servo motor or other motor. As shown in FIG. 3 , the movement path 39 includes a liquid delivery position P31 where the liquid delivery mechanism 31 delivers liquid, a culture position P33 where the culture device 33 performs culture, an opening / closing position P35 where the valve opening / closing mechanism 35 opens and closes the valve, and an installation position P37 where the cooling device 37 installs a cooling body. Note that while the liquid delivery position P31 and the opening / closing position P35 are arranged so as not to overlap in the Z direction in FIG. 3 , they may also be arranged to overlap in the Z direction. The moving mechanism 39 supports the cartridge 2 so that it can be positioned at a liquid sending position P31, an incubation position P33, an opening / closing position P35, and a mounting position P37.

[0016] The control device 30 is a processor that controls the liquid supply mechanism 31, the culture device 33, the valve opening / closing mechanism 35, the cooling device 37, and the movement mechanism 39. The control device 30 produces iPS cells in the cartridge 2 by sequentially controlling the liquid supply mechanism 31, the culture device 33, the valve opening / closing mechanism 35, the cooling device 37, and the movement mechanism 39 according to a control sequence. The control device 30 controls the liquid supply mechanism 31 to supply various liquids to the flow paths in the cartridge 2 positioned at the liquid supply position P31. The control device 30 controls the culture device 33 to culture iPS cells in a culture vessel in the cartridge 2 positioned at the culture position P33. The control device 30 controls the valve opening / closing mechanism 35 to open and close a valve in the cartridge 2 positioned at the opening / closing position P35. The control device 30 controls the cooling device 37 to attach a cooling body to the side of the housing of the cartridge 2 positioned at the attachment position P37.

[0017] The control method by the control device 30 can be, for example, an indirect control method and / or a direct control method. In the indirect control method, the control device 30 transmits drive commands and operation details corresponding to the drive commands to each of the liquid supply mechanism 31, the culture device 33, the valve opening and closing mechanism 35, the cooling device 37, and the movement mechanism 39 in an order determined by a control sequence. Upon receiving the drive commands, each of the controlled devices 31, 33, 35, 37, and 39 supplies a drive signal to its own drive device in accordance with the operation details to operate its internal mechanism. In the direct control method, the control device 30 supplies a drive signal to the drive device of each of the controlled devices 31, 33, 35, 37, and 39 in an order determined by the control sequence to each of the liquid supply mechanism 31, the culture device 33, the valve opening and closing mechanism 35, the cooling device 37, and the movement mechanism 39 to operate their internal mechanisms. The control method of the control device 30 does not need to be common to all of the control target devices 31, 33, 35, 37, and 39, and the control device 30 may adopt an indirect control method as the control method for some devices and a direct control method for the remaining devices.

[0018] Fig. 4 is a schematic perspective view of the inside of the cartridge 2. Fig. 5 is a development view of the flow path configuration of the cartridge. The flow path configuration shown in Fig. 5 is integrated into the cartridge 2 shown in Fig. 4.

[0019] As shown in FIG. 4 , the cartridge 2 has a housing 20 having a substantially rectangular parallelepiped shape. One side in the Z direction is called the main side, and the side opposite the main side is called the back side. A flow path is formed on the main side. Various storage containers, etc. (not shown) are arranged on the back side. One side in the X direction is called the front side, and the side opposite the front side is called the back side. The front side faces the culture device 33, and the back side faces the cooling device 37. One side in the Y direction is called the top side, and the side opposite the top side is called the bottom side. A liquid delivery port 21 to which a liquid delivery pad 311 of the liquid delivery mechanism 31 is connected is provided on the top side. The bottom side is in contact with the movement mechanism 39. The housing 20 is covered by an external housing (not shown) so that the top side is exposed. The external housing protects the flow path within the cartridge 2 from the outside air.

[0020] The interior of the housing 20 is filled with flow paths for various liquids used in the process of producing iPS cells. To reduce contact with outside air, the cartridge 2 has a closed flow path. Specifically, the interior of the housing 20 is provided with liquid supply tubes 23 that form the flow paths for various liquids. The liquid supply tubes 23 are made of a stretchable material such as vinyl or resin. Both ends of the liquid supply tube 23 are connected to various containers or instruments to reduce the intrusion of outside air into the liquid supply tube 23. Valves are provided at arbitrary locations on the liquid supply tube 23. The valves open and close the liquid supply tube 23, thereby switching the flow paths formed by the liquid supply tube 23. The valves are opened and closed individually by a valve opening and closing mechanism 35. The liquid supply tube 23 may be molded integrally with the housing 20.

[0021] The valve opening / closing method is not particularly limited, but a magnetic valve method is used as an example. The magnetic valve is composed of a combination of a first magnet and a magnetic body such as an iron piece, arranged on either side of the liquid supply pipe 23. The valve opening / closing mechanism 35 has a cylinder that moves toward and away from the first magnet, with a second magnet attached to the tip of the cylinder. When opening the valve, the valve opening / closing mechanism 35 contracts the cylinder to bring the second magnet closer to the first magnet. The second magnet is attracted to the first magnet, which separates the first magnet from the magnetic body, thereby opening the liquid supply pipe 23. When closing the valve, the valve opening / closing mechanism 35 extends the cylinder to separate the second magnet from the first magnet. This attracts the first magnet to the magnetic body, thereby closing the liquid supply pipe 23.

[0022] A container chamber 25 in which various containers are placed is provided within the housing 20. Containers that may be placed in the container chamber 25 include, for example, a culture container 250, a tapered container 254, sample containers 255, 257, 259, 262, and 263, an expansion culture container 258, an infection container 261, a pre-culture container 264, and a collection container 265.

[0023] As shown in FIG. 4 , the top surface of the housing 20 is provided with a plurality of holes (ports) 21 arranged in a row along the X direction. An air filter is provided at the opening of each port 21. The air filter is a filter that prevents or reduces the intrusion of unwanted substances contained in the outside air into the housing 20. Each port 21 communicates with a port chamber 24 provided in the cartridge 2. Aspirators / dischargers 27, 28, and 29 (shown in FIG. 5 ) are provided in the port chamber 24. The aspirators / dischargers 27, 28, and 29 are devices that include a syringe with a discharge port and a plunger that reciprocates within the syringe. A liquid delivery pad 311 provided in a liquid delivery mechanism 31 is connected to (accessed by) the port 21. In the following description, it is assumed that the liquid delivery method used by the liquid delivery mechanism 31 is a pressure delivery method.

[0024] When the pressure-feeding method is used, the liquid feed pad 311 uses air pressure to feed various liquids. An ejector and a compressor are branch-connected to the liquid feed pad 311 via a hollow tube through which a gas such as air or gas flows. The ejector depressurizes the port chamber 24 that communicates with the port 21 connected to the liquid feed pad 311. The depressurization of the port chamber 24 pulls the plungers from the syringes of the suction / dischargers 27, 28, and 29, and various liquids are transported into the syringes. The compressor pressurizes the port chamber 24 that communicates with the port 21 connected to the liquid feed pad 311. The pressurization of the port chamber 24 pushes the syringes of the suction / dischargers 27, 28, and 29 into the plungers, and various liquids are pressure-fed from the syringes.

[0025] The suction and discharge devices 27, 28, and 29 are classified into a liquid delivery device 27, a collection device 28, and a liquid waste device 29. The liquid delivery device 27 is connected to a blood bag or a reagent bag via a suction tube that forms a flow path for various liquids. The blood bag is a container that stores donor blood. The reagent bag is a container that stores reagents such as culture medium liquid, PBS, and reprogramming factor liquid. The blood bag and the reagent bag are collectively referred to as a storage container. The suction tube connecting the storage container and the liquid delivery device 27 is opened or closed by a valve or a one-way valve. The valve or one-way valve is opened or closed by a valve opening / closing mechanism 35. Hereinafter, the port 21 in which the liquid delivery device 27 is disposed will be referred to as a liquid delivery port, the port 21 in which the collection device 28 is disposed will be referred to as a collection port, and the port 21 in which the liquid waste device 29 is disposed will be referred to as a waste port. The fluid delivery ports 21 include a blood delivery port for delivering blood, a reprogramming factor delivery port for delivering a reagent containing a reprogramming factor, a culture medium delivery port for delivering culture medium liquid, and an iPS cell delivery port for delivering iPS cells.

[0026] Here, the liquid delivery operation of the liquid to be delivered (hereinafter referred to as the target liquid) will be described. First, under the control of the control device 30, the movement mechanism 39 moves the cartridge 2 so that the port 21 corresponding to the liquid to be delivered (hereinafter referred to as the target liquid) is located at the liquid delivery position P31. Next, under the control of the control device 30, the liquid delivery pad 311 of the liquid delivery mechanism 31 connects to the port 21 located at the liquid delivery position P31, and delivers the target liquid from the liquid delivery source to the liquid delivery destination.

[0027] When a target liquid is delivered from a storage container using the liquid delivery instrument 27, a liquid delivery pad 311 is connected to the liquid delivery port 21. The liquid delivery pad 311 delivers the target liquid to a destination via the liquid delivery instrument 27 arranged in the port chamber 24 communicating with the liquid delivery port 21 and through the liquid delivery tube 23 by applying pressure and decompression. Specifically, the liquid delivery pad 311 transports the target liquid from a storage container to the liquid delivery instrument 27 by applying pressure, and then pressure-feeds the target liquid from the liquid delivery instrument 27 to the destination via the liquid delivery tube 23 by applying pressure. Possible liquid delivery destinations include the culture vessel 250, filters 251, 256, and 260, the spiral channel 252, the waste liquid container 253, the tapered container 254, the sample containers 255, 257, 259, 262, and 263, the expansion culture container 258, the infection container 261, the pre-culture container 264, and the collection container 265.

[0028] When the target liquid is delivered from a liquid delivery source other than a storage container using the recovery tool 28, a liquid delivery pad 311 is connected to the recovery port 21. The liquid delivery pad 311 transports the target liquid present in the liquid delivery source in the cartridge 2 to the recovery tool 28 arranged in the port chamber 24 communicating with the recovery port 21 by reducing the pressure, and then pressurizes the target liquid from the recovery tool 28 to the liquid delivery destination via the liquid delivery tube 23. Possible liquid delivery sources and destinations include a culture vessel 250, filters 251, 256, and 260, a spiral channel 252, a waste liquid container 253, a tapered container 254, sample containers 255, 257, 259, 262, and 263, an expansion culture container 258, an infection container 261, a pre-culture container 264, and a recovery container 265, as shown in FIG. 4 .

[0029] When the target liquid is to be discarded into the waste liquid device 29, a liquid supply pad 311 is connected to the waste port 21. The liquid supply pad 311 uses reduced pressure to transport the target liquid present in the cartridge 2 to the waste liquid device 29 arranged in the port chamber 24 that communicates with the waste port 21. The waste liquid device 29 is removed from the cartridge 2 and discarded by an operator or the like.

[0030] As shown in Figure 5, the flow path configuration of cartridge 2 is divided along the X direction into a compartment used for culture medium (culture medium compartment), a compartment used for the blood cell separation process (blood cell separation compartment), a compartment used for the expansion culture process (expansion culture compartment), a compartment used for the reprogramming factor introduction process (factor introduction compartment), and a compartment used for the iPS cell culture process and detachment and recovery process (culture & detachment and recovery compartment).

[0031] The medium compartment has a flow path configuration for transferring the medium liquid from the reagent bag to the culture vessel 250. Specifically, the medium compartment has reagent bags for storing various medium liquids, a liquid transfer device 27 for the various medium liquids, a liquid waste device 29 for discarding the various medium liquids, a liquid transfer tube 23 connecting the above various elements, and the like.

[0032] The blood cell separation compartment has a flow path configuration for separating blood cell components from blood. Specifically, the blood cell separation compartment includes a blood bag for storing the donor's blood, a reagent bag for storing a reagent such as PBS, a liquid delivery device 27 for delivering the blood or reagent, a recovery device 28 for absorbing the blood or reagent, a filter 251 for extracting PBMCs from the blood, a spiral flow path 252 for extracting CD34-positive cells from the PBMCs, a waste liquid container 253 for containing waste matter extracted by the filter 251 and / or the spiral flow path 252, a tapered container 254 for containing the CD34-positive cells, a sample container 255, and a liquid delivery tube 23 connecting the above various elements.

[0033] The expansion culture compartment has a flow path configuration for expansion culture of CD34-positive cells. Specifically, the expansion culture compartment includes a reagent bag for storing a culture medium, a liquid delivery device 27 for delivering the culture medium, a liquid waste device 29 for disposing of various unnecessary liquids, a filter 256, a sample container 257, an expansion culture container 258 in which expansion culture of CD34-positive cells is performed, and a liquid delivery pipe 23 connecting the various elements described above.

[0034] The factor introduction compartment has a flow path configuration for introducing reprogramming factors into CD34-positive cells. Specifically, the factor introduction compartment includes a reagent bag for storing a reagent containing the reprogramming factors, a liquid delivery device 27 for delivering the reagent, a liquid delivery device 27 for delivering CD34-positive cells, a sample container 259, a filter 260, an infection container 261 in which the reagent is introduced into the CD34-positive cells, a sample container 262, and a liquid delivery tube 23 connecting the various elements described above. iPS cells are established in the infection container 261 by the action of the reagent on the CD34-positive cells.

[0035] The culture & detachment / recovery compartment has a flow path configuration for culturing iPS cells in a culture vessel and detaching and recovering iPS cells from the culture vessel. Specifically, the culture & detachment / recovery compartment has a reagent bag for storing a culture medium, a liquid delivery device 27 for delivering the culture medium, a sample container 263, a pre-culture container 264 for storing iPS cells before culture, a recovery device 28 for delivering iPS cells from the pre-culture container to the culture vessel, a culture container 250 for culturing iPS cells, a liquid delivery device 27 for delivering PBS for detaching iPS cells from the culture vessel, a recovery container 265 for recovering the detached iPS cells, and a liquid delivery tube 23 connecting the various elements described above.

[0036] 6 is a diagram showing an example of the processing procedure for producing iPS cells using the iPS cell production system 1. As shown in Fig. 6, first, the cartridge 2 is placed on the moving mechanism 39 (step SA1). It is assumed that the cartridge 2 is placed on the moving mechanism 39 manually by an operator. However, this may also be done by a mechanical device that can place the cartridge 2 on the moving mechanism 39 under automatic control.

[0037] When step SA1 is performed, the control device 30 controls the liquid delivery mechanism 31, the valve opening / closing mechanism 35, and the moving mechanism 39 to deliver the donor's blood into the cartridge 2 (step SA2). Specifically, first, the control device 30 controls the moving mechanism 39 to move the cartridge 2 so that the liquid delivery port 21 for blood is positioned at the liquid delivery position P31. Next, the control device 30 sequentially controls the liquid delivery operation by the liquid delivery mechanism 31 and the valve opening / closing operation by the valve opening / closing mechanism 35, and delivers the blood from the blood bag into the cartridge 2 via the liquid delivery tube 23. The blood bag may be attached to the cartridge 2 at any timing.

[0038] After step SA2 is performed, the control device 30 sequentially controls the liquid delivery mechanism 31, the valve opening / closing mechanism 35, and the movement mechanism 39 to separate blood cells in the blood cell separation compartment of the cartridge 2 (step SA3). In step SA3, the control device 30 executes the liquid delivery operation by the liquid delivery mechanism 31 and the valve opening / closing operation by the valve opening / closing mechanism 35 according to a predetermined sequence, captures PBMCs from the blood delivered in step SA2 with the filter 251, and delivers other waste matter to the waste container 253. Next, the control device 30 executes the liquid delivery operation by the liquid delivery mechanism 31 and the valve opening / closing operation by the valve opening / closing mechanism 35 according to a predetermined sequence, separates CD34-positive cells from PBMCs in the spiral channel 252, delivers the CD34-positive cells to the tapered container 254, and delivers other waste matter to the waste container 253.

[0039] After step SA3 is performed, the control device 30 controls the liquid supply mechanism 31, the culture device 33, the valve opening / closing mechanism 35, and the movement mechanism 39 to expand and culture the CD34-positive cells (step SA4). In step SA4, the control device 30 executes the liquid supply operation by the liquid supply mechanism 31, the valve opening / closing operation by the valve opening / closing mechanism 35, the culture operation by the culture device 33, and the movement operation by the movement mechanism 39 in a predetermined sequence, thereby expanding and culturing the CD34-positive cells in the expansion culture container 258.

[0040] After step SA4 is performed, the control device 30 controls the liquid supply mechanism 31, the valve opening / closing mechanism 35, and the moving mechanism 39 to supply the reprogramming factors into the cartridge 2 (step SA5). In step SA5, the control device 30 executes the liquid supply operation by the liquid supply mechanism 31 and the valve opening / closing operation by the valve opening / closing mechanism 35 according to a predetermined sequence, thereby supplying CD34-positive cells and various reagents containing the reprogramming factors to the infection container 261. Specifically, the control device 30 controls the moving mechanism 39 to move the cartridge 2 so that the liquid supply port 21 for the reagent containing the reprogramming factors is positioned at the liquid supply position P31. Next, the control device 30 controls the liquid supply mechanism 31 and the valve opening / closing mechanism 35 to supply the reagent containing the reprogramming factors and the CD34-positive cells to the infection container 26. The action of the reprogramming factors on the CD34-positive cells establishes iPS cells in the infection container 261.

[0041] After step SA5 is performed, the control device 30 controls the cooling device 37 and the moving mechanism 39 to attach the cooling body to the cartridge 2 (step SA7). In step SA7, the control device 30 executes the cooling body attachment operation by the cooling device 37 and the movement operation by the moving mechanism 39 according to a predetermined sequence, thereby attaching the cooling body to the cartridge 2. The cooling body is attached to a predetermined attachment area on the rear side of the housing 20. The attachment area is provided at a position on the rear side close to the medium liquid storage container. Therefore, the cooling body can cool the medium liquid stored in the medium liquid storage container. The attachment method is not particularly limited, and may be, for example, structurally by combining a hook and a claw portion, or magnetically by using a magnet. It is assumed that the medium liquid storage container has been attached to the cartridge 2 by an operator prior to step SA7.

[0042] After step SA6 is performed, control device 30 controls liquid supply mechanism 31, culture device 33, valve opening / closing mechanism 35, and movement mechanism 39 to culture iPS cells (step SA7). In step SA7, control device 30 executes the liquid supply operation by liquid supply mechanism 31, the valve opening / closing operation by valve opening / closing mechanism 35, the culture operation by culture device 33, and the movement operation by movement mechanism 39 in a predetermined sequence, thereby controlling the culture environment in culture container 250 and culturing iPS cells in culture container 250. Details of the culture process in step SA7 will be described later.

[0043] After step SA7 is performed, the control device 30 controls the liquid supply mechanism 31, the valve opening / closing mechanism 35, and the moving mechanism 39 to detach and recover iPS cells (step SA8). In step S7, the control device 30 executes the liquid supply operation by the liquid supply mechanism 31 and the valve opening / closing operation by the valve opening / closing mechanism 35 according to a predetermined sequence, spraying a detachment solution such as PBS into the culture vessel 250 to detach iPS cells from the culture vessel 250, and recovering the detached iPS cells in the recovery vessel 265. Specifically, the control device 30 controls the moving mechanism 39 to move the cartridge 2 so that the liquid supply port 21 for the PBS used for detachment is positioned at the liquid supply position P31. Next, the control device 30 controls the liquid supply mechanism 31 and the valve opening / closing mechanism 35 to spray PBS onto the culture vessel 250. The control device 30 controls the moving mechanism 39 to move the cartridge 2 so that the recovery port 21 for recovering iPS cells is positioned at the liquid supply position P31. The control device 30 controls the liquid sending mechanism 31 and the valve opening / closing mechanism 35 to send the iPS cells from the culture vessel 250 to the collection vessel 265. In this way, the iPS cells are collected by the collection vessel 265.

[0044] This completes the process for producing iPS cells.

[0045] The procedure for the iPS cell manufacturing process shown in Figure 6 is an example, and various processes can be added, deleted, and / or modified. As an example, if expansion culture is not required, the expansion culture step (SA4) can be omitted. The cooling body attachment step (SA6) does not have to be performed between steps (SA5) and (SA7), and can be performed at any stage of the culture step (SA7), for example, before step (SA5). The iPS cell detachment and recovery step (SA8) can be omitted if performed manually by an operator.

[0046] Next, the culture step (SA7) in the iPS cell production process shown in FIG. 6 will be described in detail with reference to FIG. 7 . FIG. 7 is a diagram showing an example of the processing procedure for the culture step (SA7) in the iPS cell production process shown in FIG. 6 . FIG. 8 is a plan view showing the arrangement of the cartridge 2 in step SB1. FIG. 9 is a plan view showing the arrangement of the cartridge 2 in step SB3. FIG. 10 is a plan view showing the arrangement of the cartridge 2 in step SB5. FIG. 11 is a perspective view showing the arrangement of the cartridge 2 in step SB5. FIG. 12 is a plan view showing the arrangement of the cartridge 2 in step SB10. Note that in FIGS. 8 to 12 , to avoid cluttering the drawings, only the medium liquid supply port 211 and the iPS cell supply port 212 are shown among the multiple ports, and only the medium liquid storage container 221 is shown among the multiple storage containers.

[0047] 7, first, the control device 30 controls the moving mechanism 39 to transport the cartridge 2 so that the medium liquid delivery port 211 in the cartridge 2 is positioned at a liquid delivery position P31 (step SB1), as shown in Fig. 8. After step SB1 is performed, the control device 30 controls the liquid delivery mechanism 31 and the valve opening / closing mechanism 35 to deliver the medium liquid stored in the medium liquid storage container 221 to the culture container 250 in the cartridge 2 (step SB2).

[0048] 9, the control device 30 controls the moving mechanism 39 to transport the cartridge 2 so that the iPS cell delivery port 212 in the cartridge 2 is positioned at delivery position P31 (step SB3). After step SB3, the control device 30 controls the delivery mechanism 31 and the valve opening / closing mechanism 35 to deliver the iPS cells to the culture vessel 250 in the cartridge 2 (step SB4).

[0049] When step SB4 is performed, the control device 30 controls the moving mechanism 39 to insert the cartridge 2 into the storage chamber 331 of the culture device 33 (step SB5), as shown in FIGS. 10 and 11 . Specifically, as shown in FIGS. 10 and 11 , the control device 30 controls the moving mechanism 39 to insert a portion of the cartridge 2 into the storage chamber 331 so that the culture vessel 250 is placed at the culture position P33 located in the storage chamber 331. More specifically, a portion of the cartridge 2 is inserted into the storage chamber 331 of the culture device 33 so that the culture vessel 250 in the cartridge 2 is placed at the culture position P33 in the storage chamber 331 and the medium solution storage container 221 in the cartridge 2 is placed outside the storage chamber 331. Because the cooling body 371 is attached to the rear side of the cartridge 2, placing the medium solution storage container 221 outside the storage chamber 331 also results in the cooling body 371 being placed outside the storage chamber 331. This makes it possible to cool the culture medium stored in the culture medium storage container 221 by the cooling body 371 while controlling the culture environment of the culture container 250 by the culture device 33 .

[0050] 11 , a sealing member 333 for restricting the flow of air between the inside and outside of the storage container 331 may be provided on all or part of the edge of the opening 332 of the storage container 331. By providing the sealing member 333, it is possible to prevent the culture environment of the culture vessel 250 from being disturbed.

[0051] After step SB5 is performed, the control device 30 controls the culture device 33 to control the culture environment (step SB6). Under the control of the control device 30, the culture device 33 maintains the temperature, humidity, and / or carbon dioxide gas concentration in the culture container 250 in the storage chamber 331 as the culture environment at constant values ​​(physiological condition values) determined based on physiological conditions in a living body. The physiological condition values ​​are not particularly limited, but are set to, for example, a temperature of 37°C, a relative humidity of 90%, and a carbon dioxide gas concentration of 5%.

[0052] After step SB6 is performed, the control device 30 determines whether the culture termination condition has been satisfied (step SB7). The culture termination condition is a condition for terminating the culture of iPS cells in the culture device 33. Specifically, the culture termination condition is set to the passage of a predetermined culture time (first threshold), such as 14 days (i.e., 24 hours x 14 days = 336 hours) from the start of culture. The start of culture may be set to the time when the cartridge 2 is first inserted into the storage chamber 331, or the time when control of the culture environment is first started. The control device 30 measures the elapsed time from the start of culture using a software timer, a hardware timer, or the like, and determines whether the current elapsed time has exceeded the first threshold. If the elapsed time has not exceeded the first threshold, the control device 30 determines that the culture termination condition has not been satisfied. If the elapsed time has exceeded the first threshold, the control device 30 determines that the culture termination condition has been satisfied.

[0053] If it is determined that the culture termination condition is not satisfied (step SB7: NO), the control device 30 determines whether the medium liquid replenishment condition is satisfied (step SB8). The medium liquid replenishment requirement is a condition for replenishing the medium liquid. Specifically, the medium liquid replenishment condition is set to a predetermined time (second threshold), such as two days (i.e., 24 hours x 2 days = 48 hours), since the most recent completion of medium liquid replenishment. The control device 30 measures the elapsed time from the most recent completion of medium liquid replenishment using a software timer or hardware timer, and determines whether the current elapsed time has exceeded the second threshold. If the elapsed time has not exceeded the second threshold, the control device 30 determines that the medium liquid replenishment condition is not satisfied. If the elapsed time has exceeded the second threshold, the control device 30 determines that the medium liquid replenishment condition is satisfied. The control device 30 waits until the elapsed time exceeds the second threshold.

[0054] During the standby period, the culture environment is maintained within the culture vessel 250, and the iPS cells immersed in the culture medium within the culture vessel 250 divide and grow on the bottom surface of the culture vessel 250. Since the cooling body 371 is attached to the cartridge 2, it is possible to continue to cool the culture medium stored in the culture medium storage container 221 within the cartridge 2 even during culture.

[0055] If it is determined that the medium liquid replenishment requirement has been met (step SB8: YES), the control device 30 controls the culture device 33 to stop controlling the culture environment (step SB9).

[0056] After step SB9 is performed, the control device 30 controls the moving mechanism 39 to remove the cartridge 2 and transport the cartridge 2 so that the medium liquid delivery port 211 in the cartridge 2 is positioned at the liquid delivery position P31, as shown in FIG. 12 (step SB10). After step SB10 is performed, the control device 30 controls the liquid delivery mechanism 31 and the valve opening / closing mechanism 35 to deliver the medium liquid stored in the medium liquid storage container 221 to the culture vessel 250 in the cartridge 2 (step SB11). If all of the medium liquid stored in the medium liquid storage container 221 has been delivered in step SB2, a new medium liquid storage container 221 needs to be attached to the cartridge 2 by step SB11. If the medium liquid storage container 221 contains all of the medium liquid to be used for 14 days of culture, there is no need to replace the medium liquid storage container 221. In this case, two days' worth of medium liquid is delivered from the medium liquid storage container 221 in each of steps SB2 and SB11.

[0057] After step SB11 is performed, the control device 30 again controls the moving mechanism 39 to insert the cartridge 2 into the storage chamber 331 of the culture device 33 (step SB5), and controls the culture device 33 to control the culture environment (step SB6). The control device 30 repeats steps SB8 → SB9 → SB10 → SB11 → SB5 → SB6 until it is determined in step SB7 that the culture termination condition is satisfied.

[0058] If it is determined in step SB7 that the culture termination condition is satisfied (step SB7: YES), the control device 30 terminates the culture process.

[0059] The processing procedure of the culture step shown in FIG. 7 is merely an example, and various processes can be added, deleted, and / or modified. As an example, steps SB1 and SB2 related to the supply of culture medium and steps SB3 and SB4 related to the supply of iPS cells may be reversed in order. As another example, the step of controlling the culture environment (SB6) may be performed prior to the step of inserting the cartridge 2 into the storage chamber 331 (SB5). As another example, the step of stopping control of the culture environment (SB9) may be omitted. In this case, the culture environment may be maintained by the culture device 33 at the same physiological condition values ​​as those in step SB6, or may be maintained at values ​​more relaxed than the physiological condition values. CD34-positive cells can also be expanded by performing steps similar to those in steps SB1 to SB11.

[0060] In the above embodiment, the iPS cell production apparatus 3 is equipped with one culture device 33. However, this embodiment is not limited to this. The iPS cell production apparatus 3 may be equipped with multiple culture devices 33. In this case, the multiple culture devices 33 are connected in a branched manner to one liquid supply mechanism 31 and one valve opening / closing mechanism 35 by the movement mechanism 39. This allows multiple cartridges 2 to be sequentially distributed to multiple culture devices 33, making it possible to culture iPS cells in parallel using multiple cartridges 2.

[0061] As in some of the above-described embodiments, the iPS cell production system 1 includes a cartridge 2 having a flow path and an iPS cell production device 3 for producing iPS cells within the cartridge 2. The iPS cell production device 3 includes a liquid delivery mechanism 31, a culture device 33, and a control device 30. The liquid delivery mechanism 31 applies energy to the flow path within the cartridge 2 to deliver a cell solution containing the donor's target cells and reagents used to treat the cell solution. The culture device 33 controls the culture environment within the cartridge to culture iPS cells established within the cartridge by the action of reprogramming factors on the target cells. The control device 30 controls the liquid delivery operation by the liquid delivery mechanism 31 and the environment control operation by the culture device 33 to produce iPS cells from the target cells.

[0062] The above configuration makes it possible to automatically control the process of feeding the cell solution and reagents into the cartridge 2 and the process of culturing the iPS cells in the cartridge 2. Automation can reduce the variation in quality of the iPS cells compared to manual control, and can also reduce labor costs.

[0063] As in some of the above-described embodiments, the cartridge 2 has a culture vessel 250 for culturing iPS cells, and the liquid delivery mechanism 31 further delivers a culture medium for culturing iPS cells to the culture vessel 250. This configuration also makes it possible to automatically control the process of delivering the culture medium. Furthermore, it becomes possible to culture iPS cells in the culture vessel 250 in the cartridge 2.

[0064] As in some of the above-described embodiments, the cartridge 2 has a culture vessel 250 for culturing iPS cells, and the culture device 33 controls the temperature, humidity, and / or carbon dioxide gas concentration in the culture vessel 250 as the culture environment. This configuration makes it possible to automatically control the temperature, humidity, and / or carbon dioxide gas concentration during the culture process.

[0065] As in several of the above embodiments, the cartridge 2 has a culture vessel 250 for culturing iPS cells. The iPS cell producing apparatus 3 further includes a movement mechanism 39 that supports the cartridge 2 so that it can move between a liquid delivery position P31 where liquid delivery is performed by the liquid delivery mechanism 31 and a culture position P33 where culture is performed by the culture device 33. The control device 30 controls the movement mechanism 39 to position the liquid delivery port 21 for the target liquid in the cartridge 2 at the liquid delivery position P31 and to position the culture vessel 250 provided on the cartridge 2 at the culture position P33. This configuration also makes it possible to automatically control the movement of the cartridge 2 to the liquid delivery position P31 and the culture position P33.

[0066] As in some of the above embodiments, the culture device 33 has a storage container 331 provided with an opening 332. The storage container 331 is arranged on the movement path P39 of the cartridge 2 so that the cartridge 2 can be inserted through the opening 332. The control device 30 controls the movement mechanism 39 to insert a portion of the cartridge 2 into the storage container 331 so that the culture vessel 250 is placed at a culture position P33 located in the storage container 331. With this configuration, it becomes possible to insert the cartridge 2 into the storage container 331 via the movement mechanism 39.

[0067] As in some of the above-described embodiments, a sealing member 333 is provided on all or part of the edge of the opening 332 of the storage container 331 to restrict the flow of air between the inside air of the storage container 331 and the outside air. By providing the sealing member 333, it is possible to suppress disturbance of the culture environment of the culture vessel 250.

[0068] As in some of the above-described embodiments, the cartridge 2 has a medium liquid storage container 221 that stores a medium liquid, which is a reagent, in a portion that is not inserted into the storage chamber 331. The iPS cell production apparatus 3 further includes a cooling device 37 that cools the medium liquid stored in the medium liquid storage container 221. This configuration makes it possible to cool the medium liquid stored in the medium liquid storage container 221 by the cooling device 37 while controlling the culture environment of the culture vessel 250 by the culture device 33.

[0069] As in several of the above-described embodiments, the cooling device 37 has a cooling body 371. The moving mechanism 39 movably supports the cartridge 2 so that it can be placed at the mounting position P37 of the cooling body 371 by the cooling device 37. The cooling device 37 attaches the cooling body 371 to the cartridge 2 placed at the mounting position P37. Specifically, the cooling body 371 is attached to the housing 20 of the cartridge 2 in the mounting region near the medium liquid storage container 221. The cooling body 371 can cool the medium liquid stored in the medium liquid storage container 221. Furthermore, because the cooling body 371 is attached to the cartridge 2, it is possible to continue cooling the medium liquid stored in the medium liquid storage container 221 in the cartridge 2 even during culture.

[0070] As in some of the above embodiments, when the medium liquid replenishment conditions are satisfied, the iPS cell production apparatus 3 controls the movement mechanism 39 to remove the cartridge 2 from the storage chamber 331 and place it at the liquid delivery position P31, controls the liquid delivery mechanism 31 to deliver the medium liquid from the medium liquid storage container 221 of the cartridge to the culture vessel 250, and controls the movement mechanism 39 to insert a portion of the cartridge 2 into the storage chamber 331. This configuration enables automatic control of medium liquid replacement, thereby reducing the effort required for changing the medium liquid.

[0071] As described in several embodiments above, when iPS cell cultivation by the culture device 33 is completed, the iPS cell production apparatus 3 controls the movement mechanism 39 to remove the cartridge 2 from the storage chamber 331 and place it at the liquid delivery position P31, and controls the liquid delivery mechanism 31 to spray a detachment solution onto the culture vessel 250 and recover the iPS cells detached from the culture vessel 250. This configuration enables automatic control of the detachment and recovery of iPS cells. This reduces the effort required for detachment and recovery of iPS cells. Furthermore, by performing detachment by spraying a detachment solution using the liquid delivery mechanism 31, there is no need to install a new mechanism for detachment, thereby reducing equipment costs and installation space. Similarly, by performing iPS cell recovery using the liquid delivery mechanism 31, there is no need to install a new mechanism for iPS cell recovery, thereby reducing equipment costs and installation space.

[0072] As in some of the above embodiments, the iPS cell production apparatus 3 further includes a valve opening / closing mechanism 35 that opens and closes the valve. The cartridge 2 has a valve for switching the flow path. The movement mechanism 39 further supports the cartridge 2 so that it can be moved to an opening / closing position P35 where the valve opening / closing mechanism 35 opens and closes the valve. The control device 30 controls the valve opening / closing mechanism 35 to switch the valve located at the opening / closing position P35. This configuration makes it possible to automatically control the switching of the flow paths within the cartridge 2. This reduces the effort required for switching the flow paths. Furthermore, by adopting a flow path switching method, it is possible to reduce the installation space for the flow paths within the cartridge 2 compared to when this method is not adopted.

[0073] According to at least one of the embodiments described above, high-quality iPS cells can be produced at low cost.

[0074] The iPS cell production system according to the embodiment described above can also be applied to the production of cells other than iPS cells. That is, such a cell production system includes a cartridge having a flow path and a cell production device for producing cells within the cartridge. The cell production device includes a liquid delivery mechanism, a culture device, and a control device. The liquid delivery mechanism applies energy to the flow path within the cartridge to deliver a cell solution containing the donor's target cells and reagents used to treat the cell solution. The culture device 3 controls the culture environment within the cartridge to culture the cells established within the cartridge. The control device controls the liquid delivery operation by the liquid delivery mechanism and the environment control operation by the culture device to produce cells from the target cells.

[0075] The term "processor" used in the above description refers to a circuit such as a CPU, a GPU, an application specific integrated circuit (ASIC), a programmable logic device (e.g., a simple programmable logic device (SPLD), a complex programmable logic device (CPLD), and a field programmable gate array (FPGA)). A processor realizes its function by reading and executing a program stored in a memory circuit. Note that instead of storing a program in a memory circuit, the program may be directly embedded in the processor circuit. In this case, the processor realizes its function by reading and executing the program embedded in the circuit. On the other hand, if the processor is, for example, an ASIC, instead of storing a program in a memory circuit, the function is directly embedded in the processor circuit as a logic circuit. Note that each processor in this embodiment is not limited to being configured as a single circuit for each processor, but may be configured as a single processor by combining multiple independent circuits to realize its function. Furthermore, the functions of the multiple components in FIG. 1 may be realized by integrating them into a single processor.

[0076] Although several embodiments have been described, these embodiments are presented as examples and are not intended to limit the scope of the invention. These embodiments can be implemented in various other forms, and various omissions, substitutions, modifications, and combinations of embodiments can be made without departing from the spirit of the invention. These embodiments and their modifications are included within the scope and spirit of the invention, as well as within the scope of the invention and its equivalents as defined in the claims.

[0077] 1 iPS cell production system 2 Cartridge 3 iPS cell production device 20 Housing 21 Port 23 Liquid supply pipe 24 Port chamber 25 Container chamber 27 Liquid supply tool 28 Recovery tool 29 Liquid waste tool 30 Control device 31 Liquid supply mechanism 33 Culture device (incubator) 35 Valve opening / closing mechanism 37 Cooling device 39 Transfer mechanism 211 Medium liquid supply port 212 iPS cell liquid supply port 221 Medium liquid storage container 250 Culture container 251 Filter 252 Spiral channel 253 Liquid waste container 254 Tapered container 255 Sample container 256 Filter 257 Sample container 258 Expansion culture container 259 Sample container 260 Filter 261 Infection container 262 Sample container 263 Sample container 264 Pre-culture container 265 Collection container 311 Liquid supply pad 331 Storage container 332 Opening 333 Sealing member 351 Cylinder 371 Cooling body

Claims

1. An iPS cell production system comprising: a cartridge provided with a flow path; and a production device for producing iPS cells within the cartridge, wherein the production device has a fluid delivery mechanism that applies energy to deliver a cell fluid containing a donor's target cells and a reagent used for processing the cell fluid to the flow path within the cartridge; a culture device that controls the culture environment within the cartridge in order to culture iPS cells established within the cartridge by the action of an initialization factor on the target cells to initialize the target cells; and a control device that controls the fluid delivery operation by the fluid delivery mechanism and the environment control operation by the culture device in order to produce the iPS cells from the target cells.

2. The iPS cell manufacturing system of claim 1, wherein the reagent includes the reprogramming factor.

3. The iPS cell manufacturing system according to claim 1 or 2, wherein the cartridge has a culture container for culturing the iPS cells, and the liquid delivery mechanism further delivers a medium liquid for culturing the iPS cells to the culture container.

4. An iPS cell manufacturing system as claimed in any one of claims 1 to 3, wherein the cartridge has a culture container for culturing the iPS cells, and the culture device controls the temperature, humidity and / or carbon dioxide gas concentration in the culture container as the culture environment.

5. An iPS cell manufacturing system as described in any one of claims 1 to 4, wherein the cartridge has a culture container for culturing the iPS cells, the manufacturing apparatus further comprises a moving mechanism that supports the cartridge so that it can be moved between a liquid delivery position where liquid delivery is performed by the liquid delivery mechanism and a culture position where culture is performed by the culture device, and the control device controls the moving mechanism to position a liquid delivery port for the target liquid in the cartridge at the liquid delivery position and to position the culture container provided in the cartridge at the culture position.

6. The iPS cell production system of claim 5, wherein the culture device has a storage container with an opening, the storage container is arranged on a movement path of the cartridge so that the cartridge can be inserted through the opening, and the control device controls the movement mechanism to insert a portion of the cartridge into the storage container so that the culture vessel is positioned at the culture position located within the storage container.

7. An iPS cell production system as described in claim 6, wherein a sealing member is provided on all or part of the edge of the opening of the container to restrict the flow of air between the inside and outside of the container.

8. The iPS cell manufacturing system of claim 6, wherein the cartridge has a medium liquid storage container for storing the reagent medium liquid in a portion not inserted into the storage chamber, and the manufacturing apparatus further comprises a cooling device for cooling the medium liquid stored in the medium liquid storage container.

9. The iPS cell production system of claim 8, wherein the cooling device has a cooling body, the moving mechanism movably supports the cartridge so that it can be positioned at an installation position of the cooling body by the cooling device, and the cooling device attaches the cooling body to the cartridge placed at the installation position.

10. The iPS cell production system according to claim 9, wherein the cooling device is configured to attach the cooling body to the cartridge housing in the vicinity of the culture medium storage container.

11. The iPS cell production system of claim 6, wherein the control device, upon satisfaction of a medium liquid replenishment condition, controls the moving mechanism to pull the cartridge out of the storage chamber and place it at the liquid delivery position, controls the liquid delivery mechanism to deliver a predetermined amount of medium liquid from the medium liquid storage container of the cartridge to the culture vessel, and controls the moving mechanism to insert the portion of the cartridge into the storage chamber.

12. The iPS cell manufacturing system of claim 6, wherein the control device, when the cultivation of iPS cells by the cultivation device is completed, controls the moving mechanism to pull out the cartridge from the storage chamber and place it at the liquid delivery position, and controls the liquid delivery mechanism to spray a detachment liquid into the cultivation vessel and recover the iPS cells that have detached from the cultivation vessel.

13. The iPS cell manufacturing system of claim 5, wherein the manufacturing apparatus further comprises a valve opening and closing mechanism that opens and closes the valve, the cartridge has the valve for switching the flow path, the moving mechanism further supports the cartridge so that it can be moved to an opening and closing position where the valve opening and closing operation is performed by the valve opening and closing mechanism, and the control device controls the valve opening and closing mechanism to open and close the valve in the cartridge when positioned at the opening and closing position.

14. An iPS cell manufacturing device comprising: a fluid delivery mechanism that applies energy to deliver a cell fluid containing a donor's target cells and a reagent used in processing the cell fluid to a flow path within a cartridge; a culture device that controls the culture environment within the cartridge in order to culture iPS cells established within the cartridge by the action of an initialization factor on the target cells to initialize the target cells; and a control device that controls the fluid delivery operation by the fluid delivery mechanism and the environmental control operation by the culture device in order to produce the iPS cells from the target cells.

Images