Cell Culture Systems

Abstract

This cell culture system (10) is provided with: a treatment unit (24) which cultures cells; a reactor installation device (68) where the treatment unit (24) can be installed; a connection circuit (26) which is connected to the treatment unit (24); a circuit control device (66) to which the connection circuit (26) can be detachably attached; and a tank device (64) which has a culture medium housing unit (74) for housing a culture medium. The treatment unit (24) has multiple bioreactors (30). The culture medium in the culture medium housing unit (74) is supplied to the treatment unit (24) via the connection circuit (26). The culture medium housing unit (74) can house the amount of culture medium necessary to culture cells in the treatment unit (24).

Description

[Technical Field]

[0001] The present invention relates to a cell culture system. [Background technology]

[0002] For example, JP 2019-517247 A discloses a cell culture device that includes a reactor installation unit capable of installing one bioreactor for culturing cells, and a circuit control unit that can detachably connect a connection circuit connected to the bioreactor. The circuit control unit is used to supply cells and culture medium from the connection circuit to the bioreactor and to recover cultured cells from the bioreactor to the connection circuit. Summary of the Invention

[0003] Generally, a cell culture device is formed by integrating a reactor installation unit and a circuit control unit. Therefore, if it is desired to increase the amount of cell culture, it is necessary to prepare multiple cell culture devices. In other words, the same number of circuit control units as the number of bioreactors is required. This results in a problem of rising costs.

[0004] The present invention has been made in consideration of these problems, and aims to provide a cell culture system that can efficiently increase the amount of cell culture while suppressing cost increases.

[0005] One aspect of the present invention is a cell culture system comprising: a processing unit for culturing cells; a reactor installation device in which the processing unit can be installed; a connection circuit connected to the processing unit; a circuit control device that allows the connection circuit to be attached and detached and that supplies the cells and culture medium from the connection circuit to the processing unit and recovers the cultured cells from the processing unit to the connection circuit; and a tank device having a culture medium storage unit for storing the culture medium, wherein the processing unit has a plurality of bioreactors, and the culture medium in the culture medium storage unit is supplied to the processing unit via the connection circuit, and the culture medium storage unit is capable of storing the amount of culture medium necessary for culturing cells in the processing unit.

[0006] According to the present invention, since a circuit control device is provided for each treatment section, the number of circuit control devices is less than the number of bioreactors. Therefore, the amount of cell culture can be efficiently increased while suppressing cost increases. Furthermore, since the culture medium storage section can store the amount of culture medium necessary to culture cells in the treatment section, even if a large amount of culture medium is required when culturing cells using multiple bioreactors, it is not necessary to replace the culture medium storage section during cell culture. Therefore, cell culture can be performed smoothly and efficiently. [Brief explanation of the drawings]

[0007] [Figure 1] 1 is a schematic configuration diagram of a cell culture system according to a first embodiment of the present invention. [Figure 2] FIG. 2 is a circuit diagram of the cell culture system of FIG. 1. [Figure 3] FIG. 3 is a diagram showing the configuration of the processing unit in FIG. 2 and its surrounding circuits. [Figure 4] FIG. 2 is a cross-sectional view of the tank device of FIG. 1. [Figure 5] FIG. 5 is a cross-sectional view taken along line VV in FIG. [Figure 6] FIG. 2 is a perspective view of the circuit control device and reactor installation device of FIG. 1. [Figure 7] FIG. 7 is a perspective view illustrating the circuit control device of FIG. 6. [Figure 8] 2 is a flowchart of a cell culture method using the cell culture system of FIG. 1. [Figure 9] FIG. 10 is a schematic diagram of a cell culture system including a cell culture device according to a modified example. [Figure 10] FIG. 1 is a schematic configuration diagram of a cell culture system according to a second embodiment of the present invention. [Figure 11] FIG. 11 is a circuit diagram of the cell culture system of FIG. 10. [Figure 12] FIG. 11 is a cross-sectional explanatory view of the tank device of FIG. 10, with a portion thereof omitted. DETAILED DESCRIPTION OF THE INVENTION

[0008] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS A preferred embodiment of a cell culture system according to the present invention will be described below with reference to the accompanying drawings.

[0009] A cell culture system 10 according to one embodiment of the present invention is for culturing (growing) cells isolated from biological tissue.

[0010] As shown in FIGS. 1 and 2, a cell culture system 10 includes two cell culture kits 12 capable of flowing a liquid, a cell culture device 14 in which the two cell culture kits 12 are set, and a controller 16. The cell culture system 10 includes the two cell culture kits 12, a first cell culture kit 12a and a second cell culture kit 12b. The first cell culture kit 12a and the second cell culture kit 12b have the same configuration. In the following description, when there is no need to distinguish between the first cell culture kit 12a and the second cell culture kit 12b, they will simply be referred to as cell culture kits 12.

[0011] Liquids flowing within the cell culture kit 12 include a solution containing cells (hereinafter referred to as cell liquid), a culture medium (culture medium) for growing cells, a cleaning liquid for cleaning the inside of the cell culture kit 12, and a detachment liquid for detaching cells.

[0012] Examples of the cells that can be used include blood cells (such as T cells) and stem cells (such as ES cells, iPS cells, and mesenchymal stem cells). The culture medium can be selected appropriately depending on the cells of the living organism, and can be prepared by adding various amino acids, vitamins, serum, and the like to a balanced salt solution (BSS) as a base solution. A buffer solution or physiological saline solution can be used as the washing solution. Examples of buffer solutions include PBS (Phosphate Buffered Salts) and TBS (Tris-Buffered Saline). Examples of the detachment solution include trypsin or EDTA solution. However, the cell solution, culture medium, washing solution, and detachment solution are not limited to those described above.

[0013] As shown in FIG. 2, the cell culture kit 12 includes a cell solution bag 18, a detachment solution bag 20, a collection bag 22, a processing unit 24, a connection circuit 26, and a gas exchanger .

[0014] The cell solution bag 18, the detachment solution bag 20, and the collection bag 22 are each made in a bag shape from a flexible material such as soft resin, for example, polyvinyl chloride or polyolefin.

[0015] The cell solution bag 18 contains a cell solution. The detachment solution bag 20 contains a detachment solution. The collection bag 22 is for containing the cultured cells. The collection bag 22 is an empty bag that does not contain any liquid before use of the cell culture kit 12.

[0016] As shown in Figure 3, the processing unit 24 includes five bioreactors 30 arranged in parallel. The five bioreactors 30 have the same configuration. However, the five bioreactors 30 may differ from one another in size, shape, etc. The bioreactors 30 are configured as so-called hollow fiber bioreactors. The bioreactor 30 includes a large number (plurality) of hollow fibers 32 and a cylindrical housing 34 that accommodates these hollow fibers 32.

[0017] The hollow fibers 32 extend along the longitudinal direction of the housing 34. Both ends of the hollow fibers 32 are open. One end of the hollow fibers 32 is fixed to one end of the housing 34. The other end of the hollow fibers 32 is fixed to the other end of the housing 34. A plurality of pores (not shown) are formed in the wall of the hollow fibers 32. The pores communicate between an IC (intra capillary) region, which is the lumen of the hollow fibers 32, and an EC (extra capillary) region located outside the hollow fibers 32 within the housing 34. The diameter of the pores is set to a size that prevents the passage of macromolecules (such as cells) while allowing the passage of small molecules (such as water, ions, oxygen, and lactate). The diameter of the pores is set to, for example, approximately 0.005 μm to 10 μm.

[0018] Examples of materials constituting the hollow fibers 32 include polymer materials such as polyolefin resins such as polypropylene and polyethylene, polysulfone, polyethersulfone, polyacrylonitrile, polytetrafluoroethylene, polystyrene, polymethyl methacrylate, cellulose acetate, cellulose triacetate, and regenerated cellulose, but the materials constituting the hollow fibers 32 are not limited to those mentioned above.

[0019] The housing 34 is provided with an IC inlet port 36a, an IC outlet port 36b, an EC inlet port 38a, and an EC outlet port 38b. The IC inlet port 36a is provided at one end of the housing 34. The IC inlet port 36a introduces liquids (cell solution, culture medium, washing solution, and detachment solution) guided from the connection circuit 26 (IC circulation circuit 44) into the IC region of the bioreactor 30. The IC outlet port 36b is provided at the other end of the housing 34. The IC outlet port 36b guides liquids that have circulated through the IC region of the bioreactor 30 to the connection circuit 26 (IC circulation circuit 44).

[0020] The EC inlet port 38a and the EC outlet port 38b are provided on the outer peripheral surface of the housing 34. The EC inlet port 38a introduces liquids (culture medium and cleaning solution) guided from the connection circuit 26 (EC circulation circuit 48) into the EC region of the bioreactor 30. The EC outlet port 38b guides the liquid that has circulated through the EC region of the bioreactor 30 to the connection circuit 26 (EC circulation circuit 48).

[0021] In FIG. 2 , the connection circuit 26 extends linearly. The connection circuit 26 is formed into a tube shape using a soft resin material. However, the connection circuit 26 may also be formed, for example, by stacking two sheets together in the thickness direction and joining (fusing or sealing) portions other than the flow path. In this case, the wall portion (non-sealed portion) forming the connection circuit 26 is preferably formed to protrude outward from the sealed portion so that the connection circuit 26 becomes an open flow path in its natural state. In this case, excess sheet on both sides of the flow path of the connection circuit 26 may be removed. The connection circuit 26 includes an IC supply flow path 40, a culture medium supply line 42, an IC circulation circuit 44, an EC supply flow path 46, an EC circulation circuit 48, a connection line 50, a sampling line 52, a recovery line 54, and a waste liquid flow path 56.

[0022] The IC supply flow path 40 includes a first IC supply line 40a, a second IC supply line 40b, and a third IC supply line 40c. One end of the first IC supply line 40a is aseptically joined to the cell solution bag 18. The other end of the first IC supply line 40a is connected to the IC circulation circuit 44. One end of the second IC supply line 40b is aseptically joined to the stripping solution bag 20. The other end of the second IC supply line 40b is connected to a midpoint of the first IC supply line 40a. One end of the third IC supply line 40c is connected to the culture medium supply line 42. The other end of the third IC supply line 40c is connected to a midpoint of the second IC supply line 40b.

[0023] When the cell culture kit 12 is set in the cell culture device 14, one end of the culture medium supply line 42 is aseptically joined to a connection tube of a culture medium storage unit 74 (described later) of the cell culture device 14. The other end of the culture medium supply line 42 is connected to the third IC supply line 40c. The culture medium supply line 42 is provided with an intermediate culture medium flow path 58 for heating the culture medium (cooled culture medium) guided from the culture medium storage unit 74 to a desired temperature. The intermediate culture medium flow path 58 is provided between the culture medium storage unit 74 and the processing unit 24.

[0024] 2 and 3, the IC circulation circuit 44 circulates the liquid introduced into the IC circulation circuit 44 from the IC supply channel 40 to the IC region of each bioreactor 30. In Fig. 3, the IC circulation circuit 44 includes five IC inlet lines 44a, five IC outlet lines 44b, and an IC circulation line 44c.

[0025] The five IC inlet lines 44a are connected to the IC inlet ports 36a of the five bioreactors 30. The five IC outlet lines 44b are connected to the IC outlet ports 36b of the five bioreactors 30. One end of the IC circulation line 44c is connected to the five IC inlet lines 44a. The other end of the IC circulation line 44c is connected to the five IC outlet lines 44b. The IC circulation line 44c is provided with an IC intermediate flow path 60 for heating the liquid flowing through the IC circulation line 44c to a desired temperature.

[0026] 2, the EC supply flow path 46 includes a first EC supply line 46a and a second EC supply line 46b. One end of the first EC supply line 46a is connected to the culture medium supply line 42. The other end of the first EC supply line 46a is connected to the EC circulation circuit 48. One end of the second EC supply line 46b is aseptically joined to a connecting tube of a cleaning liquid storage unit 76 (described later) of the cell culture device 14 when the cell culture kit 12 is set in the cell culture device 14. The other end of the second EC supply line 46b is connected to a midpoint of the first EC supply line 46a.

[0027] 2 and 3, the EC circulation circuit 48 circulates the liquid introduced from the EC supply channel 46 to the EC circulation circuit 48 through the EC region of each bioreactor 30. In Fig. 3, the EC circulation circuit 48 includes five EC introduction lines 48a, five EC withdrawal lines 48b, and an EC circulation line 48c.

[0028] The five EC introduction lines 48a are connected to the EC inlet ports 38a of the five bioreactors 30. The five EC outlet lines 48b are connected to the EC outlet ports 38b of the five bioreactors 30. One end of the EC circulation line 48c is connected to the five EC introduction lines 48a. The other end of the EC circulation line 48c is connected to the five EC outlet lines 48b. The EC circulation line 48c is provided with an EC intermediate flow path 62 for heating the liquid flowing through the EC circulation line 48c to a desired temperature.

[0029] 2, the connecting line 50 connects the IC supply flow path 40 and the EC supply flow path 46. Specifically, one end of the connecting line 50 is connected to the second IC supply line 40b downstream of the connecting portion with the third IC supply line 40c. The other end of the connecting line 50 is connected to the first EC supply line 46a downstream of the connecting portion with the second EC supply line 46b.

[0030] The sampling line 52 is a flow path for collecting a portion of the culture medium that has circulated through the EC region of each bioreactor 30. One end of the sampling line 52 is connected to the EC circulation line 48c downstream of the processing unit 24. The other end of the sampling line 52 is aseptically joined to a connection tube of a sensor device 70 (described later) of the cell culture device 14 when the cell culture kit 12 is set in the cell culture device 14. In this embodiment, one end of the sampling line 52 is provided in the set state in the circuit control device 66 (see FIG. 1). However, one end of the sampling line 52 may also be provided in the reactor installation device 68 in the set state.

[0031] The recovery line 54 is a flow path for guiding the cultured cells from the IC circulation circuit 44 to the recovery bag 22. One end of the recovery line 54 is connected to the IC circulation line 44c downstream of the processing unit 24. The other end of the recovery line 54 is aseptically joined to the recovery bag 22.

[0032] The waste liquid flow path 56 is a flow path for guiding used liquid (waste liquid) to a waste liquid storage unit 78 (described later) of the cell culture device 14. The waste liquid flow path 56 includes an IC waste liquid line 56a and an EC waste liquid line 56b. One end of the IC waste liquid line 56a is connected to a section of the IC circulation line 44c between the processing unit 24 and the connecting portion with the recovery line 54. The other end of the IC waste liquid line 56a is aseptically joined to the connecting tube of the waste liquid storage unit 78 when the cell culture kit 12 is set in the cell culture system 10. One end of the EC waste liquid line 56b is connected to a section of the EC circulation line 48c between the connecting portion with the sampling line 52 and the connecting portion with the first EC supply line 46a. The other end of the EC waste liquid line 56b is connected to the IC waste liquid line 56a.

[0033] The gas exchanger 28 is provided between the EC circulation line 48c and the EC intermediate flow path 62 at a connecting portion with the first EC supply line 46a. The gas exchanger 28 mixes predetermined gas components into the liquid (culture medium) flowing through the EC circulation line 48c. Examples of the gas components to be mixed include components similar to those found in natural air (nitrogen N2: 75%, oxygen O2: 20%, carbon dioxide CO2: 5%).

[0034] The structure of the gas exchanger 28 is not particularly limited, and similar to the bioreactor 30, a gas exchanger having a plurality of hollow fibers 32 provided in a housing 34 can be applied.

[0035] As shown in FIGS. 1 and 2, the cell culture device 14 includes one tank device 64, two circuit control devices 66, two reactor installation devices 68, and one sensor device 70. The cell culture device 14 has two circuit control devices 66, a first circuit control device 66a and a second circuit control device 66b. The cell culture device 14 has two reactor installation devices 68, a first reactor installation device 68a and a second reactor installation device 68b. In the following description, when there is no need to distinguish between the first circuit control device 66a and the second circuit control device 66b, they will simply be referred to as the circuit control device 66. Furthermore, when there is no need to distinguish between the first reactor installation device 68a and the second reactor installation device 68b, they will simply be referred to as the reactor installation device 68.

[0036] 1 and 4, the tank device 64 includes a box-shaped base 72 that is placed on the floor or the like, a culture medium storage section 74 that stores a culture medium, a cleaning liquid storage section 76 that stores a cleaning liquid, and a waste liquid storage section 78 that can store waste liquid. The base 72 has a first case section 77 and a second case section 80. The first case section 77 includes a first case main body 82 in which the culture medium storage section 74 can be placed, and a first door section 84 (see FIGS. 1 and 5) that is provided on the front surface of the first case main body 82 in an openable and closable manner.

[0037] The first case 77 is a cooling section that cools the culture medium to a desired temperature (for example, 4°C or higher and 8°C or lower). The second case 80 includes a second case body 86 in which the cleaning liquid storage section 76 and the waste liquid storage section 78 can be placed, and a second door 88 (see FIG. 1) that is provided on the front surface of the second case body 86 in an openable and closable manner. The second case 80 does not have a cooling function.

[0038] 4 and 5, the culture medium storage unit 74 has a culture medium tank 90 molded into a box shape from hard resin, and a culture medium installation member 92 capable of storing the culture medium tank 90. ​​The culture medium tank 90 is preferably a disposable item. However, the culture medium tank 90 may also be a reusable item. The culture medium supply line 42 of each cell culture kit 12 is connected to the culture medium tank 90 when the cell culture kit 12 is set in the cell culture device 14 (hereinafter referred to as the "set state"). That is, the culture medium storage unit 74 (culture medium tank 90) is shared by the two processing units 24 (two cell culture kits 12) to supply culture medium from the culture medium storage unit 74 to the two processing units 24 via the two connection circuits 26.

[0039] The culture medium tank 90 can accommodate an amount of culture medium necessary for culturing cells in two processing units 24 (two cell culture kits 12). The culture medium tank 90 accommodates an amount of culture medium necessary for culturing cells using two cell culture kits 12 (ten bioreactors 30) connected to the culture medium tank 90. ​​Specifically, if 20 L of culture medium is required for one bioreactor 30, for example, the culture medium tank 90 accommodates 200 L of culture medium. In this way, if the amount of culture medium necessary from the start to the end of cell culture is accommodated in the culture medium tank 90 in advance, replacement of the culture medium accommodation unit 74 is unnecessary, which is efficient. The culture medium is accommodated in the culture medium tank 90 in a clean bench.

[0040] Furthermore, if the culture medium is stored at room temperature (e.g., 22°C) or in a bright place for the duration of cell culture (e.g., 7 days or more), there is a risk that the components of the culture medium (protein, glutamine, etc.) will denature. However, in this embodiment, the culture medium is stored in the first case part 77, which is a low-temperature, dark place, and therefore, denaturation of the components of the culture medium is effectively suppressed.

[0041] The culture medium setting member 92 is molded from hard resin. The culture medium setting member 92 is a reusable product. The culture medium setting member 92 is open at the top. A plurality of rollers 94 (wheels) are provided on the bottom surface of the culture medium setting member 92. This allows the relatively heavy culture medium accommodating section 74 to be smoothly moved by the plurality of rollers 94 with the culture medium tank 90 placed inside the culture medium setting member 92. Therefore, the culture medium accommodating section 74 can be easily and efficiently moved in and out of the first case section 77. The culture medium setting member 92 is not limited to the above-mentioned configuration and may be a cart.

[0042] 4, the cleaning liquid storage unit 76 has a cleaning liquid tank 96 molded into a box shape from hard resin, and a cleaning liquid installation member 98 capable of storing the cleaning liquid tank 96. The cleaning liquid tank 96 is preferably a disposable item. However, the cleaning liquid tank 96 may also be a reusable item. The second EC supply line 46b of each cell culture kit 12 is connected to the cleaning liquid tank 96 in an assembled state. That is, the cleaning liquid storage unit 76 (cleaning liquid tank 96) is shared by the two processing units 24 (two cell culture kits 12) to supply the cleaning liquid from the cleaning liquid storage unit 76 to the two processing units 24 via the two connection circuits 26.

[0043] The cleaning solution tank 96 can contain the amount of medium necessary to wash two processing units 24 (two cell culture kits 12). The cleaning solution tank 96 contains the amount of cleaning solution necessary to wash two cell culture kits 12 connected to the cleaning solution tank 96. In this case, there is no need to replace the cleaning solution tank 96 during cell culture, which is efficient.

[0044] The cleaning liquid setting member 98 is molded from hard resin. The cleaning liquid setting member 98 is a reusable product. The cleaning liquid setting member 98 is open at the top. A plurality of rollers 100 (wheels) are provided on the bottom surface of the cleaning liquid setting member 98. This allows the relatively heavy cleaning liquid storage section 76 to be smoothly moved by the plurality of rollers 100 with the cleaning liquid tank 96 placed inside the cleaning liquid setting member 98. Therefore, the cleaning liquid storage section 76 can be easily and efficiently moved in and out of the second case section 80. The cleaning liquid setting member 98 is not limited to the above-mentioned configuration and may be a dolly.

[0045] The waste liquid storage section 78 is molded into a box shape from hard resin. The waste liquid storage section 78 is a reusable item. However, the waste liquid storage section 78 may also be a disposable item. The waste liquid flow path 56 (IC waste liquid line 56a) of each cell culture kit 12 is connected to the waste liquid storage section 78 in an assembled state. That is, the waste liquid storage section 78 is shared by the two processing sections 24 (two cell culture kits 12) in order to discharge waste liquid from the two processing sections 24 to the waste liquid storage section 78 via the two connection circuits 26.

[0046] The waste liquid storage section 78 can store waste liquid discharged from two processing sections 24 (two cell culture kits 12). That is, the waste liquid storage section 78 is formed to a size that can store waste liquid (liquid) used in the two cell culture kits 12 connected to the waste liquid storage section 78. In this case, there is no need to replace the waste liquid storage section 78 during cell culture, which is efficient.

[0047] A plurality of rollers 102 (wheels) are provided on the bottom surface of the waste liquid storage section 78. This allows the waste liquid storage section 78 to be moved smoothly by the plurality of rollers 102. Therefore, the waste liquid storage section 78 can be easily and efficiently moved in and out of the second case section 80.

[0048] The culture medium tank 90 and the cleaning liquid tank 96 are not limited to the example in which they are made of hard resin, but may be, for example, large-capacity bags made of soft resin in a pouch shape.

[0049] 1, the first circuit controller 66a, the first reactor installation device 68a, the second circuit controller 66b, the second reactor installation device 68b, and the sensor device 70 are arranged on an upper surface 72a of a base 72. The first circuit controller 66a and the first reactor installation device 68a are adjacent to each other. The second circuit controller 66b and the second reactor installation device 68b are adjacent to each other.

[0050] The connection circuit 26 of the first cell culture kit 12a is detachably attached to the first circuit control device 66a. The first circuit control device 66a is used to supply cells and culture medium from the connection circuit 26 to the processing unit 24 and to recover cultured cells from the processing unit 24 to the connection circuit 26.

[0051] 2 and 6, the first circuit control device 66a includes a box-shaped housing 104, a plurality of clamps 106, a plurality of pumps 108, and a first holding unit 110. In Fig. 6, the housing 104 has an internal space 105 in which the connection circuit 26 can be installed. The housing 104 includes a housing main body 112 and a housing door unit 114 provided on the front surface of the housing main body 112 in an openable and closable manner.

[0052] The housing 104 has a temperature control function that maintains the internal space 105 of the housing 104 at a desired temperature (e.g., 37°C). That is, the housing 104 functions as a temperature raising mechanism 107 that raises the temperature of the intermediate culture medium flow path 58. In FIG. 1, a bag support part 116 for suspending multiple bags (cell solution bag 18, detachment solution bag 20, recovery bag 22) is provided on the top surface of the housing 104. A display part 118 that displays the current process of cell culture, etc. is provided on the outer surface of the housing door part 114 (see FIG. 1).

[0053] 2, the multiple clamps 106 are on-off valves that open and close the internal flow paths of the lines (tubes) of the connection circuit 26 by pressing from the outside against the wall portions that constitute the lines. The first circuit control device 66a has the multiple clamps 106: a first clamp 106a, a second clamp 106b, a third clamp 106c, a fourth clamp 106d, a fifth clamp 106e, a sixth clamp 106f, a seventh clamp 106g, an eighth clamp 106h, and a ninth clamp 106i.

[0054] The first clamp 106a is disposed opposite the first IC supply line 40a in the set state and opens and closes the internal flow path of the first IC supply line 40a. The second clamp 106b is disposed opposite the second IC supply line 40b in the set state and opens and closes the internal flow path of the second IC supply line 40b. The third clamp 106c is disposed opposite the third IC supply line 40c in the set state and opens and closes the internal flow path of the third IC supply line 40c.

[0055] The fourth clamp 106d is disposed opposite the first EC supply line 46a in the set state and opens and closes the internal flow path of the first EC supply line 46a. The fifth clamp 106e is disposed opposite the second EC supply line 46b in the set state and opens and closes the internal flow path of the second EC supply line 46b. The sixth clamp 106f is disposed opposite the connecting line 50 in the set state and opens and closes the internal flow path of the connecting line 50.

[0056] The seventh clamp 106g is disposed opposite the recovery line 54 in the set state, and opens and closes the internal flow path of the recovery line 54. The eighth clamp 106h is disposed opposite the IC waste liquid line 56a in the set state, and opens and closes the internal flow path of the IC waste liquid line 56a. The ninth clamp 106i is disposed opposite the EC waste liquid line 56b in the set state, and opens and closes the internal flow path of the EC waste liquid line 56b.

[0057] The multiple pumps 108 apply a flow force to the liquid inside by rotating in a manner that squeezes the wall portions that make up the lines (tubes) of the connection circuit 26. The circuit control device 66 has, as the multiple pumps 108, an IC supply pump 108a and an EC supply pump 108b.

[0058] When set, the IC supply pump 108a is positioned so that it is in contact with the first IC supply line 40a downstream of the connection point with the second IC supply line 40b, and imparts a flow force to the liquid flowing through the first IC supply line 40a in a direction toward the IC circulation circuit 44.

[0059] The EC supply pump 108b is positioned so that when set, it is in contact with the first EC supply line 46a downstream of the second EC supply line 46b, and imparts a flow force to the liquid flowing through the second EC supply line 46b in a direction toward the EC circulation circuit 48.

[0060] 2 and 6, the first holding part 110 holds the intermediate culture medium flow path 58 of the culture medium supply line 42 in a predetermined shape (serpentine shape). The first holding part 110 is provided in the internal space 105 of the housing 104. Specifically, in FIGS. 6 and 7, the first holding part 110 includes a rectangular first frame 120, a first inner frame 122 provided on the first frame 120, and an attachment part 124.

[0061] The first inner frame 122 is formed in a cross shape. The first inner frame 122 is connected to the center of each side of the first box-shaped frame 120. In FIG. 6, the medium intermediate flow path 58 has a serpentine shape and is locked to the first box-shaped frame 120 and the first inner frame 122 by locking members (not shown). As shown in FIG. 7, the attachment portion 124 is a cylindrical portion protruding from the center of the first inner frame 122. The attachment portion 124 is attached to a mounting portion 126 provided inside the housing 104. The position, shape, size, and number of the attachment portions 124 can be changed as appropriate.

[0062] 2, the length of the medium intermediate flow path 58 held in the first holding unit 110 is set to a length that allows the medium to circulate for only the first temperature rise time. Here, the first temperature rise time refers to the time required for the temperature of the medium cooled in the medium storage unit 74 (e.g., 5°C) to rise to a desired temperature (e.g., 37°C). In addition to the above-mentioned configuration, the first circuit control device 66a is also equipped with a pressure sensor, a liquid level sensor, etc. (not shown).

[0063] In this embodiment, it is preferable that the mounting portion 126 (see Figure 7) is formed so as to be able to rotatably support the bioreactor 30, and that the first circuit control device 66a further has an IC circulation pump 127a and an EC circulation pump 127b (see Figure 2).

[0064] With this configuration, for example, when cell culture using one bioreactor is required (when a small amount of cell culture is required), a cell culture kit having only one bioreactor can be set in the first circuit control device 66a and cell culture can be performed. At this time, the bioreactor is set in the mounting part 126.

[0065] Furthermore, the IC circulation pump 127a applies a flow force to the liquid flowing through the IC circulation line of the cell culture kit in a direction toward the bioreactor. Furthermore, the EC circulation pump 127b applies a flow force to the liquid flowing through the EC circulation line of the cell culture kit in a direction toward the bioreactor. Note that in cell culture using a cell culture kit 12 having multiple (five) bioreactors 30 as in this embodiment, the IC circulation pump 127a and the EC circulation pump 127b are not used.

[0066] 2, the connection circuit 26 of the second cell culture kit 12b is set in the second circuit control device 66b. The configuration of the second circuit control device 66b is the same as the configuration of the first circuit control device 66a. Therefore, a description of the configuration of the second circuit control device 66b will be omitted.

[0067] As shown in FIGS. 3 and 6, the processing unit 24 of the first cell culture kit 12a is set in the first reactor installation device 68a. The first reactor installation device 68a includes a box-shaped reactor case 128, five reactor support units 130, a plurality of pumps 132, and a second holding unit 134. In FIG. 6, the reactor case 128 has an internal space 129 in which the processing unit 24 (five bioreactors 30) can be installed. The reactor case 128 includes a reactor case main body 136 and a door 138 provided on the front surface of the reactor case main body 136 in an openable and closable manner. The reactor case 128 has a temperature control function for maintaining the internal space 129 of the reactor case 128 at a desired temperature (e.g., 37°C). That is, the reactor case 128 functions as a temperature raising mechanism 131 for raising the temperature of the IC intermediate flow path 60.

[0068] In Figure 3, the reactor support part 130 is provided in the internal space 129 of the reactor case part 128. The reactor support part 130 is formed so that the bioreactor 30 can be attached and detached. The reactor support part 130 supports the bioreactor 30 so that it can rotate around the rotation axis Ax. The rotation axis Ax is located at the center of the extension direction of the bioreactor 30. The rotation axis Ax extends in a direction perpendicular to the extension direction of the bioreactor 30.

[0069] The first reactor installation device 68a has five IC circulation pumps 132a and five EC circulation pumps 132b as the plurality of pumps 132. The IC circulation pump 132a is arranged so as to contact the IC introduction line 44a in the set state, and applies a flow force to the liquid flowing through the IC introduction line 44a in the direction toward the bioreactor 30. The EC circulation pump 132b is arranged so as to contact the EC introduction line 48a in the set state, and applies a flow force to the liquid flowing through the EC introduction line 48a in the direction toward the bioreactor 30.

[0070] 3 and 6, the second holding portion 134 holds the IC intermediate flow path 60 of the IC introduction line 44a and the EC intermediate flow path 62 of the EC circulation line 48c in a predetermined shape (serpentine shape). The second holding portion 134 is provided in the internal space 129 of the reactor case portion 128. Specifically, in FIG. 6, the second holding portion 134 includes a rectangular second frame 140 and a second inner frame 142 provided inside the second frame 140.

[0071] The second inner frame 142 is formed in a cross shape. The second inner frame 142 is connected to the center of each side of the second framework 140. The IC intermediate flow path 60 and the EC intermediate flow path 62 are each serpentine and locked to the second framework 140 and the second inner frame 142 by locking members (not shown). The second holding portion 134 is fixed to the inner surface of the door portion 138.

[0072] As shown in FIGS. 1, 2, and 6, the first reactor installation device 68a is provided separately from the first circuit control device 66a. Therefore, in FIGS. 2 and 6, the first cell culture kit 12a, when set up, has an IC outer flow path 45 and an EC outer flow path 49 located outside the first circuit control device 66a and the first reactor installation device 68a. The first cell culture kit 12a according to this embodiment includes a first IC outer flow path 45a and a second IC outer flow path 45b as the IC outer flow path 45. As shown in FIG. 2, the first IC outer flow path 45a is located in a section of the IC circulation line 44c from the connection with the first IC supply line 40a to the IC intermediate flow path 60. The second IC outer flow path 45b is located in a section of the IC circulation line 44c from the processing unit 24 to the connection with the IC waste liquid line 56a.

[0073] The liquid flowing through the IC circulation line 44c is cooled at the positions of the first IC outer flow path 45a and the second IC outer flow path 45b. In other words, the liquid flowing through the IC circulation line 44c may be cooled to room temperature (e.g., 30°C) at the positions of the first IC outer flow path 45a and the second IC outer flow path 45b.

[0074] The length of the IC intermediate flow path 60 held in the second holding portion 134 is set to a length that allows the liquid to circulate for only the second temperature rise time. Here, the second temperature rise time refers to the time required for the temperature (e.g., 30°C) of the liquid cooled in the first IC outer flow path 45a or the second IC outer flow path 45b to rise to a desired temperature (the temperature of the internal space 129 of the reactor case portion 128) when circulating through the IC circulation line 44c.

[0075] The first cell culture kit 12a also includes a first EC outer flow path 49a and a second EC outer flow path 49b as the EC outer flow path 49. The first EC outer flow path 49a is located in a section of the EC circulation line 48c between the gas exchanger 28 and the EC intermediate flow path 62. The second EC outer flow path 49b is located in a section of the EC circulation line 48c between the processing unit 24 and the connecting portion with the EC waste liquid line 56b.

[0076] The liquid flowing through the EC circulation line 48c is cooled at the positions of the first EC outer flow path 49a and the second EC outer flow path 49b. In other words, the liquid (culture medium) flowing through the EC circulation line 48c may be cooled to room temperature (e.g., 30°C) at the positions of the first EC outer flow path 49a and the second EC outer flow path 49b.

[0077] The length of the EC intermediate flow path 62 held in the second holding portion 134 is set to a length that allows the liquid to circulate for only the third temperature rise time. Here, the third temperature rise time refers to the time required for the temperature (e.g., 30°C) of the liquid cooled in the first EC outer flow path 49a or the second EC outer flow path 49b to rise to a desired temperature (the temperature of the internal space 129 of the reactor case portion 128) when circulating through the EC circulation line 48c.

[0078] The processing unit 24 of the second cell culture kit 12b is installed (set) in the second reactor installation device 68b. The configuration of the second reactor installation device 68b is the same as the configuration of the first reactor installation device 68a. Therefore, a description of the configuration of the second reactor installation device 68b will be omitted.

[0079] As shown in Fig. 2, the sensor device 70 is connected to the first cell culture kit 12a and the second cell culture kit 12b in an installed state. The sensor device 70 has a box-shaped sensor case 144 (see Figs. 1 and 6), two pumps 146, a sensor unit 148, and a waste liquid bag 150. A bag support 152 for suspending the waste liquid bag 150 is provided on the upper surface of the sensor case 144 (see Figs. 1 and 6). The two pumps 146 and the sensor unit 148 are disposed inside the sensor case 144.

[0080] The pump 146 has a configuration similar to the pump 108 described above. The sensor device 70 has two pumps 146, a first sampling pump 146a and a second sampling pump 146b. The first sampling pump 146a is arranged so as to contact the sampling line 52 of the first cell culture kit 12a in the set state, and applies a flow force toward the sensor unit 148 to the liquid (culture medium) flowing through the sampling line 52. The second sampling pump 146b is arranged so as to contact the sampling line 52 of the second cell culture kit 12b in the set state, and applies a flow force toward the sensor unit 148 to the liquid (culture medium) flowing through the sampling line 52.

[0081] The sensor unit 148 measures the components (concentrations of pH, O2, CO2, glucose, lactic acid, etc.) of the culture medium introduced through the sampling line 52. The culture medium is discharged into the waste liquid bag 150 after measurement by the sensor unit 148 is completed.

[0082] In the cell culture device 14, the sensor device 70 (sensor unit 148 and waste fluid bag 150) is shared by the first cell culture kit 12a and the second cell culture kit 12b. Also, the tank device 64 is shared by the first cell culture kit 12a and the second cell culture kit 12b.

[0083] 1, the controller 16 is a computer having a processor, memory, and input / output interface (not shown). The controller 16 performs overall control of the entire system by having the processor execute a program stored in the memory. The controller 16 is connected to a first circuit control device 66a, a first reactor installation device 68a, a second circuit control device 66b, a second reactor installation device 68b, and a sensor device 70 by communication means such as wired, wireless, a network, or a combination thereof.

[0084] That is, the first circuit control device 66a and the second circuit control device 66b each control the operation of the multiple clamps 106 and the multiple pumps 108 based on control signals from the controller 16. The first reactor installation device 68a and the second reactor installation device 68b each control the operation of the multiple IC circulation pumps 132a and the multiple EC circulation pumps 132b, and also control the rotational operation of each bioreactor 30, based on control signals from the controller 16.

[0085] The sensor unit 148 acquires (samples) the culture medium circulating through the first cell culture kit 12a or the second cell culture kit 12b based on a control signal from the controller 16, and measures the components of the acquired culture medium. The sensor unit 148 also transmits the measurement results to the controller 16. The controller 16 may estimate the number of cells cultured in the first cell culture kit 12a and the second cell culture kit 12b based on the measurement results. The controller 16 feedback-controls the operations of the first circuit control device 66a, the first reactor installation device 68a, the second circuit control device 66b, and the second reactor installation device 68b based on the measurement results from the sensor device 70.

[0086] Next, a cell culture method using the cell culture system 10 will be described.

[0087] As shown in FIG. 8, the cell culture method includes a preparation step, a priming step, a medium replacement step, a seeding step, a culture step, a detachment step, and a recovery step.

[0088] 2 and 8, in a preparation step (step S1), the culture medium storage section 74 is placed in the first case section 77, and the cleaning liquid storage section 76 and the waste liquid storage section 78 are placed in the second case section 80. Then, the processing section 24 (five bioreactors 30) of the first cell culture kit 12a is placed in the first reactor installation device 68a, and the connection circuit 26 of the first cell culture kit 12a is set in the first circuit control device 66a. At this time, the multiple bags of the first cell culture kit 12a (the cell solution bag 18, the detachment solution bag 20, and the recovery bag 22) are suspended from the bag support section 116 of the first circuit control device 66a. Furthermore, the connection circuit 26 of the first cell culture kit 12a is aseptically joined to the culture medium storage section 74, the cleaning liquid storage section 76, the waste liquid storage section 78, and the sensor section 148, respectively.

[0089] Next, the processing unit 24 (five bioreactors 30) of the second cell culture kit 12b is installed in the second reactor installation device 68b, and the connection circuit 26 of the second cell culture kit 12b is set in the second circuit control device 66b. At this time, the multiple bags of the second cell culture kit 12b (the cell solution bag 18, the detachment solution bag 20, and the recovery bag 22) are hung from the bag support part 116 of the second circuit control device 66b. In addition, the connection circuit 26 of the second cell culture kit 12b is aseptically joined to the culture medium storage part 74, the cleaning solution storage part 76, the waste liquid storage part 78, and the sensor part 148, respectively.

[0090] Thereafter, in the priming step (step S2), the circuit control device 66 and the reactor installation device 68 drive the predetermined clamps 106 and pumps 108, 132 to introduce the cleaning solution from the cleaning solution storage section 76 into the connection circuit 26 and each bioreactor 30. This fills the connection circuit 26 and each bioreactor 30 (IC region and EC region) with the cleaning solution. At this time, air that was present in the connection circuit 26 and the bioreactor 30 is discharged into the waste solution storage section 78 together with the cleaning solution.

[0091] Then, in the culture medium replacement step (step S3), the circuit control device 66 and the reactor installation device 68 drive the predetermined clamp 106 and pumps 108, 132 to guide the culture medium in the culture medium storage section 74 to the connection circuit 26 and each bioreactor 30. As a result, the cleaning solution present in the connection circuit 26 and each bioreactor 30 (IC region and EC region) is replaced with the culture medium.

[0092] Next, in the seeding step (step S4), the circuit control device 66 and the reactor installation device 68 drive the predetermined clamps 106 and pumps 108, 132 to supply the cell solution in the cell solution bag 18 to the IC region of each bioreactor 30. Specifically, the cell solution introduced from the cell solution bag 18 to the IC circulation line 44c via the first IC supply line 40a is divided into five IC introduction lines 44a and introduced to the IC region of each bioreactor 30 (see FIG. 3). At this time, the five IC circulation pumps 132a impart flow force to the liquid (cell solution) flowing through the five IC introduction lines 44a, so that the cell solution is supplied to the five bioreactors 30 approximately evenly.

[0093] Thereafter, in the culturing step (step S5), the circuit control device 66 and the reactor installation device 68 drive the predetermined clamps 106 and pumps 108, 132 to supply the culture medium from the culture medium storage section 74 to the IC region and EC region of each bioreactor 30, thereby culturing (growing) the cells in the hollow fibers 32 of the bioreactor 30. The supply of the culture medium to the IC region of each bioreactor 30 and the supply of the culture medium to the EC region of each bioreactor 30 may be performed simultaneously or separately. Also, in the culturing step, the culture medium may be supplied only to the EC region of each bioreactor 30, without supplying the culture medium to the IC region of each bioreactor 30.

[0094] Specifically, in the culturing step, the culture medium at a low temperature (for example, 5°C) in the culture medium storage section 74 flows through the culture medium supply line 42 and is led from the tank device 64 to the intermediate culture medium flow path 58 provided in the internal space 105 of the housing 104 of the circuit control device 66. The culture medium flowing through the intermediate culture medium flow path 58 is heated to a desired temperature (for example, 37°C).

[0095] When culture medium is supplied to the IC region of each bioreactor 30, the culture medium heated in the culture medium intermediate flow path 58 is introduced into the IC circulation line 44c via the third IC supply line 40c, the second IC supply line 40b, and the first IC supply line 40a. The temperature of the culture medium introduced into the IC circulation line 44c drops (for example, to 30°C) as it flows through the first IC outer flow path 45a.

[0096] The cooled culture medium is then introduced into the IC intermediate flow path 60 provided in the internal space 129 of the reactor case 128. The culture medium flowing through the IC intermediate flow path 60 is heated to a desired temperature (e.g., 37°C). The culture medium flowing through the IC intermediate flow path 60 branches into five IC introduction lines 44a and is introduced into the IC regions of each bioreactor 30, thereby replacing the culture medium in the IC region of each bioreactor 30 with fresh medium. This allows nutrients such as oxygen to be efficiently supplied to the cells seeded on the inner surface of the hollow fibers 32 in each bioreactor 30.

[0097] In addition, in the culture process, the culture medium circulates within the IC circulation circuit 44. At this time, the temperature of the culture medium decreases as it flows through the first IC outer flow path 45a and the second IC outer flow path 45b, but since the temperature is increased in the IC intermediate flow path 60, the temperature of the culture medium supplied to the IC region of each bioreactor 30 is maintained at a desired temperature.

[0098] Furthermore, when supplying culture medium to the EC region of each bioreactor 30, the culture medium heated in the culture medium intermediate flow path 58 is introduced into the EC circulation line 48c via the first EC supply line 46a. After passing through the gas exchanger 28, the temperature of the culture medium introduced into the EC circulation line 48c is reduced (for example, to 30°C) when it flows through the first EC outer flow path 49a.

[0099] The cooled culture medium is then guided to the EC intermediate flow path 62 provided in the internal space 129 of the reactor case 128. The culture medium flowing through the EC intermediate flow path 62 is heated to a desired temperature (e.g., 37°C). The culture medium flowing through the EC intermediate flow path 62 branches into five EC introduction lines 48a and is guided to the EC regions of each bioreactor 30. In each bioreactor 30, nutrients and the like are exchanged between the culture medium in the IC region and the culture medium in the EC region. This allows nutrients such as oxygen to be efficiently supplied to the cells seeded on the inner surface of the hollow fibers 32 in each bioreactor 30.

[0100] Furthermore, in the culturing step, the culture medium circulates within the EC circulation circuit 48. At this time, the temperature of the culture medium drops as it flows through the first EC outer flow path 49a and the second EC outer flow path 49b, but the temperature is increased in the EC intermediate flow path 62, so that the temperature of the culture medium supplied to the EC region of each bioreactor 30 is maintained at a desired temperature. Furthermore, the culture medium circulating within the EC circulation circuit 48 undergoes gas exchange as it flows through the gas exchanger 28. Therefore, a culture medium containing desired gas components is supplied to the EC region of each bioreactor 30.

[0101] The culture process further includes a measurement process (step S5a). In the measurement process, the sensor device 70 drives the pump 146 to guide the culture medium flowing through the portion of the EC circulation line 48c downstream of the processing unit 24 to the sensor unit 148. The sensor unit 148 measures the components of the culture medium (culture medium in the processing unit 24). The measurement results of the sensor unit 148 are transmitted to the controller 16. The controller 16 determines the time (timing), duration, number of times, etc. of culture medium replacement based on the measurement results. After the measurement by the sensor unit 148 is completed, the culture medium is discharged into the waste liquid bag 150. The time (timing), number of times, etc. of the measurement process performed during the culture process can be set as appropriate.

[0102] After the culture step is completed, in the detachment step (step S6), the circuit control device 66 and the reactor installation device 68 drive the predetermined clamps 106 and pumps 108, 132 to introduce the detachment solution into the IC region of each bioreactor 30. This allows the cells cultured (grown) in the IC region of each bioreactor 30 to be detached from the inner surface of the hollow fibers 32.

[0103] Subsequently, in the recovery step (step S7), the circuit control device 66 and the reactor installation device 68 drive the predetermined clamps 106 and pumps 108, 132 to supply culture medium to the IC region of each bioreactor 30 while guiding the cells detached in the detachment step from each bioreactor 30 to the recovery bag 22. After the recovery step is completed, the operation of this cell culture method ends.

[0104] The cell culture system 10 according to this embodiment has the following advantages.

[0105] The cell culture system 10 includes a processing unit 24 for culturing cells, a reactor installation device 68 in which the processing unit 24 can be installed, a connection circuit 26 connected to the processing unit 24, a plurality of circuit control devices 66 to which the connection circuit 26 can be detached and which supply cells and culture medium from the connection circuit 26 to the processing unit 24 and recover the cultured cells from the processing unit 24 to the connection circuit 26, and a tank device 64 having a culture medium storage unit 74 for storing the culture medium. The processing unit 24 has a plurality of bioreactors 30. The culture medium in the culture medium storage unit 74 is supplied to the processing unit 24 via the connection circuit 26. The culture medium storage unit 74 can store an amount of culture medium necessary for culturing cells in the processing unit 24.

[0106] According to this configuration, it is only necessary to provide a circuit control device 66 for each processing section 24 (plurality of bioreactors 30), and therefore the number of circuit control devices 66 is less than the number of bioreactors 30. Therefore, the amount of cell culture can be efficiently increased while suppressing increases in costs. Furthermore, since the culture medium storage section 74 can store the amount of culture medium necessary to culture cells in the processing section 24, even if a large amount of culture medium is required when culturing cells using multiple bioreactors 30, it is not necessary to replace the culture medium storage section 74 during cell culture. Therefore, cell culture can be carried out smoothly and efficiently.

[0107] The tank device 64 cools the culture medium in the culture medium storage section 74 .

[0108] With this configuration, it is possible to prevent the components of the culture medium in the culture medium storage section 74 from denaturing during the cell culture period.

[0109] The connection circuit 26 has an intermediate medium flow path 58 provided between the medium storage section 74 and the processing section 24. The cell culture system 10 has a heating mechanism 107 for heating the intermediate medium flow path 58.

[0110] With this configuration, the low-temperature culture medium introduced from the culture medium storage section 74 can be heated as it flows through the culture medium intermediate flow path 58. Therefore, a decrease in the temperature of the culture medium in each bioreactor 30 (IC region and EC region) can be suppressed.

[0111] The circuit control device 66 has an internal space 105 maintained at a desired temperature and a housing 104 that functions as a temperature raising mechanism 107. The intermediate medium flow path 58 is heated by being placed in the internal space 105 of the housing 104.

[0112] With this configuration, there is no need to prepare a heating device for heating the culture medium intermediate flow path 58 separately from the housing 104, so costs can be reduced while preventing the configuration of the circuit control device 66 from becoming too complicated.

[0113] The flow path length of the intermediate medium flow path 58 is set to a length such that the culture medium guided from the culture medium storage section 74 is heated to the temperature of the internal space 105 of the housing 104 when flowing through the intermediate medium flow path 58.

[0114] With this configuration, the temperature of the culture medium flowing through the intermediate culture medium flow path 58 can be raised to the temperature of the internal space 105 of the housing 104.

[0115] The intermediate medium channel 58 extends linearly. The cell culture system 10 has a first holding part 110 that holds the intermediate medium channel 58 in a serpentine state.

[0116] According to this configuration, the intermediate culture medium channel 58 can be compactly arranged in the internal space 105 of the housing 104. Furthermore, it is possible to prevent the intermediate culture medium channel 58 from being bent and thereby blocking the channel.

[0117] The culture medium storage section 74 has a culture medium tank 90 that stores the culture medium, and a culture medium installation member 92 that installs the culture medium tank 90. ​​Rollers 94 for moving the culture medium installation member 92 are provided on the bottom surface of the culture medium installation member 92.

[0118] With this configuration, the culture medium storage section 74 can be easily taken in and out of the tank device 64.

[0119] The cell culture system 10 includes a sensor device 70 for measuring the components of the culture medium introduced to the processing section 24 .

[0120] According to this configuration, the components of the culture medium in the processing section 24 can be measured by the sensor device 70, so that cell culture can be carried out efficiently.

[0121] The cell culture system 10 includes a controller 16 that controls the operation of the circuit control device 66. The controller 16 feedback-controls the operation of the circuit control device 66 based on the measurement results of the sensor device .

[0122] With this configuration, cell culture can be carried out more efficiently.

[0123] Each of the plurality of bioreactors 30 includes a plurality of hollow fibers 32 .

[0124] With this configuration, cell culture can be carried out efficiently in each bioreactor 30.

[0125] The cell culture system 10 is not limited to the above-described configuration. The number of bioreactors 30 that can be installed in the reactor installation device 68 is not limited to five, but may be two, three, four, or six or more. In the cell culture system 10, three or more circuit control devices 66 and three or more reactor installation devices 68 may be provided. In this case, two or more tank devices 64 and two or more sensor devices 70 may be provided.

[0126] In the cell culture system 10, the IC intermediate channel 60 or the EC intermediate channel 62 may be omitted. Also, in the cell culture system 10, both the IC intermediate channel 60 and the EC intermediate channel 62 may be omitted, and the second holding unit 134 may be omitted. Furthermore, in the cell culture system 10, the medium intermediate channel 58 and the first holding unit 110 may be omitted.

[0127] As shown in FIG. 9, the cell culture device 14 includes a tank device 64, a first circuit control device 66a (one circuit control device 66), a first reactor installation device 68a (one reactor installation device 68), and a sensor device 70, and the second circuit control device 66b and the second reactor installation device 68b may be omitted.

[0128] (Second embodiment) Next, a cell culture system 10A according to a second embodiment will be described. In the cell culture system 10A according to this embodiment, the same components as those in the above-described cell culture system 10 are denoted by the same reference numerals, and detailed descriptions thereof will be omitted.

[0129] 10 and 11, the cell culture system 10A includes one cell culture kit 12A, a cell culture device 14A, and a controller 16. The cell culture kit 12A is configured similarly to the above-described cell culture kit 12, except that it does not have the IC intermediate flow path 60 and the EC intermediate flow path 62.

[0130] The cell culture device 14A has one tank device 64A, a culture device main body 200, and one sensor device 70. The tank device 64A includes a base 202, a culture medium storage section 74, a cleaning liquid storage section 76, a waste liquid storage section 78, and a holder 204. The culture device main body 200 and the sensor device 70 are arranged adjacent to each other on an upper surface 202a of the base 202. The base 202 includes a first case section 77, a second case section 80, and a third case section 206.

[0131] As shown in FIG. 12 , the third case portion 206 is provided, for example, above the first case portion 77. However, the position of the third case portion 206 can be set as appropriate. The third case portion 206 has a temperature control function that maintains the internal space 208 of the third case portion 206 at a desired temperature (for example, 37°C). The holding portion 204 maintains the medium intermediate flow path 58 in a predetermined shape (serpentine shape). The holding portion 204 is provided in the internal space 208 of the third case portion 206. That is, the third case portion 206 functions as a temperature raising mechanism 210 that raises the temperature of the medium intermediate flow path 58. The holding portion 204 is configured, for example, in the same manner as the first holding portion 110 or the second holding portion 134 described above.

[0132] 10 and 11, the culture device main body 200 includes a box-shaped case member 212, a circuit control device 66A and a reactor installation device 68A disposed in an internal space 214 of the case member 212, and a bag support section 216 provided in the case member 212. That is, in this embodiment, the circuit control device 66A and the reactor installation device 68A are not provided separately, but are provided integrally in the internal space 214 of the case member 212. A display section 218 is provided on the front surface of the case member 212.

[0133] As shown in FIG. 11, the circuit control device 66A includes a plurality of clamps 106 and a plurality of pumps 108, similar to the circuit control device 66 described above. Note that the circuit control device 66A does not include the housing 104 and the first holding unit 110 described above. The reactor installation device 68A is configured so that a processing unit 24 (five bioreactors 30) can be installed therein. The reactor installation device 68A includes five reactor support units 130 and a plurality of pumps 132, similar to the reactor installation device 68 described above (see FIG. 3). Note that the reactor installation device 68A does not include the reactor case unit 128 and the second holding unit 134 described above (see FIG. 2). The bag support unit 216 is configured so that a plurality of bags (cell solution bag 18, detachment solution bag 20, and recovery bag 22) can be suspended therefrom.

[0134] In the cell culture system 10A according to this embodiment, the same configuration as that of the cell culture system 10 described above provides the same effects.

[0135] In the cell culture system 10A, the temperature raising mechanism 210 is provided in the tank device 64A. With this configuration, the configuration of the circuit control device 66A can be made more compact than when the temperature raising mechanism 210 is provided in the circuit control device 66A.

[0136] The present invention is not limited to the above-described embodiment, and various modifications are possible without departing from the gist of the present invention.

[0137] The above embodiments can be summarized as follows.

[0138] The above embodiment discloses a cell culture system (10, 10A) comprising: a processing unit (24) for culturing cells; a reactor installation device (68, 68A) in which the processing unit can be installed; a connection circuit (26) connected to the processing unit; a circuit control device (66, 66A) that allows the connection circuit to be detached and that supplies the cells and culture medium from the connection circuit to the processing unit and recovers the cultured cells from the processing unit to the connection circuit; and a tank device (64, 64A) having a culture medium storage unit (74) for storing the culture medium, wherein the processing unit has a plurality of bioreactors (30), the culture medium in the culture medium storage unit is supplied to the processing unit via the connection circuit, and the culture medium storage unit is capable of storing the amount of culture medium necessary for culturing cells in the processing unit.

[0139] In the above cell culture system, the tank device may cool the culture medium in the culture medium storage section.

[0140] In the above cell culture system, the connection circuit may have a medium intermediate flow path (58) provided between the medium storage section and the processing section, and the cell culture system may have a heating mechanism (107, 210) for heating the medium intermediate flow path.

[0141] In the above cell culture system, the temperature raising mechanism may be provided in the tank device or the circuit control device.

[0142] In the above cell culture system, the circuit control device has a housing (104) that has an internal space (105) maintained at a desired temperature and functions as the heating mechanism, and the intermediate medium flow path may be heated by being placed in the internal space of the housing.

[0143] In the above-mentioned cell culture system, the flow path length of the intermediate culture medium flow path may be set to a length such that the culture medium guided from the culture medium storage section is heated to the temperature of the internal space of the housing when flowing through the intermediate culture medium flow path.

[0144] In the above cell culture system, the intermediate medium channel may extend linearly, and the cell culture system may have a holding section (110, 204) that holds the intermediate medium channel in a serpentine state.

[0145] In the above cell culture system, the culture medium storage section has a culture medium tank (90) in which the culture medium is stored and a culture medium installation member (92) in which the culture medium tank is installed, and rollers (94) for moving the culture medium installation member may be provided on the bottom surface of the culture medium installation member.

[0146] The above cell culture system may further include a sensor device (70) for measuring components of the culture medium introduced to the processing section.

[0147] The above cell culture system may further include a controller (16) that controls the operation of the circuit control device, and the controller may feedback-control the operation of the circuit control device based on the measurement results of the sensor device.

[0148] In the above cell culture system, each of the plurality of bioreactors may include a plurality of hollow fibers (32).

Claims

1. a processing unit for culturing cells; a reactor installation device in which the processing unit can be installed; a connection circuit connected to the processing unit; a circuit control device that allows the connection circuit to be detached and that supplies the cells and culture medium from the connection circuit to the processing unit and recovers the cultured cells from the processing unit to the connection circuit; a tank device having a culture medium storage section for storing the culture medium; the processing section includes a plurality of bioreactors; The culture medium in the culture medium storage unit is supplied to the processing unit via the connection circuit, the culture medium storage unit is capable of storing an amount of the culture medium necessary for culturing cells in the processing unit, each of the plurality of bioreactors comprises a plurality of hollow fibers; The connection circuit includes: a first circulation circuit for circulating the culture medium through an inner region of the plurality of hollow fibers of each of the bioreactors; a second circulation circuit for circulating the culture medium in an area outside the plurality of hollow fibers of each of the bioreactors; a culture medium supply line for supplying the culture medium in the culture medium storage section to each of the first circulation circuit and the second circulation circuit; A cell culture system comprising:

2. 2. The cell culture system of claim 1, The tank device cools the culture medium in the culture medium storage section.

3. 3. The cell culture system according to claim 2, the connection circuit has an intermediate medium flow path provided between the medium storage unit and the processing unit, The cell culture system has a heating mechanism for heating the intermediate medium flow path.

4. The cell culture system according to claim 3, A cell culture system, wherein the temperature raising mechanism is provided in the tank device or the circuit control device.

5. 5. The cell culture system according to claim 4, the circuit control device has a housing having an internal space maintained at a desired temperature and functioning as the temperature raising mechanism; A cell culture system, wherein the intermediate medium flow path is heated by being placed in the internal space of the housing.

6. 6. The cell culture system according to claim 5, A cell culture system, wherein the flow path length of the intermediate culture medium flow path is set to a length such that the culture medium guided from the culture medium storage section is heated to the temperature of the internal space of the housing when flowing through the intermediate culture medium flow path.

7. 7. The cell culture system according to claim 6, The intermediate medium flow path extends linearly, The cell culture system has a holding section that holds the intermediate medium flow path in a serpentine state.

8. The cell culture system according to any one of claims 1 to 7, The culture medium storage unit is a culture medium tank containing the culture medium; a culture medium installation member in which the culture medium tank is installed, A cell culture system, wherein a roller for moving the culture medium installation member is provided on the bottom surface of the culture medium installation member.

9. The cell culture system according to any one of claims 1 to 8, A cell culture system comprising a sensor device for measuring components of the culture medium introduced to the processing section.

10. 10. The cell culture system of claim 9, a controller for controlling the operation of the circuit control device; The controller feedback-controls the operation of the circuit control device based on the measurement results of the sensor device.

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