JP5035043B2 - Cell culture facility - Google Patents

Description

  The present invention relates to a cell culture facility with differential pressure control.

  In recent years, research and development of regenerative medicine for artificially creating a target tissue or organ by cell culture has been promoted. In order to carry out the cell culturing operation, a cell culture facility satisfying a predetermined standard, for example, GMP (Good Manufacturing Practice) is used. Such a cell culture facility requires aseptic management and aseptic operation. Therefore, in order to maintain the cleanliness of the air, each room formed in the cell culture facility usually adopts the structure of a clean room that is used, and the air supply system is provided with a filter such as a HEPA filter. Used to supply clean air. Moreover, in order to suppress the disorder of the cleanliness by the workers in the cell culture room, the cell culture room is provided with a changing room and a dressing room, and pressure control of each room is performed (see Patent Document 1).

In addition, for the purpose of performing such cell culture in large quantities, cell culture chambers are arranged in parallel, automatic cell culture devices are introduced into each cell culture chamber, and cells are automatically loaded and unloaded by robots outside the cell culture chamber A culture facility has been proposed. Thus, in addition to the above purpose, since it is not necessary for an operator to enter the cell culture chamber, there is an advantage that the cell culture chamber can be designed in a compact manner.
JP 2003-47457 A

  However, in such a cell culture facility, in order to prevent cross-contamination between the cell culture rooms, it is necessary to provide a layout in which a dressing room and a dressing room are provided in each room, and access to and from a corridor connected to these rooms. . Here, the dressing room is set to the highest pressure to prevent air flow in the hallway and the cell culture chamber, and the dressing room is set to the lowest pressure to prevent air flow in the hallway and the cell culture chamber. Accordingly, the corridor, the dressing room, the cell culture room, and the dressing room need to control the inter-room differential pressure. As a method for controlling the chamber pressure, a method is generally employed in which the supply air volume is made constant and the exhaust air volume is controlled by a motor damper, or a differential pressure adjusting damper is provided in the adjacent chamber to release air.

  Therefore, in the conventional cell culture facility, a dressing room and a dressing room are required for each cell culture room, so that the facility space becomes large, and the air conditioning system becomes complicated, which increases costs and automates cell culture. The merit of was reduced.

  Accordingly, the present invention focuses on the above-described problems, and an object thereof is to provide a cell culture apparatus that can be operated with a simple facility air-conditioning system in a compact facility space.

To achieve the above object, a cell culture facility according to the present invention, the cell culture facility, a front chamber whose pressure positive, the rear chamber and the disposed between the front chamber and the rear chamber said front chamber and a plurality of cell culture chambers connected in parallel with the rear chamber, is divided into, in the front chamber side of the cell culture chamber is provided with a ventilation window to flow air in the front chamber to the cell culture chamber, said cells A differential pressure damper that maintains the pressure in the cell culture chamber higher than the pressure in the rear chamber is provided on the rear chamber side of the culture chamber.

  According to the cell culture facility of the present invention, since it is possible to arrange a dressing room and a dressing room in the rear room, only one dressing room and one dressing room are provided for a plurality of cell culture rooms. Operators have access to all cell culture rooms and can operate with a simple and cost-effective air conditioning system. In addition, each cell culture chamber receives pressure from the positively pressurized front chamber and maintains a substantially uniform pressure, and since it is always maintained at a higher pressure than the rear chamber, air flows back from the rear chamber to the cell culture chamber. And cross contamination of cells due to air movement between cell culture chambers can be prevented. Moreover, since positive pressure control of each chamber is performed with a mechanical and simple configuration, positive pressure control with high stability can be performed.

  Hereinafter, the present invention will be described in detail with reference to embodiments shown in the drawings. However, the components, types, combinations, shapes, relative arrangements, and the like described in this embodiment are merely illustrative examples and not intended to limit the scope of the present invention only unless otherwise specified. .

  A cell culture facility according to this embodiment is shown in FIG. The cell culture facility 10 according to the present embodiment has a layout in which a corner of a building is partitioned by a partition and the interior thereof is partitioned into chambers according to each operation, and a plurality of cell culture chambers 12 and a front of the cell culture chambers 12 are arranged. There are a cell transfer chamber 14 that is a chamber, and a material installation chamber 16a, a clothing chamber 16b, a dressing chamber 16c, and an apparatus carry-in / out chamber 16d that are rear chambers 16.

  The cell culture facility 10 further includes a raw material storage chamber 18 for temporarily storing cells to be cultured, a raw material processing chamber 20 for pretreatment of cells to be cultured, and a product processing chamber 22 for post-treatment of cells after culture. A product storage chamber 24 for temporarily storing the post-treated cells is provided. In addition, a material preparation chamber 26 for allowing an operator to enter and leave each of the above-described rooms is provided, and the material preparation chamber 26 is connected to a secondary changing room 28 for the operator to enter and exit from an entrance 28a. The raw material storage chamber 18 is connected to the raw material processing chamber 20 and the dressing chamber 18a and the undressing chamber 18b connected to the material preparation chamber 26, and can enter and leave the raw material storage chamber 18 and the raw material processing chamber 20 from the material preparation chamber 26. is there. The product storage room 24 is connected to the product processing room 22 and the dressing room 24a and the dressing room 24b connected to the material preparation room 26, and enters the product storage room 24 and the product preparation room 22 from the material preparation room 26. You can leave the room. A pass box 30 having a double window door structure is provided at a predetermined position in each of the above-described chambers, so that an article with a side wall sandwiched can be delivered without affecting the environment of each chamber.

A plurality of the cell culture chambers 12 are arranged in parallel to the cell transfer chamber 14 and the material installation chamber 16a at a position between the cell transfer chamber 14 and the material installation chamber 16a. The cell culture chamber 12 is provided with a cell culture device (not shown), and the temperature, humidity, CO ₂ concentration and the like can be adjusted according to the culture conditions of the cells to be cultured.

  A leak window 12a is disposed on the side wall of the cell culture chamber 12 on the cell transfer chamber 14 side. The leak window 12a is a window through which an arm (not shown) of a transfer robot (not shown), which will be described later, is inserted to deliver cells, and the air in the cell transfer chamber 14 is vented to the cell culture chamber 12. However, the closed state is maintained except when an arm (not shown) is introduced into the cell culture chamber 12. However, even in this state, the leak window 12a is not completely closed, and air flows from the cell transfer chamber 14 to the cell culture chamber 12 due to the positive pressure gradient described later. On the other hand, a differential pressure damper 12b for maintaining the cell culture chamber 12 side at a higher pressure than the material installation chamber 16a side is disposed on the side wall of the cell culture chamber 12 on the material installation chamber 16a side. As a result, when the pressure in the material setting chamber 16a is higher than that in the cell culture chamber 12, the backflow of air is prevented and a certain amount of air corresponding to a certain differential pressure is allowed to flow from the cell culture chamber 12 to the material setting chamber 16a. be able to. Here, the leak window 12a and the differential pressure damper 12b disposed in each cell culture chamber 12 are of the same standard. In addition, a door 12d is provided on the side surface where the differential pressure damper 12b is provided, and an operator can perform a default operation of the cell culture device 12a.

  The material installation chamber 16a is a hub area for accessing each of the cell culture chambers 12 for the purpose of performing a default operation or the like of the cell culture apparatuses 12a of the cell culture chambers 12 arranged in a row by an operator entering and leaving the room. By automating the culture, the operator mainly performs default work, and the operator rarely has the opportunity to work by putting the entire body into the cell culture chamber 12, so that each cell culture chamber 12 can be designed to be small and the material can be installed. The chamber 16a can also be designed to be small while maintaining a size that allows the operator to enter and leave the room. Between the material installation chamber 16a and the material preparation chamber 26, there are a clothing installation chamber 16b and a dressing chamber 16c connected to the material installation chamber 16a and the material preparation chamber 26. A differential pressure damper 16e similar to that described above is also provided on the side wall of 16c, and the positive pressure on the material installation chamber side is designed to be high. Therefore, the operator can access all the cell culture chambers 12 through the single dressing room 16b and the dressing room 16c. The apparatus carry-in / out port 16d is a place where goods are transferred between the material installation chamber 16a and the material preparation chamber 26 via the pass box 30 without passing through the dressing room 16b and the dressing room 16c.

  The cell transfer chamber 14 has a side wall at one end in the longitudinal direction of the raw material processing chamber 20 that provides cells that have not been cultured in a cell transfer container (not shown), and a product that receives cultured cells at the other side wall. Each is connected to the processing chamber 22 via a bus box 32. On the other hand, the side wall at one end in the short side direction is connected to the plurality of cell culture chambers 12 via the leak window 12a. The cell transfer chamber 14 is provided with a transfer robot (not shown) movable in the longitudinal direction, and cell culture is performed by an arm operation by an extendable arm (not shown) that can hold a cell transfer container attached to the transfer robot. The cell set in the apparatus and the cultured cell can be carried out to the product processing chamber. At this time, the above-described leak window 12a is controlled to be opened in conjunction with a predetermined arm operation so that the leak window 12a does not interfere with an arm (not shown). For maintenance of the transfer robot (not shown) in the cell transfer chamber 14, the cell culture chamber 12 and the material installation chamber 16a are connected via a communication path 14a disposed next to the cell culture chamber 12. Normally, the door 14b of the common path 14b is closed.

  FIG. 2 shows a schematic diagram of the air conditioning system 34 of the cell culture facility 10 according to the present embodiment. The arrows in the figure indicate the direction of air flow. The air conditioning system 34 maintains the indoor temperature and oxygen concentration while constantly taking in fresh air from the outside and ventilating while maintaining a positive pressure (atmospheric pressure or more) outside the system. The air conditioning system 34 removes dust and the like from outside air taken from outside the system by an outside air processing air conditioner 36 with a filter means 38 such as a HEPA filter, and the cell transfer chamber 14, the cell culture chamber 12, and the material installation chamber on the way. Branching into a first path 40 passing through 16 a, a third path 44 passing through the raw material processing chamber 20 and the raw material storage chamber 18, and a second path 42 passing through the product processing chamber 22 and the product storage chamber 24. The exhaust fan 46 exhausts the system through the secondary changing room 28. At this time, by making the amount of outside air taken in by the outside air processing air conditioner 36 larger than the amount of air exhausted by the exhaust fan 46, the entire system becomes positive pressure. Here, in the second path 42 and the third path 44, the raw material processing chamber 20 and the product processing chamber 22 are designed to have the highest degree of positive pressure, and the degree of positive pressure decreases toward the downstream. The secondary changing room 28 prevents dust from the entrance / exit 28a from entering the cell culture facility 10, and prevents air from the material preparation room 26 from being discharged from the entrance / exit 28a and contaminating the building. Negative pressure (atmospheric pressure or lower) is set.

  In the present embodiment, air is supplied to the cell transfer chamber 14, the cell culture chamber 12, and the material installation chamber 16a of the first path 40 in parallel. On the other hand, in the first path 40, the discharge to the material preparation chamber 26 side close to the exhaust fan 46 takes the cell transfer chamber 14 as the upstream side, the cell culture chamber 12, the material installation chamber 16a, the dressing chamber 16b (and the dressing chamber 16c). , A serial flow path is formed in the order of the apparatus loading / unloading chamber 16d). At this time, the cell culture chamber 12 is connected to the material installation chamber 16a and the air flow path by the differential pressure damper 12b, and the cell transfer chamber 14 is connected to the cell culture chamber 12 and the air flow path by the leak window 12a. Therefore, in this path, the positive pressure in the clothing chamber 16b is the lowest, and a positive pressure gradient occurs in which the positive pressure increases in the order of the material installation chamber 16a, the cell culture chamber 12, and the cell transfer chamber 14. That is, the cell transfer chamber 14 maintains a positive pressure with respect to the cell culture chamber 12 and the material installation chamber 16a. Furthermore, the cell culture chamber 12 also maintains a positive pressure with respect to the material installation chamber 16a by the differential pressure damper 12b. Further, as shown in FIG. 1, each cell culture chamber 12 is connected to the cell transfer chamber 14 via the leak window 12a and is connected to the material installation chamber via the differential pressure damper. Since it has a pressure, it can maintain a positive pressure uniformly with respect to the material installation chamber 16a. Therefore, since one cell culture chamber 12 does not have a relationship of sucking air discharged from the other cell culture chamber 12, the air discharged from each cell culture chamber 12 is parallel and parallel to each other as indicated by an arrow 48. The air does not collide with each other, the backflow of air to the cell culture chamber 12 can be prevented, dust contamination from the material installation chamber 16a, and cross contamination between the cell culture chambers 12 can be prevented.

  Therefore, according to the cell culture facility 10 according to the present embodiment, since the dressing room 16b and the dressing room 16c can be arranged on the downstream side of the first path 40 of the rear chamber 16, the plurality of cell culture rooms 12 are An operator can access all the cell culture rooms 12 only by arranging one dressing room 16b and one dressing room 16c, and a simple air conditioning system 34 can be operated without cost. Each of the cell culture chambers 12 receives a pressure from the positive front chamber and maintains a substantially uniform pressure, and is always maintained at a higher pressure than the rear chamber 16. It is possible to prevent cross-contamination of cells due to air flowing back into the chamber 12 and air movement between the cell culture chambers 12. Moreover, since positive pressure control (pressure control) of each chamber is performed with a mechanical and simple configuration including the leak window 12a and the differential pressure damper 12b, highly stable positive pressure control (pressure control) can be performed.

  In the present embodiment, the cell culture chambers are arranged in a line, but the present invention is not limited to this. For example, a plurality of cell culture chambers are arranged in a ring shape, a cell transfer chamber in which the inside of the ring is positively pressurized, and a material outside the ring A concentric layout including an installation chamber, a raw material processing chamber, and a product processing chamber is also possible. At this time, a part of the ring is used as a pass box connected to the raw material processing chamber, a pass box connected to the product processing chamber, and a passage connecting to the material installation chamber, and the transfer robot is configured to rotate around the center of the concentric circle. You can do it. At this time, air from the cell transfer chamber flows radially through the cell culture chamber.

  It can be used as a cell culture facility that prevents cross-contamination of cells with a simple air conditioning system.

It is a mimetic diagram showing the layout of the cell culture facility concerning this embodiment. It is a mimetic diagram showing an air-conditioning system of a cell culture facility concerning this embodiment.

Explanation of symbols

10 ......... Cell culture facility, 12 ...... Cell culture room, 12a ......... Leak window, 12b ......... Differential pressure damper, 12c ......... Door, 14 ...... Cell transfer chamber, 14a ... Road, 16 ......... Rear room, 16a ......... Material installation room, 16b ......... Clothing room, 16c ......... Undressing room, 16d ......... Device loading / unloading room, 16e ......... Differential pressure damper, 18 ... ... Raw material storage room, 20 ... ... Raw material processing room, 22 ... ... Product processing room, 24 ... ... Product storage room, 26 ... ... Material preparation room, 28 ... ... Secondary changing room, 28a ......... Entrance / exit 30 ......... Pass box, 32 ......... Pass box, 34 ......... Air conditioning system, 36 ......... Outside air processing air conditioner, 38 ......... Filter means, 40 ......... First path, 42 ... ... second path, 44 ......... third path, 46 ......... exhaust fan, 48 ......... arrows.

Claims (1)

A cell culture facility is a positive pressure front chamber, a rear chamber, a plurality of cell culture chambers arranged between the front chamber and the rear chamber and connected in parallel to the front chamber and the rear chamber , is divided into,
A vent window is provided on the anterior chamber side of the cell culture chamber to allow the air in the anterior chamber to flow to the cell culture chamber, and the air pressure of the cell culture chamber is adjusted to the rear chamber side of the cell culture chamber. A cell culture facility characterized by a differential pressure damper that is maintained above atmospheric pressure.

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