JP4803196B2 - Automated cell culture facility - Google Patents

Description

  The present invention relates to the structure of an automated cell culture facility.

  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.

  For this reason, each room formed in the cell culture facility must be separated structurally and in an air conditioning system so that the source cells, the cells being cultured, or the product cells are not contaminated. In the air conditioning system, the structure of a clean room that is normally used is adopted, and clean air is supplied to the air supply system using a filter such as a HEPA filter (see Patent Document 1). .

  In addition, as for the facility structure, the rooms formed in the cell culture facility are separated from each other, and the storage room for the source cells, the treatment room, the cell culture room, etc. are also separated, The cell culture room is separated into a changing room and a dressing room to prevent disturbance of cleanliness by the workers in the cell culture room. Is provided to control the atmospheric pressure in each chamber. Specifically, the changing room for entering and leaving the hallway and the changing room of the culture room are separated, and in order to avoid contamination due to changing of the culture room, a structure is provided in which a changing room is provided for each culture room. .

For this reason, in a conventional cell culture facility, an operator holds the raw material cells pretreated in the raw material processing chamber, carries them through a corridor to a predetermined culture chamber, and puts them in a pass box of the culture chamber. A worker in the culture room takes out from the pass box and processes it. When processing is complete, place it in a pass box for unloading. Workers on the corridor side take out the processed cells from the pass box and carry out the work continuously in such a procedure that they are transported to the work room where they are shipped as products.
JP 2003-47457 A

  By the way, in the conventional cell culture facility as described above, in order to increase the production efficiency, the number of culture chambers must be increased. However, the multi-room structure causes a problem that a large space is required for a changing room attached to each room. In addition, there is a problem that the possibility of mistakes such as cell mistakes cannot be excluded.

  The object of the present invention is to solve the above-mentioned problems and to ensure the elimination of human error and the prevention of cross contamination due to unmanned operation. More specifically, the object is to reduce the space of a cell culture facility having a plurality of culture chambers and improve cost performance.

  In order to achieve the above object, an automatic cell culture facility according to the present invention includes a plurality of cell culture chambers, and a robot that automatically transfers cells between each culture chamber, a raw material processing chamber, and a product processing chamber. The housed cell transfer robot room is arranged, and a material installation room for setting a medium in a culture apparatus for automatically culturing cells in the cell culture room is provided in each culture room.

Further, the common material installation room is provided with a clothes room for entering and exiting the room and a dressing room.
In addition, the product processing chamber is connected to an inspection room or a product shipping room that is spaced apart from each other by a ceiling conveyance path, and the product is transferred through a pass box.
A pressure gradient with a positive pressure in the product processing chamber is provided between the rooms connected via the ceiling conveyance path.

  According to the present invention, an automatic cell culturing device is placed in each cell culture chamber, and raw material cells are automatically supplied to the selected cell culture chamber by a transfer robot, and the cultured product cells are automatically sent to the product processing chamber. Can be removed. This automates the setting of the cells into the automatic cell culture apparatus and the removal after the culture, and can be automated, cleaned and saved in space. In addition, the material installation room for supplying the culture medium to the cell culture room is a shared space for the plurality of cell culture rooms. By installing the dressing room and the dressing room in and out of the room, cross contamination can be prevented. It is possible to effectively use the facility space while preventing it. Moreover, if it is configured to connect rooms that are spaced apart via a ceiling conveyance path, it is possible to eliminate human error during product transfer and to improve the certainty of preventing cross contamination.

  Hereinafter, specific embodiments of an automatic cell culture facility according to the present invention will be described in detail with reference to the drawings. 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.

  FIG. 1 is a plan view of a main part of an automatic cell culture facility 10 according to the embodiment. The cell culture facility 10 has a layout in which a corner of a building is partitioned by a partition wall and partitioned into rooms corresponding to each work so as to roughly follow the culture work process. A raw material storage chamber 12 for temporarily storing cells to be cultured is formed, and a raw material processing chamber 14 for pretreatment of the cells to be cultured is provided in parallel therewith. Further, a plurality of cell culture chambers 16 (161, 162, 163... 16n) for culturing raw material cells are arranged close to the raw material processing chamber. In the embodiment, the plurality of cell culture chambers 16 are arranged in tandem, and a common cell transfer chamber 18 is formed facing the plurality of cell culture chambers 16. Further, on the opposite side of the plurality of cell culture chambers 16, a common material installation chamber 20 a facing each cell culture chamber 16 is formed. The material installation chamber 20a performs preparatory steps necessary for culturing a medium or the like, and communicates with each cell culture chamber 16 by a door. In addition, the dressing room 20b, the undressing room 20c, and the apparatus carry-in / out room 20d are respectively connected to the material installation room 20 to an air-lock type door so that workers and apparatus devices can enter and exit.

  Further, the cell culture facility 10 is provided with a product processing chamber 22 that performs post-treatment of cells after culture, and a product storage chamber 24 that temporarily stores the post-treated cells. 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 12 communicates with the raw material processing chamber 14 and also communicates with the material preparation chamber 26, the dressing chamber 30 a, and the undressing chamber 30 b, and enters and leaves the raw material storage chamber 18 and the raw material processing chamber 20 from the material preparation chamber 26. Is possible. The product storage room 24 is connected to the product processing room 22 and the dressing room 32a and the dressing room 32b connected to the material preparation room 26, and enters the product storage room 24 and the product processing room 22 from the material preparation room 26. You can leave the room. A GMP area is formed by the above-described series of rooms. A pass box 32 for communication with the outside of the GMP area having a double window door structure is disposed at a predetermined position of each room, which affects the environment of each room. It is possible to deliver the article with the side wall sandwiched without giving any. In addition, an in-system pass box 34 is provided for transferring treated cells between adjacent chambers according to the cell culture work process. This is also a double window structure, and each compartment is separated from each other. It is possible to deliver treated cells without affecting the environment.

As described above, a plurality of cell culture chambers 161, 162, 163,..., 16n are provided, and the cells are transported between the culture chambers 161, 162, 163,. Although the chamber 18 is provided as a shared space, in this embodiment, the cell transfer chamber 18 is configured as a cell transfer robot chamber containing a transfer robot 36 that automatically transfers cells. The cell culture chamber 16 is equipped with an automatic cell culture device 38, and an operator sets materials necessary for cell culture such as a medium from the material installation chamber 20a in the device 38. . The automatic cell culture device 38 can adjust the temperature, humidity, CO ₂ concentration and the like according to the culture conditions of the cells to be cultured.

  An automatic opening / closing door 40 is formed on the side wall of each cell culture chamber 16 on the cell transfer robot chamber 18 side, and the transfer robot 36 receives the source cells from the source processing chamber 14 and tags attached to the source cell storage container. The identification symbol is read by, for example, moving to the cell culture chamber 16 to be loaded, the automatic opening / closing door 40 is opened, and the raw material cells are introduced into the automatic cell culture device 38. It is assumed that such an operation is performed by a controller (not shown), and takes in signals of the transfer robot 36, the automatic opening / closing door 40, the automatic cell culture device 38, sensors and switches attached thereto, and performs necessary control driving. I have to. In addition, the transfer robot 36 is moved to the cell culture chamber 16 where the culture process has been completed, the automatic opening / closing door 40 is opened to take out the product cells, and the product cells are moved to the product processing chamber 22 to be carried out. A series of these operations is also performed by the controller. Accordingly, automation and unmanned operations of transferring the source cells to the cell culture chamber 16 and transferring the product cells to the product processing chamber 22 by the automatic transfer robot 36 are realized.

  The transfer robot 36 may have a structure that can be self-propelled or run on a rail and has a multi-joint arm on a swivel base, and is equipped with a cleaning device at the end of the arm. This cleaning device is equipped to keep the periphery of the cell transfer container held by the arm clean. For example, a clean air blowing means comprising a fan and a high performance filter is provided on the upper part of the casing, and the housing portion surrounded by the casing below the high performance filter is used as the housing portion for the cell transfer container. The lower end of the casing is opened and used as a clean air outlet to maintain the cleanliness of the interior. What is necessary is just to hold | grip and move a cell conveyance container by the chuck | zipper of the front-end | tip part inserted in the casing.

  The material installation chamber 20a is a hub area for accessing each of the cell culture chambers 16 for the purpose of performing a default operation or the like such as a medium set to the cell culture devices 38 of the cell culture chambers 16 arranged in a row by the operator entering and leaving the room. It is said. By automating the culture, the operator mainly performs default work such as setting of the medium, and the operator rarely has the opportunity to work by putting the whole body into the cell culture chamber 16, so each cell culture chamber 12 should be designed to be small. The material installation chamber 16a can also be designed to be small while maintaining a size that allows the operator to enter and leave the room. Therefore, as shown in FIG. 2, the cell culture chamber 16 is configured such that the working space and the accommodation space of the cell culture device 38 are partitioned by the shutter 42.

  Between the material installation chamber 20a and the material preparation chamber 26, there is a dressing room 20b and a dressing room 20c connected to the material installation chamber 20a and the material preparation chamber 26, and they pass through the single dressing room 20b and the dressing room 20c. Thus, the operator can access all the cell culture chambers 16. The apparatus carry-in / out port 20d is a place where articles are transferred between the material installation chamber 20a and the material preparation chamber 26 via the pass box 34 without passing through the dressing room 20b and the dressing room 20c.

  Further, in the automatic cell culture facility 10 according to the present embodiment, an inspection room 44 and a shipping room 46 for performing inspection of product cells, DNA inspection, and the like are provided outside the GMP area where cell culture is performed by the series of processing chambers described above. ing. This is done by checking whether the product cells are accurate before shipping, and the product cells that pass the inspection are finally transferred to the shipping room to be ready for final shipment. Yes. Therefore, when there is a transfer of product cells between the inside and outside of the GMP area, there is a possibility that contamination occurs in this transfer process. From this point of view, in this embodiment, the ceiling is provided between the product processing chamber 22 and the inspection chamber 44 that is spaced apart from the processing chamber 22 or between the product storage chamber 24 and the shipping chamber 46. The products are transported through a pass box by connecting and communicating with conveyance paths 48 and 50 (broken lines in FIG. 1). As shown in FIGS. 1 and 2, the exit-side pass box 32 of the product processing chamber 22 and the pass box 52 provided in the inspection chamber 44 are connected by a ceiling conveyance path 48, and product cells are collected by a sealed passage. Carry in and out. Similarly, the ceiling conveyance path 50 communicates between the pass box 53 of the product storage room 24 and the pass box 54 of the product shipping room 46 (see FIG. 2).

  A specific configuration of the ceiling conveyance path will be described by taking the inspection ceiling conveyance path 48 as an example. FIG. 3 shows a specific structure of the inspection ceiling conveyance path 48 for transferring the finished product cells to the inspection room 44. As shown in the drawing, an elevator 56 capable of vertical conveyance is provided in the product processing chamber 22, and an elevator 58 is provided in the inspection chamber 44 in the same manner. Pass boxes 32 and 52 capable of delivering product cells are formed below the elevators 56 and 58 so that the products can be delivered while air-locking. And the ceiling transfer tube 62 which incorporated the conveyor 60 in the ceiling side of both the elevators 56 and 58 is provided, a product cell is put into a conveyance container, and it is made to transfer from the product processing chamber 22 to the test | inspection chamber 44. FIG. At this time, the product processing chamber 22 side is set to a positive pressure, the inspection chamber 44 is set to a lower pressure state, the pressure of the ceiling conveyance path is set to an intermediate pressure, and the air from the inspection chamber to the product processing chamber is Prevent backflow. For example, a pressure gradient is applied such that the transfer chamber elevator 56 side is +45 Pa, the ceiling transfer path is +30 Pa, and the inspection room elevator 58 side is +15 Pa. This connects the supply pipe 64 of the conditioned air to the top end of the elevator 56 on the product processing chamber 22 side, and connects the exhaust pipe 66 to the top end of the elevator 58 in the inspection room 44. An adjustment damper 68 is attached to the exhaust side to form a pressure gradient. This prevents contamination to the GPM area side. Such a configuration is the same between the product storage room 24 and the product shipping room 46.

  In the GMP area, the air conditioning system maintains the positive pressure (atmospheric pressure above atmospheric pressure) outside the system, while taking in fresh air from outside and ventilating the room temperature and oxygen concentration. Is maintained. The air conditioning system passes through the cell transfer chamber 18, the cell culture chamber 16, and the material installation chamber 20 a while removing dust and the like from outside air taken from outside the system by an outside air processing air conditioner using a filter means such as a HEPA filter. The first route, the third route passing through the raw material processing chamber 14 and the raw material storage chamber 12, and the second route passing through the product processing chamber 22 and the product storage chamber 24 are branched and joined together in the material preparation chamber 26, respectively. It is discharged out of the system by an exhaust fan via 28. At this time, the amount of outside air taken in by the outside air processing air conditioner is made larger than the amount of air exhausted by the exhaust fan, so that the entire system becomes a positive pressure.

  As described above, in the automatic cell culture facility 10 according to the present embodiment, a multi-cell cell culture room 16 is formed, and a space for changing rooms (clothing and undressing) for entering and exiting workers is shared. It is only necessary to provide one place using the material installation chamber 20a, and the cell raw material to the plurality of culture chambers 16 can also be performed through the transfer robot 36 that operates the shared transfer chamber 18, which is also saved in this respect. Space can be realized. In addition, since automatic and unmanned processing using the transfer robot 36 is possible, it is possible to eliminate the possibility of mistakes such as cell misplacement, and to ensure the elimination of human errors and prevention of cross contamination due to unmanned operations. Can do. In addition, the ceiling conveyance paths 48 and 50 can be used to transport the product cells outside the GMP area by using a dedicated air-conditioned path, and in this respect as well, the worker can prevent contamination and improve the effect. The effect of eliminating the risk of contamination due to passing through a region with a low degree of cleanness can be obtained. In particular, since it is transported to the ceiling, the product cells can be transferred without causing traffic obstruction, so that further space saving can be realized.

  It can be used as a cell culture facility that prevents cross-contamination of cells.

It is a top view which shows the layout of the cell culture facility which concerns on this embodiment. It is a schematic diagram which shows the arrangement | positioning relationship of each working room of the facility. It is explanatory drawing of the ceiling conveyance path utilized for the said facility.

Explanation of symbols

10 ......... Automatic cell culture facility, 12 ......... Material storage room, 14 ......... Material processing room, 16 (161, 162, 163 ......... 16n) ......... Cell culture room, 18 ......... Cell transfer Room, 20a ......... Material installation room, 20b ......... Clothing room, 20c ......... Undressing room, 20d ......... Device loading / unloading room, 22 ......... Product processing room, 24 ......... Product storage room, 26 ... ...... Material preparation room, 28 ......... Secondary changing room, 28a ......... Entrance / exit, 30a ......... Clothing room, 30b ......... Undressing room, 32a ......... Clothing room, 32b ......... Undressing room, 34 ……… Contact pass box, 35 ……… In-system pass box, 36 ……… Transport robot, 38 ……… Automatic cell culture device, 40 ……… Automatic open / close door, 42 ……… Shutter, 44 …… ... Inspection room, 46 ......... Product shipping room, 48 ......... Ceiling transport path (inspection), 50 ......... Ten Transport path (shipment), 52 ......... pass box, 54 ......... pass box, 56 ......... transfer room elevator, 58 ......... inspection room elevator, 60 ......... conveyor, 62 ......... transport tube, 64 ……… Air supply pipe, 66 ……… Exhaust pipe, 68 ……… Adjustment damper.

Claims (3)

A plurality of cell culture chambers are installed, and a cell transfer robot chamber containing a robot that automatically transfers cells is placed between each culture chamber, the raw material processing chamber, and the product processing chamber. Each culture room has a common material installation room for setting the culture medium in the culture apparatus for culturing .
An automatic cell culture facility characterized in that the product processing chamber is connected to an inspection room or a product shipping room that is spaced apart from each other by a ceiling conveyance path, and the product is transferred via a pass box. .   2. The automatic cell culture facility according to claim 1, wherein the shared material installation room is provided with a clothes room for taking in and out of the room and a dressing room. The automatic cell culture facility according to claim 1 , wherein a pressure gradient with a product processing chamber as a positive pressure is provided between the rooms connected via the ceiling conveyance path.

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