WO2012098931A1 - 細胞培養処理システム及び細胞培養処理システムのモジュール接続方法 - Google Patents
細胞培養処理システム及び細胞培養処理システムのモジュール接続方法 Download PDFInfo
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- WO2012098931A1 WO2012098931A1 PCT/JP2012/050064 JP2012050064W WO2012098931A1 WO 2012098931 A1 WO2012098931 A1 WO 2012098931A1 JP 2012050064 W JP2012050064 W JP 2012050064W WO 2012098931 A1 WO2012098931 A1 WO 2012098931A1
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/44—Multiple separable units; Modules
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M1/00—Apparatus for enzymology or microbiology
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/50—Means for positioning or orientating the apparatus
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M3/00—Tissue, human, animal or plant cell, or virus culture apparatus
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M37/00—Means for sterilizing, maintaining sterile conditions or avoiding chemical or biological contamination
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/48—Automatic or computerized control
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16L—PIPES; JOINTS OR FITTINGS FOR PIPES; SUPPORTS FOR PIPES, CABLES OR PROTECTIVE TUBING; MEANS FOR THERMAL INSULATION IN GENERAL
- F16L55/00—Devices or appurtenances for use in, or in connection with, pipes or pipe systems
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T137/00—Fluid handling
- Y10T137/0318—Processes
- Y10T137/0402—Cleaning, repairing, or assembling
Definitions
- the present invention relates to a cell culture treatment system for cells and the like that is optimal in the fields of medicine, biology, drug discovery, pharmacy, and the like.
- the present invention relates to a cell culture treatment system for cells, tissues, organs, etc. (hereinafter referred to as cells) for regenerative medicine or biopharmaceutical production.
- the process of culturing cells includes various processes. Although not particularly limited, for example, a step of separating cells from tissues collected from humans, a step of isolating target cells from the separated cells, a step of primary culture of cells, a step of amplification culture, Examples include subculturing, differentiation of cells into arbitrary cells, organization, and cell / tissue packaging. These steps may be appropriately selected according to the purpose of treatment, the cell type to be handled, etc., and are not particularly limited.
- a myoblast cell sheet used for heart treatment a process of collecting muscle tissue from a patient, isolating myoblasts for primary culture, amplifying culture, a subculture, a monolayer cell A sheet is manufactured through a process of stacking.
- a step of amplifying and culturing ES cells or iPS cells a step of differentiating into any cells such as myoblasts or cardiomyocytes, monolayer cells
- the sheet is manufactured through a process of manufacturing a sheet and a process of stacking.
- a step of collecting oral mucosa tissue a step of isolating cells from the tissue, and a step of producing a monolayer cell sheet.
- An object of the cell culture treatment system of the present invention is to provide a system capable of treating various culture processes at low cost. It is another object of the present invention to provide a rational cell culture treatment system that can flexibly handle various cell / tissue culture processes according to the purpose of use.
- a plurality of modules that can be connected to each other, a first closed space provided in the module, and a door that opens and closes an opening of the first closed space.
- a depleting agent supply module for supplying a decontaminating agent, and supplying the decontaminating agent to the first closed space by the slow dyeing agent supplying module.
- the cell culture treatment system of the present invention makes it easy to increase or decrease modules (also referred to as units) according to the type of culture process, throughput, and production volume (detaching modules from the system and connecting modules to the system).
- the cell culture treatment system of the present invention can perform various cell culture treatments inside the first closed space.
- the door is closed in order to maintain the environmental conditions (temperature, humidity, sterility, etc.) for performing the cell culture treatment.
- the first closed space is shut off from the external atmosphere (outside the closed space).
- a gate is used for the purpose of maintaining a wafer manufacturing condition at a predetermined temperature and a vacuum level during manufacturing of a semiconductor wafer. This is common in that the valve is closed to make the inside a closed space.
- the cell culture treatment system of the present invention is different from the conventional system in the following points.
- the cell culture processing system of the present invention can move the position by physically separating the module from the system.
- the detached module can maintain the environment inside the first closed space by closing the door.
- the inside of the first closed space is once decontaminated and sterilized by a door that allows the first closed space to be sealed and opened (decontamination / sterilization operation is stopped). After that, the first closed space can be closed or sealed by closing the door, and the decontamination / sterilization state can be maintained for a certain period.
- the door (or lid) of one module to be connected and the door (or lid) of the other module are closely connected to each other. Some (or the lid) can be opened in the closed space at the same time so that both closed spaces can be connected.
- the outside of the door touches the outside air and is different from the human-derived cell that is the subject of the cell culture treatment, Various bacteria are attached.
- both doors of the module and connecting members of both modules are connected between the first closed space of one module to be connected and the first closed space of the other module. Then, a second closed space is formed so as to be hermetically sealed, and a module is connected after decontamination and sterilization by supplying a decontamination agent into the closed space.
- a decontamination agent into the closed space.
- cell culture can be performed even in a clean room (class 100,000 or less when not working) with a lower cleanliness than before.
- a system can be installed. Even if an operator contaminates the outside of the module door, the cell culture system of the present invention connects the modules after decontamination and sterilization of the outside of the module door. Reduce pollution control measures.
- the module control device that controls the module to execute a predetermined process according to a command
- the module of the module connected via the connection member
- an integrated control device that is electrically connected to the control device and controls the operation of each module.
- the integrated control device communicates with the plurality of connected modules, recognizes the ID of the module, and issues an operation command corresponding to the ID to the module. Then, a series of processing steps of various culture processes are integrated by associating a plurality of connected modules, or various cell culture processes are executed separately.
- the process when performing the cell culture treatment differs depending on the type of cells or the like, or the amount of cells produced as a result of the cell culture treatment varies depending on individual differences in human-derived cells or the like. Even in such a case, in the cell culture processing system of the present invention, additional modules can be additionally connected during the cell culture processing, specifically, the modules can be removed and the modules can be additionally connected. Further, during the cell culture treatment by the cell culture treatment system of the present invention, the cell culture treatment of another treatment step can be performed. In this case, it is possible to remove a module that has become unnecessary in the previous cell culture treatment step and to connect a module required in the next cell culture treatment step.
- each module is provided with a unique ID that can be identified, and by reading the ID, the connection or disconnection of a plurality of modules can be recognized, and the measurement results of the operation log, communication log, and environmental information of each module It can also be configured such that it is transmitted as an electrical signal to the integrated control device together with the ID of the module as the information source and recorded in the storage unit. As a result, it is possible to accurately manage cells and the like that are specimens so as not to be mixed with other cells.
- a transport robot is provided inside, and a transport module to which the modules are connected is provided.
- the transfer robot moves the object to be transferred from the first closed space of one connected module to the first closed space of another module via the second closed space. To do.
- This cell culture treatment system is equipped with a transfer module, so that plates and bottles containing cells, culture media, etc., and other materials necessary for cell culture treatment work can be placed inside the closed space inside the cell culture treatment system or others. Can be transported between the closed spaces. Thereby, various cell culture processing operations can be performed by integrally using a plurality of sterile closed spaces of the cell culture processing system.
- the seal member that fills the gap between the joining members causes the decontamination agent to leak from the gap between the connection members to the outside, and during the cell culture treatment, It is possible to prevent contamination with other cells.
- a slight gap between connecting members generated when connecting a plurality of modules can be filled with a sealing member.
- a gas or the like (a gas or the like means a gas, a liquid, a gel, or the like) is injected into the seal member to expand the seal member, and the seal member and the connection member or another seal member Can be closed to fill the gap between the connecting members. Thereby, the inside of the second closed space can be reliably blocked from the outside air.
- the step of connecting the plurality of modules via the connection member, and the second closed space formed by the plurality of connection members and the plurality of doors Supplying the decontaminating agent from the decontaminating agent supply module to decontaminate the inside of the second closed space; and opening the door to communicate the first closed space and the second closed space. And forming a one-piece aseptic closed space.
- a door is provided by providing a seal member (a seal receiving member on the other side) on both or one of the connection member of one module and the connection member of another module. After decontamination and sterilization by decontaminating the region formed by the connecting member, a plurality of closed spaces can be communicated by opening the door. For this reason, it is possible to prevent contamination of bacteria, foreign matters, and other cells that adversely affect the cell culture treatment inside the closed space.
- the cell culture processing system of the present invention can replace a module by disconnecting a module that is no longer necessary in the processing step and connecting another separately prepared module during the cell culture processing. .
- a step of installing a plurality of the modules with a gap and a seal member provided in the plurality of modules are expanded so as to fill the gap. And connecting the plurality of modules, supplying the decontamination agent from the decontamination agent supply module to the second closed space formed by the plurality of connection members and the plurality of doors.
- the hollow shape By injecting gas or the like into the inside of the sealing member (gas or the like means gas, liquid, gel, etc.), the sealing member swells to fill (seal) the gap between the connecting members.
- gas or the like means gas, liquid, gel, etc.
- the cell culture treatment system of the present invention can increase or decrease the number of treatment modules used in the system while performing reliable decontamination and sterilization. Thereby, the freedom degree of the combination of each processing module can be improved significantly, and there exists an advantage that it can respond to culture
- FIG. 1 is a plan view showing a cell culture treatment system.
- FIG. 2 is a plan view showing a cell culture processing system different from the embodiment of FIG.
- FIG. 3 is a partially cutaway perspective view of the (conveyance) module 11 of the present invention.
- FIG. 4 is a perspective view showing the transfer robot 22.
- FIG. 5 is a perspective view showing the door 25a.
- FIG. 6 is an explanatory diagram for explaining the operation when two modules are connected.
- FIG. 7 is a perspective view showing the attaching / detaching means 16.
- FIG. 8 is an explanatory diagram for explaining the connecting operation of the attaching / detaching means 16.
- FIG. 9 is a control block diagram of the cell culture processing system.
- FIG. 10 is a perspective view showing a culture plate and the like.
- FIG. 11 is a partially cutaway perspective view of a (dispensing) module different from FIG. 3.
- FIG. 12 is an explanatory view showing the dispensing operation of the (dispensing) module 12.
- FIG. 13 is an explanatory view showing the drainage recovery operation of the (dispensing) module 12.
- FIG. 14 is a perspective view showing a module (cell sheet stacking module) 14 different from FIG.
- a cell culture treatment system consisting of various modules used in various types of culture processes has been realized with the smallest floor-occupying area and reduced processing time.
- FIG. 1 is a plan view of an embodiment of the cell culture treatment system of the present invention.
- 1a is one Example of a cell culture processing system.
- Reference numeral 11 denotes a transfer module.
- Reference numeral 12 denotes a dispensing module.
- Reference numeral 13 denotes a constant temperature module.
- Reference numeral 14 denotes a cell sheet laminated module.
- Reference numeral 15 denotes a carry-in / out module such as a culture plate. Note that these modules 11 to 15 are examples, and modules having other functions may be used. Further, more modules may be connected.
- the attachment / detachment means 16 is provided on the side surface of the hexagonal conveyance module 11 in the center of the drawing.
- the attaching / detaching means 16 removably connects the transport module 11 and modules indicated by 12 to 15.
- the transfer module 11 and the other modules 12 to 15 also referred to as processing devices
- the decontamination / sterilization gas supply pipes 35a to 35c (decontamination / sterilization gas supply port 36) from the decontamination agent supply module 18 are also provided. Connected. Thereby, a decontamination agent can be supplied into each processing module, and decontamination and sterilization are possible in every corner of the cell stacking system 1a.
- 35a is a sterilization gas supply pipe for directly supplying the decontamination agent from the decontamination agent supply module 18 to the transport module 11, and the pipe 35b is a decontamination agent from the decontamination agent supply module 18. This is a sterilization gas supply pipe on the module 18 side that supplies the other modules 12-15.
- the pipe 35c is connected to the pipe 35b via a pipe (not shown) inside the transfer module 11.
- the pipe 35c is a sterilization gas supply pipe on the module 12-15 side for supplying the decontamination agent from the decontamination agent supply module 18 to the other modules 12-15.
- the decontaminating agent supply piping 35 is not limited to piping to another module via a conveyance module like a present Example. As another embodiment, the pipe may be directly connected from the decontamination supply module.
- each module is provided with a closed space such as a housing, and a clean atmosphere (class 1000 or less, preferably class 100 or less) having a fan filter module at the top of the housing may be used.
- the fan filter module includes a fan that blows normal air or the like inside the casing, and a filter that prevents dust, viruses, or the like contained in the ventilation from being brought into the casing.
- the fan and the filter are provided in close proximity as an integral module. In addition, you may provide so that it may become the position which separated them via the ventilation pipe between the fan and the filter.
- the cell culture treatment system 1a can connect modules via the attaching / detaching means 16, the number of modules can be increased or decreased. For this reason, the combination of each module can be changed so that it can respond to culture
- the uses include storage of cell suspension, cell seeding on culture plates, medium exchange, stacking of cell sheets, shipping of stacked cell tissues, and the like.
- the decontamination agent supply module 18 shown in the present embodiment includes a liquid supply unit that supplies a hydrogen peroxide solution, a vaporization unit that vaporizes the hydrogen peroxide solution, a gas supply unit that supplies a gas to each module, A gas pipe that connects between the module and the gas supply means, a pipe that collects exhaust gas from each module, and an exhaust pipe that exhausts the collected gas after detoxification through the catalyst.
- the hydrogen peroxide gas generated by the decontamination agent supply module 18 can flow into the first closed space and the second closed space (described later) of each module. This makes it possible to kill bacteria, human-derived cells, and the like that are present inside the first closed space 23 (including actuators, sensors, container exteriors, and the like provided in a module such as a transfer module).
- the type of decontamination agent supplied from the decontamination agent supply module 18 is not particularly limited.
- hydrogen peroxide as in this embodiment may be used, but peracetic acid, formaldehyde, ozone, chlorine dioxide, or the like may be used. In particular, what supplies these as a decontamination agent made into vapor
- the cell culture processing system of the present invention may be used to perform cell culture processing operations on cells derived from one or more patients simultaneously. Even if cells are derived from the same patient, a plurality of types of cells having different culture processes may be handled in parallel. An example in which a cell culture processing operation is performed on cells derived from a plurality of patients simultaneously in parallel using the cell culture processing system of the present invention will be described below.
- a plurality of human-derived or the same human-derived cells can be subjected to different or same-type cell culture treatments simultaneously. Furthermore, in the case where another human-derived cell is being cultured, if the cell culture treatment has already been performed and the cell culture is performed in the thermostat module, the cell culture state is maintained while maintaining the cell culture condition.
- the module can be detached from the cell culture treatment system and another thermostat module can be connected. Modules that require a long process may be temporarily disconnected from the cell culture system until the process is completed, and the same type of module is connected separately to minimize the waiting time of the entire system. it can.
- the cell culture treatment system shown in FIG. 2 shows another embodiment of the present invention.
- This cell culture processing system 1b connects various processing modules to the outer periphery of the transfer module 11a.
- a delivery module 17 is provided on the left side of the transport module 11 a via an attaching / detaching means 16.
- Another transfer module 11 b is connected to the left side of the delivery module 17 via the attaching / detaching means 16.
- the delivery module 17 refers to a module that includes, for example, a mounting table such as a culture plate, a decontamination agent supply port 36 that supplies decontamination gas and a sterilization gas, and the like inside the housing.
- the enclosure is provided with a door (door) capable of sealing and opening an opening for transferring a culture plate or the like.
- a plurality of modules having the same function can be combined. Since the cell culture treatment system 1b can be operated by a single module in parallel or can be operated (controlled) by a single module in parallel, high-throughput and efficient production can be achieved.
- the cell culture treatment systems 1a and 1b can be configured by combining various modules according to the process of culturing cells and tissues.
- Each module is equipped with commands for operating actuators such as motors, fans, valves, cylinders, Peltier, and heaters.
- Each module is equipped with electrical signals such as signals from environmental monitors (various sensors, such as temperature sensors, optical sensors, gas concentration meters, hygrometers, particle counters, position measuring instruments, and weight meters), measurement information, and operation logs.
- a module control unit for transmitting, receiving, and recording a target signal.
- Each module performs predetermined various processing functions based on various processing procedures stored in advance in the module control device or based on control commands from an integrated control device described later.
- the cell culture processing systems 1a and 1b coordinate the operation between modules, and the measurement results (operation log and environment log) including the ID information and environmental information of the module that executed the culture processing process, and the cell tissue
- an integrated control device capable of storing and managing information associated with sample information such as. Recognizing the ID even when another module is disconnected from one module and another module is connected by transmitting and receiving electrical signals from the module controller of each module to the integrated controller in association with the module ID information.
- the integrated control apparatus can recognize which module has exchanged electrical signals. As a result, it is possible to deal with various culture processes, labor-saving and efficient production of cells and tissues, and manufacturing costs can be reduced.
- the conventional large system is an integrated system equipped with all functions necessary for the culture process. Unlike the system of the present invention, the conventional system cannot be separated for each module. For this reason, in the conventional system, it is difficult to interrupt the processing of cells derived from other patients while processing the cells derived from one patient. The reason is that in a conventional system, when one module is operating for a long time, the other modules cannot be used, and the time for occupying the system becomes long.
- modules can be attached and detached as necessary. For this reason, in the system of the present invention, it is possible to prevent the operating module from occupying the system by leaving the module operating for a long time from the system.
- the module when there is a module that requires long-term culture in a series of processing steps, the module can be temporarily detached from the system and moved to another location. The module can continue culturing at another location. If necessary, the module can be connected to the system again after completion of the culture to continue with other processes. As a result, the system can be used for other culture processes while the module is detached and cultured independently. Thereby, in this system, this system can be efficiently operated by the system operation which considered each module occupation time.
- the system of the present invention is effective in a medical field where a processing schedule is different for each patient or a quick response to a failure of a module is required.
- the cell culture processing system of the present invention includes a module control device having a function of managing a culture processing procedure of a cell tissue and a communication means for transmitting a measurement result of the progress of culture and culture environment.
- This module control device can instruct each module to execute a culture process, and can organize and store data. According to this system, it becomes possible to produce cells and the like in accordance with GMP (Good Manufacturing Practice: Preparation and quality standards for pharmaceutical preparations).
- FIG. 3 is a partially cutaway perspective view of a transfer module 11 which is a kind of module of the present invention.
- Reference numeral 21 is a base that is hexagonal when viewed in plan, and 22 is a transfer robot provided at the upper center of the base 21.
- Reference numeral 23 denotes a housing that is configured to shield the SCARA-type transport robot 22 from the external atmosphere (consisting of a housing side wall 23a and a housing ceiling 23b).
- Reference numeral 24 denotes an opening for carrying in / out the object to be conveyed between the outside of the housing 23 and the inside of the housing.
- 25a and 25b are doors for sealing and releasing the opening 24.
- Reference numeral 16 denotes attachment / detachment means for attaching / detaching the transfer module 11 attached to the side surface of the base and the dispensing module 12, which is another module.
- the transport module 11 can be coupled or detached while maintaining hermeticity and sterility.
- the modules By connecting the modules in a sealed state while maintaining sterility, it is possible to prevent the cells inside the module from being contaminated with germs or other cells. For this reason, in this system, the safety
- it in order to minimize the amount of dust inside the module, it may be configured to include a fan filter module (air purification module) 28 using a HEPA filter 27 or the like.
- the fan 29 at the upper part of the ceiling 23b of the transport module 11 is provided with a decontamination supply pipe 35b (decontamination agent supply port 36) from the decontamination agent supply module (decontamination agent supply module) 18, and a housing.
- a decontaminant exhaust recovery pipe 37 (decontamination agent supply port 38) for exhausting and collecting decontamination / sterilization gas from the inside of the housing and sending it to the decontamination agent supply module can be provided.
- Decontamination and sterilization are performed in order to kill bacteria and cells attached to the outer surface of the sealed container introduced into the inside of the closed space of the module or from the outside of the closed space.
- Various decontamination means for supplying hydrogen peroxide vapor, ozone and the like can be considered for the decontaminating agent supply module.
- effective and safe can be secured, and a decontamination / sterilization validation can be established.
- the housing 23 has an internal space in a range slightly larger than the operating range of the SCARA type transfer robot 22.
- a range surrounded by the casing 23 constitutes the first closed space V1 (the same applies to the other modules 12 to 15).
- the operating range means that when the arm of the SCARA-type transfer robot 22 is folded and horizontally turned to the minimum turning radius as shown in FIG. 3, the SCARA-type transfer robot 22 interferes with peripheral devices and the like. This refers to the range (occupied space) of the space that can be operated without any problems.
- the internal space shape of the housing is a cylindrical shape.
- the inner space is a hemispherical shape. Thereby, the volume of the internal space of the housing can be minimized.
- a gas supply port and an exhaust port for supplying decontamination gas into the housing are provided at the top of the housing.
- ⁇ Use a material that is less deteriorated by a decontamination agent such as hydrogen peroxide gas as the material inside the housing, and perform appropriate coking at the joint of the member to maintain a predetermined sealing degree.
- a decontamination agent such as hydrogen peroxide gas
- the metal inside the casing is stainless steel
- the movable part and the caulking material are silicone rubber.
- the cell culture treatment system of the present invention has a closed space with a minimum size. It is not a large-sized one that workers enter like a clean room used in the semiconductor and food manufacturing fields. For this reason, the decontamination / sterilization time can be shortened, the sterility can be easily maintained, and the production can be performed at low cost. In addition, since combinations can be made as necessary, the entire system combining a plurality of modules is inexpensive. Therefore, the cost of cells and tissues to be produced can be reduced.
- the SCARA type transport robot 22 can minimize the internal volume of the housing 23 when the operating range is minimized. For this reason, when supplying gas for decontamination, a predetermined decontamination / sterilization concentration can be reached in a short time by supplying a minimum amount of gas.
- first closed space V1 if the internal volume of the first closed space V1 is large, gas does not flow inside the first closed space V1. Further, if the structure of the first closed space V1 is complicated, there are places where decontamination cannot be achieved. Such a problem can also be prevented by reducing its volume to a simple shape.
- the SCARA-type transfer robot 22 has a robot base 41 fixed to the base 21. On the upper part of the robot base 41, an elevating means 43 for elevating the SCARA type transfer robot 22 is provided.
- the elevating means 43 is capable of linear movement in the Z direction in the figure (not shown) by rotating the ball screw shaft by the operation of a motor.
- a swiveling means 45 is provided above the lifting means 43. The turning means 45 turns the SCARA-type transfer robot 22 around the vertical direction (in the ⁇ direction).
- the first arm 46 is rotatably provided on the upper part of the turning means 45.
- a second arm 47 is provided at the upper end of the first arm 46.
- an end effector 48 is provided on the second arm 47 to place a culture plate, which is a transported object, on the top.
- the SCARA-type transfer robot 22 can move the culture plate or the like on the end effector 48 linearly or in a curved manner by the first arm 46, the second arm 47, and the end effector 48 operating in synchronization. Note that the various actuators provided in the SCARA-type transfer robot 22 are operated based on electrical signals from the control device 50 (indicated by a thick frame in the figure).
- the SCARA type transport robot 22 transports a microplate, a bottle, a disposable chip of a dispensing module (consumable supplies supplied to various modules) or the like inside the decontamination / sterilization atmosphere covered with the housing 23. Can do.
- the rotation part of the SCARA type transfer robot 22 is provided with an O-ring such as a fluorine resin or a seal member that can withstand the decontamination agent. This prevents the decontamination gas from flowing into the SCARA-type transfer robot 22 and corroding the internal members.
- an O-ring such as a fluorine resin or a seal member that can withstand the decontamination agent. This prevents the decontamination gas from flowing into the SCARA-type transfer robot 22 and corroding the internal members.
- a resin bellows seal 44 is attached between the periphery of the robot base 41 of the SCARA-type transfer robot 22 and the periphery of the movable member of the elevating means 43. For this reason, even when the SCARA-type transfer robot 22 is moved up and down, gas for decontamination and sterilization is prevented from flowing into the SCARA-type transfer robot 22 and corroding the internal members.
- an industrial articulated robot, a slider robot, or the like may be used as a transfer means.
- FIG. 5 includes a driving means 55 and a door member 56.
- the driving means 55 is an air cylinder, and can open and close the door 56 by moving up and down.
- a bellows seal 57 is attached to the movable part of the driving means 55. This prevents the decontamination agent from flowing into the door driving means and corroding the internal member.
- FIG. 5A shows that the door member 56 is lowered by the operation of the door driving means 55, and the inside V1 (side shown as 23in) and the outside V2 (side shown as 23out) of the first closed space V1 through the opening 24. Indicates a state of communication.
- FIG. 5B shows a state where the door member 56 is similarly raised and the opening 24 is closed, and the inside of the first closed space V1 is sealed.
- a silicone seal 58 is attached to the door member 56, the first closed space V1 (periphery of the opening 24), and the contact portion (on the door side or the housing side).
- This silicone seal is tube-shaped. By injecting compressed gas into the tube, the space between the bulging housing and the door member 56 is sealed. In addition to this embodiment, the seal may be crushed and sealed by pressing by opening and closing the door.
- the door 25b shown in FIG. 3 is a revolving door having a rotation axis parallel to the wall surface 23a of the first closed space V1.
- a silicone seal is attached to the door member 56, the first closed space V1 (periphery of the opening 24), and the contact portion (on the door side or the housing side).
- it can be set as the structure which rotates a door by attaching a motor or a cylinder, and a link member to a rotating shaft.
- sealing can be performed by crushing the silicone seal evenly between the door and the wall surface inside the housing by rotational force.
- Fluorine-based resin material O-rings or fluorine-based V seals are used at the rotational drive location, so that gas for decontamination and sterilization flows into the inside of the rotating means and the internal members corrode. Is preventing.
- FIG. 6 is an explanatory diagram for explaining a state when a module and another module are connected.
- 23a is a wall surface 23a of the first closed space V1 of the module.
- the right side of the door 56 in the drawing (region indicated by ⁇ S in the drawing) is the inside of the housing, and the left side (region indicated by U in the drawing) is outside the first closed space V ⁇ b> 1 of the transfer module 11.
- a region on the right side of the door member 56a of another module (region indicated by ⁇ T in the drawing) is outside the first closed space V1.
- the region V2 (the region of V2 is referred to as a second closed space) is a module different from the module.
- the openings 24 and 24a of the module different from the module communicate with each other, it is an area that becomes the inside of the closed space.
- FIG. 6A shows a state before a module (referred to as a first module) is connected to another module (referred to as a second module).
- 6B shows a state in which the second module (the module on the left side in the figure) is moved from the state shown in FIG. 6A to the right side in the figure until the position immediately before the seal member 58c and the seal receiver 58b come into contact with each other. Is shown.
- the inside has a tube shape, and a gas is injected into the tube to inflate it so that the seal receiver 58b and the seal member 58c are brought into contact with each other.
- the gas is extracted from the sealing member 58d that is inflated by injecting the gas into the interior, and the door member 56a and the sealing member are spaced apart from each other.
- the gas is extracted from the sealing member 58a which is inflated by injecting gas into the interior, and the door member 56 and the sealing member are spaced apart from each other.
- the first module and the second module region V communicate with each other.
- Reference numeral 66 denotes a pipe connector for supplying a decontamination agent from the decontamination agent supply module via a pipe.
- 67 is a pipe connector that collects exhaust of the decontamination / sterilization gas exhausted from the inside of the first closed space V1 of the module.
- the decontamination / sterilization gas exhaust recovery port is piped to the decontamination supply module.
- the attaching / detaching means 16 operates the key driving means 62 to advance the key member 62 in the direction of the arrow shown in FIG. 7A, and then moves the key member 62 (in the rotational direction shown in FIG. 7B). ) After that, the first module and the second module are connected by retreating the key member 62 in the direction of the arrow shown in FIG. 7C.
- the positioning pin 61 is fitted to a positioning pin guide member (a member having a recess and a hole slightly larger than the outer shape of the positioning pin) attached at a position corresponding to the positioning pin of the second module to be connected.
- the sensor 64 that protrudes from the wall surface detects that the module is connected, and transmits an electrical signal indicating the detection to the control device or the integrated management processing module.
- the connector 65 of the communication line is also connected by module connection (in the case of connection by wireless LAN, connected by receiving an electrical signal from the sensor 64, etc.), the second module control unit 2 By sending an electrical signal to the integrated control device, the integrated control device can recognize which ID of the second processing module connected to the first module. Furthermore, the pipe connectors 66 and 67 are also connected by this module connection, and the decontamination agent can be supplied to the second module through the first module.
- the sensor 64 detects that a module connection is to be made, and starts the pull-in operation. Thereby, it can be set as the structure which supports attachment / detachment.
- the pull-in operation will be described with reference to FIG.
- FIG. 8A shows a state where the attaching / detaching means 16 of the first module and the attaching / detaching means receiver 16a of the second module are separated and not connected.
- FIG. 8B shows a state where the sensor 64 and the sensor receiver 64a are in contact with each other when the second module is moved to the right side in the drawing. The distal end of the positioning pin 61 is inserted into the recess of the positioning pin receiver 61a.
- the attaching / detaching means 16 is provided between the base 21 of the plurality of modules, and the mechanism can exert its function regardless of which side it is provided.
- a block member having a recess on the upper surface of the member is provided on the floor, and positioning can be performed by inserting a pin from above, so that the connector can be connected and disconnected by attaching / detaching operation. It may be an attaching / detaching means attached with the connector facing in the direction.
- the modules 11 to 15 are connected to the module control devices 50 and 71a to c through wiring, respectively.
- various actuators can be operated in response to electrical signals from the module control devices 50 and 71a to 71c.
- the decontaminating agent supply module and each module are connected, and the decontaminating agent is supplied to each module via a pipe.
- the actuator or the decontaminating agent supply module can be operated by receiving the electric signals from the control devices 50 and 71a to 71c directly or indirectly.
- it is connected to the compression pump module and the vacuum pump module via piping.
- the actuator or the compression pump module and the vacuum pump module can be operated by directly or indirectly receiving the electrical signals from the control devices 50 and 71a to 71c.
- power is supplied because it is connected to the power supply means via wiring.
- the attachment / detachment means 16 is supplied and exhausted with a connector 65 of wiring for transmitting and receiving electrical signals from the control devices 50 and 71a to 71c and a decontamination / sterilization gas from the decontamination agent supply module 18. It is also possible to have a configuration including a connector 66 for the pipe to be connected and a power connector (65). By arranging the connector 65 at a position corresponding to each connector 65 of the second module to be connected, the connection is made when the modules are connected. Thus, an electrical signal or the like from the control devices 50 and 71a to 71c can be transmitted and received.
- the second module may include a vacuum pump, a compressor, a battery, an electric signal receiver using a wireless LAN, and a module control device separately from the first module.
- a vacuum pump By connecting to the first closed space V1 of the first module, power is turned on to the module control devices 50, 71a to c, or a communication start signal is transmitted to and received from the integrated control device 70. It is good also as a structure which operate
- the module refers to a transport module, a carry-in / out module, an isolated primary culture module, a subculture module, a tube connection robot, an automatic warehouse module, a transport lane module, a cell seeding module, a medium dispensing module, and a cell sheet stack.
- Modules, measurement modules, carry-in / out modules such as plates, and decontamination / sterilization gas supply modules.
- the transfer module 11 which is a type of module, blocks the base, the robot that transports the culture plate and the like provided on the base, and the movable atmosphere of the robot from outside air (covers the side and ceiling of the module and decontaminates the module). -Prevents sterilization from filling the inside of the gas and preventing it from leaking to the outside), a door that opens and closes the opening for transferring culture plates and the like outside and inside the body, and the inside of the first closed space V1 It can be set as the structure provided with the decontaminant supply module which supplies a dye, and an attachment or detachment means. As another configuration, a moving unit may be provided at the lower part of the module.
- the base and the first closed space V1 that covers the side and the ceiling of the module in the upper part of the base and prevents the decontamination / sterilization from filling the inside of the gas and leaking to the outside are formed.
- An opening for delivering the culture plate and the like inside and outside the first closed space V1, a door capable of opening and closing the opening, and moving means such as a roller or a car at the bottom of the base It is good also as a structure provided.
- the loading / unloading module includes a door for loading / unloading equipment, and cells, culture solution, medicine, culture dish and centrifuge tube necessary for culture are introduced into the loading / unloading module from this door.
- the loading / unloading module is equipped with an operation glove made of an elastomer material that allows the operator to move, open, and open the equipment from the outside of the loading / unloading module. It can be moved and installed manually near the culture processing module using a glove. Instead of the operator, the movement may be performed using a belt conveyor or a robot.
- the isolated primary culture module includes a subdivision module for subdividing a tissue piece. In addition to tissue pieces, centrifuge tubes, petri dishes, culture solutions, etc. are introduced. Although the means of subdivision is not limited, a method of minimizing damage to cells is taken. Moreover, the cell separation module for taking out a cell is provided. The cell separation module decomposes the extracellular tissue of the fragmented tissue pieces with an enzyme, rotates (while decomposing), and isolates the cells. Furthermore, the target cell can be taken out by utilizing the difference in cell adhesion, cell size and the like.
- the isolated primary culture module includes a mixer as a subdivision module for subdividing the cell debris, and a moving means 8 (for example, a separator) that puts the cell debris from a container (for example, a bottle or a plate) containing the cell debris into the mixer. It is possible to adopt a configuration provided with a pouring means, a single pipetter or the like.
- the primary culture module includes a constant temperature module capable of maintaining an appropriate gas concentration, in which cells are grown in a culture solution under an appropriate environment until the number of cells that can be subcultured is reached.
- the isolated primary culture module has a means for taking out the subdivided cell pieces from the mixer, a medium supply means for supplying the medium to the subdivided cell pieces, and a constant temperature shake that operates while shaking the cells at 37 ° C. It can be set as the structure provided with a means or the like.
- tissue subdivision module, cell separation module, and primary culture extracted from the living body are combined to form an isolated primary culture processing module.
- the subdivision processing module, cell separation processing module, primary culture module, The culture processing module and each may be separate modules.
- the subculture module is a module that further increases the number of cells after the primary culture to proliferate to the number of cells sufficient for treatment.
- the cells are cultured in a closed closed container. By culturing a large amount of cells, it becomes a large module, so it is not directly connected to the culture processing system, but a cell suspension made of a closed closed container and an isolated primary culture processing module is connected by connecting tubes. Then, it is transported to a closed closed container in the primary culture processing module.
- the modules may be connected to each other and transferred by a transfer robot. If necessary, a plurality of the same modules may be connected and cultured.
- the constant temperature module provided in the subculture module, the culture medium can be periodically exchanged and proliferated in an appropriate environment.
- the dispensing module uniformly and accurately seeds a predetermined number of temperature-sustained cell suspensions on a predetermined number of temperature-responsive culture dishes, removes the culture medium from the culture dish as necessary, and supplies a predetermined amount of fresh medium. It is a module to add.
- the cell suspension transported by the tube from the subculture module is stored in the layer processing module and is then seeded in a plurality of temperature-responsive culture dishes, or is not stored via the storage module. Seeded in multiple dishes. Cells in the seeded suspension adhere uniformly to the temperature-responsive culture dish.
- the dispensing module of the present invention has a turntable on which a plurality of culture plates and the like can be placed, a liquid supply means that has a dispensing nozzle to supply liquid, and a drainage recovery nozzle that collects drainage. Drainage recovery means, nozzle drive means for allowing the dispensing nozzle and drainage nozzle to move in a plane, and nozzle lifting / lowering drive means for enabling the dispensing nozzle and the drainage recovery nozzle to move separately in the height direction; And a weight measuring means for measuring the weight of the culture plate and the like from below the turntable, and an elevating means for the weight measuring means.
- This dispensing module is characterized in that the weight of the culture plate or the like is measured by raising the weight measurement means through the opening of the turntable before and after supplying the liquid to the culture plate.
- This dispensing module can dispense a plurality of plates continuously with good dispensing accuracy.
- the speed of the dispensing work can be increased.
- the accuracy of dispensing and aspiration can be easily managed.
- storing the weight data for each plate is an effective means for showing the validity of the medium supply and medium suction operations.
- the cell sheet stacking module is a module that creates a new tissue for transplantation having a very high cell density by stacking a plurality of sheet-like cell sheets.
- the thin sheet-like cells formed on the cell adhesion surface of the temperature-responsive culture dish are separated from the dish by changing (decreasing) the temperature. Therefore, the temperature of the culture dish is lowered by a cooler (Peltier) or the like to take out a cell sheet, and a plurality of the sheets are overlapped by a robot or an actuator.
- the stacked cell sheets are integrated into a new tissue with a very high cell density.
- the cell sheet stacking module is responsible for a process of stacking a plurality of cell sheets through cell seeding, cell sheeting, and cell sheet peeling to create a transplantable new tissue.
- the cell sheet laminated module includes a housing that forms a first closed space V1 in which the inside of the module is sealed to make a decontamination / sterilization gas atmosphere, and an opening of the first closed space V1 that carries in and out a culture plate and the like. And a door for closing (opening / closing) the inside of the apparatus.
- the cell sheet stacking module includes a turntable on which a plurality of culture plates and the like can be placed, a base member that can move up and down, and a base member that can swing within a vertical plane.
- a pressing member that presses the cell sheet between the holding part and the culture plate by the lifting and lowering operation of the base member on the other side with the holding member holding the cell sheet via gelatin on one side with the arm and the center axis of swinging Pressing force measuring means for measuring.
- the cell sheet stacking module includes a turntable on which a plurality of culture plates and the like can be placed, a base member that can be moved up and down, an arm that is swingable in a vertical plane with respect to the base member, and a central axis of swinging.
- a holding member that holds the cell sheet on one side via gelatin, and a pressing force measuring unit that measures the pressure pressing the cell sheet between the holding unit and the culture plate by the lifting and lowering operation of the base member on the other side It is characterized by providing.
- This cell sheet laminating apparatus can continuously laminate a plurality of plates. Place the culture plate with the cell sheet on the turntable, and measure the pressing force that presses the cell sheet between the holding member and the culture plate quickly by the holder of the cell stacking device in order. The pressure can be stacked constant. This apparatus facilitates uniform cell sheet lamination. Furthermore, storing the pressing force data for each cell sheet is an effective means for showing the validity of the layering operation.
- the constant temperature module (incubator) is used to appropriately maintain gas concentration, temperature, and humidity for growing cells and storing new tissues until transplantation.
- ⁇ Tube connection module> The tube connecting robot moves a cell suspension or the like in a closed space to a closed space of another processing module.
- this tube connection module the tube between one processing module and the other module can be connected or disconnected. According to this module, sterility and hermeticity are maintained even when the socket (connection portion or connection connector) is connected or disconnected.
- This module can be used when the suspension is transported between processing modules by a tube.
- the automatic warehouse module stores the culture fluid (medium), growth factors, drugs, cells, containers, etc. necessary for the cells and tissues to be cultured, and automatically issues them according to the cells to be cultured.
- the processing module is supplied to each processing module from the equipment loading door portion.
- the transportation lane module is a guide for guiding to a predetermined place in order to connect the closed space of each module and the tube of the tube connection module.
- This guide is made of metallic tape, rails, guide posts, or the like. Such a module can be used when a tube is automatically connected.
- modules include 3D module processing modules that form 3D new tissue using 3D scaffolds, various bioreactors, modules that apply stress, strain such as pressure, tension and compression, packaging for transportation In some cases, a packaging module or the like is added.
- FIG. 9 is a control block diagram of the cell culture processing system.
- the integrated control apparatus of the present invention will be described below with reference to FIG.
- the module of this embodiment includes a control device that transmits and receives electrical signals to and from other modules.
- the control device can transmit and receive electrical signals to and from the integrated control device.
- the integrated controller coordinates the operation of each module (operates by sending and receiving electrical commands to individual processing modules according to the program), or records the progress of culture and changes in environmental conditions, and manages the database (Collect and manage information from the control device of each processing module).
- the integrated control device outputs an electrical signal of the data to an external printer, computer, or storage device in response to a user request.
- the integrated control device includes a communication means for sharing data with each processing module and exchanging signals. Even if the communication means is RS23C iEEE, or wired or wireless, it is sufficient to solve the security problem. Furthermore, an input module is provided for inputting the culture condition setting, cell or patient ID, etc., and instructing to start operation, culture status, database browsing, and the like. Furthermore, a display module that displays culture condition settings, cell or patient ID, culture status, and the like is provided.
- the integrated control device may be separated into CPU 70a and RAM 70c that are control devices, and a storage unit 70b that is a database management module that records the progress of culture and changes in environmental conditions and manages the database.
- the integrated control device 70 determines whether or not work is possible depending on the combination of modules.
- the CPU 70a reads the processing program stored in the storage unit 203, develops it in the RAM 70c, and executes it, thereby controlling the entire cell culture processing system 1.
- the RAM 70c expands the processing program executed by the CPU 70a in the program storage area in the RAM 70c, and stores the input data and the processing result generated when the processing program is executed in the data storage area.
- the storage unit 70b has, for example, a recording medium (not shown) in which programs, data, and the like are stored in advance, and the recording medium is configured by a semiconductor memory or the like. Further, the storage unit 70b is processed by the CPU 70a executing various processing programs such as the cell culture processing program 70d and various data for realizing the function of controlling the entire cell culture processing system 1 (1a, 1b) and the execution of these programs. Data is stored.
- a recording medium not shown
- the recording medium is configured by a semiconductor memory or the like.
- the storage unit 70b is processed by the CPU 70a executing various processing programs such as the cell culture processing program 70d and various data for realizing the function of controlling the entire cell culture processing system 1 (1a, 1b) and the execution of these programs. Data is stored.
- the cell culture processing program 70d causes the CPU 70a to realize a function of culturing a cell or the like to be processed based on an operation command to each combined module, environment information of each module, and information on presence / absence of decontamination work. It is a program.
- the module may include a power storage device, a control device, various actuators (heaters, motors, cylinders), an input module, a display module, a compressor, a decontamination agent supply module, and the like.
- Reference numeral 50 denotes a control device for the transport module 11.
- 71 a is a control device of the dispensing module 12.
- 71 b is a control device for the thermostatic module 13.
- 71 c is a control device for the cell sheet stacking module 14.
- Reference numeral 71d denotes a control device for the carry-in / out module 15 such as a culture plate.
- the integrated control device 70 has an input module for setting culture conditions, inputting information on cells to be cultured, etc., and instructing to start a culture process, and a display module for displaying information on culture conditions, cells, operating conditions, etc. And communication means for receiving an instruction signal in response to information from each module and transmitting data sent from each module to the storage unit, and a control device for controlling each module.
- Each module can be operated independently. Further, the integrated control device 70 can perform communication between the respective modules and cooperate with the cell culture treatment process to perform automatic operation. Each module and the integrated control device 70 communicate with each other by a run cable, a wireless LAN, or other communication means. Data such as operation process progress information, culture environment data, and culture process pass / fail judgment is sent from each module to the integrated control device 70. Each module is instructed to start a decontamination / sterilization process or a cell culture treatment process from the integrated controller.
- the storage unit 70b includes an input module for inputting instructions such as data retrieval and storage destination, a database management module for organizing sent data and creating a database, a display module for displaying instruction contents and results, and another storage of data. It is electrically connected to an output module that outputs data to a device or a printer.
- a tissue removed from a living body is introduced into a closed space, subdivided, decomposed with an enzyme, and cells are separated and isolated.
- the isolated cells are subjected to primary culture, amplification culture, and organization to form a transplantable cell suspension or a new tissue that is maintained in a sterile state.
- Cell suspensions and new tissue are examined, packaged, shipped and cultured.
- Various data (such as information from the environmental monitor) in these processes is transmitted to and stored (saved) in the storage unit 70b of the integrated control device 70 or a separate storage device.
- A1 The operator inputs the ID and password using the input module.
- the integrated controller receives an electrical signal from the input module.
- the integrated control device distinguishes possible operation contents depending on the authority of the operator.
- an authorized operator inputs necessary items such as a patient ID and culture conditions from the input module.
- the operator can select an appropriate driving procedure program from various driving procedure programs incorporated in the integrated control apparatus.
- Each module used for operation transmits a signal indicating that preparation for operation is completed to the integrated control device.
- the integrated control device confirms an operation preparation completion signal from each module involved in the operation. A4. When the confirmation is completed, the integrated control device issues a command to connect the first closed spaces V1 of the modules to each module. A5. The controller of the connected module checks with a sensor or the like that the connection has been made securely. A6. When it is confirmed that the connection is surely completed, a message is transmitted from the module control device to the integrated control device. A7. The integrated control device issues an instruction to start the decontamination process to the decontamination agent supply module. A8. The decontamination agent supply module executes decontamination of the first closed space V1 and the second closed space V2. A9. When the decontamination is completed, a decontamination completion signal is transmitted from the decontamination agent supply module to the integrated control device.
- the decontamination status (decontaminated or not decontaminated) of each module is stored in the integrated controller together with the module ID.
- the integrated control device that has received the signal of completion of decontamination / sterilization gives an operation instruction by a program to the module that operates first.
- the module that receives the operation command operates with the instructed program.
- the operating module periodically sends data of predetermined items such as operation time, environmental data, and checkpoint confirmation results to the integrated control device. These data may be stored in each module.
- the integrated control apparatus stores the sent data in a database. A11. When it is detected that a failure or abnormality has occurred during operation of the module, this data is transmitted to the integrated control device. Depending on this content, the restoration work is automatically performed inside the module.
- the data (contents, time, etc.) is transmitted to the integrated control device.
- the integrated control device stores abnormal data and repair data in a database.
- the integrated control device issues a separation command when the modules need to be separated, and sends a separation command when the modules need to be combined.
- the operation of each of the following modules is repeated from A2 to A14.
- A16. When all the processing is completed, various data sent from each module is stored as a series of data for each sample, and is output to another storage device or printer as necessary.
- the culture plate or the like of the present invention includes the culture plate shown in FIG. 10A, the reagent bottle 81, the reagent bottle bracket 82, and the sheet cell holding member plate of the cell sheet stacking module shown in FIG. .
- a guide member 82a is attached to the reagent bottle bracket 82 so that the reagent bottle 81 can be conveyed in an upright state in the reagent bottle bracket 82 for conveying the reagent bottle 81.
- a module (dispensing module) 12 shown in FIG. 11 includes a turntable 93 on which a plurality of culture plates and the like 80 can be placed, a liquid supply means that has a dispensing nozzle 91 and supplies liquid, and a drainage recovery nozzle 92.
- a drainage collecting means for collecting the drainage a nozzle driving means for allowing the dispensing nozzle 91 and the drainage collecting nozzle 92 to move within a plane, and the dispensing nozzle 91 and the drainage collecting nozzle 92 separately.
- Nozzle raising / lowering driving means (not shown) that can move in the height direction, weight measuring means 97 for lifting the culture plate 80 from below the rotary table 93 and measuring the weight, and lifting means 95 for the weight measuring means. And measuring the weight of the culture plate 80 and the like by raising the weight measuring means through the opening 24 (not shown) of the turntable before and after supplying the liquid.
- the turntable 93 has an opening 93b below the place where the culture plate 80 is placed so that the culture plate 80 and the like can be placed by the transfer robot 22 (not shown).
- a plurality of culture plates 80 can be placed on the turntable 93.
- a lid opening / closing means for opening and closing the lid of the culture plate 80 is disposed around the turntable 93.
- the transfer robot 22 can scoop up the culture plate 80 from the turntable by inserting the end effector 48 below the culture plate 80 and moving up. As a result, the transfer robot 22 can smoothly transfer the culture plate 80 without dropping or tilting the culture plate 80 during transfer.
- the culture plate 80 can be rotated and moved to the vicinity of the dispensing nozzle 91 (double solution recovery nozzle 92) (in the ⁇ direction in the figure) by the operation of the turntable. Further, the dispensing nozzle 91 is movable in the Z1, X1, and Y1 directions in the drawing, and the drainage recovery nozzle 92 is movable in the Z2, X1, and Y1 directions.
- Each of the driving means is provided at the lower part of the base 21 and is sealed by a bellows seal 96. For this reason, the risk of corrosion or deterioration due to the decontamination / sterilization gas can be reduced in the driving means.
- FIG. 12A shows a state where the culture plate 80 is placed on the turntable 93. 12 (B), the rotating shaft 93a of the turntable 93 is rotated 180 degrees from the state of FIG. 12 (A), and the weight measuring means 95 below the turntable 93 is lifted and placed on the measurement table 97.
- FIG. 12C shows a state where the culture plate 80 is placed (weight measurement is performed).
- FIG. 12C shows a state where the weight measuring means 95 is lowered from the state of FIG. Show.
- FIG. 12D shows a state in which, after the dispensing operation, the dispensing nozzle 91 is lifted and then the weight measuring means 95 is lifted to perform weight measurement. Thereafter, an operation command and weight measurement are performed by the control device 71a, and an operation log and weight measurement data are transmitted and received together with the module ID to the integrated control device.
- FIG. 13 is an explanatory view showing the drainage collecting operation of the module (dispensing module) 12.
- FIG. 13A shows a state in which a culture plate 80 that requires replacement of the culture medium is placed on a turntable 93.
- FIG. 13B shows a state where the plate is tilted by raising the plate tilting means 94 and lifting the bottom of one side of the culture plate 80.
- FIG. 13C shows a state where the waste liquid is recovered by lowering the waste liquid recovery nozzle 92. Thereafter, an operation command is issued by the control device 71a, and an operation log and various data are transmitted / received together with the module ID to the integrated control device.
- FIG. 14 is a perspective view showing the cell sheet laminated module 14.
- Reference numeral 100 denotes a holding member that holds the cell sheet.
- the holding member 100 is detachably provided at the lower end of the tip of the arm 101.
- a gel-like material is applied to the portion of the holding member 100 that contacts the cell sheet.
- the gel-like material is, for example, gelatin. Thereby, a cell sheet can be stuck and lifted.
- the arm 100 is attached to the upper part of the base member (in the shape of a quadrangular prism) so as to be swingable within a vertical plane.
- a holding member 100 is provided on the left side in the drawing with the swinging rotation shaft 102 of the arm interposed therebetween, and a pressing force measuring means 103 for measuring the pressing force (weight) is provided on the right side in the drawing.
- the lower part of the base member 105 is sealed with a bellows seal 104.
- drive means (not shown) for allowing the base member 105 to move in the X2 direction and Y2 direction in the horizontal plane, and a lift drive means for moving the base member up and down.
- the pressing force measuring means 103 In order to measure the pressing force by the pressing force measuring means 103, it can be measured by lowering the base member 105 by the operation of the elevating means and pressing the holding part against the cell sheet in the culture plate 80. At that time, the holding member 100 (power point) attached to the tip of the arm 101 swings about the swinging rotation shaft (fulcrum) and presses the pressure measuring means 103 (working point).
- the pressing force measuring means 103 is, for example, a load cell.
- the result information measured by the pressing force measuring means 103 is transmitted and received as an electrical signal via the control device 71c (not shown) of the cell sheet stacking module 14 or directly to the integrated control device 70.
- stacking module 14 can form a uniform cell layer by performing operation control (feedback control etc.) so that pressing force may become fixed based on a measurement result.
- the turntable 106 is a turntable on which a plurality of culture plates 80 and the like can be placed.
- the turntable 106 includes a rotation shaft 106a.
- the rotating shaft 106a is sealed with an O-ring or the like, and can be driven to rotate at the lower part of the base 21 by the operation of the rotation driving means.
- This system can be installed and used in existing limited spaces, such as hospitals, and even in such locations, it meets GMP (Good Manufacturing Practice).
- Cells and tissues for treatment can be prepared. It also contributes to the creation of a cell and tissue culture business that installs multiple systems and undertakes and cultures the tissues brought in from each hospital.
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Abstract
Description
本発明はこれらの問題点に鑑みてなされたものである。本発明の細胞培養処理システムは、多種多様な培養プロセスを低コストで処理できるシステムを提供することを目的とする。また使用目的に応じて多種の細胞・組織等の培養プロセスに柔軟に対応できる合理的な細胞培養処理システムを提供することを目的とする。
搬出入モジュールは、機材搬入用のドアを備え、培養に必要な細胞や培養液、薬剤、培養皿や遠沈管などの機材は、このドアから搬出入モジュールに導入される。
搬出入モジュールには、作業者が搬出入モジュールの外側から機材の移動や開封、開栓などを行うための、材質がエラストマからなる操作用グローブが備えて、モジュール内部に持ち込んだ機材を、操作用グローブを使って手動的に培養処理モジュール付近まで移動・設置できるようになっている。作業者の代わりに、ベルトコンベヤやロボットを使用して、移動を行ってもよい。
単離初代培養モジュールは、組織片を細分化するための細分化モジュールを備える。組織片の他、遠沈管やシャーレ、培養液などが導入される。細分化の手段は限定しないが、細胞に与えるダメージを最小に押さえる方法をとる。また、細胞を取り出すための細胞分離モジュールを備える。細胞分離モジュールは、細分化された組織片の細胞外組織を酵素で分解し、(分解しつつ)回転させ、細胞を単離する。更に細胞の接着性や、細胞の大きさ形などの違いを利用して、目的の細胞を取り出すことができる。
継代培養モジュールは、初代培養後の細胞の数を更に増やして、治療に足るだけの細胞数まで、増殖させるモジュールである。
本実施例では、細胞は、閉鎖形の密閉容器の中で培養される。細胞を大量に培養することにより、大きなモジュールとなるため直接培養処理システムへの結合はせず、閉鎖形の密閉容器と単離初代培養処理モジュールでできた細胞懸濁液を、チューブの結合によって、初代培養処理モジュール内の閉鎖形の密閉容器に搬送する。むろんモジュール同士を結合して、搬送ロボットによる移送を行ってもよい。必要に応じて、同じモジュールを複数台連結して培養してもよい。
継代培養モジュールが備える恒温モジュールの中で、適切な環境下で、定期的な培養液の交換を行い、増殖させることができる。
分注モジュールは、大量に増幅した細胞の懸濁液を所定の枚数の温度応答性培養皿に均一かつ正確に播種し、必要に応じて培養皿の培地を取り除き、所定の量の新鮮な培地を添加するモジュールである。
継代培養モジュールからチューブで搬送された細胞懸濁液は、積層処理モジュール内に貯蔵されそこから複数の温度応答性培養皿に播種されるか、貯蔵モジュール等に経由して貯蔵されることなく複数の皿に播種される。播種された懸濁液内の細胞は、温度応答性培養皿に均一に接着する。
細胞シート積層化モジュールは、シート状になった細胞シートを複数枚重ね合わせ、細胞密度の非常に高い、移植用新生組織を作成するモジュールである。
温度応答性培養皿の細胞接着面上に形成した薄いシート状の細胞は、温度を変える(低下させる)ことによって皿から離れる。そのため、培養皿の温度をクーラ(ペルチェ)等によって低下させて細胞シートを取り出し、これを、ロボットやアクチュエータによって複数枚を重ね合わせる。重ね合わされた細胞シートは、一体化し、細胞密度の非常に高い新生組織となる。この様に、細胞シート積層化モジュールは、細胞の播種、細胞シート化、細胞シートの剥離、を経て複数の細胞シートを積層化して、移植可能な新生組織を作る工程を担っている。
恒温モジュール(インキュベータ)は、細胞を増殖させたり、新生組織を移植までの間、保存したりするための、ガス濃度、温度、湿度を適切に維持するためにある。
チューブ連結ロボットは、閉鎖空間内にある細胞懸濁液等を他の処理モジュールの閉鎖空間に移動するものである。このチューブ連結モジュールにより一方の処理モジュールと他方のモジュール間のチューブを連結または離脱させることができる。このモジュールによれば、ソケット(接続部又は接続コネクタ)の連結または離脱時も無菌性、密閉性を維持する。なお、このモジュールは、チューブにより処理モジュール間等で懸濁液を輸送する場合に使用することができる。
自動倉庫モジュールは、培養する細胞や組織に必要な、培養液(培地)、グロースファクター、薬剤、細胞、容器等を保管し、培養する細胞等に応じて、自動的に出庫し、搬出入モジュールや各処理モジュールの機器搬入様ドア部から各処理モジュールに供給する。
搬送用レーンモジュールは、各モジュールの閉鎖空間やチューブ連結モジュールのチューブを結合させるために所定の場所に誘導するためのガイドである。このガイドは、金属性のテープあるいは、レール、ガイドポストなどが使われる。なお、このようなモジュールは、自動でチューブを接続する場合に使用することができる。
その他モジュールは、三次元スキャフォルドを用いて三次元新生組織を形成する三次元化モジュール処理モジュール、種々のバイオリアクタや圧力、引っ張り、圧縮などのストレス・ストレインを与えるモジュール、輸送のためのパッケージングを行う包装モジュールなどを付加する場合がある。
本発明の統合制御装置について図9を参照して以下に説明する。
本実施例のモジュールは、他のモジュールとの間で電気信号を送受信する制御装置を備える。また、制御装置は、統合制御装置との間で電気信号を送受信することができる。
統合制御装置は、各モジュールの動作の連係をとり(プログラムに従って、個別の処理モジュールに電気的な命令を送受信して動作させ)もしくは、培養の経過や環境状態の変化を記録し、データベースを管理する(各処理モジュールの制御装置からの情報を収集して管理する)。さらに統合制御装置は、前記データを、外部のプリンタやコンピュータ、記憶装置にユーザの要求に応じて電気信号を出力する。
A1.操作者は入力モジュールによりIDおよびパスワードを入力する。入力モジュールからの電気的信号を統合制御装置が受ける。統合制御装置は、操作者の権限によって可能な操作内容を区別する。さらに、権限のある操作者は、入力モジュールから患者ID、培養条件、等の必要な項目を入力する。
これによって、操作者は、統合制御装置内に組み込まれた種々の運転手順のプログラムの中から、適切な運転手順のプログラムが選択することができる。
A2.運転に使われる各モジュールは、運転準備が完了している旨の信号をそれぞれ統合制御装置に発信する。
A3.統合制御装置は運転に関与する各モジュールからの運転準備完了信号を確認する。
A4.確認ができたら、統合制御装置は、モジュールの第1の閉鎖空間V1同士を接続する指令を各モジュールに出す。
A5.接続したモジュールの制御装置は、確実に接続をしたことをセンサ等でチェックする。
A6.確実に接続の完了をしたことを確認したらモジュールの制御装置から統合制御装置に発信する。
A7.統合制御装置は、除染剤供給モジュールに除染工程開始の指示を出す。
A8.除染剤供給モジュールにより第1の閉鎖空間V1および第2の閉鎖空間V2の除染が実行される。
A9.除染が完了すると除染剤供給モジュールから統合制御装置に除染完了信号が発信される。(各モジュールの除染状態(除染済みか未除染か)はモジュールIDとともに統合制御装置に記憶される。
A7.除染・除菌完了の信号を受けた統合制御装置は、最初に運転するモジュールにプログラムによる運転の指令を与える。
A8.運転指令を受けたモジュールは、指示されたプログラムで運転する。
A9.運転中のモジュールは、動作の時刻、環境データ、チェックポイントの確認結果など、あらかじめ定められた項目のデータを定期的に統合制御装置に送る。これらのデータは、各モジュールでも保存してもよい。
A10.統合制御装置は送られてきたデータをデータベースに保存する。
A11.モジュールの運転中に不具合や異常が発生したことが検知された場合、このデータは統合制御装置に発信される。この内容によっては、モジュール内部で復旧作業が自動で行われる。復旧した場合は、そのデータ(内容や時刻など)を統合制御装置に発信する。
A12.統合制御装置は、異常データや修復データをデータベースに保存する。
A13.モジュール内のプログラムが終了したら、終了信号を統合制御装置に発信する。
A14.統合制御装置は、モジュールを分離する必要があるときは分離指令を発信し、モジュールを結合する必要があるときは分離指令を発信する。途中で結合するときは、新たに結合するモジュールのモジュールIDから除染・除菌状態を確認してから実施する。
A15.以下、次の各モジュールの運転をA2~A14まで繰り返す。
A16.全て終了したら、各モジュールから送られた各種データを検体ごとの一連のデータとして保存し、必要に応じて、他の記憶装置やプリンタなどに出力させる。
試薬ボトル81を搬送するための試薬ボトルブラケット82には、試薬ボトル81を立てた状態で搬送できるように試薬ボトルブラケット82上にガイド部材82aを取り付けている。
また、複数システムを設置して、各病院から持ち込まれる組織を引き受けて培養する、細胞、組織の培養ビジネスの創出にも寄与する。
11 搬送モジュール
12 分注モジュール
13 恒温モジュール
14 細胞シート積層化モジュール
15 培養プレート等の搬出入モジュール
16 着脱手段
Claims (6)
- 相互に接続可能である複数のモジュールと、
前記モジュールに設ける第1の閉鎖空間と、
前記第1の閉鎖空間に設ける開口部を開閉する扉と、
前記開口部の周縁部に設ける接続部材と、
除染剤を供給する除染剤供給モジュールと、
を備え、
前記徐染剤供給モジュールにより前記第1の閉鎖空間に前記除染剤を供給し、接続する一方の前記モジュールの前記接続部材及び前記扉と他方の前記モジュールの前記接続部材と前記扉で形成する第2の閉鎖空間に前記除染剤を供給し、接続した複数の前記モジュールを無菌状態に保った一体的な閉鎖空間にすることを特徴とする細胞培養処理システム。 - 命令に応じてモジュールが所定の処理を実行するよう制御するモジュール制御装置と、
前記接続部材を介して接続されている前記モジュールの前記モジュール制御装置と電気的に接続されており、前記各モジュールの動作を制御する統合制御装置と、
を備え、
前記統合制御装置により、前記接続された複数の前記モジュールと通信を行い、前記モジュールのIDを認識して、前記IDに応じた動作命令を前記モジュールに対して行うことで、接続した複数の前記モジュールを関連付けて各種培養処理の一連の処理工程を統合処理し、又は別々に各種細胞培養処理を実行することを特徴とする請求項1記載の細胞培養処理システム。 - 内部に搬送ロボットを備えており、前記各モジュールが接続される搬送モジュールを備え、
前記搬送ロボットにより、接続された1のモジュールの前記第1の閉鎖空間から他のモジュールの前記第1の閉鎖空間へ、前記第2の閉鎖空間を介して被搬送物を移動させることを特徴とする請求項1または2に記載の細胞培養処理システム。 - 前記接続部材は、内部が中空形状であるシール部材と、前記シール部材の内部に気体等注入手段とを備えており、前記シール部材を膨張させて前記第2の閉鎖空間内を密閉にシールすることを特徴とする請求項1乃至3のいずれか1項に記載の細胞培養処理システム。
- 前記接続部材を介して複数の前記モジュールを接続する工程と、
複数の前記接続部材と複数の前記扉により形成される前記第2の閉鎖空間に、前記除染剤供給モジュールより前記除染剤を供給して前記第2の閉鎖空間内を除染する工程と、
前記扉を開けて前記第1の閉鎖空間及び前記第2の閉鎖空間を連通して一体の無菌閉鎖空間を形成する工程とを備えることを特徴とする請求項1乃至4の何れか1項に記載の細胞培養処理システムのモジュール接続方法。 - 複数の前記モジュールを、隙間をあけて設置する工程と、複数の前記モジュールに備えるシール部材を、前記隙間を埋めるように膨張させて複数の前記モジュールを接続する工程と、複数の前記接続部材と複数の前記扉により形成される前記第2の閉鎖空間に前記除染剤供給モジュールからの前記除染剤を供給して前記第2の閉鎖空間内を除染する工程と、前記扉を開けて前記第1の閉鎖空間及び前記第2の閉鎖空間を連通して一体の無菌閉鎖空間を形成する工程とを備えることを特徴とする請求項4に記載の細胞培養処理システムのモジュール接続方法。
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004350640A (ja) | 2003-05-30 | 2004-12-16 | Olympus Corp | 培養処理装置および自動培養装置 |
JP2005253331A (ja) * | 2004-03-10 | 2005-09-22 | Ishikawajima Harima Heavy Ind Co Ltd | 培養システム及び方法 |
JP2006115798A (ja) * | 2004-10-25 | 2006-05-11 | Kawasaki Heavy Ind Ltd | オートクレーブ滅菌を利用した自動細胞培養装置及びその使用方法 |
JP2008054690A (ja) | 2007-10-11 | 2008-03-13 | Kawasaki Heavy Ind Ltd | 自動細胞培養装置及びその使用方法 |
JP2011004613A (ja) | 2009-06-23 | 2011-01-13 | Cellseed Inc | 採取物調製用パーソナルボックスおよび採取物調製システムならびに採取物調製方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3907389A (en) * | 1973-12-12 | 1975-09-23 | Marion E Cox | Glove box chamber |
US5892200A (en) * | 1996-09-19 | 1999-04-06 | The Boc Group, Inc. | Transfer port system |
CN1219049C (zh) * | 2002-04-26 | 2005-09-14 | 叶大林 | 无菌隔离操作系统 |
EP1612262A4 (en) | 2003-04-09 | 2009-07-22 | Olympus Corp | DEVICE FOR TREATING CULTURES AND AUTOMATIC DEVICE FOR TREATING CULTURES |
JP4300863B2 (ja) * | 2003-04-25 | 2009-07-22 | 澁谷工業株式会社 | 無菌システムとその使用方法 |
-
2012
- 2012-01-05 CN CN201280005645.3A patent/CN103370409B/zh not_active Expired - Fee Related
- 2012-01-05 WO PCT/JP2012/050064 patent/WO2012098931A1/ja active Application Filing
- 2012-01-05 EP EP12736296.0A patent/EP2604679B1/en not_active Not-in-force
- 2012-01-05 JP JP2012520847A patent/JP5051677B2/ja not_active Expired - Fee Related
- 2012-01-05 KR KR1020137021658A patent/KR101361025B1/ko active IP Right Grant
-
2013
- 2013-01-18 US US13/745,247 patent/US9279099B2/en not_active Expired - Fee Related
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004350640A (ja) | 2003-05-30 | 2004-12-16 | Olympus Corp | 培養処理装置および自動培養装置 |
JP2005253331A (ja) * | 2004-03-10 | 2005-09-22 | Ishikawajima Harima Heavy Ind Co Ltd | 培養システム及び方法 |
JP2006115798A (ja) * | 2004-10-25 | 2006-05-11 | Kawasaki Heavy Ind Ltd | オートクレーブ滅菌を利用した自動細胞培養装置及びその使用方法 |
JP2008054690A (ja) | 2007-10-11 | 2008-03-13 | Kawasaki Heavy Ind Ltd | 自動細胞培養装置及びその使用方法 |
JP2011004613A (ja) | 2009-06-23 | 2011-01-13 | Cellseed Inc | 採取物調製用パーソナルボックスおよび採取物調製システムならびに採取物調製方法 |
Non-Patent Citations (1)
Title |
---|
See also references of EP2604679A4 * |
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WO2016042956A1 (ja) * | 2014-09-18 | 2016-03-24 | 富士フイルム株式会社 | 細胞培養装置および方法 |
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US11168297B2 (en) | 2015-03-31 | 2021-11-09 | Thrive Bioscience, Inc. | Cell maintainer for autologous cell therapy production |
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Also Published As
Publication number | Publication date |
---|---|
EP2604679B1 (en) | 2016-09-28 |
KR20130105743A (ko) | 2013-09-25 |
EP2604679A1 (en) | 2013-06-19 |
US20130130361A1 (en) | 2013-05-23 |
JPWO2012098931A1 (ja) | 2014-06-09 |
KR101361025B1 (ko) | 2014-02-11 |
JP5051677B2 (ja) | 2012-10-17 |
EP2604679A4 (en) | 2013-12-25 |
US9279099B2 (en) | 2016-03-08 |
CN103370409B (zh) | 2017-05-10 |
CN103370409A (zh) | 2013-10-23 |
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