WO2018154833A1 - Système de culture cellulaire - Google Patents

Système de culture cellulaire Download PDF

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Publication number
WO2018154833A1
WO2018154833A1 PCT/JP2017/036228 JP2017036228W WO2018154833A1 WO 2018154833 A1 WO2018154833 A1 WO 2018154833A1 JP 2017036228 W JP2017036228 W JP 2017036228W WO 2018154833 A1 WO2018154833 A1 WO 2018154833A1
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WO
WIPO (PCT)
Prior art keywords
chamber
aseptic
isolator
connection port
incubator
Prior art date
Application number
PCT/JP2017/036228
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English (en)
Japanese (ja)
Inventor
秀和 金澤
真昭 友永
Original Assignee
川崎重工業株式会社
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Filing date
Publication date
Application filed by 川崎重工業株式会社 filed Critical 川崎重工業株式会社
Publication of WO2018154833A1 publication Critical patent/WO2018154833A1/fr

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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
    • 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

Definitions

  • the present invention relates to a cell culture system including an isolator in which a working chamber capable of ensuring sterility is provided, and a sterile chamber that is detachably connected to the isolator.
  • Patent Documents 1 and 2 disclose techniques related to this type of cell culture system.
  • the culture apparatus described in Patent Document 1 includes an isolator in which a culture work chamber is provided, and an incubator connected to the isolator via a sterile connection apparatus.
  • the incubator is mounted on the carriage and is movable. When the incubator is connected to the isolator, the work room of the isolator and the inside of the incubator are communicated with each other while maintaining sterility.
  • this culture apparatus by replacing the incubator connected to the isolator, it is possible to culture a large amount and various types of cells with one isolator.
  • Patent Document 2 discloses a personal box including a plurality of storage chambers that are independent closed spaces. Of the plurality of storage chambers of the personal box, at least one is configured as an incubator, and the other is configured as a cold storage for storing articles associated with cells stored in the incubator. In this personal box, the incubator and the low temperature storage are handled together to prevent cross-contamination between cells from different subjects and prevention of material (including culture vessels) and cells. .
  • the present invention has been made in view of the above circumstances, and an object of the present invention is to simplify connection work by an operator when an aseptic chamber is connected to an isolator.
  • a cell culture system includes a cell culture system including an isolator in which a working chamber that is maintained in a sterile state is provided, and a movable sterile chamber that is detachably connected to the isolator.
  • the isolator has an isolator side aseptic connection port for communicating the working chamber with the inside of the aseptic chamber
  • the aseptic chamber has a chamber side aseptic connection port connected to the isolator side aseptic connection port,
  • a loading position where the isolator side aseptic connection port and the chamber side aseptic connection port are aligned in the vertical direction and the width direction and face each other with a predetermined interval, the isolator side aseptic connection port and the chamber
  • the joint position where the side aseptic connection port joins is defined, A guide device for guiding the movement of the sterile chamber to the loading position; And an attracting device that draws the aseptic chamber from the loading position to the joining position toward the isolator.
  • the sterile chamber is guided to the guide device and moved to the loading position. Therefore, high accuracy is not required for the operator who moves the sterile chamber. Further, according to the cell culture system, when the sterile chamber is moved from the carry-in position to the joining position, an operation for carefully adjusting the force applied by the operator to the sterile chamber is omitted. Therefore, when connecting the aseptic chamber to the isolator, the connection work by the operator can be simplified.
  • the guide device includes a rail and a guided member that is provided in the aseptic chamber and is guided by the rail.
  • the height from the floor may be the same as or higher than the height of the guided member from the floor.
  • the guided member is guided by the rail, so that the vertical position and the width direction position of the chamber-side sterile connection port with respect to the isolator-side sterile connection port are simultaneously positioned.
  • the cell culturing system receives a detection signal from the carry-in sensor that detects that the sterile chamber has been carried into the carry-in position, and receives the detection signal from the carry-in sensor, and starts the drawing of the sterile chamber. And a control device for controlling the operation of the above.
  • the drawing device automatically operates to automatically join the isolator side sterile connection port and the chamber side sterile connection port.
  • the attracting device may apply a force to the aseptic chamber to maintain pressure contact between the isolator-side aseptic connection port and the chamber-side aseptic connection port.
  • an openable / closable incubator having an independent closed space and at least one openable / closable storage having an independent closed space are provided in the aseptic chamber, Materials related to cells stored in the incubator may be stored.
  • the incubator and the storage are arranged vertically in the aseptic chamber, and the aseptic connection port on the chamber side is an opening having an area larger than the surface area of the door of the incubator and the door of the storage. May have a part.
  • the aseptic connection port is not required for the opening / closing part of the incubator or the storage. Therefore, it is sufficient to provide a set of aseptic connection ports for connecting the inside of the incubator or the storage room and the work room. Thereby, the configuration of the cell culture system is simplified, and in addition, the cost can be reduced.
  • FIG. 1 is a diagram showing an overall configuration of a cell culture system according to an embodiment of the present invention.
  • FIG. 2 is a plan view of the cell culture system.
  • FIG. 3 is a block diagram showing the configuration of the control system of the cell culture system.
  • FIG. 4 is a view of the incubator unit as viewed from the front side.
  • FIG. 5 is a view showing a state of the incubator unit with the panel removed in FIG.
  • FIG. 6 is a schematic diagram showing the configuration of the sterile connection port.
  • FIG. 7 is an enlarged view of the sealing structure portion of the sterile connection port.
  • FIG. 8 is an enlarged view of the sealing structure portion of the sterile connection port.
  • FIG. 9 is a schematic view showing a state in which the door of the incubator of the incubator unit is opened.
  • FIG. 1 is a diagram showing an overall configuration of a cell culture system 1 according to an embodiment of the present invention
  • FIG. 2 is a plan view of the cell culture system 1
  • FIG. 3 is a configuration of a control system of the cell culture system 1
  • FIG. FIGS. 1 and 2 show a state in which the incubator unit 4 is connected to one of the two aseptic connection ports 8 provided in the culture unit 2.
  • a cell culture system 1 includes a culture unit 2, a pass box unit 3 connected to the culture unit 2, and a culture unit 2 detachably connected.
  • the incubator unit 4 and a control device 6 for controlling the operation of the cell culture system 1 are provided.
  • the surface of the culture unit 2 to which the incubator unit 4 is connected is referred to as the front surface of the culture unit 2.
  • cultivation unit 2 among the incubator units 4 be the front surface of the incubator unit 4.
  • the culture unit 2 includes an isolator 20 that can ensure sterility, and a working chamber 21 is formed inside the isolator 20.
  • the isolator 20 is a box that can be sealed, and has a decontamination function for decontaminating the work chamber 21.
  • Examples of the decontamination function include a ventilator that ventilates the work chamber 21, a hydrogen peroxide decontamination device that ejects hydrogen peroxide mist into the work chamber 21, a UV lamp that emits ultraviolet rays that perform spot-like sterilization, An internal environment sensor for monitoring the environment of the chamber 21 may be included.
  • the sterility of the work chamber 21 is ensured by the decontamination function and the pressure difference inside and outside the work chamber 21.
  • the work chamber 21 has an operation stage, a transfer robot that transports the culture container, a monitoring camera that reflects the interior of the work chamber 21, a waste chamber that collects waste, and an ID read that reads an ID tag attached to the culture container, chemical container, etc.
  • a device, a storage, and the like are provided (all not shown).
  • Each work stage is provided with a machine, an inspection device, a container, a chemical solution shelf, etc. that automatically perform work according to the content of the work (all not shown).
  • the work stage includes at least one of work stages related to a culture process such as a cell observation stage, a centrifuge stage, a tapping stage, a capper stage, a heating stage, a culture stage, and a loading / unloading stage. Good.
  • the aseptic connection port 8 is provided on the front wall forming the front surface of the isolator 20.
  • the culture unit 2 according to this embodiment includes two aseptic connection ports 8 and can connect two incubator units 4 at the same time.
  • the number of aseptic connection ports 8 provided in the culture unit 2 is not limited to this embodiment.
  • the structures of the two aseptic connection ports 8 are substantially the same, and each aseptic connection port 8 is provided with an opening 81 that penetrates the wall of the isolator 20, and includes a shutter 82 that seals the opening 81. It has been.
  • the structure of the sterile connection port 8 will be described in detail later.
  • a piping / wiring interface 25 is provided on the front wall of the isolator 20 and below each aseptic connection port 8.
  • the piping / wiring interface 25 is connected to a piping / wiring interface 77 of the incubator unit 4 described later.
  • a guide member 26 is provided on the front wall of the isolator 20 and below each piping / wiring interface 25.
  • the guide member 26 is for guiding the movement of the incubator unit 4 when connecting the culture unit 2 and the incubator unit 4.
  • the guide member 26 of the culture unit 2 according to the present embodiment is a pipe having a U-shape in plan view including two rail portions 26a extending in a direction orthogonal to the main surface of the shutter 82 of the aseptic connection port 8.
  • the culture unit 2 is provided with a pair of attracting devices 28 in the vertical direction.
  • the drawing device 28 according to the present embodiment includes a rod 28b extending in a horizontal direction perpendicular to the main surface of the shutter 82 from the front wall of the isolator 20, an arm 28a provided at the tip of the rod 28b, and a rod 28b. It is a rotary clamp cylinder provided with the mechanism extended and contracted in a longitudinal direction. The longitudinal direction of the rod 28b and the longitudinal direction of the arm 28a are orthogonal to each other.
  • the posture of the arm 28a is changed between a posture in which the arm 28a protrudes downward from the rod 28b and a posture in which the arm 28a protrudes in the horizontal direction from the rod 28b. Can do.
  • the operation of the attracting device 28 is controlled by the control device 6.
  • the pass box unit 3 is connected to the front wall of the isolator 20 of the culture unit 2.
  • the interior of the pass box unit 3 can communicate with the work chamber 21, and materials such as culture containers and chemicals are taken into and out of the work chamber 21 through the pass box unit 3.
  • the pass box unit 3 is a decontamination pass box including a decontamination function, an ID reading device that reads an ID tag attached to a culture container, a chemical container, and the like, and a work glove (all not shown).
  • the decontamination function may be a ventilation device, a UV light, an internal environment sensor, or the like.
  • FIG. 4 is a view of the incubator unit 4 as seen from the front side
  • FIG. 5 is a view showing the state of the incubator unit 4 with the panel 72 removed in FIG.
  • the incubator unit 4 includes a box-shaped aseptic chamber 41 that can be sealed.
  • a sterile connection port 7 connected to the sterile connection port 8 of the culture unit 2 is provided on the front surface of the sterile chamber 41.
  • the aseptic connection port 7 is provided with an opening 71 that penetrates the wall of the aseptic chamber 41, and a panel 72 that seals the opening 71 is provided.
  • the aseptic connection port 7 will be described in detail later.
  • a piping / wiring interface 77 is provided in front of the aseptic chamber 41 and below the aseptic connection port 7.
  • the piping / wiring interface 77 is provided with an incubator unit side wiring connector and an incubator unit side piping connector.
  • the culture unit side wiring connector and the culture unit side piping connector are provided in the above-described piping / wiring interface 25 of the culture unit 2.
  • the culture unit side wiring connector and the incubator unit side wiring connector to be connected are arranged at corresponding positions so as to be connected when the piping / wiring interfaces 77 and 25 are joined.
  • the connector of the culture unit side piping to be connected and the connector of the incubator unit side piping are arranged at corresponding positions so as to be connected when the piping / wiring interfaces 77 and 25 are brought into contact with each other.
  • Each connector employs a connector that is connected by a butting operation.
  • a wheel 42 is provided at the bottom of the aseptic chamber 41, and the incubator unit 4 is movable.
  • wheels 42 are provided at each of the four corners of the bottom surface of the aseptic chamber 41.
  • the incubator unit 4 may include driving wheels and be configured to automatically travel by remote control or a program.
  • a guided member 43 that is guided by the guide member 26 provided in the culture unit 2 is provided.
  • a guide device 9 that guides the movement of the sterile chamber 41 is constituted by the guide member 26 and the guided member 43.
  • the guided member 43 is a pulley having a U-shaped or V-shaped circumferential groove into which a pipe as a guiding member is fitted.
  • the guided member 43 is not limited to the pulley, and may be a member guided by the guide member 26.
  • a pair of pulleys is provided on each of the front side and the rear side of the sterilization chamber 41.
  • engaging members 48 that can engage with the arms 28a of the attracting device 28 provided in the culture unit 2 are provided.
  • the engaging member 48 according to the present embodiment is a block-like member protruding from the side surface of the sterilization chamber 41.
  • the engaging member 48 is not limited to this embodiment as long as the arm 28a of the attracting device 28 can be engaged.
  • an incubator 44 and at least one storage 45 are provided in the aseptic chamber 41.
  • the incubator 44 is a constant temperature incubator having a container that can be closed and having a function of adjusting the container to a temperature and humidity suitable for cell culture.
  • a door 441 is provided on the front surface of the incubator 44, and the door 441 is opened and closed by an automatic opening / closing device 442 (see FIG. 3).
  • the automatic opening / closing device 442 of the incubator 44 is constituted by, for example, an electric motor or the like, and its operation is controlled by the control device 6.
  • the incubator unit 4 is provided with a low temperature storage 45a and a room temperature storage 45b as the storage 45.
  • the room temperature storage 45 b is disposed on the side of the incubator 44.
  • the room temperature storage 45b is a shelf exposed to the inside of the sterile chamber 41.
  • the low temperature storage 45 a is disposed below the incubator 44. That is, the incubator 44 and the low temperature storage 45a are arranged side by side.
  • the low-temperature storage 45a is a box having an accommodating portion that can be closed, and includes a door 451 provided on the front surface and an automatic opening / closing device 452 (see FIG. 3) for the door 451.
  • the automatic opening / closing device 452 of the storage 45 is constituted by, for example, an electric motor or the like, and its operation is controlled by the control device 6. Furthermore, the low temperature storage 45a is provided with a cooling mechanism that cools the storage portion and keeps it at a low temperature.
  • the storage 45 stores materials associated with cells stored in the incubator 44.
  • materials associated with cells stored in the incubator 44 include a medium, an additive, a reagent, and the like that are specific to the donor who collected the cells accommodated in the incubator 44.
  • FIG. 6 is a schematic diagram showing the configuration of the sterile connection ports 8 and 7.
  • the aseptic connection port 8 of the culture unit 2 includes a shutter 82 that can seal the opening 81, an automatic opening / closing device 80 for the shutter 82, and a shutter lock 83.
  • the shutter 82 is supported by the isolator 20 so as to be rotatable about a rotation shaft 82a extending in the vertical direction. That is, the shutter 82 is a door that can be pulled into the work chamber 21. However, the shutter 82 may be configured as a sliding door that opens and closes the opening 81 by sliding parallel to the main surface.
  • the automatic opening / closing device 80 is a device that moves the shutter 82 between a closed position (see FIG. 6) for sealing the opening 81 and an open position (see FIG. 9).
  • the shutter 82 in the closed position is held in the opening 81 by the shutter lock 83.
  • the shutter lock 83 according to the present embodiment includes a lever that restricts the movement of the shutter 82 from the closed position, and a lever drive unit.
  • the opening edge of the opening 81 is edged by an endless seal member 84.
  • the surface of the shutter 82 is bordered by an edge frame 85.
  • An endless seal member 88 is provided so as to surround the area exposed to the outside air in the shutter 82.
  • a seal member 88 is provided on the surface of the edge frame 85.
  • An electromagnet 86 is provided on the surface of the shutter 82.
  • the electromagnets 86 are provided at the four corners of the outer surface, but the number and arrangement of the electromagnets 86 are not limited thereto. Generation and disappearance of the magnetic force of the electromagnet 86, that is, supply of current to the electromagnet 86 is controlled by the control device 6.
  • the aseptic connection port 7 of the incubator unit 4 includes a panel 72 capable of sealing the opening 71 described above.
  • the opening 71 of the incubator unit 4 and the opening 81 of the culture unit 2 are substantially the same or similar in shape.
  • the shutter 82 and the panel 72 have substantially the same shape and have shapes corresponding to the openings 81 and 71.
  • these openings 81 and 71 have a rectangular shape whose longitudinal direction is the vertical direction, and conventionally, the door 441 of the incubator 44 and the door 451 of the storage 45 arranged side by side can pass through.
  • the opening area is sufficiently larger than the opening of the isolator 20.
  • the opening areas of the openings 81 and 71 are larger than the area obtained by adding the surface area of the door 441 of the incubator 44 and the surface area of the door 451 of the storage 45.
  • the shape of the openings 81 and 71 is not limited to a rectangle, and may be a circle including an ellipse or a polygon.
  • the panel 72 is detachable from the aseptic chamber 41 and is held in the opening 71 by a panel lock 73.
  • the panel lock 73 according to the present embodiment is composed of a rotation advance type pin and its drive unit, and is provided at four locations around the panel 72.
  • the opening edge of the opening 71 of the aseptic chamber 41 is edged by an endless seal member 74.
  • the panel 72 is bordered by an edge frame 75.
  • a metal plate 76 is attached to the surface of the panel 72 at a position corresponding to the electromagnet 86 provided on the shutter 82.
  • the electromagnet 86 and the metal plate 76 constitute a magnetic electronic lock.
  • the panel 72 is provided with an adsorption sensing device 79 that detects that the panel 72 is adsorbed to the shutter 82 by the electromagnet 86 adsorbing the metal plate 76.
  • control device 6 is a so-called computer, and includes an arithmetic processing unit such as a CPU and a storage unit such as a ROM and a RAM (all not shown).
  • the storage unit stores a control program executed by the control device 6, various fixed data, and the like.
  • the arithmetic processing unit transmits / receives data to / from an external device.
  • the arithmetic processing unit inputs detection signals from various sensors and outputs control signals to each control target.
  • processing for controlling various operations of the cell culture system 1 is performed by the arithmetic processing unit reading and executing software such as a program stored in the storage unit.
  • the control device 6 may execute each process by centralized control by a single computer, or may execute each process by distributed control by cooperation of a plurality of computers. Moreover, the control apparatus 6 may be comprised from the microcontroller, the programmable logic controller (PLC), etc.
  • PLC programmable logic controller
  • the control device 6 is wirelessly connected to the automatic opening / closing device 442 of the incubator 44, the automatic opening / closing device 452 of the storage 45, the panel lock 73, the automatic opening / closing device 80 of the shutter 82, the attracting device 28, the electromagnet 86, and the shutter lock 83. They are connected so that they can communicate with each other by wire, and control their operations. Further, the control device 6 is connected to detection devices such as the adsorption sensing device 79 and the carry-in sensor 89 so as to be communicable wirelessly or by wire, and can receive a detection signal therefrom.
  • the incubator unit 4 is stored in a storage location not shown. When culturing the cells housed in the incubator 44, the incubator unit 4 is moved from the storage location and connected to the culture unit 2. First, the operator moves the incubator unit 4 to the front of the sterile connection port 8 of the culture unit 2 so that the sterile connection port 8 of the culture unit 2 and the sterile connection port 7 of the incubator unit 4 face each other (FIG. 2, reference). A handle may be provided on the back of the sterilization chamber 41 so that the operator can push and move the incubator unit 4.
  • the operator aligns the guide member 26 of the culture unit 2 and the guided member 43 of the incubator unit 4.
  • the rail portion 26 a of the guide member 26 is inserted between the pair of pulleys so that the rail portion 26 a of the guide member 26 fits into the groove of the pulley that is the guided member 43.
  • the operator moves the sterile connection port 7 of the incubator unit 4 closer to the sterile connection port 8 of the culture unit 2.
  • the incubator unit 4 reaches a loading position defined in advance in the incubator unit 4 (sterile chamber 41).
  • the aseptic connection port 7 is aligned with the aseptic connection port 8 in the vertical direction and the width direction, and faces each other with a predetermined interval.
  • the fact that the aseptic connection ports 8 and 7 are aligned in the vertical direction and the width direction means that the main surface of the panel 72 and the main surface of the shutter 82 face each other in parallel, and the vertical direction of the panel 72 with respect to the shutter 82 It means that the position in the direction and the width direction are matched.
  • the height from the floor of the rail portion 26a of the guide member 26 is the same as or slightly higher than the height from the floor of the pulley that is the guided member 43 in at least the portion including the transport position in the guide member 26.
  • the carry-in sensor 89 is an optical object detection sensor having a light projecting unit and a light receiving unit.
  • the attracting device 28 engages with the engaging member 48 of the incubator unit 4 and draws the incubator unit 4 to the culture unit 2 side to a joining position defined in advance in the incubator unit 4 (sterile chamber 41).
  • the posture of the arm 28a is changed so as to engage with the engaging member 48 of the attracting device 28, and the rod 28b contracts while maintaining the engagement between the arm 28a and the engaging member 48.
  • the aseptic connection port 8 and the aseptic connection port 7 are joined. Specifically, the opening edge of the opening 71 of the incubator unit 4 and the opening edge of the opening 81 of the culture unit 2 are in pressure contact. As shown in FIG. 7, when the seal member 74 at the edge of the opening 71 of the incubator unit 4 is pressed against the seal member 84 at the edge of the opening 81 of the culture unit 2, the seal members 74 and 84 are brought into close contact with each other. To do. In this way, the periphery of the openings 71 and 81 is sealed by the seal members 74 and 84.
  • the attracting device 28 moves the incubator unit 4 at a sufficiently low speed so that the cultured cells accommodated in the incubator unit 4 are not damaged by the impact when the incubator unit 4 contacts the culture unit 2. Furthermore, the attracting device 28 gives the incubator unit 4 a force for holding the pressure contact so that the pressure contact between the sterile connection port 8 and the sterile connection port 7 is maintained.
  • the opening edge of the opening 71 of the incubator unit 4 and the opening edge of the opening 81 of the culture unit 2 are in pressure contact with each other, and at the same time, the piping / wiring interface 25 of the culture unit 2 and the piping / wiring interface 77 of the incubator unit 4. And the corresponding pipes and wirings are connected. Thereby, it is possible to supply power from the culture unit 2 to the incubator unit 4 (or vice versa), a gas such as carbon dioxide and oxygen, a control signal, and the like.
  • the control signal from the control device 6 may be directly transmitted to the incubator unit 4 by radio, or may be transmitted to the incubator unit 4 via the wiring / wiring interface 25 of the culture unit 2.
  • the control device 6 generates a magnetic force in the electromagnet 86.
  • the electromagnet 86 of the shutter 82 strongly attracts the metal plate 76 of the panel 72, so that the panel 72 is attracted to the shutter 82.
  • the edge frame 75 of the panel 72 and the edge frame 85 of the shutter 82 are pressed against each other as shown in FIG.
  • the seal member 88 is crushed. In this way, when not connected, the surface of the panel 72 exposed to the outside air is brought into contact with the surface of the shutter 82, and the periphery thereof is sealed.
  • the control device 6 unlocks the panel lock 73 when the adsorption sensing device 79 detects that the panel 72 is adsorbed to the shutter 82.
  • the panel lock 73 is unlocked, the panel 72 held in the opening 71 of the aseptic chamber 41 becomes free.
  • the control device 6 unlocks the shutter lock 83, further operates the automatic opening / closing device 80, and moves the shutter 82 to the release position as shown in FIGS.
  • the panel 72 that has become free from the opening 71 moves together with the shutter 82.
  • the opening 81 of the culture unit 2 and the opening 71 of the incubator unit 4 are connected, and the working chamber 21 of the culture unit 2 and the interior of the aseptic chamber 41 of the incubator unit 4 ensure sterility. It is communicated by.
  • the control device 6 When the work chamber 21 and the inside of the aseptic chamber 41 communicate with each other, the control device 6 operates the automatic opening / closing device 442 so as to open the door 441 of the incubator 44 according to the content of the next process.
  • the automatic opening / closing device 452 is operated so as to open the door 451 of the storage 45. Since the inside of the aseptic chamber 41 is assured of sterility, there is no restriction on opening and closing of the incubator 44 and the storage 45.
  • the control device 6 When separating the incubator unit 4 from the culture unit 2, the control device 6 operates the automatic opening / closing device 80 so that the shutter 82 moves to the closed position. If the door 441 of the incubator 44 and the door 451 of the storage 45 are open, the automatic opening / closing devices 442 and 452 are operated to close the doors 441 and 451 before the shutter 82 is closed.
  • the control device 6 locks the shutter lock 83 and locks the panel lock 73.
  • the shutter 82 is held in the opening 81 of the isolator 20, and the panel 72 is held in the opening 71 of the aseptic chamber 41.
  • the control device 6 eliminates the magnetic force of the electromagnet 86 and releases the adsorption of the shutter 82 and the panel 72. Further, the control device 6 causes the attracting device 28 to disengage the arm 28a and the engaging member 48, and the opening edge of the opening 81 of the culture unit 2 and the opening edge of the opening 71 of the incubator unit 4 Release the pressure contact. As a result, the connection between the sterile connection port 7 of the incubator unit 4 and the sterile connection port 8 of the culture unit 2 is released. Then, the operator can separate the incubator unit 4 from the culture unit 2 by pulling the incubator unit 4 away from the culture unit 2 along the guide member 26.
  • the cell culture system 1 of the present embodiment includes the isolator 20 in which the working chamber 21 maintained in a sterile state is provided, and the movable aseptic that is detachably connected to the isolator 20. And a chamber 41.
  • the isolator 20 has an isolator side aseptic connection port 8 for communicating the working chamber 21 with the inside of the aseptic chamber 41, and the aseptic chamber 41 has a chamber side aseptic connection port 7 connected to the isolator side aseptic connection port 8. ing.
  • the isolator-side aseptic connection port 8 and the chamber-side aseptic connection port 7 are aligned in the vertical direction and the width direction and face each other with a predetermined interval therebetween, and the isolator-side aseptic connection port 8 And the joining position where the chamber side aseptic connection port 7 is joined is defined.
  • the cell culture system 1 includes a guide device (guide member 26 and guided member 43) for guiding the movement of the sterile chamber 41 to the carry-in position, and a pull for pulling the sterile chamber 41 from the carry-in position to the joining position toward the isolator 20 side. It is characterized by comprising a feeding device 28.
  • the aseptic chamber 41 is guided by the guide device 9 and reliably moves to the loading position. Therefore, when the operator moves the aseptic chamber 41 to the loading position, high accuracy is not required for the operation of the operator. Further, according to the cell culture system 1, the aseptic chamber 41 is moved from the carry-in position to the joining position by the attracting device 28. Therefore, when the operator brings the aseptic chamber 41 close to the isolator 20, an operation for carefully adjusting the force applied to the aseptic chamber 41 by the operator is omitted. As described above, when the aseptic chamber 41 is connected to the isolator 20, the aseptic chamber 41 at the joining position can be satisfactorily positioned with respect to the isolator 20 while simplifying the connection work by the operator. As a result, the sealing accuracy of the aseptic connection ports 8 and 7 can be improved.
  • the guide device 9 includes a rail (rail portion 26a of the guide member 26) and a guided member 43 provided in the aseptic chamber 41 and guided by the rail. Yes. And in the part including the conveyance position at least of the rail, the height from the floor of the rail is the same as or higher than the height from the floor of the guided member 43.
  • the guided member 43 is guided by the guide member 26, whereby the vertical position and the width direction position of the chamber-side sterile connection port 7 with respect to the isolator-side sterile connection port 8 are simultaneously positioned.
  • the cell culture system 1 receives the detection signal from the carry-in sensor 89 and the carry-in sensor 89 that detects that the sterile chamber 41 has been carried into the carry-in position, and starts drawing the sterile chamber 41.
  • the control device 6 for controlling the operation of the drawing device 28 is further provided.
  • the isolator-side sterile connection port 8 and the chamber-side sterile connection port 7 are automatically connected by the guide device 9 and the drawing device 28 provided in the culture unit 2. To be joined.
  • the attracting device 28 is an actuator that applies a force to the sterile chamber 41 to maintain the pressure contact between the joined isolator-side sterile connection port 8 and the chamber-side sterile connection port 7.
  • a force for example, a clamp cylinder.
  • an openable / closable incubator 44 having an independent closed space and at least one openable / closable storage 45 having an independent closed space are provided in the aseptic chamber 41.
  • the storage 45 materials related to cells stored in the incubator 44 are stored.
  • an independent lid is provided for each storage chamber.
  • Each lid is fitted with a connection lid provided at the opening of the isolator, and the inside of the isolator and the accommodation chamber are communicated with each other by opening the lid together with the connection lid. That is, with respect to one personal box, the isolator is provided with a plurality of connection lids, which increases the initial cost. In addition, since it takes time to operate each connection lid, the cycle time becomes long and workability may be reduced.
  • the incubator 44 and the storage 45 are provided in the sterilization chamber 41 in which sterility is ensured. It is unnecessary. Therefore, it is sufficient to provide a set of aseptic connection ports to connect the incubator 44 and the storage 45 containing materials related to the cells contained in the incubator 44 to the isolator 20. Thereby, the configuration of the cell culture system 1 is simplified, and in addition, the cost can be reduced.
  • the incubator 44 and the storage 45 are arranged side by side in the aseptic chamber 41, and the chamber-side aseptic connection port 7 includes the door 441 and the storage of the incubator 44.
  • the opening 71 has an area larger than the surface area of the 45 doors 451.
  • the movable range of the robot installed in the isolator 20 can be expanded through the opening 71, and the robot can move to the incubator 44 and the storage 45. Can be accessed by a relatively simple route.
  • the robot performs the work in the work chamber 21 of the culture unit 2, but an operator may perform the work in addition to / in place of the robot.
  • the guide device 9 that guides the movement of the incubator unit 4 includes a rail as the guide member 26 and a pulley as the guided member 43.
  • the configuration of the guide device 9 is not limited to this embodiment.
  • a rail or a groove on which the wheel 42 of the incubator unit 4 travels may function as the guide device 9.
  • the incubator 44 and the storage 45 are accommodated in the aseptic chamber 41, but one of the incubator 44 and the storage 45 of the aseptic chamber 41 is accommodated. Also good. Further, the sterilization chamber 41 itself connected to the culture unit 2 may be an incubator.
  • the electromagnet 86 (magnet type electronic lock) is used for the adsorption between the panel 72 and the shutter 82.
  • an air adsorption device may be used.
  • a known aseptic connection port may be employed as the aseptic connection ports 8 and 7.

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  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Microbiology (AREA)
  • Biochemistry (AREA)
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  • Virology (AREA)
  • Cell Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne un système de culture cellulaire comprenant un isolateur, ledit isolateur comportant un orifice de connexion aseptique du côté isolant, et une chambre aseptique, ladite chambre aseptique comportant un orifice de connexion aseptique du côté chambre. En ce qui concerne la chambre aseptique, il est spécifié une position de transport, au niveau de laquelle l'orifice de connexion aseptique du côté isolateur et l'orifice de connexion aseptique du côté chambre sont positionnés l'un avec l'autre dans la direction verticale et dans la direction de la largeur et se font face séparés par un espace prédéfini, et une position de jonction, au niveau de laquelle l'orifice de connexion aseptique du côté isolateur et l'orifice de connexion aseptique du côté chambre sont joints l'un à l'autre. Le système de culture cellulaire comprend : l'isolateur ; la chambre aseptique ; un dispositif de guidage pour guider le mouvement de la chambre aseptique vers la position de transport ; et un dispositif de traction pour tirer la chambre aseptique de la position de transport à la position de jonction du côté isolateur.
PCT/JP2017/036228 2017-02-24 2017-10-05 Système de culture cellulaire WO2018154833A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2017-033448 2017-02-24
JP2017033448A JP2018138008A (ja) 2017-02-24 2017-02-24 細胞培養システム

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WO2018154833A1 true WO2018154833A1 (fr) 2018-08-30

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4105873A4 (fr) * 2020-02-13 2024-03-20 Airex Co Ltd Système de journalisation totale

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011050289A (ja) * 2009-08-31 2011-03-17 Shibuya Kogyo Co Ltd 接続装置
WO2015083638A1 (fr) * 2013-12-04 2015-06-11 パナソニックヘルスケアホールディングス株式会社 Système de transport d'incubateurs, unité de stockage d'incubateurs, et système isolateur
JP2016013062A (ja) * 2014-06-30 2016-01-28 澁谷工業株式会社 培養装置
JP2016067232A (ja) * 2014-09-26 2016-05-09 公立大学法人横浜市立大学 細胞培養システム

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011050289A (ja) * 2009-08-31 2011-03-17 Shibuya Kogyo Co Ltd 接続装置
WO2015083638A1 (fr) * 2013-12-04 2015-06-11 パナソニックヘルスケアホールディングス株式会社 Système de transport d'incubateurs, unité de stockage d'incubateurs, et système isolateur
JP2016013062A (ja) * 2014-06-30 2016-01-28 澁谷工業株式会社 培養装置
JP2016067232A (ja) * 2014-09-26 2016-05-09 公立大学法人横浜市立大学 細胞培養システム

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4105873A4 (fr) * 2020-02-13 2024-03-20 Airex Co Ltd Système de journalisation totale

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