WO2018154833A1

WO2018154833A1 - Cell culture system

Info

Publication number: WO2018154833A1
Application number: PCT/JP2017/036228
Authority: WO
Inventors: 秀和金澤; 真昭友永
Original assignee: 川崎重工業株式会社
Priority date: 2017-02-24
Filing date: 2017-10-05
Publication date: 2018-08-30
Also published as: JP2018138008A

Abstract

A cell culture system comprising an isolator, said isolator having an aseptic connection port on the isolator side, and an aseptic chamber, said aseptic chamber having an aseptic connection port on the chamber side. With regard to the aseptic chamber, a carrying-in position, at which the aseptic connection port on the isolator side and the aseptic connection port on the chamber side are positioned with each other in the vertical direction and in the width direction and face each other with a preset space apart, and a joining position, at which the aseptic connection port on the isolator side and the aseptic connection port on the chamber side are joined together, are specified. The cell culture system comprises: the isolator; the aseptic chamber; a guiding device for guiding the movement of the aseptic chamber to the carrying-in position; and a drawing device for drawing the aseptic chamber from the carrying-in position to the joining position on the isolator side.

Description

Cell culture system

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.

In recent years, a large number of cultured cells have been used in the drug discovery research and medical fields, and a system capable of stably culturing a large amount and various types of cells with high quality and stability has been demanded. Therefore, a cell culture system has been proposed that includes an isolator provided with a working chamber capable of ensuring sterility in which cell culture operations such as medium exchange and subculture are performed, and an incubator removable from the isolator. ing.

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. In 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. .

JP 2016-013062 A JP 2011-4613 A

In the cell culture system exemplified in Patent Document 1, when connecting a movable aseptic chamber including an incubator or the like to an isolator, an operator carries the sterile chamber to a connection position with the isolator and positions the sterile chamber with respect to the isolator. . This positioning requires a high degree of accuracy for the operator operating the aseptic chamber to ensure sterility in the aseptic connection device. In addition, when the sterile chamber and the isolator collide when moving the sterile chamber, there is a risk of impacting the contents of the sterile chamber (for example, cultured cells). The chamber must be moved into contact with the isolator.

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 according to an embodiment of the present invention 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. A system,
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,
Regarding the aseptic chamber, 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.

According to the cell culture system, 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.

In the cell culture system, the guide device includes a rail and a guided member that is provided in the aseptic chamber and is guided by the rail. In a portion including at least the carry-in position of the rail, The height from the floor may be the same as or higher than the height of the guided member from the floor.

Thus, 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.

Thus, after the operator carries the sterile chamber to the loading position, the drawing device automatically operates to automatically join the isolator side sterile connection port and the chamber side sterile connection port.

In the cell culture system, 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.

Thus, after the isolator side aseptic connection port and the chamber side aseptic connection port are joined, the joining is held by the attracting device.

In the cell culture system, 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.

In the above case, 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.

As described above, since the incubator and the storage are provided in the aseptic chamber in which sterility is ensured, 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.

According to the present invention, when an aseptic chamber is connected to an isolator, connection work by an operator can be simplified.

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.

Next, an embodiment of the present invention will be described with reference to the drawings. 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, and 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.

As shown in FIGS. 1 to 3, a cell culture system 1 according to an embodiment of the present invention 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. Hereinafter, for convenience of explanation, 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. Moreover, let the surface connected with the culture | cultivation unit 2 among the incubator units 4 be the front surface of the incubator unit 4.

[Structure of culture unit 2]
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. However, 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.

Furthermore, on the front wall of the isolator 20 and on both sides of the aseptic connection port 8, a pair of attracting devices 28 are provided. The culture unit 2 according to this embodiment 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. In this embodiment, when the rod 28b rotates, 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.

[Structure of pass box unit 3]
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). Similar to the isolator 20, the decontamination function may be a ventilation device, a UV light, an internal environment sensor, or the like.

[Structure of incubator unit 4]
4 is a view of the incubator unit 4 as seen from the front side, and FIG. 5 is a view showing the state of the incubator unit 4 with the panel 72 removed in FIG.

As shown in FIGS. 4 and 5, 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. On the other hand, 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. Similarly, 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. By matching the piping / wiring interface 77 of the incubator unit 4 and the piping / wiring interface 25 of the culture unit 2, the corresponding culture unit side piping And incubator unit side piping, corresponding culture unit side wiring and incubator unit side wiring are respectively connected.

A wheel 42 is provided at the bottom of the aseptic chamber 41, and the incubator unit 4 is movable. In the incubator unit 4 according to this embodiment, wheels 42 are provided at each of the four corners of the bottom surface of the aseptic chamber 41. Note that the incubator unit 4 may include driving wheels and be configured to automatically travel by remote control or a program.

Further, at the bottom of the aseptic chamber 41, 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 according to the present embodiment is a pulley having a U-shaped or V-shaped circumferential groove into which a pipe as a guiding member is fitted. However, 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.

On both sides 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. However, the engaging member 48 is not limited to this embodiment as long as the arm 28a of the attracting device 28 can be engaged.

In the aseptic chamber 41, an incubator 44 and at least one storage 45 are provided. 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 according to the present embodiment 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. Specific examples of such a material 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.

[Structure of sterile connection ports 8 and 7]
Here, the sterile connection port 8 of the culture unit 2 and the sterile connection port 7 of the incubator unit 4 will be described. The

aseptic connection ports

8 and 7 are devices for connecting a plurality of aseptic containers without sacrificing sterility for the purpose of aseptic transfer of articles and the like. FIG. 6 is a schematic diagram showing the configuration of the

sterile connection ports

8 and 7.

As shown in FIGS. 1 and 6, 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. Yes. 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. In the present embodiment, 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. In the shutter 82 according to the present embodiment, 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.

As shown in FIGS. 4, 5 and 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.

In the present embodiment, 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. For example, 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. However, 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. Further, 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]
Returning to FIG. 3, the 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. In the control device 6, 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.

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.

[Removal of incubator unit 4 from culture unit 2]
Here, the operation of the cell culture system 1 when the incubator unit 4 is connected to the culture unit 2 having the above configuration will be described.

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.

Next, the operator aligns the guide member 26 of the culture unit 2 and the guided member 43 of the incubator unit 4. In the present embodiment, 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. When the guided member 43 can be guided to the guide member 26 in this way, 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.

As the guided member 43 is guided by the guide member 26, the incubator unit 4 reaches a loading position defined in advance in the incubator unit 4 (sterile chamber 41). When the incubator unit 4 is in the loading position, 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.

In addition, 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. Thereby, by moving the incubator unit 4 along the guide member 26, the vertical position and the width direction position of the sterile connection port 7 with respect to the sterile connection port 8 can be positioned simultaneously.

In this way, when the incubator unit 4 reaches the carry-in position, the control device 6 operates the attracting device 28. The arrival of the incubator unit 4 at the carry-in position is detected by a carry-in sensor 89 provided at the sterile connection port 8. The carry-in sensor 89 according to the present embodiment 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). In this embodiment, 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.

When the incubator unit 4 is in the joining position, 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.

In addition, 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.

Subsequently, the control device 6 generates a magnetic force in the electromagnet 86. Then, 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. When the panel 72 is attracted to the shutter 82 in this manner, 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. Thus, 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. When the panel lock 73 is unlocked, the panel 72 held in the opening 71 of the aseptic chamber 41 becomes free.

Subsequently, 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. As described above, the panel 72 that has become free from the opening 71 moves together with the shutter 82. Thereby, 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.

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.

Subsequently, the operation of the cell culture system 1 when the incubator unit 4 is disconnected from the culture unit 2 will be described.

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.

When the shutter 82 reaches the closed position, the control device 6 locks the shutter lock 83 and locks the panel lock 73. As a result, 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.

Subsequently, 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.

As described above, 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. With respect to the aseptic chamber 41, 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. Then, 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.

According to the cell culture system 1, 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.

In the cell culture system 1 according to the above embodiment, 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.

Thus, 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.

In addition, the cell culture system 1 according to the above embodiment 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.

Thus, after the operator carries the sterile chamber 41 to the carry-in position, 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.

In the cell culture system 1 according to the above embodiment, 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. For example, a clamp cylinder).

Thereby, even after the isolator side aseptic connection port 8 and the chamber side aseptic connection port 7 are joined, the joining is held by the attracting device 28. Therefore, a dedicated mechanism for maintaining the connection of the

aseptic connection ports

8 and 7 becomes unnecessary.

In the cell culture system 1 according to the above embodiment, 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. In the storage 45, materials related to cells stored in the incubator 44 are stored.

In the personal box shown in Patent Document 2, 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.

On the other hand, in the cell culture system 1 according to the above-described embodiment, 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.

In the cell culture system 1 according to the above-described embodiment, 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.

Thus, by providing a larger opening 71 as compared with the prior art, 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 preferred embodiments of the present invention have been described above, but the present invention may include modifications in the specific structure and / or function details of the above embodiments without departing from the spirit of the present invention. . The structure of said cell culture system 1 can be changed as follows, for example.

For example, in the cell culture system 1 according to the above embodiment, 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.

Further, for example, in the cell culture system 1 according to the above embodiment, 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. For example, a rail or a groove on which the wheel 42 of the incubator unit 4 travels may function as the guide device 9.

Further, for example, in the cell culture system 1 according to the above embodiment, 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.

Further, for example, in the

aseptic connection ports

8 and 7 of the cell culture system 1 according to the above embodiment, the electromagnet 86 (magnet type electronic lock) is used for the adsorption between the panel 72 and the shutter 82. Instead, an air adsorption device may be used. Furthermore, a known aseptic connection port may be employed as the

aseptic connection ports

8 and 7.

1: Cell culture system 2: Culture unit 3: Pass box unit 4: Incubator unit 6: Control device 7: (chamber side) Aseptic connection port 8: (isolator side) Aseptic connection port 8: Guide device 20: Isolator 21: Work Chamber 25: Wiring interface 26: Guide member 26a: Rail portion 28: Pulling device 28a: Arm 28b: Rod 41: Aseptic chamber 42: Wheel 43: Guided member 44: Incubator 45: Storage 45a: Low temperature storage 45b: Room temperature storage 48: engagement member 71: opening 72: panel 73: panel lock 74: seal member 75: edge frame 76: metal plate 77: wiring interface 79: adsorption sensing device 80: automatic opening / closing device 81: opening 82 : Shutter 82a: Time Axis 83: shutter lock 84: Seal member 85: edge frame 86: electromagnet 88: Seal member 89: carry-sensor 441: Door 442: automatic opening and closing device 451: Door 452: automatic openers

Claims

A cell culture system comprising an isolator in which a working chamber maintained in a sterile state is provided, and a movable aseptic 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,
Regarding the aseptic chamber, 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;
An attracting device that draws the aseptic chamber from the carry-in position to the joining position toward the isolator,
Cell culture system.
The guide device includes a rail and a guided member provided in the sterile chamber and guided by the rail,
In a portion including at least the carry-in position of the rail, the height of the rail from the floor is the same as or higher than the height of the guided member from the floor,
The cell culture system according to claim 1.
A loading sensor for detecting that the sterile chamber has been loaded into the loading position;
A control device that receives a detection signal from the carry-in sensor and controls the operation of the drawing device to start drawing the sterile chamber;
The cell culture system according to claim 1 or 2.
The attracting device applies a force to the aseptic chamber to maintain a pressure contact between the isolator-side aseptic connection port and the chamber-side aseptic connection port.
The cell culture system according to any one of claims 1 to 3.
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,
In the storage, materials related to cells stored in the incubator are stored,
The cell culture system according to any one of claims 1 to 4.
The incubator and the storage are arranged side by side in the aseptic chamber,
The chamber side aseptic connection port has an opening having an area larger than the surface area of the door of the incubator and the door of the storage.
The cell culture system according to claim 5.