Pass box and cell culture system

Abstract

To provide a pass box that can further reduce the possibility of contamination occurring between first and second chambers.SOLUTION: A pass box includes: a first chamber having a first environment; a second chamber having a second environment; a box body communicating with each of the first chamber and the second chamber and disposed between the first chamber and the second chamber; a first door for switching between an open state and a closed state between the first chamber and the box body; a second door for switching between an open state and a closed state between the second chamber and the box body; a transport mechanism disposed in the box body for transporting a culture vessel between the first chamber and the second chamber; and a control unit for controlling the operation of the transport mechanism, the first door, and the second door. The control unit includes: an opening / closing unit for switching between the open and closed states of the doors; and a determination unit for determining the open and closed states of the doors. When the determination unit determines that one of the doors is in a closed state, the opening / closing unit opens the other door.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present disclosure relates to a pass box and a cell culture system. [Background technology]

[0002] Patent Document 1 discloses a transport mechanism for transporting a culture vessel between two points. Conventionally, a technique has been proposed in which such a transport mechanism is used to sequentially move a culture vessel between a first chamber (incubator) for culturing cells and a second chamber (clean bench) for subjecting the cells to various treatments. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Patent No. 4778984 Summary of the Invention [Problem to be solved by the invention]

[0004] When moving the culture vessel, it is necessary to avoid as much as possible the situation (contamination) in which the atmosphere and various environmental conditions are mixed between the first chamber (incubator) and the second chamber (clean bench). However, in the past, sufficient measures to avoid such contamination were not taken. For this reason, there was an increasing demand for a technology that can further reduce the possibility of contamination occurring.

[0005] The present disclosure has been made to solve the above-mentioned problems, and aims to provide a pass box that can further reduce the possibility of contamination occurring between the first chamber and the second chamber. [Means for solving the problem]

[0006] In order to solve the above problems, the pass box according to the present disclosure includes a first chamber having a first environment, a second chamber having a second environment different from the first environment, a box body communicating with the first chamber and the second chamber, respectively, and provided between the first chamber and the second chamber, a first door switching an open / closed state between the first chamber and the box body, a second door switching an open / closed state between the second chamber and the box body, a transport mechanism provided in the box body and transporting a culture vessel between the first chamber and the second chamber, and a control unit controlling the operation of the transport mechanism and the operation of the first door and the second door, wherein the control unit includes an opening / closing unit switching the open / closed states of the first door and the second door, and a determination unit determining the open / closed states of the first door and the second door, and the opening / closing unit opens the other door when the determination unit determines that one of the first door and the second door is in a closed state.

[0007] The cell culture system of the present disclosure comprises an incubator forming a culture area in which flasks are housed, a clean bench forming a liquid handling area in which dispensing operations are performed on the flasks, a transport device capable of transporting the flasks between the culture area and the liquid handling area, and a pass box capable of transferring the flasks between the incubator and the clean bench. Effect of the Invention

[0008] According to the pass box and cell culture system of the present disclosure, the possibility of contamination occurring between the first chamber and the second chamber can be further reduced. [Brief description of the drawings]

[0009] [Figure 1] FIG. 1 is a schematic plan view showing a schematic configuration of a cell culture system according to a first embodiment of the present disclosure. [Diagram 2] FIG. 2 is a plan view showing a configuration of a pass box according to the first embodiment of the present disclosure. [Diagram 3]11 is a graph showing a change in angular velocity during movement of an arm according to the first embodiment of the present disclosure. [Figure 4] FIG. 2 is a functional block diagram of a control unit according to the first embodiment of the present disclosure. [Diagram 5] 5 is a flowchart showing a control flow of a control unit according to the first embodiment of the present disclosure. [Figure 6] 13 is a graph showing a change in angular velocity during movement of an arm according to a modified example of the first embodiment of the present disclosure. [Figure 7] 11 is a side view showing a main configuration of a pass box according to a second embodiment of the present disclosure. FIG. [Figure 8] 13 is a side view showing a main configuration of a pass box according to a third embodiment of the present disclosure. FIG. [Figure 9] 13 is a plan view showing a configuration of a main part of a pass box according to a modified example common to each embodiment of the present disclosure. FIG. [Figure 10] FIG. 2 is a hardware configuration diagram of a control unit according to each embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] First Embodiment A first embodiment of the present disclosure will be described in detail below with reference to Figures 1 to 6. As shown in Figure 1, a cell culture system 100 of this embodiment is a system that performs cell culture and analysis of the cultured cells using a flask unit 1 as a processing unit, and these processes are performed, for example, unmanned and automatically.

[0011] The flask unit 1 is composed of a flask tray 11 and a plurality of flasks 12 (culture vessels) (for example, two in this embodiment) placed on the flask tray 11. The flasks 12 contain a culture solution including a medium to which cells and nutrients necessary for cell growth have been added.

[0012] <Cell culture system> 1, the cell culture system 100 includes a stocker 110, an incubator 130, a clean bench 140, and a pass box 150. The cell culture system 100 of this embodiment further includes a carry-in booth 120, a measuring device 160, a culture medium supplying device 161, a waste liquid tank 162, and a transporting device 170.

[0013] <Stocker> The stocker 110 is a facility for storing a plurality of flask units 1. The stocker 110 has a stocker body 111, a rack 112, a first stocker door 113, and a second stocker door 114. Stocker body 111 is a housing that forms storage area R1 as a warehouse inside. Stocker body 111 is made of a transparent material such as acrylic or glass. The rack 112 is disposed within the storage area R1 and is capable of storing a plurality of flask units 1 horizontally and vertically.

[0014] The first stocker door 113 is a door for carrying in the flask unit 1 and the like from the outside, and can be opened and closed by sliding, for example, horizontally. The second stocker door 114 is a door for carrying the flask unit 1 out to the clean bench 140, and can be opened and closed by, for example, sliding horizontally.

[0015] <Delivery Booth> The loading booth 120 is a booth used for loading the flask unit 1 and the like from outside into the stocker 110. The loading booth 120 has a booth body 121 and a loading door 122. The booth body 121 is a housing arranged adjacent to the stocker 110 and is made of a transparent material. The space inside the loading booth 120 is a loading space, which can communicate with the storage area R1 via the stocker second door 114. The loading door 122 is a door for loading flask units 1 and the like into the loading booth 120 from the outside, and can be opened and closed, for example, by sliding up and down. The inside of the loading space is controlled, for example, to a negative pressure lower than the atmosphere of the storage area R1. This prevents outside air and the like from entering the stocker 110 when the loading door 122 is open.

[0016] <Incubator> The incubator 130 is a facility for growing cells in a culture solution. The incubator 130 includes an incubator body 131 and a shaking stage 132. The incubator body 131 is a housing that forms a culture area R3 inside. The culture area R3 is controlled to have a temperature, humidity, and carbon dioxide concentration suitable for cell culture. The incubator body 131 is made of a transparent material such as acrylic or glass. The shaking stage 132 is a device for shaking the flask unit 1. A plurality of shaking stages 132 are arranged in the culture area R3, each holding a plurality of flask units 1. The shaking stage 132 is configured to be able to shake the flask unit 1 by, for example, rotating eccentrically about a vertical axis.

[0017] <Clean bench> The clean bench 140 is a facility for performing various operations and treatments on the flask unit 1. The clean bench 140 includes a clean bench main body 141, a dispensing device 142, a waste liquid extracting device 145, and a stage 149.

[0018] The clean bench body 141 is a housing that forms a liquid handling area R4, which is a highly clean and sterile space (bio-clean room) inside. In the clean space, air flows and circulates as a downflow from above to below. The clean bench body 141 is made of a transparent material such as acrylic or glass.

[0019] The dispensing device 142 is provided in the clean room. The dispensing device 142 performs various dispensing operations and other processes for the flask unit 1. It should be noted that not only one but also a plurality of dispensing devices 142 may be provided.

[0020] Waste liquid extractor 145 is provided in liquid handling area R4, and is a device for extracting unused culture liquid from flask 12 of flask unit 1 as waste liquid. A plurality of stages 149 are provided in liquid handling area R4. On stage 149, flask unit 1 is temporarily placed.

[0021] <passbox> The pass box 150 is provided between the incubator 130 (first chamber) and the clean bench 140 (second chamber). The pass box 150 moves the flask 12 body between the incubator 130 and the clean bench 140. The pass box 150 has a box body 151, a first door 152 (first door), a second door 153 (second door), and a rotary transport device 154 (transport device 170).

[0022] The box body 151 is a housing formed so as to be sandwiched between the incubator body 131 and the clean bench body 141 . The first door 152 switches between a communicating state and an unblocked state between the space within the box body 151 and the incubation area R3, for example, by opening and closing in a horizontal direction. Second door 153 switches between a communication state and a non-communication state between the space within box main body 151 and liquid handling area R4, for example, by opening and closing in a horizontal direction. First door 152 and second door 153 are never open at the same time, so that culture area R3 and liquid handling area R4 are not directly connected to each other.

[0023] The rotary transport device 154 is housed in the pass box 150. The rotary transport device 154 is capable of rotating around a vertical axis between the culture area R3 and the liquid handling area R4 while supporting the flask unit 1. When the rotary transport device 154 rotates, the first door 152 and the second door 153 are in an open state, but the first door 152 and the second door 153 are never in an open state at the same time. This allows the flask unit 1 to move between the culture area R3 and the liquid handling area R4 without the culture area R3 and the liquid handling area R4 being directly connected to each other.

[0024] <Measurement equipment> The measuring device 160 is disposed adjacent to the clean bench 140. The measuring device 160 is capable of measuring and analyzing the number of cells in the culture solution. The culture solution dispensed from the flask 12 by the dispensing device 142 is transferred to the measuring device 160 via a tube (not shown).

[0025] <Culture supply device> The culture medium supplying device 161 is disposed adjacent to the clean bench 140. The culture medium supplying device 161 is a device capable of supplying the culture medium contained in the flask 12. The culture medium supplied from the culture medium supplying device 161 is transferred to the dispensing device 142, and is supplied into the flask 12 of the flask unit 1 in the dispensing device 142.

[0026] <Waste tank> The waste liquid tank 162 is disposed adjacent to the clean bench 140. The waste liquid tank 162 is connected to the waste liquid extractor 145 via a tube (not shown). The waste liquid is transferred from the waste liquid extractor 145 to the waste liquid tank 162 via the tube.

[0027] <Transportation equipment> The transfer device 170 is a device for realizing unmanned transfer of the flask unit 1 within the cell culture system 100. The transfer device 170 has a first transfer robot 171, a second transfer robot 172, a third transfer robot 173, a fourth transfer robot 174, and a conveyor 175.

[0028] The first transport robot 171, the second transport robot 172, the third transport robot 173 and the fourth transport robot 174 are each capable of horizontal movement, rotational movement and telescopic movement, and are configured to be able to grasp a flask tray 11 with a gripper provided at the tip. The first transfer robot 171 is provided in the storage area R1. The second transfer robot 172 is provided in the culture area R3. The third transfer robot 173 and the fourth transfer robot 174 are provided in the liquid handling area R4.

[0029] Conveyor 175 is provided in liquid handling area R4, and horizontally transports flask unit 1 placed on its upper surface. Conveyor 175 is disposed along the inner surface of the main body of liquid handling area R4.

[0030] <Cell culture system operation> In the cell culture system 100 configured as described above, cell proliferation is promoted by shaking the culture solution in the flask unit 1 in the incubator 130. The flask unit 1 in which cell proliferation has progressed is transferred to liquid manipulation area R4 via the third transfer robot 173 and the pass box 150. The flask unit 1 transferred to liquid manipulation area R4 is transferred to the dispensing device 142 via the third transfer robot 173. In the dispensing device 142, the culture solution is dispensed from inside the flask 12 of the flask unit 1, and the culture solution is transferred to the measuring device 160. In the measuring device 160, the number of cells in the culture solution is measured, the liquid properties are analyzed, and the like are performed.

[0031] When adding a medium to the flask 12, the flask 12 is transported into the dispensing device 142. Then, in the dispensing device 142, the medium is supplied from a medium supplying device 161 to the flask 12.

[0032] Furthermore, when cell proliferation is carried out using a new flask unit 1, the following procedure is carried out, for example. That is, first, the third transport robot 173 transports the flask unit 1 on the rack 112 that does not contain culture medium into the liquid handling area R4 via the stocker first door 113. The flask unit 1 is transferred to the dispensing device 142 via the third transport robot 173, and the culture medium is supplied.

[0033] At the same time, a proliferated flask tray 11 in which cell proliferation has progressed is transferred to the dispensing device 142. Then, the culture medium in the flasks 12 of this proliferated flask tray 11 is dispensed into the flasks 12 of a new flask tray 11. This completes the subculture operation of the cells into the tray of the new flask tray 11. The flask unit 1 that has undergone the subculture operation is transferred to the incubator 130, where the cells are proliferated.

[0034] Next, the pass box 150 according to this embodiment will be described in detail with reference to Fig. 2 to Fig. 5. The above-mentioned rotary conveying device 154 has an arm driving unit 201, an arm 202, a holding unit 203, and a control unit 204. The arm driving unit 201 is provided in the pass box 150, and is a driving device for rotating an arm 202 extending horizontally from the arm driving unit 201.

[0035] The arm driver 201 rotates the arm 202 around the arm rotation axis X extending in the vertical direction (up-down direction). The arm 202 extends from a base end on the arm driver 201 side in the radial direction of the arm rotation axis X. The tip of the arm 202 has a length that allows it to reach the culture area R3 and the liquid handling area R4 through the first door 152 and the second door 153, respectively. As will be described in detail later, the arm driver 201 is controlled so that the angular velocity of the arm 202 changes during rotation (see FIG. 3). Specifically, the angular velocity increases for a predetermined time from the start of rotation, then takes a constant value, and then the angular velocity becomes zero over a predetermined time. Such changes in angular velocity are repeated until the rotation is completed. In other words, the arm 202 rotates intermittently.

[0036] A holding part 203 capable of holding the flask unit 1 is provided at the tip of the arm 202. The holding part 203 is in the shape of a dish that supports the flask unit 1 from below.

[0037] As shown in Fig. 4, the control unit 204 has an opening / closing unit 301, a determination unit 302, a transport drive unit 303, an adjustment unit 304, and a storage unit 305. The opening / closing unit 301 generates and transmits an electric signal for switching between opening and closing of the above-mentioned first door 152 and second door 153. The determination unit 302 determines the opening / closing state of each of the first door 152 and second door 153. That is, although not shown in detail, the first door 152 and the second door 153 are provided with a microswitch, a light sensor, or the like for detecting the opening / closing state. The determination unit 302 determines whether the first door 152 and the second door 153 are in an open state or a closed state based on the detection results of the microswitch and the light sensor.

[0038] Based on the determination result of determination unit 302, transport drive unit 303 transmits a drive signal to arm drive unit 201 to drive arm 202. For example, when flask unit 1 is moved from culture area R3 toward liquid manipulation area R4, flask unit 1 is taken into box body 151 through first door 152. Thereafter, while rotating arm 202, when it is determined that first door 152 is completely closed, second door 153 is opened and flask unit 1 is delivered to liquid manipulation area R4. In this manner, a state in which first door 152 and second door 153 are simultaneously opened is avoided.

[0039] The adjustment unit 304 generates an electric signal for adjusting the rotation speed (transport speed) of the arm 202 caused by the arm driving unit 201. That is, a signal is sent to the arm driving unit 201 so as to cause the angular velocity change described above with reference to Fig. 3. The storage unit 305 stores information about such angular velocity change in advance.

[0040] Next, the control flow of the control unit 204 will be described with reference to Fig. 5. In this control flow, first, in step S1, the determination unit 302 determines whether the second door 153 is closed or not. If the determination in step S1 is No, step S1 is repeated. If the determination in step S1 is Yes, the first door 152 is opened in step S2. Thereafter, in step S3, the arm 202 is moved to the culture area R3. When the arm 202 reaches the culture area R3, a flask unit 1 (culture vessel) is placed on the holder 203 at the tip of the arm 202 (step S4).

[0041] Next, the arm driving unit 201 rotates the arm 202 to start transporting the flask unit 1 (step S5). When the arm 202 leaves the culture area R3, the opening / closing unit 301 closes the first door 152 (step S6). Then, the determination unit 302 determines whether the first door 152 is completely closed (step S7). If the determination is No in step S7, step S6 is executed again. If the determination is Yes in step S7, the opening / closing unit 301 opens the second door 153 (step S8). Then, the arm driving unit 201 rotates the arm 202 again to transport the flask unit 1 through the second door 153 to the liquid handling area R4 (step S9). Next, the flask unit 1 is delivered to the liquid handling area R4 (step S10). Finally, the arm driving unit 201 returns the arm 202 to its initial position (step S11). This completes the transfer of the flask unit 1 through the pass box 150. This flow is repeated for each flask unit 1 in sequence.

[0042] (Action and effect) Here, when transporting the flask unit 1, it is necessary to avoid as much as possible the situation (contamination) in which the atmosphere and various environmental conditions are mixed between the culture area R3 (incubator 130) and the liquid handling area R4 (clean bench 140). In particular, the culture area R3 and the liquid handling area R4 are different in temperature, humidity, and components in the atmosphere. Therefore, if these environments come into contact with each other, the destruction of the environmental conditions, which is called contamination, occurs. However, in the past, sufficient measures were not taken to avoid such contamination. For this reason, there was an increasing demand for a technology that can further reduce the possibility of contamination occurring. Therefore, the above-mentioned configurations are adopted in this embodiment.

[0043] According to the above configuration, first door 152 and second door 153 are configured to be open only when the other is closed. For this reason, culture area R3 and liquid handling area R4 do not communicate with each other via box body 151. Therefore, different environmental conditions such as atmosphere, pressure, and temperature do not mix between culture area R3 and liquid handling area R4. In other words, contamination can be avoided. As a result, the respective environmental conditions can be stably maintained in culture area R3 and liquid handling area R4, which can further improve the quality of the cells that are ultimately cultured.

[0044] Furthermore, according to the above configuration, the transport speed of the transport mechanism changes between the culture area R3 and the liquid manipulation area R4. In other words, the transport mechanism operates with an acceleration. Therefore, the flask unit 1 is stirred (shaken) by the change in speed. Then, the surface of the culture solution becomes wavy and the surface area increases. This allows more oxygen to be taken in the culture solution. Therefore, more oxygen can be supplied to the cells in the culture vessel. As a result, it is possible to maintain the activity of the cells in a good state even during transport. Furthermore, the stirring of the culture solution also causes the cells to move, so that the activity of the cells can be maintained even better.

[0045] In particular, according to the above configuration, the transport mechanism intermittently repeats transport and stopping, causing the transport speed to change over time. Therefore, the culture vessel is agitated (shaken) every time the speed changes. Therefore, more oxygen can be supplied to the cells in the culture vessel. As a result, it is possible to maintain the activation state of the cells in a better condition even during transport.

[0046] Moreover, according to the above configuration, by rotating the arm 202 by the arm driving unit 201, the flask unit 1 can be quickly transferred between the culture area R3 and the liquid handling area R4. Moreover, since the arm 202 rotates around the arm rotation axis X extending in the vertical direction, the dimensions of the device in the vertical direction can be kept small compared to a configuration in which another robot arm or the like is inserted into the box to transfer the culture vessel. Therefore, the area of ​​the first door 152 and the second door 153 can be minimized. Therefore, it is possible to further reduce the possibility of contamination through the first door 152 and the second door 153. Furthermore, since the culture vessel can be stirred by changing the angular velocity during the rotation of the arm 202, it is also possible to further maintain the activity of the cells during transportation.

[0047] The first embodiment of the present disclosure has been described above. Various changes and modifications can be made to each of the above configurations without departing from the gist of the present disclosure. For example, the change in the rotation speed (angular velocity) of the arm 202 by the arm driving unit 201 is not limited to the aspect shown in FIG. 3. As a modified example, as shown in FIG. 6, it is also possible to change the angular velocity to take a negative value intermittently after starting the rotation. In other words, the flask unit 1 is transported while repeating acceleration / deceleration and reciprocation multiple times. According to this configuration, the flask unit 1 can be shaken more efficiently, so that the decrease in cell activity can be further suppressed.

[0048] Second Embodiment Next, a second embodiment of the present disclosure will be described with reference to Fig. 7. Note that the same components as those in the first embodiment are denoted by the same reference numerals, and detailed description thereof will be omitted.

[0049] As shown in FIG. 7, in this embodiment, the configuration of the holding portion 203 is different from that of the first embodiment. The holding portion 203 has a receiving tray portion 211, a movable tray portion 212, an elastic member 213, and a support piece 214. The receiving tray portion 211 is fixed to a position slightly offset inward from the radially outer end of the upper surface of the arm 202. The receiving tray portion 211 has a circular shape centered on a central axis O extending in the up-down direction (vertical direction), and has a concave surface portion 215 that is concave downward. In other words, the concave surface portion 215 has a triangular shape in a cross section including the central axis O. In other words, the concave surface portion 215 has a conical surface shape.

[0050] The movable dish portion 212 is supported movably on the concave surface portion 215. The movable dish portion 212 has a convex surface portion 216 that fits into the concave surface portion 215. The convex surface portion 216 is convex downward and has a conical surface shape that corresponds to the shape of the concave surface portion 215. When the arm 202 is in a stationary state, the apex of the convex surface portion 216 is located on the central axis O of the concave surface portion 215.

[0051] The elastic member 213 supports the movable disk portion 212 at least at two points facing each other in the diameter direction with respect to the central axis O with respect to a support piece 214 provided on the arm 202. The elastic member 213 is a coil spring extending in the diameter direction with respect to the central axis O, with one end connected to the support piece 214 and the other end connected to the movable disk portion 212. As an example, two elastic members 213 are provided with an interval of 180° between them.

[0052] (Action and effect) According to the above configuration, the movable dish part 212 can slide on the concave surface part 215 of the saucer part 211 along the concave surface part 215. Therefore, the inertial force due to the change in angular velocity when the arm 202 rotates and the elastic restoring force of the elastic member 213 are counterbalanced, so that the movable dish part 212 rotates like a top on the saucer part 211. This allows the contents (culture solution) of the flask unit 1 to be further stirred. Therefore, it is possible to maintain the activity of the cells well during transportation. In addition, since the saucer part 211 is supported by the arm 202 by the elastic member 213, when the arm 202 stops and the inertial force becomes zero, the saucer part 211 returns to a state (initial state) in which its central axis O coincides with the central axis O of the convex surface part 216 by the elastic member 213. This allows the flask unit 1 to maintain a constant posture when the culture vessel is transferred. Therefore, it is possible to execute various processes more smoothly and stably before and after passing through the pass box 150.

[0053] The second embodiment of the present disclosure has been described above. Various changes and modifications can be made to the above configuration without departing from the gist of the present disclosure. For example, in the second embodiment, an example in which two elastic members 213 are provided at 180° intervals has been described. However, four elastic members 213 may be provided at 90° intervals. Furthermore, five or more elastic members 213 may be provided. With such a configuration, the same effects as those described above can be obtained.

[0054] <Third embodiment> Next, a third embodiment of the present disclosure will be described with reference to Fig. 8. Note that the same components as those in the above embodiments are given the same reference numerals, and detailed description thereof will be omitted.

[0055] 8, in this embodiment, the configuration of the holder 203 is different from that of each of the above-mentioned embodiments. Specifically, the holder 203 has a holder main body 221 and a rotation drive unit 222. The rotation drive unit 222 is a mechanism for rotating the holder main body 221 in which the flask unit 1 is arranged.

[0056] The rotation drive unit 222 has a drive unit main body 231, a pulley unit 232, and a guide rail 233. The drive unit main body 231 is an electric motor, and a disk-shaped first pulley 241 is attached to its output shaft. The output shaft rotates the first pulley 241 around a rotation axis Y extending in the vertical direction. The drive unit main body 231 is provided at the end of the arm 202 on the inner periphery side.

[0057] The pulley unit 232 has the above-mentioned first pulley 241, the second pulley 242 integrally attached to the lower surface of the holding body 221, and a belt 243. The second pulley 242 is connected to the lower surface of the holding body 221 via a connection piece 244. The connection piece 244 is provided at a position radially eccentric from the axis Z of the second pulley 242. This is for efficiently transmitting torque caused by the rotation of the second pulley 242 to the holding body 221. The guide rail 233 is an annular member provided to support the second pulley 242 from below and to guide the rotation direction of the second pulley 242.

[0058] A belt 243 made of an elastic material is stretched between the first pulley 241 and the second pulley 242. The belt 243 is annular and abuts against a part of the outer circumferential surface of the first pulley 241 and a part of the outer circumferential surface of the second pulley 242. When the first pulley 241 rotates, the rotational force is transmitted to the second pulley 242 via the belt 243. As a result, the holder main body 221 and the flask unit 1 arranged on the holder main body 221 rotate around the axis Z of the second pulley 242.

[0059] (Action and effect) According to the above configuration, the holder body 221 is rotated by the rotation drive unit 222, so that the contents of the culture vessel can be stirred (shaken) regardless of whether the arm 202 is rotating or stopped. This causes the surface of the culture solution to ripple, increasing the surface area, and more oxygen is taken in by that amount. This makes it possible to maintain the activity of the cells even better during transportation. As a result, the activity and quality of the cells finally obtained can be further improved.

[0060] The third embodiment of the present disclosure has been described above. Note that various changes and modifications can be made to the above configuration without departing from the gist of the present disclosure.

[0061] <Other embodiments> Although each embodiment of the present disclosure has been described in detail above with reference to the drawings, the specific configuration is not limited to this embodiment, and design changes and the like that do not deviate from the gist of the present disclosure are also included.

[0062] For example, in each of the above embodiments, an example in which the flask unit 1 is transported using the arm 202 has been described. However, it is also possible to use a belt conveyor 400 (linear motion part) as shown in FIG. 9 as the transport device 170. In this case, the belt conveyor 400 is provided in a direction connecting the first door 152 and the second door 153. The transport speed of this belt conveyor 400 changes during transport as in each of the above embodiments, so that the flask unit 1 can be shaken. This makes it possible to obtain the same action and effect as described above. It is also possible to use a linear actuator instead of the belt conveyor 400.

[0063] Furthermore, the concave surface 215 of the receiving tray 211 and the convex surface 216 of the movable tray 212 in the second embodiment described above may each be spherical. In this case, the movable tray 212 slides more smoothly, so that shaking can be applied stably.

[0064] Furthermore, the driving unit main body 231 described in the third embodiment may be the same driving source as the arm driving unit 201. In this case, the rotational force transmitted from the arm driving unit 201 by gears is applied to the pulley unit 232. This makes it possible to obtain the same effects as those described above while reducing the number of parts.

[0065] It is also possible to use a combination of the configuration described in the second embodiment and the configuration described in the third embodiment. That is, the tray part 211 and the movable tray part 212 are rotated by the rotary drive part 222, while the movable tray part 212 slides by centrifugal force and inertial force. With this configuration, it is possible to give a larger and more complicated shaking to the flask unit 1. Therefore, it is possible to maintain the activity of the cells more satisfactorily.

[0066] It should be noted that the order of the processes performed by the control unit 204 in the embodiment of the present disclosure may be changed as long as appropriate processes are performed.

[0067] The storage unit 305 and other storage devices in the embodiment of the present disclosure may be provided anywhere within the range where appropriate information is transmitted and received. Also, the storage unit 305 and other storage devices may be present in multiple locations within the range where appropriate information is transmitted and received, and data may be stored in a distributed manner.

[0068] The above-mentioned process steps of the control unit 204 are stored in the form of a program in a recording medium readable by the computer 500, and the above-mentioned process is performed by the computer 500 reading and executing this program. A specific example of the computer 500 is shown below.

[0069] As shown in FIG. 6, a computer 500 includes a CPU 501, a main memory 502, a storage 503, and an interface 504. For example, the above-mentioned control unit 204 is implemented in a computer 500. The operations of the above-mentioned processing units are stored in the form of a program in a storage 503. The CPU 501 reads the program from the storage 503, loads it in the main memory 502, and executes the above-mentioned processing in accordance with the program. The CPU 501 also secures a storage area in the main memory 502 corresponding to the above-mentioned storage unit 305 in accordance with the program.

[0070] Examples of the storage 503 include a hard disk drive (HDD), a solid state drive (SSD), a magnetic disk, a magneto-optical disk, a compact disc read only memory (CD-ROM), a digital versatile disc read only memory (DVD-ROM), and a semiconductor memory. The storage 503 may be an internal medium directly connected to the bus of the computer 500, or an external medium connected to the computer 500 via the interface 504 or a communication line. In addition, when the program is distributed to the computer 500 via a communication line, the computer 500 that has received the program may expand the program in the main memory 502 and execute the above-mentioned process. The storage 503 is a non-transitory tangible storage medium.

[0071] The program may also realize some of the functions described above. Furthermore, the program may be a file that can realize the functions described above in combination with a program already recorded in computer 500, that is, a so-called difference file (difference program).

[0072] In addition to or instead of the above configuration, a custom LSI (Large Scale Integrated Circuit) such as a PLD (Programmable Logic Device), an ASIC (Application Specific Integrated Circuit), a GPU (Graphics Processing Unit), or a processing device similar thereto may be provided. Examples of PLDs include PAL (Programmable Array Logic), GAL (Generic Array Logic), CPLD (Complex Programmable Logic Device), and FPGA (Field Programmable Gate Array). In this case, some or all of the functions realized by the processor may be realized by the integrated circuit.

[0073] <Additional Notes> The pass box 150 described in each embodiment can be understood, for example, as follows.

[0074] (1) A pass box 150 according to a first aspect includes a first chamber having a first environment, a second chamber having a second environment different from the first environment, a box body 151 communicating with the first chamber and the second chamber, respectively, and provided between the first chamber and the second chamber, a first door switching an open / closed state between the first chamber and the box body 151, a second door switching an open / closed state between the second chamber and the box body 151, and a culture medium provided in the box body 151. The system includes a transport mechanism that transports a culture container between the first chamber and the second chamber, and a control unit 204 that controls the operation of the transport mechanism and the operation of the first door and the second door, and the control unit 204 includes an opening / closing unit 301 that switches the open / closed state of the first door and the second door, and a determination unit 302 that determines the open / closed state of the first door and the second door, and when the determination unit 302 determines that either one of the first door or the second door is in a closed state, the opening / closing unit 301 opens the other door.

[0075] According to the above configuration, when either the first door or the second door is in a closed state, the other door is in an open state. Therefore, the first chamber and the second chamber do not communicate with each other via the box body 151. Therefore, different environmental conditions such as atmosphere, pressure, temperature, etc. are not mixed between the first chamber and the second chamber. In other words, contamination can be avoided.

[0076] (2) A pass box 150 according to a second aspect is the pass box 150 of (1), wherein the control unit 204 has an adjustment unit 304 that adjusts the conveying speed of the conveying mechanism to change between the first chamber and the second chamber.

[0077] According to the above configuration, the transport speed of the transport mechanism changes between the first chamber and the second chamber. In other words, the transport mechanism operates with an acceleration. Therefore, the culture vessel is agitated by the speed change. Therefore, more oxygen can be supplied to the cells in the culture vessel. As a result, it is possible to maintain the activity state of the cells in a good condition even during transport.

[0078] (3) A pass box 150 according to a third aspect is a pass box 150 according to (1) or (2), wherein the adjustment section 304 is configured so that the conveying mechanism repeats conveying and stopping between the first chamber and the second chamber.

[0079] According to the above configuration, the transport mechanism intermittently repeats transport and stopping, so that the transport speed changes over time. Therefore, the culture vessel is agitated every time the speed changes. Therefore, more oxygen can be supplied to the cells in the culture vessel. As a result, it is possible to maintain the activity state of the cells in a better condition even during transport.

[0080] (4) A pass box 150 according to a fourth embodiment is a pass box 150 according to any one of the embodiments (1) to (3), wherein the transport mechanism includes an arm drive unit 201 provided within the pass box 150 and having an output shaft rotatable around an arm rotation axis X extending in the vertical direction, an arm 202 supported by the arm drive unit 201 so as to be rotatable and rotates around the arm rotation axis X between the first chamber and the second chamber, and a holder 203 provided on the arm 202 and capable of holding the culture vessel, and the control unit 204 changes the angular velocity when the arm 202 rotates between the first chamber and the second chamber.

[0081] According to the above configuration, the arm 202 is rotated by the arm driving unit 201, so that the culture vessel can be quickly transferred between the first chamber and the second chamber. In addition, since the arm 202 rotates around the arm rotation axis X extending in the vertical direction, the dimensions of the device in the vertical direction can be kept small compared to a configuration in which another robot arm or the like is inserted into the box to transfer the culture vessel. Therefore, the areas of the first door and the second door can be minimized. Therefore, it is possible to further reduce the possibility of contamination through the first door and the second door. Furthermore, since the culture vessel can be stirred by changing the angular velocity during the rotation of the arm 202, it is also possible to maintain good cell activity during transportation.

[0082] (5) A pass box 150 according to a fifth aspect is the pass box 150 of (4), wherein the holding portion 203 is provided on the arm 202, has a circular shape centered on a central axis O extending in the vertical direction, has a receiving portion 211 having a concave portion 215 that is concave downward, and a convex portion 216 that fits into the concave portion 215 of the receiving portion 211, a movable dish portion 212 that can hold the culture vessel, and an elastic member 213 that supports the movable dish portion 212 against the arm 202 at at least two points that face each other in the diameter direction relative to the central axis O.

[0083] According to the above configuration, the movable dish part 212 can slide on the concave surface part 215 of the saucer part 211 along the concave surface part 215. Therefore, the movable dish part 212 rotates like a top on the saucer part 211 due to the inertial force caused by the change in angular velocity when the arm 202 rotates. This allows the contents of the culture vessel to be further stirred. Therefore, it is possible to maintain the activity of the cells well during transportation. In addition, since the saucer part 211 is supported by the arm 202 by the elastic member 213, when the arm 202 stops and the inertial force becomes zero, the elastic member 213 returns the saucer part 211 to a state (initial state) in which its central axis O coincides with the central axis O of the convex surface part 216. This allows the posture when the culture vessel is transferred to be kept constant.

[0084] (6) The pass box 150 of the sixth aspect is the pass box 150 of (4), wherein the holding unit 203 has a holding unit body 221 capable of holding the culture vessel, and a rotation drive unit 222 that rotates the holding unit body 221 around its own central axis O extending in the vertical direction.

[0085] According to the above configuration, the holder body 221 is rotated by the rotation drive unit 222, so that the contents of the culture vessel can be stirred regardless of whether the arm 202 is rotating or stopped. This makes it possible to maintain the activity of the cells in an even better condition.

[0086] (7) A pass box 150 according to a seventh aspect is a pass box 150 according to any one of the aspects (1) to (3), wherein the transport mechanism extends in a transport direction connecting the first chamber and the second chamber and has a linear motion part capable of moving the culture vessel in the transport direction, and the control unit 204 controls the transport speed of the linear motion part.

[0087] According to the above configuration, since the linear motion part transports the culture vessel in a straight line, the culture vessel can be transported over the shortest distance between the first chamber and the second chamber, thereby shortening the processing time required for the entire process.

[0088] (8) The cell culture system 100 of the eighth aspect comprises an incubator 130 forming a culture area R3 in which a flask 12 is accommodated, a clean bench 140 forming a liquid handling area R4 in which dispensing operations are performed on the flask 12, a transport device capable of transporting the flask 12 between each of the culture area R3 and the liquid handling area R4, and a pass box 150 of any one of (1) to (7) capable of transferring the flask 12 between the incubator 130 and the clean bench 140.

[0089] By providing the pass box 150, contamination can be avoided. [Explanation of symbols]

[0090] 1...flask unit 11...flask tray 12...flask 100...cell culture system 110...stocker 111...stocker body 112...rack 113...stocker first door 114...stocker second door 120...loading booth 121...booth body 122...loading door 130...incubator 131...incubator body 132...shaking stage 140...clean bench 141...clean bench body 142...dispensing device 145...waste liquid extraction device 149...stage 150...pass box 151...box body 152...first door 153...second door 154...rotating transport device 160...measuring device 161...culture medium supply device 162...waste liquid tank 170...transport device 171...first transport robot 172...second transport robot 173...third transport robot 174...fourth transport robot 175...conveyor 201...arm drive unit 202...arm 203...holding unit 204...control unit 211...receiver 212...movable tray 213...elastic member 214...support piece 215...concave portion 216...convex portion 221...holding unit main body 222...rotation drive unit 231...drive unit main body 232...pulley unit 233...guide rail 241...first pulley 242...second pulley 243...belt 244...connection piece 301...opening / closing unit 302...determination unit 303...transport drive unit 304...adjustment unit 305...storage unit 400...belt conveyor 500...computer 501...CPU 502...main memory 503...storage 504...interface O...center axis R1...storage area R2: Loading area R3: Cultivation area R4: Liquid handling area X: Arm rotation axis

Claims

1. a first chamber having a first environment; a second chamber having a second environment different from the first environment; a box body communicating with the first chamber and the second chamber, respectively, and disposed between the first chamber and the second chamber; a first door that switches between an open and closed state between the first chamber and the box body; a second door that switches between an open and closed state between the second chamber and the box body; a transport mechanism provided in the box body and configured to transport a culture vessel between the first chamber and the second chamber; a control unit that controls an operation of the transport mechanism, the first door, and the second door; Equipped with The control unit is an opening / closing unit that switches between an open / closed state of the first door and an open / closed state of the second door; a determination unit that determines whether the first door and the second door are open or closed; The opening / closing unit is a pass box that opens either the first door or the second door when the determination unit determines that the other door is in a closed state.

2. 2. The pass box according to claim 1, wherein the control unit has an adjustment unit that adjusts the conveying speed of the conveying mechanism so as to change between the first chamber and the second chamber.

3. The pass box according to claim 2 , wherein the adjustment section is configured so that the transport mechanism repeats transport and stop between the first chamber and the second chamber.

4. The transport mechanism includes: an arm driving unit provided in the pass box and having an output shaft rotatable around an arm rotation shaft extending in a vertical direction; an arm that is rotatably supported by the arm drive unit and rotates around the arm rotation axis between the first chamber and the second chamber; A holder provided on the arm and capable of holding the culture vessel; having The pass box according to claim 1 , wherein the control unit changes an angular velocity when the arm rotates between the first chamber and the second chamber.

5. The holding portion is a receiving tray provided on the arm, the receiving tray having a circular shape centered on a central axis extending in a vertical direction and a concave surface portion recessed downward; a movable dish part having a convex part that fits into the concave part of the receiving dish part and capable of holding the culture vessel; an elastic member that supports the movable plate portion against the arm at at least two points that face each other in a diametric direction with respect to the central axis; 5. The pass box of claim 4, comprising:

6. The holding portion is A holder body capable of holding the culture vessel; A rotation drive unit that rotates the holding unit body about its own central axis extending in the vertical direction; The pass box according to claim 4, comprising:

7. The transport mechanism includes: a linear motion part extending in a transport direction connecting the first chamber and the second chamber and capable of moving the culture vessel in the transport direction; The pass box according to claim 1 , wherein the control unit controls a conveying speed of the linear motion unit.

8. an incubator forming a culture area in which the flasks are housed; a clean bench forming a liquid handling area in which a dispensing operation is performed on the flask; a transport device capable of transporting the flask in each of the culture area and the liquid handling area; 2. The pass box according to claim 1, which is capable of transferring the flask between the incubator and the clean bench; A cell culture system comprising:

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