Dispensing apparatus and dispensing method
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- SINFONIA TECHNOLOGY CO LTD
- Filing Date
- 2025-12-18
- Publication Date
- 2026-07-23
Smart Images
Figure JP2025044332_23072026_PF_FP_ABST
Abstract
Description
Liquid Dispensing Device and Liquid Dispensing Method
[0001] The present invention relates to a liquid dispensing device and a liquid dispensing method for automating the liquid dispensing process in a cell culture process.
[0002] The liquid dispensing process refers to a process of separately dispensing a certain amount of a liquid such as a cell-cultured suspension into a dedicated container (vial or bag). As an example, there is the one shown in Patent Document 1.
[0003] In the automation of this type of cell culture process, it is desirable to be a closed system as a premise. A closed system means keeping the internal space of the flow path through which a suspension or the like flows in a state where it does not come into contact with the outside air. Particularly in the cell culture process, it is desirable to make the internal space sterile using γ-ray sterilization or ethylene oxide gas sterilization (EOG) etc. and maintain that state. The merit of a closed system is that the possibility of cells being exposed to bacteria is reduced because direct human intervention is eliminated.
[0004] Patent No. 6727349
[0005] However, there are few devices that automate the liquid dispensing process in a closed system, and there is no device corresponding to liquid dispensing containers that require a large amount of liquid dispensing. The main reason why a large amount of liquid dispensing cannot be achieved is considered to be that there are problems in liquid feeding in a closed system.
[0006] That is, after constructing a liquid feeding line of a closed system, in order to enable stable liquid feeding, first, it is necessary to perform operations such as liquid feeding and valve opening / closing from the outside of the tube. Also, in order to appropriately perform a large amount of processing, it is necessary to construct a stable control system, and for liquid feeding, dealing with air or bubbles in the liquid, dealing with injection unevenness, etc. are important issues.
[0007] The present invention aims to solve these problems and realize a liquid dispensing device and a liquid dispensing method suitable for a large amount of liquid dispensing in a closed system.
[0008] In order to achieve such an object, the present invention has taken the following means.
[0009] In other words, the dispensing device of the present invention comprises a suspension introduction unit, a tube pump, a pinch valve, a dispensing container sealing unit, and a control unit that controls the suspension introduction unit, the tube pump, the pinch valve, and the dispensing container sealing unit, wherein a plurality of dispensing containers are associated with the suspension introduction unit, the tube pump, the pinch valve, and the dispensing container sealing unit through common piping and branch piping while maintaining a closed system, and the control unit performs the following steps: a liquid supply step of sending the suspension from the culture medium introduction unit downstream toward the dispensing containers via the common piping and branch piping; a dispensing step of sequentially injecting the suspension into each of the dispensing containers; and a sealing step of sealing the dispensing containers.
[0010] In this way, a closed system can be maintained by using a tube pump or pinch valve, and during the liquid delivery process, air and bubbles are expelled downstream by supplying the suspension from the upstream side, ensuring liquid delivery performance and preventing uneven injection. Finally, by sealing the dispensing container, it can be detached while the liquid is still sealed.
[0011] In order to more reliably fill the dispensing container with the suspension, it is preferable to provide a gas introduction section in the common piping, and for the steps performed by the control unit in the dispensing process to include a supply step of supplying the suspension to the dispensing container through the common piping, a recovery step of recovering the suspension remaining on the common piping to the suspension introduction section, and a pushing step of introducing gas into the common piping to push the suspension remaining between the common piping and the dispensing container into the dispensing container.
[0012] In order to prevent air or bubbles discharged from one dispensing container from flowing into the next dispensing container, it is preferable to perform the dispensing process from the downstream dispensing container toward the upstream dispensing container.
[0013] In order to properly distribute the suspension through the common piping, it is preferable to place a liquid level sensor that detects the liquid level in the common piping at a position higher than the main line, in the exhaust line located downstream of the main line to which the dispensing container is connected, and for the control unit to continue dispensing liquid in the liquid supply process until the liquid level sensor detects the liquid level.
[0014] To improve the operational efficiency of the dispensing device, it is preferable to arrange the dispensing containers in multiple chambers, and to allow the control unit to replace the dispensing containers in other chambers while dispensing to the dispensing containers in some chambers.
[0015] In order to obtain the same effects as the above-mentioned dispensing device regardless of the device configuration, it is preferable to adopt a dispensing method that involves dispensing to each dispensing container through a dispensing line formed from a suspension introduction part connected to the common pipe to a branch of the common pipe, to a dispensing unit in which a plurality of dispensing containers are linked in parallel through a common pipe and branch pipes, and the dispensing method being characterized by performing: a liquid supply step of sending the suspension from the suspension introduction part to the dispensing containers from the downstream side through the common pipe and branch pipes; a dispensing step of sequentially injecting the suspension into each dispensing container; and a sealing step of sealing the dispensing containers.
[0016] According to the present invention described above, by appropriately addressing the problems of liquid delivery, it becomes possible not only to dispense in a closed system but also to dispense with stable liquid delivery performance. Furthermore, by dispensing in a closed system, it becomes possible to reduce the cleanliness of the dispensing room.
[0017] A diagram showing a dispensing device according to one embodiment of the present invention. A diagram showing the dispensing area constituting the dispensing device. A diagram showing a dispensing unit attached to the dispensing area. A diagram explaining the function of the dispensing area. A flowchart showing the procedure executed by the control unit of the dispensing device. A diagram explaining the state corresponding to step S1. A diagram explaining the state corresponding to step S2. A diagram explaining the state corresponding to step S3. A diagram explaining the state corresponding to step S4. A diagram explaining the state corresponding to step S5. A diagram explaining the state corresponding to step S6. A diagram explaining the state corresponding to step S7. A diagram explaining the state corresponding to step S8. A diagram explaining the state corresponding to step S9. A diagram explaining the state corresponding to step S10. A diagram explaining the state corresponding to step S11. A diagram explaining the state corresponding to step S12. A diagram explaining the operation switching of the dispensing device 1.
[0018] Embodiments of the present invention will be described below with reference to the drawings.
[0019] The dispensing device 1 of this embodiment, shown in Figure 1, has a liquid delivery area A1 and a dispensing area A2 in the housing of the device body (not shown).
[0020] The liquid supply area A1 is where the culture medium inlet 12, gas inlet 11, and tube pump 13, which are the sources of the culture medium suspension, are located and are interconnected via the main piping 10. Pinch valves 12a and 11a are provided at the inlets and outlets of the culture medium inlet 12 and gas inlet 11.
[0021] The dispensing areas A2 are physically located in the left and right compartments of the housing that constitutes the dispensing device 1, and the same piping routes are configured on both sides. In each dispensing area A2, a tube set including a dispensing container 3, called a vial, is installed. The tube set consists of multiple dispensing containers 3 arranged in parallel via branch pipes 32 to maintain a closed system on a common pipe 31. The dispensing container 3 in this embodiment is of the type with one inlet port, and the culture medium is injected into the container through the inlet port.
[0022] As shown in Figure 2, the dispensing area A2 is equipped with a row of branch valves 21 that temporarily closes the branch pipe 32, a row of heat sealers 22 that liquid-tightly seals the dispensing container 3, a liquid supply valve 23 that opens and closes a portion of the liquid supply side of the common pipe 31, an exhaust valve 24 that opens and closes a portion of the exhaust side, and a liquid level sensor 25 that detects the liquid level on the exhaust side of the common pipe 31.
[0023] Each of the above-mentioned mechanical elements located in the liquid delivery area A1 and the dispensing area A2 is controllably connected to the control unit 4 shown in Figure 1. The control unit 4 is equipped with a microcomputer unit including a CPU, memory, and interface, and the memory stores a program for performing dispensing. The CPU sequentially reads the program and performs actions such as opening and closing the valve 12a of the culture medium introduction unit 12, opening and closing the valve 11a of the gas introduction unit 11, driving the tube pump 13, opening and closing the liquid delivery valve 23, exhaust valve 24, branch valve row 21, and controlling the heat sealer row 22, thereby executing a procedure to automatically dispense the culture medium c from the culture medium introduction unit 12 into each dispensing container 3.
[0024] The control unit 4 also switches the controlled object between the left and right dispensing areas A2 within the chamber. To allow the tube unit to be replaced in the other dispensing area A2 while dispensing is progressing in one dispensing area A2, the dispensing container 3 is connected to the main pipe 10 via a joint 50, maintaining a closed system by connecting the common pipe 31 and branch pipe 32 shown in Figure 1. The joint 50 is a T-joint. Functionally, the tube unit of the liquid delivery area A1 and the tube unit of the dispensing area A2 are connected at a sterile connection part 50x located downstream of the joint 50. The tube unit of the dispensing area A2 referred to here is the same as the tube set of the dispensing area A2 described above.
[0025] The common piping 31 and branch piping 32 are made of flexible tubing. Therefore, in order to maintain a predetermined routing shape and enable handling, they are attached to a support base plate 30 at appropriate positions and integrated as a dispensing unit U, as shown in Figure 3.
[0026] As shown in Figure 1, the specific tubing configurations in each section are as follows: the tubing units constituting the main piping 10 in the liquid delivery area A1 are mainly composed of tubing t10 with an inner diameter of φa, located upstream of the fitting 51. In addition, among the common piping 31 in the dispensing area A2, the main line L1 located between fittings 52 and 53 is mainly composed of tubing t11 with an inner diameter of φb, while the piping for liquid delivery lines L2 and other lines located between fittings 51 and 52 is mainly composed of tubing t12 with an inner diameter of φc. Furthermore, the exhaust line L3 located on the exhaust side (air filter 31a side) of fitting 53 is mainly composed of tubing t13 with an inner diameter of φd.
[0027] As an example, in this embodiment, φa = φb < φc < φd (φa = 1.6 mm, φb = 1.6 mm, φc = 3.2 mm, φd = 6.4 mm).
[0028] Aseptic connectors, closed-system tube connection devices, etc., are suitably used for the aseptic connection section 50x and fittings 51, 52, and 53. The dispensing unit U is replaced by disconnecting it at the aseptic connection section 50x, in which case the closed system is maintained through heat welding or the like, as described later, based on Figure 18.
[0029] In Figure 1, etc., a flow rate correction unit 5 is connected to a branch of a portion of the main piping 10. This flow rate correction unit 5 plays a role in correcting the flow rate through its internal pump function so that a predetermined flow rate flows into the common piping 31, by measuring the actual flow rate each time the tube set is replaced, because the tubes set in the tube pump 13 are made of resin and therefore have large manufacturing tolerances, and the tube sets are disposable.
[0030] The dispensing unit U and the dispensing device 1 will be described in detail below.
[0031] The common piping 31 of the dispensing unit U is partially folded back to form a main line L1 that extends horizontally and spans two levels, with the dispensing containers 3 connected in a row.
[0032] Of the common piping 31, the upstream end of the lower main line L1 is designated as the liquid delivery line L2, and its starting end is connected to the joint 50. Specifically, of the common piping 31, the upstream end of the lower main line L1 is connected to one end of the liquid delivery line L2, and the other end of the liquid delivery line L2 is connected to the main piping 10. The connection between the other end of the liquid delivery line L2 and the main piping 10 can be made at any position within the sterile connection part 50x. This connection is made, for example, by welding using a welding machine. Of the common piping 31, the downstream end of the upper main line L1 is designated as the exhaust line L3, and an air filter 31a is connected to its end. Specifically, of the common piping 31, the downstream end of the upper main line L1 is connected to one end of the exhaust line L3, and an air filter 31a is connected to the other end of the exhaust line L3. The dispensing unit U delivers liquid from the lower side to the upper side and exhausts it from the upper side. A portion of the exhaust line L3 (L31) is maintained in a curved shape at a higher position than the main line L1.
[0033] The air filter 31a uses a sterile filter made of nonwoven fabric that prevents bacteria from entering, so that bacteria do not enter the internal space of the dispensing unit U. This allows the internal space of the dispensing unit U to be kept closed and easy to handle. The pressure loss in the air filter 31a is basically reduced in the direction in which the air is exhausted from the dispensing unit U than in the direction in which it enters the dispensing unit U, but it can also be used in the reverse direction.
[0034] To ensure a clean environment, the dispensing unit U is subjected to sterilization in a sterilization device (not shown). In this embodiment, gamma ray sterilization is performed, sterilizing the tubes constituting the common piping 31, the tubes constituting the branch piping 32, and other component parts such as the plate material 30 before use. For this reason, these component parts are made of materials resistant to gamma ray sterilization.
[0035] Next, we will describe the dispensing device 1 shown in Figures 1 and 2.
[0036] First, the liquid delivery area 1A of the dispensing device 1 has the following configuration.
[0037] The culture medium introduction section 12 in this case is a bag filled with a suspension. The bag is filled with a suspension in which cells are mixed with culture medium, cultured in a cell culture system (not shown in the figure), which has been concentrated and replaced using a concentration and replacement device, and this is then set into the main dispensing device 1. This culture medium introduction section 12 may also be a transfer line or the like through which the suspension is delivered from the cell culture system along the line.
[0038] The tube pump 13 has the function of pressurizing the tube from the outside and compressing it while sending out the liquid in order to deliver the liquid without releasing the closed system. The culture medium in the culture medium introduction section 12 is sent from the main pipe 10 to the common pipe 31 of the dispensing area A2 by the tube pump 13, and the culture medium present in the dispensing area A2 is collected from the common pipe 31 of the dispensing area A2 to the culture medium introduction section 12 by the tube pump 13.
[0039] The gas introduction section 11 also serves as part of the suction section for drawing gas (air) from inside the tube. It works in cooperation with the tube pump 13 to introduce air from the main pipe 10 into the common pipe 31, and to draw air from the common pipe 31 and release it into the atmosphere.
[0040] On the other hand, the dispensing area A2 of the dispensing device 1 has the following configuration.
[0041] The liquid level sensor 25 is positioned in the middle of the upward path of a section of the exhaust line L3 of the common piping 31 that is held in a curved shape, in order to detect the liquid level position.
[0042] The liquid delivery valve 23 of the common piping 31 is positioned to pinch the liquid delivery line L2, which is located upstream of the dispensing container 3. This liquid delivery valve 23 is a pinch valve that opens and closes the liquid delivery line L2 by pressurizing the tube from the outside and compressing it in order to maintain a closed system.
[0043] The exhaust valve 24 of the common piping 31 is positioned to pinch the exhaust line L3, which is located downstream of the dispensing container 3. This exhaust valve 24 is also a pinch valve that opens and closes the exhaust line L3 by pressurizing it from outside the tube to compress it in order to maintain a closed system.
[0044] The dispensing unit U is pre-set at its mounting position inside the storage. In the dispensing area A2, at the position where the branch pipe 32 of the dispensing container 3 is arranged when the dispensing unit U is set as shown in Fig. 4(a), there is provided a branch valve 21a for closing / releasing the dispensing line L4 by applying pressure from the outside of the tube to crush it. In the figure, the reference numeral 30a indicates a through-hole 30a provided in the plate material 30 for operating the branch valve 21a.
[0045] Also, in the dispensing area A2, as shown in Fig. 4(b), there is provided a heat sealer 22a which is a sealing part at a position corresponding to the heat seal part 3a set in a part of the dispensing container 3. The heat sealer 22a is configured to weld the heat seal part 3a with the heat of the heater 22a2 in a state where the heat seal part 3a is crushed between the heater 22a2 provided on the door 4x side facing the dispensing device 4 inside the storage by causing the metal block 22a1 to project and retract through the through-hole 30b of the plate material 30. A high-frequency sealer may be used instead of the heat sealer 22a.
[0046] Fig. 5 is a flowchart showing an outline of the control procedure executed by the control unit 4, and Figs. 6 to 17 are explanatory diagrams of the liquid feeding state corresponding to each step of the flowchart. Hereinafter, the operation will be described along each step.
[0047] <Step S1> As shown in Fig. 6, gas (air) g is sucked from the dispensing container 3. For this purpose, the control unit 4 closes the exhaust line L3 with the exhaust valve 24, opens the branch valve 21a, and sucks the inside of the dispensing container 3 with the tube pump 13 in a state where the valve 11a of the atmosphere release part (gas introduction part) 11 is open.
[0048] The dispensing container 3 is a so-called soft vial made of a resin having a deformability such that it contracts by suction. As a result, the air inside the dispensing container 3 is sucked out and it is in a crushed state. After suction, the valve 11a is closed.
[0049] <Step S2> As shown in Fig. 7, the control unit 4 opens the exhaust valve 24 to release the common pipe 31 to the atmosphere. The branch valve 21a of the dispensing container 3 is closed.
[0050] <Step S3> As shown in Figure 8, the control unit 4 opens the valve 12a of the culture medium introduction unit 12, opens the exhaust valve 24, and operates the tube pump 13 to send the culture medium c from the main pipe 10 to the common pipe 31 of the dispensing area A2.
[0051] <Step S4> As shown in Figure 9, when the liquid level sensor 25 detects the liquid level, the control unit 4 stops the liquid supply by the tube pump 13. This allows the control unit 4 to detect that each main line L1 of the common piping 31 has been reliably filled with culture medium c.
[0052] <Step S5> As shown in Figure 10, the control unit 4 waits for a certain period of time (or until a certain pressure is reached) after the liquid level sensor 25 detects the liquid level, in order to release the pressure in the common piping 31 to the atmosphere, and then releases the pressure from the liquid level sensor 25.
[0053] If the liquid level sensor 25 were to be placed at the very top (horizontal portion) of the curved section, the liquid would be located in the lower layer of the tube and the air in the upper layer, preventing the tube from being filled with liquid, and thus the liquid level sensor 25 would not be able to detect the liquid level. In contrast, if the liquid level sensor 25 is placed in the middle of the ascending path as described above, the tube will be filled with liquid, making it possible to properly detect the liquid level. In addition, by placing the liquid level sensor 25 in this position, the disadvantages of placing the liquid level sensor 25 on the descending side of the curved section, namely, wasted liquid and the air filter 31a getting wet and unable to supply liquid, can be avoided. Once the liquid level sensor 25 detects the liquid level, the exhaust valve 24 is closed.
[0054] <Step S6> As shown in Figure 11, the control unit 4 delivers liquid to each dispensing container 3. Specifically, after opening each branch valve 21a of the branch line L4, the control unit 4 operates the tube pump 13 to deliver the culture solution c from the culture solution introduction section 12 toward the main line L1 of the common piping 31, thereby sending the culture solution c to the dispensing container 3. This operation is performed sequentially from the downstream dispensing container 3 (closer to the air filter 31a) to the upstream dispensing container 3 (closer to the tube pump 13) in the row of dispensing containers 3 located on the upper side, and then similarly sequentially from the downstream to the upstream in the row of dispensing containers 3 located on the lower side.
[0055] <Step S7> Once Step S6 is complete and all dispensing containers 3 have been fed in the inlet direction, as shown in Figure 12, the control unit 4 operates the tube pump 13 in the reverse direction to collect the culture medium c in the common piping 31 into the bag that constitutes the culture medium introduction unit 12. In this state, the culture medium c accumulates at the bottom of the dispensing containers 3, and the culture medium c remains in the branch line L4.
[0056] <Step S8> In step S7, some culture medium cx enters another pathway and remains. Therefore, as shown in Figure 13, the control unit 4 returns this to the bag that constitutes the culture medium introduction unit 12. To do this, the control unit 4 closes the liquid delivery valve 23 and operates the tube pump 13 in the reverse direction, thereby recovering the culture medium cx that remained in Figure 12.
[0057] <Step S9> As a result of step S8, the area upstream of the liquid supply valve 23 becomes negative pressure. Therefore, as shown in Figure 14, the control unit 4 opens the liquid supply valve 23 and releases the pressure in the common piping 31 to the atmosphere.
[0058] <Step S10> As shown in Figure 15, the control unit 4 closes the valve 12a of the culture medium introduction unit 12, closes the exhaust valve 24, and opens the valve 11a of the gas introduction unit 11 to send gas (air) g into the common piping 31. At this time, the culture medium c remaining in the branch line L4 is pushed into the dispensing container 3, and the air remaining in the dispensing container 3 is replaced with the culture medium c. This operation is performed by opening and closing each branch valve 21a one by one from the downstream dispensing container 3 to the upstream dispensing container 3.
[0059] <Step S11> Once all the dispensing containers 3 have been filled with culture medium c, the control unit 4 opens the exhaust valve 24 and the branch valve 21a, as shown in Figure 16, to release the inside of the dispensing containers 3 into the atmosphere.
[0060] <Step S12> As shown in Figure 17, the control unit 4 operates the heat sealer 22a to seal the heat seal portion 3a of the dispensing container 3. When heat sealing is performed, the heat seal portion 3a of the dispensing container 3 is crushed, sealing the containment portion 3b filled with culture medium 3c, and the gas (air) g that is pushed out at this time is discharged from the downstream air filter 31a.
[0061] <Replacing the dispensing unit U> Once the liquid supply to dispensing unit U1 on one side (for example, the left chamber in the diagram above) is complete, the control unit 4 starts supplying liquid to dispensing unit U2 in the right chamber. Specifically, as shown in Figure 18, while supplying liquid to dispensing unit U2 in the right chamber, the connection part x set on the tube of the liquid supply line L2 is heat-welded and replaced with a new set of dispensing unit U3. The new dispensing unit U3 has a newly connected connection part x and starts supplying liquid after the liquid supply to dispensing unit U2 is completed. In this way, a large amount of liquid is dispensed into the dispensing containers 3.
[0062] The dispensing container 3, filled with culture medium c, is separated from the dispensing unit U by cutting off the required portion and then cryopreserved.
[0063] As described above, the dispensing device 1 of this embodiment comprises a culture medium introduction unit 12, a tube pump 13, a pinch valve such as a branch valve 21a, a heat sealer 22a which is a dispensing container sealing unit, and a control unit 4 which controls the culture medium introduction unit 12, the tube pump 13, the branch valve 21a, and the heat sealer 22a. With a plurality of dispensing containers 3 connected to the culture medium introduction unit 12, the tube pump 13, and the branch valve 21a via a common pipe 31 and a branch pipe 32 while maintaining a closed system, the control unit 4 performs the following steps: a liquid supply step (steps S3 to S4) in which culture medium c is sent from the culture medium introduction unit 12 to the dispensing containers 3 from the downstream side via the common pipe 31 and the branch pipe 32; a dispensing step (steps S5 to S10) in which culture medium c is sequentially injected into each dispensing container 3; and a sealing step (steps S11 to S12) in which the dispensing containers 3 are sealed.
[0064] In this way, by using the tube pump 13 and pinch valve 21, a closed system can be maintained, and in the liquid delivery process (steps S3 to S4), the culture medium c is delivered from the upstream side to expel air and bubbles to the downstream side, thereby ensuring liquid delivery performance and preventing uneven injection. Finally, by sealing the dispensing container 3 in the sealing process (steps S11 to S12), the dispensing container 3 can be detached while it is still sealed.
[0065] Furthermore, the dispensing device 1 of this embodiment is provided with a gas introduction unit 11 in the common pipe 31, and the steps performed by the control unit 4 in the dispensing process (steps S5 to S10) include a supply step (steps S5, S6) of supplying culture medium c to the dispensing container 3 through the common pipe 31, a recovery step (steps S7, S8) of recovering the culture medium c remaining on the common pipe 31 into the culture medium introduction unit 12, and a pushing step (steps S9, S10) of introducing gas g into the common pipe 31 to push the culture medium c remaining between the common pipe 31 and the dispensing container 3 into the dispensing container 3.
[0066] After supplying the culture medium c to the common pipe 31, the remaining culture medium c in the common pipe 31 is temporarily collected to empty the common pipe 31. Then, gas g is introduced to push the unfilled culture medium c into the dispensing container 3. This ensures that the contents of the dispensing container 3 are reliably replaced with culture medium c, and at the same time, no culture medium c is wasted. In this case, the amount of liquid supplied from the tube pump 13 should be controlled considering the remaining amount of culture medium c in the flow path.
[0067] Furthermore, in the dispensing process (steps S5 to S10), dispensing is performed from downstream to upstream, which prevents air and bubbles discharged from one dispensing container 3 from flowing into the next dispensing container 3. This also ensures liquid delivery performance and prevents uneven injection.
[0068] Furthermore, in this embodiment, the dispensing device 1 has a liquid level sensor 25 positioned higher than the main line L1 in the exhaust line L3, which is located downstream of the main line L1 to which the dispensing container 3 is connected, within the common piping 31. The control unit 4 then continues dispensing liquid in the liquid supply process (steps S3 to S4) until the liquid level sensor 25 detects the liquid level.
[0069] Therefore, it is possible to appropriately detect when the culture medium c has spread throughout the entire system. In addition, by preventing the formation of air pockets along the way, it is possible to prevent the air from being compressed and thus prevent a decrease in liquid delivery performance.
[0070] Furthermore, in this embodiment, the dispensing device 1 is configured such that the control unit 4 closes the exhaust line L3 downstream of the main line L1 to which the dispensing container 3 is connected in the common piping 31 before the liquid delivery process (steps S3 to S4), and performs a suction process (steps S1, S2) to suck the dispensing container 3 through the common piping 31.
[0071] In this way, the air inside the dispensing container 3 can be removed in advance. In particular, even when it is necessary to use a single-port type dispensing container 3, the gas (air) g inside the dispensing container 3 can be appropriately replaced with the culture medium c.
[0072] Furthermore, in this embodiment, the dispensing device 1 has dispensing containers 3 arranged in multiple compartments, and the control unit 4 can replace the dispensing containers 3 in other compartments while dispensing to the dispensing containers 3 in some compartments.
[0073] In this way, it becomes possible to process a large volume of material by continuously dispensing into the dispensing container 3 without stopping the dispensing device 1.
[0074] Furthermore, in terms of methodology, this dispensing method is a dispensing method in which a dispensing unit U is formed by linking a plurality of dispensing containers 3 in parallel via a common pipe 31 and branch pipes 32, and dispensing to each dispensing container 3 from a culture medium introduction section 12 connected to the common pipe 31 via a dispensing line L4 configured at a branch of the common pipe 31, and the method comprises: a liquid supply step of sending culture medium c from the culture introduction section 12 to the dispensing containers 3 from the downstream side via the common pipe 31 and branch pipes 32; a dispensing step of sequentially injecting culture medium c into each dispensing container 3; and a sealing step of sealing the dispensing containers 3.
[0075] This method is applicable regardless of the configuration of the dispensing device or the function of the control unit, and can achieve effects and benefits similar to those of the above-mentioned dispensing device.
[0076] In this embodiment, the reason for using different tube diameters in different parts is as follows: If the tube is narrow, it becomes difficult for air and pressure that have entered the piping to escape. If air bubbles enter the piping, the amount of liquid that is delivered will decrease. Also, if the piping is narrow, it becomes difficult for pressure to escape, making it impossible to deliver the liquid as intended. On the other hand, if the tube is wide, the amount of liquid delivered from the liquid delivery line at one time will be large, making fine adjustments difficult.
[0077] From this, it can be concluded that if all the tubes are made of the same diameter, the accuracy of fluid delivery will be reduced.
[0078] In contrast, in the configuration of this embodiment, the diameter φa of the tube t10 of the pump section where the tube pump 13 is located upstream of the liquid delivery path (main piping 10) is made relatively the same as or thinner than the other tubes, making it possible to finely adjust the amount of liquid delivered. Also, the diameter φd of the tube t13 of the exhaust section where the liquid level sensor 25 is located downstream of the liquid delivery path is made relatively thicker than the other tubes, making it possible to easily release air and pressure from inside the piping.
[0079] In this way, by combining various pipe diameters, the disadvantages of each pipe diameter are canceled out, making it possible to deliver liquid to each dispensing container 3 with high precision.
[0080] Although one embodiment of the present invention has been described above, the specific configuration of each part is not limited to the embodiment described above.
[0081] For example, in the above embodiment, a one-port type dispenser was used, but a two-port type or the like may also be used. In this case, injection and aspiration can be performed in parallel, so steps S1 and S2 of the flowchart become unnecessary.
[0082] In addition to vials, dispensing containers can also be in the form of bags.
[0083] In the above embodiment, the main line is formed in two stages, upper and lower, but it may also be in one stage, or even three or more stages.
[0084] Other configurations can also be modified in various ways without departing from the spirit of the present invention.
[0085] The present invention can be used as a dispensing device and dispensing method for automating the dispensing process in a cell culture process.
[0086] 1…Dispensing device 3…Vial (dispensing container) 4…Control unit 11…Gas introduction unit 12…Culture medium introduction unit 13…Tube pump 21a…Branching valve 21a (tube valve) 22a…Heat sealer (dispensing container sealing unit) 25…Liquid level sensor 31…Common piping c…Culture medium (suspension) g…Air (gas) L1…Main line L3…Exhaust line S1, S2…Suction process S3-S4…Liquid delivery process S5-S10…Dispensing process S5, S6…Supply process S7, S8…Recovery process S9, S10…Pushing process S11-S12…Sealing process
Claims
1. A dispensing device comprising: a suspension introduction section, a tube pump, a pinch valve, a dispensing container sealing section, and a control unit that controls the suspension introduction section, the tube pump, the pinch valve, and the dispensing container sealing section, wherein a plurality of dispensing containers are associated with the suspension introduction section, the tube pump, the pinch valve, and the dispensing container sealing section through common piping and branch piping while maintaining a closed system, and the control unit performs: a liquid delivery step of sending the suspension from the culture medium introduction section downstream toward the dispensing containers via the common piping and branch piping; a dispensing step of sequentially injecting the suspension into each of the dispensing containers; and a sealing step of sealing the dispensing containers.
2. The dispensing apparatus according to claim 1, wherein the common piping is provided with a gas introduction section, and the steps performed by the control unit in the dispensing step include: a supply step of supplying a suspension to the dispensing container through the common piping; a recovery step of recovering the suspension remaining on the common piping to the suspension introduction section; and a pushing step of introducing gas into the common piping to push the suspension remaining between the common piping and the dispensing container into the dispensing container.
3. The dispensing apparatus according to claim 1, wherein the dispensing step is performed from the dispensing container located downstream toward the dispensing container located upstream.
4. The dispensing apparatus according to claim 1, wherein a liquid level sensor for detecting the liquid level in the common piping is placed at a position higher than the main line, in the exhaust line located downstream of the main line to which the dispensing container is connected, and the control unit continues to dispense liquid in the liquid dispensing process until the liquid level sensor detects the liquid level.
5. The dispensing apparatus according to claim 1, characterized in that the dispensing containers are arranged in a plurality of chambers, and the control unit can replace the dispensing containers in other chambers while dispensing to the dispensing containers in some of the chambers.
6. A dispensing method for dispensing a suspension from a suspension introduction section connected to the common piping to each dispensing container via a dispensing line formed at a branch of the common piping, to a dispensing unit in which a plurality of dispensing containers are linked in parallel via a common piping and branch piping, characterized in that the method includes: a liquid supply step of sending the suspension from the suspension introduction section to the dispensing containers from the downstream side via the common piping and branch piping; a dispensing step of sequentially injecting the suspension into each dispensing container; and a sealing step of sealing the dispensing containers.