Dispensing device

Abstract

By pre-setting the discharge rate of the liquid delivery pump to match the appropriate liquid volume for each dispensing container, and by taking advantage of the fact that compression and expansion of the liquid are less likely to occur, the system appropriately reflects this in the liquid delivery volume, thereby achieving highly accurate dispensing. [Solution] The system comprises a common pipe 31, a plurality of vials 3 connected to the common pipe 31, a tube pump 13 communicating with the common pipe 31, and a control unit 4 that controls the operation of dispensing from the tube pump 13 to each vial 3 through the common pipe 31. The tube pump 13 has a variable discharge rate, and the control unit 4 is configured to control the tube pump 13 with a predetermined discharge rate for each vial 3 so that a predetermined amount of liquid is delivered when dispensing to each vial 3 connected to the common pipe 31.

Description

[Technical Field]

[0001] The present invention relates to a dispensing device that enables high-precision liquid feeding. [Background Art]

[0002] The dispensing step refers to a step of aliquoting a fixed amount of liquid such as a cell-cultured suspension into dedicated containers (vials or bags). An example is the one disclosed in Patent Document 1.

[0003] This document describes a method of feeding liquid to a plurality of containers by pressure. When flowing a liquid containing cells or the like, a high flow rate may damage the cells, so it is necessary to reduce the pressure to achieve a low flow rate. However, when liquid is fed at low pressure and low speed, the flow rate is not stable, resulting in variations in liquid feeding accuracy.

[0004] Therefore, in order to stabilize liquid feeding accuracy, attempts have been made to achieve this by controlling pressure using pressure switches and level sensors.

[0005] Figure 6 of the same document shows a configuration in which the pressure in a primary tank (10) is adjusted by a primary-side pressure adjustment unit (61) to transfer liquid to secondary tanks (21, 22, 23).

[0006] Figure 10 of the same document is the configuration shown in Figure 6 of the same document with pressure sensors (81, 82, 83) added. The pressure sensors detect the pressure inside the secondary tanks. It is determined whether the liquid volume in the secondary tanks has reached a predetermined amount based on the values of the pressure sensors. When it is detected from the pressure value that the predetermined amount has been reached, a control unit (50) closes valves (V11, V12, V13). Variations are eliminated by this method.

[0007] Figure 13 in the same document shows Figure 6 with level sensors (91, 92, 93) added. The level sensors detect the liquid volume from the water level in the secondary tank. The system determines whether the liquid volume in the secondary tank has reached a predetermined amount based on the level sensor values. When it detects that the water level has reached the predetermined amount, the control unit (50) closes the valves (V11, V12, V13). This method eliminates variations. [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] Patent No. 6727349 [Overview of the Initiative] [Problems that the invention aims to solve]

[0009] However, the sensorless design shown in Figure 6 lacks a method for detecting the liquid volume in the secondary tank, resulting in poor liquid delivery accuracy if the secondary tank's capacity is not constant. The designs with pressure and level sensors shown in Figures 10 and 13 suffer from poor accuracy due to the time required for the signal to travel from the sensor to the primary pressure adjustment unit and the time required for the pressure to fully transfer after the primary pressure adjustment unit stops.

[0010] This inconvenience stems from the fact that when liquid is transferred from a commonly pressurized primary tank to multiple secondary tanks located at different locations, the liquid level in each tank is fed back into the valve opening and closing mechanism.

[0011] These problems are likely to increase as the distance between tanks increases, and imbalances in liquid volume may also occur if there are differences in elevation between tanks.

[0012] This invention focuses on these problems and aims to solve them by controlling the amount of liquid dispensed by pre-setting an appropriate liquid dispensed volume for each dispensing container. [Means for solving the problem]

[0013] To achieve this objective, the present invention employs the following means.

[0014] In other words, the dispensing apparatus of the present invention is The system comprises a common pipe, a plurality of dispensing containers connected to the common pipe, a liquid transfer pump communicating with the common pipe, and a control unit that controls the operation of dispensing from the liquid transfer pump to each of the dispensing containers through the common pipe, The liquid delivery pump has a variable discharge rate, and the control unit controls the liquid delivery pump with a predetermined discharge rate for each of the dispensing containers connected to the common piping so that a predetermined liquid delivery rate is achieved when dispensing to each of the dispensing containers connected to the common piping.

[0015] While Patent Document 1 determines whether the liquid volume has reached a predetermined amount using pressure sensors and level sensors installed in the secondary tank, the present invention allows for the pre-adjustment of the appropriate liquid volume for each dispensing container through the discharge rate of the liquid delivery pump. This suppresses errors in the dispensing volume, including imbalances caused by the arrangement of the dispensing containers. In particular, while Patent Document 1 may cause errors due to the progression of liquid delivery between sensor detection and valve opening / closing, the present invention utilizes the small compression ratio of the liquid to immediately reflect the liquid volume delivered to the dispensing container through the discharge rate control of the liquid delivery pump. Therefore, it is less prone to errors due to time lag compared to feedback control, and eliminates the need to install sensors for each dispensing container.

[0016] In a configuration where the dispensing containers are distributed and connected from upstream to downstream of the common piping, it is preferable that the control unit controls the liquid delivery pump with a discharge rate corresponding to the distance from the liquid delivery pump to each of the dispensing containers.

[0017] In a configuration where the dispensing container is connected to the common piping with a difference in height, it is preferable that the control unit controls the liquid delivery pump with a discharge rate corresponding to the height difference of the dispensing container.

[0018] When the control unit sequentially performs dispensing to each dispensing container after closing a part of the exhaust line located downstream of the main line to which the dispensing container is connected in the common pipe with an exhaust valve, it is preferable that a liquid level sensor is disposed in a part of the exhaust line, and the exhaust valve is disposed upstream of the liquid level sensor.

[0019] In a case comprising a main pipe that is located upstream of the main line to which the dispensing container is connected in the common pipe and has one end connected to the discharge port of the liquid feed pump, and an exhaust line that is located downstream of the main line to which the dispensing container is connected in the common pipe and has an air filter connected to the end, it is preferable that the tube diameter of the main pipe is substantially equal to the tube diameter of the main line, and the tube diameter of the exhaust line is larger than the tube diameter of the main line.

[0020] In a case where an exhaust line is located downstream of the main line to which the dispensing container is connected and at a position higher than the main line, it is preferable that a part of the exhaust line is configured to be arched, a liquid level sensor is disposed in the middle of the ascending path, and the control unit detects the filling of liquid into the main line through the liquid level sensor. Effects of the Invention

[0021] According to the present invention described above, high-precision dispensing can be achieved by previously setting the discharge amount of the liquid feed pump that provides an appropriate liquid feeding amount for each dispensing container, and appropriately reflecting the discharge amount in the liquid feeding amount by utilizing the property that compression and expansion of the liquid are less likely to occur. Brief Description of the Drawings

[0022] [Figure 1] A configuration diagram showing a dispensing device according to an embodiment of the present invention. [Figure 2] A flowchart showing a procedure executed by a control unit of the dispensing device. [Figure 3] An explanatory diagram of the state of a vial corresponding to the flowchart. [Figure 4] A diagram showing the flow of liquid to a dispensing area corresponding to the flowchart. [Figure 5] A graph showing a state where an imbalance between vials and liquid feed amount has occurred. [Figure 6] A table storing settings for varying the number of pulses of a liquid feed pump according to distance. [Figure 7] A graph showing a state where the imbalance between vials and liquid feed amount has been improved according to Fig. 6. [Figure 8] A table storing settings for varying the number of pulses of a liquid feed pump according to elevation difference. [Figure 9] A graph showing a state where the imbalance between vials and liquid feed amount has been improved according to Fig. 8. [Figure 10] A diagram showing the relationship before and after changing the position of an exhaust valve. [Figure 11] A table obtained by merging Fig. 7 and Fig. 9. [Figure 12] A graph showing a state where the imbalance between vials and liquid feed amount has been further improved according to Fig. 11. Mode for Carrying Out the Invention

[0023] Hereinafter, embodiments of the present invention will be described with reference to the drawings.

[0024] The dispensing apparatus 1 of the present embodiment shown in Fig. 1 is provided with a liquid feeding area A1 and a dispensing area A2 in a housing of an apparatus main body (not shown), and feeds liquid to a vial 3 serving as a dispensing container disposed in the dispensing area A2 through discharge control of liquid from a tube pump 13 serving as a liquid feeding pump, which will be described later, disposed in the liquid feeding area A1.

[0025] In the liquid feeding area A1, a culture solution introduction part 12 serving as a supply source of a suspension culture solution, a gas introduction part 11, and the tube pump 13 are disposed, and these are associated with each other via a main pipe 10. Pinch valves 12a and 11a are provided at the inlets and outlets of the culture solution introduction part 12 and the gas introduction part 11, respectively.

[0026] 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. A tube set including the vial 3 is installed in each dispensing area A2. The tube set consists of multiple vials 3 arranged in parallel via branch pipes 32 to maintain a closed system on a common pipe 31. The vial 3 in this embodiment is of the type with one inlet port, and the culture medium is injected into the containment section through the inlet port.

[0027] Dispensing area A2 is equipped with a row of branch valves 21 for temporarily blocking the branch pipe 32, a row of heat sealers 22 for liquid-tight sealing of vials 3, a liquid supply valve 23 for opening and closing a portion of the liquid supply side of the common pipe 31, an exhaust valve 24 for opening and closing a portion of the exhaust line, and a liquid level sensor 25 for detecting the liquid level on the exhaust side of the common pipe 31.

[0028] 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. 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.

[0029] The control unit 4 also switches the controlled object between the left and right dispensing areas A2 within the chamber. To allow switching to the other dispensing area A2 while dispensing is in progress 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. 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.

[0030] The main pipe 10, common pipe 31, and branch pipe 32 are made of flexible tubing.

[0031] Regarding the specific tubing configurations in each section, 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.

[0032] 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).

[0033] Aseptic connectors, closed-system tube connection devices, etc., are suitably used for the aseptic connection section 50x and fittings 51, 52, and 53. The tube unit U is replaced by disconnecting it at the aseptic connection section 50x.

[0034] Furthermore, a flow rate correction unit 5 is connected to a branch 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 with an electronic balance 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.

[0035] The dispensing unit U and the dispensing device 1 will be described in detail below.

[0036] The common piping 31 of the dispensing unit U is folded back in part to form a main line L1, to which vials 3 are connected in a row, extending horizontally across two levels, upper and lower.

[0037] Of the common piping 31, the upstream of the lower main line L1 is designated as the liquid supply line L2, and its starting end is connected to the joint 50. Of the common piping 31, the downstream of the upper main line L1 is designated as the exhaust line L3, and an air filter 31a is connected to its end. In the dispensing unit U, liquid is supplied from the lower side to the upper side, and the air inside is exhausted from the upper side. The exhaust line L3 is positioned higher than the main line L1 in order to exhaust air.

[0038] The air filter 31a uses a sterile filter made of nonwoven fabric that prevents bacteria from entering, ensuring that no bacteria enter the internal space of the dispensing unit U. Therefore, the internal space of the dispensing unit U can be kept closed during handling. The pressure loss in the air filter 31a is generally minimized when the air is exhausted from the dispensing unit U than when it enters the unit U, but it can also be used in the reverse direction.

[0039] To ensure the dispensing unit U is placed in a clean environment, the entire unit is subjected to sterilization in a sterilization device (not shown). In this embodiment, gamma ray sterilization is performed, and the tubes constituting the common piping 31, the tubes constituting the branch piping 32, and other component parts such as plate materials (not shown) that hold them are sterilized and ready for use. For this reason, these component parts are made of materials resistant to gamma ray sterilization.

[0040] Next, we will describe the dispensing device 1.

[0041] First, the liquid delivery area A1 of the dispensing device 1 consists of the following configuration.

[0042] The culture medium introduction section 12 is, in this case, a bag filled with a suspension. The bag is filled with a suspension in which cells are mixed with culture medium, which has been cultured in a cell culture system (not shown in the diagram), and this is set into the 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.

[0043] The tube pump 13 has the function of pumping out liquid by applying pressure from the outside of the tube with rollers, squeezing the tube to compress it, in order to deliver 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 any culture medium remaining in the dispensing area A2 after dispensing is completed is recovered from the common pipe 31 of the dispensing area A2 to the culture medium introduction section 12 by the tube pump 13.

[0044] The gas inlet 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.

[0045] On the other hand, the dispensing area A2 of the dispensing device 1 has the following configuration.

[0046] 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 configured to be curved, in order to detect the liquid level position.

[0047] The liquid supply valve 23 of the common piping 31 is positioned to pinch the liquid supply line L2, which is located upstream of the main line L1. This liquid supply valve 23 is a pinch valve that opens and closes the liquid supply line L2 by pressurizing the tube from the outside and compressing it in order to maintain a closed system.

[0048] The exhaust valve 24 of the common piping 31 is positioned to pinch the exhaust line L3, which is located downstream of the vial 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.

[0049] The dispensing unit U has a predetermined mounting position inside the storage area. In the dispensing area A2, a branch valve 21a is provided at the position where the branch pipe 32 of vial 3 is positioned when the dispensing unit U is set up. This valve pressurizes the tube from the outside, crushing it and closing / releasing the dispensing line L4.

[0050] Furthermore, in the dispensing area A2, a heat sealer row 22, which is a sealing section, is provided at a position corresponding to the heat seal section 3a set on a part of the vial 3. The heat sealer row 22 is configured to seal the inside by welding it with the heat of a heater while the area near the inlet port of the vial 3 is crushed.

[0051] Figure 2 is a flowchart showing an overview of the control procedure performed by the control unit 4, and Figure 3 is an explanatory diagram of the liquid delivery state corresponding to the flowchart. The operation of the dispensing device 1 in Figure 1 will be explained below in accordance with the flowchart.

[0052] In this dispensing device 1, 25 vials 3 are arranged on the lower level and 25 vials on the upper level. For convenience, they are numbered starting from the position closest to the tube pump 13, as shown in Figures 4(A) and (B), with the lower level numbered from No. 1 to No. 25 and the upper level numbered from No. 26 to No. 50. The number of vials 3 can be set appropriately depending on the purpose and application, and the number of levels is not limited to two levels; it can be one level or three or more levels.

[0053] <Step T1: Vial aspiration process> First, gas (air) g is drawn from each vial 3. To do this, the control unit 4 closes the exhaust line L3 with the exhaust valve 24, opens the branch valve 21a, and with the valve 11a of the atmospheric vent (gas inlet) 11 open, the tube pump 13 is used to draw gas from inside the vials 3.

[0054] Vial 3 is a so-called soft vial, made of a resin that is deformable enough to shrink when suctioned. This causes the air inside Vial 3 to be sucked out and it to collapse (see Figure 3(a)). After suctioning the inside, close the branch valve 21a (see Figure 3(b)). This operation is performed separately for the upper vials No. 50 to 26 and the lower vials No. 25 to 1 (see Figure 4(A)). There are differences in distance from the pump and height between the upper and lower rows, but by separating the suction operation between the upper and lower rows, it is possible to reduce variations in the amount of suction due to the pressure difference between the upper and lower rows. Of course, if the pressure difference between the upper and lower rows is small or there are no particular problems, it is not necessary to separate the suction operation between the upper and lower rows.

[0055] The air intake from vial 3 creates negative pressure in the common piping 31. Therefore, the control unit 4 opens the exhaust valve 24, venting the common piping 31 to the atmosphere. The branch valve 21a of vial 3 remains closed.

[0056] <Step T2: Liquid filling process> 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 deliver the culture medium c from the main piping 10 to the common piping 31 in the dispensing area A2. The delivery continues from the upstream vial No. 1 through the downstream vial No. 50 until the liquid enters the exhaust line L3 (see Figure 4(B)).

[0057] As shown in Figures 3(c)→(d), when the liquid level rises and the liquid level sensor 25 detects the liquid level, the control unit 4 stops the liquid supply by the tube pump 13. This confirms that the culture medium c has been reliably filled into the main line L1 of the common piping 31. In order to release the pressure inside the common piping 31 to the atmosphere, 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, and then releases the pressure inside the piping.

[0058] If the liquid level sensor 25 were to be placed at the very top of the curved section of the exhaust line L3 shown in Figure 1 (in this case, the horizontal section of the trapezoid), then liquid would be located in the lower layer of the tube and 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 upward path as shown in Figures 3(c) and (d), 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 downward side of the curved section, namely, wasted liquid and the filter 31a becoming wet and unable to supply liquid, can be avoided.

[0059] <Step T3: Liquid transfer process to vial> The control unit 4 delivers the culture medium c to each vial 3. Specifically, it closes the exhaust valve 24, opens the branch valve 21a, and operates the tube pump 13 to deliver the culture medium c from the culture medium introduction unit 12 towards the main line L1 of the common piping 31. At the same time, it opens each branch 21a of the branch line L4 one by one to deliver the culture medium c to the vial 3, and then closes the branch valve 21a. Since the vial 3 is under suction, opening the valve causes negative pressure to draw in the culture medium c (see Figure 3(e)). This operation is performed sequentially from vial No. 50 to No. 26 located on the upper side, as shown in Figure 4(A), and then sequentially from vial No. 25 to No. 1 located on the lower side.

[0060] <Step T4: Returning the suspension to the bag> Once step T3 is complete and all vials 3 have been fed towards the inlet ports, 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 section 12. In this state, as shown in Figure 3(f), the culture medium c accumulates at the bottom of the vial 3's containment section, and the culture medium c remains in the branch line L4.

[0061] Additionally, some culture medium c remains in the alternative pathway x shown in Figure 1. Therefore, the control unit 4 returns this to the bag that constitutes the culture medium introduction unit 12. To do this, the control unit 4 recovers the remaining culture medium c by closing the liquid delivery valve 23 and operating the tube pump 13 in the reverse direction.

[0062] <Step T5: Pre-pressurizing the piping> Step T4 creates a negative pressure upstream of the liquid supply valve 23, so the control unit 4 opens the liquid supply valve 23 and releases the pressure in the common piping 31 to the atmosphere. Subsequently, 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 and create a pre-pressurized state. The gas is introduced so that it spreads throughout the entire common piping 31 (see Figure 4(B)).

[0063] <Step T6: Vial air purge (upper section)> Next, the culture medium c remaining in branch line L4 is pushed into vial 3, and air purging is performed with gas g to replace the air remaining in vial 3 with culture medium c (see Figure 3(g)). This operation is carried out by opening and closing each branch valve 21a one by one from downstream to upstream (see Figure 4(A)). First, in step T6, the air purging of the upper vials No. 50 to No. 26 is completed.

[0064] <Step T7: Vial air purge (lower section)> The control unit 4 then continues to perform an air purge on the lower vials No. 25 → No. 1 using the same procedure.

[0065] <Step T8: Depressure of vial> Once all vials 3 have been filled with culture medium c, the control unit 4 opens the exhaust valve 24 and the branch valve 21a, releasing the contents of vials 3 into the atmosphere.

[0066] The control unit 4 activates the heat sealer 22a to seal the heat seal portion 3a of the vial 3 shown in Figure 3(h). When heat sealing, the heat seal portion 3a of the vial 3 is crushed, sealing the containment portion 3b filled with culture medium c, and the gas (air) g that is pushed out at this time is discharged from the downstream air filter 31a. This operation may be performed simultaneously for all vials 3, or it may be performed sequentially from vial No. 50 on the downstream side to vial No. 1 on the upstream side, as shown in Figure 4(A).

[0067] Figure 5 shows the amount of liquid dispensed for each vial number when the tube pump 13 is rotated uniformly at a pulse rate (e.g., 300 pulses / second) that would result in 1 ml of liquid being dispensed per second through the main pipe 10 using the dispensing device 1 in Figure 1. As a trend, the amount of liquid dispensed decreases to the right as you move towards vial 3 (the vial on the right side of the figure), which is further away from the tube pump 13. Also, the amount of liquid dispensed by vial No. 25, the downstream vial in the lower row shown in Figure 4, is significantly higher than that of vial No. 24 upstream of it and vial No. 26 in the upper row immediately downstream, and the amount of liquid dispensed by vial No. 50, the downstream vial in the upper row, is significantly higher than that of vial No. 49 upstream of it. There is a general trend of increasing liquid dispensed from upstream to downstream, but it can be seen that No. 50 and No. 25 deviate from this trend.

[0068] Considering these points, the following can be inferred. (1) Pressure loss in piping is affected by the length of the piping, and the longer the distance along the tube the liquid is delivered, the greater the pressure loss.

[0069] (2) The volume of fluid delivered increases due to backflow, influenced by the height of vial 3. From the second vial No. 26 to the first vial No. 25, backflow pressure is applied due to the difference in height between the first and second stages, so the volume of fluid to vial No. 25 increases in particular. A pressure difference of 1 kPa is estimated for a height difference of 10 cm.

[0070] (3) The installation position of the exhaust valve 24 affects the amount of liquid delivered, which increases due to backflow. Regarding vial No. 50, although the downstream exhaust line L3 is at a high position, the difference in elevation is not as significant as that between vials No. 26 and 25, so the effect of backflow here is not thought to be very large. Rather, it is more likely that the liquid volume is increasing due to the position of exhaust valve 24.

[0071] As described above, in this embodiment, a portion of the exhaust line L3 is configured to be curved, and the exhaust valve 24 is placed in the middle of its upward path. However, when the data in Figure 5 was collected, the measurement was taken with the exhaust valve 24 located downstream of the curved portion, as shown in Figure 10 which shows the positional relationship of the exhaust valve 24 before and after the modification.

[0072] When injecting liquid into vial 3 after filling, the exhaust valve 24 is closed, and then the branch valves 21a are opened and closed sequentially from vial No. 50 to vial No. 1 to dispense the liquid. However, as shown by the dashed line in Figure 10, if the exhaust valve 24 is located downstream of the liquid level sensor 25, an air pocket is likely to form in the piping between the exhaust valve 24 and the liquid level sensor 25 when the exhaust valve 24 is closed. As a result, even when pressure is applied during liquid delivery, the air layer is compressed and absorbs the pressure. When the exhaust valve 24 is closed and liquid delivery and dispensing are performed, the air layer expands, allowing the liquid in the exhaust line L3 to flow back into the main line L1, and it is thought that this liquid then flowed into vial No. 50.

[0073] Based on the considerations in (1) to (3) above, in this embodiment, measures were taken to change the number of pulses of the tube pump 13 by the difference between the amount of fluid delivered to each vial 3 and the target amount of fluid delivered.

[0074] Specifically, measures were taken to address imbalances in the amount of fluid delivered due to the distance of each vial 3 from the tube pump 13, imbalances in the amount of fluid delivered due to differences in the height of the vials 3, and imbalances in the amount of fluid delivered due to the mounting position of the exhaust valve 24.

[0075] 1. <Measures to address imbalance depending on the distance from the tube pump 13> This is addressed by rewriting the fluid delivery table. Figure 6 shows the first fluid delivery table, which the control unit 4 has newly stored in memory to drive the tube pump 13, indicating the number of drive pulses for each vial 3. The number of pulses during fluid delivery gradually decreases from 300 depending on the distance from the tube pump 13 to the vial 3, with the number of pulses increasing for vials 3 that are farther away and decreasing for vials that are closer. Here, the number of pulses is adjusted individually based on the difference between the target value and the measured value, so it is not perfectly proportional, but it is also acceptable to approximate the imbalance with a proportional formula and perform pulse adjustment.

[0076] Figure 7 shows the corrected vial numbers and fluid delivery volumes. Overall, the tendency to show a rightward slump has been eliminated, and it was confirmed that fluid delivery is nearly stable at all positions. Note that the increase in fluid volume for vials No. 25 and No. 50 is not due to distance, and therefore this increase has not been resolved.

[0077] 2. <Measures to address imbalances based on differences in vial height> This was addressed by rewriting the fluid delivery table. Figure 8 shows the second fluid delivery table stored in memory. While the overall pulse rate was set to 300 pulses / second, the pulse rate of the tube pump 13 was reduced to 90 when dispensing into vial No. 25. As a result, as shown in Figure 9, it was confirmed that the amount of fluid delivered to vial 25 was reduced, although the overall trend was downward.

[0078] 3. <Measures to address imbalance by changing the mounting position of exhaust valve 24> As described above based on Figure 10, one of the improvements in this embodiment is that the exhaust valve 24 was repositioned from the position shown by the dashed line in the figure to the position shown by the solid line, i.e., to a position upstream of the liquid level sensor 25. This ensures that the exhaust valve 24 closes when the vial is completely filled with liquid during delivery. As a result, since the compression and expansion coefficient of the liquid is close to 1, backflow of liquid from the exhaust line L3 to the main line L2 is less likely to occur when injecting into vial No. 50, and it was confirmed that the increase in the amount of liquid in vial No. 50 as shown in Figure 9 was improved. By moving the exhaust valve 24, the overall liquid delivery volume became more stable, and in particular, the liquid delivery volume to vial No. 50 was stabilized. Furthermore, for vial No. 24, the effect of air pockets was eliminated, and the only problem was backflow in the height direction. The aforementioned protruding liquid volume was reproducible and could be stabilized by adjusting the pulse amount.

[0079] 4. <Measures based on a combination of the above 1 and 2> Figure 11 shows the third liquid delivery table stored in memory, which is a combination of the first and second liquid delivery tables. As a result, as shown in Figure 12, the downward sloping characteristic is eliminated, the increase in liquid volume to vials No. 25 and 50 is also eliminated, and it was confirmed that more accurate liquid delivery can be achieved overall.

[0080] As described above, the dispensing device of this embodiment is The system comprises a common pipe 31, multiple vials 3 which are dispensing containers connected to the common pipe 31, a tubular pump 13 which is a liquid transfer pump that communicates with the common pipe 31, and a control unit 4 which controls the operation of dispensing from the tubular pump 13 to each vial 3 through the common pipe 31. The tube pump 13 has a variable discharge rate, and the control unit 4 controls the tube pump 13 with a predetermined discharge rate for each vial 3 connected to the common piping 31 so that a predetermined amount of liquid is delivered to each vial 3.

[0081] Thus, in this embodiment, the appropriate liquid delivery volume is adjusted in advance for each vial 3 through the discharge volume of the tube pump 13, so that errors in the dispensing volume, including imbalances caused by the arrangement of the vials 3, can be appropriately suppressed. Moreover, since this embodiment utilizes the small compression ratio of the liquid to immediately reflect the liquid delivery volume to the vials 3 in a feedforward manner through the discharge volume control of the tube pump 13, errors due to time lag are less likely to occur compared to feedback control, and there is no need to install sensors for each vial 3.

[0082] In this embodiment, the vials 3 are connected in a distributed manner from upstream to downstream along the common piping 31, and the control unit 4 is configured to control the tube pump 13 with a discharge rate corresponding to the distance from the tube pump 13 to each vial 3.

[0083] By implementing this type of control, pressure loss can be compensated for, and the liquid delivery rate can be kept constant or close to constant regardless of the length of the piping, thereby appropriately improving the accuracy of liquid delivery.

[0084] Furthermore, in this embodiment, the vial 3 is connected to the common piping 31 with a difference in height, and the control unit 4 is configured to control the tube pump 13 with a discharge rate corresponding to the height difference of the vial 3.

[0085] Liquid delivery performance is affected by differences in pipe elevation, with higher positions being more difficult to access. Therefore, by implementing the control described above, it becomes possible to maintain a constant or near-constant liquid delivery rate regardless of elevation differences, thereby appropriately improving liquid delivery accuracy.

[0086] Furthermore, the control unit 4 sequentially dispenses to each vial 3 after closing a portion of the exhaust line L3, which is located downstream of the main line L1 to which the vials 3 are connected, using an exhaust valve 24. A liquid level sensor 25 is placed in a portion of the exhaust line L3, and the exhaust valve 24 is placed upstream of the liquid level sensor 25.

[0087] This method makes it less likely for air pockets to form upstream of the exhaust valve 24, thereby effectively preventing liquid from flowing back into the main line L1 due to the compression and expansion of air.

[0088] 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. For these reasons, if all the tubes were made of the same diameter, the liquid delivery accuracy would be poor.

[0089] In contrast, in the configuration of this embodiment, the diameter φa of tube t10 of the main pipe 10, which is located upstream of the main line L1 to which vial 3 is connected and has one end connected to the discharge port of tube pump 13, is made approximately equal to the diameter φb of tube t11 of the main line L1, while the diameter φd of tube t13 of the liquid delivery line L3 is made thicker than the diameter φa of tube t10 of the main line L1.

[0090] Therefore, by reducing the tube diameter of the main line L1 and the main piping 10, the accuracy of liquid delivery can be improved, and by increasing the tube diameter of the exhaust line L3, it becomes possible to properly release the air and pressure that has entered the piping to the air filter 31a side.

[0091] Furthermore, an exhaust line L3 is provided located downstream of the main line L1 to which vial 3 is connected, and at a higher position than the main line L1. Part of the exhaust line L3 is configured to be curved, and a liquid level sensor 25 is placed along its ascending path. The control unit 4 detects the filling of liquid into the main line L1 through the liquid level sensor 25.

[0092] Therefore, the tube to be detected by the liquid level sensor 25 can be filled with liquid, making it possible to appropriately detect the liquid level.

[0093] 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.

[0094] For example, in the above embodiment, a one-port vial was used, but a two-port vial or the like may also be used. In this case, injection and aspiration can be performed in parallel, so steps T1 and T2 in the flowchart become unnecessary.

[0095] In addition to vials, dispensing containers can also be in the form of bags.

[0096] Other configurations may also include, for example, suspensions that have been concentrated and replaced for cryopreservation. As a cell culture production system, various modifications are possible without departing from the spirit of the present invention, such as transferring a suspension containing cells cultured in a cell culture device from the suspension containment section of the cell culture device to a cell concentration and replacement device, and then transferring the concentrated and replaced suspension with a freezing solution to the cell introduction section of a cell dispensing device. [Explanation of Symbols]

[0097] 3… Dispensing container (vial) 4…Control Unit 10…Main piping 13…Liquid transfer pump (tubular pump) 25…Liquid level sensor 31…Common Piping L1...Main line L3... Exhaust line

Claims

1. The system comprises a common pipe, a plurality of dispensing containers connected to the common pipe, a liquid transfer pump communicating with the common pipe, and a control unit that controls the operation of dispensing from the liquid transfer pump to each of the dispensing containers through the common pipe, The dispensing device is characterized in that the liquid delivery pump has a variable discharge rate, and the control unit controls the liquid delivery pump with a predetermined discharge rate for each dispensing container connected to the common piping so that a predetermined liquid delivery rate is achieved.

2. In a configuration in which the dispensing containers are distributed and connected from upstream to downstream of the common piping, the control unit controls the liquid delivery pump with a discharge rate corresponding to the distance from the liquid delivery pump to each of the dispensing containers.

3. A dispensing device characterized in that, in a configuration in which the dispensing container is connected to the common piping with a difference in height, the control unit controls the liquid delivery pump with a discharge amount corresponding to the height difference of the dispensing container.

4. The dispensing apparatus according to claim 3, wherein the control unit sequentially dispenses to each dispensing container after closing a portion of the exhaust line located downstream of the main line to which the dispensing containers are connected in the common piping with an exhaust valve, and a liquid level sensor is placed in a portion of the exhaust line, and the exhaust valve is placed upstream of the liquid level sensor.

5. The dispensing device according to claim 1, comprising: a main pipe located upstream of the main line to which the dispensing container is connected, and one end of which is connected to the discharge port of the liquid transfer pump; and an exhaust line located downstream of the main line to which the dispensing container is connected, and an air filter is connected to its end, wherein the tube diameter of the main pipe is approximately equal to the tube diameter of the main line, and the tube diameter of the exhaust line is larger than the tube diameter of the main line.

6. The dispensing device according to claim 1, wherein an exhaust line is provided located downstream of the main line to which the dispensing container is connected and at a higher position than the main line, a portion of the exhaust line is configured to be curved, a liquid level sensor is placed in the middle of the upward path, and the control unit detects the filling of liquid into the main line through the liquid level sensor.

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