Cell fluid dispensing method

Abstract

A cell fluid dispensing method. The dispensing method is applied to a cell fluid dispensing system, and the cell fluid dispensing system comprises a peristaltic pump, package bags (20), a calibration container (10) and a diaphragm pump which are connected in sequence in the extending direction of a same dispensing pipeline. The dispensing method comprises: first pumping a cell fluid into the package bags (20), then discharging gas mixed into the cell fluid and gas originally remaining in the package bags (20) out of the package bags (20) by means of withdrawing, and transferring same to the dispensing pipeline, and then discharging the residual gas mixed in the dispensing pipeline by means of the calibration container (10) and the diaphragm pump on the dispensing pipeline to obtain a gas-liquid separated cell fluid, and finally pumping the gas-liquid separated cell fluid into the package bags (20) again, thereby obtaining dispensed products without residual bubbles, improving the dispensing quality.

Description

A method for packaging cell fluid Technical Field

[0001] The present invention relates to the technical field of preparation subpackaging, in particular to a cell fluid subpackaging method. Background Art

[0002] In the field of cell therapy, cell fluid packaging technology is very important. The cell fluid must be kept in a sterile environment during the packaging process, and the finished packaged products generally have unified specifications and standards, and there are also high requirements for packaging accuracy. In addition, during the preparation and packaging of cell fluid, since the packaging pumps, pipelines and other parts are not in a vacuum state, air is trapped inside, which can easily mix in and form bubbles during the transfer and packaging of the cell fluid, resulting in poor packaging specifications and accuracy of the cell fluid, and also reducing the quality of the cell fluid itself.

[0003] Summary of the Invention

[0004] The main purpose of the present invention is to provide a cell fluid packaging method to solve the problems of low cell fluid packaging efficiency, low packaging precision and poor finished product effect in the prior art.

[0005] To achieve the above-mentioned object, the present invention provides the following technical solution: a cell fluid subpackaging method, the subpackaging method being applied to a cell fluid subpackaging system, the cell fluid subpackaging system comprising a peristaltic pump, a subpackaging bag, a calibration container, and a diaphragm pump connected in sequence along the extension direction of the same subpackaging pipeline; wherein the subpackaging bag is connected to a branch of the subpackaging pipeline via a branch valve, the subpackaging method comprising the following steps:

[0006] Opening the branch valve and closing the inlet of the calibration container, and pumping the cell solution into the sub-packaging bag through the peristaltic pump;

[0007] The peristaltic pump is used to sequentially withdraw the residual gas and cell fluid from each of the sub-packaging bags and close the corresponding branch valve;

[0008] Opening the inlet of the calibration container and pumping the withdrawn cell fluid into the calibration container through the peristaltic pump;

[0009] performing gas-liquid separation on the pumped cell fluid through the calibration container to obtain gas-liquid separated cell fluid;

[0010] The branch valve is opened again and the cell solution is pumped into the sub-packaging bag through the peristaltic pump.

[0011] Optionally, a gas-liquid detector is provided on the inlet and outlet of the calibration container, respectively; wherein the inlet and outlet of the calibration container are respectively arranged at the bottom and the top, and the cell fluid is pumped into the calibration container from the bottom to the top; the closed ends on the upper and lower sides of the calibration container are arranged at an angle, and the inlet and outlet of the calibration container are respectively located at the lowest position and the highest position of the two closed ends of the calibration container;

[0012] The step of performing gas-liquid separation on the pumped cell fluid through the calibration container to obtain the gas-liquid separated cell fluid comprises:

[0013] The cell fluid is pumped into the calibration container from its inlet, the calibration container is used to perform gas-liquid separation on the cell fluid, and the separated gas is discharged from the outlet at the top to obtain the gas-liquid separated cell fluid remaining in the calibration container.

[0014] Optionally, after pumping cell fluid into the calibration container from the inlet, performing gas-liquid separation on the cell fluid using the calibration container, and discharging the separated gas from the outlet at the top to obtain the gas-liquid separated cell fluid remaining in the calibration container, the method further comprises:

[0015] The gas-liquid separated cell fluid is pumped back from the inlet of the calibration container by the peristaltic pump, and the pumping is stopped when the gas-liquid detector at the inlet of the calibration container detects gas and the first step number of the peristaltic pump at this time is recorded;

[0016] injecting the gas-liquid separation cell solution into the calibration container through the peristaltic pump and recording the second step number of the peristaltic pump when the gas-liquid detector at the outlet of the calibration container detects liquid;

[0017] Calculating a calibration coefficient of the peristaltic pump according to the first number, the second number of steps, and the volume of the calibration container;

[0018] The step of opening the branch valve again and pumping the cell solution into the sub-packaging bag through the peristaltic pump comprises:

[0019] The branch valve is opened again, and the cell solution is pumped into the sub-packaging bag through the peristaltic pump according to the quantitative relationship determined by the calibration coefficient.

[0020] Optionally, before the branch valve is opened and the inlet of the calibration container is closed, and the cell solution is pumped into the sub-packaging bag through the peristaltic pump, an emptying operation of the peristaltic pump is performed, including the following steps:

[0021] Starting the peristaltic pump to be tested at a first speed;

[0022] When the gas-liquid detector located at the outlet end of the calibration container detects that the flow medium is converted from air to liquid, it sends a control signal to control the peristaltic pump to stop;

[0023] The peristaltic pump is controlled to reverse at a second speed. When the gas-liquid detector located at the inlet end of the calibration container detects that the flow medium is converted from liquid to air, a control signal is sent to control the peristaltic pump to be detected to stop.

[0024] Optionally, the first rotational speed is less than 120 rpm, and the second rotational speed is 5-20 rpm.

[0025] Optionally, when obtaining the first step number and the second step number of the peristaltic pump, the rotation speed of the peristaltic pump is 5-20 rpm.

[0026] Optionally, the calibration coefficients satisfy V r =V / S, where V represents the volume of the standard container, and S satisfies S=S1-S2, where S1 represents the first step number, and S2 represents the second step number.

[0027] Optionally, the cell fluid packaging system further includes an air pressure sensor provided at one end of the packaging pipeline close to the diaphragm pump; and before opening the branch valve and closing the inlet of the calibration container and pumping the cell fluid into the packaging bag through the peristaltic pump, the system further includes:

[0028] Open all the branch valves and extract the gas in each sub-bag through the diaphragm pump;

[0029] After reaching a defined negative pressure value, the pressure sensor is used to detect whether the internal pressure of the cell solution dispensing system remains unchanged;

[0030] If so, complete the air tightness test of the cell liquid packaging system.

[0031] Optionally, the cell fluid packaging system further comprises a plurality of preparation pipelines for injecting different preparations, wherein the preparation pipelines merge into one pipeline at one end and are connected to a mixing bag, and a preparation pump is further provided between the mixing bag and the preparation pipeline; before opening the branch valve and closing the inlet of the calibration container and pumping the cell fluid into the packaging bag through the peristaltic pump, the system further comprises:

[0032] Prepare the preparation according to the cell fluid preparation specifications and inject it into the mixing bag through the preparation pipeline;

[0033] The injected preparation is mixed by the mixing bag to obtain the cell fluid to be packaged.

[0034] Optionally, the cell fluid packaging system further includes a sampling pipeline connected to the mixing bag; after the injected preparation is mixed by the mixing bag to obtain the cell fluid to be packaged, the system further includes:

[0035] The cell fluid in the mixing bag is extracted through a sampling pipeline and tested to see if the cell fluid is qualified.

[0036] Optionally, after reopening the branch valve and pumping the cell solution into the sub-packaging bag through the peristaltic pump, the method further comprises:

[0037] When all the sub-packaging bags are completely filled, the branch valve is closed and the sub-packaging bags that have been injected with cell fluid are removed.

[0038] Optionally, after closing the branch valve and removing the sub-packaging bag into which the cell solution has been injected, the method further comprises:

[0039] The steps of assembling a sub-packaging bag without cell solution on the sub-packaging pipeline, returning to open the branch valve and closing the inlet of the calibration container, and pumping cell solution into the sub-packaging bag through the peristaltic pump.

[0040] Optionally, before opening the branch valve and closing the inlet of the calibration container and pumping the cell solution into the sub-packaging bag through the peristaltic pump, the process further comprises:

[0041] Opening the inlet of the calibration container, and pumping the treated cell fluid free of residual gas into the calibration container through the peristaltic pump, and recording the third step number of the peristaltic pump when the gas-liquid detector at the inlet of the calibration container detects liquid;

[0042] recording a fourth step number of the peristaltic pump when the gas-liquid detector at the outlet of the calibration container detects liquid;

[0043] A calibration coefficient of the peristaltic pump is calculated according to the third number of steps, the fourth number of steps, and the volume of the calibration container.

[0044] Optionally, the packaging bag includes a bag body, a liquid tube and puncture bodies respectively arranged on both sides of the liquid tube, the liquid tube is connected to the bag body, and the puncture bodies are parallel to the liquid tube and penetrate into the side of the bag body close to the liquid tube to form a cavity.

[0045] Compared with the existing cell fluid packaging method, the present application has at least the following beneficial effects: based on a cell fluid packaging system including a peristaltic pump, a packaging bag, a calibration container and a diaphragm pump connected in sequence in the extension direction of the same packaging pipeline, the initial cell fluid in the packaging process is directly pumped into the packaging bag by opening the branch valve and closing the inlet of the calibration container. After the cell fluid enters the packaging bag, the residual gas mixed therein and the inherent gas in the packaging bag will be located above the packaging bag body due to their low density. At the same time, the pumping process can form a certain degree of gas-liquid separation; then the gas in the packaging bag is extracted into the packaging pipeline by back-pumping the peristaltic pump and the branch valve is closed. The back-pumping can contain a certain amount of pumped-in cell fluid so that the cell fluid inside the packaging bag contacts the bag body under the action of negative pressure and is fully filled; then the inlet of the calibration container is opened and the cell fluid mixed with gas is pumped into the calibration container by the peristaltic pump, and the residual gas and the cell fluid are separated in the calibration container to obtain gas-liquid separated cell fluid; finally, the branch valve is reopened, The gas-liquid separated cell fluid is pumped into the packaging bag so that there is little or no residual gas in the packaging bag filled with the cell fluid, thereby improving the packaging efficiency, packaging accuracy, finished product qualification rate and the quality of the packaged finished product. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] FIG1 is a schematic structural diagram of a packaging system using the packaging method of the present application;

[0047] FIG2 is a schematic flow chart of an embodiment of the packaging method of the present application;

[0048] FIG3 is a schematic structural diagram of an embodiment of a calibration container in the packaging system used in the present application;

[0049] FIG4 is a schematic structural diagram of an embodiment of a packaging bag in the packaging system used in the present application;

[0050] Serial number description: 10, calibration container; 101, inlet; 102, outlet; 103, vertical baffle; 20, filling bag; 201, bag body; 202, liquid bag pipeline; 203, puncture port; 204, bag tail;

[0051] The realization of the objectives, functional features and advantages of this application will be further explained in conjunction with embodiments and with reference to the accompanying drawings. DETAILED DESCRIPTION

[0052] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0053] The terms "first," "second," and "third" in this application are used only for descriptive purposes and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Thus, a feature defined as "first," "second," or "third" may explicitly or implicitly include at least one of such features. In the description of this application, "multiple" means at least two, for example, two, three, etc., unless otherwise specifically defined. All directional indications in the embodiments of this application (such as up, down, left, right, front, back...) are only used to explain the relative positional relationship, movement, etc. between the components under a specific posture (as shown in the accompanying drawings). If the specific posture changes, the directional indications also change accordingly. In addition, the terms "including" and "having," as well as any variations thereof, are intended to cover non-exclusive inclusions. For example, a process, method, system, product, or device that includes a series of steps or units is not limited to the listed steps or units, but may optionally include steps or units that are not listed, or may optionally include other steps or units that are inherent to these processes, methods, products, or devices.

[0054] References to "embodiments" herein mean that a particular feature, structure, or characteristic described in connection with the embodiments may be included in at least one embodiment of the present application. The appearance of the phrase in various places in the specification does not necessarily refer to the same embodiment, nor does it constitute an independent or alternative embodiment that is mutually exclusive of other embodiments. It is understood, both explicitly and implicitly, by those skilled in the art that the embodiments described herein may be combined with other embodiments.

[0055] In the cell slurry packaging process, the more conventional method is to transport the cell slurry through a closed piping system through a hydraulic pump, inject the cell slurry into the packaging consumables, and seal and package it. However, during the process from cell slurry preparation to packaging, it is not always in a vacuum environment. Affected by the preparation container, pipelines and packaging consumables, the cell slurry is often mixed with gas, which not only leads to a deterioration in the fluid uniformity of the cell slurry, but also affects the quality of the cell slurry itself when the residual gas can react with the substances in the cell slurry. On the other hand, when injecting the packaging consumables, it may not be able to be accurately packaged according to the expected specifications. For example, when there is residual gas in the cell slurry, after packaging according to the predetermined specifications, the actual value of the cell slurry in the packaging consumables will be less than the predetermined specifications due to the presence of residual gas, resulting in a volume deviation of even 10%, thereby affecting the packaging yield.

[0056] To address the problems existing in the above-mentioned packaging process, one embodiment of the present application provides a cell fluid packaging method, which is applied to a cell fluid packaging system. The cell fluid packaging system includes a peristaltic pump, a packaging bag, a calibration container, and a diaphragm pump connected in sequence along the extension direction of the same packaging pipeline; wherein the packaging bag is connected to a branch of the packaging pipeline via a branch valve. Referring to FIG2 , the packaging method includes the following steps:

[0057] Step S1, opening the branch valve and closing the inlet of the calibration container, and pumping the cell solution into the sub-packaging bag through the peristaltic pump;

[0058] Step S2, using the peristaltic pump to sequentially pump back the residual gas and cell fluid in each of the packaging bags and close the corresponding branch valve;

[0059] Step S3, opening the inlet of the calibration container, and pumping the withdrawn cell fluid into the calibration container through the peristaltic pump;

[0060] Step S4, performing gas-liquid separation on the pumped cell fluid through the calibration container to obtain gas-liquid separated cell fluid;

[0061] Step S5, opening the branch valve again and pumping the cell solution into the sub-packaging bag through the peristaltic pump.

[0062] Furthermore, before step S1, the peristaltic pump is emptied, which specifically includes the following steps:

[0063] S01, starting the peristaltic pump to be tested at a first speed;

[0064] S02, when the gas-liquid detector located at the outlet end of the calibration container detects that the flowing medium is converted from air to liquid, it sends a control signal to control the peristaltic pump to stop;

[0065] S03, controlling the peristaltic pump to reverse at a second speed, and when the gas-liquid detector located at the inlet end of the calibration container detects that the flow medium is converted from liquid to air, sending a control signal to control the peristaltic pump to be detected to stop.

[0066] It should be noted that the first rotation speed is less than 120 rpm, and the second rotation speed is 5-20 rpm.

[0067] The above operation steps belong to the adjustment process of the peristaltic pump. When the peristaltic pump is not working, a large amount of air will enter its interior. The above operation can discharge the inherent air in the peristaltic pump, ensuring that the cell fluid completely fills the working space of the peristaltic pump, thereby ensuring that the peristaltic pump outputs only cell fluid, thereby improving the accuracy of the peristaltic pump operation.

[0068] Secondly, the first and second speeds must be set in accordance with regulations. This is because, in actual operation, both the first and second detectors have detection response times. If the first speed is too fast, the conversion rate between air and cell fluid will be accelerated, which will cause the detectors to be unable to detect the phase transition in the first place, affecting the accuracy of detection.

[0069] At the same time, although too low a rotation speed can ensure the accuracy of detection, it is not conducive to improving the detection efficiency. Therefore, the above-mentioned rotation speed setting ensures a balance between detection accuracy and detection efficiency, thereby improving the overall performance of the equipment.

[0070] Finally, in the above control process, the emptying is terminated based on the control signal of the second detector. The entire emptying operation is stopped when the standard container is just filled. On the one hand, this provides sufficient operating time for the peristaltic pump to be tested to ensure that the air in the peristaltic pump to be tested can be completely discharged; on the other hand, the entire emptying operation can be stopped in time, which not only improves work efficiency but also avoids waste of cell fluid.

[0071] The end of the liquid extraction process is based on the detection signal of the first detector, so the end of the entire liquid extraction process can be controlled in time. On the one hand, the particularity of the installation point of the first detector can avoid the occurrence of cell fluid residue in the standard container, thereby ensuring the accuracy of the injected cell fluid volume; on the other hand, it can prevent air from entering the peristaltic pump again due to liquid extraction, thereby ensuring the stability of the environment inside the peristaltic pump to be tested;

[0072] At the same time, through the above operation, the air in the peristaltic pump can be discharged as soon as the equipment is working, ensuring the reliability and accuracy of subsequent operations.

[0073] Specifically, FIG1 shows a packaging system using the packaging method of the present application, which includes a peristaltic pump, a packaging bag, a calibration container, and a diaphragm pump connected in sequence along the extension direction of the same pipeline; wherein the packaging bag is connected to a branch of the packaging pipeline via a branch valve;

[0074] The peristaltic pump is arranged in the input direction of the cell fluid and can peristalsize in both directions to pump the cell fluid into or withdraw it from the filling pipeline.

[0075] Multiple sub-packaging bags can be arranged in a side-by-side manner on the branch of the sub-packaging pipeline to form a group to improve the sub-packaging efficiency. The sub-packaging bag is also provided with a pinch valve for opening or closing the bag body. The sub-packaging bag can be a conventional freezing bag.

[0076] The calibration container is arranged on the filling pipeline, and its inlet and outlet are respectively connected to the filling pipeline and are respectively provided with gas-liquid detectors. The gas-liquid detectors can detect whether there is air or liquid at the inlet and outlet to judge the filling status of the calibration container.

[0077] The diaphragm pump is arranged at one end of the filling pipeline, forming a barrier between the filling system and the external environment to block the air from the external environment from entering the filling system. At the same time, when the cell fluid is injected into the filling pipeline, the diaphragm pump can discharge the gas inherent in the filling pipeline and the gas separated from the cell fluid out of the filling system.

[0078] The present embodiment is based on a cell fluid packaging system comprising a peristaltic pump, a packaging bag, a calibration container and a diaphragm pump connected in sequence in the extension direction of the same packaging pipeline. By opening the branch valve and closing the inlet of the calibration container, the initial cell fluid in the packaging process is directly pumped into the packaging bag. After the cell fluid enters the packaging bag, the residual gas mixed with it and the inherent gas in the packaging bag will be located above the packaging bag body due to its low density. At the same time, the pumping process can form a certain degree of gas-liquid separation; then the gas in the packaging bag is pumped out to the packaging pipeline by back-pumping through the peristaltic pump. The bypass valve is closed and a certain amount of cell fluid that has been pumped in is withdrawn, so that the cell fluid inside the sub-packaging bag contacts the bag body under the action of negative pressure and is fully filled; then the inlet of the calibration container is opened and the cell fluid mixed with gas is pumped into the calibration container through a peristaltic pump, and the residual gas and the cell fluid are separated in the calibration container to obtain gas-liquid separated cell fluid; finally, the bypass valve is reopened and the gas-liquid separated cell fluid is pumped into the sub-packaging bag so that there is very little or no residual gas in the sub-packaging bag filled with the cell fluid, thereby improving the sub-packaging efficiency, the qualified rate of finished products and the quality of the sub-packaging products.

[0079] In this embodiment, the calibration container can be implemented as any container with two openings (i.e., an inlet and an outlet). Its main function is to allow the cell fluid to be ejected at a smaller flow rate in the container due to the presence of the inlet and outlet, thereby separating it from the mixed gas to obtain gas-liquid separated cell fluid.

[0080] As an embodiment, the present application provides a specific structure of a calibration container to further explain its working principle in this embodiment.

[0081] 1 and 3 , the inlet 101 and outlet 102 of the calibration container 10 are respectively provided with gas-liquid detectors; wherein the inlet 101 and outlet 102 of the calibration container 10 are respectively arranged at the bottom and the top, and the cell fluid is pumped into the calibration container 10 from the bottom to the top; the closed ends on the upper and lower sides of the calibration container 10 are arranged at an angle, and the inlet 101 and outlet 102 of the calibration container 10 are respectively located at the lowest position and the highest position of the two closed ends of the calibration container 10;

[0082] Correspondingly, step S4 is more specifically as follows: pumping the cell fluid from the inlet 101 of the calibration container 10, performing gas-liquid separation on the cell fluid using the calibration container 10, and discharging the separated gas from the outlet 102 at the top to obtain the gas-liquid separated cell fluid remaining in the calibration container 10.

[0083] In this embodiment, the upper and lower closed ends of the calibration container 10 are tilted at a certain angle. When liquid enters the calibration container 10, the space becomes larger. As gravity outweighs tension, bubbles rise to the surface of the liquid, most of which burst, leaving only very small bubbles. The upper and lower closed ends of the calibration container 10 are both tilted. The tilt at the upper end prevents any remaining bubbles from being trapped at the upper end of the container, but instead allows them to be discharged preferentially through the outlet 102, ensuring that the residual bubble level within the calibration container 10 is kept very low and that residual gas within the cell fluid is removed. Furthermore, the tilt at the lower end allows the liquid within the calibration container 10 to be completely drained when it is withdrawn from the lower end, thereby ensuring that the volume of the incoming and outgoing liquid is equal to the volume of the calibration container 10 itself. Furthermore, in conjunction with the gas-liquid detectors at the inlet 101 and outlet 102 of the calibration container 10, the flow rate of the peristaltic pump can be accurately calibrated.

[0084] Preferably, a vertical baffle 103 is further provided on the closed end surface of the calibration container 10 close to the outlet 102 to prevent liquid splashed onto the end surface from flowing along the inner wall toward the outlet 102 and then out of the calibration container 10 .

[0085] The following describes how to calibrate the flow rate of a peristaltic pump using a calibration container:

[0086] In the above embodiment, since the volume parameters of the calibration container are fixed, while the cell fluid is injected into the calibration container by the peristaltic pump to separate the residual gas, the fixed volume of the cell fluid filling the calibration container can be utilized to further associate the volume parameters of the calibration container with the number of rotation steps (number of turns) of the peristaltic pump. By recording the number of rotation steps (number of turns) of the peristaltic pump to fill the calibration container, the quantitative relationship between the number of rotation steps (number of turns) and the volume of the injected liquid can be obtained, thereby expanding the metering function of the peristaltic pump.

[0087] Therefore, in some embodiments, step S4 further includes the following steps:

[0088] S41, pumping the gas-liquid separated cell fluid back from the inlet of the calibration container by the peristaltic pump, and stopping the pumping when the gas-liquid detector at the inlet of the calibration container detects gas and recording the first step number of the peristaltic pump at this time;

[0089] S42, injecting the gas-liquid separated cell solution into the calibration container through the peristaltic pump and recording the second step number of the peristaltic pump when the gas-liquid detector at the outlet of the calibration container detects liquid;

[0090] It should be noted that when measuring the first and second step numbers, the rotation speed of the peristaltic pump is 5-20 rpm; this ensures that the relevant detector can detect the above changes as soon as the phase transition occurs, thereby ensuring the accuracy of the parameters.

[0091] S43. Calculate a calibration coefficient of the peristaltic pump according to the first number, the second number of steps, and the volume of the calibration container.

[0092] The calibration coefficient of the peristaltic pump satisfies V r =V / S, where V represents the volume of the standard container, and S satisfies S=S1-S2, where S1 represents the first step number, and S2 represents the second step number.

[0093] Specifically, after the residual gas mixed in the cell fluid is separated by the calibration container to obtain pure liquid gas-liquid separated cell fluid, the gas-liquid separated cell fluid in the calibration container is first withdrawn by a peristaltic pump, and detected by means of a gas-liquid detector at the inlet of the calibration container. When it detects gas, it means that the liquid in the calibration container has been emptied. At this time, the withdrawal is stopped and the first step of the peristaltic pump is recorded; then the peristaltic pump is changed to re-inject the gas-liquid separated cell fluid into the calibration container until the gas-liquid detector at the outlet of the calibration container detects liquid, which means that the calibration container is now filled with gas-liquid separated cell fluid. Since there is no residual gas in the gas-liquid separated cell fluid, the volume of the liquid in the calibration container is equal to the volume of the calibration container, and the second step of the peristaltic pump is recorded at this time; finally, the calibration coefficient is calculated based on the difference between the second step number and the first step number and the volume value of the calibration container, thereby obtaining the pumping flow corresponding to each further step or rotation of the peristaltic pump, thereby determining the quantitative relationship and completing the calibration.

[0094] It should be noted that the quantitative calibration of the operating status of the peristaltic pump through the calibration container is carried out simultaneously with the gas-liquid separation in the above embodiment, but there is no necessary connection between the two. The quantification of the pumping in and out of the peristaltic pump using the calibration container can also be performed before or after the gas-liquid separation operation.

[0095] Optionally, before opening the branch valve and closing the inlet of the calibration container and pumping the cell solution into the sub-packaging bag through the peristaltic pump, the method further comprises:

[0096] Opening the inlet of the calibration container, and pumping the treated cell fluid free of residual gas into the calibration container through the peristaltic pump, and recording the third step number of the peristaltic pump when the gas-liquid detector at the inlet of the calibration container detects liquid;

[0097] recording a fourth step number of the peristaltic pump when the gas-liquid detector at the outlet of the calibration container detects liquid;

[0098] A calibration coefficient of the peristaltic pump is calculated according to the third number of steps, the fourth number of steps, and the volume of the calibration container.

[0099] In the aforementioned embodiment, the peristaltic pump has been calibrated using a calibration container. For example, the number of steps or one rotation of the peristaltic pump is equivalent to the flow rate or volume of the injected cell fluid, which can be used to calculate the packaging amount. Specifically, step S5 may include: opening the branch valve again, and pumping the cell fluid into the packaging bag through the peristaltic pump according to the quantitative relationship determined by the calibration coefficient; so as to achieve more accurate packaging.

[0100] 4 , the sub-packaging bag 20 includes a bag body 201, a bag tail 204, a liquid bag pipeline 202, and a puncture port 203. The liquid bag pipeline 202 of the sub-packaging bag and the cavities in the areas of the left and right liquid bag protective membrane flaps are connected as one. When viewed from the side, the upper half is bulging. When the liquid enters the bag body 201, the original gas in the pipeline is passed into the bag body 201 and retained in the cavity area. The bag body 201 is initially in a bulging state, and the liquid will not be retained in the cavity due to tension. The liquid flows to the bottom of the bag body 201 under the action of gravity. When the liquid and gas in the bag are pumped back, the gas in the cavity is discharged first, and the liquid at the bottom gradually fills the cavity area, thereby removing the residual gas inherent in the bag.

[0101] After the cell fluid is initially pumped into the sub-packaging bag 20, that is, after executing step S1 in the aforementioned embodiment, the peristaltic pump reverses and draws back the cell fluid in the sub-packaging bag 20, pumping the gas and liquid in the sub-packaging bag 20 back into the sub-packaging pipeline. Since the liquid is heavier, combined with the structure of the sub-packaging bag 20, the gas in the sub-packaging bag 20 is discharged first, and only a small amount of cell fluid remains in the pipeline of the sub-packaging bag 20. The branch valve is closed, and the volume of cell fluid in the sub-packaging bag 20 is fixed at this time (it should be noted that the withdrawal can be carried out under the conditions of completing the calibration of the peristaltic pump by the calibration container in the aforementioned embodiment, thereby making the withdrawal operation quantitative). When there are multiple sub-packaging bags 20, the above-mentioned operations are performed on all sub-packaging bags 20 in turn until the gas in all sub-packaging bags 20 is completely emptied; at this time, since the sub-packaging pipeline is relatively long, the gas discharged from the sub-packaging bag 20 will still remain in the sub-packaging main pipeline, and the cell fluid in the main pipeline needs to be eliminated with bubbles, and the calibration container is used again to separate and eliminate the residual gas: the cell fluid is continuously pumped into the calibration container until the gas-liquid detector at the outlet of the calibration container detects liquid, confirming that the bubbles in the sub-packaging pipeline have been emptied, and sub-packaging begins, and the set volume minus the fixed residual cell fluid volume is pumped into each sub-packaging bag 20 in turn until all sub-packaging bags 20 are filled and the sub-packaging is completed.

[0102] In this embodiment, by withdrawing the gas that has been injected into the sub-packaging bag 20 and then repeating the sub-packaging steps in the aforementioned embodiment, the gas remaining in the sub-packaging pipeline and the sub-packaging bag 20 can be separated from the cell fluid through the special structure and setting of the calibration container and discharged from the sub-packaging system, thereby reducing the residual gas content in the sub-packaging product and improving the quality of the sub-packaging product; on the other hand, using the calibration container in the aforementioned embodiment to calibrate the range of the peristaltic pump can control the sub-packaging amount, thereby improving the accuracy of the sub-packaging amount under the premise of removing the residual gas.

[0103] Optionally, the cell fluid packaging system further includes an air pressure sensor provided at one end of the packaging pipeline close to the diaphragm pump; before closing the branch valve and pumping the cell fluid into the packaging pipeline through the peristaltic pump, the system further includes:

[0104] Open all the branch valves and operate the diaphragm pump to extract the gas from each sub-bag;

[0105] After reaching a defined negative pressure value, the pressure sensor is used to detect whether the internal pressure of the cell solution dispensing system remains unchanged;

[0106] If so, complete the air tightness test of the cell liquid packaging system.

[0107] Specifically, see Figure 1. An air pressure sensor is provided at one end of the subpackaging pipeline. Before the subpackaging work is carried out, in order to avoid the air tightness of the subpackaging system being poor and causing air to enter the system and affect the quality of the subpackaging work, the overall air tightness of the subpackaging system needs to be tested. Specifically, the branch valve is opened and the gas is extracted from the subpackaging pipeline through a diaphragm pump. As the gas is extracted, the internal pressure of the subpackaging system decreases. After the negative pressure reaches a certain value, the diaphragm pump stops working. The air pressure is monitored by the air pressure sensor. When the air pressure is stable for a certain period of time, it can be confirmed that the air tightness of the subpackaging system is good, and subpackaging can be carried out directly or after the pressure is released.

[0108] In this embodiment, before the subpackaging work is carried out, a diaphragm pump is used to evacuate air from the inside of the subpackaging system to reduce the pressure and the air tightness of the entire system is detected by using an air pressure sensor to avoid interference with the system itself during subpackaging, which is beneficial to ensuring the realization of improved subpackaging efficiency and quality.

[0109] Optionally, the cell fluid packaging system further comprises a plurality of preparation pipelines for injecting different preparations, wherein the preparation pipelines merge into one pipeline at one end and are connected to a mixing bag, and a preparation pump is further provided between the mixing bag and the preparation pipeline; the process of opening the branch valve and pumping the cell fluid into the pipeline through the peristaltic pump further comprises:

[0110] Prepare different preparations according to the cell fluid preparation specifications and inject them into the mixing bag through the preparation pipeline;

[0111] The injected preparation is mixed by the mixing bag to obtain the cell fluid to be packaged.

[0112] Before packaging, the cell fluid preparation to packaging process is transported through the preparation pipeline, mixing bag and preparation pump in the cell fluid packaging system. The preparation pipeline includes multiple preparation liquid channels for injecting different cell fluid raw materials respectively, and the injection can be modulated on demand in this pipeline, replacing or being equivalent to the weighing step in conventional preparation; the preparation in the preparation pipeline enters the mixing bag for mixing under the action of the preparation pump, thereby completing the preparation of the cell fluid.

[0113] Likewise, the preparation pump is also a peristaltic pump.

[0114] The mixing bag also has a refrigeration function or is in a refrigeration system to meet the temperature conditions for cell fluid preparation.

[0115] Before preparation, the pipeline also needs to be tested for air tightness. Therefore, an air pressure sensor can be connected between the preparation pipeline and the preparation pump through a branch line, and observation can be performed by extracting air to form a negative pressure, which is specifically the same as the air tightness test operation in the aforementioned embodiment.

[0116] In this embodiment, the cell fluid preparation part is formed by connecting the preparation pipeline, the preparation pump and the mixing bag, and the cell fluid to be packaged can be prepared according to different specification requirements.

[0117] Optionally, the cell fluid packaging system further includes a sampling pipeline connected to the mixing bag; after the injected preparation is mixed by the mixing bag to obtain the cell fluid to be packaged, the system further includes:

[0118] The cell fluid in the mixing bag is extracted through a sampling pipeline.

[0119] In this embodiment, a sampling pipeline is formed by connecting a branch to the mixing bag, which can facilitate the understanding of the component ratio of the cell fluid in the mixing bag. If necessary, different raw materials can be injected through the preparation pipeline to adjust and obtain the expected cell fluid quality.

[0120] Optionally, after reopening the branch valve and pumping the cell solution into the sub-packaging bag through the peristaltic pump, the method further comprises:

[0121] When all the sub-packaging bags are completely filled, the branch valve is closed and the sub-packaging bags that have been injected with cell fluid are removed.

[0122] Optionally, after closing the branch valve and removing the sub-packaging bag into which the cell solution has been injected, the method further comprises:

[0123] The steps of assembling a sub-packaging bag without cell solution on the sub-packaging pipeline, returning to open the branch valve and closing the inlet of the calibration container, and pumping cell solution into the sub-packaging bag through the peristaltic pump.

[0124] This embodiment improves the efficiency of group packaging through the detachable packaging bag replacement method.

[0125] The above detailed description of the specific embodiments of the invention is intended to be illustrative only, and the present invention is not limited to the specific embodiments described above. For those skilled in the art, any equivalent modifications or substitutions to the invention are also within the scope of the present invention. Therefore, equivalent changes, modifications, and improvements made without departing from the spirit and scope of the present invention are also encompassed within the scope of the present invention.

Claims

1. A cell fluid packaging method, the packaging method is applied to a cell fluid packaging system, the cell fluid packaging system comprises a peristaltic pump, a packaging bag, a calibration container and a diaphragm pump connected in sequence in the extension direction of the same packaging pipeline; wherein: The subpackaging bag is connected to a branch of the subpackaging pipeline through a branch valve, and the subpackaging method comprises the following steps: Open the branch valve and close the inlet of the calibration container, and pump the cell solution into the dispensing bag through the peristaltic pump; The residual gas and cell fluid in each of the sub-packaging bags are sequentially pumped back by the peristaltic pump and the corresponding branch valve is closed; Opening the inlet of the calibration container, and pumping the withdrawn cell fluid into the calibration container through the peristaltic pump; The pumped cell fluid is subjected to gas-liquid separation through the calibration container to obtain gas-liquid separated cell fluid; The branch valve is opened again and the cell solution is pumped into the dispensing bag through the peristaltic pump.

2. The packaging method according to claim 1, characterized in that: Gas-liquid detectors are provided on the inlet and outlet of the calibration container, respectively; wherein the inlet and outlet of the calibration container are respectively arranged at the bottom and the top, and the cell fluid is pumped into the calibration container from the bottom to the top in the calibration container; the closed ends on the upper and lower sides of the calibration container are arranged obliquely, and the inlet and outlet of the calibration container are respectively located at the lowest position and the highest position of the two closed ends of the calibration container; The step of performing gas-liquid separation on the pumped cell fluid through the calibration container to obtain the gas-liquid separated cell fluid comprises: The cell fluid is pumped into the calibration container from its inlet, the calibration container is used to perform gas-liquid separation on the cell fluid, and the separated gas is discharged from the outlet at the top to obtain the gas-liquid separated cell fluid remaining in the calibration container.

3. The packaging method according to claim 2, characterized in that: After the cell solution is pumped into the calibration container from the inlet, the calibration container is used to perform gas-liquid separation on the cell solution, and the separated gas is discharged from the outlet at the top to obtain the gas-liquid separated cell solution remaining in the calibration container, the method further includes: The gas-liquid separated cell fluid is pumped back from the inlet of the calibration container by the peristaltic pump, and the pumping is stopped when the gas-liquid detector at the inlet of the calibration container detects gas and the first step number of the peristaltic pump at this time is recorded; injecting the gas-liquid separation cell solution into the calibration container through the peristaltic pump and recording the second step number of the peristaltic pump when the gas-liquid detector at the outlet of the calibration container detects liquid; Calculating a calibration coefficient of the peristaltic pump according to the first number of steps, the second number of steps, and the volume of the calibration container; The step of opening the branch valve again and pumping the cell solution into the dispensing bag through the peristaltic pump comprises: The branch valve is opened again, and according to the quantitative relationship determined by the calibration coefficient, the cell solution is pumped into the sub-packaging bag through the peristaltic pump.

4. The packaging method according to claim 1, characterized in that: The process of opening the branch valve and closing the inlet of the calibration container and before pumping the cell solution into the sub-packaging bag through the peristaltic pump also includes an emptying operation of the peristaltic pump, including the following steps: Starting the peristaltic pump to be tested at a first speed; When the gas-liquid detector located at the outlet end of the calibration container detects that the flow medium is converted from air to liquid, a control signal is sent to control the peristaltic pump to stop; The peristaltic pump is controlled to reverse at a second speed, and when the gas-liquid detector located at the inlet end of the calibration container detects that the flow medium is converted from liquid to air, a control signal is sent to control the peristaltic pump to be detected to stop.

5. A calibration method according to claim 4, characterized in that: The first rotation speed is less than 120 rpm, and the second rotation speed is 5-20 rpm.

6. A calibration method according to claim 3, characterized in that: When obtaining the first step number and the second step number of the peristaltic pump, the rotation speed of the peristaltic pump is 5-20 rpm.

7. A calibration method according to claim 3, characterized in that: The calibration coefficients satisfy V r =V / S, where V represents the volume of the standard container, and S satisfies S=S1-S2, where S1 represents the first step number, and S2 represents the second step number.

8. The packaging method according to claim 2, characterized in that: The cell fluid dispensing system further includes an air pressure sensor disposed at one end of the dispensing pipeline close to the diaphragm pump; before the branch valve is opened and the inlet of the calibration container is closed, and the cell fluid is pumped into the dispensing bag through the peristaltic pump, the system further includes: Open all the branch valves and extract the gas in each sub-packaging bag through the diaphragm pump; After the defined negative pressure value is reached, the air pressure sensor is used to detect whether the internal pressure of the cell liquid dispensing system remains unchanged; If so, complete the air tightness test of the cell liquid packaging system.

9. The packaging method according to claim 1, characterized in that: The cell fluid dispensing system further comprises a plurality of preparation pipelines for injecting different preparations, wherein the preparation pipelines merge into one pipeline at one end and are connected to a mixing bag, and a preparation pump is further provided between the mixing bag and the preparation pipeline; before the branch valve is opened and the inlet of the calibration container is closed, and the cell fluid is pumped into the dispensing bag by the peristaltic pump, the system further comprises: Prepare the preparation according to the cell fluid preparation specifications and inject it into the mixing bag through the preparation pipeline; The injected preparation is mixed by the mixing bag to obtain the cell fluid to be packaged.

10. The packaging method according to claim 9, characterized in that: The cell fluid packaging system further includes a sampling pipeline, which is connected to the mixing bag; after the injected preparation is mixed by the mixing bag to obtain the cell fluid to be packaged, the system further includes: The cell fluid in the mixing bag is extracted through a sampling pipeline to check whether the cell fluid is qualified.

11. The packaging method according to claim 1, characterized in that: After the branch valve is opened again and the cell solution is pumped into the dispensing bag through the peristaltic pump, the method further comprises: When all the sub-packaging bags are completely filled, the branch valve is closed and the sub-packaging bags that have been injected with cell solution are removed.

12. The packaging method according to claim 11, characterized in that: After closing the branch valve and removing the sub-packaging bag into which the cell solution has been injected, the method further comprises: The steps of assembling a dispensing bag without cell solution injected on the dispensing pipeline, returning to open the branch valve and closing the inlet of the calibration container, and pumping cell solution into the dispensing bag through the peristaltic pump.

13. The packaging method according to claim 1, characterized in that: Before the branch valve is opened and the inlet of the calibration container is closed, and the cell solution is pumped into the dispensing bag by the peristaltic pump, the method further comprises: Opening the inlet of the calibration container, and pumping the treated cell fluid without residual gas into the calibration container through the peristaltic pump, and recording the third step number of the peristaltic pump when the gas-liquid detector at the inlet of the calibration container detects liquid; recording a fourth step number of the peristaltic pump when the gas-liquid detector at the outlet of the calibration container detects liquid; A calibration coefficient of the peristaltic pump is calculated according to the third number of steps, the fourth number of steps, and the volume of the calibration container.

14. The packaging method according to claim 1, characterized in that: The packaging bag comprises a bag body, a liquid tube and puncture bodies respectively arranged on both sides of the liquid tube. The liquid tube is connected to the bag body. The puncture bodies are parallel to the liquid tube and penetrate into the bag body on one side close to the liquid tube to form a cavity.

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