A cell packaging method based on dropper

Abstract

The present invention provides a cell packaging method based on a drip bucket, which is used to solve the problem of poor packaging efficiency and accuracy caused by manual packaging in the prior art. The packaging method includes: closing the control valve used to introduce gas into the drip bucket, opening the packaging valve arranged in the pipeline between the cryopreservation container and the drip bucket, and pumping the cell fluid in the final product bag into the drip bucket through a peristaltic pump to exhaust the gas and then transport it to each cryopreservation container; during the packaging process, if it is identified that the cell fluid volume in the cryopreservation container reaches the preset capacity, the packaging valve before the corresponding cryopreservation container is closed.

Description

Technical Field

[0001] The present application relates to the biomedical field, and specifically to a cell packaging method based on a dropper. Background Art

[0002] The working process of existing cell preparation packaging equipment is mainly manual operation and the installation and operation process is cumbersome, so the packaging volume accuracy is low. In addition, due to manual operation, it is difficult to ensure the same volume during multiple packaging processes, and the consistency is low, thus reducing the packaging efficiency and accuracy of cell preparations. Summary of the invention

[0003] The present invention provides a cell packaging method based on a dropper, which is used to solve the problems of poor packaging efficiency and accuracy caused by manual packaging in the prior art.

[0004] The technical solution of the present invention is:

[0005] A cell packaging method based on a dropper, the packaging method comprising:

[0006] Close the control valve for introducing gas into the drip bucket, open the dispensing valve provided in the pipeline between the cryopreservation container and the drip bucket, and pump the cell fluid in the final product bag into the drip bucket through a peristaltic pump to exhaust the gas and then transport it to each cryopreservation container;

[0007] During the filling process, if it is identified that the volume of the cell fluid in the freezing container reaches the preset volume, the filling valve in front of the corresponding freezing container is closed.

[0008] Preferably, it also includes:

[0009] By monitoring the cell fluid pressure before and after the peristaltic pump, the blockage of the cell fluid in the pipeline is monitored;

[0010] By monitoring the bubbles in the cell solution before and after the peristaltic pump, the flow of the cell solution infusion in the pipeline is monitored.

[0011] Preferably, it also includes:

[0012] When it is identified that the cell fluid in the final product bag has been completely pumped out, the control valve is opened so that the remaining cell fluid is pumped into the freezing container by the peristaltic pump along with the gas entering the drip bucket;

[0013] When overflow of the cell fluid from the freezing container is detected, the overflowing cell fluid is pumped back into the freezing container by a peristaltic pump.

[0014] Preferably, the cell fluid volume in each cryopreservation container is monitored according to a light sensor provided corresponding to each cryopreservation container.

[0015] Preferably, the freezing container is a multi-link freezing bag, the multi-link freezing bag has multiple rows, and a filling valve is connected in front of the inlet of a row of multi-link freezing bags;

[0016] During packaging, after the cell solution packaging of the previous row of multi-link cryopreservation bags is completed, the packaging valve in front of its entrance is closed; then the packaging valve in front of the entrance of the next row of multi-link cryopreservation bags is opened to carry out the cell solution packaging of the next row of multi-link cryopreservation bags.

[0017] Preferably, the freezing container is a multi-link freezing tube, the multi-link freezing tube is in multiple rows, and a filling valve is connected to the inlet of each row of the multi-link freezing tube;

[0018] In a row of the multi-link cryopreservation tubes, the tube root heights of the inlet and outlet are adjusted according to their cryopreservation capacity.

[0019] Preferably, the cryopreservation container is a heat-sealable cryopreservation tube, and a filling valve is connected to the inlet of each cryopreservation tube;

[0020] During the subpackaging, after the previous cryopreservation tube has completed the cell solution subpackaging, the subpackaging valve in front of its inlet is closed and its inlet is heat-sealed; then the subpackaging valve in front of the inlet of the next cryopreservation tube is opened to perform the cell solution subpackaging of the next cryopreservation tube.

[0021] Preferably, the inlet of the freezing container is below or above it.

[0022] Preferably, whether the cell fluid overflows from the freezing container is determined based on the monitoring results of a light sensor and / or a bubble sensor arranged in the pipeline after the last row or the last freezing container.

[0023] Preferably, when the overflowing cell fluid is pumped back into the cryopreservation container by the peristaltic pump, the reverse rotation of the peristaltic pump is timed and controlled.

[0024] The beneficial effects of the present invention are:

[0025] After the peristaltic pump pumps the cell fluid to be packaged into the drop bucket, due to the different densities of gas and liquid, the cell fluid droplets will naturally settle under the action of gravity, thereby separating from the gas and achieving the exhaust of the cell fluid. In addition, by monitoring the volume of the cell fluid in the cryopreservation container, the consistency of the volume of the cell fluid in each cryopreservation container after packaging can be ensured. In addition, the packaging method of using a peristaltic pump to drive the cell fluid to flow into the cryopreservation container can improve the packaging efficiency of the cell fluid. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is a schematic diagram of the cell solution packaging system in Example 1 of the present application;

[0027] Figure 2This is a schematic diagram of the cell solution packaging system in Example 2 of the present application;

[0028] Figure 3 This is a schematic diagram of the cell solution packaging system in Example 3 of the present application;

[0029] Figure 4 This is a schematic diagram of the cell solution packaging system in Example 4 of the present application;

[0030] Explanation of the accompanying drawings: 1-final product bag; 2-peristaltic pump; 3-drip bucket; 4-freezing container; 5-filling valve; 6-control valve; 7-first filter; 8-first bubble sensor; 9-second filter; 101-first pipeline; 102-second pipeline; 103-third pipeline; 104-fourth pipeline; 10-first pressure sensor; 11-second pressure sensor; 12-second bubble sensor; 13-third bubble sensor. DETAILED DESCRIPTION

[0031] The method of the present invention is further described below in conjunction with the embodiments and accompanying drawings. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and specific operation process, but the protection scope of the present invention is not limited to the following embodiments.

[0032] Reference Figure 1 , Embodiment 1 of the present application provides a cell fluid packaging system, comprising: a final product bag 1, a peristaltic pump 2, a dripping bucket 3 and a freezing container 4 connected in sequence through pipelines. Specifically, the inlet of the peristaltic pump 2 and the outlet of the final product bag 1 are connected through a first pipeline 101, and the outlet of the peristaltic pump 2 and the inlet of the dripping bucket 3 are connected through a second pipeline 102. The final product bag 1 stores cell fluid that has not yet been packaged. When the peristaltic pump 2 rotates forward, the cell fluid in the final product bag 1 is pumped into the dripping bucket 3; in the process of the cell fluid dripping into the dripping bucket 3, due to the different densities of the liquid and the gas, the liquid droplets will naturally settle under the action of gravity, thereby separating from the gas, thereby achieving gas-liquid separation.

[0033] The outlet of the drip bucket 3 is connected to the filling valve 5 through the third pipeline 103, and the outlet of the filling valve 5 is connected to the inlet of the freezing container 4 through the fourth pipeline 104. In order to allow the cell fluid in the drip bucket 3 and the pipeline to flow into the freezing container 4, the drip bucket 3 is connected with a control valve 6 into which gas can be introduced. When there is a ventilation demand, the control valve 6 is opened, and the external gas enters the drip bucket 3 through the control valve 6. In order to prevent the external gas introduced into the drip bucket 3 from contaminating the cell fluid, a first filter 7 can also be provided at the front end of the control valve 6, so that the external gas is filtered and then introduced into the drip bucket 3.

[0034] In the first embodiment of the present application, the cryopreservation container 4 is a multi-link cryopreservation bag, which is arranged in multiple rows, and each row of the multi-link cryopreservation bags is connected to a filling valve 5. Figure 1 The multi-link cryopreservation bags in the first row are 5-link cryopreservation bags, and the volume of each bag can be 1 mL; the multi-link cryopreservation bags in the second row are 6-link cryopreservation bags, among which the volume of the first 5 bags is 1 mL, and the volume of the 6th bag can be a capacity value smaller than 1 mL for sampling.

[0035] Reference Figure 1 In order to accurately detect the volume of the cell fluid in the multi-joint cryopreservation bag, in the first embodiment of the present application, a first bubble sensor 8 is also connected to the tail end of each multi-joint cryopreservation bag through a pipeline. If the first bubble sensor 8 detects bubbles, it indicates that the corresponding multi-joint cryopreservation bag is full. Of course, in the embodiment of the present application, the liquid level in each multi-joint cryopreservation bag can also be detected by a light sensor to identify whether the volume of the packaged cell fluid reaches the preset capacity. A second filter 9 can also be provided at the tail end of the first bubble sensor 8 to prevent the cell fluid overflowing from the multi-joint cryopreservation bag from being contaminated by external gas.

[0036] In order to detect whether cell fluid blockage occurs in the pipeline, in the first embodiment of the present application, a first pressure sensor 10 and a second pressure sensor 11 are respectively arranged in the pipelines before and after the peristaltic pump 2. According to the cell fluid pressure deviation monitored by the first pressure sensor 10 and the second pressure sensor 11, it can be identified whether blockage occurs before and after the peristaltic pump 2; when blockage occurs, an alarm is given and the operation is stopped. The current rotation direction can be reversed to reduce damage to the cells in the pipeline, and then the blockage is manually cleared.

[0037] In addition, in embodiment 1 of the present application, a second bubble sensor 12 and a third bubble sensor 13 are respectively arranged in the pipelines before and after the peristaltic pump 2. According to the detection data of the second bubble sensor 12 and the third bubble sensor 13, the infusion situation in the pipeline is monitored, including monitoring the start and / or end of the infusion process.

[0038] When the cell fluid is packaged, the cell fluid in the final product bag 1 is transferred to the multi-link cryopreservation bag through the rotation of the peristaltic pump 2. The first row of filling valves 5 are opened first, and the cell fluid after the gas-liquid separator passes through the drip bucket 3 and flows into the first row of multi-link cryopreservation bags.

[0039] In the first embodiment of the present application, the cell solution dispensing system can be equipped with a central control unit for monitoring each bubble sensor, each pressure sensor, each light sensor and adjusting the speed of the peristaltic pump 2, the switch state of the dispensing valve 5 and the ventilation demand of the control valve 6. This control unit can be a computer or a microprocessor, which automates the entire dispensing process through a preset program.

[0040] In the first embodiment of the present application, the cell liquid packaging system can also be equipped with a sound and visual alarm system. When an abnormal situation is detected, such as blockage in the pipeline or abnormal liquid level in the freezing container, an alarm is immediately issued to prompt the operator to take corresponding measures.

[0041] In Example 1 of the present application, the cell liquid packaging system can also provide an intuitive user interface, and the operator can monitor the system status, input parameters, and start and stop the packaging process through a touch screen or a computer interface.

[0042] In Example 1 of the present application, when the cell fluid dispensing system is used to dispensing the cell fluid, the following process is followed:

[0043] (1) Start the peristaltic pump 2 and open the first row of dispensing valves 5 first. The cell solution will flow into the multi-link cryopreservation bags in the first row.

[0044] (2) When the multi-link cryopreservation bags in the first row are filled and the cell fluid flows to the first bubble sensor 8 at the rear end of the multi-link cryopreservation bags in the row, the peristaltic pump 2 is stopped, the dispensing valve 5 before the multi-link cryopreservation bags in the first row is closed, and the dispensing valve 5 before the multi-link cryopreservation bags in the second row is opened, so that the cell fluid fills the multi-link cryopreservation bags in the second row.

[0045] (3) Since the liquid in the final product bag 1 is generally more accurate, when it comes to the multi-link cryopreservation bag in the last row, the liquid cell fluid in the pipeline and the cell fluid in the drip bucket 3 need to be filled into the multi-link cryopreservation bag in the last row. After all the cell fluid in the final product bag 1 is transported, since the final product bag 1 is emptied, the cell fluid transported in the pipeline will be difficult to move. It is necessary to open the control valve 6 above the drip bucket 3 to connect the drip bucket 3 with the external air filtered by the first filter 7. At this time, the remaining cell fluid in the drip bucket 3 and the pipeline can be easily emptied into the multi-link cryopreservation bag in the last row; when the first bubble sensor 8 detects that the cell fluid has passed, the forward rotation of the peristaltic pump 2 is immediately stopped; the reverse rotation of the peristaltic pump 2 is started, so as to draw back some cell fluid, so that the cell fluid in the pipeline between the multi-link cryopreservation bag in the last row and the first bubble sensor 8 flows back into the multi-link cryopreservation bag in the last row.

[0046] When the peristaltic pump 2 rotates in the reverse direction to draw back the cell fluid, the first embodiment of the present application performs timing control on the peristaltic pump 2; the specific time of the timing control is pre-calibrated, and the time for the peristaltic pump 2 to rotate in the reverse direction is determined based on the ratio of the length of the pipeline between the first bubble sensor 8 and the multi-link cryopreservation bag to the reverse rotation speed of the peristaltic pump 2.

[0047] By using the above-mentioned cell fluid packaging system in the embodiment of the present application, the cell fluid to be packaged is pumped into the drip bucket 3 by the peristaltic pump 2. Due to the different densities of gas and liquid, the cell fluid droplets will naturally settle under the action of gravity, thereby separating from the gas and achieving the exhaust of the cell fluid. In addition, by monitoring the cell fluid capacity in the multi-link cryopreservation bag, the consistency of the cell fluid volume in each multi-link cryopreservation bag after packaging can be ensured. In addition, the packaging method that uses the peristaltic pump 2 to drive the cell fluid to flow into the multi-link cryopreservation bag can improve the packaging efficiency of the cell fluid.

[0048] The cell solution packaging system in the second embodiment of the present application has the same structure as the cell solution packaging system in the first embodiment, except that the cryopreservation container 4 is replaced by a multi-linked multi-storage bag in the first embodiment with a multi-linked cryopreservation tube connection. Figure 2 The multi-link cryopreservation tube in the second embodiment of the present application is a 20-link cryopreservation tube. Since the cryopreservation tube is made of hard material, it will not be deformed due to the problem of freezing. In addition, the tube roots at the inlet and outlet of each cryopreservation tube can be adjusted according to the liquid level in the cryopreservation tube.

[0049] Among them, in the second embodiment, the inlet of the cryotube is at the top, that is, the cryotube is placed upright.

[0050] In order to improve the accuracy of detecting the volume of cell fluid in the cryopreservation tube, a light tube sensor may be used to monitor the liquid level in each cryopreservation tube.

[0051] The cell solution packaging system in the third embodiment of the present application has the same structure as the cell solution packaging system in the first embodiment, except that the multi-linked cryopreservation bag in the first embodiment of the cryopreservation container 4 is changed into a cryopreservation tube type with an integral valve and heat-sealable. Figure 3 , the liquid level height of each cryogenic tube is detected by a light sensor to monitor the injection of cell fluid into the cryogenic tube at all times. When the liquid level reaches the preset scale line, the filling valve 5 corresponding to the cryogenic tube is closed, the injection is stopped, and then the filling valve 5 corresponding to the next cryogenic tube is opened; each cryogenic tube will have an air filter connected to facilitate the injection of cell fluid. After the filling valve 5 corresponding to the cryogenic tube is closed, the process of heat-sealing the tube is entered, that is, the metal part of the heating valve mouth is heated. The filling valve can simultaneously control the injected tube and the tube connected to the second filter 9, and then the metal part can be two heat-sealing points, so that the cryogenic tube will not fall due to the melting of the heat seal at one place.

[0052] Furthermore, in the third embodiment, the inlet of the cryotube is at the top, that is, the cryotube is placed upright.

[0053] Reference Figure 4 In the fourth embodiment of the present application, based on the above-mentioned third and second embodiments, the cryogenic tube is changed to be placed inverted. At this time, the entrance of the cryogenic tube is at the bottom to prevent it from falling after heat sealing.

[0054] It should be noted that the various embodiments in this specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referenced to each other.

[0055] Although the preferred embodiments of the present invention have been described, those skilled in the art may make additional changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the embodiments of the present invention.

[0056] It should also be noted that, in this article, the orientation or position relationship indicated by the terms "center", "up", "down", "left", "right", "vertical", "horizontal", "inside", "outside", etc. is based on the orientation or position relationship shown in the drawings, which is for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation of the present invention. In addition, relational terms such as "first" and "second" are used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply that there is any such actual relationship or order between these entities or operations, nor can they be understood as indicating or implying relative importance. Moreover, the terms "include", "comprise" or any other variant thereof are intended to cover non-exclusive inclusion, so that a process, method, article or terminal device including a series of elements does not include those elements, but also includes other elements not explicitly listed, or also includes elements inherent to such a process, method, article or terminal device. In the absence of further restrictions, the elements defined by the sentence "including one..." do not exclude the existence of other identical elements in the process, method, article or terminal device including the elements.

[0057] The technical solution provided by the present invention is described in detail above. The principle and implementation mode of the present invention are described in this article using specific examples. The description of the above embodiments is only used to help understand the present invention, and the content of this specification should not be understood as limiting the present invention. At the same time, for those skilled in the art, according to the present invention, there will be different forms of changes in the specific implementation mode and application scope. It is not necessary and impossible to list all the implementation modes here, and the obvious changes or modifications derived therefrom are still within the protection scope of the present invention.

Claims

1. A cell packaging method based on a dropper, characterized in that: include: The control valve (6) for introducing gas into the dripping funnel (3) is closed, and the dispensing valve (5) provided in the pipeline between the cryopreservation container and the dripping funnel (3) is opened, and the cell fluid in the final product bag (1) is pumped into the dripping funnel (3) by the peristaltic pump (2) to exhaust the gas and then transported to each cryopreservation container (4); During the subpackaging process, if it is identified that the volume of the cell fluid in the cryopreservation container (4) reaches a preset volume, the subpackaging valve (5) in front of the corresponding cryopreservation container (4) is closed.

2. The method for cell packaging based on a dropper according to claim 1, characterized in that: Also includes: By monitoring the cell fluid pressure before and after the peristaltic pump (2), the blockage of the cell fluid in the pipeline is monitored; By monitoring the bubbles in the cell fluid before and after the peristaltic pump (2), the flow condition of the cell fluid infusion in the pipeline is monitored.

3. The method for cell packaging based on a dropper according to claim 1, characterized in that: The cell preparation packaging method further comprises: When it is identified that the cell fluid in the final product bag (1) has been completely drawn out, the control valve (6) is opened, so that the remaining cell fluid is pumped into the freezing container (4) by the peristaltic pump (2) along with the gas entering the drip bucket (3); When it is detected that the cell fluid overflows from the freezing container (4), the overflowing cell fluid is pumped back into the freezing container (4) by the peristaltic pump (2).

4. The method for cell packaging based on a dropper according to claim 1, characterized in that: The cell fluid volume in each freezing container (4) is monitored according to the light sensor arranged corresponding to each freezing container (4).

5. The method for cell packaging based on a dropper according to claim 1 or 4, characterized in that: The freezing container (4) is a multi-link freezing bag, which has multiple rows, and a dispensing valve (5) is connected in front of the inlet of a row of multi-link freezing bags; During subpackaging, after the cell solution is packed in the previous row of multi-link cryopreservation bags, the subpackaging valve (5) in front of the inlet is closed; then the subpackaging valve (5) in front of the inlet of the next row of multi-link cryopreservation bags is opened to carry out the cell solution packing of the next row of multi-link cryopreservation bags.

6. The method for cell packaging based on a dropper according to claim 1 or 4, characterized in that: The freezing container (4) is a multi-link freezing tube, which is arranged in multiple rows, and a dispensing valve (5) is connected in front of the inlet of each row of the multi-link freezing tubes; In a row of the multi-link cryopreservation tubes, the tube root heights of the inlet and outlet are adjusted according to their cryopreservation capacity.

7. The method for cell packaging based on a dropper according to claim 1 or 4, characterized in that: The freezing container (4) is a heat-sealable freezing tube, and a filling valve (5) is connected to the inlet of each freezing tube; During subpackaging, after the cell solution of the previous cryopreservation tube is filled, the subpackaging valve (5) in front of the inlet is closed and the inlet is heat-sealed; then the subpackaging valve (5) in front of the inlet of the next cryopreservation tube is opened to fill the cell solution of the next cryopreservation tube.

8. The method for cell packaging based on a dropper according to claim 7, characterized in that: The inlet of the freezing container (4) is below or above it.

9. The method for cell packaging based on a dropper according to claim 3, characterized in that: Whether the cell fluid overflows from the freezing container (4) is determined based on the monitoring results of the light sensor and / or the bubble sensor arranged in the pipeline after the last row or the last freezing container (4).

10. The method for cell packaging based on a dropper according to claim 4, characterized in that: When the overflowing cell fluid is pumped back into the freezing container (4) through the peristaltic pump (2), the reverse rotation of the peristaltic pump (2) is timed and controlled.

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