Cell preparation packaging method and system

Abstract

The present application relates to the field of cell preparation packaging, and provides a cell preparation packaging method and system. The method comprises: determining a preset packaging flow rate according to the rated capacity of the packaging bag and the preset packaging time; controlling a first peristaltic pump to extract the cell preparation into the packaging bag; obtaining the flow rate of the cell preparation in the quantitative tube according to the capacity of the quantitative tube between the first bubble sensor and the second bubble sensor, and the time difference between the cell preparation flowing through the two bubble sensors; if the absolute value of the error between the flow rate in the quantitative tube and the preset packaging flow rate is less than or equal to the error threshold, controlling the first peristaltic pump to maintain the current speed until all packaging bags meet the preset conditions. The cell preparation packaging method provided in the present application can improve the capacity accuracy of the cell preparation by strictly controlling the accuracy of the preset packaging time and the preset packaging flow rate, so that the volume of the cell preparation injected into the packaging bag is infinitely close to the rated capacity of the packaging bag.

Description

Technical Field

[0001] The present application relates to the technical field of cell preparation packaging, and in particular to a cell preparation packaging method and system. Background Art

[0002] Cell preparation packaging technology is an important part of the field of biomedical technology and is crucial to cell therapy and pharmaceutical preparation.

[0003] During the packaging process of cell preparations, the volume of the cell preparation in the packaging bag should reach its rated capacity as much as possible to achieve the therapeutic effect of the cell preparation. Therefore, it is necessary to measure the volume of the cell preparation in the packaging bag to evaluate whether the actual volume of the cell preparation injected reaches the rated capacity.

[0004] Among the current packaging methods on the market, the measurement of cell preparation capacity is usually achieved by manually starting and stopping peristaltic pumps, weighing, and manual recording. Since the packaging bag remains connected to the packaging pipeline during the weighing process, this method is easily affected by the vibration of the pipeline and other devices, resulting in large deviations in measurement accuracy, which in turn causes the cell preparation capacity in the packaging bag to differ significantly from the rated capacity of the packaging bag, affecting the capacity accuracy of the cell preparation, which will greatly affect the therapeutic effect of the cell preparation. Summary of the Invention

[0005] The embodiments of the present application provide a cell preparation packaging method and system to solve the technical problem that traditional cell preparation packaging methods are easily affected by vibrations of pipelines and other devices when measuring the capacity of cell preparations, resulting in large deviations in measurement accuracy, and further resulting in a large difference between the capacity of the cell preparation in the packaging bag and the rated capacity of the packaging bag, thereby affecting the capacity accuracy of the cell preparation.

[0006] In a first aspect, the present invention provides a method for packaging a cell preparation, comprising:

[0007] Determine the preset dispensing flow rate of the cell preparation based on the rated capacity of the dispensing bag and the preset dispensing time;

[0008] Controlling the first peristaltic pump to extract the cell preparation in the refrigeration and mixing device into a filling bag connected to the filling pipeline;

[0009] The flow rate of the cell preparation in the quantitative tube is obtained based on the capacity of the quantitative tube between the first bubble sensor and the second bubble sensor, and the time difference between the flow of the cell preparation through the first bubble sensor and the second bubble sensor. The first peristaltic pump, the first bubble sensor, the second bubble sensor, and the quantitative tube are arranged in a pipeline between the refrigeration and mixing device and the filling pipeline.

[0010] If the absolute value of the error between the flow rate in the quantitative tube and the preset filling flow rate is less than or equal to the error threshold, controlling the first peristaltic pump to maintain the current speed, and returning to the step of controlling the first peristaltic pump to extract the cell preparation in the refrigeration and mixing device into the filling bag connected to the filling pipeline, until all the filling bags in the filling pipeline meet the preset conditions;

[0011] The preset condition is: among all the filling bags in the filling pipeline, there is at least one unfinished filling bag, and the remaining filling bags are completed filling bags; the unfinished filling bag is a filling bag whose filling time has not reached the corresponding preset filling time, and the completed filling bag is a filling bag whose filling time has reached the corresponding preset filling time.

[0012] In one embodiment, controlling the first peristaltic pump to extract the cell preparation from the refrigeration and mixing device into a filling bag connected to the filling pipeline includes:

[0013] Controlling the first peristaltic pump to pump the cell preparation in the refrigeration and mixing device into the pipeline to be processed until the pipeline to be processed is full of liquid; the pipeline to be processed is the pipeline between the sub-packaging control valve and the farthest sub-packaging bag, the sub-packaging control valve is arranged on the pipeline between the refrigeration and mixing device and the sub-packaging bag, and the farthest sub-packaging bag is the sub-packaging bag having the longest pipeline length between the sub-packaging control valve and the sub-packaging bag;

[0014] The first peristaltic pump is controlled to sequentially extract the cell preparation into different filling bags connected to the filling pipeline.

[0015] In one embodiment, after all the sub-packaging bags in the sub-packaging pipeline meet the preset conditions, the process includes:

[0016] The air inlet control valve is controlled to open, and the cell preparation in the pipeline to be processed, which is in a full liquid state, is pushed into the unfinished filling bag by using the outside air.

[0017] In the preset condition, the absolute value of the difference between the total rated capacity of the unfinished filling bags and the total capacity of the cell preparations injected into the unfinished filling bags is equal to the full liquid capacity when the pipeline to be processed reaches a full liquid state.

[0018] In one embodiment, after using external air to push the cell preparation in the pipeline to be processed, which is in a full liquid state, into the unfinished filling bag, the method includes:

[0019] Control the liquid inlets of all filling bags to remain open for a preset time and then close;

[0020] Controlling the liquid inlet of the current sub-packaging bag to open, and controlling the first peristaltic pump to reverse, so as to evacuate the bubbles in the current sub-packaging bag;

[0021] The pressure sensor is controlled to monitor the internal pressure of the sub-packaging pipeline. If the internal pressure reaches a preset internal pressure, the other sub-packaging bags are controlled to serve as the current sub-packaging bags, and the control of the liquid inlet of the current sub-packaging bag is returned to open, and the first peristaltic pump is controlled to reverse to evacuate the bubbles in the current sub-packaging bag until all the bubbles in the sub-packaging bags are evacuated.

[0022] In one embodiment, before controlling the first peristaltic pump to extract the cell preparation from the refrigeration and mixing device into the filling bag connected to the filling pipeline, the method includes:

[0023] Controlling the reverse rotation of the second peristaltic pump to evacuate the air from the mixing bag in the refrigeration and mixing device; the second peristaltic pump is disposed on a pipeline between the sample bag and the refrigeration and mixing device, and the second peristaltic pump is connected to the atmosphere;

[0024] Controlling the refrigeration and mixing device to cool down the ambient temperature of the mixing bag to a preset temperature;

[0025] controlling the second peristaltic pump to extract the cell preparation in the sample bag into the mixing bag;

[0026] When the volume of the cell preparation in the mixing bag reaches a preset mixing volume, the refrigeration mixing device is controlled to mix the cell preparation according to preset mixing parameters within a preset mixing time; the preset mixing parameters include mixing frequency, mixing amplitude, and mixing acceleration.

[0027] In one embodiment, controlling the first peristaltic pump to extract the cell preparation from the refrigeration and mixing device into a filling bag connected to the filling pipeline includes:

[0028] The first peristaltic pump is controlled to extract the cell preparation in the refrigeration and mixing device into a sub-packaging bag connected to the sub-packaging pipeline through a dropper; the dropper is arranged on the pipeline between the refrigeration and mixing device and the first peristaltic pump.

[0029] In one embodiment, before controlling the first peristaltic pump to extract the cell preparation from the refrigeration and mixing device into the filling bag connected to the filling pipeline, the method includes:

[0030] The ambient temperature of the packaging bag is controlled to drop to the preset temperature.

[0031] In a second aspect, an embodiment of the present application provides a cell preparation packaging system for implementing the cell preparation packaging method described in the first aspect, comprising: a packaging control module and a quantitative control module;

[0032] The packaging control module includes a packaging pipeline and a packaging bag, and the packaging control module is used to determine a preset packaging flow rate of the cell preparation according to the rated capacity of the packaging bag and the preset packaging time;

[0033] The quantitative control module includes a first peristaltic pump, a first bubble sensor, a second bubble sensor and a quantitative tube. The quantitative control module is used to control the first peristaltic pump to extract the cell preparation into a sub-packaging bag connected to the sub-packaging pipeline, and obtain the flow rate of the cell preparation in the quantitative tube according to the capacity of the quantitative tube between the first bubble sensor and the second bubble sensor, and the time difference between the cell preparation flowing through the first bubble sensor and the second bubble sensor. If the absolute value of the error between the flow rate in the quantitative tube and the preset sub-packaging flow rate is less than or equal to the error threshold, the first peristaltic pump is controlled to maintain the current speed, and the process returns to the step of controlling the first peristaltic pump to extract the cell preparation into the sub-packaging bag connected to the sub-packaging pipeline until all the sub-packaging bags in the sub-packaging pipeline meet the preset conditions;

[0034] The preset condition is: among all the filling bags in the filling pipeline, there is at least one unfinished filling bag, and the remaining filling bags are completed filling bags; the unfinished filling bag is a filling bag whose filling time has not reached the corresponding preset filling time, and the completed filling bag is a filling bag whose filling time has reached the corresponding preset filling time.

[0035] In one embodiment, the further comprising: an intake control module;

[0036] The air intake control module includes an air intake control valve, which is used to control the opening of the air intake control valve and use external air to push the cell preparation in a liquid-filled state in the pipeline to be processed into the unfinished packaging bag.

[0037] In one embodiment, the invention further comprises: a mixing control module;

[0038] The mixing control module includes a sample bag, a mixing bag, a refrigeration mixing device and a second peristaltic pump. The mixing control module is used to control the reverse rotation of the second peristaltic pump to evacuate the air in the mixing bag in the refrigeration mixing device, control the refrigeration mixing device to cool down, so as to reduce the ambient temperature of the mixing bag to a preset temperature, and control the second peristaltic pump to extract the cell preparation in the sample bag into the mixing bag. When the capacity of the cell preparation in the mixing bag reaches the preset mixing capacity, the refrigeration mixing device is controlled to mix the cell preparation according to preset mixing parameters within a preset mixing time.

[0039] The cell preparation packaging method and system provided in the present application first determine the preset packaging flow rate of the cell preparation based on the rated capacity of the packaging bag and the preset packaging time, then control the first peristaltic pump to extract the cell preparation in the refrigeration and mixing device into the packaging bag connected to the packaging pipeline, and then obtain the flow rate of the cell preparation in the quantitative tube based on the capacity of the quantitative tube between the first bubble sensor and the second bubble sensor, and the time difference between the cell preparation flowing through the first bubble sensor and the second bubble sensor. If the absolute value of the error between the flow rate in the quantitative tube and the preset packaging flow rate is less than or equal to the error threshold, the first peristaltic pump is controlled to maintain the current speed, and the process returns to the step of controlling the first peristaltic pump to extract the cell preparation in the refrigeration and mixing device into the packaging bag connected to the packaging pipeline, until all packaging bags in the packaging pipeline meet the preset conditions. The flow rate of the cell preparation in the quantitative tube is the actual packaging flow rate of the cell preparation. When the error between the actual packaging flow rate and the preset packaging flow rate is small, the actual packaging flow rate is infinitely close to the preset packaging flow rate. Maintaining the speed of the first peristaltic pump at this time can maintain the actual packaging flow rate at a level infinitely close to the preset packaging flow rate. Since the preset packaging flow rate is determined based on the rated capacity and preset packaging time of the packaging bag, when all packaging bags meet the preset conditions, that is, the packaging time of all completed packaging bags reaches the preset packaging time, the preset packaging time and the actual packaging flow rate can be used to determine that the capacity of the cell preparation in the completed packaging bag is infinitely close to the rated capacity. Therefore, by strictly controlling the accuracy of the preset packaging time and the actual packaging flow rate, the vibration of pipelines and other devices used in traditional methods can be avoided, thereby improving the capacity accuracy of the cell preparation. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] In order to more clearly illustrate the technical solutions in the present application or the prior art, a brief introduction will be given below to the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0041] Figure 1 This is one of the flow diagrams of the cell preparation packaging method provided in the examples of the present application;

[0042] Figure 2 This is the second flow diagram of the cell preparation packaging method provided in the examples of the present application;

[0043] Figure 3 This is the third flow chart of the cell preparation packaging method provided in the examples of the present application;

[0044] Figure 4 This is the fourth flow chart of the cell preparation packaging method provided in the examples of the present application;

[0045] Figure 5 Schematic diagram of the structure of the cell preparation packaging system provided in the embodiment of the present application;

[0046] Figure 6 It is a structural diagram of an electronic device provided in an embodiment of the present application.

[0047] Reference numerals:

[0048] 1-packaging control module; 11-packaging pipeline; 12-packaging bag; 13-first sterile filter; 14-second sterile filter; 2-quantification control module; 21-first peristaltic pump; 22-first bubble sensor; 23-second bubble sensor; 24-quantification tube; 25-dropper; 3-air intake control module; 31-air intake control valve; 32-packaging control valve; 33-third sterile filter; 34-air inlet; 4-mixing control module; 41-sample bag; 42-mixing bag; 43-refrigeration mixing device; 44-second peristaltic pump; 45-third bubble sensor. DETAILED DESCRIPTION

[0049] To make the objectives, technical solutions, and advantages of this application more clear, the technical solutions in this application will be clearly and completely described below in conjunction with the accompanying drawings in the embodiments of this application. Obviously, the described embodiments are only part of the embodiments of this application, not all of them. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of this application.

[0050] Figure 1 This is one of the flow diagrams of the cell preparation packaging method provided in the examples of this application. Figure 1 , the present application embodiment provides a cell preparation packaging method, which may include:

[0051] 101. Determine the preset filling flow rate of the cell preparation based on the rated capacity of the filling bag and the preset filling time;

[0052] 102. Control the first peristaltic pump to extract the cell preparation in the refrigeration and mixing device into a filling bag connected to the filling pipeline;

[0053] 103. Obtaining a flow rate of the cell preparation in the quantitative tube based on the capacity of the quantitative tube between the first bubble sensor and the second bubble sensor and the time difference between the cell preparation flowing through the first bubble sensor and the second bubble sensor;

[0054] The first peristaltic pump, the first bubble sensor, the second bubble sensor and the quantitative tube are arranged on the pipeline between the refrigeration mixing device and the filling pipeline;

[0055] 104. If the absolute value of the error between the flow rate in the quantitative tube and the preset filling flow rate is less than or equal to the error threshold, control the first peristaltic pump to maintain the current speed and return to step 102;

[0056] 105. If all the filling bags in the filling pipeline meet the preset conditions, the filling will be suspended.

[0057] The preset condition is: among all the filling bags in the filling pipeline, there is at least one unfinished filling bag, and the remaining filling bags are completed filling bags; the unfinished filling bag is a filling bag whose filling time has not reached the corresponding preset filling time, and the completed filling bag is a filling bag whose filling time has reached the corresponding preset filling time.

[0058] In step 101, the number of packaging bags can be one or more, which is not limited here.

[0059] The preset dispensing flow rate of the cell preparation can be determined by the ratio of the rated capacity of the dispensing bag to the preset dispensing time.

[0060] In step 102, the number of sub-packaging pipelines can be one or more, which is not limited here. The number of sub-packaging bags connected to each sub-packaging pipeline can be one or more, which is also not limited here. In order to facilitate sub-packaging and improve sub-packaging efficiency, sub-packaging bags corresponding to the same preset sub-packaging flow rate can be connected to the same sub-packaging pipeline.

[0061] When there are multiple sub-packaging pipelines, the first peristaltic pump can be controlled to extract the cell preparation and fill multiple sub-packaging pipelines simultaneously or sequentially, and then the liquid inlet of the sub-packaging bag is opened by the control valve to control the cell preparation in the sub-packaging pipeline to be injected into the sub-packaging bag.

[0062] In addition, a sterile filter can be provided at the end of the filling pipeline and connected to the sterile filter and the air pressure sensor. The air pressure sensor can be used to monitor the internal pressure of the filling pipeline, and the sterile filter can be used to ensure the sterile environment of the filling pipeline.

[0063] The first peristaltic pump can use a small peristaltic pump or a large peristaltic pump, which is not limited here. When the volume to be packaged is small, a small peristaltic pump can be used, and when the volume to be packaged is large, a large peristaltic pump can be used.

[0064] In step 103, the quantitative tube can be a fixed pipeline between the two bubble sensors or a container of a specific capacity. The flow rate of the cell preparation in the quantitative tube, i.e., the actual packaging flow rate, can be determined by the ratio of the capacity of the quantitative tube between the first bubble sensor and the second bubble sensor to the absolute value of the time difference between the cell preparation flowing through the first bubble sensor and the second bubble sensor.

[0065] In step 104, the rotational speed of the first peristaltic pump directly affects the flow rate of the cell preparation flowing through the peristaltic pump, that is, it directly affects the actual packaging flow rate. When the error between the actual packaging flow rate and the preset packaging flow rate is small, it can be determined that the rotational speed of the first peristaltic pump at this time is relatively ideal, and the first peristaltic pump can be controlled to maintain the current rotational speed so that the actual packaging flow rate is infinitely close to the preset packaging flow rate.

[0066] It should be noted that if the absolute value of the error between the flow in the quantitative tube and the preset packaging flow is greater than the error threshold, the actual packaging flow can be adjusted by adjusting the speed of the first peristaltic pump or other parameters affecting the flow, or by replacing the peristaltic pump to reduce the error between the actual packaging flow and the preset packaging flow.

[0067] The cell preparation packaging method provided in this embodiment first determines the preset packaging flow rate of the cell preparation based on the rated capacity of the packaging bag and the preset packaging time, then controls the first peristaltic pump to extract the cell preparation in the refrigeration and mixing device into the packaging bag connected to the packaging pipeline, and then obtains the flow rate of the cell preparation in the quantitative tube based on the capacity of the quantitative tube between the first bubble sensor and the second bubble sensor, and the time difference between the cell preparation flowing through the first bubble sensor and the second bubble sensor. If the absolute value of the error between the flow rate in the quantitative tube and the preset packaging flow rate is less than or equal to the error threshold, the first peristaltic pump is controlled to maintain the current speed, and the process returns to the step of controlling the first peristaltic pump to extract the cell preparation in the refrigeration and mixing device into the packaging bag connected to the packaging pipeline, until all the packaging bags in the packaging pipeline meet the preset conditions. The flow rate of the cell preparation in the quantitative tube is the actual packaging flow rate of the cell preparation. When the error between the actual packaging flow rate and the preset packaging flow rate is small, the actual packaging flow rate is infinitely close to the preset packaging flow rate. Maintaining the speed of the first peristaltic pump at this time can maintain the actual packaging flow rate at a level infinitely close to the preset packaging flow rate. Since the preset packaging flow rate is determined based on the rated capacity and preset packaging time of the packaging bag, when all packaging bags meet the preset conditions, that is, the packaging time of all completed packaging bags reaches the preset packaging time, the preset packaging time and the actual packaging flow rate can be used to determine that the capacity of the cell preparation in the completed packaging bag is infinitely close to the rated capacity. Therefore, by strictly controlling the accuracy of the preset packaging time and the actual packaging flow rate, the vibration of pipelines and other devices used in traditional methods can be avoided, thereby improving the capacity accuracy of the cell preparation.

[0068] Figure 2 This is the second flow diagram of the cell preparation packaging method provided in the embodiment of this application. Figure 2 In one embodiment, controlling the first peristaltic pump to extract the cell preparation from the refrigeration and mixing device into a filling bag connected to the filling pipeline may include:

[0069] 201. Control the first peristaltic pump to pump the cell preparation in the refrigeration and mixing device into the pipeline to be processed until the pipeline to be processed is full of liquid;

[0070] The pipeline to be processed is the pipeline between the sub-packaging control valve and the farthest sub-packaging bag. The sub-packaging control valve is set on the pipeline between the refrigeration mixing device and the sub-packaging bag. The farthest sub-packaging bag is the sub-packaging bag with the longest pipeline between it and the sub-packaging control valve.

[0071] 202. Control the first peristaltic pump to sequentially extract the cell preparation into different filling bags connected to the filling pipeline.

[0072] In this embodiment, the pipeline to be processed is filled before packaging is started, which can ensure the continuity of cell preparation packaging. At the same time, for multiple packaging bags in the packaging pipeline, the method of sequential injection is used to facilitate capacity monitoring of a single packaging bag, avoiding the monitoring error that may be caused by the need to monitor multiple packaging bags at the same time when injecting liquid at the same time, and further improving the capacity accuracy of the cell preparation in the packaging bag.

[0073] In one embodiment, after all the filling bags in the filling pipeline meet the preset conditions, the following steps may be performed:

[0074] The air inlet control valve is controlled to open, and the outside air is used to push the cell preparation in the liquid-filled state in the pipeline to be processed into the unfinished filling bag.

[0075] The air intake control valve is arranged on the pipeline connecting the first peristaltic pump and the atmosphere, and under preset conditions, the absolute value of the difference between the total rated capacity of the unfinished filling bags and the total capacity of the cell preparations injected into the unfinished filling bags is equal to the full liquid capacity when the pipeline to be processed reaches a full liquid state.

[0076] It should be noted that when using air to push the cell preparation in the pipeline to be processed to the unfinished filling bag, it is also necessary to control the filling control valve to be closed to prevent gas loss. In addition, an air filter can be installed at the air inlet to ensure the sterile environment of the pipeline.

[0077] When the preset conditions are met, this embodiment can stop the flow of liquid into the pipeline to be processed and use the outside air to push the full liquid cell preparation in the pipeline to be processed into the unfinished filling bag, thereby ensuring that the cell preparation in the pipeline to be processed is completely emptied and used for filling, thereby ensuring the capacity accuracy of the filling bag while avoiding the waste of residual cell preparation in the pipeline.

[0078] Figure 3 This is the third flow chart of the cell preparation packaging method provided in the embodiment of this application. Figure 3 In one embodiment, after using external air to push the cell preparation in the pipeline to be processed, which is in a full liquid state, into the unfinished filling bag, the following steps may be included:

[0079] 301. Control the liquid inlets of all sub-packaging bags to remain open for a preset period of time and then close;

[0080] 302. Control the liquid inlet of the current sub-packaging bag to open, and control the first peristaltic pump to reverse, so as to evacuate the bubbles in the current sub-packaging bag;

[0081] 303. Control the pressure sensor to monitor the internal pressure of the filling pipeline. If the internal pressure reaches the preset internal pressure, control another filling bag as the current filling bag and return to step 302.

[0082] 304. If all bubbles in the packaging bags are evacuated, the first peristaltic pump is controlled to stop.

[0083] In step 301, the liquid inlets of all the filling bags are controlled to remain open for a period of time, so that the pressure inside the filling pipeline can be balanced, thereby preventing the first peristaltic pump from being unable to extract bubbles.

[0084] In steps 302 to 304, all sub-packaging bags are bubble-extracted in sequence, the liquid inlet of the current sub-packaging bag is controlled to be opened, and after the bubble extraction is completed, the liquid inlet of the current sub-packaging bag is controlled to be closed, and the liquid inlet of the next sub-packaging bag is controlled to be opened, and bubble extraction is performed on the next sub-packaging bag, and so on, until the bubbles in all sub-packaging bags are evacuated.

[0085] When extracting bubbles from each sub-packaging bag, the internal pressure of the sub-packaging pipeline is monitored. If the internal pressure reaches the preset internal pressure, it can be considered that the bubbles in the sub-packaging bag have been evacuated.

[0086] Furthermore, after all the bubbles in the existing filling bags in the filling pipeline are extracted, a sterile pipe connection machine can be used to heat-seal a new module at the connection between the filling control valve and the air intake control valve. The module includes a peristaltic pump, two bubble sensors and a quantitative tube between the two, multiple filling pipelines and filling bags connected to them, etc., to achieve multiple and diversified filling control.

[0087] In this embodiment, the bubbles in the packaging bags are extracted sequentially after the packaging is completed, which can further control the volume accuracy of the cell preparation in the packaging bags and improve the quality of the cell preparation.

[0088] Figure 4 This is the fourth flow chart of the cell preparation packaging method provided in the embodiment of the present application. Figure 4 In one embodiment, before controlling the first peristaltic pump to extract the cell preparation from the refrigeration and mixing device into the filling bag connected to the filling pipeline, the steps may include:

[0089] 401. Control the second peristaltic pump to reversely rotate to evacuate the air from the mixing bag in the refrigeration mixing device;

[0090] The second peristaltic pump is arranged on the pipeline between the sample bag and the refrigeration and mixing device, and the second peristaltic pump is connected to the atmosphere;

[0091] 402. Control the refrigeration and mixing device to lower the temperature so as to reduce the ambient temperature of the mixing bag to a preset temperature;

[0092] 403. Control the second peristaltic pump to extract the cell preparation in the sample bag into the mixing bag;

[0093] 404. When the volume of the cell preparation in the mixing bag reaches the preset mixing capacity, the refrigeration mixing device is controlled to perform a mixing operation on the cell preparation according to the preset mixing parameters within the preset mixing time.

[0094] The preset mixing parameters include mixing frequency, mixing amplitude and mixing acceleration.

[0095] In step 401, the cell preparation has not yet been injected into the mixing bag, and the second peristaltic pump is controlled to evacuate the air therein to avoid bag explosion accidents due to excessive air during the subsequent liquid injection process.

[0096] In step 402, the temperature of the refrigeration plate and the space of the device in the refrigeration and mixing device is controlled to drop to a preset temperature. A compressor refrigeration method can be used for refrigeration and cooling, and a temperature sensor in the device is used to monitor whether the temperature reaches the preset temperature. The preset temperature is a temperature that can ensure a better mixing effect and cell activity.

[0097] In step 403, the dispensing control valve and the air intake control valve need to be closed. They are then opened again for subsequent dispensing and air intake. The flow rate of the cell preparation from the sample bag into the mixing bag can be adjusted based on the cell preparation. A third bubble sensor in the pipeline between the sample bag and the mixing bag monitors whether the cell preparation has been injected into the mixing bag.

[0098] In step 404, the preset mixing capacity can be two-thirds of the rated capacity of the mixing bag, and the preset mixing time can be ten minutes. The mixing plate in the refrigeration mixing device will squeeze or slap the mixing bag at the bottom of the mixing bag according to the preset mixing frequency, mixing amplitude, and mixing acceleration, so that the cell preparation in the mixing bag flows upward and then sinks, achieving a better mixing effect.

[0099] In addition, the cumulative decrease in the cell preparation in the sample bag can be monitored by a weighing device, and the cumulative increase in the cell preparation in the mixing bag can be calculated accordingly, and the mixing parameters of the mixing plate can be changed according to the real-time capacity of the cell preparation in the mixing bag.

[0100] Among them, the refrigeration method of the refrigeration plate attached to the mixing bag in the refrigeration mixing device is centralized refrigeration. The refrigeration plate is separated from the surrounding pipes and mechanisms by a layer of insulation layer, which can prevent energy from dissipating outward and ensure the refrigeration temperature of the mixing bag.

[0101] This embodiment can maintain a relatively uniform concentration, good quality and activity of the cell preparation to be packaged through the vacuuming, cooling and mixing operations before packaging, thereby ensuring the quality of the packaged finished cell preparation.

[0102] In one embodiment, controlling the first peristaltic pump to extract the cell preparation from the refrigeration and mixing device into a filling bag connected to the filling pipeline may include:

[0103] Controlling the first peristaltic pump to extract the cell preparation in the refrigeration and mixing device into a filling bag connected to the filling pipeline through the dropper;

[0104] The dropper is arranged on the pipeline between the refrigeration and mixing device and the first peristaltic pump.

[0105] In this embodiment, a dropper is provided on the pipeline between the refrigeration and mixing device and the first peristaltic pump. The dropper can be used to collect bubbles in the cell preparation before the cell preparation passes through the first peristaltic pump, thereby ensuring that the cell preparation passing through the first peristaltic pump does not contain bubbles, thereby improving the quality and volume accuracy of the packaged cell preparation.

[0106] Reference Figure 2 In one embodiment, before controlling the first peristaltic pump to extract the cell preparation from the refrigeration and mixing device into the filling bag connected to the filling pipeline, the steps may include:

[0107] Control the ambient temperature of the packaging bags to the preset temperature.

[0108] In order to ensure better quality of cell preparations, the difference between the ambient temperature of the sub-packaging bag and the ambient temperature of the mixing bag should not be too large. Therefore, the refrigeration medium in the refrigeration mixing device can be transferred to the surrounding area of ​​the sub-packaging bag, or a refrigeration device can also be installed outside the sub-packaging bag.

[0109] This embodiment can maintain the ambient temperature of the cell preparation from the mixing bag to the sub-packaging bag by lowering the ambient temperature of the sub-packaging bag to a preset temperature, thereby ensuring its quality to the greatest extent.

[0110] Figure 5 Schematic diagram of the cell preparation packaging system provided in the embodiment of the present application. Figure 5 , the embodiment of the present application provides a cell preparation packaging system for implementing the aforementioned cell preparation packaging method, which may include: a packaging control module 1 and a quantitative control module 2;

[0111] The packaging control module 1 includes a packaging pipeline 11 and a packaging bag 12. The packaging control module 1 is used to determine a preset packaging flow rate of the cell preparation according to the rated capacity of the packaging bag 12 and the preset packaging time;

[0112] The quantitative control module 2 includes a first peristaltic pump 21, a first bubble sensor 22, a second bubble sensor 23 and a quantitative tube 24. The quantitative control module 2 is used to control the first peristaltic pump 21 to extract the cell preparation into the sub-packaging bag 12 connected to the sub-packaging pipeline 11, and obtain the flow rate of the cell preparation in the quantitative tube 24 according to the capacity of the quantitative tube 24 between the first bubble sensor 22 and the second bubble sensor 23, and the time difference between the cell preparation flowing through the first bubble sensor 22 and the second bubble sensor 23. If the absolute value of the error between the flow rate in the quantitative tube 24 and the preset sub-packaging flow rate is less than or equal to the error threshold, the first peristaltic pump 21 is controlled to maintain the current speed, and the step of controlling the first peristaltic pump 21 to extract the cell preparation into the sub-packaging bag 12 connected to the sub-packaging pipeline 11 is returned until all the sub-packaging bags 12 in the sub-packaging pipeline 11 meet the preset conditions;

[0113] The preset condition is: among all the filling bags 12 in the filling pipeline 11, there is at least one unfinished filling bag, and the remaining filling bags are completed filling bags; the unfinished filling bag is a filling bag whose filling time has not reached the corresponding preset filling time, and the completed filling bag is a filling bag whose filling time has reached the corresponding preset filling time.

[0114] It should be noted that the packaging control module 1 further includes a first sterile filter 13 and a second sterile filter 14, which are respectively arranged at Figure 5 The ends of the two sub-packaging pipelines 11 are sealed to maintain the sterile environment of the sub-packaging pipelines 11.

[0115] The quantitative control module also includes a dropper 25, which controls the cell preparation to flow through the dropper 25 and then through the first peristaltic pump 21. The dropper 25 can be used to collect bubbles in the cell preparation, ensuring that the cell preparation passing through the first peristaltic pump 21 does not contain bubbles, thereby improving the quality and volume accuracy of the packaged cell preparation.

[0116] In the cell preparation packaging system provided in this embodiment, the flow rate of the cell preparation in the quantitative tube is the actual packaging flow rate of the cell preparation. When the error between the actual packaging flow rate and the preset packaging flow rate is small, the actual packaging flow rate is infinitely close to the preset packaging flow rate. Maintaining the speed of the first peristaltic pump at this time can maintain the actual packaging flow rate at a level infinitely close to the preset packaging flow rate. Since the preset packaging flow rate is determined based on the rated capacity and preset packaging time of the packaging bag, when all packaging bags meet the preset conditions, that is, when the packaging time of all completed packaging bags reaches the preset packaging time, the preset packaging time and the actual packaging flow rate can be used to determine that the capacity of the cell preparation in the completed packaging bag is infinitely close to the rated capacity. Therefore, by strictly controlling the accuracy of the preset packaging time and the actual packaging flow rate, the vibration of pipelines and other devices used in traditional methods can be avoided, thereby improving the capacity accuracy of the cell preparation.

[0117] Reference Figure 5 , In one embodiment, the cell preparation packaging system further includes: an air intake control module 3;

[0118] The air intake control module 3 includes an air intake control valve 31 , which is used to control the opening of the air intake control valve 31 and use external air to push the cell preparation in the pipeline to be processed that is in a full liquid state into the unfinished packaging bag.

[0119] It should be noted that the air intake control module 3 also includes a filling control valve 32, a third sterile filter 33 and an air inlet 34. When using external air to push the cell preparation in the pipeline to be processed into the unfinished filling bag, it is necessary to control the filling control valve 32 to be closed to prevent the gas from flowing into other pipelines and affecting the pushing effect of the cell preparation in the pipeline to be processed; the third sterile filter 33 is set at the air inlet 34 to ensure the sterile environment of the pipeline.

[0120] This embodiment controls the opening of the air intake control valve and uses external air to push the cell preparation in the pipeline to be processed into the unfinished packaging bag, thereby avoiding the waste of the cell preparation in the pipeline to be processed while ensuring the capacity accuracy of the packaging bag.

[0121] Reference Figure 5 , in one embodiment, the cell preparation packaging system further includes: a mixing control module 4;

[0122] The mixing control module 4 includes a sample bag 41, a mixing bag 42, a refrigeration mixing device 43 and a second peristaltic pump 44. The mixing control module 4 is used to control the reverse rotation of the second peristaltic pump 44 to evacuate the air in the mixing bag 42 in the refrigeration mixing device 43, control the cooling of the refrigeration mixing device 43 to reduce the ambient temperature of the mixing bag 42 to a preset temperature, and control the second peristaltic pump 44 to extract the cell preparation in the sample bag 41 into the mixing bag 42. When the capacity of the cell preparation in the mixing bag 42 reaches the preset mixing capacity, the refrigeration mixing device 43 is controlled to mix the cell preparation according to the preset mixing parameters within the preset mixing time.

[0123] It should be noted that the mixing control module 4 further includes a third bubble sensor 45 , which can be used to monitor whether a cell preparation is injected into the mixing bag 42 .

[0124] This embodiment can maintain a relatively uniform concentration, good quality and activity of the cell preparation to be packaged through the vacuuming, cooling and mixing operations before packaging, thereby ensuring the quality of the packaged finished cell preparation.

[0125] Figure 6 An example of a physical structure diagram of an electronic device is shown below. Figure 6 As shown, the electronic device may include: a processor 610, a communication interface 620, a memory 630, and a communication bus 640, wherein the processor 610, the communication interface 620, and the memory 630 communicate with each other via the communication bus 640. The processor 610 may call a computer program in the memory 630 to execute the steps of the cell preparation packaging method, for example, including:

[0126] Determine the preset dispensing flow rate of the cell preparation based on the rated capacity of the dispensing bag and the preset dispensing time;

[0127] Controlling the first peristaltic pump to extract the cell preparation in the refrigeration and mixing device into a filling bag connected to the filling pipeline;

[0128] The flow rate of the cell preparation in the quantitative tube is obtained based on the capacity of the quantitative tube between the first bubble sensor and the second bubble sensor, and the time difference between the flow of the cell preparation through the first bubble sensor and the second bubble sensor. The first peristaltic pump, the first bubble sensor, the second bubble sensor, and the quantitative tube are arranged in a pipeline between the refrigeration and mixing device and the filling pipeline.

[0129] If the absolute value of the error between the flow rate in the quantitative tube and the preset filling flow rate is less than or equal to the error threshold, controlling the first peristaltic pump to maintain the current speed, and returning to the step of controlling the first peristaltic pump to extract the cell preparation in the refrigeration and mixing device into the filling bag connected to the filling pipeline, until all the filling bags in the filling pipeline meet the preset conditions;

[0130] The preset condition is: among all the filling bags in the filling pipeline, there is at least one unfinished filling bag, and the remaining filling bags are completed filling bags; the unfinished filling bag is a filling bag whose filling time has not reached the corresponding preset filling time, and the completed filling bag is a filling bag whose filling time has reached the corresponding preset filling time.

[0131] In addition, the logic instructions in the above-mentioned memory 630 can be implemented in the form of a software functional unit and can be stored in a computer-readable storage medium when sold or used as an independent product. Based on this understanding, the technical solution of the present application is essentially or the part that contributes to the prior art or the part of the technical solution can be embodied in the form of a software product, and the computer software product is stored in a storage medium, including a number of instructions for enabling a computer device (which can be a personal computer, a server, or a network device, etc.) to execute all or part of the steps of the method described in each embodiment of the present application. The aforementioned storage medium includes: various media that can store program codes, such as a USB flash drive, a mobile hard disk, a read-only memory (ROM), a random access memory (RAM), a magnetic disk or an optical disk.

[0132] On the other hand, embodiments of the present application further provide a computer program product, comprising a computer program, which may be stored on a non-transitory computer-readable storage medium. When the computer program is executed by a processor, the computer can perform the steps of the cell preparation packaging method provided in the above embodiments, for example, including:

[0133] Determine the preset dispensing flow rate of the cell preparation based on the rated capacity of the dispensing bag and the preset dispensing time;

[0134] Controlling the first peristaltic pump to extract the cell preparation in the refrigeration and mixing device into a filling bag connected to the filling pipeline;

[0135] The flow rate of the cell preparation in the quantitative tube is obtained based on the capacity of the quantitative tube between the first bubble sensor and the second bubble sensor, and the time difference between the flow of the cell preparation through the first bubble sensor and the second bubble sensor. The first peristaltic pump, the first bubble sensor, the second bubble sensor, and the quantitative tube are arranged in a pipeline between the refrigeration and mixing device and the filling pipeline.

[0136] If the absolute value of the error between the flow rate in the quantitative tube and the preset filling flow rate is less than or equal to the error threshold, controlling the first peristaltic pump to maintain the current speed, and returning to the step of controlling the first peristaltic pump to extract the cell preparation in the refrigeration and mixing device into the filling bag connected to the filling pipeline, until all the filling bags in the filling pipeline meet the preset conditions;

[0137] The preset condition is: among all the filling bags in the filling pipeline, there is at least one unfinished filling bag, and the remaining filling bags are completed filling bags; the unfinished filling bag is a filling bag whose filling time has not reached the corresponding preset filling time, and the completed filling bag is a filling bag whose filling time has reached the corresponding preset filling time.

[0138] On the other hand, an embodiment of the present application further provides a processor-readable storage medium, wherein the processor-readable storage medium stores a computer program, wherein the computer program is configured to cause a processor to execute the steps of the methods provided in the above embodiments, for example, including:

[0139] Determine the preset dispensing flow rate of the cell preparation based on the rated capacity of the dispensing bag and the preset dispensing time;

[0140] Controlling the first peristaltic pump to extract the cell preparation in the refrigeration and mixing device into a filling bag connected to the filling pipeline;

[0141] The flow rate of the cell preparation in the quantitative tube is obtained based on the capacity of the quantitative tube between the first bubble sensor and the second bubble sensor, and the time difference between the flow of the cell preparation through the first bubble sensor and the second bubble sensor. The first peristaltic pump, the first bubble sensor, the second bubble sensor, and the quantitative tube are arranged in a pipeline between the refrigeration and mixing device and the filling pipeline.

[0142] If the absolute value of the error between the flow rate in the quantitative tube and the preset filling flow rate is less than or equal to the error threshold, controlling the first peristaltic pump to maintain the current speed, and returning to the step of controlling the first peristaltic pump to extract the cell preparation in the refrigeration and mixing device into the filling bag connected to the filling pipeline, until all the filling bags in the filling pipeline meet the preset conditions;

[0143] The preset condition is: among all the filling bags in the filling pipeline, there is at least one unfinished filling bag, and the remaining filling bags are completed filling bags; the unfinished filling bag is a filling bag whose filling time has not reached the corresponding preset filling time, and the completed filling bag is a filling bag whose filling time has reached the corresponding preset filling time.

[0144] The processor-readable storage medium can be any available medium or data storage device that can be accessed by the processor, including but not limited to magnetic storage (such as floppy disks, hard disks, magnetic tapes, magneto-optical disks (MO)), optical storage (such as CDs, DVDs, BDs, HVDs, etc.), and semiconductor storage (such as ROMs, EPROMs, EEPROMs, non-volatile memories (NANDFLASH), solid-state drives (SSDs)), etc.

[0145] Through the description of the above embodiments, those skilled in the art can clearly understand that each embodiment can be implemented by means of software plus a necessary general hardware platform, or of course, by hardware. Based on this understanding, the essence of the above technical solution or the part that contributes to the existing technology can be embodied in the form of a software product. The computer software product can be stored in a computer-readable storage medium, such as ROM / RAM, a magnetic disk, an optical disk, etc., and includes a number of instructions for enabling a computer device (which can be a personal computer, a server, or a network device, etc.) to execute the methods described in each embodiment or certain parts of the embodiments.

[0146] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present application.

Claims

1. A cell preparation packaging method, characterized in that: include: Determine the preset dispensing flow rate of the cell preparation based on the rated capacity of the dispensing bag and the preset dispensing time; Controlling the first peristaltic pump to extract the cell preparation in the refrigeration and mixing device into a filling bag connected to the filling pipeline includes: Controlling the first peristaltic pump to pump the cell preparation in the refrigeration and mixing device into the pipeline to be processed until the pipeline to be processed is full of liquid; the pipeline to be processed is the pipeline between the sub-packaging control valve and the farthest sub-packaging bag, the sub-packaging control valve is arranged on the pipeline between the refrigeration and mixing device and the sub-packaging bag, and the farthest sub-packaging bag is the sub-packaging bag having the longest pipeline length between the sub-packaging control valve and the sub-packaging bag; controlling the first peristaltic pump to sequentially extract the cell preparation into different filling bags connected to the filling pipeline; The flow rate of the cell preparation in the quantitative tube is obtained based on the capacity of the quantitative tube between the first bubble sensor and the second bubble sensor, and the time difference between the flow of the cell preparation through the first bubble sensor and the second bubble sensor. The first peristaltic pump, the first bubble sensor, the second bubble sensor, and the quantitative tube are arranged in a pipeline between the refrigeration and mixing device and the filling pipeline. If the absolute value of the error between the flow rate in the quantitative tube and the preset filling flow rate is less than or equal to the error threshold, controlling the first peristaltic pump to maintain the current speed, and returning to the step of controlling the first peristaltic pump to extract the cell preparation in the refrigeration and mixing device into the filling bag connected to the filling pipeline, until all the filling bags in the filling pipeline meet the preset conditions; The preset condition is: among all the sub-packaging bags in the sub-packaging pipeline, there is at least one unfinished sub-packaging bag, and the remaining sub-packaging bags are all completed sub-packaging bags; the unfinished sub-packaging bag is a sub-packaging bag whose packaging time has not reached the corresponding preset packaging time, and the completed sub-packaging bag is a sub-packaging bag whose packaging time has reached the corresponding preset packaging time; The air intake control valve is controlled to open, and the cell preparation in the pipeline to be processed is pushed into the unfinished sub-packaging bag by using external air; the air intake control valve is arranged on the pipeline connecting the first peristaltic pump and the atmosphere; In the preset condition, the absolute value of the difference between the total rated capacity of the unfinished filling bags and the total capacity of the cell preparations injected into the unfinished filling bags is equal to the full liquid capacity when the pipeline to be processed reaches a full liquid state.

2. The cell preparation packaging method according to claim 1, characterized in that: After using external air to push the cell preparation in the pipeline to be processed, which is in a full liquid state, into the unfinished filling bag, the method includes: Control the liquid inlets of all filling bags to remain open for a preset time and then close; Controlling the liquid inlet of the current sub-packaging bag to open, and controlling the first peristaltic pump to reverse, so as to evacuate the bubbles in the current sub-packaging bag; The pressure sensor is controlled to monitor the internal pressure of the sub-packaging pipeline. If the internal pressure reaches a preset internal pressure, the other sub-packaging bags are controlled to serve as the current sub-packaging bags, and the control of the liquid inlet of the current sub-packaging bag is returned to open, and the first peristaltic pump is controlled to reverse to evacuate the bubbles in the current sub-packaging bag until all the bubbles in the sub-packaging bags are evacuated.

3. The cell preparation packaging method according to claim 1, characterized in that: Before controlling the first peristaltic pump to extract the cell preparation from the refrigeration and mixing device into the filling bag connected to the filling pipeline, the method includes: Controlling the reverse rotation of the second peristaltic pump to evacuate the air from the mixing bag in the refrigeration and mixing device; the second peristaltic pump is disposed on a pipeline between the sample bag and the refrigeration and mixing device, and the second peristaltic pump is connected to the atmosphere; Controlling the refrigeration and mixing device to cool down the ambient temperature of the mixing bag to a preset temperature; controlling the second peristaltic pump to extract the cell preparation in the sample bag into the mixing bag; When the volume of the cell preparation in the mixing bag reaches a preset mixing volume, the refrigeration mixing device is controlled to mix the cell preparation according to preset mixing parameters within a preset mixing time; the preset mixing parameters include mixing frequency, mixing amplitude, and mixing acceleration.

4. The cell preparation packaging method according to claim 1, characterized in that: The method of controlling the first peristaltic pump to extract the cell preparation from the refrigeration and mixing device into a filling bag connected to the filling pipeline comprises: The first peristaltic pump is controlled to extract the cell preparation in the refrigeration and mixing device into a sub-packaging bag connected to the sub-packaging pipeline through a dropper; the dropper is arranged on the pipeline between the refrigeration and mixing device and the first peristaltic pump.

5. The cell preparation packaging method according to claim 3, characterized in that: Before controlling the first peristaltic pump to extract the cell preparation from the refrigeration and mixing device into the filling bag connected to the filling pipeline, the method includes: The ambient temperature of the packaging bag is controlled to drop to the preset temperature.

6. A cell preparation packaging system for implementing the cell preparation packaging method according to any one of claims 1 to 5, characterized in that: include: Packaging control module and quantitative control module; The packaging control module includes a packaging pipeline and a packaging bag, and the packaging control module is used to determine a preset packaging flow rate of the cell preparation according to the rated capacity of the packaging bag and the preset packaging time; The quantitative control module includes a first peristaltic pump, a first bubble sensor, a second bubble sensor and a quantitative tube. The quantitative control module is used to control the first peristaltic pump to extract the cell preparation into a sub-packaging bag connected to the sub-packaging pipeline, and obtain the flow rate of the cell preparation in the quantitative tube according to the capacity of the quantitative tube between the first bubble sensor and the second bubble sensor, and the time difference between the cell preparation flowing through the first bubble sensor and the second bubble sensor. If the absolute value of the error between the flow rate in the quantitative tube and the preset sub-packaging flow rate is less than or equal to the error threshold, the first peristaltic pump is controlled to maintain the current speed, and the process returns to the step of controlling the first peristaltic pump to extract the cell preparation into the sub-packaging bag connected to the sub-packaging pipeline until all the sub-packaging bags in the sub-packaging pipeline meet the preset conditions; The preset condition is: among all the filling bags in the filling pipeline, there is at least one unfinished filling bag, and the remaining filling bags are completed filling bags; the unfinished filling bag is a filling bag whose filling time has not reached the corresponding preset filling time, and the completed filling bag is a filling bag whose filling time has reached the corresponding preset filling time.

7. The cell preparation packaging system according to claim 6, characterized in that: Also includes: Intake control module; The air intake control module includes an air intake control valve, which is used to control the opening of the air intake control valve and use external air to push the cell preparation in a liquid-filled state in the pipeline to be processed into the unfinished packaging bag.

8. The cell preparation packaging system according to claim 6, characterized in that: Also includes: Mixing control module; The mixing control module includes a sample bag, a mixing bag, a refrigeration mixing device and a second peristaltic pump. The mixing control module is used to control the reverse rotation of the second peristaltic pump to evacuate the air in the mixing bag in the refrigeration mixing device, control the refrigeration mixing device to cool down, so as to reduce the ambient temperature of the mixing bag to a preset temperature, and control the second peristaltic pump to extract the cell preparation in the sample bag into the mixing bag. When the capacity of the cell preparation in the mixing bag reaches the preset mixing capacity, the refrigeration mixing device is controlled to mix the cell preparation according to preset mixing parameters within a preset mixing time.

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