Cell product preparation method and device

Abstract

The invention relates to the technical field of cell product preparation, and provides a cell product preparation method and device. The method comprises the following steps: controlling a separation container to perform centrifugal motion so as to perform centrifugation on a cell sap sample in the separation container to obtain an intermediate product; controlling a first peristaltic pump to extract the intermediate product from the separation container; controlling a cleaning container to perform centrifugal motion, and controlling a first peristaltic pump to pump the extracted intermediate product into the cleaning container so as to clean the intermediate product in the cleaning container to obtain a minimum concentrated liquid; the volume of the minimum concentrated liquid is calibrated in advance; and controlling a second peristaltic pump to pump a resuspension solution into the cleaning container so as to resuspend and prepare the minimum concentrated solution to obtain a cell product. According to the cell product preparation method and device provided by the invention, the high-efficiency and high-purity requirements for preparing the cell product based on a large-volume cell sap sample can be met.

Description

Technical Field

[0001] The present application relates to the technical field of cell product preparation, and in particular to a method and device for preparing a cell product. Background Art

[0002] Currently, the preparation of cell products requires separating the desired cells from the cell fluid sample and cleaning them. The main methods are manual operation and automated equipment operation.

[0003] Manual operation has the advantages of flexibility and the ability to adjust operations at any time according to actual conditions, but it has extremely high requirements for the sterility of the operating environment, and manual operation is inefficient and has a high risk of contamination. Although the automated equipment operation has the advantage of low risk of contamination, the consumables are basically one-time connection solutions, and the same consumables are used to separate and clean cell fluid samples. The process requires cleaning the centrifuge containers in the same consumables. Due to the increased cleaning time of the centrifuge containers, the overall efficiency of product preparation is reduced. On the other hand, the cleaning of the centrifuge containers cannot completely clean the residues of non-required cells during the separation process, resulting in low purity of the cell product.

[0004] As the market expands, more and more large-volume cell fluid samples need to be processed in a timely manner. Existing product preparation methods cannot meet the high-efficiency and high-purity requirements required for preparing cell products based on large-volume cell fluid samples. Summary of the invention

[0005] The embodiments of the present application provide a method and device for preparing a cell product, which are used to solve the technical problem that the existing product preparation methods cannot meet the high efficiency and pollution-free requirements required when preparing cell products based on large-volume cell fluid samples.

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

[0007] Controlling the centrifugal movement of the separation container to centrifuge the cell fluid sample in the separation container to obtain an intermediate product;

[0008] extracting the intermediate product from the separation container;

[0009] Controlling the centrifugal movement of the cleaning container and pumping the extracted intermediate product into the cleaning container to clean the intermediate product in the cleaning container to obtain a minimum concentrated liquid; the volume of the minimum concentrated liquid is pre-calibrated;

[0010] The resuspended liquid is pumped into the washing container to resuspend and prepare the minimal concentrated liquid to obtain a cell product.

[0011] In one embodiment, before the controlling of the centrifugal movement of the cleaning container, the method includes:

[0012] Controlling the second peristaltic pump to pump a preset first volume of cleaning liquid into the cleaning container;

[0013] Controlling the cleaning container to start at a first rotation speed;

[0014] Controlling the first peristaltic pump to pump out the cleaning liquid in the cleaning container until a bubble sensor on the liquid outlet pipeline of the cleaning container detects gas;

[0015] The difference between the preset first volume and the volume of the extracted cleaning liquid is determined as the volume of the minimum concentrated liquid.

[0016] In one embodiment, before the controlling of the centrifugal movement of the cleaning container, the method includes:

[0017] The switching device is controlled to switch the pipeline connection from the separation container to the cleaning container.

[0018] In one embodiment, the control switching device switches the pipeline connection from the separation container to the cleaning container, including:

[0019] The first tube clamp is controlled to be closed, and the second tube clamp is controlled to be opened; the first tube clamp is a tube clamp on the pipeline only associated with the separation container, and the second tube clamp is a tube clamp on the pipeline only associated with the cleaning container.

[0020] In one embodiment, controlling the centrifugal movement of the separation container to centrifuge the cell fluid sample in the separation container to obtain an intermediate product includes:

[0021] Controlling the separation container to start at a second rotation speed;

[0022] Controlling the first peristaltic pump to pump the cell fluid sample into the separation container, and controlling the second peristaltic pump to pump the sample separation fluid into the separation container;

[0023] The separation container is controlled to maintain centrifugal motion at the second speed within a first preset time period to obtain an intermediate product.

[0024] In one embodiment, controlling the first peristaltic pump to pump the cell fluid sample into the separation container, and controlling the second peristaltic pump to pump the sample separation fluid into the separation container, comprises:

[0025] Controlling the second peristaltic pump to pump a preset second volume of sample separation liquid into the separation container;

[0026] Controlling the first peristaltic pump to pump the cell fluid sample into the separation container;

[0027] The second peristaltic pump is controlled to pump a preset third volume of sample separation liquid into the separation container.

[0028] In one embodiment, extracting the intermediate product from the separation container comprises:

[0029] Controlling the centrifugal speed of the separation container to decrease from the second speed to a third speed;

[0030] controlling the first peristaltic pump to pump a preset fourth volume of the intermediate product out of the separation container;

[0031] controlling the second peristaltic pump to pump a preset fifth volume of sample separation liquid into the separation container;

[0032] Controlling the separation container to maintain centrifugal motion at the third speed within a second preset time period;

[0033] The first peristaltic pump is controlled to pump a preset sixth volume of the intermediate product out of the separation container.

[0034] In one embodiment, the controlling of the centrifugal movement of the cleaning container and pumping the extracted intermediate product into the cleaning container to clean the intermediate product in the cleaning container to obtain a minimum concentrated liquid includes:

[0035] Controlling the centrifugal speed of the cleaning container to decrease from the first speed to a fourth speed;

[0036] controlling the first peristaltic pump to pump the intermediate product into the cleaning container;

[0037] controlling the second peristaltic pump to pump a cleaning liquid into the cleaning container to clean the intermediate product in the cleaning container;

[0038] The first peristaltic pump is controlled to discharge the waste liquid in the cleaning container until a minimum concentrated liquid is obtained.

[0039] In a second aspect, an embodiment of the present application provides a cell product preparation device, comprising:

[0040] The separation container control module is used to: control the centrifugal movement of the separation container to centrifuge the cell fluid sample in the separation container to obtain an intermediate product;

[0041] An intermediate product extraction control module is used to: extract the intermediate product from the separation container;

[0042] A cleaning container control module is used to: control the centrifugal movement of the cleaning container and pump the extracted intermediate product into the cleaning container to clean the intermediate product in the cleaning container to obtain a minimum concentrated liquid; the volume of the minimum concentrated liquid is pre-calibrated;

[0043] The resuspension and preparation control module is used to pump the resuspension liquid into the cleaning container to resuspend and prepare the minimum concentrated liquid to obtain a cell product.

[0044] In a third aspect, an embodiment of the present application provides an electronic device, comprising a processor and a memory storing a computer program, wherein when the processor executes the program, the steps of the cell product preparation method described in the first aspect are implemented.

[0045] The cell product preparation method and device provided in the present application control the centrifugal movement of the separation container to centrifuge the cell fluid sample in the separation container to obtain an intermediate product, extract the intermediate product from the separation container, control the centrifugal movement of the cleaning container, and pump the extracted intermediate product into the cleaning container to clean the intermediate product in the cleaning container to obtain a minimum concentrated liquid, the volume of the minimum concentrated liquid is pre-calibrated, and the resuspension liquid is pumped into the cleaning container to resuspend and prepare the minimum concentrated liquid to obtain a cell product. Since two centrifugal containers are used, one as a separation container and the other as a cleaning container, the centrifugal containers used for the separation operation and the cleaning operation can be separated. After the intermediate product is extracted from the separation container, the intermediate product can be directly pumped into the cleaning container for cleaning, without having to wait for the separation container to be cleaned and then pumping the intermediate product into the same separation container for cleaning. Therefore, the waiting time for the separation container to be cleaned is reduced and the efficiency of product preparation is improved. At the same time, since the intermediate product is pumped into a brand new cleaning container for cleaning, the contamination of the intermediate product caused by pumping into a separation container with residual non-desired cells is avoided, thereby improving the purity of the cell product and meeting the high efficiency and high purity requirements required for preparing cell products based on large-volume cell fluid samples. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] 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 paying any creative work.

[0047] Figure 1 It is a schematic diagram of the pipeline of the cell product preparation method provided in the embodiment of the present application;

[0048] Figure 2 This is one of the schematic diagrams of the process for preparing a cell product provided in the embodiments of the present application;

[0049] Figure 3 This is the second schematic diagram of the process for preparing a cell product provided in the embodiment of the present application;

[0050] Figure 4 This is the third flow chart of the method for preparing a cell product provided in the embodiment of the present application;

[0051] Figure 5 This is the fourth flow chart of the method for preparing a cell product provided in the embodiment of the present application;

[0052] Figure 6 This is the fifth flow chart of the method for preparing a cell product provided in the embodiment of the present application;

[0053] Figure 7 This is the sixth flow chart of the method for preparing a cell product provided in the embodiments of the present application;

[0054] Figure 8 is a schematic diagram of the structure of a cell product preparation device provided in an embodiment of the present application;

[0055] Fig. 9 It is a schematic diagram of the structure of an electronic device provided in an embodiment of the present application.

[0056] Reference numerals:

[0057] 1-separation container; 2-cleaning container; 3-first peristaltic pump; 4-second peristaltic pump; 5-bubble sensor; 6-first tube clamp; 7-second tube clamp; 8-first control valve; 9-second control valve; 10-third control valve; 11-fourth control valve; 12-fifth control valve; 13-sixth control valve; 14-seventh control valve; 15-eighth control valve; 16-ninth control valve. DETAILED DESCRIPTION

[0058] In order to make the purpose, technical solutions and advantages of this application clearer, the technical solutions in this application will be clearly and completely described below in conjunction with the drawings in the embodiments of this application. Obviously, the described embodiments are 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 creative work are within the scope of protection of this application.

[0059] Figure 1 It is a schematic diagram of the pipeline of the cell product preparation method provided in the embodiment of the present application;

[0060] Figure 2 This is one of the flow diagrams of the cell product preparation method provided in the examples of the present application.

[0061] Reference Figure 1 to Figure 2 , the present application embodiment provides a method for preparing a cell product, which may include:

[0062] 201. Control the centrifugal movement of the separation container to centrifuge the cell fluid sample in the separation container to obtain an intermediate product;

[0063] 202. Extracting the intermediate product from the separation container;

[0064] 203. Control the centrifugal movement of the cleaning container and pump the extracted intermediate product into the cleaning container to clean the intermediate product in the cleaning container to obtain a minimum concentrated liquid;

[0065] The minimum concentrated liquid volume is pre-calibrated;

[0066] 204. Pump the resuspended liquid into the cleaning container to resuspend and prepare the minimal concentrated liquid to obtain a cell product.

[0067] Among them, the cell fluid sample can be a peripheral blood sample, and the cell product can be a peripheral blood mononuclear cell product. The volume of the separation container 1 is relatively large, and the volume of the cleaning container 2 is relatively small. The large-volume separation container 1 can adapt to the processing of large-volume cell fluid samples without increasing the sample separation liquid, and the small-volume cleaning container 2 is convenient for concentrating the intermediate product to obtain a minimum concentrated liquid whose volume is relatively close to the pre-calibrated value.

[0068] The separation container 1 is used to separate various components from the cell fluid sample, so that the components that need to be extracted from the cell fluid sample can be easily extracted into the intermediate product bag, and the intermediate product bag contains the intermediate product. The cleaning container 2 is used to clean the intermediate product, so that the intermediate product can be obtained after cleaning to obtain the final cell product. The structures of the separation container 1 and the cleaning container 2 can be the same or different, and can be designed according to needs.

[0069] It should be noted that the use of intermediate product bags is not essential in the preparation of cell products, and the intermediate products can also be directly transferred from the separation container to the cleaning container.

[0070] The cell product preparation method provided in this embodiment controls the centrifugal movement of the separation container to centrifuge the cell fluid sample in the separation container to obtain an intermediate product, extracts the intermediate product from the separation container, controls the centrifugal movement of the cleaning container, and pumps the extracted intermediate product into the cleaning container to clean the intermediate product in the cleaning container to obtain a minimum concentrated liquid, the volume of the minimum concentrated liquid is pre-calibrated, and the resuspension liquid is pumped into the cleaning container to resuspend and prepare the minimum concentrated liquid to obtain a cell product. Since two centrifugal containers are used, one as a separation container and the other as a cleaning container, the centrifugal containers used for the separation operation and the cleaning operation can be separated. After the intermediate product is extracted from the separation container, the intermediate product can be directly pumped into the cleaning container for cleaning, without having to wait for the separation container to be cleaned and then pumping the intermediate product into the same separation container for cleaning. Therefore, the waiting time for the separation container to be cleaned is reduced and the efficiency of product preparation is improved. At the same time, since the intermediate product is pumped into a brand new cleaning container for cleaning, the contamination of the intermediate product caused by pumping into a separation container with residual non-desired cells is avoided, thereby improving the purity of the cell product and meeting the high efficiency and high purity requirements required for preparing cell products based on large-volume cell fluid samples.

[0071] Figure 3 This is the second flow chart of the method for preparing a cell product provided in the embodiment of the present application. Figure 1 and Figure 3 In one embodiment, before controlling the centrifugal movement of the cleaning container, the process may include:

[0072] 301. Control the second peristaltic pump to pump a preset first volume of cleaning liquid into the cleaning container;

[0073] 302. Control the cleaning container to start at a first rotation speed;

[0074] 303. Control the first peristaltic pump to pump out the cleaning liquid in the cleaning container until the bubble sensor on the liquid outlet pipeline of the cleaning container detects gas;

[0075] 304. Determine the difference between the preset first volume and the volume of the extracted cleaning liquid as the volume of the minimum concentrated liquid.

[0076] In step 301, the preset first volume can be set according to actual conditions and is not limited here. In this embodiment, the preset first volume can be 25-35 mL, and the third control valve 10 and the eighth control valve 15 can be controlled to open, and the second peristaltic pump 4 can be controlled to pump 25-35 mL of cleaning liquid into the cleaning container 2.

[0077] In step 302, the first rotational speed may be set according to actual needs and is not limited here. In this embodiment, the first rotational speed may be 1700-1900 rpm.

[0078] In step 303, in actual applications, there will always be residual cleaning liquid in the cleaning container 2, and it will not be completely emptied by the first peristaltic pump 3. When the bubble sensor 5 detects gas, it means that no more liquid can be extracted from the cleaning container 2. It can be considered that the cleaning liquid in the cleaning container 2 is approximately emptied. At this time, the volume of cleaning liquid remaining in the cleaning container 2 is the volume of the minimum concentrated liquid, which can be 1.5-2.5mL.

[0079] Since the volume of the minimum concentrated liquid is already the minimum volume of the residual liquid in the cleaning container 2, when the minimum concentrated liquid is resuspended and prepared, the volume of the resuspension is much larger than the volume of the minimum concentrated liquid. Therefore, the minimum concentrated liquid will not affect the resuspension effect and freezing effect of the resuspension. If the volume of the liquid obtained after the intermediate product in the cleaning container 2 is washed is large, it is necessary to use the resuspension to wash the liquid once, so as to replace part of the liquid volume with the resuspension, so that the remaining liquid volume is reduced, and then the resuspension is pumped in for resuspension and preparation.

[0080] By pre-calibrating the volume of the minimum concentrated liquid, this embodiment can concentrate the liquid in the cleaning container according to the calibrated volume value after the intermediate product is cleaned to obtain the minimum concentrated liquid. During the subsequent resuspension and preparation, the minimum concentrated liquid will not affect the resuspension effect and freezing effect of the resuspension liquid, thereby improving the quality of the prepared product on the one hand and eliminating the need to clean the concentrated liquid in the cleaning container again on the other hand, thereby further improving the product preparation efficiency.

[0081] Reference Figure 1 In one embodiment, before controlling the centrifugal movement of the cleaning container, the process may include:

[0082] The control switching device switches the pipeline connection from the separation container 1 to the cleaning container 2, and the specific method can be as follows:

[0083] The first tube clamp 6 is controlled to be closed, and the second tube clamp 7 is controlled to be opened; the first tube clamp 6 is a tube clamp of the first color on the pipeline only associated with the separation container 1 , and the second tube clamp 7 is a tube clamp of the second color on the pipeline only associated with the cleaning container 2 .

[0084] In addition, before initially controlling the centrifugal movement of the separation container 1, it is also necessary to control the first tube clamp 6 to be opened and the second tube clamp 7 to be closed.

[0085] The first color and the second color can be set arbitrarily and are not limited here, as long as the first color is different from the second color. In this embodiment, the first color can be blue and the second color can be white.

[0086] After the intermediate product is extracted from the separation container 1, it is necessary to switch the separation container 1 to the cleaning container 2 and pump the intermediate product into the cleaning container 2. At this time, the associated pipeline of the separation container 1 can be closed by controlling the first pipe clamp 6 and the second pipe clamp 7, and the associated pipeline of the cleaning container 2 can be opened, and the cleaning container 2 can be controlled to replace the centrifugal base where the separation container 1 is located, so as to subsequently control the centrifugal movement of the cleaning container 2.

[0087] In this embodiment, by providing pipe clamps of different colors on the separation container associated pipeline and the cleaning container associated pipeline, the control pipelines of the separation container and the cleaning container can be clearly distinguished by color, thereby facilitating the identification and switching control of the separation container and the cleaning container pipelines.

[0088] Figure 4 This is the third flow chart of the method for preparing a cell product provided in the embodiment of the present application. Figure 1 and Figure 4 In one embodiment, controlling the centrifugal movement of the separation container to centrifuge the cell fluid sample in the separation container to obtain an intermediate product may include:

[0089] 401. Control the separation container to start at a second rotation speed;

[0090] 402. Control the second peristaltic pump to pump a preset second volume of sample separation liquid into the separation container;

[0091] 403. Control the first peristaltic pump to pump the cell fluid sample into the separation container;

[0092] 404. Control the second peristaltic pump to pump a preset third volume of sample separation liquid into the separation container;

[0093] 405. Control the separation container to maintain centrifugal motion at a second speed within a first preset time period to obtain an intermediate product.

[0094] In step 401, the second rotational speed may be set according to actual needs and is not limited here. In this embodiment, the second rotational speed may be 1900-2100 rpm.

[0095] In step 402, the preset second volume can be set according to actual conditions and is not limited here. In this embodiment, the preset second volume can be 110-130 mL, and the first control valve 8 and the eighth control valve 15 can be controlled to open, and the second peristaltic pump 4 can be controlled to pump 110-130 mL of sample separation liquid into the separation container 1.

[0096] In step 403 , the second peristaltic pump 4 is controlled to maintain a second rotation speed of 1900-2100 rpm, the fourth control valve 11 and the ninth control valve 16 are controlled to open, and then the first peristaltic pump 3 is controlled to pump the cell fluid sample into the separation container 1 .

[0097] In step 404, the preset third volume can be set according to actual conditions and is not limited here. In this embodiment, the preset third volume can be 25-35 mL, and the first control valve 8 and the eighth control valve 15 can be controlled to open, and the second peristaltic pump 4 can be controlled to pump 25-35 mL of sample separation liquid into the separation container 1.

[0098] In step 405, the first preset time can be set according to actual conditions and is not limited here. In this embodiment, the first preset time can be 140-160 seconds, that is, the separation container 1 is controlled to maintain centrifugal motion at a speed of 1900-2100 rpm within 140-160 seconds to obtain an intermediate product.

[0099] In this embodiment, the sample separation solution is pumped in twice before and after the cell fluid sample is pumped in, and the centrifugal movement of the separation container is coordinated to make the intermediate product stratification more obvious, thereby improving the separation effect and the white blood cell recovery rate of the intermediate product.

[0100] Figure 5 This is the fourth flow chart of the method for preparing a cell product provided in the embodiment of the present application. Figure 1 and Figure 5 In one embodiment, extracting the intermediate product from the separation container may include:

[0101] 501. Control the centrifugal speed of the separation container to decrease from the second speed to the third speed;

[0102] 502. Control the first peristaltic pump to pump a preset fourth volume of the intermediate product out of the separation container;

[0103] 503. Control the second peristaltic pump to pump a preset fifth volume of the sample separation liquid into the separation container;

[0104] 504. Control the separation container to maintain centrifugal motion at a third speed within a second preset time period;

[0105] 505. Control the first peristaltic pump to pump out a preset sixth volume of the intermediate product from the separation container.

[0106] In step 501, the third speed may be set according to actual needs and is not limited here. In this embodiment, the third speed may be 1600-1800 rpm.

[0107] In step 502, the preset fourth volume can be set according to actual conditions and is not limited here. In this embodiment, the preset fourth volume can be 120-140 mL, and the fifth control valve 12 and the ninth control valve 16 can be controlled to open, and the first peristaltic pump 3 can be controlled to extract 120-140 mL of the intermediate product from the separation container 1.

[0108] In step 503, the preset fifth volume can be set according to actual conditions and is not limited here. In this embodiment, the preset fifth volume can be 45-55 mL, and the first control valve 8 and the eighth control valve 15 can be controlled to open, and the second peristaltic pump 4 can be controlled to pump 45-55 mL of sample separation liquid into the separation container 1.

[0109] In step 504, the second preset time length can be set according to actual conditions and is not limited here. In this embodiment, the second preset time length can be 55-65 seconds, that is, the separation container 1 is controlled to maintain centrifugal motion at a speed of 1600-1800 rpm within 55-65 seconds.

[0110] In step 505, the preset sixth volume can be set according to actual conditions and is not limited here. In this embodiment, the preset sixth volume can be 75-85 mL, which can control the fifth control valve 12 and the ninth control valve 16 to open, and control the first peristaltic pump 3 to extract 75-85 mL of the intermediate product from the separation container 1.

[0111] In this embodiment, after the intermediate product is extracted for the first time, the sample separation liquid is added and the intermediate product is extracted for the second time. The rotation speed of the separation container is reduced and maintained, which facilitates the extraction of the intermediate product and improves the separation effect of the extracted intermediate product and the white blood cell recovery rate.

[0112] Figure 6 This is the fifth flow chart of the method for preparing a cell product provided in the embodiment of the present application. Figure 1 and Figure 6 In one embodiment, controlling the centrifugal movement of the cleaning container and pumping the extracted intermediate product into the cleaning container to clean the intermediate product in the cleaning container to obtain the minimum concentrated liquid may include:

[0113] 601. Control the centrifugal speed of the cleaning container to decrease from the first speed to the fourth speed;

[0114] 602. Control the first peristaltic pump to pump the intermediate product into the cleaning container;

[0115] 603. Control the second peristaltic pump to pump a preset seventh volume of cleaning solution into the cleaning container;

[0116] 604. Control the centrifugal speed of the cleaning container to increase from the fourth speed to the fifth speed;

[0117] 605. Control the cleaning container to maintain centrifugal motion at a fifth speed within a third preset time period;

[0118] 606. Control the centrifugal speed of the cleaning container to decrease from the fifth speed to the sixth speed;

[0119] 607. Control the first peristaltic pump to discharge the waste liquid in the cleaning container;

[0120] 608. Control the second peristaltic pump to pump a preset eighth volume of cleaning solution into the cleaning container;

[0121] 609. Control the cleaning container to maintain centrifugal motion at a sixth speed within a fourth preset time period;

[0122] 610. Control the first peristaltic pump to discharge the waste liquid in the cleaning container until the minimum concentrated liquid is obtained.

[0123] In step 601, the fourth speed may be set according to actual needs and is not limited here. In this embodiment, the fourth speed may be 400-600 rpm.

[0124] In step 602 , the fifth control valve 12 and the ninth control valve 16 may be controlled to open, and the first peristaltic pump 3 may be controlled to pump all the intermediate products extracted from the separation container 1 twice previously into the cleaning container 2 .

[0125] In step 603, the preset seventh volume can be set according to actual conditions and is not limited here. The third control valve 10, the seventh control valve 14 and the ninth control valve 16 can be controlled to open, and the second peristaltic pump 4 can be controlled to pump the preset seventh volume of cleaning liquid into the cleaning container 2.

[0126] In step 604, the fifth speed may be set according to actual needs and is not limited here. In this embodiment, the fifth speed may be 2400-2600 rpm.

[0127] In step 605, the third preset time length can be set according to actual conditions and is not limited here. In this embodiment, the third preset time length can be 200-220 seconds, that is, the cleaning container 2 is controlled to maintain centrifugal motion at a speed of 2400-2600rpm within 200-220 seconds.

[0128] In step 606, the sixth speed may be set according to actual needs and is not limited here. In this embodiment, the sixth speed may be 1700-1900 rpm.

[0129] In step 607, the centrifugal movement of the cleaning container 2 will cause the cells to stick to the wall of the cleaning container, and the liquid remaining in the cleaning container 2 is waste liquid. Therefore, the sixth control valve 13 and the ninth control valve 16 can be controlled to open first, and the first peristaltic pump 3 can be controlled to discharge the waste liquid at a faster flow rate along the pipeline from the ninth control valve 16 to the sixth control valve 13 to the waste liquid bag, and then the seventh control valve 14 and the eighth control valve 15 can be controlled to open, and the first peristaltic pump 3 can be controlled to discharge the waste liquid at a slower flow rate along the pipeline where the eighth control valve 15, the seventh control valve 14 and the sixth control valve 13 are located to the waste liquid bag.

[0130] In step 608, the preset eighth volume can be set according to actual conditions and is not limited here. In this embodiment, the preset eighth volume can be 170-190 mL, and the third control valve 10, the seventh control valve 14 and the ninth control valve 16 can be controlled to open, and the second peristaltic pump 4 can be controlled to pump 170-190 mL of cleaning liquid into the cleaning container 2.

[0131] In step 609, the fourth preset time length can be set according to actual conditions and is not limited here. In this embodiment, the fourth preset time length can be 80-100 seconds, that is, the cleaning container 2 is controlled to maintain centrifugal motion at a speed of 1700-1900 rpm within 80-100 seconds.

[0132] In step 610, the first peristaltic pump 3 is controlled to discharge the waste liquid in the cleaning container 2 according to the same operation as step 609 until the minimum concentrated liquid is obtained.

[0133] In this embodiment, the intermediate product is cleaned by the cleaning liquid, and the rotation speed of the cleaning container is continuously adjusted and the waste liquid is continuously discharged, so that a large number of separated desired cells are concentrated into the minimum concentrated liquid, thereby achieving effective cleaning of the intermediate product.

[0134] Figure 7 This is the sixth flow chart of the method for preparing a cell product provided in the embodiment of the present application. Figure 1 and Figure 7 In one embodiment, pumping the resuspension into a washing container to resuspend and prepare the minimal concentrated liquid to obtain a cell product may include:

[0135] 701. Control the second peristaltic pump to pump the first specific volume of the resuspension into the cleaning container;

[0136] The first specific volume is the difference between the pre-resuspended volume and the volume of the minimum concentrated liquid;

[0137] 702. Sampling the liquid in the cleaning container to obtain a liquid sample;

[0138] 703. If the required number of cells in the liquid sample reaches a preset number, the second peristaltic pump is controlled to pump a second specific volume of the resuspension liquid into the cleaning container to obtain a cell product.

[0139] The second specific volume is the difference between the pre-formulation volume and the pre-resuspension volume.

[0140] In step 701, the pre-resuspended volume is a set volume value input into the control system before pumping the resuspension liquid, representing the total volume of liquid expected to be obtained in the cleaning container 2 after the resuspension liquid is pumped into the cleaning container 2. Since there is a minimum concentrated liquid in the cleaning container 2, in order to make the total volume of liquid in the cleaning container 2 reach the pre-set pre-resuspended volume, the volume of the resuspension liquid actually pumped into the cleaning container 2 is the difference between the pre-resuspended volume and the volume of the minimum concentrated liquid, that is, the first specific volume, and the second control valve 9 and the eighth control valve 15 can be controlled to open, and the second peristaltic pump 4 can be controlled to pump the first specific volume of the resuspension liquid into the cleaning container 2.

[0141] In step 702, sampling can be performed from the sterile sampling port reserved on the cleaning container 2. The sampling volume can be set according to actual conditions and is not limited here. In this embodiment, 0.4-0.6 mL can be sampled.

[0142] Step 703, the preformulation volume is a set volume value input into the control system before the resuspension is pumped into the cleaning container 2 again, representing the total volume of liquid expected to be obtained in the cleaning container 2 after the resuspension is pumped into the cleaning container 2 again, that is, the expected preparation volume. Since the volume in the cleaning container 2 at this time is the pre-resuspended volume, in order to make the total volume of liquid in the cleaning container 2 reach the pre-set preformulation volume, the actual volume of the resuspension pumped into the cleaning container 2 again is the difference between the preformulation volume and the pre-resuspended volume, that is, the second specific volume, and the second control valve 9, the seventh control valve 14 and the ninth control valve 16 can be controlled to open, and the second peristaltic pump 4 can be controlled to pump the second specific volume of the resuspension into the cleaning container 2 again.

[0143] It should be noted that only when the volume of the pre-preparation input into the control system is greater than the pre-resuspended volume, the second peristaltic pump 4 will be controlled to pump the second specific volume of the resuspension liquid into the cleaning container 2 again. If the volume of the pre-preparation input into the control system is less than or equal to the pre-resuspended volume, the resuspension liquid will no longer be pumped in.

[0144] In this embodiment, after the minimum concentrated liquid is resuspended, the liquid in the cleaning container is sampled and tested. When the required number of cells is met, the liquid in the cleaning container is prepared to obtain a cell product of better quality.

[0145] In one embodiment, after obtaining the cell product, the method may include:

[0146] The cell product is controlled to be packaged into a preset number of bagged products. If the error between the volume of any bagged product and the preset standard volume is less than an error threshold, the bagged product is determined to be a qualified product.

[0147] The obtained cell product can be packaged into 1 to 3 bags according to demand, and the volume error of each bag of product can be detected. The error threshold can be set according to actual conditions and is not limited here. In this embodiment, the error threshold can be 2%.

[0148] This embodiment can meet the demand for small-volume packaging of products by packaging the cell products and performing error detection.

[0149] It should also be noted that the separation container and the cleaning container mentioned in all the above embodiments can adjust the liquid outlet and the liquid inlet according to needs, which is not limited here, and the number of repeated steps in all the above embodiments can be adjusted, which is not limited here.

[0150] The cell product preparation device provided in the embodiment of the present application is described below. The cell product preparation device described below and the cell product preparation method described above can be referenced to each other.

[0151] Figure 8 This is a schematic diagram of the structure of the cell product preparation device provided in the embodiment of the present application. Figure 8 , the present application embodiment provides a cell product preparation device, which may include:

[0152] The separation container control module 801 is used to: control the centrifugal movement of the separation container to centrifuge the cell fluid sample in the separation container to obtain an intermediate product;

[0153] The intermediate product extraction control module 802 is used to: extract the intermediate product from the separation container;

[0154] The cleaning container control module 803 is used to: control the centrifugal movement of the cleaning container and pump the extracted intermediate product into the cleaning container to clean the intermediate product in the cleaning container to obtain a minimum concentrated liquid; the volume of the minimum concentrated liquid is pre-calibrated;

[0155] The resuspension and preparation control module 804 is used to pump the resuspension liquid into the cleaning container to resuspend and prepare the minimum concentrated liquid to obtain a cell product.

[0156] The cell product preparation device provided in this embodiment controls the centrifugal movement of the separation container to centrifuge the cell fluid sample in the separation container to obtain an intermediate product, extracts the intermediate product from the separation container, controls the centrifugal movement of the cleaning container, and pumps the extracted intermediate product into the cleaning container to clean the intermediate product in the cleaning container to obtain a minimum concentrated liquid, the volume of the minimum concentrated liquid is pre-calibrated, and the resuspension liquid is pumped into the cleaning container to resuspend and prepare the minimum concentrated liquid to obtain a cell product. Since two centrifugal containers are used, one as a separation container and the other as a cleaning container, the centrifugal containers used for the separation operation and the cleaning operation can be separated. After the intermediate product is extracted from the separation container, the intermediate product can be directly pumped into the cleaning container for cleaning, without having to wait for the separation container to be cleaned and then pumping the intermediate product into the same separation container for cleaning. Therefore, the waiting time for the separation container to be cleaned is reduced and the efficiency of product preparation is improved. At the same time, since the intermediate product is pumped into a brand new cleaning container for cleaning, the contamination of the intermediate product caused by pumping into a separation container with residual non-desired cells is avoided, thereby improving the purity of the cell product and meeting the high efficiency and high purity requirements required for preparing cell products based on large-volume cell fluid samples.

[0157] In one embodiment, a minimum concentrated liquid volume calibration module (not shown) is further included, which is used to:

[0158] Controlling the second peristaltic pump to pump a preset first volume of cleaning liquid into the cleaning container;

[0159] Controlling the cleaning container to start at a first rotation speed;

[0160] Controlling the first peristaltic pump to pump out the cleaning liquid in the cleaning container until a bubble sensor on the liquid outlet pipeline of the cleaning container detects gas;

[0161] The difference between the preset first volume and the volume of the extracted cleaning liquid is determined as the volume of the minimum concentrated liquid.

[0162] In one embodiment, a switching control module (not shown in the figure) is further included, which is used to:

[0163] The switching device is controlled to switch the pipeline connection from the separation container to the cleaning container.

[0164] In one embodiment, the switching control module is specifically used to:

[0165] The first tube clamp is controlled to be closed, and the second tube clamp is controlled to be opened; the first tube clamp is a tube clamp on the pipeline only associated with the separation container, and the second tube clamp is a tube clamp on the pipeline only associated with the cleaning container.

[0166] In one embodiment, the separation container control module 801 is specifically used for:

[0167] Controlling the separation container to start at a second rotation speed;

[0168] Controlling the first peristaltic pump to pump the cell fluid sample into the separation container, and controlling the second peristaltic pump to pump the sample separation fluid into the separation container;

[0169] The separation container is controlled to maintain centrifugal motion at the second speed within a first preset time period to obtain an intermediate product.

[0170] In one embodiment, the separation container control module 801 is specifically used for:

[0171] Controlling the second peristaltic pump to pump a preset second volume of sample separation liquid into the separation container;

[0172] Controlling the first peristaltic pump to pump the cell fluid sample into the separation container;

[0173] The second peristaltic pump is controlled to pump a preset third volume of sample separation liquid into the separation container.

[0174] In one embodiment, the intermediate product extraction control module 802 is specifically used to:

[0175] Controlling the centrifugal speed of the separation container to decrease from the second speed to a third speed;

[0176] controlling the first peristaltic pump to pump a preset fourth volume of the intermediate product out of the separation container;

[0177] controlling the second peristaltic pump to pump a preset fifth volume of sample separation liquid into the separation container;

[0178] Controlling the separation container to maintain centrifugal motion at the third speed within a second preset time period;

[0179] The first peristaltic pump is controlled to pump a preset sixth volume of the intermediate product out of the separation container.

[0180] In one embodiment, the cleaning container control module 803 is specifically used to:

[0181] Controlling the centrifugal speed of the cleaning container to decrease from the first speed to a fourth speed;

[0182] controlling the first peristaltic pump to pump the intermediate product into the cleaning container;

[0183] controlling the second peristaltic pump to pump a cleaning liquid into the cleaning container to clean the intermediate product in the cleaning container;

[0184] The first peristaltic pump is controlled to discharge the waste liquid in the cleaning container until a minimum concentrated liquid is obtained.

[0185] Fig. 9 An example of a physical structure diagram of an electronic device is shown in FIG. Fig. 9 As shown, the electronic device may include: a processor 910, a communication interface 920, a memory 930 and a communication bus 940, wherein the processor 910, the communication interface 920 and the memory 930 communicate with each other through the communication bus 940. The processor 910 may call a computer program in the memory 930 to execute the steps of the cell product preparation method, for example including:

[0186] Controlling the centrifugal movement of the separation container to centrifuge the cell fluid sample in the separation container to obtain an intermediate product;

[0187] extracting the intermediate product from the separation container;

[0188] Controlling the centrifugal movement of the cleaning container and pumping the extracted intermediate product into the cleaning container to clean the intermediate product in the cleaning container to obtain a minimum concentrated liquid; the volume of the minimum concentrated liquid is pre-calibrated;

[0189] The resuspended liquid is pumped into the washing container to resuspend and prepare the minimal concentrated liquid to obtain a cell product.

[0190] In addition, the logic instructions in the above-mentioned memory 930 can be implemented in the form of a software functional unit and can be stored in a computer-readable storage medium when it is sold or used as an independent product. Based on this understanding, the technical solution of the present application can be essentially or partly embodied in the form of a software product that contributes to the prior art, and the computer software product is stored in a storage medium, including several instructions to enable a computer device (which can be a personal computer, a server, or a network device, etc.) to perform 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 disk or an optical disk.

[0191] On the other hand, an embodiment of the present application further provides a computer program product, the computer program product comprising a computer program, the computer program may be stored on a non-transitory computer-readable storage medium, and when the computer program is executed by a processor, the computer can execute the steps of the cell product preparation method provided in the above embodiments, for example, including:

[0192] Controlling the centrifugal movement of the separation container to centrifuge the cell fluid sample in the separation container to obtain an intermediate product;

[0193] extracting the intermediate product from the separation container;

[0194] Controlling the centrifugal movement of the cleaning container and pumping the extracted intermediate product into the cleaning container to clean the intermediate product in the cleaning container to obtain a minimum concentrated liquid; the volume of the minimum concentrated liquid is pre-calibrated;

[0195] The resuspended liquid is pumped into the washing container to resuspend and prepare the minimal concentrated liquid to obtain a cell product.

[0196] 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 used to enable the processor to execute the steps of the methods provided in the above embodiments, for example, including:

[0197] Controlling the centrifugal movement of the separation container to centrifuge the cell fluid sample in the separation container to obtain an intermediate product;

[0198] extracting the intermediate product from the separation container;

[0199] Controlling the centrifugal movement of the cleaning container and pumping the extracted intermediate product into the cleaning container to clean the intermediate product in the cleaning container to obtain a minimum concentrated liquid; the volume of the minimum concentrated liquid is pre-calibrated;

[0200] The resuspended liquid is pumped into the washing container to resuspend and prepare the minimal concentrated liquid to obtain a cell product.

[0201] 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), etc.), optical storage (such as CD, DVD, BD, HVD, etc.), and semiconductor storage (such as ROM, EPROM, EEPROM, non-volatile memory (NANDFLASH), solid-state drive (SSD)), etc.

[0202] The device embodiments described above are merely illustrative, wherein the units described as separate components may or may not be physically separated, and the components displayed as units may or may not be physical units, that is, they may be located in one place, or they may be distributed on multiple network units. Some or all of the modules may be selected according to actual needs to achieve the purpose of the scheme of this embodiment. Ordinary technicians in this field can understand and implement it without paying creative labor.

[0203] Through the description of the above implementation methods, those skilled in the art can clearly understand that each implementation method can be implemented by means of software plus a necessary general hardware platform, and of course, it can also be implemented by hardware. Based on this understanding, the above technical solution is essentially or the part that contributes to the prior art can be embodied in the form of a software product, and the computer software product can be stored in a computer-readable storage medium, such as ROM / RAM, a disk, an optical disk, etc., including a number of instructions for 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 some parts of the embodiments.

[0204] 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 it. 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 method for preparing a cell product, characterized in that: include: Controlling the centrifugal movement of the separation container to centrifuge the cell fluid sample in the separation container to obtain an intermediate product; extracting the intermediate product from the separation container; Controlling the centrifugal movement of the cleaning container and pumping the extracted intermediate product into the cleaning container to clean the intermediate product in the cleaning container to obtain a minimum concentrated liquid; the volume of the minimum concentrated liquid is pre-calibrated; The resuspended liquid is pumped into the washing container to resuspend and prepare the minimal concentrated liquid to obtain a cell product.

2. The method for preparing a cell product according to claim 1, characterized in that: Before the centrifugal movement of the cleaning container is controlled, the method includes: Controlling the second peristaltic pump to pump a preset first volume of cleaning liquid into the cleaning container; Controlling the cleaning container to start at a first rotation speed; Controlling the first peristaltic pump to pump out the cleaning liquid in the cleaning container until a bubble sensor on the liquid outlet pipeline of the cleaning container detects gas; The difference between the preset first volume and the volume of the extracted cleaning liquid is determined as the volume of the minimum concentrated liquid.

3. The method for preparing a cell product according to claim 1, characterized in that: Before the centrifugal movement of the cleaning container is controlled, the method includes: The switching device is controlled to switch the pipeline connection from the separation container to the cleaning container.

4. The method for preparing a cell product according to claim 3, characterized in that: The control switching device switches the pipeline connection from the separation container to the cleaning container, including: The first pipe clamp is controlled to be closed, and the second pipe clamp is controlled to be opened; the first pipe clamp is a pipe clamp on the pipeline only associated with the separation container, and the second pipe clamp is a pipe clamp on the pipeline only associated with the cleaning container.

5. The method for preparing a cell product according to claim 1, characterized in that: The controlling the centrifugal movement of the separation container to centrifuge the cell fluid sample in the separation container to obtain an intermediate product comprises: Controlling the separation container to start at a second rotation speed; Controlling the first peristaltic pump to pump the cell fluid sample into the separation container, and controlling the second peristaltic pump to pump the sample separation fluid into the separation container; The separation container is controlled to maintain centrifugal motion at the second speed within a first preset time period to obtain an intermediate product.

6. The method for preparing a cell product according to claim 5, characterized in that: The controlling the first peristaltic pump to pump the cell fluid sample into the separation container, and controlling the second peristaltic pump to pump the sample separation fluid into the separation container, comprises: Controlling the second peristaltic pump to pump a preset second volume of sample separation liquid into the separation container; Controlling the first peristaltic pump to pump the cell fluid sample into the separation container; The second peristaltic pump is controlled to pump a preset third volume of sample separation liquid into the separation container.

7. The method for preparing a cell product according to claim 5, characterized in that: The step of extracting the intermediate product from the separation container comprises: Controlling the centrifugal speed of the separation container to decrease from the second speed to a third speed; controlling the first peristaltic pump to pump a preset fourth volume of the intermediate product out of the separation container; controlling the second peristaltic pump to pump a preset fifth volume of sample separation liquid into the separation container; Controlling the separation container to maintain centrifugal motion at the third speed within a second preset time period; The first peristaltic pump is controlled to pump a preset sixth volume of the intermediate product out of the separation container.

8. The method for preparing a cell product according to claim 2, characterized in that: The controlling the centrifugal movement of the cleaning container and pumping the extracted intermediate product into the cleaning container to clean the intermediate product in the cleaning container to obtain the minimum concentrated liquid includes: Controlling the centrifugal speed of the cleaning container to decrease from the first speed to a fourth speed; controlling the first peristaltic pump to pump the intermediate product into the cleaning container; Controlling the second peristaltic pump to pump cleaning liquid into the cleaning container to clean the intermediate product in the cleaning container; The first peristaltic pump is controlled to discharge the waste liquid in the cleaning container until a minimum concentrated liquid is obtained.

9. A cell product preparation device, characterized in that: include: The separation container control module is used to: control the centrifugal movement of the separation container to centrifuge the cell fluid sample in the separation container to obtain an intermediate product; An intermediate product extraction control module is used to: extract the intermediate product from the separation container; A cleaning container control module is used to: control the centrifugal movement of the cleaning container and pump the extracted intermediate product into the cleaning container to clean the intermediate product in the cleaning container to obtain a minimum concentrated liquid; the volume of the minimum concentrated liquid is pre-calibrated; The resuspension and preparation control module is used to pump the resuspension liquid into the cleaning container to resuspend and prepare the minimum concentrated liquid to obtain a cell product.

10. An electronic device comprising a processor and a memory storing a computer program, characterized in that: When the processor executes the computer program, the steps of the method for preparing a cell product according to any one of claims 1 to 8 are implemented.

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