Method and device for dispensing cell suspension
By setting a mixing operation parameter table and performing precise mixing and dispensing control during the cell fluid dispensing process, the problem of concentration and activity rate deviation before and after cell fluid dispensing was solved, and the uniformity and quality of the dispensed cell fluid were improved.
Patent Information
- Application Number
- CN202211723627.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2022-12-30
- Publication Date
- 2026-11-06
- Estimated Expiration
- 2042-12-30
AI Technical Summary
Traditional cell fluid dispensing methods fail to effectively control deviations in cell concentration and cell viability before and after dispensing, resulting in uneven quality of the dispensed cell fluid.
By setting a mixing operation parameter table, the mixing is controlled during the liquid inlet, holding and dispensing stages of the mixing bag according to the weight and type of cell fluid, and the dispensing is controlled during the dispensing stage. The flow and dispensing of cell fluid are precisely controlled by weighing sensors and bubble sensors.
The cell concentration and cell viability deviations before and after cell culture were kept within 5%, thus improving the quality of the cell culture.
Smart Images

Figure CN118270280B_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of cell fluid dispensing technology, specifically to a method and apparatus for dispensing cell fluid. Background Technology
[0002] In the field of biotherapy, cell fluid is usually a mixture of multiple solutions. In practical applications, cell fluid needs to be automatically dispensed through liquid pipelines.
[0003] However, traditional dispensing methods only provide the driving force for the cell solution to flow into multiple dispensing bags, without taking into account the changes in the cell solution before and after dispensing. Since the cell solution is a mixture of multiple solutions, the distribution of cells is not uniform. Therefore, when the cell solution flows from one cell solution bag into multiple dispensing bags, the cell concentration and cell activity rate of the cell solution in a single dispensing bag may change compared to the cell concentration and cell activity rate of the cell solution in the original cell solution bag. This results in a large deviation in cell concentration and cell activity rate before and after dispensing, thus affecting the quality of the dispensed cell solution. Summary of the Invention
[0004] This application provides a cell fluid dispensing method and apparatus to solve the technical problem that the large deviation in cell concentration and cell viability before and after cell fluid dispensing affects the quality of the dispensed cell fluid.
[0005] In a first aspect, embodiments of this application provide a method for dispensing cell fluid, including:
[0006] The mixing operation parameters are set according to the optimal mixing state of cell fluid of different weights and types, and a mixing operation parameter table is generated; the optimal mixing state is the state in which the absolute value of the difference in cell number between any two unit volumes of cell fluid is less than the difference threshold, and the cell viability rate in the cell fluid is greater than the viability rate threshold.
[0007] According to the mixing operation parameter table, the mixing of the cell solution to be dispensed is controlled during the liquid inlet stage, the holding stage, and the liquid outlet stage of the mixing bag; the holding stage is later than the liquid inlet stage, and the liquid outlet stage is later than the holding stage.
[0008] During the dispensing stage of the mixing bag, the dispensing control of the cell solution to be dispensed is performed.
[0009] In one embodiment, the mixing control of the cell solution to be dispensed during the liquid inlet, holding, and dispensing stages of the mixing bag includes:
[0010] During the liquid inlet stage of the mixing bag, the weight of the inlet bag is measured in real time using a weighing sensor. Based on the decrease in the weight of the cell solution to be dispensed in the inlet bag, the increase in the weight of the cell solution to be dispensed in the mixing bag is determined. The cell solution to be dispensed flows from the inlet bag into the mixing bag.
[0011] The real-time weight of the cell solution to be dispensed in the mixing bag is obtained based on the weight increase value.
[0012] Based on the real-time weight of the cell solution to be dispensed in the mixing bag and the type of the cell solution to be dispensed, the mixing operation parameter table is queried, and the mixing of the cell solution to be dispensed in the mixing bag is controlled according to the mixing operation parameter table.
[0013] In one embodiment, the mixing control of the cell solution to be dispensed during the liquid inlet, holding, and dispensing stages of the mixing bag includes:
[0014] During the holding phase of the mixing bag, the current mixing operation parameters are maintained to control the mixing of the cell solution to be dispensed in the mixing bag.
[0015] In one embodiment, the mixing control of the cell solution to be dispensed during the liquid inlet, holding, and dispensing stages of the mixing bag includes:
[0016] During the liquid dispensing stage of the mixing bag, the weight decrease of the cell solution to be dispensed in the mixing bag is determined based on the weight increase of the cell solution to be dispensed in the dispensing bag; the cell solution to be dispensed flows from the mixing bag into the dispensing bag.
[0017] The real-time weight of the cell solution to be dispensed in the mixing bag is obtained based on the weight reduction value.
[0018] Based on the real-time weight of the cell solution to be dispensed in the mixing bag and the type of the cell solution to be dispensed, the mixing operation parameter table is queried, and the mixing of the cell solution to be dispensed in the mixing bag is controlled according to the mixing operation parameter table.
[0019] In one embodiment, the dispensing control of the cell solution to be dispensed during the dispensing stage of the mixing bag includes:
[0020] A first bubble sensor and a second bubble sensor are provided between the mixing bag and the reference dispensing bag; wherein, the reference dispensing bag is the dispensing bag with the shortest liquid path distance from the mixing bag and the first to be dispensed among a plurality of dispensing bags, and the plurality of dispensing bags are arranged in order of increasing liquid path distance from the mixing bag;
[0021] The flow rate of the cell fluid to be dispensed is obtained based on the volume of the cell fluid to be compared and the absolute value of the time difference between the first flow of the cell fluid to be dispensed through the first bubble sensor and the second bubble sensor; the volume of the cell fluid to be compared is the volume of the cell fluid to be dispensed in the liquid path between the first bubble sensor and the second bubble sensor.
[0022] Based on the flow rate and the volume of the cell solution to be dispensed in the liquid path between the plurality of dispensing bags and the mixing bag, the injection time required for the cell solution to be dispensed to be transferred from the mixing bag to the plurality of dispensing bags is obtained.
[0023] The inlet of the corresponding dispensing bag is opened according to the injection time, and the opening and closing of the inlet of the corresponding dispensing bag is controlled according to the ratio of the volume of the cell fluid to be dispensed into the corresponding dispensing bag to the volume of the cell fluid to be compared.
[0024] In one embodiment, controlling the opening of the inlet of the corresponding dispensing bag according to the injection time includes:
[0025] The inlet of the reference dispensing bag is opened according to the injection time required for the cell solution to be dispensed from the mixing bag to the reference dispensing bag.
[0026] The inlet of the current dispensing bag is controlled to open based on the absolute value of the difference between the injection time required for the cell solution to be dispensed from the mixing bag to the current dispensing bag and the injection time required for the cell solution to be dispensed from the mixing bag to the previous dispensing bag; the current dispensing bag is a dispensing bag other than the reference dispensing bag.
[0027] In one embodiment, after controlling the opening and closing of the liquid inlet of the corresponding dispensing bag, the following steps are included:
[0028] If the absolute value of the difference between the volume of cell fluid to be dispensed and the target volume in the last dispensing bag that has not yet been dispensed is less than or equal to the preset residual cell fluid volume in the liquid path, then the outlet of the mixing bag is closed, the one-way air inlet valve is opened, and the residual cell fluid in the liquid path is pushed into the last dispensing bag that has not yet been dispensed using air pressure.
[0029] Secondly, embodiments of this application provide a cell fluid dispensing device, comprising:
[0030] The mixing operation parameter table generation module is used to: set mixing operation parameters according to the optimal mixing state of cell fluid of different weights and types, and generate a mixing operation parameter table; the optimal mixing state is the state in which the absolute value of the difference in cell number between any two unit volumes of the cell fluid is less than the difference threshold, and the cell viability rate in the cell fluid is greater than the viability rate threshold.
[0031] The mixing control module is used to: control the mixing of the cell solution to be dispensed during the liquid inlet stage, the holding stage, and the liquid outlet stage of the mixing bag according to the mixing operation parameter table; the holding stage is later than the liquid inlet stage, and the liquid outlet stage is later than the holding stage;
[0032] The dispensing control module is used to control the dispensing of cell solution to be dispensed during the liquid dispensing stage of the mixing bag.
[0033] Thirdly, embodiments of this application provide an electronic device, including a processor and a memory storing a computer program, wherein the processor executes the program to implement the steps of the cell fluid dispensing method described in the first aspect.
[0034] Fourthly, embodiments of this application provide a computer program product, including a computer program that, when executed by a processor, implements the steps of the cell fluid dispensing method described in the first aspect.
[0035] The cell solution dispensing method and apparatus provided in this application set mixing operation parameters according to the optimal mixing state of cell solutions of different weights and types, and generate a mixing operation parameter table. Then, based on the mixing operation parameter table, the mixing of the cell solution to be dispensed is controlled during the liquid inlet, holding, and liquid outlet stages of the mixing bag, and the dispensing of the cell solution to be dispensed is controlled during the liquid outlet stage of the mixing bag. By controlling the mixing of the cell solution to be dispensed according to the mixing operation parameters during the liquid inlet, holding, and liquid outlet stages of the mixing bag, this application can ensure that the cell solution to be dispensed reaches an optimal mixing state, thereby reducing cell concentration and cell viability deviations during the flow of the cell solution into the dispensing bag and improving the quality of the dispensed cell solution. Attached Figure Description
[0036] To more clearly illustrate the technical solutions in this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.
[0037] Figure 1 This is one of the flowcharts illustrating the cell fluid dispensing method provided in the embodiments of this application;
[0038] Figure 2 This is a structural diagram of the cell fluid dispensing system provided in the embodiments of this application;
[0039] Figure 3 This is a second schematic flowchart of the cell fluid dispensing method provided in the embodiments of this application;
[0040] Figure 4 This is the third schematic flowchart of the cell fluid dispensing method provided in the embodiments of this application;
[0041] Figure 5 This is the fourth flowchart illustrating the cell fluid dispensing method provided in the embodiments of this application;
[0042] Figure 6 This is a schematic diagram of the cell fluid dispensing device provided in the embodiments of this application;
[0043] Figure 7 This is a schematic diagram of the structure of the electronic device provided in the embodiments of this application.
[0044] Figure label:
[0045] 1-First control valve; 2-Second control valve; 3-Third control valve; 4-Inlet bag; 5-Mixing bag; 6-Dispensing bag; 61-Standard dispensing bag; 7-First bubble sensor; 8-Second bubble sensor; 9-One-way air inlet valve. Detailed Implementation
[0046] To make the objectives, technical solutions, and advantages of this application clearer, the technical solutions of this application will be clearly and completely described below with reference to the accompanying drawings of the embodiments. Obviously, the described embodiments are only some embodiments of this application, not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.
[0047] Figure 1 This is one of the flowcharts illustrating the cell fluid dispensing method provided in the embodiments of this application.
[0048] Reference Figure 1 This application provides a method for dispensing cell fluid, which may include:
[0049] 101. Set the mixing operation parameters according to the optimal mixing state of cell sap of different weights and types, and generate a mixing operation parameter table;
[0050] The optimal mixing state is when the absolute value of the difference in cell number between any two units of cell volume in the cell slurry is less than the difference threshold, and the cell viability in the cell slurry is greater than the viability threshold; wherein, both the difference threshold and the viability threshold are greater than zero.
[0051] 102. According to the mixing operation parameter table, the mixing control is performed on the cell solution to be dispensed during the liquid inlet stage, the holding stage and the liquid outlet stage of the mixing bag.
[0052] The holding phase is later than the liquid inlet phase, and the liquid outlet phase is later than the holding phase;
[0053] 103. Control the dispensing of cell solution to be dispensed during the dispensing stage of the mixing bag.
[0054] In step 101, multiple experiments are conducted beforehand to determine the optimal mixing state for a certain weight and type of cell solution under what mixing operation. This type can be the cell type. The optimal mixing state is mainly determined based on two aspects: cell concentration and cell viability. When the cell concentration is relatively uniform, that is, the number of cells in any two unit volumes is not significantly different (i.e., the absolute value of the difference in the number of cells in any two unit volumes is less than the difference threshold), and the cell viability is high (i.e., the cell viability is greater than the viability threshold), the cell solution is considered to be in the optimal mixing state. At this time, the mixing operation parameters required for the cell solution to reach the optimal mixing state are recorded. By analogy, the mixing operation parameters required for other weights and types of cell solutions to reach the optimal mixing state are obtained, and finally, a mixing operation parameter table is obtained.
[0055] The mixing operation parameters may include the upward and downward movement of the container holding the cell solution, the time from the end position of the previous mixing operation to the start position of the current mixing operation, the time from the start position of the current mixing operation to the end position of the current mixing operation, the waiting time after the current mixing operation reaches the start position, and the waiting time after the current mixing operation reaches the end position.
[0056] In step 102, the liquid inlet stage, the holding stage, and the liquid outlet stage are performed sequentially in chronological order.
[0057] Because the distribution of cells in the cell solution is uneven before dispensing, traditional methods of dispensing cell solution can easily lead to large deviations in cell concentration and cell viability before and after dispensing. Through practical measurement, the dispensing method of this embodiment can keep the deviation in cell concentration and cell viability before and after dispensing within 5%.
[0058] The cell fluid dispensing method provided in this embodiment sets mixing operation parameters according to the optimal mixing state of cell fluids of different weights and types, and generates a mixing operation parameter table. Then, based on the mixing operation parameter table, the mixing of the cell fluid to be dispensed is controlled during the liquid inlet, holding, and dispensing stages of the mixing bag, and the dispensing of the cell fluid to be dispensed is controlled during the liquid dispensing stage. This embodiment, by controlling the mixing of the cell fluid to be dispensed according to the mixing operation parameters during the liquid inlet, holding, and dispensing stages of the mixing bag, can ensure that the cell fluid to be dispensed reaches an optimal mixing state, thereby reducing cell concentration and cell viability deviations during the flow of the cell fluid into the dispensing bag and improving the quality of the dispensed cell fluid.
[0059] Figure 2 This is a structural diagram of the cell fluid dispensing system provided in the embodiments of this application;
[0060] Figure 3This is the second schematic flowchart of the cell fluid dispensing method provided in the embodiments of this application.
[0061] Reference Figures 2-3 In one embodiment, the mixing control of the cell solution to be dispensed during the liquid inlet, holding, and dispensing stages of the mixing bag may include:
[0062] 301. During the liquid inlet stage of the mixing bag, the weight of the liquid inlet bag is measured in real time using a weighing sensor. Based on the decrease in the weight of the cell solution to be dispensed in the liquid inlet bag, the increase in the weight of the cell solution to be dispensed in the mixing bag is determined.
[0063] The cell solution to be dispensed flows from the inlet bag into the mixing bag;
[0064] 302. Based on the increase in weight, obtain the real-time weight of the cell solution to be dispensed in the mixing bag;
[0065] 303. Based on the real-time weight of the cell solution to be dispensed in the mixing bag and the type of cell solution to be dispensed, consult the mixing operation parameter table, and control the mixing of the cell solution to be dispensed in the mixing bag according to the mixing operation parameter table.
[0066] Reference Figure 2 First, open the first control valve 1 and close the second control valve 2 and the third control valve 3, thereby opening the liquid path between the inlet bag 4 and the mixing bag 5 and closing the other liquid paths, so that the cell solution to be dispensed in the inlet bag 4 flows into the mixing bag 5. In the initial state of liquid inlet, the inlet bag 4 is filled with the cell solution to be dispensed, and the mixing bag 5 is an empty bag.
[0067] In step 301, the weighing sensor measures the weight of the inlet bag 4 in real time, which is the sum of the weight of the inlet bag 4 itself and the weight of the cell solution to be dispensed in the inlet bag 4. When the cell solution to be dispensed flows from the inlet bag 4 into the mixing bag 5, the decrease in the weight of the inlet bag 4 is the decrease in the weight of the cell solution to be dispensed in the inlet bag 4, which is also the increase in the weight of the cell solution to be dispensed in the mixing bag 5.
[0068] In step 302, the weight increase is continuously accumulated, which is the real-time weight of the cell solution to be dispensed in the mixing bag 5.
[0069] In step 303, since the weight of the cell solution to be dispensed in the mixing bag 5 changes in real time, the mixing operation performed on it also changes in real time.
[0070] In this embodiment, by selecting and adjusting the mixing operation parameters according to the type of cell solution to be dispensed and the real-time weight change in the mixing bag during the liquid feeding stage, the cell solution to be dispensed in the mixing bag is fully mixed.
[0071] Reference Figure 2In one embodiment, the mixing control of the cell solution to be dispensed during the liquid inlet, holding, and dispensing stages of the mixing bag may include:
[0072] During the holding phase of mixing bag 5, the current mixing operation parameters are maintained to control the mixing of the cell solution to be dispensed in mixing bag 5.
[0073] The holding phase of the mixing bag 5 is the phase in which the liquid feeding into the mixing bag 5 is stopped, and the weight of the cell solution to be dispensed remains unchanged (the first control valve 1, the second control valve 2, and the third control valve 3 are closed). Since the holding phase is later than the liquid feeding phase, the current mixing operation parameters are the mixing operation parameters at the last moment of the liquid feeding phase.
[0074] In this embodiment, by maintaining the current mixing operation parameters during the holding phase of the mixing bag, the mixing fluid to be dispensed in the mixing bag is controlled to ensure that the cell fluid to be dispensed in the mixing bag is fully mixed.
[0075] Figure 4 This is the third schematic flowchart of the cell fluid dispensing method provided in the embodiments of this application. (Refer to...) Figure 2 and Figure 4 In one embodiment, the mixing control of the cell solution to be dispensed during the liquid inlet, holding, and dispensing stages of the mixing bag may include:
[0076] 401. During the liquid dispensing stage of the mixing bag, determine the weight decrease of the cell solution to be dispensed in the mixing bag based on the weight increase of the cell solution to be dispensed in the dispensing bag.
[0077] The cell solution to be dispensed flows from the mixing bag into the dispensing bag;
[0078] 402. Based on the weight reduction value, obtain the real-time weight of the cell solution to be dispensed in the mixing bag;
[0079] 403. Based on the real-time weight of the cell solution to be dispensed in the mixing bag and the type of cell solution to be dispensed, consult the mixing operation parameter table, and control the mixing of the cell solution to be dispensed in the mixing bag according to the mixing operation parameter table.
[0080] Reference Figure 2 Open the second control valve 2 and close the first control valve 1 and the third control valve 3, thereby opening the liquid path between the mixing bag 5 and the dispensing bag 6 and closing other liquid paths, so that the cell solution to be dispensed in the mixing bag 5 flows into the dispensing bag 6. In the initial state of liquid discharge, the mixing bag 5 is filled with the cell solution to be dispensed, and the dispensing bag 6 is an empty bag.
[0081] In step 401, when the cell solution to be dispensed flows from the mixing bag 5 into the dispensing bag 6, the increase in weight of the cell solution to be dispensed in the dispensing bag 6 is the decrease in weight of the cell solution to be dispensed in the mixing bag 5.
[0082] In step 402, the weight reduction value is continuously subtracted from the weight of the cell solution to be dispensed in the mixing bag 5 during the holding stage, which is the real-time weight of the cell solution to be dispensed in the mixing bag 5.
[0083] In step 403, since the weight of the cell solution to be dispensed in the mixing bag 5 changes in real time, the mixing operation on it also changes in real time.
[0084] In this embodiment, by selecting and adjusting the mixing operation parameters according to the type of cell solution to be dispensed and the real-time weight change in the mixing bag during the liquid dispensing stage, the cell solution to be dispensed in the mixing bag is fully mixed.
[0085] Figure 5 This is the fourth schematic flowchart of the cell fluid dispensing method provided in the embodiments of this application. (Refer to...) Figure 2 and Figure 5 In one embodiment, controlling the dispensing of the cell solution to be dispensed during the dispensing stage of the mixing bag may include:
[0086] 501. A first bubble sensor and a second bubble sensor are installed between the mixing bag and the reference dispensing bag;
[0087] Among them, the reference dispensing bag is the dispensing bag with the shortest liquid path distance to the mixing bag and the first liquid is poured in among multiple dispensing bags, and the multiple dispensing bags are arranged from shortest to longest liquid path distance to the mixing bag.
[0088] 502. Based on the volume of the cell fluid to be compared and the absolute value of the time difference between the first and second bubble sensors when the cell fluid to be dispensed first flows through them, the flow rate of the cell fluid to be dispensed is obtained.
[0089] The volume of cell fluid to be compared is the volume of cell fluid to be dispensed in the liquid path between the first bubble sensor and the second bubble sensor.
[0090] 503. Based on the flow rate and the volume of cell solution to be dispensed in the liquid path between the multiple dispensing bags and the mixing bag, the injection time required for the cell solution to be dispensed from the mixing bag to the multiple dispensing bags is obtained.
[0091] 504. Control the opening of the inlet of the corresponding dispensing bag according to the injection time, and control the opening and closing of the inlet of the corresponding dispensing bag according to the ratio of the volume of the cell fluid to be dispensed into the corresponding dispensing bag to the volume of the cell fluid to be compared.
[0092] The liquid dispensing stage of mixing bag 5 is the dispensing stage of the cell solution to be dispensed. In this stage, mixing control and dispensing control are carried out simultaneously.
[0093] In step 501, refer to Figure 2The first bubble sensor 7 and the second bubble sensor 8 are disposed between the mixing bag 5 and the reference dispensing bag 61.
[0094] In step 502, the flow rate of the cell solution to be dispensed is obtained by dividing the volume of the cell solution to be dispensed in the liquid path between the first bubble sensor 7 and the second bubble sensor 8 by the absolute value of the time difference between the first flow of the cell solution to be dispensed through the first bubble sensor 7 and the second bubble sensor 8. The volume of the cell solution to be dispensed can be calculated based on the length of the liquid path at the corresponding position and the diameter of the liquid path. The flow rate is the flow rate of the cell solution to be dispensed per unit time.
[0095] In step 503, the volume of the cell solution to be dispensed in the liquid path between any dispensing bag and the mixing bag 5 is divided by the flow rate to obtain the injection time required for the cell solution to be dispensed from the mixing bag 5 to any dispensing bag.
[0096] In step 504, the inlet of the corresponding dispensing bag is controlled to open and close based on the ratio of the volume of the cell solution to be dispensed to the volume of the cell solution to be compared. That is, the opening and closing time of the inlet of the corresponding dispensing bag is controlled based on the precision difference between the volume of the cell solution to be dispensed and the volume of the cell solution to be compared in the corresponding dispensing bag, thereby improving the dispensing precision of the cell solution to be dispensed in the corresponding dispensing bag so that it accurately reaches the target volume.
[0097] This embodiment improves the dispensing accuracy of the cell solution by controlling the dispensing process during the liquid dispensing stage of the mixing bag.
[0098] See Figure 2 In one embodiment, controlling the opening of the inlet of the corresponding dispensing bag according to the injection time may include:
[0099] The inlet of the reference dispensing bag 61 is controlled to open based on the injection time required for the cell solution to be dispensed from the mixing bag 5 to the reference dispensing bag 61. The inlet of the current dispensing bag is controlled to open based on the absolute value of the difference between the injection time required for the cell solution to be dispensed from the mixing bag 5 to the current dispensing bag and the injection time required for the cell solution to be dispensed from the mixing bag 5 to the previous dispensing bag.
[0100] The current dispensing bag is a dispensing bag other than the reference dispensing bag 61, and the liquid path distance between the current dispensing bag and the reference dispensing bag 61 is greater than the distance between the previous dispensing bag and the reference dispensing bag 61.
[0101] Since the distance between the reference dispensing bag 61 and the mixing bag 5 is the shortest and the first to be dispensed, the inlet of the reference dispensing bag 61 can be directly controlled based on the dispensing time required for the cell solution to be dispensed from the mixing bag 5 to the reference dispensing bag 61. For the current dispensing bag, the absolute value of the difference can be added to the time point after the previous dispensing bag has completed dispensing, so as to quickly know the time point when the cell solution to be dispensed flows to the current dispensing bag, thereby accurately controlling the opening of the inlet of the current dispensing bag.
[0102] It should be noted that during the liquid dispensing stage of the mixing bag 5, that is, the dispensing stage of the cell solution to be dispensed, the multiple dispensing bags 6 are dispensed sequentially rather than simultaneously. That is, the dispensing of one dispensing bag is carried out only after the dispensing of another dispensing bag is completed.
[0103] This embodiment uses different methods to control the opening of the liquid inlet of the dispensing bag for both the reference dispensing bag and the non-reference dispensing bag, so as to make the control of the liquid inlet more accurate.
[0104] See Figure 2 In one embodiment, after controlling the opening and closing of the liquid inlet of the corresponding dispensing bag, the following may be included:
[0105] If the absolute value of the difference between the volume of cell fluid to be dispensed and the target volume in the last dispensing bag that has not yet been dispensed is less than or equal to the preset residual cell fluid volume in the liquid path, then close the outlet of the mixing bag 5, open the one-way air inlet valve 9, and use air pressure to push the residual cell fluid in the liquid path into the last dispensing bag that has not yet been dispensed.
[0106] If the absolute value of the difference between the volume of cell fluid to be dispensed in the last unfilled dispensing bag and the target volume is less than or equal to the volume of residual cell fluid in the preset liquid path, it means that the residual cell fluid in the preset liquid path is sufficient to make the volume of cell fluid to be dispensed in the dispensing bag reach the target volume. At this time, the third control valve 3 and the one-way air inlet valve 9 are opened, and the first control valve 1 and the second control valve 2 are closed, thereby opening the liquid path between the one-way air inlet valve 9 and the dispensing bag 6, closing other liquid paths, and using air pressure to push the residual cell fluid in the liquid path into the last unfilled dispensing bag.
[0107] This embodiment minimizes the loss of cell solution in the liquid path and ensures accurate dispensing by pushing the residual cell solution in the liquid path into the last dispensing bag that has not yet been dispensed.
[0108] The cell fluid dispensing apparatus provided in the embodiments of this application is described below. The cell fluid dispensing apparatus described below can be referred to in correspondence with the cell fluid dispensing method described above.
[0109] Figure 6 This is a schematic diagram of the cell fluid dispensing device provided in an embodiment of this application. (Refer to...) Figure 6This application provides a cell fluid dispensing device, which may include:
[0110] The mixing operation parameter table generation module 601 is used to: set mixing operation parameters according to the optimal mixing state of cell fluid of different weights and types, and generate a mixing operation parameter table; the optimal mixing state is the state in which the absolute value of the difference in the number of cells in any two unit volumes of the cell fluid is less than the difference threshold, and the cell activity rate in the cell fluid is greater than the activity rate threshold.
[0111] The mixing control module 602 is used to: control the mixing of the cell solution to be dispensed during the liquid inlet stage, the holding stage, and the liquid outlet stage of the mixing bag according to the mixing operation parameter table; the holding stage is later than the liquid inlet stage, and the liquid outlet stage is later than the holding stage;
[0112] The dispensing control module 603 is used to control the dispensing of cell solution to be dispensed during the liquid dispensing stage of the mixing bag.
[0113] The cell fluid dispensing device provided in this embodiment sets mixing operation parameters according to the optimal mixing state of cell fluids of different weights and types, and generates a mixing operation parameter table. Based on this table, the mixing of the cell fluid to be dispensed is controlled during the inlet, holding, and outlet stages of the mixing bag, and dispensing is controlled during the outlet stage. By controlling the mixing of the cell fluid to be dispensed according to the mixing operation parameters during the inlet, holding, and outlet stages of the mixing bag, this embodiment ensures that the cell fluid to be dispensed reaches an optimal mixing state, thereby reducing cell concentration and cell viability deviations during the flow of the cell fluid into the dispensing bag and improving the quality of the dispensed cell fluid.
[0114] In one embodiment, the mixing control module 602 is specifically used for:
[0115] During the liquid inlet stage of the mixing bag, the weight of the inlet bag is measured in real time using a weighing sensor. Based on the decrease in the weight of the cell solution to be dispensed in the inlet bag, the increase in the weight of the cell solution to be dispensed in the mixing bag is determined. The cell solution to be dispensed flows from the inlet bag into the mixing bag.
[0116] The real-time weight of the cell solution to be dispensed in the mixing bag is obtained based on the weight increase value.
[0117] Based on the real-time weight of the cell solution to be dispensed in the mixing bag and the type of the cell solution to be dispensed, the mixing operation parameter table is queried, and the mixing of the cell solution to be dispensed in the mixing bag is controlled according to the mixing operation parameter table.
[0118] In one embodiment, the mixing control module 602 is specifically used for:
[0119] During the holding phase of the mixing bag, the current mixing operation parameters are maintained to control the mixing of the cell solution to be dispensed in the mixing bag.
[0120] In one embodiment, the mixing control module 602 is specifically used for:
[0121] During the liquid dispensing stage of the mixing bag, the weight decrease of the cell solution to be dispensed in the mixing bag is determined based on the weight increase of the cell solution to be dispensed in the dispensing bag; the cell solution to be dispensed flows from the mixing bag into the dispensing bag.
[0122] The real-time weight of the cell solution to be dispensed in the mixing bag is obtained based on the weight reduction value.
[0123] Based on the real-time weight of the cell solution to be dispensed in the mixing bag and the type of the cell solution to be dispensed, the mixing operation parameter table is queried, and the mixing of the cell solution to be dispensed in the mixing bag is controlled according to the mixing operation parameter table.
[0124] In one embodiment, the dispensing control module 603 is specifically used for:
[0125] A first bubble sensor and a second bubble sensor are provided between the mixing bag and the reference dispensing bag; wherein, the reference dispensing bag is the dispensing bag with the shortest liquid path distance from the mixing bag and the first to be dispensed among a plurality of dispensing bags, and the plurality of dispensing bags are arranged in order of increasing liquid path distance from the mixing bag;
[0126] The flow rate of the cell fluid to be dispensed is obtained based on the volume of the cell fluid to be compared and the absolute value of the time difference between the first flow of the cell fluid to be dispensed through the first bubble sensor and the second bubble sensor; the volume of the cell fluid to be compared is the volume of the cell fluid to be dispensed in the liquid path between the first bubble sensor and the second bubble sensor.
[0127] Based on the flow rate and the volume of the cell solution to be dispensed in the liquid path between the plurality of dispensing bags and the mixing bag, the injection time required for the cell solution to be dispensed to be transferred from the mixing bag to the plurality of dispensing bags is obtained.
[0128] The inlet of the corresponding dispensing bag is opened according to the injection time, and the opening and closing of the inlet of the corresponding dispensing bag is controlled according to the ratio of the volume of the cell fluid to be dispensed into the corresponding dispensing bag to the volume of the cell fluid to be compared.
[0129] In one embodiment, the dispensing control module 603 is specifically used for:
[0130] The inlet of the reference dispensing bag is opened according to the injection time required for the cell solution to be dispensed from the mixing bag to the reference dispensing bag.
[0131] The inlet of the current dispensing bag is controlled to open based on the absolute value of the difference between the injection time required for the cell solution to be dispensed from the mixing bag to the current dispensing bag and the injection time required for the cell solution to be dispensed from the mixing bag to the previous dispensing bag; the current dispensing bag is a dispensing bag other than the reference dispensing bag.
[0132] In one embodiment, a liquid path residue control module (not shown) is further included for:
[0133] If the absolute value of the difference between the volume of cell fluid to be dispensed and the target volume in the last dispensing bag that has not yet been dispensed is less than or equal to the preset residual cell fluid volume in the liquid path, then the outlet of the mixing bag is closed, the one-way air inlet valve is opened, and the residual cell fluid in the liquid path is pushed into the last dispensing bag that has not yet been dispensed using air pressure.
[0134] Figure 7 An example is a schematic diagram of the physical structure of an electronic device, such as... Figure 7 As shown, the electronic device may include: a processor 710, a communication interface 720, a memory 730, and a communication bus 740, wherein the processor 710, the communication interface 720, and the memory 730 communicate with each other via the communication bus 740. The processor 710 can call a computer program stored in the memory 730 to execute steps of the cell fluid dispensing method, such as:
[0135] The mixing operation parameters are set according to the optimal mixing state of cell fluid of different weights and types, and a mixing operation parameter table is generated; the optimal mixing state is the state in which the absolute value of the difference in cell number between any two unit volumes of cell fluid is less than the difference threshold, and the cell viability rate in the cell fluid is greater than the viability rate threshold.
[0136] According to the mixing operation parameter table, the mixing of the cell solution to be dispensed is controlled during the liquid inlet stage, the holding stage, and the liquid outlet stage of the mixing bag; the holding stage is later than the liquid inlet stage, and the liquid outlet stage is later than the holding stage.
[0137] During the dispensing stage of the mixing bag, the dispensing control of the cell solution to be dispensed is performed.
[0138] Furthermore, the logical instructions in the aforementioned memory 730 can be implemented as software functional units and, when sold or used as independent products, can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of this application, in essence, or the part that contributes to the prior art, or a portion of the technical solution, can be embodied in the form of a software product. This computer software product is stored in a storage medium and includes several instructions to cause a computer device (which may be a personal computer, server, or network device, etc.) to execute all or part of the steps of the methods described in the various embodiments of this application. The aforementioned storage medium includes various media capable of storing program code, such as USB flash drives, portable hard drives, read-only memory (ROM), random access memory (RAM), magnetic disks, or optical disks.
[0139] On the other hand, embodiments of this application also provide a computer program product, which includes a computer program that can 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 fluid dispensing methods provided in the above embodiments, such as including:
[0140] The mixing operation parameters are set according to the optimal mixing state of cell fluid of different weights and types, and a mixing operation parameter table is generated; the optimal mixing state is the state in which the absolute value of the difference in cell number between any two unit volumes of cell fluid is less than the difference threshold, and the cell viability rate in the cell fluid is greater than the viability rate threshold.
[0141] According to the mixing operation parameter table, the mixing of the cell solution to be dispensed is controlled during the liquid inlet stage, the holding stage, and the liquid outlet stage of the mixing bag; the holding stage is later than the liquid inlet stage, and the liquid outlet stage is later than the holding stage.
[0142] During the dispensing stage of the mixing bag, the dispensing control of the cell solution to be dispensed is performed.
[0143] On the other hand, embodiments of this application also provide a processor-readable storage medium storing a computer program for causing a processor to perform the steps of the methods provided in the above embodiments, such as including:
[0144] The mixing operation parameters are set according to the optimal mixing state of cell fluid of different weights and types, and a mixing operation parameter table is generated; the optimal mixing state is the state in which the absolute value of the difference in cell number between any two unit volumes of cell fluid is less than the difference threshold, and the cell viability rate in the cell fluid is greater than the viability rate threshold.
[0145] According to the mixing operation parameter table, the mixing of the cell solution to be dispensed is controlled during the liquid inlet stage, the holding stage, and the liquid outlet stage of the mixing bag; the holding stage is later than the liquid inlet stage, and the liquid outlet stage is later than the holding stage.
[0146] During the dispensing stage of the mixing bag, the dispensing control of the cell solution to be dispensed is performed.
[0147] The processor-readable storage medium can be any available medium or data storage device that the processor can access, including but not limited to magnetic memory (e.g., floppy disk, hard disk, magnetic tape, magneto-optical disk (MO)), optical memory (e.g., CD, DVD, BD, HVD), and semiconductor memory (e.g., ROM, EPROM, EEPROM, non-volatile memory (NAND FLASH), solid-state drive (SSD)).
[0148] The device embodiments described above are merely illustrative. The units described as separate components may or may not be physically separate. The components shown as units may or may not be physical units; that is, they may be located in one place or distributed across multiple network units. Some or all of the modules can be selected to achieve the purpose of this embodiment according to actual needs. Those skilled in the art can understand and implement this without any creative effort.
[0149] Through the above description of the embodiments, those skilled in the art can clearly understand that each embodiment can be implemented by means of software plus necessary general-purpose hardware platforms, and of course, it can also be implemented by hardware. Based on this understanding, the above technical solutions, in essence or the part that contributes to the prior art, can be embodied in the form of a software product. This computer software product can be stored in a computer-readable storage medium, such as ROM / RAM, magnetic disk, optical disk, etc., and includes several instructions to cause a computer device (which may be a personal computer, server, or network device, etc.) to execute the methods described in the various embodiments or some parts of the embodiments.
[0150] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of this application.
Claims
1. A method for dispensing cell fluid, characterized in that, include: Set the mixing operation parameters according to the optimal mixing state of cell sap of different weights and types, and generate a mixing operation parameter table; The optimal mixing state is when the absolute value of the difference in cell number between any two unit volumes of the cell solution is less than a difference threshold, and the cell viability rate in the cell solution is greater than a viability rate threshold. According to the mixing operation parameter table, the mixing control is performed on the cell solution to be dispensed during the liquid inlet stage, the holding stage and the liquid outlet stage of the mixing bag. The holding phase is later than the liquid inlet phase, and the liquid outlet phase is later than the holding phase; During the dispensing stage of the mixing bag, the cell solution to be dispensed is controlled, including: A first bubble sensor and a second bubble sensor are provided between the mixing bag and the reference dispensing bag; wherein, the reference dispensing bag is the dispensing bag with the shortest liquid path distance from the mixing bag and the first to be dispensed among a plurality of dispensing bags, and the plurality of dispensing bags are arranged in order of increasing liquid path distance from the mixing bag; The flow rate of the cell fluid to be dispensed is obtained based on the volume of the cell fluid to be compared and the absolute value of the time difference between the first flow of the cell fluid to be dispensed through the first bubble sensor and the second bubble sensor; the volume of the cell fluid to be compared is the volume of the cell fluid to be dispensed in the liquid path between the first bubble sensor and the second bubble sensor. Based on the flow rate and the volume of the cell solution to be dispensed in the liquid path between the plurality of dispensing bags and the mixing bag, the injection time required for the cell solution to be dispensed to be transferred from the mixing bag to the plurality of dispensing bags is obtained. The inlet of the corresponding dispensing bag is opened according to the injection time, and the opening and closing of the inlet of the corresponding dispensing bag is controlled according to the ratio of the volume of the cell fluid to be dispensed into the corresponding dispensing bag to the volume of the cell fluid to be compared.
2. The cell fluid dispensing method according to claim 1, characterized in that, The mixing control of the cell solution to be dispensed during the liquid inlet, holding, and liquid outlet stages of the mixing bag includes: During the liquid inlet stage of the mixing bag, the weight of the inlet bag is measured in real time using a weighing sensor. Based on the decrease in the weight of the cell solution to be dispensed in the inlet bag, the increase in the weight of the cell solution to be dispensed in the mixing bag is determined. The cell solution to be dispensed flows from the inlet bag into the mixing bag. The real-time weight of the cell solution to be dispensed in the mixing bag is obtained based on the weight increase value. Based on the real-time weight of the cell solution to be dispensed in the mixing bag and the type of the cell solution to be dispensed, the mixing operation parameter table is queried, and the mixing of the cell solution to be dispensed in the mixing bag is controlled according to the mixing operation parameter table.
3. The cell fluid dispensing method according to claim 1, characterized in that, The mixing control of the cell solution to be dispensed during the liquid inlet, holding, and liquid outlet stages of the mixing bag includes: During the holding phase of the mixing bag, the current mixing operation parameters are maintained to control the mixing of the cell solution to be dispensed in the mixing bag.
4. The cell fluid dispensing method according to claim 1, characterized in that, The mixing control of the cell solution to be dispensed during the liquid inlet, holding, and liquid outlet stages of the mixing bag includes: During the liquid dispensing stage of the mixing bag, the weight decrease of the cell solution to be dispensed in the mixing bag is determined based on the weight increase of the cell solution to be dispensed in the dispensing bag; the cell solution to be dispensed flows from the mixing bag into the dispensing bag. The real-time weight of the cell solution to be dispensed in the mixing bag is obtained based on the weight reduction value. Based on the real-time weight of the cell solution to be dispensed in the mixing bag and the type of the cell solution to be dispensed, the mixing operation parameter table is queried, and the mixing of the cell solution to be dispensed in the mixing bag is controlled according to the mixing operation parameter table.
5. The cell fluid dispensing method according to claim 1, characterized in that, The step of controlling the opening of the inlet of the corresponding dispensing bag according to the injection time includes: The inlet of the reference dispensing bag is opened according to the injection time required for the cell solution to be dispensed from the mixing bag to the reference dispensing bag. The inlet of the current dispensing bag is controlled to open based on the absolute value of the difference between the injection time required for the cell solution to be dispensed from the mixing bag to the current dispensing bag and the injection time required for the cell solution to be dispensed from the mixing bag to the previous dispensing bag; the current dispensing bag is a dispensing bag other than the reference dispensing bag.
6. The cell fluid dispensing method according to claim 1, characterized in that, After controlling the opening and closing of the liquid inlet of the corresponding dispensing bag, the following steps are included: If the absolute value of the difference between the volume of cell fluid to be dispensed and the target volume in the last dispensing bag that has not yet been dispensed is less than or equal to the preset residual cell fluid volume in the liquid path, then the outlet of the mixing bag is closed, the one-way air inlet valve is opened, and the residual cell fluid in the liquid path is pushed into the last dispensing bag that has not yet been dispensed using air pressure.
7. A cell fluid dispensing device, characterized in that, The method for performing the cell fluid dispensing method according to claim 1 includes: The mixing operation parameter table generation module is used to: set mixing operation parameters according to the optimal mixing state of cell fluid of different weights and types, and generate a mixing operation parameter table; the optimal mixing state is the state in which the absolute value of the difference in cell number between any two unit volumes of the cell fluid is less than the difference threshold, and the cell viability rate in the cell fluid is greater than the viability rate threshold. The mixing control module is used to: control the mixing of the cell solution to be dispensed during the liquid inlet stage, the holding stage, and the liquid outlet stage of the mixing bag according to the mixing operation parameter table; the holding stage is later than the liquid inlet stage, and the liquid outlet stage is later than the holding stage; The dispensing control module is used to control the dispensing of cell solution to be dispensed during the liquid dispensing stage of the mixing bag.
8. An electronic device comprising a processor and a memory storing a computer program, characterized in that, When the processor executes the computer program, it implements the steps of the cell fluid dispensing method according to any one of claims 1 to 6.
9. A computer program product, comprising a computer program, characterized in that, When the computer program is executed by the processor, it implements the steps of the cell fluid dispensing method according to any one of claims 1 to 6.
Citation Information
Patent Citations
Hematopoietic stem cell subpackaging instrument
CN215050120U
