Liquid dispensing method, liquid dispensing system and medium

Abstract

The application discloses a liquid sub-packaging method, a liquid sub-packaging system and a medium, and relates to the technical field of liquid sub-packaging. The method comprises the following steps: sub-packaging a to-be-sub-packaged liquid in a to-be-sub-packaged container into a preset number of preparation containers through a sub-packaging pipeline; the sub-packaging pipeline comprises at least one first pipeline and at least one second pipeline corresponding to each preparation container; one end of the first pipeline is communicated with the to-be-sub-packaged container; the to-be-sub-packaged liquid flows through the at least one first pipeline and the at least one second pipeline and enters each preparation container; the diameter of the second pipeline is smaller than that of the first pipeline, and the second pipeline is softer than the first pipeline. The application improves sub-packaging accuracy.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to a liquid dispensing method, a liquid dispensing system, and a medium. Background Technology

[0002] Cell therapy is a key area of ​​international medical advancement. In recent years, the field has seen continuous breakthroughs in cell therapy research, and the development and evaluation of cell therapy products have received increasing attention. Given the rapid development of cell therapy product research, the use of automated cell harvesting equipment is the mainstream development direction. Because cell processing requires the aliquoting of cell preparations into formulations of different volumes or specifications, even slight changes in the liquid volume of the preparation can affect the quality, cell yield, and viability of the frozen preparation. Current technologies suffer from low aliquoting accuracy due to external interference, which severely impacts preparation quality, precision, and cell yield. Therefore, improving the aliquoting accuracy and reducing volume errors after aliquoting has become a pressing issue. Summary of the Invention

[0003] This invention provides a liquid dispensing method, a liquid dispensing system, and a medium to address the problems of low liquid dispensing accuracy in existing technologies.

[0004] A liquid dispensing method, comprising: The liquid to be dispensed from the container to be dispensed is dispensed into a predetermined number of formulation containers through dispensing pipelines; the dispensing pipelines include at least one first pipeline and at least one second pipeline corresponding to each of the formulation containers; one end of the first pipeline is connected to the container to be dispensed, and the liquid to be dispensed flows through at least one first pipeline and at least one second pipeline into each of the formulation containers; the diameter of the second pipeline is smaller than that of the first pipeline, and the second pipeline is softer than the first pipeline in terms of rigidity.

[0005] A liquid dispensing system includes a container to be dispensed, dispensing tubing, and a controller. The controller is used to execute the liquid dispensing method described above. The dispensing tubing includes at least one first tubing and at least one second tubing corresponding to each of the formulation containers. One end of the first tubing is connected to the container to be dispensed, and the liquid to be dispensed flows through at least one first tubing and at least one second tubing into each of the formulation containers. The diameter of the second tubing is smaller than that of the first tubing, and the second tubing is softer than the first tubing. The container to be dispensed is communicatively connected to the controller. A computer-readable storage medium storing a computer program, characterized in that the computer program, when executed by a processor, implements the above-described liquid dispensing method.

[0006] The above-mentioned liquid dispensing method, liquid dispensing system, and medium, wherein the method includes: dispensing the liquid to be dispensed from the container to be dispensed into a predetermined number of formulation containers through dispensing pipelines; the dispensing pipelines include at least one first pipeline and at least one second pipeline corresponding to each of the formulation containers; one end of the first pipeline is connected to the container to be dispensed, and the liquid to be dispensed flows through at least one first pipeline and at least one second pipeline into each of the formulation containers; the diameter of the second pipeline is smaller than that of the first pipeline, and the second pipeline is softer than the first pipeline in terms of rigidity. In this invention, since the dispensing accuracy will be affected by forces such as tensile force, eccentric force, or interference force (interference force between formulation containers or between dispensing pipelines) of the dispensing pipeline, the diameter of the second pipeline is smaller than that of the first pipeline, and the second pipeline is softer than the first pipeline in terms of hardness. In this way, by setting the hardness and diameter of the first and second pipelines, the second pipeline has the characteristic of being thin and soft, which reduces and avoids the influence of the above-mentioned forces on the dispensing accuracy, thus ensuring the dispensing accuracy and precision of the liquid to be dispensed. Attached Figure Description

[0007] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments of the present invention will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0008] Figure 1 This is a flowchart of a liquid dispensing method in one embodiment of the present invention; Figure 2 This is a flowchart of step S10 of a liquid dispensing method in one embodiment of the present invention; Figure 3 This is a flowchart of a liquid dispensing method in another embodiment of the present invention; Figure 4 This is a schematic diagram of the structure of a liquid dispensing system according to an embodiment of the present invention; Figure 5 This is a flowchart of step S20 of the liquid dispensing method in one embodiment of the present invention; Figure 6 This is a flowchart of a liquid dispensing method in another embodiment of the present invention; Figure 7 This is a schematic diagram of a computer device according to an embodiment of the present invention.

[0009] The reference numerals in the accompanying drawings are as follows: 1. Formulation container; 2. Dispensing pipeline; 21. First pipeline; 211. Return control valve; 22. Second pipeline; 221. Branch control valve; 3. Container to be dispensed; 31. First flow channel; 331. First control valve; 32. Second flow channel; 321. Second control valve; 4. Drive pump; 5. Bubble sensor; 6. Pressure sensor; 7. Sterile filter. Detailed Implementation

[0010] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0011] In one embodiment, such as Figure 1 As shown, a liquid dispensing method is provided, including the following step S10: S10: The liquid to be dispensed from container 3 is dispensed into a preset number (the preset number is set according to requirements) of formulation containers 1 through dispensing pipes 2; the dispensing pipes 2 include at least one first pipe 21 and at least one second pipe 22 corresponding to each of the formulation containers 1; one end of the first pipe 21 is connected to container 3, and the liquid to be dispensed flows through at least one first pipe 21 and at least one second pipe 22 into each of the formulation containers; furthermore, the diameter of the second pipe 22 is smaller than that of the first pipe 21, and the second pipe 22 is softer than the first pipe 21 in terms of flexibility; that is, the first pipe 21 is a conventionally used pipe, but the second pipe 22 is a thin flexible pipe; for example, the first pipe 21 is a pipe with an outer diameter of 5mm and an inner diameter of 4mm, and the second pipe 22 is a thin flexible pipe with an outer diameter of 2mm and an inner diameter of 1mm, and the length of the second pipe 22 can be set according to requirements, for example, it can be set to 50mm. Since the dispensing accuracy will be affected by the pulling force, eccentric force, or interference force (interference force between the preparation containers 1 or between the connecting pipes of the dispensing pipeline 2) of the dispensing pipeline 2, the diameter of the second pipeline 22 is smaller than that of the first pipeline 21 in this invention. The second pipeline 22 is also softer than the first pipeline 21 in terms of hardness. In this way, by setting the hardness and diameter of the first pipeline 21 and the second pipeline 22, the second pipeline 22 is made to have the characteristic of being thin and soft, so as to reduce and avoid the influence of the above forces on the dispensing accuracy. For this invention, the degree of softness / hardness represents the relative flexibility of the conduit. The softer the conduit (e.g., the first conduit 21 and the second conduit 22), the more flexible it is. In this embodiment, the second conduit 22 is softer than the first conduit 21, indicating that the second conduit 22 is a more flexible and thinner conduit than the first conduit 21. This flexibility allows the second conduit 22 to reduce and avoid the impact of tensile forces, eccentric forces, or interference forces on the dispensing accuracy. Understandably, the first conduit 21 and the second conduit 22 can be PVC (polyvinyl chloride) pipes. When the first conduit 21 and the second conduit 22 are PVC pipes, the hardness rating (e.g., Shore A) can characterize whether the pipe is softer. Specifically, the hardness rating can be determined by hardness testing standards, such as GB2411-1980 "Plastics Shore Hardness Test Method". In this invention, the smaller the hardness number, the softer the material; the larger the hardness number, the harder the material.

[0012] Furthermore, in this invention, the container to be dispensed includes, but is not limited to, a centrifuge cup or other container that can be used to contain the liquid to be dispensed. In this invention, the number of first pipes 21 can be one or more, but one end of each first pipe 21 is connected to one or more second pipes 22, and the other end is connected to the container to be dispensed 3.

[0013] In one embodiment of the present invention, such as Figure 4 As shown, the second pipe 22 is connected between the preparation container 1 and the first pipe 21. That is, one end of the second pipe 22 is directly connected to the preparation container 1, and the other end is directly connected to one of the first pipes 21.

[0014] In another embodiment, one end of the second conduit 22 is directly connected to one of the first conduits 21, while the other end is not directly connected to the formulation container 1, but is connected to the formulation container 1 through a third conduit (not shown). Understandably, in this embodiment, the third conduit in the present invention refers to one that is not the same as the second conduit, that is, at least one of its diameter, material, or hardness is different from the second conduit 22 (but the third conduit may be the same as or different from the first conduit 21 in terms of diameter, material, or hardness, for example, the third conduit may be a conduit with the same diameter as the second conduit 22, but with the same material and hardness as the first conduit 21). In this embodiment, each second conduit 22 is connected to the formulation container 1 through a third conduit.

[0015] Understandably, in this invention, if the following description mentions that the liquid to be dispensed enters the formulation container 1 from the second pipe 22, then, depending on the specific connection between the second pipe 22 and the formulation container 1, the liquid to be dispensed will directly enter the formulation container 1 from the second pipe 22 (when one end of the second pipe 22 is directly connected to the formulation container 1), or the liquid to be dispensed needs to enter the formulation container 1 from the second pipe 22 through the third pipe (when the second pipe 22 is connected to the formulation container 1 through the third pipe).

[0016] Furthermore, in one embodiment of the present invention, the liquid to be dispensed from the container 3 is dispensed into a preset number of formulation containers 1 through the dispensing pipeline 2. This can be achieved by controlling the drive pump 4 (which includes, but is not limited to, a peristaltic pump) to rotate in a first direction at a specific speed, thereby driving the liquid to be dispensed from the container to be dispensed sequentially through the first pipeline and the second pipeline connected to the target container into different formulation containers. During the dispensing process, since the diameter of the second pipeline is smaller than that of the first pipeline, the second pipeline 22 is softer than the first pipeline 21. Thus, by setting the softness and diameter of the first pipeline 21 and the second pipeline 22, the softness of the second pipeline 22 reduces and avoids the influence of the above-mentioned forces on the dispensing accuracy, ensuring the dispensing accuracy and precision of the liquid to be dispensed.

[0017] Understandably, in another embodiment, dispensing the liquid to be dispensed from container 3 into a preset number of formulation containers 1 via dispensing pipe 2 can mean that during the liquid dispensing process of the same formulation container 1, if the volume of liquid to be dispensed is the dispensing volume, before dispensing a preset proportion of the dispensing volume (the preset proportion can be set according to requirements, such as 80%) of liquid into the formulation container 1, the liquid to be dispensed needs to be driven by the drive pump 4 at a higher first speed (for example, the first speed is 80 rpm) through the dispensing pipe 2 into the formulation container 1. After the liquid of the preset proportion of the dispensing volume has been dispensed into the formulation container 1, the remaining liquid to be dispensed (when the preset proportion is 80%, the remaining liquid to be dispensed is 20% of the dispensing volume) will be driven by the drive pump 4 at a lower second speed (for example, the first speed is 80 rpm and the second speed is 20 rpm) through the dispensing pipe 2 into the formulation container 1. In this invention, firstly, the liquid in the container to be dispensed 3 is dispensed into the formulation container 1 through a dispensing operation. Thus, in the early stage of dispensing, most of the liquid to be dispensed in the formulation container 1 is dispensed at a relatively high speed (first rotation speed), ensuring the dispensing speed. Furthermore, in the later stage of dispensing, a lower speed (second rotation speed) is used for dispensing, reducing the problem of reduced accuracy caused by inertia and delayed movements between parts in the stage where dispensing is about to be completed. The above-mentioned deceleration dispensing process improves dispensing accuracy and also makes the transfer volume more stable, avoiding the generation of air bubbles, thereby improving the quality, accuracy, and cell yield of the formulation corresponding to the dispensed liquid. Meanwhile, since the diameter of the second pipeline is smaller than that of the first pipeline in the above-mentioned dispensing process (slow-down dispensing process), the second pipeline 22 is softer than the first pipeline 21 in terms of hardness. Thus, by setting the hardness and diameter of the first pipeline 21 and the second pipeline 22, the softness of the second pipeline 22 reduces and avoids the influence of the above-mentioned forces on the dispensing accuracy, thus ensuring the dispensing accuracy and precision of the liquid to be dispensed.

[0018] In one embodiment, each of the second pipelines 22 is provided with a branch control valve 221; the first pipeline 21 is provided with a drive pump 4; the branch control valve 221 includes, but is not limited to, a pinch valve, and the drive pump 4 includes, but is not limited to, a peristaltic pump. Further, as... Figure 2 As shown, step S10, namely dispensing the liquid to be dispensed from container 3 into a predetermined number of preparation containers 1 via dispensing pipe 2, includes: S101, determine the target container from all the formulation containers 1, record the branch control valve 221 on the second pipeline 22 connected to the target container as the target control valve, keep the other branch control valves 221 closed except for the target control valve, and open the target control valve; that is, since each formulation container 1 needs to be dispensed sequentially in this invention, the first target container to be dispensed needs to be determined from all the formulation containers 1. And, since only the target container needs to be dispensed, only the target control valve needs to be opened, while the other branch control valves 221 need to be kept closed to prevent the liquid to be dispensed from entering the target container from the container to be dispensed 3 and not entering the other formulation containers 1.

[0019] S102, obtain the dispensing volume corresponding to the target container, control the drive pump 4 to rotate at a first speed in a first direction, so as to drive the liquid to be dispensed in the container to be dispensed 3 to sequentially pass through at least one first pipe 21 and a second pipe 22 connected to the target container into the target container at high speed, and record the volume of liquid entering the target container in real time; in this step, the dispensing volume refers to the volume of liquid to be dispensed that needs to be injected into each formulation container 1. This dispensing volume is preset and stored in a preset storage area of ​​the controller so as to be retrieved at any time when needed. Understandably, the first direction refers to the direction in which the drive pump 4 drives the fluid in the first pipe 21 to flow from the container to be dispensed 3 towards the formulation container 1; the second direction mentioned later is the opposite of the first direction, which refers to the direction in which the drive pump 4 drives the fluid in the first pipe 21 to flow towards the container to be dispensed 3. In this embodiment, a weighing sensor can record the weight change data of the liquid entering the target container and the second pipeline 22 in real time. Then, based on the weight change data and the liquid density of the liquid to be dispensed in the dispensing container 3, the liquid volume of the liquid entering the target container and the second pipeline 22 can be determined. That is, the liquid volume is obtained by dividing the weight change data by the liquid density. In this step, before dispensing a preset proportion of the dispensing volume (the preset proportion can be set according to requirements, such as 80%) of the liquid into the formulation container 1, the liquid to be dispensed needs to be driven through the dispensing pipeline 2 into the formulation container 1 by a drive pump 4 (drive pump 4 includes, but is not limited to, a peristaltic pump) at a relatively high first rotational speed (e.g., the first rotational speed is 80 rpm). Thus, in the early stage of dispensing, most of the liquid to be dispensed in the formulation container 1 is dispensed at a relatively high speed (first rotational speed), ensuring the dispensing speed.

[0020] S103, when the volume of liquid entering the target container is equal to a preset proportion of the dispensing volume, the drive pump 4 is controlled to rotate in the first direction at a second speed to drive the liquid to be dispensed in the dispensing container 3 to enter the target container sequentially through at least one first pipe 21 and a second pipe 22 connected to the target container at a low speed, and the volume of liquid entering the target container continues to be recorded; the first speed is greater than the second speed; in this embodiment, after the liquid of a preset proportion of the dispensing volume has been dispensed into the formulation container 1, the remaining liquid to be dispensed (when the preset proportion is 80%, the remaining liquid to be dispensed is 20% of the dispensing volume) will be driven into the formulation container 1 through the dispensing pipe 2 by the drive pump 4 at a lower second speed (for example, the first speed is 80 rpm and the second speed is 20 rpm). In the later stages of dispensing, a lower speed (second rotation speed) is used for dispensing, reducing the decrease in accuracy caused by inertia and delayed movements between parts in the final dispensing stage. In this embodiment, the deceleration dispensing process of first high speed and then low speed improves dispensing accuracy. Furthermore, using low-speed liquid delivery in the later stages makes the peristaltic pump's delivery volume more stable and avoids the generation of air bubbles during the peristaltic pump's movement.

[0021] S104, when the recorded liquid volume equals the dispensing volume, the target control valve and the drive pump 4 are closed, confirming that the target container has completed the dispensing operation, and a new target container is selected from the remaining formulation containers 1 until all formulation containers 1 have completed the dispensing operation. That is, after the dispensing operation of the first formulation container 1 is completed, the target control valve and the drive pump 4 can be closed first, and then the dispensing operation of the next formulation container 1 needs to be continued. Therefore, it is necessary to select the next new target container (the selection order can be set according to the requirements, such as random selection or selection according to its spatial arrangement order), and perform the dispensing operation on it. That is, it is necessary to open the target control valve and drive pump 4 corresponding to the next new target container. Then, the subsequent steps will only be carried out after the preset number of formulation containers 1 have all completed the dispensing operation.

[0022] In one embodiment, each of the formulation containers 1 is equipped with a weighing sensor; further, in steps S102 and S103, recording the volume of liquid entering the target container includes: The weight change data of the target container and the second pipeline 22 are measured by the weighing sensor. In this embodiment, the determination of whether the preparation container 1 contains a preset volume of liquid to be dispensed is made by the weighing sensor installed on the preparation container 1 (the preparation container 1 is suspended on a bracket or other position by the weighing sensor). Since the second pipeline 22 is relatively thin and flexible and is connected to the preparation container 1, the weight measured by the weighing sensor actually includes the weight of the preparation container 1, the second pipeline 22, and all the liquid to be dispensed in the preparation container 1 and the second pipeline 22. Furthermore, since the weight of the preparation container 1 and the second pipeline 22 is fixed, the weight change data actually characterizes the weight change of all the liquid to be dispensed in the preparation container 1 and the second pipeline 22.

[0023] The volume of liquid to be dispensed into the target container and the second pipeline 22 is determined based on the weight change data and the liquid density of the liquid to be dispensed in the container 3. As can be seen from the above, since the liquid to be dispensed in the container 3 is prepared according to requirements, the final liquid density is fixed and can be directly retrieved. Therefore, dividing the weight change data by the liquid density yields the current liquid volume in the target container and the second pipeline 22.

[0024] Understandably, during the weighing of the target container and the second pipe 22 using a load cell, if the second pipe 22 is set to have the same diameter and equal hardness as the first pipe 21, for example, both being pipes with an outer diameter of 5mm and an inner diameter of 4mm, then the load cell will be affected by three factors under normal pipe diameter (outer diameter 5mm and inner diameter 4mm): tensile force, eccentric force, and interference force (interference force between the preparation containers 1 or between the connecting pipes of the dispensing pipe 2), which will lead to low accuracy of the liquid to be dispensed. However, by setting the second pipe 22 to be a thin flexible pipe that is different from the first pipe 21 (for example, the first pipe 21 is a pipe with an outer diameter of 5mm and an inner diameter of 4mm, and the second pipe 22 is a thin flexible pipe with an outer diameter of 2mm and an inner diameter of 1mm), the influence of these three factors on the weighing accuracy of the load cell can be greatly prevented.

[0025] In one embodiment, such as Figure 3 As shown, in step S10, after the liquid to be dispensed flows through at least one of the first pipelines and at least one of the second pipelines into each of the formulation containers, the method further includes: S20: Control the return of residual liquid to be dispensed in the first pipeline 21 to the dispensing container 3; that is, in this embodiment of the invention, after dispensing all the formulation containers 1 in step S10, there will still be some liquid to be dispensed in the dispensing pipeline 2. At this time, in order to avoid wasting the liquid to be dispensed in the first pipeline 21, and to avoid affecting the subsequent dispensing and metering of the remaining liquid to be dispensed in the dispensing container 3, the first pipeline 21 in the dispensing pipeline 2 is returned to ensure that the residual liquid to be dispensed in the first pipeline 21 is returned to the dispensing container 3, further reducing the impact of the residual liquid to be dispensed on the dispensing accuracy, ensuring the dispensing accuracy and precision of the liquid to be dispensed, and thus improving the quality, precision and cell yield of the formulation corresponding to the dispensed liquid.

[0026] Furthermore, in this embodiment, before step S20, it is possible to first detect whether there is any residual liquid to be dispensed in the first pipeline 21. Specifically, a pressure sensor 6 can be installed on the first pipeline 21. At this time, if the pressure sensor 6 measures that the real-time pipeline pressure in the first pipeline 21 is within the preset pressure range, it is determined that it has been emptied, and no reflow operation is required. Otherwise, it is confirmed that there is residual liquid to be dispensed in the first pipeline 21, and a reflow operation is then performed, that is, all the residual liquid to be dispensed in the first pipeline 21 is reflowed back to the container 3 to be dispensed. The preset pressure range is determined based on historical tests, that is, the error fluctuation range corresponding to the actual pressure value after the liquid to be dispensed in the first pipeline 21 has flowed out in the historical tests is the preset pressure range.

[0027] In one embodiment, such as Figure 4 As shown, each of the second pipelines 22 is equipped with a branch control valve 221; the first pipeline 21 is equipped with a drive pump 4; the branch control valve 221 includes, but is not limited to, a pinch valve, and the drive pump 4 includes, but is not limited to, a peristaltic pump. The first pipeline 21 is also equipped with a sterile filter 7 connected to the atmosphere, and a return control valve 211 located between the second pipeline 22 and the sterile filter 7; the return control valve 211 includes, but is not limited to, a pinch valve. The return control valve 211 is closed during the dispensing operation; the gas in the ambient atmosphere, after being filtered by the sterile filter 7, enters the first pipeline 21 as sterile gas to avoid contamination of the liquid to be dispensed. That is, during the dispensing operation, the first pipeline 21 cannot be connected to the atmosphere; therefore, the return control valve 211 is closed, forming a closed end. At this time, the first pipeline 21 and the second pipeline 22 are connected so that the liquid to be dispensed can enter the preparation container 1 from the dispensing container 3 via the first pipeline 21 and the second pipeline 22.

[0028] Furthermore, such as Figure 5 As shown, step S20, which is the process of controlling the return of the residual liquid to be dispensed in the first pipeline 21 to the container to be dispensed 3, includes: S201, after confirming that all the formulation containers 1 have completed the dispensing operation, keep all the branch control valves 221 closed and open the return control valve 211 so that the first pipeline 21 is connected to the atmosphere through the sterile filter 7; that is, after all the formulation containers 1 have completed the dispensing operation in step S10, there may still be some liquid to be dispensed in the first pipeline 21. At this time, in order to avoid wasting the liquid to be dispensed remaining in the first pipeline 21, and also to avoid affecting the remaining liquid in the subsequent dispensing containers 3, For the dispensing and metering of the remaining liquid to be dispensed (the weighing sensor installed on the preparation container 1 actually only weighs the liquid to be dispensed in the preparation container 1 and the second pipeline 22, but does not weigh the liquid to be dispensed in the first pipeline 21. Therefore, if the liquid to be dispensed in the first pipeline 21 does not flow back, a portion of the liquid to be dispensed in the dispensing container 3 will be missing and will not be measured), in this embodiment, the return control valve 211 will be opened first, so that the first pipeline 21 is no longer blocked by the return control valve 211, but is connected to the atmosphere through the sterile filter 7.

[0029] S202, control the drive pump 4 to rotate in the second direction at a preset return speed to drive the residual liquid to be dispensed in the first pipeline 21 back to the container to be dispensed 3; the second direction is opposite to the first direction, which means that the drive pump 4 is used to drive the fluid in the first pipeline 21 to flow towards the container to be dispensed 3; that is, after the drive pump 4 rotates in the second direction at the preset return speed, it can drive the residual liquid to be dispensed in the first pipeline 21 to flow towards the container to be dispensed 3. At this time, sterile gas can enter the first pipeline 21 through the sterile filter 7 to balance the gas pressure in the first pipeline 21. In this way, all the residual liquid to be dispensed in the first pipeline 21 can be returned to the container to be dispensed under the drive of the drive pump 4 without being affected by negative pressure.

[0030] S203, after confirming that all residual liquid to be dispensed in the first pipeline 21 has been returned to the dispensing container 3, the return control valve 211 and the drive pump 4 are closed. That is, after confirming that all residual liquid to be dispensed in the first pipeline 21 has been returned to the dispensing container 3, since the second pipeline 22 is thinner and softer than the first pipeline 21, the liquid to be dispensed in the second pipeline 22 remains in the second pipeline 22 and will not be returned to the dispensing container 3. At this time, the return control valve 211 and the drive pump 4 need to be closed, and then the process proceeds to step S30 to drain the second pipeline 22. In this embodiment, the first pipeline 21 in the dispensing pipeline 2 is subjected to a return process to ensure that all residual liquid to be dispensed in the first pipeline 21 is returned to the dispensing container 3. This further reduces the impact of residual liquid to be dispensed on dispensing accuracy, ensures the dispensing accuracy and precision of the liquid to be dispensed, and thus improves the quality, precision and cell yield of the preparation corresponding to the dispensed liquid.

[0031] In one embodiment, a bubble sensor 5 is also provided on the first pipeline 21. Further, after step S202, that is, after controlling the drive pump 4 to rotate in the second direction at a preset return speed to drive the residual liquid to be dispensed in the first pipeline 21 back to the container to be dispensed 3, the method further includes: after the bubble sensor 5 detects in real time that no more liquid is flowing through the first pipeline 21, confirming that all the residual liquid to be dispensed in the first pipeline 21 has been returned to the container to be dispensed 3. That is, in this embodiment, the bubble sensor 5 can be positioned between the drive pump 4 and the container to be dispensed 3, i.e., the bubble sensor 5 is positioned close to the container to be dispensed 3, to avoid situations where, when the bubble sensor 5 detects no liquid flowing through, there is actually still liquid flowing through the section of the first pipeline 21 near the container to be dispensed 3, thus improving measurement accuracy. Furthermore, in this invention, after the bubble sensor 5 detects in real time that no more liquid is passing through the first pipeline 21, the drive pump 4 can be controlled to continue running for a first period of time (set according to requirements) before it is confirmed that all the residual liquid to be dispensed in the first pipeline 21 has been returned to the container to be dispensed (at this time, in this embodiment, the bubble sensor 5 can also be set between the drive pump 4 and the sterile filter 7). This can also avoid the situation where, when the bubble sensor 5 detects that no liquid is passing through, there is still liquid flowing through the section of the first pipeline 21 near the container to be dispensed.

[0032] In one embodiment, a pressure sensor 6 is also provided on the first pipeline 21. Further, after step S202, that is, after controlling the drive pump 4 to rotate in the second direction at a preset return speed to drive the residual liquid to be dispensed in the first pipeline 21 back to the container to be dispensed 3, the method further includes: after the pressure sensor 6 detects in real time that the fluid pressure in the first pipeline 21 is equal to the preset empty pipe pressure, confirming that all the residual liquid to be dispensed in the first pipeline 21 has been returned to the container to be dispensed 3. That is, in this embodiment, the pressure sensor 6 is located between the drive pump 4 and the sterile filter 7. In other words, the pressure sensor 6 must be located between the drive pump 4 and the sterile filter 7 to detect that the first pipeline 21 is currently an empty pipe connected to the atmosphere (the fluid pressure is continuously equal to the preset empty pipe pressure). If the pressure sensor 6 is located between the drive pump 4 and the container to be dispensed 3, after most of the dispensed liquid has returned to the container to be dispensed 3, a negative pressure will form between the drive pump 4 and the container to be dispensed 3, and it will not be equal to the preset empty pipe pressure. Furthermore, in this invention, after the pressure sensor 6 detects in real time that the fluid pressure in the first pipeline 21 is equal to the preset empty pipe pressure, the drive pump 4 can be controlled to continue running for a second period of time (the second period can be equal to or different from the first period, depending on the requirements) (that is, at this time, the pressure sensor 6 detects that the fluid pressure in the first pipeline 21 is equal to the preset empty pipe pressure and continues for the second period of time), it is determined that the residual liquid to be dispensed in the first pipeline 21 has been completely returned to the container to be dispensed 3. In this way, it is also possible to avoid the situation that when the pressure sensor 6 measures that the fluid pressure is equal to the preset empty pipe pressure, there is still liquid flowing through the section of the first pipeline 21 near the container to be dispensed 3.

[0033] In one embodiment, such as Figure 6 As shown, in step S10, after the liquid to be dispensed flows through at least one of the first pipelines and at least one of the second pipelines into each of the formulation containers, the method further includes: S30, the residual liquid to be dispensed in the second tubing 22 is drained into the preparation container 1. Understandably, since the second tubing 22 is thinner and softer than the first tubing 21, after step S10 (or even after step S20), there may still be some residual liquid to be dispensed in the second tubing 22, which will not be returned to the preparation container 3. In this embodiment, the determination of whether the preparation container 1 contains a preset dispensing volume of liquid is made by a weighing sensor installed on the preparation container 1 (the preparation container 1 is suspended from a bracket or other location by the weighing sensor). Since the second pipe 22 is relatively thin and flexible and connects to the preparation container 1, the weight measured by the weighing sensor actually includes the weight of the preparation container 1, the second pipe 22, and all the liquid to be dispensed from both the preparation container 1 and the second pipe 22. Therefore, to ensure dispensing accuracy, in this invention, the second pipe 22 in the dispensing pipe 2 is emptied, draining the residual liquid to be dispensed from the second pipe 22 into the preparation container 1, so that... The weight actually measured by the weighing sensor is consistent with the actual weight ultimately contained in the formulation container 1. Understandably, when the second pipe 22 is connected to the formulation container 1 via the third pipe, the weight measured by the weighing sensor actually includes the weight of the formulation container 1, the second pipe 22, the third pipe, and all the liquid to be dispensed from the formulation container 1, the third pipe, and the second pipe 22. In this case, the second and third pipes in the dispensing pipe 2 are effectively emptied, draining the residual liquid to be dispensed from the second and third pipes into the formulation container 1, ensuring that the weight actually measured by the weighing sensor is consistent with the actual weight ultimately contained in the formulation container 1. Thus, this embodiment further reduces the impact of residual liquid to be dispensed on dispensing accuracy, ensuring the dispensing accuracy and precision of the liquid to be dispensed, thereby improving the quality, precision, and cell yield of the formulation corresponding to the dispensed liquid.

[0034] Understandably, when there is residual liquid to be dispensed in the first pipeline 21, step S30 can be performed after step S20; while when there is no residual liquid to be dispensed in the first pipeline 21, step S30 can be performed directly after step S10.

[0035] In one embodiment, such as Figure 4As shown, each of the second pipelines 22 is equipped with a branch control valve 221; the first pipeline 21 is equipped with a drive pump 4; the branch control valve 221 includes, but is not limited to, a pinch valve, and the drive pump 4 includes, but is not limited to, a peristaltic pump. The container to be dispensed 3 (including, but not limited to, a centrifuge cup) is provided with a receiving space for receiving the liquid to be dispensed, a first flow channel 31 connecting the bottom of the receiving space and the first pipeline 21, and a second flow channel 32 connecting the top of the receiving space. The end of the second flow channel 32 away from the container to be dispensed 3 is connected to the first pipeline 21; the container to be dispensed 3 is also provided with a filter hole connecting the atmosphere and the receiving space; that is, in this embodiment, in the above step S10, the first flow channel 31 is open and the second flow channel 32 is closed, so that the liquid to be dispensed in the receiving space enters the first pipeline 21 and the second pipeline 22 from the bottom through the first flow channel 31, and finally enters the preparation container 1. In step S20, since it is only necessary to return the residual liquid to be dispensed in the first pipeline 21 to the dispensing container 3, it does not matter whether it enters the dispensing container 3 through the first flow channel 31 or the second flow channel 32. Therefore, the first flow channel 31 can be closed and the second flow channel 32 can be opened; or the first flow channel 31 can be opened and the second flow channel 32 can be closed. Specifically, as follows... Figure 4 As shown, the first flow channel 31 is provided with a first control valve 331 for controlling the opening and closing of the first flow channel 31; the second flow channel 32 is provided with a second control valve 321 for controlling the opening and closing of the second flow channel 32.

[0036] Further, step S30, namely, draining the residual liquid to be dispensed from the second pipeline 22 into the formulation container 1, includes: The first flow channel 31 is closed, and the second flow channel 32 is opened. That is, in this embodiment, sterile gas that enters the containment space from the outside through the filter hole needs to be drawn through the second flow channel 32, and then the drawn gas enters the second pipe 22 through the second flow channel 32 and the first pipe 21, thereby pushing the liquid to be dispensed in the second pipe 22 to rise into the preparation container 1. Therefore, at this time, the second flow channel 32 needs to be opened to allow the sterile gas drawn from the top of the containment space to flow through (at the same time, the first pipe 21 is opened so that the sterile gas enters the second pipe 22 along it), and the first flow channel 31 needs to be closed to prevent the liquid to be dispensed at the bottom of the containment space from flowing into the first pipe 21 through the first flow channel 31 when the sterile gas is drawn from the top of the containment space.

[0037] From all the second pipelines 22, a target venting pipeline is identified, and the branch control valve 221 installed on the target venting pipeline is recorded as a venting control valve. All branch control valves 221 except the venting control valve are kept closed, and the venting control valve is opened. Understandably, since the second pipelines 22 are thinner and more flexible than the first pipelines 21, after step S10 (or even after step S20), the liquid to be dispensed in the second pipelines 22 will remain in the second pipelines 22 and will not be returned to the dispensing container 3. Therefore, in this step, each second pipeline 22 needs to be vented sequentially. Thus, the first target venting pipeline to be vented from all the second pipelines 22 needs to be identified. Since only the target venting pipeline needs to be vented, only the venting control valve needs to be opened, while the other branch control valves 221 need to remain closed, so that different second pipelines 22 can be vented sequentially. Understandably, when the second conduit 22 is connected to the formulation container 1 via the third conduit, the target venting conduit will include a second conduit 22 and a third conduit connecting the second conduit 22 and the formulation container 1.

[0038] The drive pump 4 is controlled to rotate in the first direction at a preset venting speed, so that sterile gas enters the containment space through the filter holes and flows sequentially along the second flow channel 32 and the first pipe 21 to the target venting pipe, thereby driving the residual liquid to be dispensed in the target venting pipe into the formulation container 1 connected to the target venting pipe; that is, the gas in the ambient atmosphere, after being filtered through the filter holes, enters the containment space as sterile gas, so as to avoid contamination of the liquid to be dispensed. The first direction also refers to the direction in which the drive pump 4 drives the fluid in the first pipe 21 to flow from the container 3 to the second pipe 22 (target venting pipe). Driven by the drive pump 4, the sterile gas flows in the first direction, that is, flows sequentially along the second flow channel 32 and the first pipe 21 to the target venting pipe. At this time, driven by the sterile gas, the residual liquid to be dispensed in the target venting pipe will be pushed up to the formulation container 1 connected to it.

[0039] After the drive pump 4 has run for a preset purging time, it is confirmed that the target purging pipeline has been purged. The purging control valve and the drive pump 4 are then closed, and a new target purging pipeline is determined from the remaining second pipelines 22 until all second pipelines 22 are purged. That is, after purging the first target purging pipeline, the purging control valve and the drive pump 4 can be closed first. Then, it is necessary to continue purging the next target purging pipeline. Therefore, it is necessary to determine the next new target purging pipeline (the determination order can be set according to the requirements, such as random selection or selection according to its spatial arrangement order) and purge it. That is, it is necessary to open the purging control valve and the drive pump 4 corresponding to the next new target purging pipeline. Then, the entire liquid dispensing process of the present invention is considered to be completed only after all second pipelines 22 have been purged. That is, the above-mentioned liquid dispensing method is completed.

[0040] In this embodiment, the determination of whether the preparation container 1 contains a preset dispensing volume of liquid to be dispensed is made by a weighing sensor installed on the preparation container 1 (the preparation container 1 is suspended from a bracket or other position by the weighing sensor). Since the second pipe 22 is relatively thin and flexible and connected to the preparation container 1, the weight measured by the weighing sensor actually includes the weight of the preparation container 1, the second pipe 22, and all the liquid to be dispensed in the preparation container 1 and the second pipe 22. Therefore, in order to ensure dispensing accuracy, in this invention, the second pipe 22 in the dispensing pipe 2 is emptied to drain the residual liquid to be dispensed in the second pipe 22 into the preparation container 1, so that the weight actually measured by the weighing sensor is consistent with the actual weight in the preparation container 1. In this way, the impact of residual liquid to be dispensed on dispensing accuracy is further reduced, ensuring the dispensing accuracy and precision of the liquid to be dispensed, thereby improving the quality, precision and cell yield of the preparation corresponding to the dispensed liquid, while also avoiding waste.

[0041] It should be understood that the sequence number of each step in the above embodiments does not imply the order of execution. The execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present invention.

[0042] like Figure 4As shown, the present invention also provides a liquid dispensing system, including a container 3 to be dispensed, a dispensing pipeline 2, and a controller, the controller being used to execute the above-described liquid dispensing method. The dispensing pipeline 2 includes at least one first pipeline 21 and at least one second pipeline 22 corresponding to each of the formulation containers 1; one end of the first pipeline 21 is connected to the container 3 to be dispensed, and the liquid to be dispensed flows through at least one first pipeline and at least one second pipeline into each of the formulation containers; the diameter of the second pipeline 22 is smaller than that of the first pipeline 21, and the second pipeline 22 is softer than the first pipeline 21 in terms of rigidity; the container 3 to be dispensed is communicatively connected to the controller. Further specific limitations regarding the liquid dispensing system and the controller can be found in the limitations of the liquid dispensing method described above, and will not be repeated here.

[0043] Specific limitations regarding the controller can be found in the liquid dispensing method section above, and will not be repeated here. Each module in the controller described above can be implemented entirely or partially through software, hardware, or a combination thereof. These modules can be embedded in hardware or independent of the processor in a computer device, or stored in software in the memory of a computer device, so that the processor can call and execute the operations corresponding to each module. Understandably, this controller can be considered as one or more computer devices, such as... Figure 7 As shown, the computer device includes a processor, memory, network interface, and database connected via a system bus. The processor provides computing and control capabilities. The memory includes a non-volatile storage medium and internal memory. The non-volatile storage medium stores an operating system, computer programs, and a database. The internal memory provides an environment for the operation of the operating system and computer programs in the non-volatile storage medium. The database stores data used in the liquid dispensing method described in the above embodiments. The network interface communicates with external terminals via a network connection. When the computer program is executed by the processor, it implements a liquid dispensing method.

[0044] In one embodiment, a computer-readable storage medium is provided, the computer-readable storage medium storing a computer program that, when executed by a processor, implements the above-described liquid dispensing method.

[0045] Those skilled in the art will understand that all or part of the processes in the methods of the above embodiments can be implemented by a computer program instructing related hardware. The computer program can be stored in a non-volatile computer-readable storage medium. When executed, the computer program can include the processes of the embodiments of the above methods. Any references to memory, storage, databases, or other media used in the embodiments provided in this application can include non-volatile and / or volatile memory. Non-volatile memory may include read-only memory (ROM), programmable ROM (PROM), electrically programmable ROM (EPROM), electrically erasable programmable ROM (EEPROM), or flash memory. Volatile memory may include random access memory (RAM) or external cache memory. By way of illustration and not limitation, RAM is available in a variety of forms, such as static RAM (SRAM), dynamic RAM (DRAM), synchronous DRAM (SDRAM), dual data rate SDRAM (DDRSDRAM), enhanced SDRAM (ESDRAM), synchronous link DRAM (SLDRAM), RAMbus direct RAM (RDRAM), direct memory bus dynamic RAM (DRDRAM), and memory bus dynamic RAM (RDRAM), etc.

[0046] Those skilled in the art will clearly understand that, for the sake of convenience and brevity, the above-described division of functional units and modules is used as an example. In practical applications, the above functions can be assigned to different functional units and modules as needed, that is, the internal structure of the device can be divided into different functional units or modules to complete all or part of the functions described above.

[0047] The above-described embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention 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 the present invention, and should all be included within the protection scope of the present invention.

Claims

1. A liquid dispensing method, characterized in that, include: The liquid to be dispensed from the container to be dispensed is dispensed into a predetermined number of formulation containers through dispensing pipelines; The dispensing pipeline includes at least one first pipeline and at least one second pipeline corresponding to each of the formulation containers; One end of the first pipeline is connected to the container to be dispensed, and the liquid to be dispensed flows through at least one of the first pipelines and at least one of the second pipelines into each of the formulation containers; The diameter of the second pipe is smaller than that of the first pipe, and the second pipe is softer than the first pipe in terms of rigidity; Each of the second pipelines is equipped with a branch control valve; the first pipeline is equipped with a drive pump; the container to be dispensed is provided with a receiving space for receiving the liquid to be dispensed, a first flow channel connecting the bottom of the receiving space and the first pipeline, and a second flow channel connecting the top of the receiving space, the end of the second flow channel away from the container to be dispensed being connected to the first pipeline; The container to be dispensed is also provided with filter holes that connect to the atmosphere and the containing space; After the liquid to be dispensed flows through at least one of the first pipelines and at least one of the second pipelines into each of the formulation containers, the process further includes: Close the first flow channel and open the second flow channel; Identify the target venting pipeline from all the second pipelines, record the branch control valve installed on the target venting pipeline as the venting control valve, keep all other branch control valves except the venting control valve closed, and open the venting control valve. The drive pump is controlled to rotate in the first direction at a preset venting speed so that sterile gas enters the containment space through the filter hole and flows sequentially along the second flow channel and the first pipeline to the target venting pipeline, thereby driving the residual liquid to be dispensed in the target venting pipeline into the preparation container connected to the target venting pipeline; After the drive pump has been running for a preset purging time, once it is confirmed that the target purging pipeline has been purged, the purging control valve and the drive pump are closed, and new target purging pipelines are identified from the remaining second pipelines until all second pipelines are purged.

2. The liquid dispensing method as described in claim 1, characterized in that, Each of the second pipelines is equipped with a branch control valve; the first pipeline is equipped with a drive pump. The step of dispensing the liquid to be dispensed from the container to a predetermined number of formulation containers via dispensing pipelines includes: Identify the target container from all the formulation containers, record the branch control valve on the second pipeline connected to the target container as the target control valve, keep all other branch control valves closed except for the target control valve, and open the target control valve; Obtain the dispensing volume corresponding to the target container, control the drive pump to rotate in the first direction at a first speed, so as to drive the liquid to be dispensed in the container to be dispensed to pass through at least one first pipeline and a second pipeline connected to the target container at high speed in sequence into the target container, and record the volume of liquid entering the target container in real time; When the volume of liquid entering the target container is equal to a preset ratio of the dispensing volume, the drive pump is controlled to rotate in the first direction at a second speed to drive the liquid to be dispensed in the dispensing container to pass through at least one of the first pipelines and a second pipeline connected to the target container at a low speed into the target container, and the volume of liquid entering the target container is continuously recorded; the first speed is greater than the second speed. When the recorded liquid volume equals the dispensing volume, the target control valve and the drive pump are closed, the target container is confirmed to have completed the dispensing operation, and new target containers are identified from the remaining formulation containers until all formulation containers have completed the dispensing operation.

3. The liquid dispensing method as described in claim 2, characterized in that, Each of the aforementioned formulation containers is equipped with a weighing sensor; The recording of the liquid volume entering the target container includes: The weight change data of the target container and the second pipeline are measured by the weighing sensor; The volume of liquid to be dispensed into the target container and the second pipeline is determined based on the weight change data and the liquid density of the liquid to be dispensed in the container to be dispensed.

4. The liquid dispensing method as described in claim 2, characterized in that, After the liquid to be dispensed flows through at least one of the first pipelines and at least one of the second pipelines into each of the formulation containers, the process further includes: The residual liquid to be dispensed in the first pipeline is controlled to be returned to the container to be dispensed.

5. The liquid dispensing method as described in claim 4, characterized in that, Each of the second pipelines is equipped with a branch control valve; the first pipeline is equipped with a drive pump; the first pipeline is also equipped with a sterile filter connected to the atmosphere, and a return control valve located between the second pipeline and the sterile filter; the return control valve is in the closed state during the dispensing operation. The control of returning residual liquid to be dispensed in the first pipeline to the container to be dispensed includes: After confirming that all the formulation containers have been dispensed, keep all the branch control valves closed and open the return control valve so that the first line is connected to the atmosphere through the sterile filter; The drive pump is controlled to rotate in the second direction at a preset return speed to drive the residual liquid to be dispensed in the first pipeline back to the container to be dispensed; After confirming that all residual liquid to be dispensed in the first pipeline has been returned to the container to be dispensed, the return control valve and the drive pump are turned off.

6. The liquid dispensing method as described in claim 5, characterized in that, A bubble sensor is also installed on the first pipeline; After controlling the drive pump to rotate in the second direction at a preset return speed to drive the residual liquid to be dispensed in the first pipeline back to the container to be dispensed, the method further includes: After the bubble sensor detects in real time that no more liquid is flowing through the first pipeline, it confirms that all the remaining liquid to be dispensed in the first pipeline has been returned to the container to be dispensed.

7. The liquid dispensing method as described in claim 5, characterized in that, A pressure sensor is also installed on the first pipeline; After controlling the drive pump to rotate in the second direction at a preset return speed to drive the residual liquid to be dispensed in the first pipeline back to the container to be dispensed, the method further includes: After the pressure sensor detects in real time that the fluid pressure in the first pipeline is equal to the preset empty pipeline pressure, it is confirmed that all the residual liquid to be dispensed in the first pipeline has been returned to the container to be dispensed.

8. A liquid dispensing system, characterized in that, The system includes a container to be dispensed, a dispensing pipeline, and a controller, wherein the controller is used to perform the liquid dispensing method as described in any one of claims 1 to 7; the dispensing pipeline includes at least one first pipeline and at least one second pipeline corresponding to each of the formulation containers; One end of the first pipeline is connected to the container to be dispensed, and the liquid to be dispensed flows through at least one of the first pipelines and at least one of the second pipelines into each of the formulation containers; The diameter of the second pipe is smaller than that of the first pipe, and the second pipe is softer than the first pipe in terms of rigidity; The container to be dispensed is communicatively connected to the controller.

9. A computer-readable storage medium storing a computer program, characterized in that, When the computer program is executed by the processor, it implements the liquid dispensing method as described in any one of claims 1 to 7.

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