Sample packaging methods, systems, and media
By setting a quantitative module between the container to be filled and the filling module, the sample liquid volume can be detected in real time, which solves the problem of low accuracy in the filling of cell preparations, realizes accurate quantitative filling, and improves the filling efficiency and treatment effect.
Patent Information
- Application Number
- CN202310297771.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-03-17
- Publication Date
- 2025-09-26
- Estimated Expiration
- 2043-03-17
AI Technical Summary
The existing technology has low packaging accuracy for cell preparations, making it difficult to achieve stable and high-precision liquid volume measurement, which affects the therapeutic effect and timing.
By setting a quantitative module between the container to be filled and the filling module, the volume of the sample liquid is detected in real time, and the flow of the sample liquid is controlled by a peristaltic pump to ensure accurate quantitative filling of the sample liquid.
It achieves accurate quantitative packaging of sample liquid, avoids waste of sample liquid, improves packaging efficiency and accuracy, and ensures the therapeutic effect of cell preparations.
Smart Images

Figure CN118665763B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of biomedical technology, and in particular to a sample packaging method, system and medium. Background Art
[0002] Cell preparation packaging technology is an important part of the biomedical technology field and is crucial to cell therapy and pharmaceutical preparation. Since cell preparations cannot directly contact sensors during packaging, contact sensors that detect flow through direct contact, while relatively accurate, cannot be used to measure the volume (i.e., capacity) of the packaged liquid. Therefore, the existing technology usually measures the volume of liquid during packaging by manually starting and stopping peristaltic pumps, weighing, and manually recording. However, the above-mentioned packaging methods often have problems such as low packaging efficiency and low accuracy. In particular, the most widely used method of measuring volume by weighing is easily affected by vibration interference from pipelines and other devices, which will lead to large accuracy deviations. In the entire cell preparation packaging process, if the requirements for stable and high-precision measurement cannot be achieved, the therapeutic effect of the cell preparation will be affected and the patient's treatment will be delayed. Summary of the Invention
[0003] The embodiments of the present invention provide a sample packaging method, system and medium to solve the problems of low packaging accuracy in the prior art.
[0004] A sample packaging method, comprising:
[0005] Receive the subpackaging instruction and control the sample liquid in the sample container to flow to the container to be subpacked;
[0006] After confirming that the volume of the sample liquid in the container to be dispensed has reached a preset dispensing volume, controlling the sample liquid in the container to be dispensed to flow to the dispensing module, and detecting the real-time volume of the sample liquid flowing into the dispensing module through a quantitative module disposed between the container to be dispensed and the dispensing module;
[0007] After determining that all the sample liquid has flowed into the subpackaging module according to the real-time capacity, the subpackaging is confirmed to be completed.
[0008] A sample packaging system comprises a control module, a sample container, a container to be packaged, a quantitative module and a packaging module; the control module is connected to the quantitative module and the packaging module; the control module is used to execute the sample packaging method.
[0009] A computer-readable storage medium stores a computer program, which implements the above-mentioned sample packaging method when executed by a processor.
[0010] The above-mentioned sample packaging method, system and medium, the method includes: receiving a packaging instruction, controlling the sample liquid in the sample container to flow to the container to be packaged; after confirming that the volume of the sample liquid in the container to be packaged reaches a preset packaging volume, controlling the sample liquid in the container to be packaged to flow to the packaging module, and detecting the real-time volume of the sample liquid flowing into the packaging module through a quantitative module arranged between the container to be packaged and the packaging module; after determining that all the sample liquid has flowed into the packaging module according to the real-time volume, confirming that the packaging is completed. The present invention first inputs a sample liquid (such as a cell preparation) of a preset packaging volume into the container to be packaged, and then detects the real-time volume of the sample liquid flowing from the module to be packaged into the packaging module in real time through a quantitative module arranged between the container to be packaged and the packaging module, and then accurately determines whether all the sample liquid has flowed into the packaging module according to the measured real-time volume, thereby achieving accurate quantitative packaging of the sample liquid and avoiding waste of the sample liquid. BRIEF DESCRIPTION OF THE DRAWINGS
[0011] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments of the present invention. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative labor.
[0012] Figure 1 is a flow chart of a sample packaging method according to one embodiment of the present invention;
[0013] Figure 2 It is a structural diagram of a sample packaging system according to one embodiment of the present invention;
[0014] Figure 3 is a flow chart of step S10 of the sample packaging method in one embodiment of the present invention;
[0015] Figure 4 is a flow chart of step S20 of the sample packaging method in one embodiment of the present invention;
[0016] Figure 5 is a flow chart of step S20 of the sample packaging method in another embodiment of the present invention;
[0017] Figure 6 is a flow chart of step S30 of the sample packaging method in one embodiment of the present invention;
[0018] Figure 7 is a schematic diagram of a computer device according to an embodiment of the present invention.
[0019] The reference numerals in the specification are as follows:
[0020] 1. Sample container; 2. Container to be sub-packed; 3. Quantitative module; 31. Second pipeline; 32. First bubble sensor; 33. Quantitative tube; 34. Second bubble sensor; 35. Second drive pump; 36. Drip bucket; 4. Sub-packaging module; 41. Delivery pipeline; 42. Sub-packaging bag; 43. Second sterile filter; 44. Air pressure sensor; 45. Sub-packaging control valve; 46. Connecting branch; 5. Transmission module; 51. First pipeline; 52. First drive pump; 53. First sterile filter; 54. First branch pipe; 55. Second branch pipe; 56. Third branch pipe; 57. First control valve; 58. Second control valve; 59. Third bubble sensor; 6. Refrigeration module; 7. Weighing module. DETAILED DESCRIPTION
[0021] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention.
[0022] In one embodiment, if Figure 1 As shown, a sample packaging method is provided, comprising the following steps S10-S30:
[0023] S10: receiving the subpackaging instruction and controlling the sample liquid in the sample container 1 to flow to the container 2 to be subpacked; wherein the sample container 1 can be a liquid bag or other container for holding sample liquid (such as various cell preparations that need to be subpacked). In the present invention, Figure 2 As shown, the sample packaging system includes a control module for executing the sample packaging method, as well as a sample container 1, a container to be packaged 2 (the container to be packaged 2 can also be a liquid bag or other container for holding sample liquid), a quantitative module 3 and a packaging module 4; and the control module (not shown) connects the quantitative module 3 and the packaging module 4. Before performing sample packaging, it is first necessary to connect the sample container 1 with the container to be packaged 2, and connect the container to be packaged 2 with the packaging module 4 through the quantitative module 3. Furthermore, the sample container 1 is hung or installed in the weighing module 7 so that the weight change of the sample container 1 can be monitored by the weighing sensor in the weighing module 7.
[0024] In this embodiment, when the control module receives the subpackaging instruction, it controls the sample liquid in the sample container 1 to flow to the container to be subpacked 2; further, in the case Figure 2In the embodiment shown, the sample liquid is transmitted between the sample container 1 and the container to be dispensed 2 via a transmission module 5; the transmission module 5 includes a first sterile filter 53, a first drive pump 52 (such as a peristaltic pump, etc.), a first pipeline 51, a first branch pipe 54, a second branch pipe 55 and a third branch pipe 56; a first control valve 57 is provided on the first branch pipe 54, and a second control valve 58 is provided on the third branch pipe 56; one end of the first branch pipe 54 is connected to the second pipeline 31, and the other end is connected between the first drive pump 52 and the container to be dispensed 2; one end of the second branch pipe 55 is connected to the first sterile filter 53 The other end is connected between the first drive pump 52 and the sample container 1. One end of the third branch pipe 56 is connected to the second branch pipe 55, and the other end is connected between the first control valve 57 and the second drive pump 35. The first drive pump 52 comprises a peristaltic pump. It is understood that the type of peristaltic pump used in the first drive pump 52 can be determined based on the volume of sample liquid to be transferred. For example, a small peristaltic pump is used for a small volume of sample liquid to be transferred (e.g., less than 50 ml), while a large peristaltic pump is used for a larger volume of sample liquid to be transferred (e.g., 50 ml to 150 ml, or even greater than 150 ml). The peristaltic pump transfers fluid by alternately squeezing and releasing the elastic delivery hose of the peristaltic pump. Negative pressure is created within the delivery pipeline 41, driving the fluid to flow. The peristaltic pump can rotate forward or reverse to drive the fluid (either gas or cell preparation) in different directions. The provision of the first sterile filter 53 prevents bacteria from the outside atmosphere from entering all pipelines of the transfer module. In this embodiment, when the control module receives the subpackaging instruction, it controls the first driving pump 52 in the transmission module 5 to open, and at the same time closes the first control valve 57 and the second control valve 58. At this time, the liquid will flow from the sample container 1 to the container 2 to be subpackaged under the drive of the first driving pump 52.
[0025] S20: After confirming that the volume of the sample liquid in the container to be dispensed 2 has reached the preset dispensing volume, the sample liquid in the container to be dispensed 2 is controlled to flow to the dispensing module 4, and the real-time volume of the sample liquid flowing into the dispensing module 4 is detected by the quantitative module 3 disposed between the container to be dispensed 2 and the dispensing module 4; wherein, the preset dispensing volume refers to the total volume of the sample liquid that needs to be dispensed into the dispensing module 4 (i.e., dispensed into all the dispensing bags 42 of the dispensing module 4) at this time. Therefore, after confirming that the volume of the sample liquid in the container to be dispensed 2 has reached the preset dispensing volume, the first driving pump 52 is controlled to be turned off to stop transferring the sample liquid from the sample container 1 to the container to be dispensed 2. Thereafter, the sample liquid in the container to be dispensed 2 is accurately dispensed into the dispensing module 4 through precise measurement by the quantitative module 3.
[0026] Furthermore, in Figure 2In the embodiment shown, the quantitative module 3 includes a second pipeline 31 connected between the container to be filled 2 and the filling module 4, and a second drive pump 35, a first bubble sensor 32, a quantitative tube 33 and a second bubble sensor 34 arranged in sequence on the second pipeline 31; the second drive pump 35 is located between the container to be filled 2 and the first bubble sensor 32; wherein, the second drive pump 35 includes a peristaltic pump. It is understandable that, here, the peristaltic pump used by the second drive pump 35 can be determined according to the preset filling capacity. For example, a small peristaltic pump is used when the preset filling capacity is small (such as less than 50ML), and a large peristaltic pump is used when the preset filling capacity is large (such as 50ML-150ML, or even greater than 150ML). In this embodiment, after confirming that the sample liquid volume in the container to be filled 2 has reached the preset filling capacity, the control Figure 2 The first control valve 57 in the dispensing module is opened, and the second control valve 58 is kept closed, and the second driving pump 35 in the quantitative module 3 is started at the same time to control the sample liquid in the container 2 to be dispensed to flow to the dispensing module 4. At the same time, the real-time volume of the sample liquid flowing into the packaging module 4 is detected by the first bubble sensor 32, the quantitative tube 33, and the second bubble sensor 34 in the quantitative module 3. Specifically, the quantitative tube 33 can be a container with an internal space or a fixed pipeline; a quantitative space is defined between the first bubble sensor 32 and the second bubble sensor 34 (including the internal space of the quantitative tube 33, the space between the first bubble sensor 32 and the quantitative tube 33, and the space between the quantitative tube 33 and the second bubble sensor 34). In this way, the time difference between the sample liquid flowing into the first bubble sensor 32 and then flowing out of the second bubble sensor 34 can be determined by the first bubble sensor 32 and the second bubble sensor 34. Based on the above time difference and the spatial capacity of the quantitative space, the current actual transmission speed of the second driving pump 35 (i.e., the real-time transmission speed mentioned below) can be determined. Then, the flow rate of the sample liquid can be precisely controlled according to the real-time transmission speed, thereby precisely controlling the packaging volume of the sample liquid entering the packaging module 4.
[0027] S30: After determining that all the sample liquid has flowed into the dispensing module 4 based on the real-time capacity, the dispensing is confirmed to be complete. That is, the volume of the sample liquid that has flowed into the dispensing module 4 can be determined based on the real-time capacity. After confirming that all the sample liquid in the to-be-dispensed container 2 has flowed into the dispensing module 4, the dispensing can be confirmed to be complete.
[0028] The present invention first inputs a sample liquid (such as a cell preparation) of a preset packaging volume into the container 2 to be packaged, and then uses the quantitative module 3 arranged between the container 2 to be packaged and the packaging module 4 to detect in real time the real-time volume of the sample liquid flowing from the module to be packaged 4 to the packaging module 4. Then, based on the measured real-time volume, it is accurately determined whether all the sample liquid has flowed into the packaging module 4, thereby achieving accurate quantitative packaging of the sample liquid and avoiding waste of the sample liquid.
[0029] In one embodiment, the sample liquid is transferred between the sample container 1 and the container to be dispensed 2 via a transfer module 5; the transfer module 5 includes a first pipeline 51 connected between the sample container 1 and the container to be dispensed 2, a first drive pump 52 provided on the first pipeline 51, and a first sterile filter 53 connected to the first pipeline 51; referring to the above, the first drive pump 52 includes a peristaltic pump, and the provision of the first sterile filter 53 can prevent bacteria in the outside atmosphere from entering all pipelines of the transfer module. Furthermore, in step S10, the control of the sample liquid in the sample container 1 to flow to the container to be dispensed 2 includes:
[0030] The preset dispensing capacity and the total capacity of the container 2 to be dispensed are obtained from the dispensing instruction. That is, in this embodiment, the preset dispensing capacity refers to the total volume of sample liquid to be dispensed into the dispensing module 4 (i.e., into all dispensing bags 42 of the dispensing module 4). The total capacity of the container 2 to be dispensed is also determined when the container 2 to be dispensed is installed. The preset dispensing capacity and the total capacity of the container 2 to be dispensed are stored in the control module for easy access when a dispensing instruction is generated.
[0031] When the preset subpackaging capacity is greater than the preset proportion of the total capacity, an emptying process is performed; the emptying process refers to driving the gas in the container to be subpacked 2 to flow along the first direction of the first pipeline 51 by the first driving pump 52, and then being discharged from the first sterile filter 53; the preset proportion can be set according to demand, for example, including but not limited to being set to two-thirds of the total capacity, etc. That is, at this time, when the preset subpackaging capacity of the sample liquid that needs to be transferred from the sample container 1 to the container to be subpacked 2 exceeds the preset proportion of the maximum total capacity of the container to be subpacked 2, the air in the container to be subpacked 2 needs to be partially or completely emptied to avoid the container to be subpacked 2 from exploding when the sample liquid is subsequently transferred from the sample container 1 to the container to be subpacked 2. Therefore, at this time, if Figure 2As shown, the first pinch valve (used to control the opening or closing of the inlet and outlet of the sample container 1) disposed on the first pipeline 51 near the sample container 1 can be closed, thereby preventing the sample liquid in the sample container 1 from flowing from the first pipeline 51 into the container 2 to be dispensed. Thereafter, the first control valve 57 and the second control valve 58 are opened, and the first drive pump 52 drives the gas in the container 2 to be dispensed to flow along the first pipeline 51 in the first direction, and then successively passes through the first branch pipe 54 and the third branch pipe 56 and is discharged from the first sterile filter 53. After the preset emptying time, the emptying process can be considered complete.
[0032] After the emptying process is completed, the first driving pump 52 drives the sample liquid in the sample container 1 to flow along the second direction of the first pipeline 51 to the container 2 to be dispensed. Figure 2 As shown, the second direction is opposite to the first direction. However, in other embodiments, due to different pipeline configurations, the second direction may also be the same as the first direction. It is understood that after the emptying process is completed, the first drive pump 52 in the control transmission module 5 is turned on, while the first control valve 57 and the second control valve 58 are closed, and the first pinch valve is opened. At this time, the liquid will flow from the sample container 1 through the first pipeline 51 to the container 2 to be dispensed under the drive of the first drive pump 52.
[0033] In one embodiment, in step S10, controlling the sample liquid in the sample container 1 to flow to the container 2 to be dispensed includes:
[0034] Obtain the first refrigeration parameter contained in the packaging instruction; wherein, the first refrigeration parameter can be set according to demand, and may include the cooling parameters of the refrigeration module 6 for cooling the first refrigeration space and the refrigeration plate, such as the temperature to which the two need to be lowered and the cooling time.
[0035] The first cooling process is performed by the refrigeration module 6; further, the refrigeration module 6 includes a refrigeration component, a temperature control sensor and a refrigeration plate attached to the container 2 to be divided; the refrigeration module 6 is provided with a first refrigeration space for accommodating the refrigeration plate and the container 2 to be divided; the first cooling process includes: controlling the refrigeration component to cool the first refrigeration space and the refrigeration plate according to the first refrigeration parameter; wherein, the refrigeration plate attached to the container 2 to be divided in the refrigeration module 6 is centralized refrigeration, and an insulation layer is provided between the refrigeration plate and other surrounding components to facilitate the barrier of the insulation layer to avoid energy dissipation to the outside, which is conducive to maintaining the temperature of the container 2 to be divided for cooling. That is, when the sample is divided, the refrigeration module 6 is required to cool the first refrigeration space for holding the container 2 to be divided so that it meets the required temperature range, and in order to achieve a temperature difference drop in a short time, a refrigeration plate is provided to attach to the container 2 to be divided for centralized refrigeration.
[0036] The temperature control sensor is used to detect and obtain a temperature set including at least one real-time temperature. After the temperature set meets the preset temperature requirement, the sample liquid in the sample container 1 is controlled to flow to the container 2 to be dispensed. The temperature control sensor includes at least one first temperature sensor arranged in the first refrigeration space and a second temperature sensor arranged on the refrigeration plate; the real-time temperature includes the first real-time temperature measured by any one of the first temperature sensors and the second real-time temperature measured by the second temperature sensor arranged on the refrigeration plate; in this embodiment, the temperature set may include only the first real-time temperature measured by the first temperature sensor in the first refrigeration space, or only the second real-time temperature measured by the second temperature sensor; or it may include both the second real-time temperature and one or more first real-time temperatures, as long as all the real-time temperatures in the temperature set meet the preset temperature requirement. Meeting the preset temperature requirement may mean that each real-time temperature in the temperature set has reached the corresponding cooling temperature requirement, or it may mean that the average value of all real-time temperatures has reached the corresponding cooling temperature requirement. That is, the refrigeration module 6 is controlled to perform a cooling process according to the first refrigeration parameter, so that the temperature in the first refrigeration space in the refrigeration module 6 or / and the temperature of the refrigeration plate are reduced to the temperature set in the first refrigeration parameter so as to meet the preset temperature requirement. The preset temperature requirement can refer to the required temperature range corresponding to the storage of the sample liquid (for example, 1-25 degrees), and the first refrigeration parameter is set according to the above-mentioned preset temperature requirement. In the present invention, if the sample liquid is a cell preparation, it is often necessary to store it within the required temperature range to avoid damaging the integrity and activity of the cell preparation. It is understandable that the temperature is monitored in real time by the temperature control sensor in the refrigeration module 6. The refrigeration components of the refrigeration module 6 may include components such as a compressor and an evaporator. The specific refrigeration method can refer to the refrigeration method of the air conditioner, etc., and will not be repeated here.
[0037] In one embodiment, the refrigeration module 6 is further provided with a second refrigeration space for accommodating the filling module 4 and communicating with the first refrigeration space; the refrigeration module 6 also includes a temperature transmission component provided between the first refrigeration space and the second refrigeration space; further, in step S10, after controlling the sample liquid in the sample container 1 to flow to the container 2 to be filled, the step further includes:
[0038] Obtain the second refrigeration parameter included in the subpackaging instruction; wherein the second refrigeration parameter can be set according to demand and can be considered as a cooling parameter for cooling the second refrigeration space, such as the temperature to which it needs to be lowered and the cooling time.
[0039] According to the second refrigeration parameter, the temperature transmission component is controlled to control the first refrigeration space and the second refrigeration space to exchange heat, so as to perform a second cooling treatment on the second refrigeration space used to accommodate the packaging module 4. That is, in this embodiment, the packaging module 4 is located in the second refrigeration space, and the temperature in the second refrigeration space also needs to meet the same preset temperature requirements as the first refrigeration space. Therefore, a temperature transmission component can be set to perform heat exchange between the first refrigeration space and the second refrigeration space. For example, the temperature transmission component can include an air duct connected between the first refrigeration space and the second refrigeration space and a fan arranged in the air duct, and then the fan can drive the cold air in the first refrigeration space into the second refrigeration space to cool the second refrigeration space, thereby making it also meet the preset temperature requirements corresponding to the second refrigeration space; it is understandable that in the present invention, the time for performing the second cooling treatment can be before the sample liquid in the container 2 to be packaged is controlled to flow to the packaging module 4 in step S20, but the second cooling treatment can also be performed on the sample liquid in the container 2 to be packaged during the process of controlling the sample liquid in the container 2 to flow to the packaging module 4 in step S20. However, in another embodiment, another refrigeration module may also be additionally provided in the second refrigeration space to refrigerate the second refrigeration space, thereby rapidly cooling the second refrigeration space to meet the preset temperature requirement.
[0040] In one embodiment, if Figure 3 As shown, after step S10, that is, after controlling the sample liquid in the sample container 1 to flow to the container 2 to be dispensed, the method further includes:
[0041] S101, after detecting that the sample liquid flows into the container 2 to be filled, obtain the first mixing parameter contained in the filling instruction; that is, in this step, the first mixing parameter can be set according to demand, for example, the first mixing parameter includes but is not limited to the first mixing frequency, first mixing amplitude, first mixing speed, first mixing acceleration, etc. for the mixing component to drive the mixing plate to squeeze or tap the container 2 to be filled.
[0042] S102, a first mixing treatment is performed on the sample liquid in the container 2 to be divided by a mixing module (not shown in the figure), and the mixing module includes a mixing plate (not shown in the figure) and a mixing component (not shown in the figure) connected to the mixing plate; the first mixing treatment includes: controlling the mixing component to drive the mixing plate to squeeze or slap the container 2 to be divided according to the first mixing parameter. In another specific embodiment, the mixing plate and the refrigeration plate are arranged relative to each other; the container 2 to be divided is located between the mixing plate and the refrigeration plate; at this time, the container 2 to be divided, which is placed on the refrigeration plate, is squeezed or slapped by the mixing plate, so that the sample liquid in the container 2 to be divided flows upward and then sinks, and the sample liquid in the container 2 to be divided can be mixed while cooling the sample liquid in the container 2 to be divided. Understandably, it can be achieved by Figure 2 A third bubble sensor 59, disposed on the first pipeline 51 near the container 2 to be dispensed, monitors whether sample liquid has flowed into the container 2 to be dispensed. Upon detecting the inflow of sample liquid into the container 2 to be dispensed, the mixing assembly in the refrigeration module 6 is activated according to the set first mixing parameter. The mixing plate in the mixing assembly presses or taps the container 2 to be dispensed according to the first mixing parameter, causing the cell preparation in the container 2 to flow upward and then sink, thereby achieving a mixing effect.
[0043] Furthermore, in step S102, the first mixing process of the sample liquid in the container 2 to be dispensed may further include:
[0044] After the mixing component is controlled to drive the mixing plate to squeeze or tap the container 2 to be dispensed according to the first mixing parameter, the amount of liquid reduced in the sample container 1 is measured by the weighing module 7 connected to the sample container 1; that is, after the first mixing process is started and the mixing plate is driven to squeeze or tap the container 2 to be dispensed, it is also necessary to change the previous first mixing parameter according to the volume of the sample liquid entering the container 2 to be dispensed, and then change the actual movement parameter of the mixing plate. For example, when the volume of the sample liquid entering the container 2 to be dispensed increases, the actual movement parameter of the mixing plate should be increased, that is, the squeezing or tapping force of the mixing plate on the sample liquid in the container 2 to be dispensed needs to be increased, thereby ensuring and improving the mixing effect. Therefore, in this step, it is necessary to first measure the amount of liquid reduced in the sample container 1 by the weighing module 7 connected to the sample container 1, and then determine the real-time transmission volume in the container 2 to be dispensed according to the amount of liquid reduced in the subsequent steps.
[0045] The real-time transmission volume in the container to be dispensed 2 is determined based on the liquid reduction amount; in this step, it can be considered that the difference between the real-time transmission volume in the container to be dispensed 2 and the pipeline capacity of the first pipeline 51 is equal to the liquid reduction amount of the sample liquid in the sample container 1.
[0046] The first mixing parameter is adjusted according to the real-time transmission volume and the preset adjustment rules, and the mixing component is controlled to drive the mixing plate to squeeze or slap the container 2 to be dispensed according to the adjusted first mixing parameter. That is, an adjustment level can be set in the preset adjustment rule, and each adjustment level corresponds to a transmission capacity range corresponding to the real-time transmission volume and an adjustment parameter group (mixing under this adjustment parameter group will not destroy the integrity and activity of the cells in the sample liquid); when the real-time transmission volume is within the transmission capacity range corresponding to a certain adjustment level, the first mixing parameter can be adjusted to the corresponding adjustment parameter group. Thereafter, the mixing effect can be further improved by controlling the mixing component to drive the mixing plate to squeeze or slap the container 2 to be dispensed according to the adjusted first mixing parameter. The above adjustment of the first mixing parameter can be one or more times, which is specifically determined by the number of times the adjustment level corresponding to the real-time transmission volume changes.
[0047] In one embodiment, in step S20, that is, after confirming that the volume of the sample liquid in the container 2 to be filled has reached the preset filling volume, controlling the sample liquid in the container 2 to be filled to flow to the filling module 4 includes:
[0048] The amount of liquid reduced in the sample container 1 is measured by a weighing module 7 connected to the sample container 1. That is, the weighing module 7 can measure the total weight of the sample container 1 and the sample liquid contained in the sample container 1. By subtracting the weight of the sample container 1 from the total weight, the real-time weight of the sample liquid contained in the sample container 1 can be obtained. Based on the change in the real-time weight (or directly based on the change in the total weight), the amount of liquid reduced in the sample container 1 can be determined.
[0049] The real-time transmission volume in the container to be dispensed 2 is determined based on the liquid reduction amount; in this step, it can be considered that the difference between the real-time transmission volume in the container to be dispensed 2 and the pipeline capacity of the first pipeline 51 is equal to the liquid reduction amount of the sample liquid in the sample container 1.
[0050] After confirming that the volume of the sample liquid in the container 2 to be filled has reached the preset filling volume according to the real-time transmission volume, the second mixing parameter included in the filling instruction is obtained; wherein, when the real-time transmission volume is equal to the preset filling volume, it is confirmed that the volume of the sample liquid in the container 2 to be filled has reached the preset filling volume. At this time, the second mixing parameter included in the filling instruction is obtained. The second mixing parameter can be set according to demand. For example, the second mixing parameter includes but is not limited to a second mixing frequency, a second mixing amplitude, a second mixing speed, a second mixing acceleration, etc.
[0051] The sample liquid in the container 2 to be dispensed is subjected to a second mixing process. The second mixing process includes: controlling the mixing component to drive the mixing plate to squeeze or tap the container 2 to be dispensed within a preset mixing time according to the second mixing parameter. That is, in this step, since the volume of the sample liquid in the container 2 to be dispensed remains unchanged, it is only necessary to continuously control the mixing component to drive the mixing plate to squeeze or tap the container 2 to be dispensed within a preset mixing time (e.g., 10 minutes) according to the second mixing parameter. A good mixing effect can be achieved without adjusting the second mixing parameter. In this embodiment, the second mixing parameter can also be the first mixing parameter obtained by the last adjustment during the first mixing process.
[0052] In one embodiment, the quantitative module 3 includes a second pipeline 31 connecting the container 2 to be filled and the filling module 4, as well as a first bubble sensor 32, a quantitative tube 33, and a second bubble sensor 34 sequentially arranged on the second pipeline 31; the first bubble sensor 32 is located between the quantitative tube 33 and the container 2 to be filled; specifically, the quantitative tube 33 can be a container with an internal space or a fixed pipeline. A quantitative space is defined between the first bubble sensor 32 and the second bubble sensor 34, and the quantitative space includes the internal space of the quantitative tube 33, the space between the first bubble sensor 32 and the quantitative tube 33, and the space between the quantitative tube 33 and the second bubble sensor 34.
[0053] Furthermore, if Figure 4 As shown, in step S20, the real-time volume of the sample liquid flowing into the subpackaging module 4 is detected by the quantitative module 3 disposed between the container 2 to be subpacked and the subpackaging module 4, including:
[0054] S201, detecting the first time when the sample liquid flows into the quantitative space through the first bubble sensor 32; the quantitative space refers to the flow space between the first bubble sensor 32 and the second bubble sensor 34 in the second pipeline 31; the quantitative space includes the internal space of the quantitative tube 33; specifically, the first bubble sensor 32 can be used to determine the first time when the sample liquid flows from the first bubble sensor 32.
[0055] S202 , detecting the second time when the sample liquid flows out of the quantitative space by the second bubble sensor 34 ; that is, the second time when the sample liquid flows out of the second bubble sensor 34 can be determined by the second bubble sensor 34 .
[0056] S203: Obtain the spatial capacity of the quantitative space and determine a real-time transmission speed based on the spatial capacity, the first time, and the second time. Specifically, the time difference between the second time and the first time is first determined, and then the spatial capacity of the quantitative space is divided by the time difference to determine the current actual transmission speed (i.e., the real-time transmission speed) of the second driving pump 35. It is understood that during the sample liquid transmission process, if the sample liquid is a cell preparation, the real-time transmission speed (i.e., the sample liquid flow rate) may affect the cell viability due to the varying densities and sizes of cells in different sample liquids. Therefore, an initial speed can be pre-set based on sample liquid parameters (including sample liquid type) (i.e., the initial speed of the sample liquid is determined based on the sample liquid parameters to ensure cell viability). The first driving pump 52 and the second driving pump 35 (when either driving pump is used) are then controlled to drive the sample liquid to flow at the initial speed. However, during the actual sample liquid transmission process, the first driving pump 52 and the second driving pump 35 cannot precisely control the sample liquid flow at the initial speed, and a certain error is inevitably present. Therefore, for the present invention, when the sample liquid mentioned in the previous step S10 flows in the first pipeline, although the first driving pump 52 cannot accurately control the real-time transmission speed at the initial speed, the error of its flow speed does not affect the volume of the sample liquid to be dispensed that eventually enters the container to be dispensed, so the error between its real-time transmission speed and the initial speed can be ignored in this process. In this step, it is necessary to determine the real-time volume of the sample liquid currently entering the dispensing module 3 based on the real-time transmission speed, and the volume of the sample liquid entering each dispensing bag during the dispensing process is closely related to the above-mentioned real-time volume. Therefore, the actual change of the initial speed must be further determined, that is, it is necessary to accurately determine the real-time transmission speed through the above-mentioned quantitative module 3, so as to ensure the accuracy of the real-time volume and further improve the dispensing accuracy. Understandably, after determining the above-mentioned real-time transmission speed, the real-time transmission speed is fed back to the control module, and the initial speed is replaced by the real-time transmission speed, so as to facilitate the subsequent dispensing process to be retrieved.
[0057] S204, obtain the real-time flow duration of the sample liquid flowing from the container 2 to be packaged to the packaging module 4, and determine the real-time capacity of the sample liquid flowing into the packaging module 4 according to the real-time transmission speed and the real-time flow duration. That is, after determining the real-time transmission speed, the real-time capacity of the sample liquid flowing into the packaging module 4 can be obtained according to the product of the real-time transmission speed and the real-time flow duration. In this embodiment, the real-time capacity of the sample liquid flowing into the packaging module 4 can be indirectly and accurately determined by volume and time. Furthermore, since the second bubble sensor 34 is installed at a position close to the packaging module 4, the real-time flow duration may refer to the time difference between the time point when the second bubble sensor 34 detects the flow of sample liquid and the current time point; Figure 2 In the embodiment shown, if the sample liquid in the container to be filled 2 is controlled to flow to the filling module 4 by the second driving pump 35, at this time, the rotation time of the second driving pump 35 can be first obtained, and then the total pipeline volume between the two when flowing from the container to be filled 2 to the filling module 4 is divided by the real-time transmission speed to obtain the error time. At this time, the real-time flow time is the difference between the rotation time and the error time.
[0058] In one embodiment, the packaging module 4 includes at least one delivery pipeline 41 and a plurality of packaging bags 42 connected to the delivery pipeline 41 (the packaging bags 42 can be cryopreservation bags or other types of liquid bags); the quantitative module 3 also includes a second driving pump 35 arranged on the second pipeline 31 and located between the container to be packaged 2 and the first bubble sensor 32; the sample liquid is transmitted between the sample container 1 and the container to be packaged 2 through the transmission module 5; the transmission module 5 includes a first sterile filter 53, a first driving pump 52, a first pipeline 51, a first branch pipe 54, a second branch pipe 55 and a third branch pipe 56; a first control valve 57 is provided on the first branch pipe 54, and a second control valve 58 is provided on the third branch pipe 56; one end of the first branch pipe 54 is connected to the second The other end of the pipeline 31 is connected between the first drive pump 52 and the container 2 to be dispensed. One end of the second branch pipe 55 is connected to the first sterile filter 53, and the other end is connected between the first drive pump 52 and the sample container 1. One end of the third branch pipe 56 is connected to the second branch pipe 55, and the other end is connected between the first control valve 57 and the second drive pump 35. The first drive pump 52 includes a peristaltic pump. It is understandable that the peristaltic pump used in the first drive pump 52 can be determined based on the volume of sample liquid to be transferred. For example, a small peristaltic pump is used for a small volume of sample liquid to be transferred (e.g., less than 50ml), while a large peristaltic pump is used for a large volume of sample liquid to be transferred (50ml-150ml, or even greater than 150ml). The provision of the first sterile filter 53 can prevent bacteria and the like from the outside atmosphere from entering all pipelines of the transfer module.
[0059] Furthermore, if Figure 5 As shown, in step S20, controlling the sample liquid in the container to be filled 2 to flow to the filling module 4, and detecting the real-time volume of the sample liquid flowing into the filling module 4 by the quantitative module 3 arranged between the container to be filled 2 and the filling module 4, includes:
[0060] S205, close the first driving pump 52 and the second control valve 58, and open the second driving pump 35 and the first control valve 57 at the same time, so that the driving force of the second driving pump 35 drives the sample liquid in the container 2 to be dispensed through the first pipeline 51, the first branch pipe 54, the second pipeline 31 and the delivery pipeline 41 in sequence to be dispensed into each of the dispensing bags 42, and the quantitative module 3 detects the real-time volume of the sample liquid flowing into the delivery pipeline 41; that is, as Figure 2As shown, after confirming that the volume of the sample liquid in the container to be divided 2 has reached the preset dividing volume, the first driving pump 52 and the second control valve 58 are first closed. At this time, the sample liquid in the sample container 1 no longer flows into the first pipeline 51, and the first sterile filter 53 is not connected to the second pipeline 31; and after opening the second driving pump 35 and the first control valve 57, the container to be divided 2 is connected to the dividing module 4 through the first pipeline 51 and the second pipeline 31. At this time, under the driving force of the second driving pump 35, the sample liquid in the container to be divided 2 is sequentially divided into each of the dividing bags 42 through the first pipeline 51, the first branch 54, the second pipeline 31 and the delivery pipeline 41. The quantitative module 3 will detect the real-time capacity (such as the above-mentioned real-time capacity or the second real-time capacity) of the sample liquid flowing into the delivery pipeline 41 in real time as described in the above embodiment. Specifically, as described in the above embodiment, Figure 2 As shown, in the process of controlling the sample liquid in the container 2 to be sub-packed to flow to the sub-packaging module 4, the sub-packaging control valve 45 corresponding to each sub-packaging bag 42 can be opened in sequence according to a preset sub-packaging order (for example, sorted according to the distance between the sub-packaging bag 42 and the second bubble sensor 34), so as to perform sub-packaging operations on each sub-packaging bag 42 respectively, thereby achieving a precise sub-packaging effect.
[0061] S206, determining the remaining unpacked capacity based on the real-time capacity and the preset packing capacity. When the unpacked capacity is less than or equal to the preset pipeline capacity, closing the first control valve 57 and simultaneously opening the second control valve 58, so that the remaining pipeline in the first branch 54 on the side of the first control valve 57 away from the first pipeline 51, the second pipeline 31, and the transport pipeline 41 are driven to be packed into each of the said packing bags 42 under the driving force of the air entering the third branch 56 through the first sterile filter 53 and the driving force of the second driving pump 35.
[0062] That is, in this embodiment, the difference between the preset filling capacity and the real-time capacity is the unfilled capacity; and the preset pipeline capacity is recorded in the control module, and the preset pipeline capacity refers to the pipeline path from the first control valve 57 to the filling bag 42 where the remaining sample liquid needs to be filled. In this embodiment, when the sample liquid is dispensed to a point where the remaining dispensing capacity is less than or equal to the preset pipeline capacity, it can be considered that the dispensing is nearing completion. At this time, the first control valve 57 can be closed and the second control valve 58 can be opened at the same time. Then, under the driving force of the air entering the third branch pipe 56 through the first sterile filter 53 and the driving force of the second drive pump 35, the remaining sample liquid in the remaining pipeline of the first branch pipe 54 on the side of the first control valve 57 away from the first pipeline 51, the second pipeline 31, and the transport pipeline 41 is driven to be dispensed into each of the dispensing bags 42. In this way, the remaining sample liquid in the pipeline (the remaining pipeline of the first branch pipe 54 on the side of the first control valve 57 away from the first pipeline 51, the second pipeline 31, and the transport pipeline 41) is transferred to the remaining dispensing bags 42 to be dispensed. In this way, the liquid in the pipeline can be fully utilized, no liquid is wasted, and waste generated during the dispensing process is avoided.
[0063] Furthermore, in the step S20, after controlling the sample liquid in the container 2 to be filled to flow to the filling module 4, the method further includes:
[0064] After both the first bubble sensor 32 and the second bubble sensor 34 detect that liquid is flowing, it is confirmed that the quantitative tube 33 is filled with sample liquid, and the first inlet end and the first outlet end of the quantitative tube 33 are controlled to be upside down. Figure 2As shown, the quantitative tube 33 is arranged vertically, with its first inlet end, connected to the first bubble sensor 32, located at the bottom, and its first outlet end, connected to the second bubble sensor 34, located at the top. (This arrangement is necessary for measuring the real-time transmission speed; otherwise, the quantitative module 3 would not be able to accurately measure the real-time transmission speed during the initial phase of sample liquid flow in the above embodiment.) If the quantitative tube 33 were maintained in this state throughout the entire dispensing process, when the sample liquid in the quantitative tube 33 is almost completely transferred (the first bubble sensor 32 has begun to detect no liquid flow, but the second bubble sensor 34 can still detect liquid flow), the sample liquid in the quantitative tube 33 cannot be driven to the first outlet end of the quantitative tube 33 due to the influence of gravity. In this case, residual sample liquid will remain in the quantitative tube 33 and cannot enter the dispensing module, ultimately resulting in sample liquid waste or reduced dispensing accuracy. Therefore, in this embodiment, the quantitative tube 33 needs to be inverted after both the first bubble sensor 32 and the second bubble sensor 34 detect liquid flow, and before the first bubble sensor 32 begins to detect no liquid flow but the second bubble sensor 34 can still detect liquid flow, so that the sample liquid affected by gravity can also be transferred to the remaining sub-packaging bags 42. When both the first bubble sensor 32 and the second bubble sensor 34 detect liquid flow, it can be determined that the quantitative tube 33 is full of sample liquid. At this point, the real-time transfer speed measurement task has been completed. Therefore, the quantitative tube 33 can then be controlled to be inverted to transfer the remaining sample liquid in the quantitative tube 33 to the delivery pipeline 41.
[0065] After both the first bubble sensor 32 and the second bubble sensor 34 detect that liquid has flowed through, if the quantitative tube 33 is not immediately turned upside down, then in the subsequent filling process, if the first bubble sensor 32 detects that no liquid has flowed through and the second bubble sensor 34 detects that liquid has flowed through, it means that the sample liquid in the quantitative tube 33 is almost finished (the first bubble sensor 32 has begun to detect that no liquid has flowed through). At this time, due to the influence of the gravity of the sample liquid in the quantitative tube 33, the current state cannot drive the sample liquid in the quantitative tube 33 to rise to the first outlet of the quantitative tube 33. At this time, the quantitative tube 33 must be inverted, otherwise the sample liquid affected by gravity cannot be transferred to the remaining sub-packaging bags 42. In this process, since the sample liquid in the quantitative tube 33 is almost transferred, the remaining sample liquid in the inverted quantitative tube (the sample liquid that does not fill the quantitative tube 33) needs to be transferred to the sub-packaging module. Therefore, it is also necessary to keep the second control valve 58 open so that the sample liquid can be pushed and transferred to the remaining sub-packaging bags 42 under the driving force of the air entering the third branch pipe 56 from the first sterile filter 53 and the driving force of the second driving pump 35. The above embodiment further fully utilizes the sample in the quantitative tube 33 and avoids waste of sample liquid.
[0066] In one embodiment, the quantitative module 3 further includes a dripping funnel 36 provided on the second pipeline 31; the dripping funnel 36 is provided on the second pipeline 31 and is located between the first bubble sensor 32 and the container 2 to be dispensed; the dripping funnel 36 is used to eliminate bubbles in the sample liquid entering the dispensing module 4; further, in the step S20, after the sample liquid in the container 2 to be dispensed is controlled to flow to the dispensing module 4, the step further includes:
[0067] When the first bubble sensor 32 detects liquid flowing through, it confirms that the dripping funnel 36 is filled with sample liquid and controls the dripping funnel 36 to turn upside down. Figure 2As shown, the second outlet end of the dripping funnel 36, which communicates with the first bubble sensor 32, is located at the upper end, while the second inlet end, which communicates with the container 2 to be filled (i.e., communicates with the first branch pipe 54), is located at the lower end. This configuration is necessary for the dripping funnel 36 to eliminate bubbles in the sample liquid entering the filling module 4. Thus, the dripping funnel 36 primarily serves to eliminate bubbles in the sample liquid entering the filling module 4 during the process of transferring the sample liquid from the container 2 to be filled. However, if the dripping funnel 36 remains in this state throughout the filling process, when the sample liquid in the dripping funnel 36 is nearly fully transferred (the first bubble sensor 32 has begun to detect no liquid flow, but the second bubble sensor 34 can still detect liquid flow), the gravity of the sample liquid in the dripping funnel 36 will prevent the sample liquid in the dripping funnel 36 from rising to the second outlet end. In this case, residual sample liquid will remain in the dripping funnel 36 and cannot enter the filling module, ultimately resulting in sample liquid waste or reduced filling accuracy. Therefore, in this embodiment, after the first bubble sensor 32 detects liquid flow (indicating that the dripping funnel 36 is already filled with sample liquid), and before the first bubble sensor 32 detects no liquid flow but the second bubble sensor 34 can still detect liquid flow (at this point, the first bubble sensor 32 has detected no liquid flow, indicating that discontinuous sample liquid transfer has occurred, with only a portion of sample liquid remaining in the pipeline, indicating that sample liquid transfer is nearly complete), the dripping funnel 36 must be inverted (inverting the dripping funnel after it is filled with liquid can also ensure that there are no bubbles in the sample liquid). This allows the sample liquid, which is affected by gravity, to be transferred to the remaining sub-packaging bags 42. During this process, the second control valve 58 must also be kept open, so that the sample liquid is pushed and transferred to the remaining sub-packaging bags 42 by the driving force of the air entering the third branch pipe 56 from the first sterile filter 53 and the driving force of the second drive pump 35. This embodiment further fully utilizes the sample liquid in the dripping funnel 36 and avoids waste of sample liquid.
[0068] In one embodiment, if Figure 2As shown, the packaging module 4 also includes a second sterile filter 43 and an air pressure sensor 44, and each end of the conveying pipeline 41 away from the container 2 to be packaged is connected to the air pressure sensor 44 through the second sterile filter 43; all the sub-packaging bags 42 are connected to the conveying pipeline 41 through a connecting branch 46 provided with a sub-packaging control valve 45; wherein, opening and closing the sub-packaging control valve 45 corresponding to each sub-packaging bag 42 can drain the sample liquid (cell preparation) into the corresponding sub-packaging bag 42; in this embodiment, before the sample liquid is packaged, all the sub-packaging bags 42 must be connected to different conveying pipelines 41 through the connecting branch 46. In this embodiment, each connecting branch 46 is provided with a sub-packaging control valve 45, and the sub-packaging bags 42 are connected to the conveying pipeline 41 through the connecting branch 46. Since the delivery pipeline 41 is connected to the sub-packaging bag 42 through the connecting branch 46, and in the present invention, the specific rising height of the sample liquid in the connecting branch 46 may need to be observed in subsequent embodiments, the mounting frame also needs to be provided with a fixing member for fixing the connecting branch 46 perpendicular to the hanging rod. In this way, each connecting branch 46 is arranged perpendicular to the hanging rod, and all connecting branches 46 are parallel to each other. Each connecting branch 46 is provided with a sub-packaging control valve 45 (the sub-packaging control valve 45 can be a pinch valve) for controlling the opening and closing of the connecting branch 46 to control the flow of fluid therein. Figure 2 As shown, there can be multiple or one delivery pipeline 41, depending on the total number of sub-packaging bags 42. For example, the total number can be divided by the maximum number of bags that can be connected to a single delivery pipeline 41, and the resultant value rounded up to the nearest integer. Preferably, all sub-packaging bags 42 connected to the same delivery pipeline 41 are located at the same level to facilitate subsequent degassing and packaging. Specifically, the sub-packaging bags 42 can be of the same specification and mounted on different hanging rods on a mounting frame (not shown), with each hanging rod corresponding to a delivery pipeline 41. Therefore, all sub-packaging bags 42 mounted on each hanging rod are at the same level, and each sub-packaging bag 42 is connected to the delivery pipeline 41 via a connecting branch 46. The mounting frame structure can be customized as needed, but each hanging rod must include multiple hooks of the same specification that can hang all sub-packaging bags 42 at the same level, with each hook being used to hang a single sub-packaging bag 42. All the packaging bags 42 have the same specifications so as to facilitate packaging of the same volume of sample liquid.
[0069] It can be understood that the second sterile filter 43 in each conveying pipeline 41 is connected to the acquisition circuit of the control module through a pipeline. Specifically, the end of each conveying pipeline 41 away from the container 2 to be packaged is connected to the air pressure sensor 44 in the acquisition circuit through the second sterile filter 43. Then, the air pressure sensor 44 in the acquisition circuit can collect the real-time pressure value in the pipe corresponding to each row of conveying pipelines 41, and then the current actual pressure value inside each conveying pipeline 41 can be monitored in real time according to the measured real-time pressure value in the pipe; and the second sterile filter 43 can ensure the sterile environment in the conveying pipeline 41 under the premise that the conveying pipeline is connected to the air pressure sensor 44.
[0070] Further, such as Figure 6 As shown, the step S30, i.e., after determining according to the real-time capacity that the sample liquid has flowed into the subpackaging module 4, confirming the completion of subpackaging, includes:
[0071] S301, after determining that the sample liquid has flowed into the sub-packaging module 4 according to the real-time capacity, open all the sub-packaging control valves 45 and the second control valve 58, so that all the sub-packaging bags 42 are connected to the atmospheric environment through the conveying pipeline 41, the second pipeline 31, the third branch 56 and the first sterile filter 53, thereby balancing the air pressure in all the conveying pipelines 41 and the sub-packaging bags 42; that is, in this embodiment, it is necessary to first open all the sub-packaging control valves 45 and the second control valve 58 in the sub-packaging module 4, so as to balance the air pressure in the conveying pipeline 41 and the sub-packaging bags 42 in the sub-packaging module 4 through the air entering from the first sterile filter 53.
[0072] S302, after closing all the sub-packaging control valves 45, perform the air pumping operation on each of the sub-packaging bags 42 in turn according to the preset air pumping sequence; the air pumping operation includes: opening the sub-packaging control valve 45 corresponding to the sub-packaging bag 42, driving the gas in the sub-packaging bag 42 through the second driving pump 35 of the quantitative module 3 (that is, the rotation direction of the second driving pump 35 is reversed compared with the rotation direction when the sample liquid is dispensed from the container to be dispensed 2 to the sub-packaging bag 42 of the sub-packaging module 4), and discharging the gas in the sub-packaging bag 42 in sequence through the delivery pipeline 41, the second pipeline 31, the third branch 56 and the first sterile filter 53, and at the same time obtaining the real-time pressure value in the pipeline of the delivery pipeline 41 measured by the air pressure sensor 44, and confirming that the air pumping operation of the sub-packaging bag 42 is completed when the real-time pressure value in the pipeline reaches the preset pressure threshold; that is, after opening all the sub-packaging control valves 45, the gas in the sub-packaging bag 42 is discharged in sequence through the delivery pipeline 41, the second pipeline 31, the third branch 56 and the first sterile filter 53. After the control valve 45 and the second control valve 58 have been operated for a preset period of time (at which time it is considered that the air pressure has been balanced), and after all the sub-packaging control valves 45 are closed, the sub-packaging control valves 45 corresponding to each sub-packaging bag 42 can be opened in sequence according to a preset air extraction sequence (for example, sorted according to the distance between the sub-packaging bag 42 and the second bubble sensor 34) to perform air extraction operations on each sub-packaging bag 42 respectively, thereby achieving accurate air extraction and improving the sub-packaging effect; and the real-time pressure value in the pipe in the conveying pipeline 41 is monitored by the air pressure sensor 44. When the real-time pressure value in the pipe reaches the preset pressure threshold, it indicates that the gas in the sub-packaging bag 42 has been evacuated. At this time, the sub-packaging control valve 45 corresponding to the sub-packaging bag 42 can be closed, and the next sub-packaging bag 42 can be evacuated in the preset air extraction sequence. In this way, the gas in each sub-packaging bag 42 can be evacuated in turn.
[0073] S303: When the vacuuming operation of all the sub-packaging bags 42 is completed, the sub-packaging is confirmed to be completed. That is, after the last sub-packaging bag 42 determined according to the preset vacuuming order has completed the vacuuming operation, it means that the sub-packaging of the sample liquid in all the sub-packaging bags 42 corresponding to the sub-packaging instruction has been finally completed. At this time, the next round of sub-packaging can be carried out. In this case, the next round of sub-packaging pipeline can be switched from the tee position where the first branch pipe, the third branch pipe and the second pipeline 31 are connected. Specifically, the pipeline between the drip hopper 36 and the tee is heat-sealed, and then the opening of the tee end is heat-sealed to the next round of sub-packaging pipeline using a sterile pipe connection machine.
[0074] It should be understood that the size of the serial numbers of the steps in the above embodiments does not mean 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.
[0075] like Figure 2As shown, the present invention also provides a sample packaging system, including a control module, a sample container 1, a container to be packaged 2, a quantitative module 3 and a packaging module 4; the control module is connected to the quantitative module 3 and the packaging module 4; the control module is used to execute the above-mentioned sample packaging method. The control module includes a central processing unit, a control circuit and an acquisition circuit. In another embodiment, as Figure 2 As shown, the sample packaging system also includes a transmission module 5 connected to the control module, a weighing module 7, a refrigeration module 6 and a mixing module, etc.; for more specific limitations on the sample packaging system and the control module and other modules in the sample packaging system, please refer to the limitations on the sample packaging method above and will not be repeated here.
[0076] Each module in the above control module can be implemented in whole or in part by software, hardware or a combination thereof. Each module can be embedded in or independent of the processor in the computer device in the form of hardware, or can be stored in the memory of the computer device in the form of software, so that the processor can call and execute the operations corresponding to each module. It is understandable that the control module can be regarded as one or more computer devices, such as Figure 7 As shown, the computer device includes a processor, a memory, a network interface and a database connected via a system bus. The processor of the computer device is used to provide computing and control capabilities. The memory of the computer device includes a non-volatile storage medium and an internal memory. The non-volatile storage medium stores an operating system, a computer program and a database. The internal memory provides an environment for the operation of the operating system and the computer program in the non-volatile storage medium. The database of the computer device is used to store the data used in the sample packaging method in the above embodiment. The network interface of the computer device is used to communicate with an external terminal via a network connection. When the computer program is executed by the processor, a sample packaging method is implemented.
[0077] In one embodiment, a computer-readable storage medium is provided, wherein the computer-readable storage medium stores a computer program, and when the computer program is executed by a processor, the sample packaging method described above is implemented.
[0078] Those skilled in the art will understand that all or part of the processes in the above-mentioned embodiments can be implemented by instructing the relevant hardware through a computer program. The computer program can be stored in a non-volatile computer-readable storage medium. When the computer program is executed, it can include the processes of the embodiments of the above-mentioned methods. Among them, any reference to memory, storage, database or other media used in the embodiments provided in this application may 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 many forms such as static RAM (SRAM), dynamic RAM (DRAM), synchronous DRAM (SDRAM), double 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.
[0079] Those skilled in the art will clearly understand that for the sake of convenience and brevity of description, only the division of the above-mentioned functional units and modules is used as an example. In actual applications, the above-mentioned functions can be distributed and completed by 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.
[0080] The embodiments described above are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. These modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present invention, and should all be included in the scope of protection of the present invention.
Claims
1. A sample packaging method, characterized in that: include: Receive the subpackaging instruction and control the sample liquid in the sample container to flow to the container to be subpacked; After confirming that the volume of the sample liquid in the container to be dispensed has reached a preset dispensing volume, controlling the sample liquid in the container to be dispensed to flow to the dispensing module, and detecting the real-time volume of the sample liquid flowing into the dispensing module through a quantitative module disposed between the container to be dispensed and the dispensing module; After determining that all the sample liquid has flowed into the subpackaging module according to the real-time capacity, confirming that the subpackaging is completed; The quantitative module includes a second pipeline connecting the container to be filled and the filling module, and a first bubble sensor, a quantitative tube and a second bubble sensor sequentially arranged on the second pipeline; the first bubble sensor is located between the quantitative tube and the container to be filled; The method of detecting the real-time volume of the sample liquid flowing into the subpackaging module by a quantitative module disposed between the container to be subpacked and the subpackaging module includes: detecting, by the first bubble sensor, a first time when the sample liquid flows into a quantitative space; the quantitative space refers to a flow space between the first bubble sensor and the second bubble sensor in the second pipeline; the quantitative space includes the internal space of the quantitative tube; detecting, by the second bubble sensor, a second time when the sample liquid flows out of the quantitative space; Obtaining a space capacity of the quantitative space, and determining a real-time transmission speed according to the space capacity, the first time, and the second time; Acquiring a real-time flow duration of the sample liquid from the container to be filled to the filling module, and determining a real-time volume of the sample liquid flowing into the filling module according to the real-time transmission speed and the real-time flow duration; After controlling the sample liquid in the container to be filled to flow to the filling module, the method further includes: After both the first bubble sensor and the second bubble sensor detect liquid flowing through, confirming that the quantitative tube is filled with sample liquid, and controlling the first inlet end and the first outlet end of the quantitative tube to be turned upside down; The quantitative module further includes a dripping hopper provided on the second pipeline; the dripping hopper is provided on the second pipeline and is located between the first bubble sensor and the container to be dispensed; the dripping hopper is used to eliminate bubbles in the sample liquid entering the dispensing module; After controlling the sample liquid in the container to be filled to flow to the filling module, the method further includes: After the first bubble sensor detects that liquid has flowed through, it is confirmed that the dripping funnel has been filled with the sample liquid, and the dripping funnel is controlled to be turned upside down.
2. The sample packaging method according to claim 1, wherein: The sample liquid is transferred between the sample container and the container to be dispensed via a transfer module; the transfer module comprises a first pipeline connected between the sample container and the container to be dispensed, a first driving pump provided on the first pipeline, and a first sterile filter connected to the first pipeline; The controlling the sample liquid in the sample container to flow to the container to be dispensed comprises: Obtaining the preset packaging capacity and the total capacity of the container to be packaged from the packaging instruction; When the preset filling capacity is greater than a preset ratio of the total capacity, an emptying process is performed; the emptying process is to drive the gas in the container to be filled to flow along the first direction of the first pipeline by the first driving pump, and then be discharged from the first sterile filter; After the emptying process is completed, the sample liquid in the sample container is driven by the first driving pump to flow along the second direction of the first pipeline toward the container to be dispensed.
3. The sample packaging method according to claim 1, wherein: The controlling the sample liquid in the sample container to flow to the container to be dispensed comprises: Obtaining a first refrigeration parameter included in the subpackaging instruction; A first cooling process is performed by a refrigeration module; the refrigeration module includes a refrigeration component, a temperature control sensor, and a refrigeration plate attached to the container to be dispensed; the refrigeration module is provided with a first refrigeration space for accommodating the refrigeration plate and the container to be dispensed; the first cooling process includes: controlling the refrigeration component to cool the first refrigeration space and the refrigeration plate according to the first refrigeration parameter; A temperature set including at least one real-time temperature is detected by the temperature control sensor, and after the temperature set meets a preset temperature requirement, the sample liquid in the sample container is controlled to flow to the container to be dispensed.
4. The sample packaging method according to claim 3, wherein: The refrigeration module is further provided with a second refrigeration space for accommodating the subpackaging module and communicating with the first refrigeration space; the refrigeration module further includes a temperature transmission component provided between the first refrigeration space and the second refrigeration space; After controlling the sample liquid in the sample container to flow to the container to be dispensed, the method further includes: Obtaining a second refrigeration parameter included in the subpackaging instruction; The temperature transmission component is controlled according to the second refrigeration parameter to control the first refrigeration space and the second refrigeration space to exchange heat, so as to perform a second temperature reduction process on the second refrigeration space for accommodating the packaging module.
5. The sample packaging method according to claim 1, wherein: After controlling the sample liquid in the sample container to flow to the container to be dispensed, the method further includes: After detecting that the sample liquid flows into the container to be filled, obtaining the first mixing parameter included in the filling instruction; The sample liquid in the container to be dispensed is subjected to a first mixing process by a mixing module, wherein the mixing module includes a mixing plate and a mixing component connected to the mixing plate; the first mixing process includes: controlling the mixing component to drive the mixing plate to squeeze or tap the container to be dispensed according to the first mixing parameter.
6. The sample packaging method according to claim 5, wherein: The first mixing process of the sample liquid in the container to be dispensed by the mixing module further includes: After controlling the mixing component to drive the mixing plate to squeeze or tap the container to be dispensed according to the first mixing parameter, measuring the amount of liquid reduced in the sample container by a weighing module connected to the sample container; Determining the real-time transfer volume in the container to be filled according to the reduced amount of liquid; The first mixing parameter is adjusted according to the real-time transmission volume and a preset adjustment rule, and the mixing component is controlled to drive the mixing plate to squeeze or tap the container to be packaged according to the adjusted first mixing parameter.
7. The sample packaging method according to claim 5, wherein: After confirming that the volume of the sample liquid in the container to be filled reaches the preset filling volume, controlling the sample liquid in the container to be filled to flow to the filling module includes: measuring the amount of liquid reduction in the sample container by a weighing module connected to the sample container; Determining the real-time transfer volume in the container to be filled according to the reduced amount of liquid; After confirming, based on the real-time transmission volume, that the volume of the sample liquid in the container to be dispensed has reached a preset dispensing volume, obtaining a second mixing parameter included in the dispensing instruction; The sample liquid in the container to be dispensed is subjected to a second mixing process, wherein the second mixing process includes: controlling the mixing component to drive the mixing plate to squeeze or tap the container to be dispensed within a preset mixing time according to the second mixing parameter.
8. The sample packaging method according to claim 1, wherein: The packaging module includes at least one conveying pipeline and a plurality of packaging bags connected to the conveying pipeline; the quantitative module also includes a second driving pump arranged on the second pipeline and located between the container to be packaged and the first bubble sensor; the sample liquid is transmitted between the sample container and the container to be packaged through the transmission module; the transmission module includes a first sterile filter, a first driving pump, a first pipeline, a first branch, a second branch and a third branch; a first control valve is provided on the first branch, and a second control valve is provided on the third branch; one end of the first branch is connected to the second pipeline, and the other end is connected between the first driving pump and the container to be packaged; one end of the second branch is connected to the first sterile filter, and the other end is connected between the first driving pump and the sample container; one end of the third branch is connected to the second branch, and the other end is connected between the first control valve and the second driving pump; The method of controlling the sample liquid in the container to be filled to flow to the filling module and detecting the real-time volume of the sample liquid flowing into the filling module by a quantitative module arranged between the container to be filled and the filling module includes: The first driving pump and the second control valve are closed, and the second driving pump and the first control valve are opened simultaneously, so that the sample liquid in the container to be dispensed is driven by the driving force of the second driving pump to sequentially pass through the first pipeline, the first branch pipeline, the second pipeline, and the delivery pipeline to be dispensed into each of the dispensing bags, and the real-time volume of the sample liquid flowing into the delivery pipeline is detected by the quantitative module; The remaining unpacked capacity is determined based on the real-time capacity and the preset packing capacity. When the unpacked capacity is less than or equal to the preset pipeline capacity, the first control valve is closed and the second control valve is opened at the same time, so that the remaining pipeline in the first branch, which is located on the side of the first control valve away from the first pipeline, the second pipeline, and the remaining sample liquid in the transport pipeline are driven to be packed into each of the packing bags under the driving force of the air entering the third branch through the first sterile filter and the driving force of the second driving pump.
9. The sample packaging method according to claim 8, wherein: The packaging module further includes a second sterile filter and an air pressure sensor. The end of each delivery pipeline away from the container to be packaged is connected to the air pressure sensor through the second sterile filter; all the packaging bags are connected to the delivery pipeline through a connecting branch equipped with a packaging control valve. After determining that all the sample liquid has flowed into the subpackaging module according to the real-time capacity, confirming that the subpackaging is completed includes: After determining that all the sample liquid has flowed into the sub-packaging module according to the real-time volume, opening all the sub-packaging control valves and the second control valve, so that all the sub-packaging bags are connected to the atmosphere through the delivery pipeline, the second pipeline, the third branch pipe, and the first sterile filter, thereby balancing the air pressure in all the delivery pipelines and the sub-packaging bags; After closing all the sub-packaging control valves, performing a degassing operation on each of the sub-packaging bags in turn according to a preset degassing sequence; the degassing operation includes: opening the sub-packaging control valve corresponding to the sub-packaging bag, driving the gas in the sub-packaging bag to be discharged in sequence through the delivery pipeline, the second pipeline, the third branch pipe and the first sterile filter by the second driving pump of the quantitative module, and simultaneously obtaining the real-time pressure value in the pipeline of the delivery pipeline measured by the air pressure sensor, and confirming that the degassing operation of the sub-packaging bag is completed when the real-time pressure value in the pipeline reaches a preset pressure threshold; When the air extraction operation of all the sub-packaging bags is completed, the sub-packaging is confirmed to be completed.
10. A sample packaging system, characterized in that: It comprises a control module, a sample container, a container to be packed, a quantitative module and a packing module; the control module is connected to the quantitative module and the packing module; the control module is used to execute the sample packing method according to any one of claims 1 to 9.
11. A computer-readable storage medium storing a computer program, characterized in that: When the computer program is executed by a processor, the sample packaging method according to any one of claims 1 to 9 is implemented.
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