Sampling method, sampling equipment and controller
Cell sampling is performed through the sampling pipeline and branch connected to the centrifugal vessel, combined with the preset sampling operation and precise sampling time control, the problems of low sampling efficiency, poor accuracy and contamination in the prior art are solved, and efficient and accurate cell sampling is achieved.
Patent Information
- Application Number
- CN202311291059.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-09-28
- Publication Date
- 2025-03-28
AI Technical Summary
In the prior art, cell sampling operations are low efficiency, poor accuracy and easy to cause contamination.
The sampling is performed by the sampling pipeline and the sampling branch in communication with the centrifugal container, and the sampling operation is performed with a preset number of sampling operations to determine the extraction time required for the liquid to be sampled to reach the sampling port, and the liquid to be sampled is accurately drawn into the sampling container through the sampling branch connecting the sampling port.
Improve the efficiency and accuracy of sampling operations and reduce the risk of contamination.
Smart Images

Figure CN119715018A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of cell processing, and in particular relates to a sampling method, equipment and controller. Background Art
[0002] In the production process of cell-based drugs, cell sampling needs to be performed regularly to detect indicators such as cell activity, loss rate, and density. In the prior art, in order to complete sampling, the experimenter needs to use a sterile sampling device for manual sampling. The existing sterile sampling method generally moves the device into a sterile environment and opens the lid for sampling. Therefore, the existing sampling process requires manual operation, the operation process is cumbersome, the sampling amount cannot be accurately controlled, and frequent opening of the device cover is prone to contamination. Summary of the invention
[0003] The present invention aims at solving the problems of low efficiency, poor precision and easy contamination in the sampling operation in the prior art, and provides a sampling method, a device and a controller.
[0004] In view of the above technical problems, an embodiment of the present invention provides a sampling method, comprising:
[0005] Performing a preset number of sampling operations, the sampling operations comprising: extracting a sampled liquid from a centrifugal container located at the starting end of a sampling pipeline at a first starting time point, recording a first ending time point when it is determined that the sampled liquid flows to a detection point of the sampling pipeline, and injecting the sampled liquid in the sampling pipeline back into the centrifugal container;
[0006] Determine, according to all the first start time points and the first end time points, and the pipeline parameters of the sampling pipeline, the extraction time required for the sampled liquid to flow from the centrifugal container to the sampling port located on the sampling pipeline during the sampling operation;
[0007] After the sampling operation is performed again and lasts for the extraction time, the liquid to be sampled that just flows to the sampling port is extracted into the sampling container through the sampling branch connected to the sampling port.
[0008] A sampling device comprises a controller, a centrifugal container, a sampling pipeline connected to the centrifugal container, a sampling branch connected to the sampling pipeline through a sampling port, and a sampling container arranged on the sampling branch; the controller is connected to the centrifugal container, and the controller is used to execute the sampling method.
[0009] A controller comprises a processor and a memory, wherein the memory stores an executable program, and the processor is used to execute the executable program to implement the sampling method.
[0010] The sampling method provided by the present invention includes performing a preset number of sampling operations, and the sampling operations include: extracting a sampled liquid from a centrifugal container located at the starting end of a sampling pipeline at a first starting time point, and when determining that the sampled liquid flows to a detection point of the sampling pipeline, recording a first ending time point, and injecting the sampled liquid in the sampling pipeline back into the centrifugal container; determining, based on all first starting time points and first ending time points, and pipeline parameters of the sampling pipeline, the extraction time required for the sampled liquid to flow from the centrifugal container to a sampling port located on the sampling pipeline during the sampling operation; after performing the sampling operation again and continuing the extraction time, extracting the sampled liquid that just flows to the sampling port into the sampling container through a sampling branch connected to the sampling port. The present invention performs sampling through a sampling pipeline and a sampling branch connected to a centrifugal container, and the sampling process is not easy to cause pollution; by performing a preset number of sampling operations, the extraction time required for the sampled liquid to reach the sampling port on the sampling pipeline is determined, and then the sampled liquid is accurately extracted to the sampling port according to the extraction time, and finally the sampled liquid that just flows to the sampling port is extracted into the sampling container through the sampling branch connected to the sampling port, thereby improving the efficiency and accuracy of the sampling operation. BRIEF DESCRIPTION OF THE DRAWINGS
[0011] The present invention is further described below in conjunction with the accompanying drawings and embodiments.
[0012] Figure 1 It is a flow chart of the sampling method provided by the first embodiment of the present invention.
[0013] Figure 2 is a flow chart of a sampling method provided by the second embodiment of the present invention.
[0014] Figure 3 It is a schematic diagram of the structure of a sampling device provided in one embodiment of the present invention.
[0015] The reference numerals in the specification are as follows:
[0016] 110, sampling pipeline; 111, sampling port; 120, sampling branch; 130, sample pipeline; 140, air inlet pipeline; 150, exhaust pipeline; 210, centrifuge container; 220, sampling container; 230, sample container; 310, first drive pump; 320, second drive pump; 330, third drive pump; 410, bubble sensor; 510, first switch valve; 520, second switch valve; 610, sterile filter. DETAILED DESCRIPTION
[0017] In order to make the technical problems, technical solutions and beneficial effects solved by the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.
[0018] It should be understood that the directions or positional relationships indicated by terms such as "upper", "lower", "left", "right", "front", "back", and "middle" are based on the directions or positional relationships shown in the accompanying drawings and are only for the convenience of describing the present invention and simplifying the description. They do not indicate or imply that the device or element referred to must have a specific direction, be constructed and operated in a specific direction, and therefore should not be understood as a limitation of the present invention.
[0019] like Figure 1 As shown, an embodiment of the present invention provides a sampling method, comprising:
[0020] S100, performing a preset number of sampling operations, the sampling operation comprising: extracting the sampled liquid from the centrifugal container 210 located at the starting end of the sampling pipeline 110 at a first starting time point, recording a first ending time point when it is determined that the sampled liquid flows to the detection point of the sampling pipeline 110, and injecting the sampled liquid in the sampling pipeline 110 back into the centrifugal container 210. It can be understood that the starting end of the sampling pipeline 110 is connected to the centrifugal container 210. The sampling operation is used to obtain the duration of the sampled liquid flowing from the starting end of the sampling pipeline 110 to the detection point, that is, the time difference between the first starting time point and the first ending time point, so that the duration of the sampled liquid flowing from the centrifugal container 210 to any point between the starting end of the sampling pipeline 110 and the detection point can be determined according to the pipeline parameters of the sampling pipeline 110 in the subsequent steps. Understandably, the sampling operation can be performed by the first driving pump 310 rotating in a first direction (clockwise or counterclockwise) at a first preset high speed (preferably, the first preset high speed is 50 mL / min to 100 mL / min) and operating the extraction time, so that the sampled liquid can flow to the sampling port 111. It should be clear that in each sampling operation of the present invention, the first driving pump 310 can be used to drive the liquid in the sampling pipeline 110 to flow, and the running direction and speed of the first driving pump 310 in each sampling operation (including the sampling operation in step S100 and the subsequent sampling operation in step S300) need to be consistent, so that the running path and running speed of the liquid in the sampling pipeline 110 are consistent within the same time. The reason for performing the sampling operation for a preset number of times (the preset number of times can be set according to demand) is to eliminate the measurement error of the first start time and the first end time obtained by multiple sampling operations, so as to make the extraction time obtained in the subsequent step S200 more accurate.
[0021] S200, according to all the first start time points and the first end time points, and the pipeline parameters of the sampling pipeline 110, determine the extraction time required for the sampled liquid to flow from the centrifugal container 210 to the sampling port 111 located on the sampling pipeline 110 during the sampling operation. It can be understood that the pipeline parameters of the sampling pipeline 110 include but are not limited to the diameter of the sampling pipeline 110 (the diameter can reflect whether the diameter of the sampling pipeline is consistent), the length from the starting end to the detection point, and the position of the sampling port 111 in the sampling pipeline 110. According to the first start time points and the first end time points corresponding to all sampling operations, the actual time for the sampled liquid to flow from the centrifugal container 210 to the detection point of the sampling pipeline 110 can be accurately determined (for example, taking the average value of multiple measurements).
[0022] S300, after the sampling operation is performed again and continues for the extraction time, the liquid to be sampled that just flows to the sampling port 111 is extracted into the sampling container 220 through the sampling branch 120 connected to the sampling port 111. It can be understood that in this step, the starting step of the sampling operation again is the same as that in step S100, and the first driving pump 310 can also be used to drive the liquid in the sampling pipeline 110 to flow, and the operation direction and speed of the first driving pump 310 in the re-sampling operation are consistent with the sampling operation in step S100. The difference between the two is that the time for re-executing the sampling operation only maintains the extraction time, and the extraction time must be less than the time difference between the first end time point and the first start time point (at the same time, in the whole process of re-executing the sampling operation in this step, the subsequent extraction of the liquid in the sampling pipeline 110 will not be performed). The sample liquid is injected back into the centrifugal container 210); that is, in this step, the first driving pump 310 only needs to rotate in the first direction at a first preset high speed and operate for a extraction time, so that the sample liquid can be extracted just to the sampling port 111, which means that the re-sampling operation is considered to be completed, and at this time, the first driving pump 310 will stop working, and then continue to the next step through the second driving pump 320 on the sampling branch 120, that is, turn on the second driving pump 320, and allow the second driving pump to extract the sample liquid that just flows to the sampling port 111 from the sampling port 111 through the sampling branch 120 into the sampling container 220.
[0023] The sampling method provided by the present invention performs sampling through the sampling pipeline 110 and the sampling branch 120 connected to the centrifugal container 210, and the sampling process is not easy to cause pollution; by performing a preset number of sampling operations, the extraction time required for the sampled liquid to reach the sampling port 111 on the sampling pipeline 110 is determined, and then the sampled liquid is accurately extracted to the sampling port 111 according to the extraction time, and finally, the sampled liquid that just flows to the sampling port 111 is extracted into the sampling container 220 through the sampling branch 120 connected to the sampling port 111, thereby improving the efficiency and accuracy of the sampling operation.
[0024] like Figure 3 As shown, an embodiment of the present invention provides a sampling device, including a controller (not shown), a centrifugal container 210, a sampling pipeline 110 connected to the centrifugal container 210, a sampling branch 120 connected to the sampling pipeline 110 through a sampling port 111, and a sampling container 220 disposed on the sampling branch 120; the controller is connected to the centrifugal container 210, and the controller is used to execute the sampling method. It can be understood that the sampling port 111 is disposed on the sampling pipeline 110 and is located between the starting end and the detection point.
[0025] like Figure 3 As shown, in one embodiment, the sampling device further includes a first driving pump 310 disposed on the sampling pipeline 110 and used to drive the liquid in the sampling pipeline 110 to flow, and a bubble sensor 410 disposed on the sampling pipeline 110 and used to monitor the flow state of the liquid in real time. It can be understood that the first driving pump 310 includes but is not limited to a liquid pump for driving the liquid flow in the pipeline. Specifically, the first driving pump 310 is a peristaltic pump, so that the liquid in the pipeline can be driven to flow without contacting the liquid, thereby preventing the liquid from being contaminated.
[0026] In one embodiment, the step S100, i.e., extracting the sampled liquid from the centrifugal container 210 located at the starting end of the sampling pipeline 110 at the first starting time point, recording the first end time point when it is determined that the sampled liquid flows to the detection point of the sampling pipeline 110, and injecting the sampled liquid in the sampling pipeline 110 back into the centrifugal container 210, includes:
[0027] S110, at the first starting time point, control the first driving pump 310 to rotate in the first direction at a first preset high speed to drive the sampled liquid to flow from the centrifugal container 210 in the sampling pipeline 110 toward the bubble sensor 410 located at the detection point of the sampling pipeline 110. In this embodiment, the sampling operation is performed by the first driving pump 310, and the bubble sensor 410 is arranged at the detection point to detect whether the sampled liquid flows through the detection point. It can be understood that the detection point is provided with a bubble sensor 410, and the first driving pump 310 can be arranged on the sampling pipeline 110 and used to drive the liquid in the sampling pipeline 110 to flow. When the first driving pump 310 rotates in the first direction (clockwise or counterclockwise), the flow direction of the sampled liquid is from the centrifugal container 210 to the detection point. The first driving pump 310 extracts the sampled liquid in the centrifugal container 210 at a first preset high speed, and can cause disturbance to the sampled liquid in the centrifugal container 210 through a high-speed flow state, so as to further mix the sampled liquid in the centrifugal container 210. The first preset high speed can be set according to actual conditions. In one embodiment, the first preset high speed is 50 mL / min to 100 mL / min, so as to achieve the effect of mixing the sampled liquid under the premise of avoiding damaging the cells in the sampled liquid.
[0028] S120, after receiving the liquid flow signal sent by the bubble sensor 410, record the first end time point corresponding to the liquid flow signal, and control the first drive pump 310 to rotate in the second direction at a second preset high speed to inject the sampled liquid extracted from the sampling pipeline 110 back into the centrifugal container 210; the second direction is opposite to the first direction (the first direction is clockwise, then the second direction is counterclockwise; the first direction is counterclockwise, then the second direction is clockwise). It can be understood that the detection point is provided with a bubble sensor 410, and when the bubble sensor 410 detects liquid flow, it can send a liquid flow signal, which means that the sampled liquid has reached the detection point. The second direction is opposite to the first direction, that is, when the first drive pump 310 rotates in the second direction, the flow direction of the sampled liquid is from the detection point to the centrifugal container 210. The first driving pump 310 injects the sampled liquid in the centrifugal container 210 back at a second preset high speed, and can also disturb the sampled liquid in the centrifugal container 210 by flowing at a high speed, so as to further mix the sampled liquid in the centrifugal container 210 (in step S110, the first driving pump 310 rotates in a first direction at a first preset high speed to drive the sampled liquid to flow from the centrifugal container 210 toward the bubble sensor 410 at a high speed, and then, in step S120, the first driving pump 310 rotates in a second direction at a second preset high speed to inject the sampled liquid extracted from the sampling line 110 back into the centrifugal container, and the high-speed back-and-forth flow of the two makes the sampled liquid pumped back and forth in the sampling line 110 and the centrifugal container 210 to achieve further mixing of the sampled liquid). The second preset high speed can be set according to actual conditions, and the second preset high speed can be equal to or different from the first preset high speed. In one embodiment, the second preset high speed is 50 mL / min to 100 mL / min, so that the effect of mixing the sampled liquid can be achieved without damaging the cells in the sampled liquid. When the second preset high speed is equal to the first preset high speed, the first driving pump 310 is controlled to rotate in the second direction at the second preset high speed, so that the injection time of the sampled liquid extracted from the sampling pipeline 110 back into the centrifugal container 210 is greater than or equal to the extraction time required for the sampled liquid to flow from the centrifugal container 210 to the sampling port 111 located on the sampling pipeline 110 in step S110, thereby ensuring that the sampled liquid in the sampling pipeline 110 completely flows back to the centrifugal container 210.
[0029] In one embodiment, the step S200, i.e., determining the extraction time required for the sampled liquid to flow from the centrifugal container 210 to the sampling port 111 located on the sampling pipeline 110 during the sampling operation according to all the first start time points and the first end time points, and the pipeline parameters of the sampling pipeline 110, includes:
[0030] S210: Determine the difference between the first end time point and the first start time point corresponding to each sampling operation as the actual duration corresponding to the sampling operation. That is, each sampling operation corresponds to an actual duration.
[0031] S220, obtaining the mean duration of all the actual durations. It can be understood that when the first driving pump 310 rotates in the first direction at a first preset high speed to perform the sampling operation, the actual duration obtained by each sampling operation may have a certain error due to factors such as equipment error; therefore, the sampling operation can be performed multiple times, and the mean of all actual durations (that is, the mean duration) can be calculated after obtaining the actual duration of the multiple sampling operations, so as to reduce the error of the actual duration. The preset number of times can be set according to the actual situation. The more the preset number of times, the more accurate the mean duration of the sampling operation obtained; the fewer the preset number of times, the higher the efficiency of the sampling operation. In one embodiment, the preset number of times is 2 to 3 times, so that both efficiency and accuracy can be taken into account. In one embodiment, after determining the actual durations corresponding to all sampling operations, the actual durations that are obviously wrong are first eliminated, and then the mean duration is calculated. That is, if the absolute value of the difference between the average duration of all actual durations and a certain actual duration exceeds the preset error threshold, the actual duration is considered to be wrong. The preset error threshold can be set according to the requirements. In this embodiment, the duration average is determined based on other actual durations after the actual durations with obvious errors have been eliminated.
[0032] S230, when it is confirmed that the diameter of the entire sampling pipeline 110 is consistent according to the pipeline parameters of the sampling pipeline 110, the position ratio of the sampling port 111 in the sampling pipeline 110 is obtained from the pipeline parameters, and the position ratio represents the ratio between the first distance between the sampling port 111 and the starting end of the sampling pipeline 110 and the second distance between the sampling port 111 and the detection point of the sampling pipeline 110. It is understandable that the pipeline parameters of the sampling pipeline 110 include but are not limited to the diameter of the sampling pipeline 110 (the diameter can reflect whether the diameter of the sampling pipeline is consistent, the length from the starting end to the detection point, and the position of the sampling port 111 in the sampling pipeline 110. The position ratio of the sampling port 111 relative to the detection point in the sampling pipeline 110 can be obtained through the pipeline parameters. It is understandable that the diameter of the sampling pipeline 110 of the present invention is preferably consistent. When the diameter of the sampling pipeline 110 is not consistent, it is necessary to obtain the sampling port 111 according to the pipeline parameters. The volume ratio of the sampling port 111 in the sampling pipeline 110 is determined by the number, and the volume ratio represents the ratio between the first volume of the first section of the sampling pipeline 111 between the sampling port 111 and the starting end of the sampling pipeline 110, and the second volume of the second section of the sampling pipeline 111 between the sampling port 111 and the detection point of the sampling pipeline 110. Then, according to the mean time value and the volume ratio, the extraction time required for the sampled liquid to flow from the centrifugal container 210 to the sampling port 111 during the sampling operation is determined.
[0033] S240, according to the mean time value and the position ratio, determine the extraction time required for the sampled liquid to flow from the centrifugal container 210 to the sampling port 111 during the sampling operation. It can be understood that the extraction time required for the sampled liquid to flow from the centrifugal container 210 to the detection point and the position ratio of the sampling port 111 in the sampling pipeline 110 can be obtained by the mean time value of the sampling operation, that is, the mean time value of the sampled liquid to flow from the centrifugal container 210 to the detection point, and the position ratio of the sampling port 111 in the sampling pipeline 110.
[0034] like Figure 3 As shown, in one embodiment, the sampling device further includes a second driving pump 320 on the sampling branch 120 and used for driving the flow of liquid in the sampling branch 120 .
[0035] In one embodiment, the step S300, i.e., after the sampling operation is performed again and the extraction time is continued, the liquid to be sampled that just flows to the sampling port 111 is extracted into the sampling container 220 through the sampling branch 120 connected to the sampling port 111, includes:
[0036] S310, the sampling operation is performed again, so as to control the first driving pump 310 to rotate in the first direction at the first preset high speed at the second starting time point, thereby driving the sampled liquid to flow from the centrifugal container 210 in the sampling pipeline 110 toward the bubble sensor 410 located at the detection point of the sampling pipeline 110. The second time point is the time point at which the sampling operation is started again. The second end time point of the sampling operation is after the extraction time is calculated from the second time point, that is, after the sampling operation is performed again and the extraction time is continued, the sampling operation is deemed to be completed.
[0037] S320, after extracting the sampled liquid for the extraction time, confirm that the sampled liquid has flowed along the sampling pipeline 110 to the sampling port 111 between the centrifugal container 210 and the bubble sensor 410, control the first drive pump 310 to be closed, and control the second drive pump 320 located on the sampling branch 120 to operate in a third direction (which can be clockwise or counterclockwise) at a first preset low speed for a target sampling time, so as to extract a preset volume of the sampled liquid from the centrifugal container 210 into the sampling container 220 through the sampling branch 120 and the sampling pipeline 110 located at the front end of the sampling port 111; the first preset low speed is less than the first preset high speed and the second preset high speed. It can be understood that the sampling container 220 is arranged on the sampling branch 120, and the sampling branch 120 is provided with a second driving pump 320. When the second driving pump 320 is operated in the third direction, the liquid to be sampled flows from the sampling port 111 to the sampling container 220, so that the preset volume of the liquid to be sampled is extracted from the centrifugal container 210 into the sampling container 220 through the sampling branch 120 and the sampling pipeline 110 located at the front end of the sampling port 111. The target sampling time can be determined according to the branch pipe diameter of the sampling branch 120, the first preset low speed, and the path length from the sampling port 111 to the sampling container 220. The preset volume can be set according to user needs. In one embodiment, the preset volume is 1mL to 2mL. The first preset low speed can be set according to actual conditions. In one embodiment, the first preset low speed is 0.3mL / min to 7.5mL / min. Preferably, the first preset low speed is 0.4 mL / min, so that the sampled liquid can flow more slowly, thereby reducing the sampling error caused by the inertia of the sampled liquid during the flow process, and thus the sampled liquid can be sampled more accurately.
[0038] In one embodiment, the step S320, that is, before the second driving pump 320 located on the sampling branch 120 is controlled to rotate in the third direction at a first preset low speed for a target sampling time, further includes:
[0039] S330, determining the target sampling duration according to the branch pipe diameter of the sampling branch 120, the first preset low speed, and the path length from the sampling port 111 to the sampling container 220. It can be understood that the extraction speed of the second driving pump 320 can be obtained by the first preset low speed of the second driving pump 320, and the volume from the sampling port 111 to the sampling container 220 can be obtained by the branch pipe diameter of the sampling branch 120 and the path length from the sampling port 111 to the sampling container 220. Then, the extraction speed of the second driving pump 320 multiplied by the target sampling duration is equal to the volume from the sampling port 111 to the sampling container 220, and the target sampling duration can be obtained.
[0040] like Figure 3 As shown, in one embodiment, the sampling device also includes a sample line 130 connected to a sample container 230, and a third driving pump 330 arranged on the sample line 130 and used to drive the flow of liquid in the sample line 130; one end of the sample line 130 away from the sample container 230 is connected to the sampling line 110 and is located between the first driving pump 310 and the centrifuge container 210.
[0041] like Figure 2 As shown, in one embodiment, before the step S100, that is, before the sampling operation is performed for a preset number of times, the following steps are also included:
[0042] S400, control the third driving pump 330 located on the sample pipeline 130 to rotate, so as to transfer the sample liquid in the sample container 230 to the centrifugal container 210 through the sample pipeline 130 and at least a portion of the sampling pipeline 110; the sample pipeline 130 is connected between the sample container 230 and the sampling pipeline 110. It can be understood that the third driving pump 330 can be arranged on the sample pipeline 130 and used to drive the liquid in the sample pipeline 130 to flow. At least a portion of the sampling pipeline 110 includes a pipeline from a preset connection point (the preset connection point refers to the connection point between the sample pipeline 130 and the sampling pipeline 110, and the preset connection point can be located between the first driving pump 310 and the centrifugal container 210, so as not to interfere with the sampling port 111, and also to avoid the first driving pump 310 interfering with the sample liquid being transferred to the centrifugal container 210) to the centrifugal container 210. The third driving pump 330 may also be disposed on at least a portion of the sampling pipeline 110, so as to transport the sample liquid in the sample container 230 to the centrifugal container 210. In this step, the third driving pump 330 rotates, and its rotation direction may be clockwise or counterclockwise, as long as the sample liquid can flow from the sample container 230 to the centrifugal container 210.
[0043] S500, controlling the centrifugal container 210 to perform cell treatment on the sample liquid to generate a sample liquid in the centrifugal container 210. It can be understood that the cell treatment includes one or more of cell separation, cell washing and cell culture. The sample liquid is the original liquid to be cell treated, including but not limited to one or more of blood or PBMC (peripheral blood mononuclear cell) liquid after incubation. The sample liquid generates the sample liquid after the cell treatment in the centrifugal container 210.
[0044] like Figure 3 As shown, in one embodiment, the sampling device also includes an intake line 140 connected to the sample line 130 and located between the sample container 230 and the third drive pump 330, a first switch valve 510 arranged on the intake line 140 and used to control the on-off of the intake line 140, a sterile filter 610 arranged on the intake line 140 and used to filter the gas flowing through, an exhaust line 150 connected to the sampling line 110 and located between the centrifugal container 210 and the first drive pump 310, and a second switch valve 520 arranged on the exhaust line 150 and used to control the on-off of the exhaust line 150.
[0045] In one embodiment, after the step S400, that is, after the third driving pump 330 on the sample pipeline 130 is controlled to rotate so as to transport the sample liquid in the sample container 230 to the centrifugal container 210 through the sample pipeline 130 and the sampling pipeline 110, the method further includes:
[0046] S600, opening the first switch valve 510 and the second switch valve 520, controlling the third driving pump 330 to enter the gas through the intake pipe 140, and allowing the entering gas to sequentially pass through the sample pipe 130, at least a portion of the sampling pipe 110, and the exhaust pipe 150, so as to discharge the residual liquid in the sample pipe 130 and the sampling pipe 110 through the exhaust pipe 150; one end of the intake pipe 140 is connected to the atmosphere (for example, connected to the atmosphere through the sterile filter 610); The first switch valve 510 is provided on the air intake pipeline 140 and is used to control the connection between the air intake pipeline 140 and the atmosphere; one end of the exhaust pipeline 150 is connected to the atmosphere (for example, connected to the atmosphere through a sterile air filter), and the other end is connected to the sampling pipeline 110, and the second switch valve 520 is provided on the exhaust pipeline 150 and is used to control the connection between the exhaust pipeline 150 and the atmosphere. Wherein, at least a part of the sampling pipeline 110 includes a pipeline from a preset connection point to a connection point between the sampling pipeline 110 and the exhaust pipeline 150. It is understandable that after liquid flows through the sample line 130 and at least a portion of the sampling line 110, liquid may remain in the sample line 130 and the sampling line 110. Therefore, in order to prevent the residual liquid (such as sample liquid, etc.) in the sampling line 110 from mixing into the liquid to be sampled, thereby affecting the composition of the liquid to be sampled, or causing measurement and sampling errors, etc., in this embodiment, the gas enters through the air intake line 140, and the incoming gas is made to pass through the sample line 130, at least a portion of the sampling line 110 and the exhaust line 150 in sequence, so that the residual liquid in the sample line 130 and the sampling line 110 can be discharged through the exhaust line 150, thereby avoiding the residue of impurities.
[0047] In one embodiment, before step S100, that is, before performing the sampling operation for a preset number of times, the process further includes:
[0048] S700, control the centrifugal container 210 to perform a mixing operation with a preset mixing number of times to mix the sampled liquid in the centrifugal container 210; the mixing operation includes: controlling the centrifugal container 210 to rotate in a first rotation direction at a first preset mixing speed for a first preset time, and then controlling the centrifugal container 210 to rotate in a second rotation direction at a second preset mixing speed for a second preset time; the second rotation direction is opposite to the first rotation direction. It can be understood that the first preset mixing speed and the second preset mixing speed can be set according to actual conditions. The first preset mixing speed can be equal to the second preset mixing speed, and the first preset mixing speed can also be different from the second preset mixing speed. In one embodiment, the first preset mixing speed and the second preset mixing speed are both 300rpm (Revolutions Per minute, revolutions per minute). The first preset duration and the second preset duration can be set according to actual conditions. In one embodiment, the first preset duration is 1 second to 10 seconds, and the second preset duration is 1 second to 10 seconds. The first preset duration may be equal to the second preset duration, or may be different from the second preset duration. The total duration of the mixing operation (ie, the sum of all the first preset durations and all the second preset durations) is 20 seconds to 200 seconds.
[0049] In one embodiment, the sampling container 220 is a dripping funnel located on the sampling branch 120; the dripping funnel is provided with a recessed space for accommodating the sampled liquid. After the step S300, that is, after the sampled liquid flowing to the sampling port 111 is extracted into the sampling container 220 through the sampling branch 120 connected to the sampling port 111, the following steps are further included:
[0050] S340, after confirming that the liquid to be sampled in the recessed space of the horizontally placed drip bucket has reached a preset volume, control the second driving pump 320 located on the sampling branch 120 to rotate in the fourth direction at a second preset low speed for a target reflux time, so as to inject the liquid to be sampled in the sampling branch 120 except the liquid to be sampled in the recessed space and the liquid to be sampled in the sampling pipeline 110 back into the centrifugal container 210; the second preset low speed is less than the first preset high speed; the fourth direction is opposite to the third direction (if the third direction is clockwise, the fourth direction is counterclockwise; if the third direction is counterclockwise, the fourth direction is clockwise). It can be understood that there is a preset distance between the bottom of the recessed space and the connection point between the drip bucket and the sampling branch 120, and the preset distance can be set according to the preset volume of the liquid to be sampled, that is, after the preset volume of the liquid to be sampled is in the recessed space, the liquid to be sampled will not submerge the connection point between the drip bucket and the sampling branch 120. Therefore, in this embodiment, the second driving pump 320 can be controlled to deliver air to the connection point between the drip bucket and the sampling branch 120 (at this time, the end of the sampling branch 120 away from the sampling port 111 will be connected to the atmosphere through a sterile air filter, and the second driving pump is arranged between the sampling port 111 and the sterile air filter), so that the liquid to be sampled in the sampling branch 120 except the recessed space and the liquid to be sampled in the sampling pipeline 110 are injected back into the centrifugal container 210 without affecting the liquid to be sampled in the recessed space. Further, the second preset low speed can be set according to actual conditions. Further, the second preset low speed can be greater than or equal to the first preset low speed so that the liquid to be sampled in the sampling branch 120 except the recessed space and the liquid to be sampled in the sampling pipeline 110 are injected back into the centrifugal container 210 more quickly, thereby avoiding the waste of the liquid to be sampled.
[0051] S350, heat-seal the sampling branch 120 at a preset position point between the drip bucket and the sampling port 111 to obtain a preset volume of the liquid to be sampled that is independently sealed in the drip bucket. It can be understood that multiple drip buckets can be set on the sampling branch 120. After each drip bucket obtains the liquid to be sampled that has reached a preset volume according to user needs, the sampling branch 120 can be heat-sealed at a preset position point between the drip bucket and the sampling port 111 to obtain a preset volume of the liquid to be sampled that is independently sealed in the drip bucket, thereby achieving the beneficial effect of multiple sampling and further improving the sampling efficiency.
[0052] In one embodiment, the step S340, i.e., after confirming that the sampled liquid in the recessed space of the horizontally placed drip bucket has reached a preset volume, controlling the second driving pump 320 located on the sampling branch 120 to rotate in the fourth direction at a second preset low speed for a target reflux time, further includes:
[0053] S360, control the drip bucket to be tilted so that the first end of the drip bucket close to the sampling port 111 is located above the second end away from the sampling port 111. In this embodiment, the recessed space is larger than the preset volume, that is, after the preset volume of the liquid to be sampled is in the recessed space and the first end of the drip bucket close to the sampling port 111 is located above the second end away from the sampling port 111, the liquid to be sampled will not submerge the first end of the drip bucket close to the sampling port 111. Therefore, the air transported into the drip bucket by the second driving pump 320 reaches the first end of the drip bucket in the form of bubbles and will not drive the liquid to be sampled in the recessed space to rise to the first end (and the liquid to be sampled will be located at a position corresponding to the second end below the drip bucket), so that the other liquid to be sampled in the sampling branch 120 except the liquid to be sampled in the recessed space and the liquid to be sampled in the sampling pipeline 110 can be further injected into the centrifuge container 210 through the second driving pump 320 without affecting the liquid to be sampled in the recessed space.
[0054] It can be understood that the above sampling method is not limited to that described in the above embodiment. The specific configuration of the sampling method of the present invention corresponds to the above sampling device one by one, and will not be repeated here.
[0055] An embodiment of the present invention further provides a controller, the controller comprising a processor and a memory, the memory storing an executable program, and the processor being configured to execute the executable program to implement the sampling method.
[0056] The specific configuration of the controller of the present invention corresponds to the above-mentioned sampling method one by one, and will not be described in detail here. Each module in the above-mentioned controller can be implemented in whole or in part by software, hardware, and a combination thereof. Each of the above-mentioned modules can be embedded in or independent of the controller in the form of hardware, or can be stored in the controller in the form of software, so that the controller can call and execute the operations corresponding to each of the above modules.
[0057] An embodiment of the present invention further provides a computer-readable storage medium, wherein the computer-readable storage medium stores a computer program, and the computer program implements the above sampling method when executed by a processor.
[0058] Those skilled in the art can understand that all or part of the processes in the above-mentioned embodiments can be implemented by instructing related hardware through computer-readable instructions. The computer-readable instructions can be stored in a non-volatile readable storage medium or a volatile readable storage medium. When the computer-readable instructions are executed, they 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 by the present invention 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 (Synchlink) DRAM (SLDRAM), memory bus (Rambus) direct RAM (RDRAM), direct memory bus dynamic RAM (DRDRAM), and memory bus dynamic RAM (RDRAM), etc.
[0059] The above are merely embodiments of the sampling method, device and controller of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.
Claims
1. A sampling method, characterized in that: include: Performing a preset number of sampling operations, the sampling operations comprising: extracting a sampled liquid from a centrifugal container located at the starting end of a sampling pipeline at a first starting time point, recording a first ending time point when it is determined that the sampled liquid flows to a detection point of the sampling pipeline, and injecting the sampled liquid in the sampling pipeline back into the centrifugal container; Determine, according to all the first start time points and the first end time points, and the pipeline parameters of the sampling pipeline, the extraction time required for the sampled liquid to flow from the centrifugal container to the sampling port located on the sampling pipeline during the sampling operation; After the sampling operation is performed again and lasts for the extraction time, the liquid to be sampled that just flows to the sampling port is extracted into the sampling container through the sampling branch connected to the sampling port.
2. The sampling method according to claim 1, characterized in that: The step of determining, based on all of the first start time points and the first end time points, and the pipeline parameters of the sampling pipeline, the extraction time required for the sampled liquid to flow from the centrifugal container to the sampling port located on the sampling pipeline during the sampling operation, includes: Determine the difference between the first end time point and the first start time point corresponding to each sampling operation as the actual duration corresponding to the sampling operation; Obtaining the average duration of all the actual durations; When it is confirmed that the diameter of the entire sampling pipeline is consistent according to the pipeline parameters of the sampling pipeline, the position ratio of the sampling port in the sampling pipeline is obtained from the pipeline parameters, and the position ratio represents the ratio between a first distance between the sampling port and the starting end of the sampling pipeline and a second distance between the sampling port and the detection point of the sampling pipeline; The extraction time required for the sampled liquid to flow from the centrifugal container to the sampling port during the sampling operation is determined according to the time mean and the position ratio.
3. The sampling method according to claim 1, characterized in that: The method comprises extracting the sampled liquid from the centrifugal container at the starting end of the sampling pipeline at a first starting time point, recording the first ending time point when it is determined that the sampled liquid flows to the detection point of the sampling pipeline, and injecting the sampled liquid in the sampling pipeline back into the centrifugal container, comprising: At the first starting time point, controlling the first driving pump to rotate in a first direction at a first preset high speed to drive the sampled liquid to flow from the centrifugal container in the sampling pipeline toward the bubble sensor located at the detection point of the sampling pipeline; After receiving the liquid flow signal sent by the bubble sensor, the first end time point corresponding to the liquid flow signal is recorded, and the first drive pump is controlled to rotate in a second direction at a second preset high speed to inject the sampled liquid extracted from the sampling pipeline back into the centrifugal container; the second direction is opposite to the first direction.
4. The sampling method according to claim 3, characterized in that: After the sampling operation is performed again and lasts for the extraction time, the liquid to be sampled that just flows to the sampling port is extracted into the sampling container through the sampling branch connected to the sampling port, including: The sampling operation is performed again to control the first driving pump to rotate in the first direction at the first preset high speed at a second starting time point, thereby driving the sampled liquid to flow from the centrifugal container in the sampling pipeline toward the bubble sensor located at the detection point of the sampling pipeline; After extracting the sampled liquid for the extraction time, confirming that the sampled liquid has flowed along the sampling pipeline to the sampling port located between the centrifugal container and the bubble sensor, the first driving pump is controlled to be closed, and the second driving pump located on the sampling branch is controlled to operate in a third direction at a first preset low speed for a target sampling time, so as to extract a preset volume of the sampled liquid from the centrifugal container into the sampling container through the sampling branch and the sampling pipeline located at the front end of the sampling port; the first preset low speed is less than the first preset high speed and the second preset high speed.
5. The sampling method according to claim 1, characterized in that: Before performing the sampling operation for a preset number of times, the method further includes: Controlling the third driving pump located on the sample pipeline to rotate so as to transport the sample liquid in the sample container to the centrifugal container through the sample pipeline and at least a portion of the sampling pipeline; the sample pipeline is connected between the sample container and the sampling pipeline; The centrifugal container is controlled to perform cell treatment on the sample liquid to obtain the liquid to be sampled in the centrifugal container.
6. The sampling method according to claim 5, characterized in that: After the third driving pump on the sample pipeline is controlled to rotate so as to transport the sample liquid in the sample container to the centrifugal container through the sample pipeline and the sampling pipeline, the method further includes: Open the first switch valve and the second switch valve, control the third drive pump to enter the gas through the intake pipe, and make the incoming gas pass through the sample pipe, at least a part of the sampling pipe and the exhaust pipe in sequence, so as to discharge the residual liquid in the sample pipe and the sampling pipe through the exhaust pipe; one end of the intake pipe is connected to the atmosphere, and the other end is connected between the sample container and the third drive pump, the first switch valve is arranged on the intake pipe and is used to control the connection between the intake pipe and the atmosphere; one end of the exhaust pipe is connected to the atmosphere, and the other end is connected to the sampling pipe, and the second switch valve is arranged on the exhaust pipe and is used to control the connection between the exhaust pipe and the atmosphere.
7. The sampling method according to any one of claims 1 to 6, characterized in that: The sampling container is a dripping funnel located on the sampling branch; After the liquid to be sampled that flows to the sampling port is extracted into the sampling container through the sampling branch connected to the sampling port, the method further comprises: After confirming that the liquid to be sampled in the recessed space of the horizontally placed drip bucket has reached a preset volume, controlling the second driving pump located on the sampling branch to rotate in a fourth direction at a second preset low speed for a target reflux time, so as to inject the liquid to be sampled in the sampling branch except the liquid in the recessed space and the liquid to be sampled in the sampling pipeline back into the centrifugal container; the second preset low speed is less than the first preset high speed; the fourth direction is opposite to the third direction; A heat sealing operation is performed on a preset position point of the sampling branch between the dripping funnel and the sampling port to obtain a preset volume of the liquid to be sampled which is independently sealed in the dripping funnel.
8. The sampling method according to claim 7, characterized in that: After confirming that the sampled liquid in the recessed space of the horizontally placed drip bucket has reached a preset volume, controlling the second driving pump on the sampling branch to rotate in the fourth direction at a second preset low speed for a target reflux time, the method further includes: The drip bucket is controlled to be tilted so that a first end of the drip bucket close to the sampling port is located above a second end away from the sampling port.
9. A sampling device, characterized in that: It includes a controller, a centrifugal container, a sampling pipeline connected to the centrifugal container, a sampling branch connected to the sampling pipeline through a sampling port, and a sampling container arranged on the sampling branch; the controller is connected to the centrifugal container, and the controller is used to execute the sampling method described in any one of claims 1 to 8.
10. A controller, characterized in that: The controller includes a processor and a memory, wherein the memory stores an executable program, and the processor is configured to execute the executable program to implement the sampling method according to any one of claims 1 to 8.