Method for cleaning a sampling line of a sample processing device, line system for performing the method and sample processing

Abstract

The invention relates to a method for cleaning a sampling pipeline of a sample processing instrument, and the sampling pipeline is communicated with a flow type pool of the sample processing instrument to a sample source. The method includes: a forward flushing step of flushing the sampling line in a first direction using a sheath fluid or a cleaning fluid different from the sheath fluid supplied through a cleaning fluid line; and / or a reverse flushing step of flushing the sampling pipeline by using the sheath fluid or the cleaning fluid along a second direction opposite to the first direction. The invention further provides a pipeline system for executing the method and a sample processing instrument comprising the pipeline system. According to the method, the pipeline system and the sample treatment instrument disclosed by the invention, the cleaning efficiency and the cleaning effect are remarkably improved.

Description

Technical Field

[0001] The present disclosure relates to a sample processing instrument such as a flow cell sorter / analyzer and a fluid pipeline system thereof, as well as a method for cleaning the pipeline system. Background Art

[0002] The contents in this section merely provide background information related to the present disclosure and may not constitute prior art.

[0003] Sample processing instruments are generally used to analyze liquid samples including small suspended particles (e.g., biological particles, non-biological particles) or cells and / or to sort the particles or cells therein. During operation of some known sample processing instruments, the sample is transported to a flow cell by a pump for detection or sorting.

[0004] After the sample analysis or sorting is completed, the sample (especially some particles in the sample) will remain in the pump and / or pipeline. Therefore, the pump and / or pipeline need to be cleaned for the processing of the next sample. For example, microspheres (beads), cells, viruses or extracellular vesicles, especially nanoparticles contained in the sample are easily captured and aggregated in the fluid pipeline of the sample processing instrument, and are difficult to clean. Summary of the invention

[0005]

[0010] This section provides a general summary of the disclosure, and is not a comprehensive disclosure of its full scope or all of its features.

[0006] In existing sample processing instruments, only sheath fluid is used or the fluid pipeline is cleaned in only one direction. When cleaning nanoparticles, existing sample processing instruments usually require a long cleaning time, for example, 30 minutes of cleaning to reduce the virus residue rate to less than 1.0%, and 40 seconds of cleaning to reduce the microsphere residue rate to less than 0.1% for 3-micron microspheres, thus consuming more cleaning fluid and negatively affecting the throughput of the instrument; on the other hand, it may be difficult to achieve the required residue rate (i.e., cleaning requirement) for nanoparticles, for example, less than 0.1%, thereby affecting the detection accuracy of the instrument.

[0007] In addition, the existing sample processing instrument needs to manually replace the sample container or sampling line with a container or cleaning line containing a cleaning fluid different from the sheath fluid, and then use the cleaning fluid to clean the fluid line. Sometimes, it may be necessary to replace the sample container / sampling line with the cleaning fluid container / cleaning line multiple times. Therefore, the cleaning process of the sample processing instrument is time-consuming, inefficient, and may cause incorrect operations.

[0008] In view of the above-mentioned problems of the existing sample processing instrument, an object of the present disclosure is to provide an improved piping system or an improved cleaning method for the sample processing instrument, so that the cleaning process is more effective or efficient.

[0009] According to one aspect of the present disclosure, a method for cleaning a sampling pipeline of a sample processing instrument is provided, wherein the sampling pipeline connects a flow cell of the sample processing instrument to a sample source. The method comprises: a forward flushing step of flushing the sampling pipeline along a first direction using a sheath fluid or a cleaning fluid different from the sheath fluid supplied via a cleaning fluid pipeline; and / or a reverse flushing step of flushing the sampling pipeline along a second direction opposite to the first direction using the sheath fluid or the cleaning fluid.

[0010] In some embodiments according to the present disclosure, the method includes: performing the forward flushing step and the reverse flushing step alternately for a predetermined number of times.

[0011] In some embodiments according to the present disclosure, the method includes: connecting a sheath fluid to a flow cell opening and / or a sample opening of the sampling pipeline.

[0012] In some embodiments according to the present disclosure, a cleaning station is provided at the sample opening of the sampling pipeline, and the cleaning station has a sheath liquid port for supplying sheath liquid and a discharge port for discharging waste liquid; and / or the flow cell has a sheath liquid port for supplying sheath liquid and a discharge port for discharging waste liquid.

[0013] In some embodiments according to the present disclosure, the method includes: selectively using the sheath fluid or the cleaning fluid to clean the sampling pipeline by means of a switching device disposed in the cleaning fluid pipeline and the sampling pipeline.

[0014] In some embodiments according to the present disclosure, the switching device is automatically controlled.

[0015] In some embodiments according to the present disclosure, the method includes: providing a peristaltic pump, and performing a forward flushing step or a reverse flushing step by controlling a rotation direction of a roller of the peristaltic pump.

[0016] In some embodiments according to the present disclosure, the method includes: providing a piston pump, and alternately performing a forward flushing step and a reverse flushing step by reciprocating motion of a piston of the piston pump.

[0017] According to another aspect of the present disclosure, a pipeline system for executing the above method is provided.

[0018] In some embodiments according to the present disclosure, the pipeline system includes a piston pump and a switching device disposed in the sampling pipeline. The switching device is configured to selectively connect the piston pump to a sample source or a flow cell. The piston pump is configured to alternately perform the forward flushing step and the reverse flushing step by reciprocating motion of its piston.

[0019] In some embodiments according to the present disclosure, the switching device is a rotary valve.

[0020] In some embodiments according to the present disclosure, the pipeline system includes a peristaltic pump, and the peristaltic pump is configured to perform a forward flushing step or a reverse flushing step by controlling a rotation direction of a roller of the peristaltic pump.

[0021] In some embodiments according to the present disclosure, the pipeline system includes a switching device disposed in the sampling pipeline and a cleaning fluid pipeline for supplying a cleaning fluid different from the sheath fluid. The switching device is configured to selectively supply the sample, the sheath fluid or the cleaning fluid.

[0022] In some embodiments according to the present disclosure, the switching device is a reversing valve or a switch valve.

[0023] In some embodiments according to the present disclosure, the switching device is a switching device that can be automatically controlled.

[0024] In some embodiments according to the present disclosure, a cleaning station is provided at the sample opening of the sampling pipeline, and the cleaning station has a sheath liquid port for supplying sheath liquid and a discharge port for discharging waste liquid; and / or.

[0025] In some embodiments according to the present disclosure, the flow cell has a sheath fluid port for supplying a sheath fluid and a discharge port for discharging a waste fluid.

[0026] According to yet another aspect of the present disclosure, a sample processing instrument including the peristaltic pump tubing system is provided.

[0027] According to the above-mentioned pipeline system, method and sample processing instrument disclosed in the present invention, the cleaning efficiency and cleaning effect can be significantly improved, thereby increasing the throughput of the instrument.

[0028] For some examples, the reciprocating cleaning method can significantly improve the cleaning efficiency and cleaning effect.

[0029] For some examples, reciprocating cleaning is performed by using a piston pump, which further improves the cleaning efficiency and cleaning effect.

[0030] In addition, for some examples, by setting the cleaning liquid pipeline and controlling the position of the switching device, the supply of the cleaning liquid can be easily controlled. There is no need to manually replace the sample source with a cleaning liquid source containing the cleaning liquid, thereby saving the time required for replacement, improving the efficiency of the sample processing instrument, and avoiding erroneous operations caused by manual replacement.

[0031] The switching device can be automatically controlled, thereby further improving the cleaning efficiency of the sample processing instrument.

[0032] The sampling pipeline can be used to supply samples for processing and also to supply sheath fluid for cleaning, thereby simplifying the pipeline system and thus simplifying the structure of the sample processing instrument.

[0033] The above and other objects, features and advantages of the present disclosure will be more fully understood from the detailed description given hereinafter and the accompanying drawings which are given by way of illustration only and thus are not to be considered as limiting the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] The features and advantages of one or more embodiments of the present disclosure will become more easily understood through the following description with reference to the accompanying drawings, in which:

[0035] Figure 1A and Figure 1B is a schematic diagram of a peristaltic pump piping system according to an embodiment of the present disclosure;

[0036] Figure 2 is a schematic diagram of a peristaltic pump piping system according to another embodiment of the present disclosure;

[0037] Figure 3 is a schematic diagram of a peristaltic pump piping system according to another embodiment of the present disclosure;

[0038] Figure 4 is a schematic diagram of a peristaltic pump piping system according to yet another embodiment of the present disclosure;

[0039] Figure 5A It is a flow chart of a method for cleaning a sampling pipeline of a sample processing instrument according to an embodiment of the present disclosure;

[0040] Figure 5B A flowchart of another method for cleaning a sampling pipeline of a sample processing instrument according to another embodiment of the present disclosure; and

[0041] Figure 6 is a schematic diagram of a piston pump piping system according to another embodiment of the present disclosure. DETAILED DESCRIPTION

[0042] The present disclosure will be described in detail below by way of exemplary embodiments with reference to the accompanying drawings. In several figures, similar reference numerals represent similar parts and assemblies. The following detailed description of the present disclosure is for illustrative purposes only and is by no means a limitation of the present disclosure and its application or use. The embodiments described in this specification are not exhaustive, but are only some of a plurality of possible embodiments. The exemplary embodiments may be implemented in many different forms and should not be construed as limiting the scope of the present disclosure. In some exemplary embodiments, well-known processes, well-known device structures, and well-known technologies may not be described in detail.

[0043] The following will refer to Figure 1A and Figure 1B The tubing system 10 with a peristaltic pump according to an embodiment of the present disclosure is described below. The peristaltic pump tubing system 10 is used to supply fluid (such as sample, sheath fluid or cleaning fluid) to a flow cell FC of a sample processing instrument (not shown) or to discharge fluid from the flow cell FC.

[0044] like Figure 1A and Figure 1B As shown, the peristaltic pump pipeline system 10 includes a peristaltic pump 11 , a sampling pipeline 12 , a switching device 13 and a cleaning liquid pipeline 14 .

[0045] The sampling line 12 connects the sample source 1 containing the sample to the flow cell FC. The sample source 1 can be, for example, a container, a bottle or a reagent kit for holding the sample. The sample contains small suspended particles to be detected or sorted in the flow cell FC, for example, biological particles such as extracellular vesicles, or non-biological particles such as beads. The flow cell FC has a sample port P1 for receiving the sampling line 12, a sheath liquid port P2 connected to the sheath liquid line for supplying sheath liquid, a detection port P3 for outputting the sample wrapped by the sheath liquid for detection, and a discharge port P4 for discharging waste liquid (for example, unused remaining fluid or cleaning fluid for cleaning the flow cell) out of the flow cell FC.

[0046] One end of the sampling line 12 connected to the flow cell FC has a flow cell opening 121, and the other end of the sampling line 12 connected to the sample source 1 has a sample opening 122. A cleaning station 17 is provided at the sample opening 122 of the sampling line 12. The cleaning station 17 has a sheath liquid port 171 for supplying a sheath liquid and a discharge port 172 for discharging a waste liquid. When the sampling line 12 is moved so that the sample opening 122 is in the sample source 1, the sample in the sample source 1 can be sucked into the flow cell FC via the sampling line 12. When the sampling line 12 is moved so that the sample opening 122 is in the cleaning station 17, the sheath liquid supplied via the sheath liquid port 171 can be sucked into the sampling line 12, or the fluid in the sampling line 12 can be discharged via the discharge port 172.

[0047] The peristaltic pump 11 is disposed in the sampling pipeline 12 and is used to pump the sample in the sample source 1 into the flow cell FC via the sampling pipeline 12 so as to process (eg, detect or sort) particles in the sample in the flow cell FC.

[0048] The cleaning liquid pipeline 14 connects the cleaning liquid source 2 to the peristaltic pump 11. The cleaning liquid source 2 is, for example, a container, a tank or a barrel containing the cleaning liquid. The "cleaning liquid" described herein refers to a solution or solvent used to rinse the sample other than the sheath fluid. The cleaning liquid can be selected or changed according to the sample.

[0049] The switching device 13 is configured to control the on-off of the cleaning liquid pipeline 14 and the on-off of the sampling pipeline 12. The supply of different fluids is controlled by controlling the on-off of the cleaning liquid pipeline 14 and the on-off of the sampling pipeline 12. When the sampling pipeline 12 is connected and the cleaning liquid pipeline 14 is disconnected, the fluid (for example, the sample in the sample source or the fluid in the flow cell) is allowed to flow between the sample source 1 and the flow cell FC via the sampling pipeline 12, while preventing the cleaning liquid from flowing through the cleaning liquid pipeline 14. When the cleaning liquid pipeline 14 is connected and the sampling pipeline 12 is disconnected, the cleaning liquid in the cleaning liquid source 2 is allowed to be supplied to the peristaltic pump 11, while preventing the fluid from flowing from the sample source 1 to the flow cell FC or from the flow cell FC to the sample source 1. That is, the switching device 13 is used to control the connection of one of the cleaning liquid pipeline 14 and the sampling pipeline 12, while controlling the disconnection of the other of the cleaning liquid pipeline 14 and the sampling pipeline 12.

[0050] The switching device 13 may be an automatically controlled switching device, for example, an electronically controlled or electromagnetically controlled switching device.

[0051] exist Figure 1A and Figure 1B In the example shown, the switching device 13 is a three-way reversing valve 16 disposed between the peristaltic pump 11, the cleaning liquid source 2, and the flow cell FC. The reversing valve 16 can switch between a first position that allows communication between the sample source 1 and the flow cell FC and a second position that allows communication between the peristaltic pump 11 and the cleaning liquid source 2. The reversing valve 16 has a first port 16a connected to the peristaltic pump 11, a second port 16b connected to the cleaning liquid source 2, and a third port 16c connected to the flow cell FC. The reversing valve 16 can connect the first port 16a with the third port 16c (i.e., connect the sample source 1 to the flow cell FC, as shown in FIG. 1 ). Figure 1A The device can be switched between a first position (as shown) and a second position in which the first port 16a is connected to the second port 16b (ie, the peristaltic pump 11 is connected to the cleaning liquid source 2).

[0052] When Figure 1AAs shown, when the sample source 1 is connected to the flow cell FC, the peristaltic pump 11 can rotate in one direction (for example, counterclockwise), thereby pumping the sample in the sample source 1 into the flow cell FC for detection or sorting of the sample, etc., or supplying the sheath fluid in the cleaning station 17 at the sample source 1 to the flow cell FC so as to use the sheath fluid to clean the sampling line 12.

[0053] When Figure 1A When the sample source 1 is connected to the flow cell FC, the peristaltic pump 11 can rotate in another opposite direction (e.g., clockwise), thereby causing the fluid in the flow cell FC to flow toward the sample source 1. For example, by rotating the peristaltic pump 11 clockwise, the sheath liquid in the flow cell FC flows through the sampling line 12 and reaches the cleaning station 17 at the sample source 1, thereby performing sheath liquid cleaning on the peristaltic pump 11 and the sampling line 12. The sheath liquid cleaning waste liquid can flow to the cleaning station 17, and then can be discharged from the waste liquid pump ( Figure 1A The liquid is discharged through the discharge port 172 under the action of (not shown).

[0054] When Figure 1B When the peristaltic pump 11 is connected to the cleaning liquid source 2, the peristaltic pump 11 can rotate clockwise, thereby supplying the cleaning liquid in the cleaning liquid source 2 to the peristaltic pump 11 and flowing through the peristaltic pump 11, thereby cleaning the peristaltic pump 11 with the cleaning liquid. The waste liquid for cleaning the peristaltic pump 11 can flow to the cleaning station 17 through the section of the sampling line 12 from the peristaltic pump 11 to the sample source 1, and then can be discharged at the waste liquid pump ( Figure 1B In addition, the peristaltic pump 11 can rotate counterclockwise to draw the sheath liquid in the cleaning station 17 into the sampling line 12 so as to use the sheath liquid to clean the section of the sampling line 12 from the sample opening 122 to the reversing valve 16.

[0055] According to the peristaltic pump pipeline system 10, the on-off of the cleaning liquid pipeline 14 can be easily controlled by setting the position of the cleaning liquid pipeline 14 and controlling the switching device 13. Therefore, it is not necessary to manually replace the sample source with a cleaning liquid source containing cleaning liquid, thereby saving the time required for replacement, improving the efficiency of the sample processing instrument, and avoiding erroneous operations caused by manual replacement.

[0056] The following will refer to Figure 2 A peristaltic pump piping system 20 according to another embodiment of the present disclosure is described. Figure 2 As shown, the peristaltic pump pipeline system 20 includes a peristaltic pump 21 , a sampling pipeline 22 , a cleaning liquid pipeline 24 and a switching device 13 . Figure 2 The peristaltic pump piping system 20 shown differs from the peristaltic pump piping system 10 shown in FIG. 1 in that the position of the switching device 13 is different.

[0057] like Figure 2 As shown, the switching device 13 is a three-way reversing valve 26, which is arranged between the peristaltic pump 21, the cleaning liquid source 2 and the sample source 1. The three-way reversing valve 26 has a first port 26a connected to the peristaltic pump 21, a second port 26b connected to the cleaning liquid source 2 and a third port 26c connected to the sample source 1. The three-way reversing valve 26 can make the first port 26a communicate with the third port 26c (that is, make the sample source 1 communicate with the flow cell FC, as shown in FIG. Figure 2 The device can be switched between a first position (as shown) and a second position in which the first port 26a is connected to the second port 26b (ie, the peristaltic pump 21 is connected to the cleaning liquid source 2).

[0058] When Figure 2 As shown, when the sample source 1 is connected to the flow cell FC, the peristaltic pump 21 can rotate counterclockwise to pump the sample in the sample source 1 into the flow cell FC for detection or sorting of the sample, or to draw the sheath fluid in the cleaning station 27 into the sampling line 22 to clean the sampling line 22 with the sheath fluid.

[0059] When Figure 2 When the sample source 1 is connected to the flow cell FC, the peristaltic pump 21 can rotate in a clockwise direction, so that the sheath liquid in the flow cell FC flows to the sample source 1, so that the sheath liquid is used to clean the peristaltic pump 21 and the sampling pipeline 22. The sheath liquid cleaning waste liquid can flow to the cleaning station 27 located at the sample source 1, and then can be discharged under the action of the waste liquid pump 28.

[0060] When the peristaltic pump 21 is connected to the cleaning liquid source 2, the peristaltic pump 21 can rotate counterclockwise, thereby supplying the cleaning liquid in the cleaning liquid source 2 to the peristaltic pump 21 and flowing through the peristaltic pump 21, thereby cleaning the peristaltic pump 21 with the cleaning liquid. The waste liquid for cleaning the peristaltic pump 21 can flow into the flow cell FC via the section of the sampling line 22 from the flow cell FC to the peristaltic pump 21, and then be discharged through the discharge port P4 connected to the flow cell FC.

[0061] The following will refer to Figure 3 A peristaltic pump piping system 30 according to another embodiment of the present disclosure is described. Figure 3 As shown, the peristaltic pump pipeline system 30 includes a peristaltic pump 31 , a sampling pipeline 32 , a cleaning liquid pipeline 34 and a switching device 13 . Figure 3 The peristaltic pump line system 30 shown differs from the peristaltic pump line system 10 shown in FIG. 1 in the configuration of the switching device 13 .

[0062] like Figure 3 As shown, the switching device 13 includes a first switch valve 35 arranged in the sampling pipeline 32 and a second switch valve 36 arranged in the cleaning liquid pipeline 34 .

[0063] When the first switch valve 35 is closed to connect the sample source 1 to the flow cell FC, the peristaltic pump 31 can rotate counterclockwise to pump the sample in the sample source 1 into the flow cell FC for detection or sorting of the sample, or to draw the sheath fluid in the cleaning station into the sampling line 32 to clean the sampling line 32 with the sheath fluid.

[0064] When the first switch valve 35 is closed to connect the sample source 1 with the flow cell FC, the peristaltic pump 31 can rotate clockwise, thereby causing the sheath fluid in the flow cell FC to flow toward the sample source 1, so that the peristaltic pump 31 and the sampling pipeline 32 are cleaned with the sheath fluid.

[0065] When the second switch valve 36 is closed to connect the peristaltic pump 31 with the cleaning liquid source 2, the peristaltic pump 31 can rotate clockwise, thereby supplying the cleaning liquid in the cleaning liquid source 2 to the peristaltic pump 31 and flowing through the peristaltic pump 31, thereby cleaning the peristaltic pump 31 with the cleaning liquid. Similarly, when the second switch valve 36 is closed to connect the peristaltic pump 31 with the cleaning liquid source 2, the peristaltic pump 31 can rotate counterclockwise to draw the sheath liquid in the cleaning station into the sampling pipeline 32, thereby cleaning the sampling pipeline 32 with the sheath liquid.

[0066] The following will refer to Figure 4 To describe a peristaltic pump piping system 40 according to another embodiment of the present disclosure. Figure 3 In the peristaltic pump tubing system shown, the sample line can also be used as the sheath line, i.e., when the peristaltic pump rotates in the opposite direction to the sample. Figure 4 In the peristaltic pump pipeline system 40 shown, a sheath liquid pipeline 43 is provided separately from the sampling pipeline 42 so as to clean the peristaltic pump 41 with sheath liquid, and the switching device 13 is also configured to control the on-off of the sheath liquid pipeline 43 .

[0067] like Figure 4 As shown, the sheath liquid pipeline 43 connects the sheath liquid source 3 containing the sheath liquid to the peristaltic pump 41. The switching device 13 is a four-way reversing valve 46. The four-way reversing valve 46 has a first port 46a connected to the peristaltic pump 41, a second port 46b connected to the cleaning liquid source 2, a third port 46c connected to the flow cell FC, and a fourth port 46d connected to the sheath liquid source 3. The four-way reversing valve 46 switches between a first position in which the first port 46a is connected to the third port 46c, a second position in which the first port 46a is connected to the second port 46b, and a third position in which the first port 46a is connected to the fourth port 46d.

[0068] When the four-way reversing valve 46 is in the first position, the first port 46a is connected to the third port 46c, and the peristaltic pump 41 rotates counterclockwise to pump the sample in the sample source 1 into the flow cell FC for detection or sorting of the sample.

[0069] When the four-way reversing valve 46 is in the second position, the first port 46a is connected to the second port 46b, that is, the cleaning liquid source 2 is connected to the peristaltic pump 41, so that the cleaning liquid in the cleaning liquid source 2 can be supplied to the peristaltic pump 41 through the cleaning liquid pipeline 44, so that the peristaltic pump 41 is cleaned with the cleaning liquid. Figure 1A The examples shown are identical and therefore will not be described in detail.

[0070] When the four-way reversing valve 46 is in the third position, the first port 46a is connected to the fourth port 46d, that is, the sheath liquid source 3 is connected to the peristaltic pump 41. When the peristaltic pump 41 rotates clockwise, the sheath liquid in the sheath liquid source 3 is sucked into the peristaltic pump 41 and flows through the peristaltic pump 41. In this way, the peristaltic pump 41 is cleaned by the sheath liquid. The waste liquid for cleaning the peristaltic pump 41 can flow to the cleaning station 47 through the section of the sampling pipeline 42 from the peristaltic pump 41 to the sample source 1, and then can be discharged under the action of the waste liquid pump 48.

[0071] It should be understood that the peristaltic pump piping system according to the present disclosure should not be limited to the specific examples shown in the figures, but can be changed as needed as long as the functions described in this document can be achieved.

[0072] The present disclosure also relates to a sample processing instrument including the above-mentioned peristaltic pump piping system. The peristaltic pump piping system transports the sample and the sheath fluid to the flow cell through fluid components including a peristaltic pump and a valve, so that the sheath fluid wraps the sample in the flow cell, and the particles contained in the sample can flow through the flow cell in a single row linearly so as to collect the signals of the particles one by one. When the particles pass through the detection area, the particles are irradiated by the light source (usually a laser light source) of the optical detection system. The irradiation can cause the particles in the sample to emit scattered light (for example, generate side scattered light signals or forward scattered light signals). In some cases, the sample may include fluorescent particles, which can emit fluorescent signals in response to the irradiation. These signals are collected by the optical detection system. The collected particle signals are processed and analyzed by the sample analysis system to obtain information about the detected particles.

[0073] See below for more information. Figure 5A A method S10 for cleaning a peristaltic pump of a sample processing instrument according to an embodiment of the present disclosure is described. Figure 5A 4 is a flow chart of a method S10 for cleaning a peristaltic pump of a sample processing instrument according to an embodiment of the present disclosure.

[0074] like Figure 5AAs shown, method S10 includes providing a cleaning liquid pipeline connecting a cleaning liquid source to the peristaltic pump (step S11) and setting a switching device in the cleaning liquid pipeline (step S13). By setting a cleaning liquid pipeline that supplies cleaning liquid to the peristaltic pump, there is no need to use a sampling pipeline to provide cleaning liquid, and thus there is no need to replace the sample source with a cleaning liquid source. By setting a switching device, the cleaning steps of the cleaning liquid and the supply steps of other fluids (for example, samples or sheath fluids) can be conveniently switched, thereby improving efficiency. Preferably, the switching device can be automatically controlled. In this way, fluid supply and switching can be performed automatically, which can significantly shorten the operating time of the sample processing instrument and greatly improve work efficiency.

[0075] After the peristaltic pump pipeline system is built, the sampling pipeline can be connected and the cleaning liquid pipeline can be disconnected by the switching device to sample (step S15). Under the action of the peristaltic pump, the sample is supplied from the sample source to the flow cell via the sampling pipeline so as to process (for example, detect or sort) the particles in the sample.

[0076] After processing the sample, it is necessary to clean the various pipelines and various pumps. In particular, in step S17, the sampling pipeline is interrupted and the cleaning liquid pipeline is connected by the switching device to clean the peristaltic pump with the cleaning liquid. The cleaning liquid can be selected according to the particles detected in the sample to effectively clean the peristaltic pump and the fluid pipeline.

[0077] In addition, method S10 may further include cleaning the peristaltic pump with sheath fluid (step S19). The sheath fluid may be provided by the peristaltic pump through the reverse rotation of the sampling line (eg Figures 1A to 3 ), or it can be provided by an additional sheath fluid line (such as Figure 4 shown).

[0078] Step S17 and step S19 can be switched alternately and performed a predetermined number of times to meet the cleaning requirements. The predetermined number of times and / or the duration of each cleaning step can be changed according to the cleaning requirements.

[0079] Figure 5B 4 is a flow chart of a method S20 for cleaning a sampling pipeline of a sample processing instrument according to another embodiment of the present disclosure.

[0080] like Figure 5B As shown, method S20 includes cleaning the sampling pipeline along a first direction, see step S21. In step S21, the sampling pipeline can be cleaned with sheath fluid or a cleaning fluid different from the sheath fluid supplied via a cleaning fluid pipeline, which can be called forward flushing. In the case of having both a sheath fluid pipeline and a cleaning fluid pipeline, the sampling pipeline can be selectively cleaned in the forward direction with sheath fluid or other cleaning fluids.

[0081] In step S23, the sampling pipeline can be flushed with sheath fluid or other cleaning fluid in a second direction opposite to the first direction, which can be called reverse flushing. Similarly, in the case of having both a sheath fluid pipeline and a cleaning fluid pipeline, the sampling pipeline can be selectively flushed with sheath fluid or other cleaning fluid.

[0082] Step S21 and step S23 may be performed alternately. Step S21 and step S23 may be performed alternately for a predetermined number of times. The predetermined number of times may be determined according to the sample to be detected, the type of cleaning solution, and the like.

[0083] The inventors of the present application have discovered that alternating forward and reverse cleaning of the sampling line can significantly shorten the cleaning time, improve the cleaning efficiency, and also significantly improve the cleaning effect. The inventors tested the alternating forward and reverse cleaning method, and compared with the existing cleaning method, the cleaning time can be shortened to half or less, that is, the cleaning efficiency can be improved by 1 times or more. For viruses, the virus residue rate is reduced to less than 1.0% after 15 minutes of cleaning. For 3-micron microspheres, the microsphere residue rate is reduced to less than 0.1% after 10 seconds of cleaning. Since the cleaning time is significantly shortened, the required amount of sheath fluid or cleaning fluid is also significantly reduced, and the throughput of the sample processor is greatly increased.

[0084] It should be understood that the method for cleaning the sampling pipeline of the sample processing instrument according to the present disclosure should not be limited to the specific examples shown in the drawings or described herein, but can be changed as needed. The steps of the method are not necessarily performed in the order described, but can be adjusted as needed.

[0085] Apart from Figures 1A to 4 The various examples with peristaltic pumps shown, pipeline systems or sample processing instruments with other pumps are also suitable for implementing the above method and can achieve similar or better technical effects.

[0086] The following will refer to Figure 6 To describe the pipeline system 50 with a piston pump and its implementation as Figure 5B The process of the method is shown.

[0087] like Figure 6 As shown, the pipeline system 50 includes piston pumps 51 and 55, a sampling pipeline 52, and a switching device 13. The piston pump 51 is used to clean the sampling pipeline 52, and the piston pump 55 is used for sampling. It should be understood that it should not be limited to the specific examples shown in the figure, but can be changed. For example, only one piston pump can be used to achieve the functions of both piston pumps 51 and 55.

[0088] exist Figure 6In the example shown, the switching device 13 is a rotary valve 56. The piston pump is switched to be connected to the sample source 1 or the flow cell FC by rotating the rotary valve 56. However, it should be understood that the switching device should not be limited to the specific examples shown in the figure, but can be changed as long as the functions described herein can be achieved.

[0089] The reciprocating motion of the piston of the piston pump 51 can be used to alternately perform Figure 5B The forward flushing of step S21 and the reverse flushing of step S23 are shown in FIG. When the piston of the piston pump 51 moves downward, the sheath liquid in the cleaning station 57 or the flow cell FC is sucked into the sampling line 52 to perform a forward flush on the sampling line. When the piston of the piston pump 51 moves upward, the sheath liquid in the sampling line 52 is pushed into the cleaning station 57 or the flow cell FC for discharge. As described above, the piston pump 51 can be selectively connected to the cleaning station 57 or the flow cell FC by the switching device 13 (rotary valve 56), thereby selectively sucking in or discharging fluid from the cleaning station 57 or the flow cell FC.

[0090] Figure 6 The piston pump piping system shown is similar to Figures 1A to 4 The peristaltic pump piping system shown can further improve the cleaning efficiency. The peristaltic pump repeatedly cleans at a speed of 1.5 to 1.8 ml / min (milliliters per minute). The piston pump has a much higher speed. For a range of 100ul (microliters), the piston pump repeatedly cleans at a speed of 6.0 ml / min; for a range of 500ul, the piston pump repeatedly cleans at a speed of 30.0 ml / min; for a range of 1000ul, the piston pump repeatedly cleans at a speed of 60.0 ml / min.

[0091] Since the speed of piston pumps is much faster than that of peristaltic pumps, their cleaning efficiency and cleaning effect are also significantly improved.

[0092] Although the present disclosure has been described with reference to exemplary embodiments, it should be understood that the present disclosure is not limited to the specific embodiments described and shown in detail herein. Those skilled in the art may make various changes to the exemplary embodiments without departing from the scope defined by the claims. In the absence of contradiction, the features of the various embodiments may be combined with each other. Alternatively, a feature in the embodiment may be omitted.

Claims

1. A method for cleaning a sampling pipeline of a sample processing instrument, wherein: The sampling pipeline is connected to the flow cell of the sample processing instrument to the sample source. The method comprises: A forward flushing step of flushing the sampling pipeline along a first direction using a sheath fluid or a cleaning fluid different from the sheath fluid supplied via a cleaning fluid pipeline; and / or A back flushing step of flushing the sampling pipeline along a second direction opposite to the first direction using the sheath fluid or the cleaning fluid.

2. The method according to claim 1, wherein: The method comprises: The forward flushing step and the reverse flushing step are alternately performed a predetermined number of times.

3. The method according to claim 1 or 2, wherein: The method comprises: The sheath fluid is connected to the flow cell opening and / or the sample opening of the sampling line.

4. The method according to claim 3, wherein: A cleaning station is provided at the sample opening of the sampling pipeline, wherein the cleaning station has a sheath liquid port for supplying sheath liquid and a discharge port for discharging waste liquid; and / or The flow cell has a sheath liquid port for supplying a sheath liquid and a discharge port for discharging a waste liquid.

5. The method according to claim 1 or 2, wherein: The method comprises: The sampling pipeline is selectively cleaned using the sheath fluid or the cleaning fluid through a switching device disposed in the cleaning fluid pipeline and the sampling pipeline.

6. The method according to claim 5, wherein: The switching device is automatically controlled.

7. The method according to claim 1 or 2, wherein: The method comprises: A peristaltic pump is provided, and a forward flushing step or a reverse flushing step is performed by controlling the rotation direction of a roller of the peristaltic pump.

8. The method according to claim 1 or 2, wherein: The method comprises: A piston pump is provided, and the forward flushing step and the reverse flushing step are alternately performed by reciprocating motion of a piston of the piston pump.

9. A pipeline system for carrying out the method according to claim 1.

10. The piping system according to claim 9, wherein: The pipeline system includes a piston pump and a switching device arranged in the sampling pipeline. The switching device is configured to selectively connect the piston pump to a sample source or a flow cell. The piston pump is configured to be capable of alternately performing the forward flushing step and the reverse flushing step through reciprocating motion of its piston.

11. The piping system according to claim 10, wherein: The switching device is a rotary valve.

12. The piping system according to claim 9, wherein: The pipeline system includes a peristaltic pump configured to be able to perform a forward flushing step or a reverse flushing step by controlling a rotation direction of a roller of the peristaltic pump.

13. The piping system according to claim 12, wherein: The pipeline system includes a switching device arranged in the sampling pipeline and a cleaning liquid pipeline for supplying a cleaning liquid different from the sheath liquid. The switching device is configured to selectively supply a sample, a sheath fluid, or a cleaning fluid.

14. The piping system according to claim 13, wherein: The switching device is a reversing valve or a switch valve.

15. The pipeline system according to claim 10 or 13, wherein: The switching device is a switching device that can be automatically controlled.

16. The piping system according to any one of claims 9 to 14, wherein: A cleaning station is provided at the sample opening of the sampling pipeline, wherein the cleaning station has a sheath liquid port for supplying sheath liquid and a discharge port for discharging waste liquid; and / or The flow cell has a sheath liquid port for supplying a sheath liquid and a discharge port for discharging a waste liquid.

17. A sample processing instrument comprising the tubing system according to any one of claims 9 to 16.

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