Tangential flow filtration system and tangential flow filtration method

Abstract

A tangential flow filtration system and method. The system comprises a storage module, a tangential flow filtering device, a pipeline module and a valve module. The storage module comprises a sample container, a cleaning liquid container and a waste liquid container. The tangential flow filtering device comprises a liquid inlet end, a backflow end and a liquid outlet end. The pipeline module comprises a first liquid inlet pipeline, a backflow pipeline, a liquid outlet pipeline, a first output pipeline and a second output pipeline. The valve module includes a first control valve and a second control valve. The first end of the first liquid inlet pipeline is connected with the sample container or the cleaning liquid container, and the second end is connected with the liquid inlet end. The second end of the backflow pipeline is connected with the first control valve. The first end of the first output pipeline is connected with the first control valve, and the second end is connected with the sample container or the cleaning liquid container. The first end of the liquid outlet pipeline is connected with the liquid outlet end, and the second end is connected with the second control valve. The first end of the second output pipeline is connected with the second control valve; the system has a cleaning mode and a filtering mode.

Description

TECHNICAL FIELD

[0001] The present application relates to the separation and purification of target substances, and in particular to a tangential flow filtration system and a tangential flow filtration method. BACKGROUND

[0002] Tangential flow filtration (TFF) is a technique commonly used for the separation and purification of biological macromolecules. A tangential flow filtration system causes the liquid to be filtered to flow parallel to the surface of the filter membrane through tangential flow, thereby reducing the clogging of the filter membrane and improving the filtration efficiency.

[0003] However, bacteria, dirt and other impurities may exist in the filter bag of the tangential flow filtration system or the pipeline connected to the filter bag, which may contaminate the solution to be filtered during the filtration process, resulting in the target substance obtained ultimately failing to meet the prescribed quality standards. SUMMARY

[0004] In view of the above, the present application provides a tangential flow filtration system and a tangential flow filtration method.

[0005] The first aspect of the present application provides a tangential flow filtration system configured to separate a target from a sample solution. The tangential flow filtration system comprises a storage module, a tangential flow filtration device, a tubing module, and a valve module. The storage module comprises a sample container configured to hold the sample solution, a first washing solution container configured to hold a first washing solution, and a waste solution container. The tangential flow filtration device comprises an inlet end, a return end, and an outlet end. The tubing module comprises a first inlet tubing, a return tubing, an outlet tubing, a first output tubing, and a second output tubing. The valve module comprises a first control valve and a second control valve. A first end of the first inlet tubing is selectively connected to the sample container or the first washing solution container, a second end of the first inlet tubing is connected to the inlet end, a first end of the return tubing is connected to the return end, a second end of the return tubing and a first end of the first output tubing are respectively connected to the first control valve, a second end of the first output tubing is selectively connected to the sample container or the first washing solution container, a first end of the outlet tubing is connected to the outlet end, a second end of the outlet tubing and a first end of the second output tubing are respectively connected to the second control valve, and a second end of the second output tubing is connected to the waste solution container. The tangential flow filtration system has a first washing mode and a tangential flow filtration mode. In the first washing mode, the first end of the first inlet tubing and the second end of the first output tubing are respectively connected to the first washing solution container, the first control valve connects the second end of the return tubing to the first end of the first output tubing, and the second control valve disconnects the second end of the outlet tubing and the first end of the second output tubing, so that the first washing solution flows through the first inlet tubing, the tangential flow filtration device, the return tubing, and the first output tubing to the first washing solution container. In the tangential flow filtration mode, the first end of the first inlet tubing and the second end of the first output tubing are respectively connected to the sample container, the first control valve connects the second end of the return tubing to the first end of the first output tubing, and the second control valve connects the second end of the outlet tubing to the first end of the second output tubing, so that the target of the sample solution flows through the first inlet tubing, the tangential flow filtration device, the return tubing, and the first output tubing to the sample container, and the remaining components of the sample solution flow through the first inlet tubing, the tangential flow filtration device, the outlet tubing, and the second output tubing to the waste solution container.

[0006] A second aspect of this application provides a tangential flow filtration method configured to separate a target analyte from a sample solution. The tangential flow filtration method includes: connecting a first end of a first inlet pipe to a first cleaning solution container containing a first cleaning solution; connecting a second end of the first inlet pipe to the inlet end of a tangential flow filtration device; connecting a first end of a return pipe to the return end of the tangential flow filtration device; connecting the second end of the return pipe and the first end of a first output pipe to a first control valve; connecting the second end of the first output pipe to the first cleaning solution container; connecting a first end of an outlet pipe to the outlet end of the tangential flow filtration device; connecting the second end of the outlet pipe and the first end of the second output pipe to a second control valve; and connecting the second end of the second output pipe to a waste liquid container, thereby constructing a tangential flow filtration system; the first control valve connects the second end of the return pipe to the first end of the first output pipe; and the second control valve connects the second end of the outlet pipe to the first end of the second output pipe. Disconnecting the flow allows the tangential flow filtration system to switch to the first cleaning mode. In the first cleaning mode, the first cleaning fluid flows through the first inlet pipe, the tangential flow filtration device, the return pipe, and the first output pipe to the first cleaning fluid container. The first end of the first inlet pipe is connected to the sample container containing the sample solution, and the second end of the first output pipe is connected to the sample container. A second control valve connects the second end of the outlet pipe to the first end of the second output pipe, thereby switching the tangential flow filtration system to the tangential flow filtration mode. In the tangential flow filtration mode, the target analyte in the sample solution flows through the first inlet pipe, the tangential flow filtration device, the return pipe, and the first output pipe to the sample container, while the remaining components of the sample solution flow through the first inlet pipe, the tangential flow filtration device, the outlet pipe, and the second output pipe to the waste liquid container.

[0007] In this application, the tangential flow filtration system can switch between a first cleaning mode and a tangential flow filtration mode through the cooperation of a valve module. In the first cleaning mode, the first cleaning fluid can clean the pipelines and tangential flow filtration device, removing dirt, bacteria, and other impurities, thereby preventing such impurities from contaminating the sample solution during subsequent tangential flow filtration. This ensures hygiene and sterility during the tangential flow filtration process and improves the automation level of the entire tangential flow filtration system. Furthermore, by designing the volume of each pipeline, the volume of the entire tangential flow filtration system can be determined. Based on the volume of the tangential flow filtration system, the required volume of the first cleaning fluid can be rationally planned, thereby improving the cleaning effect of the tangential flow filtration system. Attached Figure Description

[0008] Figure 1 This is a schematic diagram of a tangential flow filtration system provided in one embodiment of this application.

[0009] Figure 2 for Figure 1 The diagram shows the fluid path of the tangential flow filtration system in the first pre-cleaning mode.

[0010] Figure 3 for Figure 1 The diagram shows the fluid path of the tangential flow filtration system in the first cleaning mode.

[0011] Figure 4 for Figure 1 The diagram shows the fluid path of the tangential flow filtration system in the first replenishment mode and the second cleaning mode.

[0012] Figure 5 for Figure 1 The diagram shows the fluid path of the tangential flow filtration system in the second replenishment mode and the third cleaning mode.

[0013] Figure 6 for Figure 1 The diagram shows the liquid flow path of the tangential flow filtration system in tangential flow filtration mode.

[0014] Figure 7 for Figure 1 The diagram shows the liquid flow path of a tangential flow filtration system in dead-end filtration mode.

[0015] Figure 8 A flowchart of a tangential flow filtering method provided in one embodiment of this application.

[0016] Explanation of main component symbols

[0017] Tangential flow filtration system 1

[0018] Storage Module 10

[0019] Sample container 11

[0020] First cleaning fluid container 12

[0021] Waste liquid container 13

[0022] Second cleaning fluid container 14

[0023] Third cleaning fluid container 15

[0024] Fourth cleaning fluid container 16

[0025] Fifth cleaning fluid container 17

[0026] enrichment container 18

[0027] Tangential flow filter device 20

[0028] Inlet end 21

[0029] Return end 22

[0030] liquid outlet 23

[0031] First filter membrane 24

[0032] Piping Module 30

[0033] First liquid inlet pipe 31

[0034] Reflux line 32

[0035] Liquid outlet line 33

[0036] First output pipe 34

[0037] Second output pipe 35

[0038] Third output pipe 36

[0039] Second inlet pipe 37

[0040] Third liquid inlet line 38

[0041] Fourth output pipeline 39

[0042] Valve Module 40

[0043] First control valve 41

[0044] Second control valve 42

[0045] Third control valve 43

[0046] Fourth control valve 44

[0047] First power unit 50

[0048] Second power unit 51

[0049] First pressure sensing device 60

[0050] Second pressure sensing device 61

[0051] Weight sensor 70

[0052] Dead-end filter device 80

[0053] Second filter membrane 81

[0054] Fourth inlet line 391

[0055] Fifth output pipeline 392

[0056] First end 31A, 32A, 33A, 34A, 35A, 36A, 37A, 38A, 39A, 391A, 392A

[0057] The second end 31B, 32B, 33B, 34B, 35B, 36B, 37B, 38B, 39B, 391B, 392B first pre-cleaning mode My1

[0058] First cleaning mode Mx1

[0059] Second cleaning mode Mx2

[0060] Third cleaning mode Mx3

[0061] Dead End Filtering Mode Ms

[0062] Tangential flow filtering mode Mq

[0063] First fluid resuscitation mode Mb1

[0064] First rehydration mode Mb2

[0065] The following detailed description, in conjunction with the accompanying drawings, will further illustrate this application. Detailed Implementation

[0066] To better understand the above-mentioned objectives, features, and advantages of this application, the application will be described in detail below with reference to the accompanying drawings and specific embodiments. It should be noted that, unless otherwise specified, the embodiments and features described in the embodiments of this application can be combined with each other. Many specific details are set forth in the following description to provide a thorough understanding of this application; the described embodiments are only some embodiments of this application, and not all embodiments.

[0067] It should be noted that when a component is described as "fixed to" or "mounted to" another component, it can be directly on the other component or may be interspersed with an intermediate component. When a component is described as "set to" another component, it can be directly set on the other component or may be interspersed with an intermediate component. The term "and / or" as used herein includes all and any combination of one or more of the associated listed items.

[0068] It should be noted that although a logical order is shown in the flowchart, in some cases, the steps shown or described may be performed in a different order than that shown in the flowchart. The methods disclosed in the embodiments of this application include one or more steps or actions for implementing the method. Method steps and / or actions may be interchanged with each other without departing from the scope of the claims. Unless a specific order of steps or actions is specified, the order and / or use of specific steps and / or actions may be modified without departing from the scope of the claims.

[0069] Please see Figure 1This application provides a tangential flow filtration system 1 for separating target analytes from a sample solution. In some embodiments, the sample solution is a phage solution, and the target analyte separated from the sample solution is a suspension containing phage particles. The separated target analyte is collected to obtain a phage preparation. In other embodiments, the tangential flow filtration system 1 can also be used for the purification and separation of biomolecules such as proteins, peptides, polysaccharides, nucleic acids, or antibodies.

[0070] The tangential flow filtration system 1 includes a storage module 10, a tangential flow filtration device 20, a pipeline module 30, and a valve module 40.

[0071] The storage module 10 includes a sample container 11 for containing a sample solution, a first cleaning solution container 12 for containing a first cleaning solution, and a waste liquid container 13 for containing waste liquid. Each of the sample container 11, the first cleaning solution container 12, and the waste liquid container 13 can be a bottle-shaped or barrel-shaped container suitable for containing liquids. In some embodiments, the sample container 11, the first cleaning solution container 12, and the waste liquid container 13 are all bottle-shaped containers with caps.

[0072] The tangential flow filtration device 20 includes a first filter membrane 24, an inlet end 21, a reflux end 22, and an outlet end 23. The inlet end 21, reflux end 22, and outlet end 23 are respectively connected to the first filter membrane 24. The pore size of the first filter membrane 24 is smaller than the particle size of the target analyte. Therefore, after a sample solution is injected into the tangential flow filtration device 20 through the inlet end 21, the target analyte in the sample solution can be retained by the first filter membrane 24 and then returned to the sample solution through the reflux end 22 for the next cycle. Other components (including the solution itself) with a particle size smaller than the pore size of the first filter membrane 24 can pass through the first filter membrane 24 and flow out through the outlet end 23. In this way, the total volume of the sample solution is reduced, the recovery rate of the target analyte in the sample solution is increased, and after multiple cycles, the separation and concentration of the target analyte are achieved.

[0073] The piping module 30 includes a first inlet pipe 31, a return pipe 32, an outlet pipe 33, a first output pipe 34, and a second output pipe 35. The valve module 40 includes a first control valve 41 and a second control valve 42. The first end 31A of the first inlet pipe 31 is selectively connected to either the sample container 11 or the first cleaning solution container 12, and the second end 31B of the first inlet pipe 31 is connected to the inlet end 21. The first end 32A of the return pipe 32 is connected to the return end 22, and the second end 32B of the return pipe 32 is connected to the first control valve 41. The first end 34A of the first output pipe 34 is connected to the first control valve 41, and the second end 34B of the first output pipe 34 is selectively connected to either the sample container 11 or the first cleaning solution container 12. The first end 33A of the outlet pipe 33 is connected to the outlet end 23, and the second end 33B of the outlet pipe 33 is connected to the second control valve 42. The first end 35A of the second output pipe 35 is connected to the second control valve 42, and the second end 35B of the second output pipe 35 is connected to the waste liquid container 13. In some embodiments, when the sample container 11, the first cleaning solution container 12, and the waste liquid container 13 are all bottle-shaped containers with caps, the first end 31A of the first inlet pipe 31 and the second end 34B of the first output pipe 34 pass through the caps of the bottle-shaped containers, and the first end 31A of the first inlet pipe 31 and the second end 34B of the first output pipe 34 can be located below the surface of the first cleaning solution or sample solution in the bottle-shaped container. The first end 31A of the first inlet pipe 31 can contact the bottom of the bottle-shaped container so that the first cleaning solution or sample solution at the bottom can be processed. Each cap can also be provided with an interface (not shown) to connect to the atmospheric environment, avoiding atmospheric imbalance during liquid flow.

[0074] Please see Figure 3 and Figure 6 The tangential flow filtration system 1 has at least a first cleaning mode Mx1 and a tangential flow filtration mode Mq, wherein the first cleaning mode Mx1 can be executed before the tangential flow filtration mode Mq. For example... Figure 3As shown, in the first cleaning mode Mx1, the first end 31A of the first inlet pipe 31 and the second end 34B of the first outlet pipe 34 are respectively connected to the first cleaning liquid container 12. The first control valve 41 connects the second end 32B of the return pipe 32 to the first end 34A of the first outlet pipe 34, and the second control valve 42 disconnects the second end 33B of the outlet pipe 33 from the first end 35A of the second outlet pipe 35. This allows the first cleaning liquid to flow through the first inlet pipe 31, the tangential flow filter device 20, the return pipe 32, and the first outlet pipe 34 to the first cleaning liquid container 12, continuously circulating within the aforementioned path. In this way, the first cleaning liquid can clean the pipes and the tangential flow filter device 20 it flows through, removing dirt, bacteria, and other impurities, thereby preventing such impurities from contaminating the sample solution during subsequent tangential flow filtration and ensuring hygiene and sterility during the tangential flow filtration process. In some embodiments, the first cleaning liquid can be an alkaline solution, such as a sodium hydroxide solution. Because the second control valve 42 disconnects the second end 33B of the outlet pipe 33 from the first end 35A of the second output pipe 35 under the first cleaning mode Mx1, the waste of the first cleaning fluid is avoided.

[0075] like Figure 6 As shown, in the tangential flow filtration mode Mq, the first cleaning solution container 12 is replaced by the sample container 11. That is, the first end 31A of the first inlet pipe 31 and the second end 34B of the first outlet pipe 34 are respectively connected to the sample container 11. The first control valve 41 connects the second end 32B of the return pipe 32 to the first end 34A of the first outlet pipe 34, and the second control valve 42 connects the second end 33B of the outlet pipe 33 to the first end 35A of the second outlet pipe 35. This allows the target substance of the sample solution to flow to the sample container 11 through the first inlet pipe 31, the tangential flow filtration device 20, the return pipe 32, and the first outlet pipe 34. That is, the target substance can return to the sample solution through the return end 22 and enter the next cycle. The remaining components of the sample solution flow to the waste liquid container 13 through the first inlet pipe 31, the tangential flow filtration device 20, the outlet pipe 33, and the second outlet pipe 35. In this way, the total volume of the sample solution decreases, and the concentration of the target analyte in the sample solution increases. After multiple cycles, the separation and concentration of the target analyte are achieved. When the sample solution is a phage solution, the target analyte is a suspension containing phage particles. The remaining components of the sample solution flowing to waste container 13 include the solution and endotoxins. That is, after tangential flow filtration, endotoxins in the phage solution can be removed. In some embodiments, before tangential flow filtration, a lysis agent (such as Triton X-100) can be added to the phage solution to dissociate or degrade the endotoxins bound to the phage particles in the original phage solution, so that the dissociated or degraded endotoxins can be removed during tangential flow filtration.

[0076] like Figure 1As shown, in some embodiments, the tangential flow filtration system 1 may further include a first power unit 50 disposed on the first inlet pipe 31. The first power unit 50 is used to output power to drive the flow of the first cleaning fluid or sample solution. The first power unit 50 may be various types of pumps capable of driving liquid movement, such as syringe pumps, plunger pumps, diaphragm pumps, gear pumps, and peristaltic pumps.

[0077] The tangential flow filtration system 1 may further include a first pressure sensor 60 disposed on the first inlet pipe 31, located between the first power unit 50 and the inlet end 21. In the tangential flow filtration mode Mq, the first pressure sensor 60 is used to detect a first pressure value at the inlet end 21, and the first power unit 50 is also used to adjust the output power based on the first pressure value. It can be understood that in the tangential flow filtration mode Mq, as the target material is separated and concentrated, the pressure difference across the first filter membrane 24, i.e., the transmembrane pressure, gradually increases. When the first pressure value exceeds a first preset pressure value, the first power unit 50 can reduce its rotational speed to avoid damage to the target material caused by a large transmembrane pressure during concentration. In some embodiments, the first preset pressure value may be set to 0.1 MPa.

[0078] Furthermore, the tangential flow filtration system 1 may also include a second pressure sensor 61 disposed on the return pipe 32. The second pressure sensor 61 is used to detect a second pressure value at the return end 22. When the second pressure value is greater than a second preset pressure value, it indicates that the first filter membrane 24 may be damaged. The first pressure sensor 60 and the second pressure sensor 61 may be pressure gauges.

[0079] In some embodiments, the tangential flow filtration system 1 may further include a weight sensor 70, on which the first cleaning fluid container 12 and the sample container 11 may be placed sequentially, i.e., the first cleaning fluid container 12 and the sample container 11 may be detected sequentially by the same weight sensor 70. Figure 3 As shown, in the first cleaning mode Mx1, the weight sensor 70 is used to detect the weight or weight change of the first cleaning fluid container 12. For example, the weight sensor 70 detects the weight change of the first cleaning fluid container 12, and this weight change reflects the amount of first cleaning fluid used in the first cleaning fluid container 12 under the first cleaning mode Mx1. When the weight change reaches a first preset weight value, the first power unit 50 is also used to stop outputting power, thereby completing the cleaning with the first cleaning fluid. Figure 6As shown, in the tangential flow filtration mode Mq, the weight sensor 70 is also used to detect the weight or weight change of the sample container 11. For example, the weight sensor 70 detects the weight of the sample container 11, and this weight can reflect the final volume (i.e., target concentration) of the target substance in the sample container 11 under the tangential flow filtration mode Mq. When the weight reaches a second preset weight value, the first power unit 50 is also used to stop outputting power, thereby completing the separation and concentration of the target substance. The weight sensor 70 can be an electronic scale.

[0080] Furthermore, the tangential flow filtration system 1 may also include a processor and a user interface (not shown). The user interface allows the user to input a first preset weight value and a second preset weight value. The processor is electrically connected to the weight sensor 70 and the first control valve 41. The processor can control the first control valve 41 to operate accordingly based on the detection results of the weight sensor 70, thereby switching the tangential flow filtration system 1 to the desired mode. This avoids the need for the user to closely monitor the entire cleaning and filtration process, improving the automation level of the tangential flow filtration system 1. In other embodiments, the user interface may also allow the user to input the operating duration of the first cleaning mode Mx1 and the tangential flow filtration mode Mq. The processor can also control the first control valve 41 to operate accordingly based on the above operating duration, thereby switching the tangential flow filtration system 1 to the desired mode. The processor can be a Central Processing Unit (CPU), or other general-purpose processors, digital signal processors (DSPs), application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, etc. A general-purpose processor can be a microprocessor or any conventional processor.

[0081] In this application, the tangential flow filtration system 1 can switch between a first cleaning mode Mx1 (i.e., pre-cleaning mode) and a tangential flow filtration mode Mq through the cooperation of the valve module 40. In the first cleaning mode Mx1, the first cleaning fluid can clean the pipeline and the tangential flow filtration device 20, removing dirt, bacteria and other impurities, thereby preventing such impurities from contaminating the sample solution during subsequent tangential flow filtration, ensuring hygiene and sterility during the tangential flow filtration process, and improving the automation level of the entire tangential flow filtration system 1. Moreover, by designing the volume of each pipeline, the volume of the entire tangential flow filtration system 1 can be determined. Based on the aforementioned volume of the tangential flow filtration system 1, the required volume of the first cleaning fluid can be rationally planned, thereby improving the cleaning effect of the tangential flow filtration system 1.

[0082] like Figure 2As shown, in some embodiments, the tangential flow filtration system 1 may also have a first pre-cleaning mode My1, which can be executed before the first cleaning mode Mx1. Correspondingly, the piping module 30 also includes a third output pipe 36. The first end 36A of the third output pipe 36 is connected to the first control valve 41, and the second end 36B of the third output pipe 36 is connected to the waste liquid container 13. The first control valve 41 is used to selectively connect the second end 32B of the return pipe 32 to the first end 34A of the first output pipe 34 or the first end 36A of the third output pipe 36. Specifically, in the first cleaning mode Mx1, the first control valve 41 connects the second end 32B of the return pipe 32 to the first end 34A of the first output pipe 34, and the second control valve 42 disconnects the second end 33B of the outlet pipe 33 from the first end 35A of the second output pipe 35. In the first pre-cleaning mode My1, the first control valve 41 connects the second end 32B of the return pipe 32 to the first end 36A of the third output pipe 36, and the second control valve 42 connects the second end 33B of the outlet pipe 33 to the first end 35A of the second output pipe 35. Therefore, in the first pre-cleaning mode My1, the first cleaning fluid also flows to the waste liquid container 13 via the first inlet pipe 31, the tangential flow filter device 20, the return pipe 32, the outlet pipe 33, the second output pipe 35, and the third output pipe 36. By setting the first pre-cleaning mode My1, the first cleaning fluid can carry most of the impurities in the pipes (such as the first inlet pipe 31, the return pipe 32, and the outlet pipe 33) and the tangential flow filter device 20 into the waste liquid container 13 first, avoiding the flow of these impurities into the first cleaning fluid container 12 and contamination of the first cleaning fluid in the first cleaning mode Mx1, thereby minimizing the impact of these impurities on the first cleaning fluid. In some embodiments, the volume ratio of the first cleaning fluid used in the first pre-cleaning mode My1 to that used in the first cleaning mode Mx1 is not less than 3:1. In some embodiments, both the first control valve 41 and the second control valve 42 can be solenoid valves. The first control valve 41 can connect the second end 32B of the return line 32 to the first end 36A of the third output line 36 when it is open, and connect the second end 32B of the return line 32 to the first end 34A of the first output line 34 when it is closed. The second control valve 42 can connect the second end 33B of the outlet line 33 to the first end 35A of the second output line 35 when it is open, and disconnect the second end 33B of the outlet line 33 from the first end 35A of the second output line 35 when it is closed.

[0083] like Figure 4As shown, in some embodiments, the tangential flow filtration system 1 may also have a second cleaning mode Mx2, which can be executed after the first cleaning mode Mx1. Correspondingly, the storage module 10 may also include a second cleaning fluid container 14 for containing the second cleaning fluid. The piping connection method of the second cleaning mode Mx2 is the same as that of the first cleaning mode Mx1, except that the first cleaning fluid container 12 is replaced by the second cleaning fluid container 14. In the second cleaning mode Mx2, the first end 31A of the first inlet pipe 31 and the second end 34B of the first outlet pipe 34 are respectively connected to the second cleaning liquid container 14. The first control valve 41 connects the second end 32B of the return pipe 32 to the first end 34A of the first outlet pipe 34, and the second control valve 42 disconnects or connects the second end 33B of the outlet pipe 33 to the first end 35A of the second outlet pipe 35, so that at least part of the second cleaning liquid flows to the second cleaning liquid container 14 through the first inlet pipe 31, the tangential flow filter device 20, the return pipe 32, and the first outlet pipe 34. It can be understood that if the second control valve 42 connects the second end 33B of the outlet pipe 33 to the first end 35A of the second outlet pipe 35 in the second cleaning mode Mx2, then part of the second cleaning liquid will also flow to the waste liquid container 13 through the first inlet pipe 31, the tangential flow filter device 20, the outlet pipe 33, and the second outlet pipe 35. The second cleaning fluid is an aqueous solution (such as pure water), used to remove hydroxide ions remaining in the pipeline and tangential flow filter 20 from the first cleaning fluid. In some embodiments, a second pre-cleaning mode can be performed before the second cleaning mode Mx2. The pipeline connection method for the second pre-cleaning mode is similar to that of the first pre-cleaning mode My1, except that the first cleaning fluid container 12 is replaced by the second cleaning fluid container 14, which will not be described in detail here. In some embodiments, the volume ratio of the second cleaning fluid used in the second pre-cleaning mode to that used in the second cleaning mode Mx2 is approximately 3:2.

[0084] like Figure 5As shown, the tangential flow filtration system 1 may also have a third cleaning mode Mx3, which can be executed after the second cleaning mode Mx2. Correspondingly, the storage module 10 may also include a third cleaning fluid container 15 for containing the third cleaning fluid. The piping connection method of the third cleaning mode Mx3 is the same as that of the second cleaning mode Mx2, except that the second cleaning fluid container 14 is replaced by the third cleaning fluid container 15. In the third cleaning mode Mx3, the first end 31A of the first inlet pipe 31 and the second end 34B of the first outlet pipe 34 are respectively connected to the third cleaning solution container 15. The first control valve 41 connects the second end 32B of the return pipe 32 to the first end 34A of the first outlet pipe 34, and the second control valve 42 disconnects or connects the second end 33B of the outlet pipe 33 to the first end 35A of the second outlet pipe 35, so that at least part of the third cleaning solution flows to the third cleaning solution container 15 through the first inlet pipe 31, the tangential flow filter device 20, the return pipe 32, and the first outlet pipe 34. The third cleaning solution is a buffer solution, such as PBS buffer. The third cleaning solution is used to restore the environment in the pipes and the tangential flow filter device 20 to a neutral environment to ensure the cleanliness and potency of the target substance (and most drug molecules, such as bacteriophage particles, are more likely to survive in a neutral environment with a pH of 6.5-7.5). Furthermore, since the tubing and tangential flow filter 20 have been cleaned with the second cleaning solution before the third cleaning mode Mx3, the reaction of hydroxide ions with ions in the third cleaning solution (such as silicon or calcium ions in PBS buffer) to form insoluble impurities can be avoided. In some embodiments, a third pre-cleaning mode can also be performed before the third cleaning mode Mx3. The tubing connection method for the third pre-cleaning mode is the same as that for the second pre-cleaning mode, except that the second cleaning solution container 14 is replaced with the third cleaning solution container 15, which will not be described in detail here. The volume ratio of the third cleaning solution used in the third pre-cleaning mode to that used in the third cleaning mode Mx3 is approximately 3:2. In some embodiments, both the second cleaning solution container 14 and the third cleaning solution container 15 are bottle-shaped containers with caps to prevent liquid splashing.

[0085] It is understood that after the tangential flow filtration mode Mq, the tangential flow filtration system 1 can be switched back to at least one of the first cleaning mode Mx1, the second cleaning mode Mx2, and the third cleaning mode Mx3 (in which case the first cleaning mode Mx1, the second cleaning mode Mx2, or the third cleaning mode Mx3 serves as the post-cleaning mode). This allows the tangential flow filtration system 1 to remove residual target substances or other impurities from the tubing and the tangential flow filtration device 20 when used for the separation and purification of target substances in another sample solution, preventing cross-contamination between different batches or types of sample solutions and ensuring the purity and consistency of the final target substance. Furthermore, it maintains the hygienic condition and filtration efficiency of the tangential flow filtration system 1. In some embodiments, after the tangential flow filtration mode Mq, the tangential flow filtration system 1 can be switched sequentially to the second cleaning mode Mx2 and the first cleaning mode Mx1, i.e., the tubing and the tangential flow filtration device 20 are cleaned sequentially with an aqueous solution and an alkaline solution. First, the pipeline and tangential flow filter device 20 are cleaned with an aqueous solution to reduce the risk of target material or other impurities remaining in the pipeline and tangential flow filter device 20 reacting with the alkaline solution to form insoluble impurities. When cleaning is performed using the first cleaning mode Mx1, the first power unit 50 can also drive the first cleaning liquid to flow in reverse, so that the first cleaning liquid in the first cleaning liquid container 12 returns to the first cleaning liquid container 12 through the first output pipeline 34, return pipeline 32, tangential flow filter device 20, and first inlet pipeline 31, thereby causing the target material accumulated on the surface of the first filter membrane 24 to detach from the first filter membrane 24 and flow out of the tangential flow filter device 20 under the drive of the first cleaning liquid, thus improving the cleaning effect. In some embodiments, after the tangential flow filter mode Mq, the alkaline solution used in the first cleaning mode Mx1 can have a preset temperature higher than room temperature, such as 42-45°C, thereby improving the cleaning effect without damaging the tangential flow filter device 20.

[0086] like Figure 1As shown, in some embodiments, the storage module 10 may further include a fourth cleaning fluid container 16 for containing a second cleaning fluid and a fifth cleaning fluid container 17 for containing a third cleaning fluid. The piping module 30 also includes a second inlet pipe 37, a third inlet pipe 38, and a fourth outlet pipe 39. The valve module 40 further includes a third control valve 43. The first end 37A of the second inlet pipe 37 is connected to the fourth cleaning fluid container 16, and the second end 37B of the second inlet pipe 37 is connected to the third control valve 43. The first end 38A of the third inlet pipe 38 is connected to the fifth cleaning fluid container 17, and the second end 38B of the third inlet pipe 38 is connected to the third control valve 43. The first end 39A of the fourth outlet pipe 39 is connected to the third control valve 43, and the second end 39B of the fourth outlet pipe 39 is selectively connected to either the second cleaning fluid container 14 or the third cleaning fluid container 15. The third control valve 43 is used to selectively connect the first end 37A of the second inlet line 37 or the first end 38A of the third inlet line 38 to the first end 39A of the fourth outlet line 39. In some embodiments, the third control valve 43 can be a solenoid valve. The third control valve 43 can connect the first end 37A of the second inlet line 37 to the first end 39A of the fourth outlet line 39 when it is open, and connect the first end 38A of the third inlet line 38 to the first end 39A of the fourth outlet line 39 when it is closed. In some embodiments, the fourth cleaning fluid container 16 and the fifth cleaning fluid container 17 are both bottle-shaped containers with caps.

[0087] like Figure 4 and Figure 5 As shown, considering that the second and third cleaning solutions typically require larger volumes compared to the first cleaning solution, the tangential flow filtration system 1 may also have a first replenishment mode Mb1 and a second replenishment mode Mb2. For example... Figure 4 As shown, in the first replenishment mode Mb1, the third control valve 43 connects the first end 37A of the second inlet pipe 37 with the first end 39A of the fourth outlet pipe 39, allowing the second cleaning fluid in the fourth cleaning fluid container 16 to flow through the second inlet pipe 37 and the fourth outlet pipe 39 to the second cleaning fluid container 14, thereby replenishing the second cleaning fluid in the second cleaning fluid container 14. Figure 5As shown, in the second replenishment mode Mb2, the third control valve 43 connects the first end 38A of the third inlet pipe 38 with the first end 39A of the fourth outlet pipe 39, allowing the third cleaning fluid in the fifth cleaning fluid container 17 to flow through the third inlet pipe 38 and the fourth outlet pipe 39 to the third cleaning fluid container 15, thereby replenishing the third cleaning fluid in the third cleaning fluid container 15. In some embodiments, the second cleaning fluid container 14 and the third cleaning fluid container 15 may also be placed sequentially on the weight sensor 70. In the second cleaning mode Mx2, the weight sensor 70 is used to detect the weight or weight change of the second cleaning fluid container 14. For example, the weight sensor 70 detects the weight of the second cleaning fluid container 14, and this weight can reflect whether the existing content of the second cleaning fluid in the second cleaning fluid container 14 is sufficient in the second cleaning mode Mx2. When the weight does not reach the third preset weight value, the third control valve 43 connects the first end 37A of the second inlet pipe 37 to the first end 39A of the fourth output pipe 39, thereby replenishing the second cleaning fluid in the second cleaning fluid container 14. Alternatively, the weight sensor 70 detects the weight change of the second cleaning fluid container 14, and this weight change reflects the amount of second cleaning fluid used in the second cleaning mode Mx2. When the weight change reaches the fourth preset weight value, the first power unit 50 also stops outputting power, thereby completing the cleaning with the second cleaning fluid. The third cleaning mode Mx3 works similarly, and will not be elaborated further.

[0088] like Figure 6As shown, further, in the tangential flow filtration mode Mq, the third control valve 43 can also connect the first end 38A of the third inlet pipe 38 with the first end 39A of the fourth outlet pipe 39, so that the third cleaning liquid in the fifth cleaning liquid container 17 flows to the sample container 11 through the third inlet pipe 38 and the fourth outlet pipe 39. In this way, the third cleaning liquid can flow into the tangential flow filtration device 20 together with the sample solution in the sample container 11 through the first inlet pipe 31. As the target substance of the sample solution flows to the sample container 11 through the first inlet pipe 31, the tangential flow filtration device 20, the return pipe 32 and the first outlet pipe 34, the third cleaning liquid and the remaining components of the sample solution flow to the waste liquid container 13 through the first inlet pipe 31, the tangential flow filtration device 20, the outlet pipe 33 and the second outlet pipe 35, until the weight sensor 70 detects that the weight of the sample container 11 has reached the second preset weight value again. Since the concentrated target material may contain culture medium or other impurities, a third washing solution is added to the sample container 11 to dilute the target material, allowing the third washing solution and the target material to be filtered again (also known as a displacement step). This removes impurities such as culture medium from the target material, improving the purity of the final target material. The volume of the third washing solution required for the displacement step can be rationally planned based on the overall volume of the tangential flow filtration system 1, thereby maximizing the collection of target material remaining in the pipeline and tangential flow filtration device 20. In some embodiments, the displacement step can be performed multiple times to maximize the purity of the final target material.

[0089] The tangential flow filtration system 1 can also have a recovery mode (not shown). The piping connection in the recovery mode is similar to the replacement step, except that the target material collected in sample container 11 is first removed and stored. Subsequently, the third cleaning solution from the fifth cleaning solution container 17 flows to sample container 11 via the third inlet pipe 38 and the fourth outlet pipe 39, and further flows into the tangential flow filtration device 20 via the first inlet pipe 31. This draws the remaining target material in the piping and tangential flow filtration device 20 to sample container 11, thereby recovering the remaining target material. Since the target material collected in sample container 11 has been removed, the recovery mode avoids affecting the concentration or potency of the target material collected in sample container 11. The recovered target material in sample container 11 can be used in other applications where potency requirements are slightly lower.

[0090] In some embodiments, the storage module 10 further includes an enrichment container 18 for containing enrichment solution. The piping module 30 further includes a fourth inlet pipe 391 and a fifth outlet pipe 392. The valve module 40 further includes a fourth control valve 44. The first end 391A of the fourth inlet pipe 391 is connected to the enrichment container 18, and the second end 391B of the fourth inlet pipe 391, the second end 39B of the fourth outlet pipe 39, and the first end 392A of the fifth outlet pipe 392 are respectively connected to the fourth control valve 44. The second end 392B of the fifth outlet pipe 392 is connected to the sample container 11. The fourth control valve 44 is used to selectively connect the second end 391B of the fourth inlet pipe 391 or the second end 39B of the fourth outlet pipe 39 to the first end 392A of the fifth outlet pipe 392. In some embodiments, the fourth control valve 44 may be a solenoid valve. The fourth control valve 44, when open, connects the second end 39B of the fourth output line 39 to the first end 392A of the fifth output line 392, and when closed, connects the second end 391B of the fourth inlet line 391 to the first end 392A of the fifth output line 392. The processor also controls the corresponding operation of the second control valve 42, the third control valve 43, and the fourth control valve 44, thereby switching the tangential flow filtration system 1 to the desired mode. The enrichment container 18 can be a bottle-shaped container with a cap, and the first end 391A of the fourth inlet line 391 can contact the bottom of the bottle-shaped container so that the enrichment at the bottom can be treated.

[0091] like Figure 1 As shown, the tangential flow filtration system 1 may further include a dead-end filter device 80 disposed on the fourth inlet pipe 391, and the dead-end filter device 80 includes a second filter membrane 81. Figure 7 As shown, the tangential flow filtration system 1 also has a dead-end filtration mode Ms. In dead-end filtration mode Ms, the fourth control valve 44 connects the second end 391B of the fourth inlet pipe 391 with the first end 392A of the fifth outlet pipe 392, allowing the sample solution contained in the enrichment solution to flow to the sample container 11 through the fourth inlet pipe 391, the dead-end filtration device 80, and the fifth outlet pipe 392. Simultaneously, other impurities in the enrichment solution can be retained by the second filter membrane 81 (i.e., the pore size of the second filter membrane 81 is smaller than the particle size of the aforementioned impurities), thereby removing these impurities. When the enrichment solution is a phage enrichment solution, the aforementioned impurities can be bacteria or cell debris. The dead-end filtration device 80 can be a capsule filter.

[0092] like Figure 1As shown, in some embodiments, the tangential flow filtration system 1 may further include a second power unit 51 disposed in the fifth output line 392. The second power unit 51 provides power for the flow of the second cleaning fluid, the third cleaning fluid, or the enrichment fluid. The second power unit 51 may be various types of pumps capable of driving liquid movement, such as syringe pumps, plunger pumps, diaphragm pumps, gear pumps, and peristaltic pumps.

[0093] The following will combine Figure 8 Further explanation of the specific functions of each component in the tangential flow filtration system 1. Please refer to [link / reference]. Figure 8 This application also provides a tangential flow filtration method for the tangential flow filtration system 1 described above. Depending on different requirements, the order of steps in the above method can be changed, and some steps can be omitted or combined. The above synthesis method includes the following steps:

[0094] Step S1, as follows Figure 1 As shown, the first end 31A of the first inlet pipe 31 is connected to the first cleaning liquid container 12 containing the first cleaning liquid, the second end 31B of the first inlet pipe 31 is connected to the inlet end 21 of the tangential flow filter device 20, the first end 32A of the return pipe 32 is connected to the return end 22 of the tangential flow filter device 20, the second end 32B of the return pipe 32 and the first end 34A of the first output pipe 34 are respectively connected to the first control valve 41, the second end 34B of the first output pipe 34 is connected to the first cleaning liquid container 12, the first end 33A of the outlet pipe 33 is connected to the outlet end 23 of the tangential flow filter device 20, the second end 33B of the outlet pipe 33 and the first end 35A of the second output pipe 35 are respectively connected to the second control valve 42, and the second end 35B of the second output pipe 35 is connected to the waste liquid container 13, thereby constructing the tangential flow filter system 1.

[0095] In some embodiments, constructing the tangential flow filtration system 1 further includes connecting the first end 36A of the third output pipe 36 to the first control valve 41, and connecting the second end 36B of the third output pipe 36 to the waste liquid container 13.

[0096] In some embodiments, a first power unit 50 and a first pressure sensing device 60 may also be provided on the first liquid inlet pipe 31, with the first pressure sensing device 60 located between the first power unit 50 and the liquid inlet end 21.

[0097] Step S2, as follows Figure 3As shown, the first control valve 41 connects the second end 32B of the return pipe 32 to the first end 34A of the first output pipe 34, and the second control valve 42 disconnects the second end 33B of the liquid outlet pipe 33 and the first end 35A of the second output pipe 35, thereby switching the tangential flow filtration system 1 to the first cleaning mode Mx1. In the first cleaning mode Mx1, the first cleaning fluid is controlled to flow through the first inlet pipe 31, the tangential flow filtration device 20, the return pipe 32, and the first output pipe 34 to the first cleaning fluid container 12, and continuously circulates within the above path.

[0098] The first cleaning solution can be an alkaline solution, which can clean the pipeline and tangential flow filtration device 20 through which it flows, removing dirt, bacteria and other impurities, thereby preventing such impurities from contaminating the sample solution during subsequent tangential flow filtration and ensuring hygiene and sterility during the tangential flow filtration process.

[0099] In some embodiments, the first power unit 50 can be activated to output power and drive the flow of the first cleaning fluid. Further, the tangential flow filtration system 1 may also include a weight sensor 70, on which the first cleaning fluid container 12 is placed. In the first cleaning mode Mx1, the weight sensor 70 is used to detect the weight or weight change of the first cleaning fluid container 12. For example, the weight sensor 70 detects the weight change of the first cleaning fluid container 12, and this weight change reflects the amount of first cleaning fluid used in the first cleaning fluid container 12 under the first cleaning mode Mx1. When the weight change reaches a first preset weight value, the first power unit 50 is also used to stop outputting power, thereby completing the cleaning with the first cleaning fluid.

[0100] like Figure 2As shown, in some embodiments, before the first cleaning mode Mx1, the tangential flow filtration system 1 can be switched to the first pre-cleaning mode My1. Specifically, the first control valve 41 first connects the second end 32B of the return pipe 32 to the first end 36A of the third output pipe 36, and the second control valve 42 connects the second end 33B of the liquid outlet pipe 33 to the first end 35A of the second output pipe 35, thereby switching the tangential flow filtration system 1 to the first pre-cleaning mode My1. In the first pre-cleaning mode My1, the first cleaning fluid is controlled to flow through the first inlet pipe 31, the tangential flow filtration device 20, the return pipe 32, the liquid outlet pipe 33, the second output pipe 35, and the third output pipe 36 to the waste liquid container 13. Therefore, the first cleaning fluid can carry most of the impurities in the pipelines it flows through (such as the first inlet pipeline 31, the return pipeline 32, and the outlet pipeline 33) and the tangential flow filter device 20 into the waste liquid container 13 first, preventing these impurities from flowing into the first cleaning fluid container 12 and contaminating the first cleaning fluid under the first cleaning mode Mx1, thereby minimizing the impact of these impurities on the first cleaning fluid. In the first pre-cleaning mode My1, the first power device 50 can be activated to output power and drive the flow of the first cleaning fluid. The volume ratio of the first cleaning fluid used in the first pre-cleaning mode My1 to that used in the first cleaning mode Mx1 is not less than 3:1.

[0101] In some embodiments, after the first cleaning mode Mx1, the first control valve 41 connects the second end 32B of the return pipe 32 to the first end 36A of the third output pipe 36 again, and the second control valve 42 connects the second end 33B of the outlet pipe 33 to the first end 35A of the second output pipe 35. Then, the first end 31A of the first inlet pipe 31 is raised above the liquid surface of the first cleaning liquid container 12. The first power unit 50 continues to operate, allowing air to enter the first inlet pipe 31 from the first end 31A, and then flow through the first inlet pipe 31, the tangential flow filter device 20, the return pipe 32, the outlet pipe 33, the second output pipe 35, and the third output pipe 36 to the waste liquid container 13 (hereinafter referred to as the pre-venting mode). The diaphragm valve (not shown) of the tangential flow filter device 20 is tightened, and the first power unit 50 continues to operate, allowing the first cleaning liquid at the return end 22 to be discharged from the second end 36B of the third output pipe 36. The first cleaning fluid discharged from the second end 36B of the third output pipe 36 is collected, and the pH value of the first cleaning fluid is measured. When the measured pH value reaches about 13, it is determined that the tangential flow filter device 20 is filled with alkaline solution after the first cleaning mode Mx1, and the diaphragm valve is turned back to its original state. After the pre-venting mode, the first control valve 41 connects the second end 32B of the return pipe 32 with the first end 34A of the first output pipe 34, and the second control valve 42 disconnects or connects the second end 33B of the liquid outlet pipe 33 and the first end 35A of the second output pipe 35, so that at least part of the air flows through the first liquid inlet pipe 31, the tangential flow filter device 20, the return pipe 32, and the first output pipe 34 to the first cleaning fluid container 12 (hereinafter referred to as the venting mode), thereby venting the first cleaning fluid in the pipes and the tangential flow filter device 20. In some embodiments, the time ratio of the pre-venting mode to the venting mode is approximately 5:1, and the duration of the venting mode is not less than 30 seconds.

[0102] Step S3, as follows Figure 4 As shown, the first end 31A of the first inlet pipe 31 is connected to the second cleaning liquid container 14 containing the second cleaning liquid, and the second end 34B of the first outlet pipe 34 is connected to the second cleaning liquid container 14, thereby switching the tangential flow filtration system 1 to the second cleaning mode Mx2. In the second cleaning mode Mx2, the second cleaning liquid is controlled to flow through the first inlet pipe 31, the tangential flow filtration device 20, the return pipe 32, and the first outlet pipe 34 to the second cleaning liquid container 14.

[0103] The second cleaning fluid can be an aqueous solution, used to remove hydroxide ions remaining in the pipeline and tangential flow filter 20 from the first cleaning fluid. A second pre-cleaning mode can also be performed before the second cleaning mode Mx2. The pipeline connection method of the second pre-cleaning mode is similar to that of the first pre-cleaning mode My1, and the volume ratio of the second cleaning fluid used in the second pre-cleaning mode to that used in the second cleaning mode Mx2 is approximately 3:2.

[0104] In some embodiments, the first power unit 50 can be restarted to output power and drive the flow of the second cleaning fluid. Further, the second cleaning fluid container 14 can also be placed on the weight sensor 70. In the second cleaning mode Mx2, the weight sensor 70 is used to detect the weight or weight change of the second cleaning fluid container 14. For example, the weight sensor 70 detects the weight change of the second cleaning fluid container 14, and this weight change reflects the amount of second cleaning fluid used in the second cleaning fluid container 14 under the second cleaning mode Mx2. When the weight change reaches a fourth preset weight value, the first power unit 50 is also used to stop outputting power, thereby completing the cleaning with the second cleaning fluid.

[0105] Step S4, as follows Figure 5 As shown, the first end 31A of the first inlet pipe 31 is connected to the third cleaning liquid container 15 containing the third cleaning liquid, and the second end 34B of the first outlet pipe 34 is connected to the third cleaning liquid container 15, thereby switching the tangential flow filtration system 1 to the third cleaning mode Mx3. In the third cleaning mode Mx3, the third cleaning liquid is controlled to flow through the first inlet pipe 31, the tangential flow filtration device 20, the return pipe 32, and the first outlet pipe 34 to the third cleaning liquid container 15.

[0106] The third cleaning solution can be a buffer solution such as PBS buffer, used to restore the environment within the tubing and tangential flow filter device 20 to a neutral state. Furthermore, since the tubing and tangential flow filter device 20 have already been cleaned with the second cleaning solution before the third cleaning mode Mx3, the reaction of hydroxide ions with ions in the third cleaning solution (such as silicon or calcium ions in the PBS buffer) to form insoluble impurities can be avoided. A third pre-cleaning mode can also be performed before the third cleaning mode Mx3. The tubing connection method for the third pre-cleaning mode is similar to that of the second pre-cleaning mode, and the volume ratio of the third cleaning solution used in the third pre-cleaning mode to that used in the third cleaning mode Mx3 is approximately 3:2. In other embodiments, the second cleaning mode Mx2 and the third cleaning mode Mx3 can be omitted, i.e., only the first cleaning solution is used to clean the tubing and tangential flow filter device 20, thereby simplifying the operation process and reducing costs.

[0107] In some embodiments, the first power unit 50 can be restarted to output power to drive the flow of the third cleaning fluid. Furthermore, the third cleaning fluid container 15 can also be placed on the weight sensor 70. In the third cleaning mode Mx3, the weight sensor 70 is used to detect the weight or weight change of the third cleaning fluid container 15. For example, the weight sensor 70 detects the weight change of the third cleaning fluid container 15, and this weight change reflects the amount of third cleaning fluid used in the third cleaning fluid container 15 under the third cleaning mode Mx3, thereby allowing the first power unit 50 to determine when to stop outputting power.

[0108] In some embodiments, after the third cleaning mode Mx3, the pH value of the third cleaning liquid flowing out from the second end 36B of the third output pipe 36 can be measured with reference to the pre-venting mode and the venting mode. When the pH value reaches about 7.4-7.6, it is determined that the environment in the pipe and the tangential flow filter device 20 has been restored to a neutral environment after cleaning with the third cleaning liquid.

[0109] Step S5, as follows Figure 6 As shown, the first end 31A of the first inlet pipe 31 is connected to the sample container 11 containing the sample solution, the second end 34B of the first outlet pipe 34 is connected to the sample container 11, and the second control valve 42 connects the second end 33B of the outlet pipe 33 to the first end 35A of the second outlet pipe 35, thereby switching the tangential flow filtration system 1 to the tangential flow filtration mode Mq. In the tangential flow filtration mode Mq, the target analyte of the sample solution flows to the sample container 11 through the first inlet pipe 31, the tangential flow filtration device 20, the return pipe 32, and the first outlet pipe 34, while the remaining components of the sample solution flow to the waste container 13 through the first inlet pipe 31, the tangential flow filtration device 20, the outlet pipe 33, and the second outlet pipe 35.

[0110] In some embodiments, the first power unit 50 can be restarted to output power to drive the sample solution flow. Further, when the tangential flow filtration system 1 also includes a first pressure sensor 60, the first pressure sensor 60 can detect a first pressure value at the inlet end 21. When the first pressure value exceeds a first preset pressure value, the first power unit 50 can reduce its rotational speed, thereby avoiding damage to the target material caused by excessive transmembrane pressure across the first filter membrane 24 during concentration.

[0111] In addition, the liquid flow rate at the liquid outlet 23 can be observed. When the liquid flow rate is high, the diaphragm valve can be rotated counterclockwise to increase the pressure at the liquid outlet 23, thereby improving the separation and purification efficiency of the target substance, provided that the first pressure value does not exceed the first preset pressure value.

[0112] In some embodiments, under the tangential flow filtration mode Mq, the third control valve 43 can also connect the first end 38A of the third inlet pipe 38 to the first end 39A of the fourth outlet pipe 39, so that the third cleaning liquid in the fifth cleaning liquid container 17 flows to the sample container 11 through the third inlet pipe 38 and the fourth outlet pipe 39. In this way, the third cleaning liquid can flow into the tangential flow filtration device 20 together with the sample solution in the sample container 11 through the first inlet pipe 31. As the target substance of the sample solution flows to the sample container 11 through the first inlet pipe 31, the tangential flow filtration device 20, the return pipe 32 and the first outlet pipe 34, the third cleaning liquid and the remaining components of the sample solution flow to the waste liquid container 13 through the first inlet pipe 31, the tangential flow filtration device 20, the outlet pipe 33 and the second outlet pipe 35, until the weight sensor 70 detects that the weight of the sample container 11 has reached the second preset weight value again. Since the concentrated target substance may contain culture medium or other impurities, the target substance can be diluted by adding a third washing solution to the sample container 11 so that the third washing solution and the target substance are filtered again (also known as the displacement step). This can remove impurities such as culture medium from the target substance and improve the purity of the final target substance.

[0113] Furthermore, after the replacement step, the target material collected in sample container 11 can be removed and stored, and the tangential flow filtration system 1 can be switched to recovery mode. At this time, the third cleaning solution in the fifth cleaning solution container 17 flows to sample container 11 through the third inlet pipe 38 and the fourth outlet pipe 39, and further flows into tangential flow filtration device 20 through the first inlet pipe 31. The target material remaining in the pipes and tangential flow filtration device 20 can enter sample container 11 under the influence of the buffer solution, thereby collecting the target material remaining in the pipes and tangential flow filtration device 20.

[0114] Step S6, as follows Figure 4 As shown, the first end 31A of the first inlet pipe 31 is connected to the second cleaning liquid container 14 containing the second cleaning liquid, and the second end 34B of the first outlet pipe 34 is connected to the second cleaning liquid container 14. The second control valve 42 disconnects or connects the second end 33B of the outlet pipe 33 to the first end 35A of the second outlet pipe 35, thereby switching the tangential flow filtration system 1 to the second cleaning mode Mx2. In the second cleaning mode Mx2, at least a portion of the second cleaning liquid flows to the second cleaning liquid container 14 via the first inlet pipe 31, the tangential flow filtration device 20, the return pipe 32, and the first outlet pipe 34.

[0115] In the process of tangential flow filtration mode Mq, the pipeline and tangential flow filtration device 20 are cleaned with an aqueous solution to remove the target material or other impurities remaining in the pipeline and tangential flow filtration device 20. This also reduces the risk that the target material or other impurities remaining in the pipeline and tangential flow filtration device 20 will react with the alkaline solution to form insoluble impurities.

[0116] In some embodiments, the first power unit 50 can be turned on again to output power to drive the flow of the second cleaning fluid.

[0117] In some embodiments, the tangential flow filtering method may further include the following steps:

[0118] Step S7, as follows Figure 3 As shown, the first end 31A of the first inlet pipe 31 is connected to the first cleaning liquid container 12 containing the first cleaning liquid, and the second end 34B of the first outlet pipe 34 is connected to the first cleaning liquid container 12. The second control valve 42 disconnects the second end 33B of the outlet pipe 33 from the first end 35A of the second outlet pipe 35, thereby switching the tangential flow filtration system 1 to the first cleaning mode Mx1 (post-cleaning mode). In the first cleaning mode Mx1, the first power unit 50 drives the first cleaning liquid to flow in the reverse direction, causing the first cleaning liquid to return to the first cleaning liquid container 12 via the first outlet pipe 34, the return pipe 32, the tangential flow filtration device 20, and the first inlet pipe 31, continuously circulating within the aforementioned path.

[0119] Then, a new first cleaning solution container 12 is replaced, and the first power unit 50 drives the first cleaning solution to flow forward, so that the first cleaning solution flows through the first inlet pipe 31, the tangential flow filter device 20, the return pipe 32, and the first outlet pipe 34 to the first cleaning solution container 12, and continuously circulates within the above-mentioned path. The pipes and the tangential flow filter device 20 are cleaned with an alkaline solution, thereby further removing target substances or other impurities remaining in the pipes and the tangential flow filter device 20. Therefore, when the tangential flow filtration system 1 is used for the separation and purification of target substances in another sample solution, it can remove target substances or other impurities remaining in the pipes and the tangential flow filter device 20, reducing and preventing cross-contamination between different batches or types of sample solutions, and ensuring the purity and consistency of the final target substance. Furthermore, it can also maintain the hygienic condition and filtration efficiency of the tangential flow filtration system 1.

[0120] After the post-cleaning mode is executed, the first output pipe 34 and the second output pipe 35 are respectively filled with the first cleaning fluid, so that external impurities cannot enter the first output pipe 34 and the second output pipe 35 before the next operation of the tangential flow filtration system 1. Furthermore, since the first power pump 50 rotates in reverse and then in the forward direction, the target material accumulated on the surface of the first filter membrane 24 can be detached from the first filter membrane 24 during the reverse rotation and flow out of the tangential flow filtration device 20 under the drive of the first cleaning fluid, thereby improving the cleaning effect.

[0121] The present application will be described below through specific embodiments. Those skilled in the art should understand that the preparation methods described in this application are merely examples, and any other suitable preparation methods are within the scope of this application.

[0122] Example 1

[0123] Example 1 is illustrated using a 200 mL phage solution (phage is CPB0682) as an example.

[0124] (1) Preparation of bacteria: In the biosafety cabinet, a single clone of bacteria was picked up with a 200 μL pipette tip and blown 5 times into a shaker tube containing 3 mL of culture medium LB. The shaking speed of the shaker was 220 rpm, and the culture was carried out overnight at 37°C to obtain overnight bacteria. In the biosafety cabinet, 30 μL of overnight bacteria and 3 mL of culture medium LB were mixed in a shaker tube. The shaking speed of the shaker was 220 rpm, and the culture was carried out at 37°C for 2 h to obtain logarithmic bacteria.

[0125] (2) Phage amplification: Take 200 μL of logarithmic host bacteria and aliquot it into 5 mL centrifuge tubes. Cool the melted 0.4% top agarose to below 60°C and aliquot it into 5 mL centrifuge tubes containing logarithmic bacteria. Mix thoroughly and pour evenly onto LB plates. After the top agarose solidifies, take 10 μL of phage working solution and spot the plate. Repeat this process several times. After the working solution dries completely, invert the plate and incubate at 37°C for 3-4 hours until phage plaques appear. Use a clean pipette tip to collect phage plaques, including both the upper and lower agar layers, and co-culture them in the host bacteria culture medium.

[0126] Add 15 μL of 1 mol / L CaCl2 and 15 μL of 1 mol / L MgCl2 to 3 mL of logarithmic bacteria. The final concentration of the system is 5 mM. Then cut phage plaques and put them into the above system. Co-culture in a constant temperature shaker (shaking speed 220 rpm, temperature 37℃) until the co-culture solution begins to clarify or a large number of flocculent fragments appear, and the phage enrichment solution is obtained.

[0127] (3) Dead end filtration: Switch the tangential flow system to dead end filtration mode, set the speed of the second power device, i.e. the peristaltic pump, to 120 rpm, and gradually filter the phage enrichment solution through the dead end filter until the target amount of phage solution is collected.

[0128] (4) Endotoxin dissociation and degradation: Place the phage solution in an Erlenmeyer flask, with the volume of the phage solution being less than half the volume of the Erlenmeyer flask; add the lysis agent Triton X-100 to the phage solution at a ratio of 5%, and then place it in a constant temperature shaker (shaking speed of 220 rpm and temperature of 37 ℃) for 2 h. After incubation, centrifuge at 10000 rpm / min for 10 min, remove the bottom 2-3 mL of liquid, and use an electric pipette to collect the supernatant, which is the phage solution, and store it in a 2 L solution bottle at 4 ℃ for later use.

[0129] (5) First cleaning solution cleaning: Place a 0.5 mol / L NaOH solution with a volume of at least 400 mL (the pH value of the NaOH solution is approximately 13.5, and the volume is preferably 2 L) into the first cleaning solution container. Switch the tangential flow system to the first pre-cleaning mode and the first cleaning mode in sequence, and turn on the first power device, i.e., the peristaltic pump, at a speed of 180 rpm. In the first pre-cleaning mode, clean with 300 mL of alkaline solution. In the first cleaning mode, the peristaltic pump continues to work for 30 minutes. After the first cleaning solution cleaning is completed, lift the first end of the first output pipeline. After purging air for 150 seconds in the pre-venting mode, tighten the diaphragm valve clockwise to discharge the alkaline solution at the return end. Collect at least 8.5 mL of alkaline solution discharged from the return end and determine whether the pH value of the discharged alkaline solution reaches 13. If so, it is determined that the tangential flow filter device 20 is filled with alkaline solution after the first cleaning mode Mx1. After the pre-venting mode, turn the diaphragm valve back to its original state counterclockwise and continue to purge air for 30 seconds in the venting mode.

[0130] (6) Second cleaning solution cleaning: Switch the tangential flow system to the second pre-cleaning mode and the second cleaning mode in sequence. The peristaltic pump speed is 200 rpm. Use 1.2L of pure water for cleaning in the second pre-cleaning mode and 0.8L of pure water for cleaning in the second cleaning mode. After the second cleaning solution cleaning is completed, lift the first end of the first output pipeline and vent the air in a manner similar to step (5) so that the pure water in the return pipeline is discharged.

[0131] (7) Third cleaning solution cleaning: Switch the tangential flow system to the third pre-cleaning mode and the third cleaning mode in sequence. The peristaltic pump speed is 200 rpm. In the third pre-cleaning mode, use 0.72 L of PBS buffer for cleaning, and in the third cleaning mode, use 0.48 L of PBS buffer for cleaning. After the third cleaning solution cleaning is completed, lift the first end of the first output pipeline and vent the air in a manner similar to step (5) to drain the PBS buffer in the return pipeline. Collect the PBS buffer drained from the return end and determine whether the pH value of the drained PBS buffer is 7.4-7.6. If so, it is determined that the environment in the pipeline and the tangential flow filter device 20 has returned to a neutral environment after the third cleaning mode Mx3.

[0132] (8) Tangential Flow Filtration: The phage solution treated with the lysis agent is placed in the sample container. The volume of the phage solution is checked to see if it exceeds 200 mL. If so, the tangential flow system is switched to tangential flow filtration mode for purification and concentration of the phage particles. The peristaltic pump speed is 160 rpm. When the volume of the suspension containing phage particles in the sample container is concentrated to 200 mL, PBS buffer is added to the sample container through the fifth washing solution container and the concentration is repeated. This constitutes one replacement. The above operation is repeated 10 times. After the fourth replacement, the suspension in the sample container is sampled to obtain the phage preparation sample. During the final replacement, the volume of the suspension in the sample container is concentrated to 75 mL. Then, the first end of the first output tube is lifted, and air is purged for 1 minute to remove all residual PBS buffer from the tube and the tangential flow filtration device.

[0133] (9) Phage particle recovery: The target material collected by the sample container is removed and stored. The tangential flow system is switched to recovery mode. 200 mL of PBS buffer is added to the sample container through the fifth washing solution container and concentrated again until the remaining liquid volume in the sample container is 25 mL. Then, the first end of the first output tube is lifted and the air is purged for 90 seconds to remove all the residual PBS buffer in the tube and the tangential flow filter device.

[0134] The phage preparation samples of Example 1 were tested for potency, endotoxin content, sterility, and phage recovery rate. The test results are recorded in Table 1.

[0135] The specific steps for titer detection are as follows: (1) Dilute the sample with PBS buffer at a ratio of 1:10 to prepare phage dilutions of eight dilution gradients: 10⁻¹, 10⁻², 10⁻³, 10⁻⁴, 10⁻⁵, 10⁻⁶, 10⁻⁷, and 10⁻⁸; (2) Add 200 μL of host logarithmic bacteria and 3 mL of LB agar at 55℃ to a 5 mL centrifuge tube, seal tightly, invert and shake well, and immediately pour into the pre-divided six regions: 10⁻³, 10⁻⁴, 10⁻⁵, 10⁻⁶, 10⁻⁷, and 10⁻⁸. (3) After the bacterial plate is dried, 5 μL of phage dilution solution of each dilution gradient is dropped into the host bacterial plate and repeated 3 times. The plate is left to stand at room temperature for 20 minutes until the phage dilution solution is dried. Then it is transferred to a 37℃ incubator for 6-8 hours. (4) Calculate the number of plaque forming units (PFU) on the agar plate and then calculate the phage titer. Phage titer (PFU / mL) = average number of plaques in three replicates × dilution factor × 200.

[0136] Endotoxin levels can be detected using the endpoint colorimetric method with a horseshoe crab reagent kit.

[0137] The specific steps for sterility testing are as follows: (1) Take 200 μL of sample and spread it on a Columbia blood plate. Incubate it upside down in a 37°C incubator for 48 hours. (2) Observe whether there are colonies growing at two time points, 24 hours and 48 hours. If no bacteria grow, the phage preparation is judged to have passed the sterility test.

[0138] Table 1

[0139]

[0140] In Table 1, the collected liquid refers to the mixture obtained by mixing the suspension containing phage particles obtained from the displacement with the recovered liquid. As shown in Table 1, Example 1 can prepare a phage preparation with low endotoxin levels (endotoxin concentration below 5 EU / mL) and high potency (potency greater than 10⁹ PFU / ml), suitable for clinical treatment. Furthermore, the entire process from obtaining drug-resistant bacteria and screening for targeted phages to completing the phage preparation takes only 2 days, which helps to shorten the preparation cycle.

[0141] Example 2

[0142] The difference from Example 1 is that the volume of the phage solution is 2000 mL.

[0143] At a specific stage, the suspension in the sample container was sampled to obtain phage preparation samples. The phage preparation samples of Example 2 were subjected to potency testing, endotoxin content testing, sterility testing, and phage recovery rate testing. The test results are recorded in Table 2.

[0144] Table 2

[0145]

[0146] As shown in Table 2, Example 2 yielded a phage preparation with low endotoxin levels (endotoxin concentration below 5 EU / mL), and the phage preparation exhibited high potency (potency greater than 10⁹ PFU / mL). This indicates that the tangential flow filtration system and method of this application can be used not only for the concentration and purification of small-volume phage solutions but also for the concentration and purification of large-volume phage solutions. Furthermore, as shown in Tables 1 and 2, the tangential flow filtration system and method of this application also demonstrate good phage recovery rates.

[0147] Example 3

[0148] The difference from Example 1 is that the cells containing exosomes were cultured and expanded in a culture medium, and the supernatant was collected as the cell exosome solution. The phage solution obtained after endotoxin dissociation and degradation was replaced with the above cell exosome solution, and the cell exosomes were separated and purified.

[0149] The particle size and concentration of cell exosomes in Example 2 were detected using nanoparticle tracking analysis (NTA), and the results are recorded in Table 3.

[0150] Table 3

[0151] Sample Average particle size Concentration (Particles / mL) 20 mL of extracellular vesicles solution 123.9 nm 5.9E+9 Extracellular vesicles after replacement twice 113.2 nm 3.9E+9 Extracellular vesicles after replacement four times 117.6 nm 4.2E+9 Extracellular vesicles after replacement six times 115.8 nm 3.8E+9

[0152] As can be seen from the data in Table 3, the exosome particles prepared in Example 3 are uniform in size and have a high concentration.

[0153] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application and are not intended to limit it. Although this application has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of this application without departing from the spirit and scope of the technical solutions of this application.

Claims

1. A tangential flow filtration system configured to separate a target analyte from a sample solution, characterized in that, The tangential flow filtration system comprises: a storage module comprising a sample container configured to hold the sample solution, a first washing liquid container configured to hold a first washing liquid, and a waste liquid container; a tangential flow filtration device comprising an inlet end, a backflow end, and an outlet end; a pipeline module comprising a first inlet pipeline, a backflow pipeline, an outlet pipeline, a first output pipeline, and a second output pipeline; a valve module comprising a first control valve and a second control valve, a first end of the first inlet pipeline being selectively connected to the sample container or the first washing liquid container, a second end of the first inlet pipeline being connected to the inlet end, a first end of the backflow pipeline being connected to the backflow end, a second end of the backflow pipeline and a first end of the first output pipeline being respectively connected to the first control valve, a second end of the first output pipeline being selectively connected to the sample container or the first washing liquid container, a first end of the outlet pipeline being connected to the outlet end, a second end of the outlet pipeline and a first end of the second output pipeline being respectively connected to the second control valve, a second end of the second output pipeline being connected to the waste liquid container; the tangential flow filtration system has a first washing mode and a tangential flow filtration mode; in the first washing mode, the first end of the first inlet pipeline and the second end of the first output pipeline are respectively connected to the first washing liquid container, the first control valve connects the second end of the backflow pipeline and the first end of the first output pipeline, and the second control valve disconnects the second end of the outlet pipeline and the first end of the second output pipeline, so that the first washing liquid flows through the first inlet pipeline, the tangential flow filtration device, the backflow pipeline, and the first output pipeline to the first washing liquid container; in the tangential flow filtration mode, the first end of the first inlet pipeline and the second end of the first output pipeline are respectively connected to the sample container, the first control valve connects the second end of the backflow pipeline and the first end of the first output pipeline, and the second control valve connects the second end of the outlet pipeline and the first end of the second output pipeline, so that the target substance of the sample solution flows through the first inlet pipeline, the tangential flow filtration device, the backflow pipeline, and the first output pipeline to the sample container, and the remaining components of the sample solution flow through the first inlet pipeline, the tangential flow filtration device, the outlet pipeline, and the second output pipeline to the waste liquid container.

2. The tangential flow filtration system of claim 1, wherein, the pipeline module further comprises a third output pipeline, a first end of the third output pipeline being connected to the first control valve, and a second end of the third output pipeline being connected to the waste liquid container; The tangential flow filtration system further has a first pre-washing mode; in the first pre-washing mode, the first control valve connects the second end of the backflow pipeline with the first end of the third output pipeline, and the second control valve connects the second end of the liquid outlet pipeline with the first end of the second output pipeline, so that the first washing liquid further flows through the first liquid inlet pipeline, the tangential flow filtration device, the backflow pipeline, the liquid outlet pipeline, the second output pipeline and the third output pipeline to the waste liquid container.

3. The tangential flow filtration system of claim 1, wherein, The storage module further comprises a second washing liquid container configured to contain a second washing liquid; The tangential flow filtration system has a second washing mode; in the second washing mode, the first end of the first liquid inlet pipeline and the second end of the first output pipeline are connected to the second washing liquid container respectively, and the first control valve connects the second end of the backflow pipeline with the first end of the first output pipeline, so that the second washing liquid flows through the first liquid inlet pipeline, the tangential flow filtration device, the backflow pipeline and the first output pipeline to the second washing liquid container, the first washing liquid is an alkaline solution, and the second washing liquid is an aqueous solution; and / or The storage module further comprises a third washing liquid container configured to contain a third washing liquid; The tangential flow filtration system has a third washing mode; in the third washing mode, the first end of the first liquid inlet pipeline and the second end of the first output pipeline are connected to the third washing liquid container respectively, and the first control valve connects the second end of the backflow pipeline with the first end of the first output pipeline, so that the third washing liquid flows through the first liquid inlet pipeline, the tangential flow filtration device, the backflow pipeline and the first output pipeline to the third washing liquid container, and the third washing liquid is a buffer solution.

4. The tangential flow filtration system of any one of claims 1 to 3, wherein, A first power device is further arranged on the first liquid inlet pipeline, and the first power device is configured to output power to drive the first washing liquid or the sample solution to flow; The first power device is further configured to drive the first washing liquid to flow reversely, and the reverse flow is that the first washing liquid returns to the first washing liquid container through the first washing liquid container, the first output pipeline, the backflow pipeline, the tangential flow filtration device and the first liquid inlet pipeline.

5. The tangential flow filtration system of claim 4, wherein, A first pressure sensing device is further arranged on the first liquid inlet pipeline, and the first pressure sensing device is located between the first power device and the liquid inlet end, and the first pressure sensing device is configured to detect a first pressure value at the liquid inlet end in the tangential flow filtration mode, and the first power device is further configured to adjust the output power based on the first pressure value.

6. The tangential flow filtration system of claim 4, wherein, A weight sensing device and a processor are further included, the weight sensing device is configured to detect the weight or weight change of the sample container, and the weight sensing device is further configured to detect the weight or weight change of the first washing liquid container, and the first power device is further configured to stop outputting the power based on the weight or the weight change; The processor is electrically connected with the weight sensing device and the first control valve, and is configured to control the first control valve to operate correspondingly based on the detection of the weight sensing device.

7. The tangential flow filtration system of claim 3, wherein, The storage module further comprises a fourth cleaning liquid container configured to contain the second cleaning liquid and a fifth cleaning liquid container configured to contain the third cleaning liquid. The pipeline module further comprises a second liquid inlet pipeline, a third liquid inlet pipeline and a fourth liquid outlet pipeline, and the valve module further comprises a third control valve. A first end of the second liquid inlet pipeline is connected with the fourth cleaning liquid container, a first end of the third liquid inlet pipeline is connected with the fifth cleaning liquid container, a second end of the second liquid inlet pipeline, a second end of the third liquid inlet pipeline and a first end of the fourth liquid outlet pipeline are respectively connected with the third control valve, and a second end of the fourth liquid outlet pipeline is selectively connected with the second cleaning liquid container or the third cleaning liquid container. The tangential flow filtration system has a first liquid supplementing mode and a second liquid supplementing mode; in the first liquid supplementing mode, the third control valve connects the first end of the second liquid inlet pipeline with the first end of the fourth liquid outlet pipeline, so that the second cleaning liquid in the fourth cleaning liquid container flows to the second cleaning liquid container through the second liquid inlet pipeline and the fourth liquid outlet pipeline; in the second liquid supplementing mode, the third control valve connects the first end of the third liquid inlet pipeline with the first end of the fourth liquid outlet pipeline, so that the third cleaning liquid in the fifth cleaning liquid container flows to the third cleaning liquid container through the third liquid inlet pipeline and the fourth liquid outlet pipeline.

8. The tangential flow filtration system of claim 7, wherein, In the tangential flow filtration mode, the third control valve connects the first end of the third liquid inlet pipeline with the first end of the fourth liquid outlet pipeline, so that the third cleaning liquid in the fifth cleaning liquid container flows to the sample container through the third liquid inlet pipeline and the fourth liquid outlet pipeline.

9. The tangential flow filtration system of claim 7, wherein, The storage module further comprises an enrichment liquid container configured to contain enrichment liquid. The pipeline module further comprises a fourth liquid inlet pipeline and a fifth liquid outlet pipeline, and the valve module further comprises a fourth control valve. A first end of the fourth liquid inlet pipeline is connected with the enrichment liquid container, a second end of the fourth liquid inlet pipeline, a second end of the fourth liquid outlet pipeline and a first end of the fifth liquid outlet pipeline are respectively connected with the fourth control valve, and a second end of the fifth liquid outlet pipeline is connected with the sample container. The tangential flow filtration system further comprises a dead-end filtration device arranged on the fourth liquid inlet pipeline. The tangential flow filtration system further has a dead-end filtration mode; in the dead-end filtration mode, the fourth control valve connects the second end of the fourth liquid inlet pipeline with the first end of the fifth liquid outlet pipeline, so that the sample solution contained in the enrichment liquid flows to the sample container through the fourth liquid inlet pipeline, the dead-end filtration device and the fifth liquid outlet pipeline.

10. A tangential flow filtration method configured to isolate a target from a sample solution, characterized in that, The tangential flow filtration method comprises: connecting a first end of a first liquid inlet pipe to a first cleaning liquid container containing a first cleaning liquid, connecting a second end of the first liquid inlet pipe to a liquid inlet end of a tangential flow filtration device, connecting a first end of a backflow pipe to a backflow end of the tangential flow filtration device, connecting a second end of the backflow pipe and a first end of a first liquid outlet pipe to a first control valve respectively, connecting a second end of the first liquid outlet pipe to the first cleaning liquid container, connecting a first end of a liquid outlet pipe to a liquid outlet end of the tangential flow filtration device, connecting a second end of the liquid outlet pipe and a first end of a second liquid outlet pipe to a second control valve respectively, and connecting a second end of the second liquid outlet pipe to a waste liquid container, thereby constructing a tangential flow filtration system; the first control valve connects the second end of the backflow pipe to the first end of the first liquid outlet pipe, and the second control valve disconnects the second end of the liquid outlet pipe and the first end of the second liquid outlet pipe, thereby switching the tangential flow filtration system to a first cleaning mode; in the first cleaning mode, controlling the first cleaning liquid to flow through the first liquid inlet pipe, the tangential flow filtration device, the backflow pipe, and the first liquid outlet pipe to the first cleaning liquid container; connecting a first end of the first liquid inlet pipe to a sample container containing the sample solution, connecting a second end of the first liquid outlet pipe to the sample container, and connecting the second end of the liquid outlet pipe to the first end of the second liquid outlet pipe by the second control valve, thereby switching the tangential flow filtration system to a tangential flow filtration mode; and in the tangential flow filtration mode, controlling a target of the sample solution to flow through the first liquid inlet pipe, the tangential flow filtration device, the backflow pipe, and the first liquid outlet pipe to the sample container, and controlling the remaining components of the sample solution to flow through the first liquid inlet pipe, the tangential flow filtration device, the liquid outlet pipe, and the second liquid outlet pipe to the waste liquid container.

11. The tangential flow filtration method of claim 10, wherein, constructing the tangential flow filtration system further comprises connecting a first end of a third liquid outlet pipe to the first control valve, and connecting a second end of the third liquid outlet pipe to the waste liquid container; before switching the tangential flow filtration system to the first cleaning mode, the tangential flow filtration method further comprises: the first control valve connects the second end of the backflow pipe to the first end of the third liquid outlet pipe, and the second control valve connects the second end of the liquid outlet pipe to the first end of the second liquid outlet pipe, thereby switching the tangential flow filtration system to a first pre-cleaning mode; in the first pre-cleaning mode, controlling the first cleaning liquid to flow through the first liquid inlet pipe, the tangential flow filtration device, the backflow pipe, the liquid outlet pipe, the second liquid outlet pipe, and the third liquid outlet pipe to the waste liquid container.

12. The tangential flow filtration method of claim 11, wherein, after controlling the first cleaning liquid to flow to the first cleaning liquid container, the tangential flow filtration method further comprises: connecting a second end of the return pipeline with a first end of the third output pipeline, connecting a second end of the liquid outlet pipeline with a first end of the second output pipeline, and lifting a first end of the first liquid inlet pipeline to above a liquid level of the first cleaning liquid container, so as to switch the tangential flow filtration system to a pre-evacuation mode; in the pre-evacuation mode, controlling air to flow through the first liquid inlet pipeline, the tangential flow filtration device, the return pipeline, the liquid outlet pipeline, the second output pipeline, and the third output pipeline to the waste liquid container; connecting a second end of the return pipeline with a first end of the first output pipeline, so as to switch the tangential flow filtration system to an evacuation mode; and in the evacuation mode, controlling air to flow through the first liquid inlet pipeline, the tangential flow filtration device, the return pipeline, and the first output pipeline to the first cleaning liquid container.

13. The tangential flow filtration method of claim 10, wherein, After controlling the first cleaning liquid to flow to the first cleaning liquid container, the tangential flow filtration method further comprises: connecting a second end of the first liquid inlet pipeline with a second cleaning liquid container containing a second cleaning liquid, and connecting a second end of the first output pipeline with the second cleaning liquid container, so as to switch the tangential flow filtration system to a second cleaning mode; in the second cleaning mode, controlling the second cleaning liquid to flow through the first liquid inlet pipeline, the tangential flow filtration device, the return pipeline, and the first output pipeline to the second cleaning liquid container, the first cleaning liquid being an alkali solution, and the second cleaning liquid being an aqueous solution; connecting a second end of the first liquid inlet pipeline with a third cleaning liquid container containing a third cleaning liquid, and connecting a second end of the first output pipeline with the third cleaning liquid container, so as to switch the tangential flow filtration system to a third cleaning mode; and in the third cleaning mode, controlling the third cleaning liquid to flow through the first liquid inlet pipeline, the tangential flow filtration device, the return pipeline, and the first output pipeline to the third cleaning liquid container, the third cleaning liquid being a buffer solution.

14. The tangential flow filtration method of any one of claims 10 to 13, wherein, Controlling the first cleaning liquid to flow to the first cleaning liquid container specifically comprises: providing a first power device on the first liquid inlet pipeline and starting the first power device, so that the first power device outputs power to drive the first cleaning liquid to flow; Controlling the sample solution to flow to the sample container specifically comprises: starting the first power device again, so that the first power device outputs power to drive the sample solution to flow.

15. The tangential flow filtration method of claim 14, wherein, Constructing the tangential flow filtration system further comprises: providing a first pressure sensing device on the first liquid inlet pipeline, the first pressure sensing device being located between the first power device and the liquid inlet end; After controlling the sample solution to flow to the sample container, the tangential flow filtration method further comprises: the first pressure sensing device detects a first pressure value at the liquid inlet end; and the first power device adjusts the output power based on the first pressure value.

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