Tangential flow filtration apparatus

Abstract

The invention discloses tangential flow filtering equipment, and relates to the technical field of exosome extraction. The tangential flow filtering equipment comprises a buffer container, a liquid storage container and a tangential flow filtering device, the liquid inlet end of the liquid storage container is communicated with the liquid outlet end of the buffer container through a first pipeline; the liquid inlet end of the tangential flow filtering device is communicated with the liquid outlet end of the liquid storage container through a second pipeline, and the liquid outlet end of the tangential flow filtering device is communicated with the backflow end of the liquid storage container through a third pipeline; wherein the first pipeline is communicated with the second pipeline through a fourth pipeline, a first valve is arranged at the communication position of the first pipeline and the fourth pipeline, and a second valve is arranged at the communication position of the second pipeline and the fourth pipeline. The pipeline structure of the tangential flow filtering equipment is improved, the steps of alkali circulation washing, alkali one-way washing, water washing, top washing and the like are executed in one pipeline system, the pipeline does not need to be disassembled and assembled for many times, the tangential flow filtering efficiency of the exosome is greatly improved, and the integrity of the system is better.

Description

Technical Field

[0001] This invention relates to the field of exosome extraction technology, and more particularly to a tangential flow filtration device. Background Technology

[0002] Tangential flow filtration (TFF) is a filtration technique where the liquid flow direction is perpendicular to the filtration direction, utilizing the pore size and pressure difference of a membrane for filtration. In conventional filtration, the liquid passes directly through the membrane into the downstream environment, while large particles or molecules are trapped at the top of the membrane, eventually forming a filter cake that clogs the pores. In TFF, because the liquid flows parallel to the membrane surface, it continuously flushes the membrane during filtration, preventing the formation of a filter cake that can clog the filter. Therefore, TFF can filter a significantly larger volume of liquid than conventional filtration. TFF is widely used in downstream purification processes in biopharmaceuticals, including solution concentration, dialysis, purification, and buffer replacement.

[0003] Exosomes are tiny vesicles with a diameter between 40 and 150 nm, containing lipid structures and contents such as proteins and RNA. Due to their small size, yet significantly larger than small molecule impurities such as salts and free proteins, they can be separated and extracted from cell supernatant or tissue fluid using transfiltration fractionation (TFF). After removing larger impurities through a filter, tangential flow filtration is performed using a high-molecular-weight membrane or hollow fiber column. By continuously filtering out small molecules such as salts and free proteins, exosomes can be extracted for subsequent experiments and research.

[0004] The TFF system for exosome extraction typically involves several steps: alkali circulation washing of tubing, membrane / hollow fiber column → ultrapure water washing of tubing, membrane / hollow fiber column → ultrafiltration and buffer replacement → top washing → water washing of tubing, membrane / hollow fiber column → alkali circulation washing of tubing, membrane / hollow fiber column → unidirectional alkali washing of tubing, membrane / hollow fiber column.

[0005] Existing tangential flow systems include replenishment bottles, storage tanks, waste tanks, membrane packs or hollow fiber columns, which can perform ultrafiltration and buffer replacement steps. However, steps such as alkaline circulation washing, alkaline one-way washing, water washing, and top washing cannot be completed in existing systems. These steps require manual reconnection of tubing, which is cumbersome, greatly reduces the efficiency of exosome extraction, and compromises the integrity of the system. Summary of the Invention

[0006] The main objective of this invention is to provide a tangential flow filtration device that aims to improve the efficiency of exosome extraction, facilitate operation, and enhance the integrity of the tangential flow filtration system.

[0007] To achieve the above objectives, the present invention provides a tangential flow filtration device, comprising:

[0008] Buffer container, used to hold buffer solutions;

[0009] A liquid storage container for storing sample solutions, wherein the inlet of the liquid storage container is connected to the outlet of the buffer container via a first conduit; and

[0010] A tangential flow filter is used to perform tangential flow filtration on a sample solution to extract the target analyte. The inlet end of the tangential flow filter is connected to the outlet end of the storage container through a second pipeline, and the outlet end of the tangential flow filter is connected to the reflux end of the storage container through a third pipeline. The outlet end of the tangential flow filter is used to discharge the waste liquid after tangential flow filtration.

[0011] The first pipeline and the second pipeline are connected by a fourth pipeline, and a first valve is provided at the connection between the first pipeline and the fourth pipeline, and a second valve is provided at the connection between the second pipeline and the fourth pipeline.

[0012] Optionally, the tangential flow filtration device further includes a waste liquid container, which is connected to the discharge end of the tangential flow filter device through a fifth pipeline and is used to store the waste liquid after tangential flow filtration.

[0013] Optionally, the first valve has at least a tee fitting, and the second valve has at least a tee fitting.

[0014] Optionally, the tangential flow filtration device further includes an alkali circulation container for storing alkali solution and an ultrapure water container for storing ultrapure water. The alkali circulation container and the ultrapure water container are connected via a sixth pipeline. The sixth pipeline is connected to the first pipeline via a first valve. The alkali circulation container is connected to the fifth pipeline via a seventh pipeline. A third valve is provided at the connection between the fifth pipeline and the seventh pipeline. The alkali circulation container and the third pipeline are connected via an eighth pipeline. The eighth pipeline is connected to the waste liquid container via a ninth pipeline. A fourth valve is provided at the connection between the eighth pipeline and the third pipeline. A fifth valve is provided at the connection between the eighth pipeline and the ninth pipeline.

[0015] Optionally, the first valve has at least a five-way connector, the second valve has at least a three-way connector, the third valve has at least a three-way connector, the fourth valve has at least a three-way connector, and the fifth valve has at least a three-way connector.

[0016] Optionally, the tangential flow filtration device further includes an alkali one-way liquid container for storing alkali solution. The alkali one-way liquid container is connected to a first valve on the first pipeline via a tenth pipeline, the third pipeline is connected to the waste liquid container via a ninth pipeline, and the third pipeline and the ninth pipeline are connected via a fourth valve.

[0017] Optionally, the first valve has at least a four-way connector, the second valve has at least a three-way connector, and the fourth valve has at least a three-way connector.

[0018] Optionally, the tangential flow filtration device further includes an alkaline one-way liquid container for storing alkaline solution, the alkaline one-way liquid container being connected to a first valve on the first pipeline via a tenth pipeline.

[0019] Optionally, the first valve has at least a six-way connector, the second valve has at least a three-way connector, the third valve has at least a three-way connector, the fourth valve has at least a three-way connector, and the fifth valve has at least a three-way connector.

[0020] Optionally, the tangential flow filter element is a membrane envelope or a hollow fiber column; and / or

[0021] The tangential flow filtration device further includes a first drive pump and a second drive pump, wherein the first drive pump is disposed on the first pipeline and the second drive pump is disposed on the second pipeline.

[0022] In the technical solution of the present invention, the tangential flow filtration device includes a buffer container, a storage container, and a tangential flow filter element; the buffer container is used to contain a buffer solution; the storage container is used to store a sample solution, and the inlet end of the storage container is connected to the outlet end of the buffer container through a first pipeline; the tangential flow filter element is used to perform tangential flow filtration on the sample solution to extract the target substance, and the inlet end of the tangential flow filter element is connected to the outlet end of the storage container through a second pipeline, the outlet end of the tangential flow filter element is connected to the reflux end of the storage container through a third pipeline, and the drain end of the tangential flow filter element is used to discharge the waste liquid after tangential flow filtration; wherein, the first pipeline and the second pipeline are connected through a fourth pipeline, and a first valve is provided at the connection between the first pipeline and the fourth pipeline, and a second valve is provided at the connection between the second pipeline and the fourth pipeline. It is understood that by employing the tangential flow filtration device with the above-described structure, the present invention can achieve at least two steps of ultrafiltration and buffer replacement and top washing during exosome extraction by controlling the operation of the first and second valves, which greatly improves the efficiency of exosome extraction, makes operation more convenient, and enhances the integrity of the tangential flow filtration system. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the structures shown in these drawings without creative effort.

[0024] Figure 1 This is a schematic diagram of the structure of an embodiment of the tangential flow filtration device of the present invention;

[0025] Figure 2 This is a schematic diagram of another embodiment of the tangential flow filtration device of the present invention;

[0026] Figure 3 This is a schematic diagram of another embodiment of the tangential flow filtration device of the present invention;

[0027] Figure 4 This is a schematic diagram of another embodiment of the tangential flow filtration device of the present invention.

[0028] Explanation of icon numbers:

[0029] 10. Buffer container; 20. Liquid storage container; 30. Tangential flow filter device; 40. Waste liquid container; 50. Alkali circulation liquid container; 60. Ultrapure water container; 70. Alkali one-way liquid container; 101. First pipeline; 102. Second pipeline; 103. Third pipeline; 104. Fourth pipeline; 105. Fifth pipeline; 106. Sixth pipeline; 107. Seventh pipeline; 108. Eighth pipeline; 109. Ninth pipeline; 110. Tenth pipeline; 201. First valve; 202. Second valve; 203. Third valve; 204. Fourth valve; 205. Fifth valve; 301. First drive pump; 302. Second drive pump.

[0030] The realization of the objective, functional features and advantages of the present invention will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0031] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0032] It should be noted that all directional indications (such as up, down, left, right, front, back, etc.) in the embodiments of the present invention are only used to explain the relative positional relationship and movement of each component in a certain specific posture (as shown in the figure). If the specific posture changes, the directional indication will also change accordingly.

[0033] In the description of this invention, it should also be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0034] Furthermore, the use of terms such as "first" and "second" in this invention is for descriptive purposes only and should not be construed as indicating or implying their relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined with "first" or "second" may explicitly or implicitly include at least one of those features. The word "and / or" throughout the text means including three parallel solutions; for example, "A and / or B" includes solution A, solution B, or a solution that simultaneously satisfies A and B. The technical solutions of the various embodiments can be combined with each other, but this must be based on the ability of those skilled in the art to implement them. When the combination of technical solutions is contradictory or impossible to implement, it should be considered that such a combination of technical solutions does not exist and is not within the scope of protection claimed by this invention.

[0035] This invention proposes a tangential flow filtration device, which can be applied to the extraction of exosomes, etc., and is not limited to this.

[0036] Example 1

[0037] Reference Figure 1 In one embodiment of the present invention, the tangential flow filtration device includes a buffer container 10, a storage container 20, and a tangential flow filter element 30; the buffer container 10 is used to contain a buffer solution; the storage container 20 is used to store a sample solution, and the inlet end of the storage container 20 is connected to the outlet end of the buffer container 10 through a first pipe 101; the tangential flow filter element 30 is used to perform tangential flow filtration on the sample solution to extract the target substance, and the inlet end of the tangential flow filter element 30 is connected to the outlet end of the storage container 20 through a second pipe 102, the outlet end of the tangential flow filter element 30 is connected to the reflux end of the storage container 20 through a third pipe 103, and the drain end of the tangential flow filter element 30 is used to discharge the waste liquid after tangential flow filtration. The first pipeline 101 and the second pipeline 102 are connected through the fourth pipeline 104, and a first valve 201 is provided at the connection between the first pipeline 101 and the fourth pipeline 104, and a second valve 202 is provided at the connection between the second pipeline 102 and the fourth pipeline 104.

[0038] In this embodiment, the tangential flow filter device 30 may be a membrane pack or a hollow fiber column, etc. The membrane pack is not limited to 300Kda or 500Kda, etc., and the hollow fiber column is not limited to 300Kda or 500Kda, etc.

[0039] In this embodiment, the first valve 201 can be a manual or automatic valve with three or more passages, or a combination of a manual valve and an automatic valve. The automatic valve can be a solenoid valve, an electric valve, or a pneumatic valve, etc. The second valve 202 and other valves mentioned herein are similar and are not limited here.

[0040] Furthermore, all pipelines mentioned in this article can be one, two, or more pipelines; no limitation is made here.

[0041] To accelerate the fluid flow rate and improve the tangential flow filtration effect and efficiency, in this embodiment, the tangential flow filtration device may further include a first drive pump 301 and a second drive pump 302. The first drive pump 301 is disposed on the first pipeline 101, and the second drive pump 302 is disposed on the second pipeline 102. Both the first drive pump 301 and the second drive pump 302 may preferably be peristaltic pumps or the like, and are not limited here.

[0042] In this embodiment, the tangential flow filtration device may further include a waste liquid container 40 for collecting waste liquid. The waste liquid container 40 is connected to the discharge end of the tangential flow filter device 30 through a fifth pipeline 105 and is used to store the waste liquid after tangential flow filtration. This also enables the tangential flow filtration device to achieve more process flows.

[0043] The tangential flow filtration device of this embodiment can perform at least ultrafiltration and buffer replacement steps and top washing steps. The following description uses the first valve 201 as a three-way valve and the second valve 202 as an example. (Refer to...) Figure 1 The specific workflow is as follows:

[0044] S11. In the ultrafiltration and buffer replacement steps, the ab end of the first valve 201 is opened and the c end is closed to connect the buffer container 10 and the storage container 20. The first drive pump 301 is also controlled to operate, so that the buffer solution is transported from the buffer container 10 through the first pipeline 101 and the first drive pump 301 to the storage container 20 to replenish the buffer solution. The xz end of the second valve 202 is opened and the y end is closed to connect the outlet end of the storage container 20 and the inlet end of the tangential flow filter element 30. The second drive pump 302 is also controlled to operate, so that the buffer solution and sample are transported from the buffer container 10 through the second pipeline 102 and the second drive pump 302 to the tangential flow filter element 30. The outlet end of the tangential flow filter element 30 can be directly connected to the waste liquid container 40, and the outlet end can be directly connected to the return end of the storage container 20.

[0045] It should be noted that during ultrafiltration and buffer replacement, the tangential flow filter device 30 can use a membrane pack with a molecular weight of 300kDa / 500kDa or a hollow fiber column. The sample solution passes through the filter membrane under pressure. Molecules larger than the membrane pore size (exosomes) are retained on the membrane (called retentate) and return to the solution through the reflux end, flowing into the storage container 20. Molecules smaller than the membrane pore size (such as salts, small molecule impurities, denaturants, etc.) flow out with the buffer solution (called percolate) into the waste container 40. By continuously adding new buffer solution to the system and controlling the percolation rate, impurities or unwanted components in the original buffer solution can be gradually removed, thereby achieving sample extraction and separation as well as buffer replacement.

[0046] S12. In the top washing step, the ac end of the first valve 201 is opened and the b end is closed, and the yz end of the second valve 202 is opened and the x end is closed, so as to connect the first pipeline 101 and the second pipeline 102 through the fourth pipeline 104, so that the buffer solution starts from the buffer container 10, passes through the ac end of the first valve 201 and through the fourth pipeline 104, and then passes through the yz end of the second valve 202 and is delivered to the tangential flow filter device 30 under the drive of the second drive pump 302; wherein, the discharge end of the tangential flow filter device 30 can be directly connected to the waste liquid container 40, and the outlet end of the tangential flow filter device 30 can be directly connected to the return end of the storage container 20.

[0047] It should be noted that after buffer replacement, a top-washing step is usually required. This involves connecting the buffer container 10 to the second tubing 102, and using the second drive pump 302 to directly top-wash and displace the feed solution from the tubing and membrane pack using the buffer solution, which is then recycled into the storage container 20. Because the feed solution concentration is high after the ultrafiltration concentration process, some liquid residue remains in the system tubing and membrane pack. The top-washing operation maximizes the collection of feed solution, ensuring a high recovery rate.

[0048] It is understood that by adopting the tangential flow filtration device with the above-described structure, the present invention can achieve at least the two steps of ultrafiltration and buffer replacement and top washing during exosome extraction by controlling the operation of the first valve 201 and the second valve 202, which greatly improves the efficiency of exosome extraction, makes operation more convenient, and enhances the integrity of the tangential flow filtration system.

[0049] Example 2

[0050] In another embodiment, to achieve more steps related to exosome extraction, refer to Figure 2Based on the aforementioned embodiments, the tangential flow filtration device may further include an alkali circulation container 50 for storing alkali solution and an ultrapure water container 60 for storing ultrapure water. The alkali circulation container 50 and the ultrapure water container 60 are connected through a sixth pipeline 106. The sixth pipeline 106 is connected to the first pipeline 101 through a first valve 201. The alkali circulation container 50 is connected to the fifth pipeline 105 through a seventh pipeline 107. A third valve 203 is provided at the connection between the fifth pipeline 105 and the seventh pipeline 107. The alkali circulation container 50 and the third pipeline 103 are connected through an eighth pipeline 108. A fourth valve 204 is provided at the connection between the eighth pipeline 108 and the third pipeline 103. The eighth pipeline 108 is connected to the waste liquid container 40 through a ninth pipeline 109. A fifth valve 205 is provided at the connection between the eighth pipeline 108 and the ninth pipeline 109.

[0051] In this embodiment, the first valve 201 differs from the previous embodiment in that it has at least a five-way connector, and can be a five-way / six-way / seven-way valve, etc. Here, a five-way valve is selected. Similarly, the second valve 202 is a three-way valve. In addition, this embodiment also adds an alkali circulation liquid container 50, an ultrapure water container 60, and multiple connecting pipelines, as well as a third valve 203, a fourth valve 204, and a fifth valve 205 on them. The third valve 203, the fourth valve 204, and the fifth valve 205 are all three-way valves.

[0052] The tangential flow filtration device in this embodiment can perform at least the following steps: alkaline circulation washing of the tubing and membrane / hollow fiber column → ultrapure water cleaning of the tubing and membrane / hollow fiber column → ultrafiltration and buffer replacement → top washing → water washing of the tubing and membrane / hollow fiber column → alkaline circulation washing of the tubing and membrane / hollow fiber column. The specific workflows for the alkaline circulation washing and water washing steps of the tubing and membrane / hollow fiber column are as follows:

[0053] S21. In the alkali circulation washing steps of the pipeline and membrane / hollow fiber column, control the DC end of the first valve 201 to be open and the ABE end to be closed, the YZ end of the second valve 202 to be open and the X end to be closed, and control the UW end of the third valve 203 to be open and the V end to be closed, control the PQ end of the fourth valve 204 to be open and the O end to be closed, and control the MIL end of the fifth valve 205 to be open and the N end to be closed, so that the alkali circulation liquid starts from the alkali circulation liquid container 50, passes through the sixth pipeline 106, and passes through the first valve 201. The liquid flows from the DC end to the fourth pipeline 104, and then, driven by the second drive pump 302, is transported through the second pipeline 102 to the tangential flow filter element 30. The liquid discharged from the drain end of the tangential flow filter element 30 flows sequentially through the UW end of the third valve 203 and the seventh pipeline 107 to the alkali circulation liquid container 50. The liquid from the outlet end of the tangential flow filter element 30 flows sequentially through the PQ end of the fourth valve 204 and the ml end of the fifth valve 205, and then through the eighth pipeline 108 to the alkali circulation liquid container 50.

[0054] S22. In the pipeline and membrane / hollow fiber column washing steps, the EC end of the first valve 201 is opened and the ABD end is closed, and the YZ end of the second valve 202 is opened and the X end is closed, so that ultrapure water flows from the ultrapure water container 60 sequentially through the sixth pipeline 106, the EC end of the first valve 201, the fourth pipeline 104, the second pipeline 102 and the second drive pump 302 on it to the tangential flow filter element 30. The liquid discharged from the drain end of the tangential flow filter element 30 is discharged to the waste liquid container 40 through the UV end of the third valve 203. The solution from the outlet end of the tangential flow filter element 30 flows to the waste liquid container 40 through the PQ end of the fourth valve 204 and the MN end of the fifth valve 205.

[0055] Example 3

[0056] In yet another embodiment, to achieve the alkaline one-way washing step, refer to Figure 3 Based on the aforementioned embodiment 1, the tangential flow filtration device may further include an alkali one-way liquid container 70 for storing alkali solution. The alkali one-way liquid container 70 is connected to the first valve 201 on the first pipeline 101 through the tenth pipeline 110. The third pipeline 103 is connected to the waste liquid container 40 through the ninth pipeline 109. The third pipeline 103 and the ninth pipeline 109 are connected through the fourth valve 204. A fifth valve 205 may also be provided on the ninth pipeline 109.

[0057] The difference between this embodiment and the first embodiment described above is that an alkali one-way liquid container 70 and its connecting pipeline are added, and the first valve 201 has at least a four-way connector, which is selected here. In addition, the second valve 202, the fourth valve 204 and the fifth valve 205 in this embodiment are all three-way valves.

[0058] The tangential flow filtration device of this embodiment can perform at least the following steps: ultrafiltration and buffer replacement → top washing → alkaline one-way washing of tubing, membrane pack / hollow fiber column. The specific workflow of the alkaline one-way washing step is as follows:

[0059] S31. In the step of alkali one-way washing of pipelines, membrane packs / hollow fiber columns, the fc end of the first valve 201 is opened and the ab end is closed, the yz end of the second valve 202 is opened and the x end is closed, the pq end of the fourth valve 204 is opened and the o end is closed, and the mn end of the fifth valve 205 is opened and the l end is closed, so that the alkali one-way liquid flows from the alkali one-way liquid container 70 sequentially through the tenth pipeline 110, the fc end of the first valve 201, the fourth pipeline 104, the yz end of the second valve 202, and the second pipeline 102, and then flows into the tangential flow filter element 30 under the drive of the second drive pump 302, and the liquid at the discharge end of the tangential flow filter element 30 is discharged into the waste liquid container 40, and the solution flowing out of the outlet end of the tangential flow filter element 30 flows to the waste liquid container 40 through the pq end of the fourth valve 204 and the mn end of the fifth valve 205.

[0060] Example 4

[0061] In yet another embodiment, to achieve more exosome extraction process steps, refer to... Figure 4 The tangential flow filtration device may further include an alkali circulation container 50 for storing alkali solution, an ultrapure water container 60 for storing ultrapure water, and an alkali one-way liquid container 70 for storing alkali solution. The alkali circulation container 50 and the ultrapure water container 60 are connected through a sixth pipeline 106. The sixth pipeline 106 is connected to the first pipeline 101 through a first valve 201. The alkali circulation container 50 is connected to the fifth pipeline 105 through a seventh pipeline 107. A third valve 203 is provided at the connection between the fifth pipeline 105 and the seventh pipeline 107. The alkali circulation container 50 and the third pipeline 103 are connected through an eighth pipeline 108. A fourth valve 204 is provided at the connection between the eighth pipeline 108 and the third pipeline 103. The eighth pipeline 108 is connected to the waste liquid container 40 through a ninth pipeline 109. A fifth valve 205 is provided at the connection between the eighth pipeline 108 and the ninth pipeline 109. The alkali one-way liquid container 70 is connected to the first valve 201 on the first pipeline 101 via the tenth pipeline 110.

[0062] The difference between this embodiment and the aforementioned Embodiment 2 is that an alkaline one-way liquid container 70 and its connecting pipeline are added, and the first valve 201 has at least a six-way connector, which is selected here. In addition, the second valve 202, the third valve 203, the fourth valve 204, and the fifth valve 205 are all three-way valves.

[0063] The tangential flow filtration device of this embodiment can perform at least the following steps: alkaline circulation washing of pipelines, membrane pack / hollow fiber column → ultrapure water cleaning of pipelines, membrane pack / hollow fiber column → ultrafiltration and buffer replacement → top washing → water washing of pipelines, membrane pack / hollow fiber column → alkaline circulation washing of pipelines, membrane pack / hollow fiber column → unidirectional alkaline washing of pipelines, membrane pack / hollow fiber column.

[0064] S41. During the ultrafiltration and buffer replacement steps, the ab end of the first valve 201 is opened and the cdef end is closed; the xz end of the second valve 202 is opened and the y end is closed; the uv end of the third valve 203 is opened and the w end is closed; and the op end of the fourth valve 204 is opened and the q end is closed. This allows the buffer solution to flow from the buffer container 10 through the first pipeline 101, the ab end of the first valve 201, and under the drive of the first drive pump 301, to the storage container 20 to replenish the buffer solution. Then, the solution is sequentially transported through the second pipeline 102, the xz end of the second valve 202, and the second drive pump 302 to the tangential flow filter element 30. The discharge end of the tangential flow filter element 30 is discharged into the waste container 40 through the uv end of the third valve 203. The outlet end of the tangential flow filter element 30 is transported into the storage container 20 through the op end of the fourth valve 204.

[0065] S42. In the topwash step, the ac end of the first valve 201 is opened and the bdef end is closed, the yz end of the second valve 202 is opened and the x end is closed, the uv end of the third valve 203 is opened and the w end is closed, and the op end of the fourth valve 204 is opened and the q end is closed, so that the buffer solution starts from the buffer container 10, passes through the first pipeline 101, the ac end of the first valve 201, the fourth pipeline 104, the yz end of the second valve 202, and is delivered to the tangential flow filter element 30 through the second pipeline 102 and the second drive pump 302 thereon; the liquid at the drain end of the tangential flow filter element 30 is discharged to the waste liquid container 40 through the uv end of the third valve 203, and the solution at the outlet end of the tangential flow filter element 30 flows back to the storage container 20 through the op end of the fourth valve 204.

[0066] S43. In the alkali circulation washing step, control the DC end of the first valve 201 to be open and the ABEF end to be closed, the YZ end of the second valve 202 to be open and the X end to be closed, the UW end of the third valve 203 to be open and the V end to be closed, the PQ end of the fourth valve 204 to be open and the O end to be closed, and the MIL end of the fifth valve 205 to be open and the N end to be closed, so that the alkali circulation liquid starts from the alkali circulation liquid container 50 and passes sequentially through the sixth pipeline 106, the DC end of the first valve 201, the fourth pipeline 104, and the second valve 205. The liquid from the yz end of 02, the second pipeline 102 and the second drive pump 302 thereon are delivered to the tangential flow filter element 30; the liquid from the discharge end of the tangential flow filter element 30 is delivered to the alkali circulation liquid container 50 via the fifth pipeline 105 and the uw end of the third valve 203 thereon and the seventh pipeline 107; the liquid from the outlet end of the tangential flow filter element 30 is delivered to the alkali circulation liquid container 50 via the third pipeline 103, the pq end of the fourth valve 204, the ml end of the fifth valve 205 and the eighth pipeline 108.

[0067] S44. During the water washing step, control the following: the EC end of the first valve 201 is open, and the ABDF end is closed; the YZ end of the second valve 202 is open, and the X end is closed; the UV end of the third valve 203 is open, and the W end is closed; the PQ end of the fourth valve 204 is open, and the O end is closed; the MN end of the fifth valve 205 is open, and the L end is closed, so that ultrapure water flows from the ultrapure water container 60 through the sixth pipeline 106, the EC end of the first valve 201, and the fourth pipeline 104. The liquid from the second valve 202 (YZ), the second pipeline 102, and the second drive pump 302 is transported to the tangential flow filter element 30; the liquid from the discharge end of the tangential flow filter element 30 is transported to the waste liquid container 40 via the fifth pipeline 105 and the uv end of the third valve 203; the liquid from the outlet end of the tangential flow filter element 30 is transported to the waste liquid container 40 via the third pipeline 103, the pq end of the fourth valve 204, the mn end of the fifth valve 205, and the ninth pipeline 109.

[0068] S45. In the alkali one-way washing step, control the fc end of the first valve 201 to be open and the abed end to be closed; control the yz end of the second valve 202 to be open and the x end to be closed; control the uv end of the third valve 203 to be open and the w end to be closed; control the pq end of the fourth valve 204 to be open and the o end to be closed; control the mn end of the fifth valve 205 to be open and the l end to be closed, so that the alkali one-way liquid starts from the alkali one-way liquid container 70 and passes sequentially through the tenth pipeline 110, the fc end of the first valve 201, and the fourth pipeline 104. The solution from the yz end of the second valve 202 is then transported to the tangential flow filter element 30 via the second pipeline 102 and the second drive pump 302 thereon; the solution from the discharge end of the tangential flow filter element 30 is transported to the waste liquid container 40 via the uv end of the third valve 203 and the fifth pipeline 105; the solution from the outlet end of the tangential flow filter element 30 is transported to the waste liquid container 40 via the third pipeline 103, the pq end of the fourth valve 204, the mn end of the fifth valve 205, and the ninth pipeline 109.

[0069] The above description is merely an optional embodiment of the present invention and does not limit the patent scope of the present invention. All equivalent structural transformations made using the contents of the present invention's specification and drawings under the inventive concept of the present invention, or direct / indirect applications in other related technical fields, are included within the patent protection scope of the present invention.

Claims

1. A tangential flow filtration device, characterized in that, include: Buffer container, used to hold buffer solutions; A liquid storage container for storing sample solutions, wherein the inlet of the liquid storage container is connected to the outlet of the buffer container via a first pipeline; as well as A tangential flow filter is used to perform tangential flow filtration on a sample solution to extract the target analyte. The inlet end of the tangential flow filter is connected to the outlet end of the storage container through a second pipeline, and the outlet end of the tangential flow filter is connected to the reflux end of the storage container through a third pipeline. The outlet end of the tangential flow filter is used to discharge the waste liquid after tangential flow filtration. The first pipeline and the second pipeline are connected by a fourth pipeline, and a first valve is provided at the connection between the first pipeline and the fourth pipeline, and a second valve is provided at the connection between the second pipeline and the fourth pipeline.

2. The tangential flow filtration device as described in claim 1, characterized in that, The tangential flow filtration device also includes a waste liquid container, which is connected to the discharge end of the tangential flow filter device through a fifth pipeline and is used to store the waste liquid after tangential flow filtration.

3. The tangential flow filtration device as described in claim 1, characterized in that, The first valve has at least a three-way connector, and the second valve has at least a three-way connector.

4. The tangential flow filtration device as described in claim 2, characterized in that, The tangential flow filtration device further includes an alkali circulation container for storing alkali solution and an ultrapure water container for storing ultrapure water. The alkali circulation container and the ultrapure water container are connected via a sixth pipeline. The sixth pipeline is connected to the first pipeline via a first valve. The alkali circulation container is connected to the fifth pipeline via a seventh pipeline. A third valve is provided at the connection between the fifth pipeline and the seventh pipeline. The alkali circulation container is connected to the third pipeline via an eighth pipeline. The eighth pipeline is connected to the waste liquid container via a ninth pipeline. A fourth valve is provided at the connection between the eighth pipeline and the third pipeline. A fifth valve is provided at the connection between the eighth pipeline and the ninth pipeline.

5. The tangential flow filtration device as described in claim 4, characterized in that, The first valve has at least a five-way connector, the second valve has at least a three-way connector, the third valve has at least a three-way connector, the fourth valve has at least a three-way connector, and the fifth valve has at least a three-way connector.

6. The tangential flow filtration device as described in claim 2, characterized in that, The tangential flow filtration device further includes an alkali one-way liquid container for storing alkali solution. The alkali one-way liquid container is connected to the first valve on the first pipeline through a tenth pipeline. The third pipeline is connected to the waste liquid container through a ninth pipeline. The third pipeline and the ninth pipeline are connected through a fourth valve.

7. The tangential flow filtration device as described in claim 6, characterized in that, The first valve has at least a four-way connector, the second valve has at least a three-way connector, and the fourth valve has at least a three-way connector.

8. The tangential flow filtration device as described in claim 4, characterized in that, The tangential flow filtration device also includes an alkaline one-way liquid container for storing alkaline solution, and the alkaline one-way liquid container is connected to the first valve on the first pipeline through a tenth pipeline.

9. The tangential flow filtration device as described in claim 8, characterized in that, The first valve has at least a six-way connector, the second valve has at least a three-way connector, the third valve has at least a three-way connector, the fourth valve has at least a three-way connector, and the fifth valve has at least a three-way connector.

10. The tangential flow filtration device according to any one of claims 1 to 9, characterized in that, The tangential flow filter element is a membrane envelope or a hollow fiber column; and / or The tangential flow filtration device further includes a first drive pump and a second drive pump, wherein the first drive pump is disposed on the first pipeline and the second drive pump is disposed on the second pipeline.

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