Continuous chromatography system based on tangential flow chromatographic column and use method thereof

Abstract

The invention provides a continuous chromatographic system based on tangential flow chromatographic columns and a use method of the continuous chromatographic system. The continuous chromatographic system comprises a sample loading pipeline, an elution pipeline and a plurality of tangential flow chromatographic columns, a sample loading pump is arranged on the sample loading pipeline, and the outlet end of the sample loading pipeline is respectively connected with an inlet end pipeline and an outlet end pipeline at the bottom of each tangential flow chromatographic column through valves; an elution pump is arranged on the elution pipeline, and the outlet end of the elution pipeline is respectively connected with an inlet end pipeline and an outlet end pipeline at the bottom of each tangential flow chromatographic column through valves; an inlet end pipeline and an outlet end pipeline at the top of each tangential flow chromatographic column are respectively connected with a first collecting pipeline and a second collecting pipeline through valves; a backflow port pipeline of the tangential flow chromatographic column is communicated with the sample loading pipeline through a filtering module or a liquid storage tank; during use, one is in a loading mode, and the other is in an elution mode; the invention has the advantages that the flow path and the circulation loop are almost free of residues, and the circulation loop does not need to be stopped and restarted for many times.

Description

Technical Field

[0001] The present invention relates to downstream separation and purification of biomedicine, and in particular to a continuous chromatography system based on a tangential flow chromatography column and a use method thereof. Background Art

[0002] The chromatography columns used in the chromatographic system of the downstream of biomedicine are structurally that the sample to be processed enters from one end of the chromatography column and flows out from the other end for collection. Therefore, it is impossible to process particle sediments and cannot backwash the distribution screen plate, and it is impossible to achieve the ability of high-efficiency chromatography and particle processing at the same time. In the prior art, for example, the patent number is: 202120067489.X, and the utility model name is a hydraulically driven dynamic chromatography device. When the separation liquid needs to be added, the liquid is injected from the liquid inlet and flows out from the liquid outlet for collection; or for example, the patent number is: 201820028656.8, and the utility model name is a moving beam type fully automatic chromatography column, the structure of which is a sieve plate, a diverter plate and a base at the bottom, and a lower nozzle is arranged at the center of the sieve plate. When the separation liquid needs to be added, the liquid enters from the chromatography port of the upper nozzle and flows out from the chromatography port of the lower nozzle for collection, or enters from the chromatography port of the lower nozzle and flows out from the chromatography port of the upper nozzle for collection. Its disadvantages are: 1. It cannot achieve flushing or elution on the upper part of the column head; 2. It does not support back flushing of the filter plate (sieve plate), which can easily lead to blockage; 3. It cannot achieve high linear flow rate and overload loading at the same time, and the dynamic loading capacity is low.

[0003] The applicant has proposed a tangential flow chromatography column, patent number: 202220697921.8, and the patent name is a radial and tangential flow bottom for a chromatography column and a chromatography system used in combination. The tangential flow structure is adopted to realize tangential flow filtration and chromatographic loading at the same time, thereby achieving high linear flow rate and overload loading, and achieving extremely high dynamic loading capacity. Therefore, in order to meet production needs, a continuous flow chromatography system that can utilize tangential flow chromatography columns is required. Summary of the invention

[0004] In order to achieve the above-mentioned purpose, the present invention provides a continuous chromatography system based on a tangential flow chromatography column and a method for using the same, which can realize that a portion of the chromatography column is in a loading mode and a portion is in an elution mode, so that the sample can be continuously loaded into the tangential flow chromatography column without any residue in the flow path and the circulation loop.

[0005] In order to achieve the above object, the technical solution adopted by the present invention is:

[0006] The first aspect disclosed by the present invention provides a continuous chromatography system based on a tangential flow chromatography column, comprising a loading pipeline, an elution pipeline and a plurality of tangential flow chromatography columns; a loading pump is arranged on the loading pipeline, and the outlet end of the loading pipe is respectively connected to the inlet and outlet pipelines at the bottom of each tangential flow chromatography column through a valve; an elution pump is arranged on the elution pipeline, and the outlet end of the elution pipeline is respectively connected to the inlet and outlet pipelines at the bottom of each tangential flow chromatography column through a valve; the inlet and outlet pipelines at the top of each tangential flow chromatography column are respectively connected to a first collecting pipeline and a second collecting pipeline through a valve; the reflux port pipeline of the tangential flow chromatography column is connected to the loading pipeline through a filtration module or a liquid storage tank.

[0007] In some embodiments, two tangential flow chromatography columns are used, one in loading mode and the other in elution mode.

[0008] In some embodiments, the outlet pipelines of the loading line and the elution line are respectively connected to the first valve array; the first valve array is a rectangular valve array formed by four connected ends; a group of opposite sides of the rectangular valve array are respectively connected to the outlet ends of the loading line and the elution line; another group of opposite sides of the rectangular valve array are respectively connected to the bottom inlet and outlet ends of the two chromatography columns.

[0009] In some embodiments, the two top inlet and outlet pipelines are respectively connected to the second valve array, and the first valve array is a rectangular valve array formed by four connected ends; a group of opposite sides of the rectangular valve array respectively correspond to the two top inlet and outlet pipelines, and another group of opposite sides of the rectangular valve array respectively correspond to the inlet ends of the first collection pipe and the second collection pipe.

[0010] In some embodiments, the filtration module uses multiple filters, and the inlet and outlet at one end of each filter are connected to the reflux ends of two tangential flow chromatography columns through valves, and the other end of the filter is connected to the sample loading pipeline.

[0011] In some embodiments, two filters are used.

[0012] In some embodiments, the reflux end pipelines of the two tangential flow chromatography columns are connected to the two filters through a third valve array, and the third valve array is formed by a rectangular valve array with four ends connected; one group of opposite sides of the rectangular valve array corresponds to the inlet and outlet pipelines at one end of the two filters; another group of opposite sides of the rectangular valve array corresponds to the reflux end pipeline and the waste discharge pipeline; the other ends of the two filters are connected to the sample loading pipeline through a fourth valve array, and the fourth valve array is formed by four ends connected to form a rectangular valve array; one group of opposite sides of the rectangular valve array corresponds to the inlet and outlet pipelines at the other end of the two filters, and another group of opposite sides of the rectangular valve array corresponds to the liquid inlet pipeline and the sample loading pipeline.

[0013] In some embodiments, a reflux pump is provided on the reflux port pipeline of the tangential flow chromatography column.

[0014] In some embodiments, the outlet pipeline of the filtration module or the liquid storage tank is connected to the sample loading pipeline through a mixer.

[0015] In some embodiments, the outlet end of the elution pipeline is connected to the liquid inlet end pipelines at the top of multiple tangential flow chromatography columns through valves.

[0016] The second aspect disclosed by the present invention provides a method for using a continuous chromatography system based on a tangential flow chromatography column, and the steps include: loading and elution; loading: the sample to be processed enters the bottom inlet and outlet of a part of the tangential flow chromatography column through a loading pipeline, and part of the solution flows back to the loading pipeline through the reflux port of the tangential flow chromatography column through a filtration module or a liquid storage tank to form a cycle. After the sample solution to be processed is processed by the tangential flow chromatography column, the waste solution flows from the solution inlet and outlet pipeline at the top of the tangential flow chromatography column to the first collecting pipeline for collection; elution: the eluent enters the bottom inlet and outlet of the remaining part of the tangential flow chromatography column that has been loaded with the sample through the elution pipeline, and after passing through the chromatography column, the solution flows from the solution inlet and outlet pipeline at the top of the tangential flow chromatography column to the second collecting pipeline for collection; then the operation is alternated, with one part in the loading mode and the other part in the elution mode.

[0017] In some embodiments, two tangential flow chromatography columns are used, one in loading mode and the other in elution mode.

[0018] In some embodiments, the outlet end of the elution pipeline is connected to the liquid inlet end pipelines at the top of two tangential flow chromatography columns through valves.

[0019] In some embodiments, the method for using the continuous chromatography system of the tangential flow chromatography column also includes the steps of flushing after loading: the buffer enters the top inlet and outlet of the tangential flow chromatography column where the loading is completed through the elution pipeline, passes through the chromatography column, and flows out from the reflux port of the tangential flow chromatography column, and is collected using a collection pipeline connected to the reflux port pipeline.

[0020] In some examples, the method for using the continuous chromatography system of the tangential flow chromatography column also includes the steps of regeneration after elution: the cleaning agent enters the top inlet and outlet of the tangential flow chromatography column where the elution is completed through the elution pipeline, passes through the chromatography column, flows out from the reflux port of the tangential flow chromatography column, and is collected using a collection pipeline connected to the reflux port pipeline.

[0021] Beneficial effects of the present invention:

[0022] 1. Two tangential flow chromatography columns are used in the present invention, which are operated alternately: one is in loading mode and the other is in elution mode. By doing so, the feed can be continuously loaded into the RTF column, and there is almost no residue in the flow path and circulation loop, and the circulation loop does not have to be stopped and restarted many times.

[0023] 2. A circulation loop is used at the reflux end of the tangential flow to drive the circulation while loading the tangential flow chromatography column.

[0024] 3. Utilize the filtration module to remove particulate matter or contaminants from the feed and keep the particulate matter concentration constant (lower than the feed concentration). BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 A schematic diagram of the structure of the present invention. DETAILED DESCRIPTION

[0026] The present invention will be further described below in conjunction with the accompanying drawings.

[0027] The technical content of the present invention is described below by specific embodiments. Those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments. Those skilled in the art can make various modifications and changes without departing from the spirit of the present invention.

[0028] Before describing the specific embodiments of the present disclosure in detail, some terms used in the present disclosure are first explained.

[0029] Unless otherwise defined below, the meaning of all technical terms and scientific terms used herein is intended to be the same as those commonly understood by those skilled in the art. Mentioning the technology used in this article is intended to refer to the technology commonly understood in the art, including those changes in technology that are obvious to those skilled in the art or the replacement of equivalent technology. Although it is believed that the following terms are well understood by those skilled in the art, the following definitions are still set forth to better explain the present invention. When a top-grade product name appears in this article, it is intended to refer to its corresponding top-grade product. All patents, published patent applications and publications cited herein are incorporated herein by reference.

[0030] As used herein, the terms “connected”, “connected”, “coupled” or “coupled” and the like are not limited to direct connections but also include indirect connections.

[0031] As used herein, a "sample" is a biomolecule, including proteins, nucleic acids, lipids, carbohydrates, small nucleotides, amino acids and their derivatives.

[0032] As used herein, the term "online monitoring" or "real-time monitoring" refers to real-time detection of certain parameters or properties of buffers, reaction fluids, and fluids flowing out of flow reactors during use of the chromatography system, such as pH, pressure, flow rate, conductivity, etc. Unlike offline detection or analysis, online monitoring or real-time monitoring can provide real-time feedback of the detection results.

[0033] The position relationship words "up", "down", "left", "right", "front", "back", etc. involved in this article are determined according to the layout direction of the drawings in the specification. They are only used to indicate relative position relationships. When the absolute position of the object being described changes, the relative position relationship may also change accordingly.

[0034] The RTF chromatography column (tangential flow chromatography column) mentioned in this article is a patented chromatography column independently developed by our company, with patent number: 202220697921.8; it has a radial and tangential flow structure, and can be loaded through the tangential flow at the bottom of the column, while the upper part of the column head can be flushed and eluted at the same time, cyclic loading and cleaning mode with equilibrium liquid can be achieved, thereby achieving high linear flow rate and overload loading, and achieving extremely high dynamic loading capacity.

[0035] Reference Figure 1 As shown, a continuous chromatography system based on a tangential flow chromatography column comprises a sample loading pipeline 1 and an elution pipeline 2; the inlet end of the sample loading pipeline 1 is connected to a first tank 3 through a valve AV1, and the first tank 3 can be used to hold samples to be processed. The inlet end of the sample loading pipeline 1 is connected to a second tank 4 through a valve AV4. The sample loading pipeline 1 is provided with a sample loading pump 5 and a first flow indicating transmitter 6. The outlet end of the sample loading pipeline 1 is connected to a first valve array 7, and the first valve array 7 is a rectangular valve array composed of valves AV10, AV11, AV12 and AV13 connected end to end, and the sample loading pipeline 1 is connected between valves AV10 and AV11. The inlet end of the elution pipeline 2 is connected to the second tank 5 through a valve AV5, to the third tank 8 through a valve AV2, and to the fourth tank 9 through a valve AV3. The elution pipeline 2 is provided with an elution pump 10, a second flow indicating transmitter 11 and a bubble trap 33. The outlet of the elution pipeline 2 is connected between valve AV12 and valve AV13 through a pipeline, and a valve AV14 is provided on the pipeline. The bottom inlet and outlet of the first tangential flow chromatography column 12 are connected between valve AV10 and valve AV12 through a pipeline; the bottom outlet of the second tangential flow chromatography column 13 is connected between valve AV11 and valve AV13 through a pipeline.

[0036] The pipelines at the top inlet and outlet of the first tangential flow chromatography column 12 and the second tangential flow chromatography column 13 are connected to the second valve array 14, and the second valve array 14 is a rectangular valve array composed of valves AV17, AV18, AV19 and AV20 connected at the end. The pipelines at the top inlet and outlet of the first tangential flow chromatography column 12 are connected between valves AV19 and AV20, and the pipelines at the top inlet and outlet of the second tangential flow chromatography column 13 are connected between valves AV17 and AV18. The first collection pipeline 15 is connected between valves AV17 and AV19; the second collection pipeline 16 is connected between valves AV18 and AV20. The first collection pipeline 15 is provided with sensors for real-time monitoring of data: a first UV sensor 17, a first conductivity transmitter 18, and a first pH sensor 19. The second collection pipeline 16 is provided with sensors for real-time monitoring of data: a second UV sensor 20, a second conductivity transmitter 21, and a second pH sensor 22.

[0037] The reflux port pipeline of the first tangential flow chromatography column 12 is connected to the inlet end of the connecting pipeline 23 through valve AV6, and the reflux port pipeline of the second tangential flow chromatography column 13 is connected to the connecting pipeline 23 through valve AV7. The connecting pipeline 23 is provided with a circulation pump 24 and a third flow indicating transmitter 25. The outlet end of the connecting pipeline 23 is connected to the third valve array 26, which is a rectangular valve array composed of a pressure control valve PCV1, a pressure control valve PCV2, a valve AV26 and a valve AV27 connected end to end. The connecting pipeline 23 is connected between the pressure control valve PCV1 and the pressure control valve PCV2; the first inlet and outlet end pipelines of the first filter 27 are connected between the pressure control valve PCV1 and the valve AV26; the first inlet and outlet end pipelines of the second filter 28 are connected between the pressure control valve PCV2 and the valve AV27; and the waste discharge pipeline 29 is connected between the valve AV26 and the valve AV27. The second inlet and outlet ends of the first filter 27 and the second filter 28 are connected to the fourth valve array 30. The fourth valve array 30 is a rectangular valve array composed of valves AV22, AV23, AV24 and AV25 connected end to end. The second inlet and outlet pipelines of the first filter 27 are connected between valves AV22 and AV23; the second inlet and outlet pipelines of the second filter 28 are connected between valves AV24 and AV25; the liquid inlet pipeline 31 is connected between valves AV22 and AV24; the sample loading pipeline 1 is connected between valves AV23 and AV25 through a pipeline; and valve AV21 is provided on the left side of the connection point between the pipeline and the sample loading pipeline 1.

[0038] The outlet end of the elution pipeline 2 is connected to the top inlet and outlet pipelines of the first tangential flow chromatography column 12 and the second tangential flow chromatography column 13 through pipelines, and valves AV16 and AV15 are respectively provided on the pipelines.

[0039] The pipelines at the bottom reflux ports of the first tangential flow chromatography column 12 and the second tangential flow chromatography column 13 are connected to the solution collecting pipeline through valves AV18 and AV19 respectively.

[0040] A mixer 32 is provided between the sample loading pipeline 1 and the fourth valve array 30 .

[0041] A method for using a continuous chromatography system based on a tangential flow chromatography column, wherein a first tangential flow chromatography column 12 and a second tangential flow chromatography column 13 can be loaded with samples at the same time, can be eluted at the same time, or can be loaded with samples one at a time and eluted with the other one.

[0042] 1. When loading samples simultaneously: the sample to be processed flows out from the first tank 3 and enters the sample loading pipeline 1 under the action of the sample loading pump 5. The valves AV10 and AV11 are opened, and the sample to be processed respectively enters the inlet and outlet pipelines at the bottom of the first tangential flow chromatography column 12 and the second tangential flow chromatography column 13. Part of the solution enters the connecting pipe 23 through the reflux end pipelines at the bottom of the first tangential flow chromatography column 12 and the second tangential flow chromatography column 13, and enters the filtration module through the connecting pipe 23.

[0043] The filtering module uses a first filter 27 and a second filter 28. The first filter 27 and the second filter 28 can perform filtering work at the same time or one can perform filtering work and the other can perform backwashing; they can also perform filtering or backwashing at the same time. Here is an example: the first filter 27 filters and the second filter 28 performs backwashing.

[0044] At this time, the pressure control valve PCV1 and the valve AV23 are opened, and the solution flows in through the first inlet and outlet of the first filter 27, flows out through the second inlet and outlet of the first filter 27, and finally flows into the sample loading pipeline 1 to form a cycle; the sample to be processed passes through the first tangential flow chromatography column 12 and the second tangential flow chromatography column 13, and the waste solution flows out from the inlet and outlet pipelines at the top of the first tangential flow chromatography column 12 and the second tangential flow chromatography column 13. At this time, the valves AV19 and AV17 are opened, and the waste solution enters the first collection pipeline 15 for collection.

[0045] The second filter 28 is backwashed: valve AV24 and valve AV27 are opened, and the WFI solution enters from the second inlet and outlet of the second filter 28 through valve AV24. After backwashing, the waste solution enters the waste pipeline 29 after passing through valve AV27.

[0046] 2. When eluting simultaneously: the eluent enters the elution pipeline 2 under the action of the elution pump 10, and the valves AV12 and AV13 are opened. The eluent enters the inlet and outlet pipelines at the bottom of the first tangential flow chromatography column 12 and the second tangential flow chromatography column 13 respectively, passes through the first tangential flow chromatography column 12 and the second tangential flow chromatography column 13, and the solution flows out from the inlet and outlet pipelines at the top of the first tangential flow chromatography column 12 and the second tangential flow chromatography column 13. At this time, valves AV20 and AV18 are opened, and the solution enters the second collection pipeline 16 for collection.

[0047] 3. One is loading and the other is eluting: (1) The first tangential flow chromatography column 12 is loaded and the second tangential flow chromatography column 13 is eluted: the sample to be processed flows out from the first tank 3 and enters the sample loading pipeline 1 under the action of the sample loading pump 5. The valve AV10 is opened, and the sample to be processed enters the inlet and outlet pipelines at the bottom of the first tangential flow chromatography column 12 respectively. Part of the solution enters the connecting pipe 23 through the reflux end pipeline at the bottom of the first tangential flow chromatography column 12, and enters the filtration module through the connecting pipe 23. The filtration module adopts a first filter 27 and a second filter 28. The first filter 27 and the second filter 28 can perform filtering work at the same time or one can perform filtering work and the other can perform backwashing; they can also perform filtering or backwashing at the same time. Here is an example: the first filter 27 is backwashed and the second filter 28 is filtered. At this time, the pressure control valve PCV2 and valve AV25 are opened, the solution flows in through the first inlet and outlet of the second filter 28, flows out through the second inlet and outlet of the second filter 28, and finally flows into the sample loading pipeline 1 to form a cycle; the sample to be processed passes through the first tangential flow chromatography column 12, and the waste solution flows out from the inlet and outlet pipeline at the top of the first tangential flow chromatography column 12. At this time, valve AV19 is opened to allow the waste solution to enter the first collection pipeline 15 for collection. The first filter 27 is backwashed: valves AV22 and AV26 are opened, and the WFI solution enters from the second inlet and outlet of the first filter 27 through valve AV22. After backwashing, the waste solution passes through valve AV26 and enters the waste discharge pipeline 29.

[0048] At the same time, the eluent enters the elution pipeline 2 under the action of the elution pump 10, and the valve AV13 is opened. The eluent enters the inlet and outlet pipelines at the bottom of the second tangential flow chromatography column 13, passes through the second tangential flow chromatography column 13, and the solution flows out from the inlet and outlet pipelines at the top of the second tangential flow chromatography column 13. At this time, the valve AV18 is opened, and the solution enters the second collection pipeline 16 for collection.

[0049] (2) Elution of the first tangential flow chromatography column 12 and loading of the second tangential flow chromatography column 13: The sample to be processed flows out of the first tank 3 and enters the loading pipeline 1 under the action of the loading pump 5. The valve AV11 is opened, and the sample to be processed flows into the inlet and outlet pipelines at the bottom of the second tangential flow chromatography column 13. Part of the solution enters the connecting pipeline 23 through the reflux pipeline at the bottom of the second tangential flow chromatography column 13, and enters the filtration module through the connecting pipeline 23. The filtration module uses a first filter 27 and a second filter 28. The first filter 27 and the second filter 28 can perform filtering work at the same time or one can perform filtering work and the other can perform backwashing; they can also perform filtering or backwashing at the same time. Here is an example: the first filter 27 filters and the second filter 28 performs backwashing.

[0050] At this time, the pressure control valve PCV1 and the valve AV23 are opened, and the solution flows in through the first inlet and outlet of the first filter 27, flows out from the second inlet and outlet of the first filter 27, and finally flows into the sample loading pipeline 1 to form a cycle; the sample to be processed passes through the second tangential flow chromatography column 13, and the waste solution flows out from the inlet and outlet pipelines at the top of the second tangential flow chromatography column 13. At this time, the valve AV17 is opened, and the waste solution enters the first collection pipeline 15 for collection.

[0051] The second filter 28 is backwashed: valve AV24 and valve AV27 are opened, and the WFI solution enters from the second inlet and outlet of the second filter 28 through valve AV24. After backwashing, the waste solution enters the waste pipeline 29 after passing through valve AV27.

[0052] At the same time, the eluent enters the elution pipeline 2 under the action of the elution pump 10, and the valve AV12 is opened. The eluent enters the inlet and outlet pipelines at the bottom of the first tangential flow chromatography column 12, passes through the first tangential flow chromatography column 12, and the solution flows out from the inlet and outlet pipelines at the top of the first tangential flow chromatography column 12. At this time, the valve AV20 is opened, and the solution enters the second collection pipeline 16 for collection.

Claims

1. A continuous chromatography system based on a tangential flow chromatography column, characterized in that: It comprises a loading pipeline, an elution pipeline and a plurality of tangential flow chromatography columns; the loading pipeline is provided with a loading pump, and the outlet end of the loading pipe is respectively connected to the inlet and outlet pipelines at the bottom of each tangential flow chromatography column through a valve; the elution pipeline is provided with an elution pump, and the outlet end of the elution pipeline is respectively connected to the inlet and outlet pipelines at the bottom of each tangential flow chromatography column through a valve; the inlet and outlet pipelines at the top of each tangential flow chromatography column are respectively connected to a first collecting pipeline and a second collecting pipeline through a valve; the reflux port pipeline of the tangential flow chromatography column is connected to the loading pipeline through a filtering module or a liquid storage tank.

2. A continuous chromatography system based on a tangential flow chromatography column according to claim 1, characterized in that: The tangential flow chromatography columns are two, one in loading mode and the other in elution mode.

3. A continuous chromatography system based on a tangential flow chromatography column according to claim 2, characterized in that: The outlet pipelines of the sample loading pipeline and the elution pipeline are respectively connected to the first valve array; the first valve array is a rectangular valve array formed by four ends connected together; one group of opposite sides of the rectangular valve array are respectively connected to the outlet ends of the sample loading pipeline and the elution pipeline; the other group of opposite sides of the rectangular valve array are respectively connected to the bottom inlet and outlet ends of the two chromatography columns.

4. A continuous chromatography system based on a tangential flow chromatography column according to claim 2, characterized in that: The two top inlet and outlet pipelines are respectively connected to the second valve array, and the first valve array is a rectangular valve array formed by four connected ends; one group of opposite sides of the rectangular valve array corresponds to the two top inlet and outlet pipelines, and the other group of opposite sides of the rectangular valve array corresponds to the inlet ends of the first collection pipeline and the second collection pipeline.

5. A continuous chromatography system based on a tangential flow chromatography column according to claim 1, characterized in that: The filtration module adopts a plurality of filters, and the inlet and outlet at one end of each filter are connected to the reflux ends of two tangential flow chromatography columns through valves, and the other end of the filter is connected to the sample loading pipeline.

6. A continuous chromatography system based on a tangential flow chromatography column according to claim 1, characterized in that: The filter is provided in two pieces.

7. A continuous chromatography system based on a tangential flow chromatography column according to claim 6, characterized in that: The reflux end pipelines of the two tangential flow chromatography columns are connected to the two filters through the third valve array, and the third valve array is formed by a rectangular valve array with four ends connected; one group of opposite sides of the rectangular valve array is respectively connected to the inlet and outlet pipelines of one end of the two filters; the other group of opposite sides of the rectangular valve array is respectively connected to the reflux end pipeline and the waste discharge pipeline; the other ends of the two filters are connected to the sample loading pipeline through the fourth valve array, and the fourth valve array is formed by four ends connected to form a rectangular valve array; one group of opposite sides of the rectangular valve array is respectively connected to the inlet and outlet pipelines of the other ends of the two filters, and the other group of opposite sides of the rectangular valve array is respectively connected to the liquid inlet pipeline and the sample loading pipeline.

8. A continuous chromatography system based on a tangential flow chromatography column according to claim 1, characterized in that: A reflux pump is arranged on the reflux port pipeline of the tangential flow chromatography column.

9. A continuous chromatography system based on a tangential flow chromatography column according to claim 1, characterized in that: The outlet pipeline of the filtering module or the liquid storage tank is connected to the sample feeding pipeline through a mixer.

10. A continuous chromatography system based on a tangential flow chromatography column according to claim 1, characterized in that: The outlet ends of the elution pipelines are connected to the liquid inlet end pipelines at the tops of a plurality of tangential flow chromatography columns through valves.

11. A method for using a continuous chromatography system based on a tangential flow chromatography column, characterized in that: The steps include: loading and eluting; loading: the sample to be processed enters the bottom inlet and outlet of a part of the tangential flow chromatography column through a loading pipeline, part of the solution flows back to the loading pipeline through a reflux port of the tangential flow chromatography column through a filter module or a liquid storage tank to form a cycle, after the sample solution to be processed is processed by the tangential flow chromatography column, the waste solution flows from the solution inlet and outlet pipeline at the top of the tangential flow chromatography column to the first collecting pipeline for collection; elution: the eluent enters the bottom inlet and outlet of the remaining part of the tangential flow chromatography column that has been loaded with the sample through an elution pipeline, and after passing through the chromatography column, the solution flows from the solution inlet and outlet pipeline at the top of the tangential flow chromatography column to the second collecting pipeline for collection; and then the operation is alternated, with one part in the loading mode and the other part in the elution mode.

12. The method for using a continuous chromatography system based on a tangential flow chromatography column according to claim 11, characterized in that: The tangential flow chromatography columns are two, one in loading mode and the other in elution mode.

13. The method for using a continuous chromatography system based on a tangential flow chromatography column according to claim 12, wherein the outlet end of the elution pipeline is connected to the liquid inlet end pipelines at the top of two tangential flow chromatography columns through valves.

14. A method for using a continuous chromatography system based on a tangential flow chromatography column according to claim 13, wherein the method for using the continuous chromatography system based on a tangential flow chromatography column further comprises flushing after sample loading: the buffer solution enters the top inlet and outlet ends of the tangential flow chromatography column where sample loading is completed through an elution pipeline, passes through the chromatography column, flows out from the reflux port end of the tangential flow chromatography column, and is collected using a collection pipeline connected to the reflux port end pipeline.

15. A method for using a continuous chromatography system based on a tangential flow chromatography column according to claim 13, wherein the method for using the continuous chromatography system of the tangential flow chromatography column further comprises the step of regeneration after elution: the cleaning agent enters the top inlet and outlet ends of the tangential flow chromatography column where the elution is completed through the elution pipeline, passes through the chromatography column, and then flows out from the reflux port end of the tangential flow chromatography column, and is collected using a collection pipeline connected to the reflux port end pipeline.

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