Full-automatic non-interruption liquid preparation chromatography system and use method thereof

Abstract

The invention provides a full-automatic non-interruption liquid preparation chromatography system and a use method thereof. The full-automatic non-interruption liquid preparation chromatography system comprises a first liquid inlet main pipeline, a pure water tank, an alkali liquor tank, a plurality of mother liquor tanks, a following tank, a product tank, a bubble trap, a plurality of chromatographic columns, a first liquid inlet main pipeline, a collection tank and a waste discharge tank, the first liquid inlet main pipeline is connected with the outlet of the alkali liquor tank, the outlet of the pure water tank and the outlets of the mother liquor tanks through pipelines; an outlet pipeline of each mother liquor tank is connected with the first liquid inlet main pipeline through a connecting pipeline, and a mother liquor pump is arranged on each connecting pipeline; the first liquid inlet main pipeline is connected with the inlet ends of the corresponding chromatographic columns through different pipelines, and the outlet ends of the chromatographic columns are connected with the first liquid inlet main pipeline through corresponding pipelines; the device has the advantages that the problems of disqualified liquid preparation interruption and pressure change are solved, the working efficiency is improved, meanwhile, self-circulation can be achieved, and quick formula conversion is achieved after the target flow speed is achieved.

Description

Technical Field

[0001] The present invention relates to liquid preparation chromatography in the field of biopharmaceuticals, and particularly to a fully automatic uninterrupted liquid preparation chromatography system and a method for using the same. Background Art

[0002] In the prior art, liquid preparation chromatography systems connect mother liquid tanks, buffer tanks, CIP, chromatography columns, and various valves, pumps, sensors, etc. together. First, the pump configures the mother liquid into each buffer tank according to the set ratio; then, the solutions with different concentrations in the buffer tanks are delivered to the chromatography column through the delivery pump as needed for separation and purification. Its disadvantages are as follows: The traditional liquid preparation + chromatography operation is cumbersome; a large number of process buffer tanks need to be configured, occupying a large amount of space and making the cleaning and sterilization process troublesome; the mother liquid needs to reach the set flow rate to enter the buffer tank, resulting in waste of resources; the instrument accuracy is poor, the signal is easily interfered with and attenuated, resulting in system instability, and thus problems such as interrupted liquid preparation due to unqualified liquid preparation and pressure changes occur.

[0003] At the same time, the currently adopted pipeline flow paths directly connect each liquid addition tank to the mixing tank, and its disadvantage is that the outlet pipeline on the connection pipeline cannot be cleaned and cannot meet the hygiene requirements. Summary of the Invention

[0004] In order to overcome the above deficiencies of the prior art, the present invention provides a fully automatic uninterrupted liquid preparation chromatography system and a method for using the same, which can realize the circulation of the mother liquid and the conversion of rapid formulation; and can solve the problems of interruption and pressure change caused by unqualified liquid preparation.

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

[0006] In view of the above technical problems, the first aspect of the disclosure of the present invention provides a fully automatic non-stop liquid dispensing chromatography system, including a first main liquid inlet pipeline, a pure water tank, an alkali solution tank, a plurality of mother liquid tanks, a follow-up tank, a product tank, a bubble trap, a plurality of chromatography columns, a first main liquid inlet pipeline, a collection tank and a waste discharge tank; the first main liquid inlet pipeline is sequentially connected to the outlet of the alkali solution tank, the outlet of the pure water tank, and the outlets of each mother liquid tank through pipelines in sequence; the outlet pipelines of each mother liquid tank are respectively connected to the first main liquid inlet pipeline through connecting pipelines, and mother liquid pumps are respectively arranged on the connecting pipelines; a main pump is arranged on the first main liquid inlet pipeline; the inlet end and the outlet end of the follow-up tank are respectively connected to the first main liquid inlet pipeline through pipelines; the first main liquid inlet pipeline is connected to the product tank through a pipeline; the first main liquid inlet pipeline is respectively connected to the inlet end and the outlet end of the bubble trap through pipelines; the first main liquid inlet pipeline is connected to the inlet ends of the corresponding respective chromatography columns through different pipelines, and the outlet ends of each chromatography column are connected to the first main liquid inlet pipeline through corresponding pipelines; the outlet end of the first main liquid inlet pipeline is respectively connected to the collection tank and the waste discharge tank through valves; pumps are arranged on the first main liquid inlet pipeline, the connecting pipelines between each mother liquid tank and the first main liquid inlet pipeline, and the connecting pipelines between the follow-up tank and the first main liquid inlet pipeline.

[0007] Further, the first main liquid inlet pipeline is connected to the inlet end of the alkali solution tank through a pipeline to realize the circulation of the alkali solution.

[0008] Further, the outlet pipeline of the alkali solution tank and the outlet pipeline of the pure water tank are connected to a second main liquid inlet pipeline, and the second main liquid inlet pipeline is respectively connected to the outlet ends of the outlet pipelines of each mother liquid tank.

[0009] Further, the outlet ends of the outlet pipelines of each mother liquid tank are respectively connected to a cleaning discharge tank.

[0010] Further, the bottom of the connecting pipeline between the outlet pipeline of each mother liquid tank and the first main liquid inlet pipeline is connected to the top inlet end of the connecting pipeline between the pipeline mother liquid tank and the first main liquid inlet pipeline through a bypass pipeline to form a closed loop.

[0011] Further, the outlet end of the bypass pipeline is connected to the waste discharge tank.

[0012] Further, a valve array is arranged on the first main liquid inlet pipeline, and the valve array is a rectangular valve array composed of four valves connected end to end. One pair of opposite sides of the rectangular valve array is connected to the first main liquid inlet pipeline; the other pair of opposite sides of the rectangular valve array are respectively connected to the upper and lower inlet and outlet ports of the chromatography column.

[0013] Further, the outlet of the alkali solution tank and the outlet pipeline of the pure water tank are connected to the first main liquid inlet pipeline through a connecting pipeline.

[0014] Further, the second main liquid inlet pipe is connected to the cleaning discharge pipe.

[0015] Further, the connections of the respective pipes are connected through valves.

[0016] Further, flow sensors are provided on the first main liquid inlet pipe, the connecting pipes between each mother liquid tank and the first main liquid inlet pipe, and the connecting pipe between the follow-up tank and the first main liquid inlet pipe.

[0017] In view of the above technical problems, the first aspect of the disclosed content of the present invention proposes a method for using a fully automatic non-stop Oh-eh chromatography system, and the steps are as follows:

[0018] Step 1: Preparing in the follow-up tank while loading the product; according to the formula, the solution and pure water in the corresponding mother liquid tank are transported to the follow-up tank through the first main liquid inlet pipe; at the same time, the product solution in the product tank enters the inner layer of the chromatography column through the bubble trap for chromatography and then is collected;

[0019] Step 2: Chromatography in the follow-up tank; the solution in the follow-up tank enters the inner layer of the chromatography column through the bubble trap for chromatography and then is collected;

[0020] Step 3: If different liquid preparations are required according to the formula, at this time, the solution in the mother liquid tank can be directly passed through the chromatography column for chromatography and then collected;

[0021] Step 4: Preparation of the alkali solution, the preparation of the alkali solution: the solution in the pure water tank and the solution in the corresponding mother liquid tank flow into the inlet end of the alkali solution tank after passing through the first main liquid inlet pipe.

[0022] Step 5: Cleaning.

[0023] Further, the cleaning includes (1) alkali solution circulation; (2) pure water direct discharge; (3) cleaning of the follow-up tank pipeline.

[0024] Further, the alkali solution circulation: the alkali solution flows out from the outlet of the alkali solution tank, passes through the first main liquid inlet pipe, and then flows into the inlet of the alkali solution tank; the alkali solution flows through the second main liquid inlet pipe into the connecting pipes between each mother liquid tank and the first main liquid inlet pipe, and then enters the waste discharge tank through the bypass pipe, and also flows into the connecting pipe between the first main liquid inlet pipe and the product tank outlet pipeline and the follow-up tank outlet pipeline, enters the first main liquid inlet pipe, and then enters the alkali solution tank;

[0025] Further, the pure water direct discharge: the pure water in the pure water tank flows through the first main liquid inlet pipe, the first main liquid inlet pipe, and then flows into the waste discharge pipe for collection and / or the pure water flows through the second main liquid inlet pipe into the connecting pipes between each mother liquid tank and the first main liquid inlet pipe, and then enters the waste discharge tank through the bypass pipe, and also flows into the connecting pipe between the first main liquid inlet pipe and the product tank outlet pipeline and the follow-up tank outlet pipeline, enters the first main liquid inlet pipe, and then enters the waste discharge tank;

[0026] Further, for the cleaning of the follow-up tank pipeline: The lye flows into the inlet end of the follow-up tank through the first main liquid inlet pipeline, and then flows into the inlet of the lye tank through the outlet end of the follow-up tank and the first main liquid inlet pipeline; The pure water flows into the inlet end of the follow-up tank through the first main liquid inlet pipeline, and then flows into the waste discharge pipeline through the outlet end of the follow-up tank and the first main liquid inlet pipeline.

[0027] Advantages of the present invention:

[0028] 1. A follow-up tank is provided, which can realize the liquid preparation to the follow-up tank; From the follow-up tank to the chromatography column, it can realize the interruption of unqualified liquid preparation and the problem of pressure change;

[0029] 2. Adding a cleaning lye tank can enable multiple chromatography columns to work staggered, that is, some are chromatographing while some are being cleaned, improving the work efficiency.

[0030] 3. The addition of the mother liquor pump can realize self-cleaning and defoaming; At the same time, it can realize self-circulation, and achieve rapid formula conversion after reaching the target flow rate. Description of the Drawings

[0031] Figure 1 It is a schematic structural diagram of the present invention. Specific Embodiments

[0032] The following further describes the present invention with reference to the drawings.

[0033] The following illustrates the technical content of the present invention through specific specific embodiments. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments. Those skilled in the art make various modifications and changes without departing from the spirit of the present invention.

[0034] Before introducing the specific embodiments of the present disclosure in detail, some terms used in the present disclosure are first explained.

[0035] Unless otherwise defined hereinafter, the meanings of all technical terms and scientific terms used herein are intended to be the same as those commonly understood by those skilled in the art. Referring to the technologies used herein refers to the technologies commonly understood in the art, including those changes to the technologies that are obvious to those skilled in the art or equivalent technology substitutions. 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 trade name appears herein, it is intended to refer to its corresponding product. All patents, published patent applications, and publications cited herein are incorporated herein by reference.

[0036] Unless otherwise specified in the text, multiple referents such as "a" or "the" include plural referents. The expressions "one or more" or "at least one" can mean 1, 2, 3, 4, 5, 6, 7, 8, 9 or more.

[0037] As used herein, terms such as "connected", "linked", "coupled" or "coupling" and similar words are not limited to direct connection, but also include indirect connection.

[0038] As described herein, a "sample" is a biomolecule, including proteins, nucleic acids, lipids, carbohydrates, small nucleotides, amino acids and their derivatives.

[0039] As used herein, the terms "online monitoring" or "real-time monitoring" refer to the real-time detection of certain parameters or properties of the buffer, reaction fluid, fluid flowing out of the flow reactor during the use of the chromatography system, such as pH value, pressure, flow rate, conductivity, etc. Different from offline detection or analysis, online monitoring or real-time monitoring can provide real-time feedback of the detection results.

[0040] As used herein, the positional relationship words such as "above", "below", "left", "right", "front", "rear", etc. are determined according to the layout direction of the specification drawings, and they are only used to represent the relative positional relationship. When the absolute position of the object being described changes, the relative positional relationship may also change accordingly.

[0041] Refer to Figure 1As shown, this embodiment uses a chromatography column and five mother liquor tanks. A fully automatic uninterrupted liquid dispensing chromatography system includes an alkali liquor storage tank 1, a pure water tank 2, a mother liquor A tank 3, a mother liquor B tank 4, a mother liquor C tank 5, a mother liquor D tank 6, a mother liquor H tank 7, a follow-up tank 8, and a product tank 9. The outlet ends of the outlet pipelines of the pure water tank 2 and the alkali liquor storage tank 1 are respectively connected to the inlet end of the first liquid inlet main pipeline 10 and the inlet end of the second liquid inlet main pipeline 11. Valves are provided on the outlet pipeline of the pure water tank 2, and a valve is provided at the inlet end of the first liquid inlet main pipeline 10; a valve is provided on the outlet pipeline of the alkali liquor storage tank 1; the mother liquor A tank 3, the mother liquor B tank 4, the mother liquor C tank 5, the mother liquor D tank 6, and the mother liquor H tank 7 are arranged in sequence from left to right. The outlet pipeline of the mother liquor A tank 3 is connected to the first liquid inlet main pipeline 10 through a first connection pipeline 12 via a valve. A valve is provided on the outlet pipeline of the mother liquor A tank 3, and a valve is provided at the liquid inlet end of the first connection pipeline 12. The outlet pipeline of the mother liquor A tank 3 is connected to the cleaning discharge tank 24 through a valve. The first connection pipeline 12 is provided with a first mother liquor pump 13 and a first flow sensor 14. The bottom of the first connection pipeline 12 is connected to the inlet end of a first bypass pipeline 15 through a valve. The outlet end of the first bypass pipeline 15 is respectively connected to the top inlet end of the first connection pipeline 12 and the waste discharge tank 16 through valves; and so on for the mother liquor B tank 4, the mother liquor C tank 5, the mother liquor D tank 6, and the mother liquor H tank 7, and the mother liquor A tank 3 is connected to the first liquid inlet main pipeline 10 in the same way in sequence. A first liquid inlet pump 17 is provided on the first liquid inlet main pipeline 10. The liquid inlet pump 17 is located on the right side of the connection point between the mother liquor H tank 7 and the first liquid inlet main pipeline 10. The first liquid inlet main pipeline 10 is also respectively provided with a second flow sensor 18, a first pressure sensor 19, a first conductivity transmitter 20, and a first pH sensor 21; the first liquid inlet main pipeline 10 is connected to the inlet end of the follow-up tank 22 through a connection pipeline; the outlet pipelines of the product tank 23, the follow-up tank 22, and the cleaning discharge tank 24 are respectively connected to the inlet end of a second connection pipeline 26 through valves. The outlet end of the second connection pipeline 26 is connected to the first liquid inlet main pipeline 10 through a valve. The second connection pipeline 26 is respectively provided with a second liquid inlet pump 27 and a third flowmeter 28. The second liquid inlet main pipeline 11 is respectively connected to the outlet pipelines of the mother liquor A tank 3, the mother liquor B tank 4, the mother liquor C tank 5, the mother liquor D tank 6, and the mother liquor H tank 7 through connection pipelines, and valves are respectively provided on the connection pipelines to control the on-off; and the second liquid inlet main pipeline 11 is connected to the outlet pipeline of the cleaning discharge tank 24. The first liquid inlet main pipeline 10 is respectively connected to the inlet end and the outlet end of a bubble trap 29 through connection pipelines. Valves are respectively provided on the connection pipelines and on the first liquid inlet main pipeline 10 between the inlet and outlet ends. The connection point between the bubble trap 29 and the first liquid inlet main pipeline 10 is located on the right side of the connection point between the second connection pipeline 26 and the first liquid inlet main pipeline 10.A valve array is provided on the first main liquid inlet pipe 10. The valve array is a rectangular valve array composed of four valves connected end to end. One pair of opposite sides of the rectangular valve array communicates with the first main liquid inlet pipe 10, and there are 10 valves provided on the first main liquid inlet pipe; the other pair of opposite sides of the rectangular valve array respectively communicate with the upper and lower inlets and outlets of the chromatography column 30. The UV sensor 31, the second conductivity transmitter 32, and the second pH sensor 33 are respectively provided on the first main liquid inlet pipe 10 on the right side of the rectangular valve array; the outlet end of the first main liquid inlet pipe 10 is respectively connected to the inlet end of the lye storage tank 1, the inlet of the collection tank 34, and the inlet of the waste discharge tank 16 through connecting pipes, and valves are respectively provided on the connecting pipes. The connection point between the follow-up tank 22 and the first main liquid inlet pipe 10 is connected to the inlet of the waste discharge tank 16 through a connecting pipe, and a valve is provided on the connecting pipe; the connection point between the outlet end of the bubble trap 29 and the first main liquid inlet pipe 10 is connected to the inlet of the waste discharge tank 16 through a connecting pipe, and the top outlet of the bubble trap 29 is connected to the inlet of the waste discharge tank 16 through a connecting pipe, and valves are respectively provided on the connecting pipes. A bubble sensor 35 and a second pressure sensor 36 are provided on the first main liquid inlet pipe 10 between the bubble trap 29 and the rectangular valve array.

[0042] During use: First: Product sampling and pre-preparation in the follow-up tank (1) For product sampling, the valve on the outlet pipeline of the product tank 23 is opened, and the second liquid inlet pump 27 on the second connecting pipe 26 is opened. The product liquid to be processed passes through the first main liquid inlet pipe 10, the bubble trap 29, and the rectangular valve array group and enters the chromatography column 30. The processed product liquid is discharged into the waste discharge tank 16 for collection after passing through the first main liquid inlet pipe 10 from the outlet of the chromatography column 30. (2) Pre-preparation in the follow-up tank. For example, when preparing buffer solution A, the first liquid inlet pump 17 on the first main liquid inlet pipe 10 is opened at this time, and at the same time, the first mother liquid pump 13 on the first connecting pipe 12 communicating with the mother liquid tank is opened, such as the mother liquid A tank 3, the mother liquid C tank 5, and the mother liquid D tank 6. At this time, the solutions in the pure water tank 2, the mother liquid A tank 3, the mother liquid C tank 5, and the mother liquid D tank 6 all enter the first main liquid inlet pipe 10. The second flow sensor 18, the first pressure sensor 19, the first conductivity transmitter 20, and the first pH sensor 21 monitor the data in real time. The non-compliant buffer solution in the early stage will enter the waste discharge tank 16 through the connecting pipe at the connection point between the follow-up tank 22 and the first main liquid inlet pipe 10; when the buffer solution is qualified, the valve on the connecting pipe communicating with the waste discharge tank 16 is closed at this time, and the valve on the connecting pipe connecting the first main liquid inlet pipe 10 and the inlet of the follow-up tank 22 is opened at this time. At this time, buffer solution A will enter the follow-up tank 22.

[0043] II. Follow-up tank chromatography: When the chromatography of the product liquid is completed and elution is required, buffer A is used as the eluent at this time. Then, the valve of the outlet pipeline of the follow-up tank 22 is opened, and the buffer solution in the follow-up tank 22 enters the chromatography column 30 through the second connecting pipeline 26, the bubble trap 29, and the rectangular valve array group. After eluting the product adsorbed in the chromatography column 30, it is discharged into the collection tank 34 through the first main liquid inlet pipeline 10.

[0044] III. If different liquid preparations are required according to the formula, the solution in the mother liquid tank can be directly collected after chromatography through the chromatography column: For example, when cleaning is required and buffer B needs to be prepared, the first liquid inlet pump 17 on the first main liquid inlet pipeline 10 is opened, and at the same time, the first mother liquid pump 13 on the first connecting pipeline 12 connected to the mother liquid tank is opened, such as the mother liquid C tank 5 and the mother liquid H tank 7. At this time, the solution in the pure water tank 2, the solutions in the mother liquid C tank 5 and the mother liquid H tank 7 all enter the first main liquid inlet pipeline 10. The second flow sensor 18, the first pressure sensor 19, the first conductivity transmitter 20, and the first pH sensor 21 monitor the data in real time. After passing through the bubble trap 29 and the shaped valve array group, they enter the chromatography column 30 and are collected in the waste discharge tank 16 after flowing out from the outlet of the chromatography column 30.

[0045] IV. Preparation of lye: When lye needs to be prepared, the first liquid inlet pump 17 on the first main liquid inlet pipeline 10 is opened, and at the same time, the first mother liquid pump 13 on the first connecting pipeline 12 connected to the mother liquid tank is opened, for example, the mother liquid D tank 6. At this time, the solution in the pure water tank 2 and the solution in the mother liquid D tank 6 all enter the first main liquid inlet pipeline 10. The second flow sensor 18, the first pressure sensor 19, the first conductivity transmitter 20, and the first pH sensor 21 monitor the data in real time, and then flow into the inlet end of the lye storage tank 1 through the outlet end of the first main liquid inlet pipeline 10 and enter the lye storage tank 1.

[0046] V. Cleaning

[0047] (1) Lye circulation:

[0048] At this time, the first liquid inlet pump 17 on the first main liquid inlet pipeline 10, the first mother liquid pump 13 on the first connecting pipeline 12, and the second liquid inlet pump 27 on the second connecting pipeline 26 are respectively opened, and lye enters the first main liquid inlet pipeline 10 and the second main liquid inlet pipeline 11 respectively. Part of the lye in the second main liquid inlet pipeline 11 enters the first connecting pipelines 12 of each mother liquid tank and the first bypass pipeline 15 connected thereto through the second main liquid inlet pipeline 11 and then enters the waste discharge tank 16. Another part of the lye enters the lye storage tank 1 after entering the first main liquid inlet pipeline 10 through the second connecting pipeline 26; the lye directly entering the first main liquid inlet pipeline 10 enters the lye storage tank 1 along the first main liquid inlet pipeline 10.

[0049] (2) Direct discharge of pure water

[0050] At this time, the first liquid inlet main pump 17 on the first liquid inlet main pipeline 10, the first mother liquid pump 13 on the first connection pipeline 12, and the second liquid inlet pump 27 on the second connection pipeline 26 are respectively opened, and pure water enters the first liquid inlet main pipeline 10 and the second liquid inlet main pipeline 11 respectively; part of the pure water in the second liquid inlet main pipeline 11 enters the first connection pipeline 12 of each mother liquid tank through the second liquid inlet main pipeline 11 and enters the waste discharge tank 16 through the first bypass pipeline 15. There is also a part of the lye that enters the first liquid inlet main pipeline 10 through the second connection pipeline 26 and then enters the waste discharge tank 16; the lye directly entering the first liquid inlet main pipeline 10 enters the waste discharge tank 16 along the first liquid inlet main pipeline 10.

[0051] (3) Follow the cleaning of the tank pipeline

[0052] Open the first liquid inlet pump 17 on the first liquid inlet main pipeline 10. The lye water in the lye storage tank 1 enters the follow-up tank 22 through the first liquid inlet main pipeline 10, then flows out from the outlet of the follow-up tank 22 to the first liquid inlet main pipeline 10, and finally returns to the lye storage tank 1; open the first liquid inlet pump 17 on the first liquid inlet main pipeline 10. The pure water in the pure water tank 2 enters the follow-up tank 22 through the first liquid inlet main pipeline 10, then flows out from the outlet of the follow-up tank 22 to the first liquid inlet main pipeline 10, and finally returns to the waste discharge tank 16.

Claims

1. A fully automatic non-stop liquid preparation chromatography system, characterized in that: The invention comprises a first liquid inlet main pipeline, a pure water tank, an alkali liquid tank, a plurality of mother liquid tanks, a follower tank, a product tank, a bubble trap, a plurality of chromatography columns, a first liquid inlet main pipeline, a collection tank and a waste discharge tank; the first liquid inlet main pipeline is connected to the outlet of the alkali liquid tank, the outlet of the pure water tank and the outlets of the mother liquid tanks in sequence through pipelines; the outlet pipelines of the mother liquid tanks are connected to the first liquid inlet main pipeline through connecting pipelines, and mother liquid pumps are respectively arranged on the connecting pipelines; a main pump is arranged on the first liquid inlet main pipeline; the inlet end and the outlet end of the follower tank are respectively connected to the first liquid inlet main pipeline through pipelines The first liquid inlet main pipeline is connected to the product tank through a pipeline; the first liquid inlet main pipeline is respectively connected to the inlet end and the outlet end of the bubble trap through pipelines; the first liquid inlet main pipeline is connected to the inlet end of the corresponding chromatography column through different pipelines, and the outlet end of each chromatography column is connected to the first liquid inlet main pipeline through a corresponding pipeline; the outlet end of the first liquid inlet main pipeline is respectively connected to the collection tank and the waste tank through a valve; the first liquid inlet main pipeline, the connecting pipelines between each mother liquid tank and the first liquid inlet main pipeline, and the connecting pipeline between the follower tank and the first liquid inlet main pipeline are all provided with pumps.

2. A fully automatic non-stop liquid preparation chromatography system according to claim 1, characterized in that: The first liquid inlet main pipeline is connected to the inlet end of the alkali liquid tank through a pipeline to realize the circulation of the alkali liquid.

3. A fully automatic non-stop liquid preparation chromatography system according to claim 1, characterized in that: The outlet pipeline of the alkali liquid tank and the outlet pipeline of the pure water tank are connected to the second liquid inlet main pipeline, and the second liquid inlet main pipeline is respectively connected to the outlet ends of the outlet pipelines of each mother liquid tank.

4. The fully automatic non-stop liquid preparation chromatography system according to claim 1, characterized in that: The second liquid inlet main pipeline is connected to the cleaning discharge pipeline.

5. The fully automatic non-stop liquid preparation chromatography system according to claim 1, characterized in that: The outlet ends of the outlet pipelines of the respective mother liquid tanks are respectively connected to the cleaning discharge tanks.

6. The fully automatic non-stop liquid preparation chromatography system according to claim 1, characterized in that: The bottom of the connecting pipe between each mother liquid tank outlet pipeline and the first liquid inlet main pipeline is connected to the top inlet end of the connecting pipe between the pipeline mother liquid tank and the first liquid inlet main pipeline through a bypass pipeline to form a closed loop.

7. The fully automatic non-stop liquid preparation chromatography system according to claim 6, characterized in that: The outlet end of the bypass pipeline is connected to the waste discharge tank.

8. The fully automatic non-stop liquid preparation chromatography system according to claim 1, characterized in that: A valve array is provided on the first liquid inlet main pipeline, and the valve array is a rectangular valve array composed of four valves connected end to end. One group of opposite sides of the rectangular valve array is connected to the first liquid inlet main pipeline; the other group of opposite sides of the rectangular valve array are respectively connected to the upper inlet and lower inlet of the chromatography column.

9. The fully automatic non-stop liquid preparation chromatography system according to claim 1, characterized in that: The outlet of the liquid tank and the outlet pipeline of the pure water tank are connected to the first liquid inlet main pipeline through a connecting pipeline.

10. The fully automatic non-stop liquid preparation chromatography system according to claim 1, characterized in that: The connecting parts of the pipelines are connected through valves.

11. The fully automatic non-stop liquid preparation chromatography system according to claim 1, characterized in that: Flow sensors are arranged on the first liquid inlet main pipeline, the connecting pipelines between each mother liquid tank and the first liquid inlet main pipeline, and the connecting pipelines between the follower tank and the first liquid inlet main pipeline.

12. A method for using a fully automatic non-interruption liquid preparation chromatography system, characterized in that: The steps are as follows: Step 1: The follow-up tank is pre-mixed and the product is loaded at the same time; according to the formula, the solution in the corresponding mother liquid tank and pure water are transported to the follow-up tank through the first liquid inlet main pipeline; at the same time, the product solution in the product tank enters the chromatography column through the bubble trap and is collected after chromatography; Step 2: Following tank chromatography: The solution in the following tank enters the chromatography column through the bubble trap and is collected after chromatography; Step 3: If different solutions are required according to the formula, the solution in the mother liquid tank can be directly collected after chromatography on the chromatography column; Step 4: Preparation of alkali solution: the solution in the pure water tank and the solution in the corresponding mother liquid tank flow into the inlet end of the alkali solution tank through the first liquid inlet main pipeline. Step 5: Cleaning.

13. A method for using a fully automatic non-interruption liquid preparation chromatography system according to claim 12, characterized in that: The cleaning includes: (1) alkaline solution circulation; (2) pure water direct discharge; (3) follow-up tank pipeline cleaning.

14. The method for using the fully automatic non-interruption liquid preparation chromatography system according to claim 12, characterized in that: The alkali liquid circulation is as follows: the alkali liquid flows out from the alkali liquid tank outlet through the first liquid inlet main pipeline and then flows into the alkali liquid tank inlet; the alkali liquid flows into the connecting pipelines of each mother liquid tank and the first liquid inlet main pipeline through the second liquid inlet main pipeline and then enters the waste tank through the bypass pipeline, and flows into the connecting pipelines of the first liquid inlet main pipeline and the product tank outlet pipeline and the follower tank outlet pipeline and enters the first liquid inlet main pipeline and then enters the alkali liquid tank.

15. The method for using the fully automatic non-interruption liquid preparation chromatography system according to claim 12, characterized in that: The direct discharge of pure water: the pure water in the pure water tank passes through the first liquid inlet main pipeline, and then flows into the waste discharge pipeline for collection and / or the pure water passes through the second liquid inlet main pipeline and respectively flows into the connecting pipelines of each mother liquid tank and the first liquid inlet main pipeline, and then enters the waste discharge tank through the bypass pipeline, and flows into the connecting pipelines of the first liquid inlet main pipeline and the product tank outlet pipeline and the follow-up tank outlet pipeline to enter the first liquid inlet main pipeline and then enter the waste discharge tank.

16. The method for using the fully automatic non-interruption liquid preparation chromatography system according to claim 12, characterized in that: The following tank pipeline cleaning: the alkali solution flows into the inlet end of the following tank through the first liquid inlet main pipeline, and then flows into the alkali solution tank inlet through the following tank outlet end and the first liquid inlet main pipeline; the pure water flows into the inlet end of the following tank through the first liquid inlet main pipeline, and then flows into the waste discharge pipeline through the following tank outlet end and the first liquid inlet main pipeline.

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