A production-level continuous flow chromatography system and method

Abstract

The present invention relates to a chromatography system and method, and in particular to a production-level continuous flow chromatography system and method, comprising a chromatography unit, a loading combination valve and an elution combination valve, wherein a plurality of inlets and outlets are arranged on the combination valve, and a flow path that can be conducted is formed between the inlets and outlets. The valve combines numerous valves and switching components of a traditional continuous flow chromatography system into a whole by arranging a loading combination valve and an elution combination valve, thereby improving the use efficiency of the chromatography column, optimizing the composition architecture of the system, reducing the number of valves in the continuous flow chromatography column system, simplifying the system flow path, and being easier to maintain and move. At the same time, the system can realize free switching of 2 columns or 3 columns without adding or reducing pipelines and valves, so that the production continuous flow chromatography system provided by the present invention is particularly suitable for industrial production.

Description

Technical Field

[0001] The invention relates to a chromatography system and method, and in particular to a production-level continuous flow chromatography system and method. Background Art

[0002] In the fields of biochemistry, clinical medicine, food science, biopharmaceuticals, etc., many production processes involve products with a lot of impurities, such as antibodies, vaccines, proteins, blood products, etc. In these production processes, in order to purify the target product, it is usually necessary to use a chromatographic column for separation. Currently, the most commonly used preparative chromatography system is a single-column system, which has the advantages of simple operation and applicability to a variety of production scenarios, but has the disadvantages of low work efficiency and low filler utilization.

[0003] In order to solve these problems, researchers have developed a multi-column continuous flow chromatography system based on a single-column system in recent years. This system usually connects 2 to 8 columns in series, and greatly improves the chromatography efficiency through the combination of multiple columns. Using smaller columns and less volume of filler can achieve the same sample processing volume, or significantly improve production capacity under the same filler volume and column size conditions.

[0004] At present, there are 2-column, 3-column, 4-column and 6-column continuous flow chromatography equipment on the market. However, these devices have numerous switching components, complex pipeline connections, and complex control systems. For example, a 3-column continuous flow system requires at least 6 inlet switching components, 6 outlet switching components, and several three-way components to achieve arbitrary switching between 3 columns and 2 columns. As the number of columns increases, the number of inlet and outlet switching components and tees also increases. Although this system can significantly improve processing efficiency, its main problem is that the structure is too complex, maintenance is difficult, and the size is large. This restricts the application of production-type continuous flow chromatography systems in industrial production and limits their promotion. Summary of the invention

[0005] In order to solve the deficiencies in the prior art, the present invention constructs a new production-type continuous flow chromatography system and method, which solves the problems of numerous switching components, complex connections and complex controls in current continuous flow chromatography systems through the structural design of a continuous flow valve.

[0006] In order to solve the above technical problems, the present invention adopts the following technical solutions: The first aspect of the present invention is to provide a production-level continuous flow chromatography system, including a chromatography unit, a loading combination valve and an elution combination valve, the chromatography unit includes multiple groups of chromatography components, and the valve bodies of the loading combination valve and the elution combination valve are respectively provided with multiple inlets and outlets, wherein two of the inlets and outlets of the loading combination valve are respectively used as the initial loading inlet and the final elution outlet, and the remaining inlets and outlets are used as connecting ports and are divided into two groups, one group is used as the liquid inlet of each chromatography component, and the other group is used as the front-path connecting port connected to other chromatography components, the initial loading inlet can be selected to be connected to different liquid inlets, and the final elution outlet can be selected to be connected to different liquid inlets. Connected with different front-end connection ports; two of the inlets and outlets of the elution combination valve are used as the initial elution inlet and the final sample loading outlet respectively, and the remaining inlets and outlets are used as connection ports, which are divided into two groups, one group is used as the liquid outlet of each chromatography component, and the other group is used as the rear-end connection ports connected to other chromatography components, the initial elution inlet can be selected to be connected with different rear-end connection ports, and the final sample loading outlet can be selected to be connected with different liquid outlets; in the sample loading combination valve and the elution combination valve, a valve is provided between the inlets and outlets forming the flow path, which is used to open or cut off the corresponding flow path, and any rear-end connection port is connected with the adjacent front-end connection port, so that each chromatography component can be selectively connected in series with the remaining chromatography components.

[0007] As a preferred embodiment, in the valve body of the loading combination valve and / or the elution combination valve, each group of liquid inlets and / or liquid outlets includes N inlets and outlets, each group of front connection ports and / or rear connection ports includes N inlets and outlets, and the chromatography unit includes N-1 groups or N groups of chromatography components, where N is an integer ≥3.

[0008] As a preferred embodiment, in the chromatography unit, each chromatography component is circularly connected through a loading combination valve and an elution combination valve: the rear connection port of each chromatography component is connected to the front connection port of the next chromatography component, and the rear connection port of the last chromatography component is connected to the front connection port of the first chromatography component.

[0009] As a preferred embodiment, the chromatography unit includes N-1 groups of chromatography components, each group of chromatography components is connected between any liquid inlet and any liquid outlet, the rear connection port of the N-2 group of chromatography components is connected to the front connection port of the N-1 group of chromatography components, so that the N-1 group of chromatography components can be selectively connected in series after the N-2 group of chromatography components; the rear connection port of the N-1 group of chromatography components is connected to the front connection port of the N group, the Nth liquid inlet is connected to the Nth liquid outlet, and the Nth rear connection port is connected to the front connection port of the first group of chromatography components, so that the N-2 group of chromatography components and / or the first group of chromatography components can be selectively connected in series after the N-1 group of chromatography components.

[0010] As a preferred embodiment, the chromatography unit includes N groups of chromatography components, each group of chromatography components is connected between any liquid inlet and any liquid outlet, the rear connecting port of the N-2 group of chromatography components is connected to the front connecting port of the N-1 group of chromatography components, so that the N-1 group of chromatography components can be selectively connected in series after the N-2 group of chromatography components; the rear connecting port of the N-1 group of chromatography components is connected to the front connecting port of the N group of chromatography components, so that the N group of chromatography components can be selectively connected in series after the N-1 group of chromatography components; the rear connecting port of the N group of chromatography components is connected to the front connecting port of the first group of chromatography components, so that the first group of chromatography components can be selectively connected in series after the N group of chromatography components.

[0011] As a preferred embodiment, the flow path valves used for opening or cutting off in the loading combination valve and the elution combination valve are both provided with a feedback mechanism; in the loading combination valve and the elution combination valve, the flow path calibers and volumes between the connection ports are the same, so that the dead volumes of the branch pipelines led out from each connection port are the same; the valve bodies of the loading combination valve and the elution combination valve are both symmetrical, and the valve group can be divided into multiple equal parts by connecting the two inlets and outlets.

[0012] As a preferred embodiment, in the valve bodies of the loading combination valve and the elution combination valve, the flow paths formed between the two inlets and outlets are independent passages that do not interfere with each other, and there is no mixing of liquids in the loading combination valve and the elution combination valve; in the chromatography unit, the chromatography component includes at least one chromatography column, and the specifications, filler type, filling height and column efficiency of each chromatography column in each chromatography component are consistent.

[0013] The second aspect of the present invention is to provide a production-level continuous flow chromatography method, which specifically comprises the following steps:

[0014] a. Providing the above-mentioned production-grade continuous flow chromatography system, the initial loading inlet and the initial elution inlet are connected to the loading pump and the elution pump respectively;

[0015] b. The sample pump balances each chromatographic component through the initial sample inlet, and selects to enter any chromatographic component each time, and the remaining chromatographic components are connected in series in sequence, and the fluid passes through all the chromatographic components in sequence, and finally discharged from the final sample outlet;

[0016] c. The sample is loaded into each chromatographic component through the initial loading inlet by the loading pump, and each time any chromatographic component is selected to enter, the loading flow-through liquid is directly discharged from the final loading outlet;

[0017] d. When the sample of one of the chromatography components flows through, another chromatography component is connected in series to the back of the chromatography component through which the sample flows, and the sample loading continues;

[0018] e. When one of the chromatography components reaches a full load state, the chromatography component is kept in series with another chromatography component, and the two chromatography components are eluted by the loading pump through the initial loading inlet;

[0019] f. When one of the fully loaded chromatography components has completed elution, its series connection with the other chromatography component ends, and the loading pump continues to load the partially loaded chromatography component; at the same time, the elution pump elutes, cleans, and rebalances the fully loaded chromatography component through the initial elution inlet; the rebalanced chromatography component waits for series loading with other chromatography components that have sample flow-through.

[0020] As a preferred embodiment, the production-level continuous flow chromatography method comprises:

[0021] a. The sample loading pump balances each chromatographic component. The balancing liquid enters from the initial loading inlet and enters any chromatographic component. The balancing liquid passes through all the chromatographic components in sequence and is discharged from the final loading outlet;

[0022] b. The sample is loaded by the loading pump, and the sample is injected from the initial loading inlet, and selected to enter any chromatography component, and the loading flow-through liquid is discharged from the final loading outlet;

[0023] c. When 1% of the sample flows through the first group of chromatography components, the second group of chromatography components is connected in series to the first group of chromatography components, and the sample flows through the first group of chromatography components to continue loading, and the sample flow-through liquid is discharged through the final loading outlet;

[0024] d. After the first chromatography component reaches full load, the first chromatography component and the second chromatography component are kept in series, and the sample pump is used for elution. The elution liquid enters from the initial sample inlet, passes through the first chromatography component and the second chromatography component in sequence, and is discharged from the final sample outlet;

[0025] e. After the elution is completed, the first chromatography component and the second chromatography component end the series connection state, and the sample is loaded on the second chromatography component by the sample loading pump. At the same time, the first chromatography component is eluted, cleaned, and rebalanced by the elution pump through the initial elution inlet, and the eluent is collected from the elution final outlet. After the elution peak is collected, the first chromatography component is discharged through the elution final outlet;

[0026] f. When the second chromatography component is loaded with 1% sample flow-through and the first chromatography component is re-equilibrated, the first chromatography component starts to be connected in series with the second chromatography component, and the sample flow-through of the second chromatography component continues to be loaded, and the sample flow-through is discharged through the final loading outlet;

[0027] g. After the second chromatography component reaches full load, the first chromatography component and the second chromatography component are kept in series, and the eluent is eluted by the loading pump. After the eluent passes through the second chromatography component and the second chromatography component in turn, it is discharged from the final loading outlet;

[0028] h. After the elution is completed, the first chromatography component and the second chromatography component end the series connection state, and the sample is loaded on the first chromatography component by the sample loading pump. At the same time, the second chromatography component is eluted, cleaned, and rebalanced by the elution pump through the initial elution inlet. The eluent is collected from the elution final outlet for elution peak collection. After the elution peak is collected, the second chromatography component is discharged through the elution final outlet;

[0029] I. Repeat the above steps c~h in sequence to achieve continuous flow chromatography.

[0030] As a preferred embodiment, the production-level continuous flow chromatography method comprises:

[0031] a. The sample loading pump balances each chromatographic component. The balancing liquid enters from the initial loading inlet and enters any chromatographic component. The balancing liquid passes through all the chromatographic components in sequence and is discharged from the final loading outlet;

[0032] b. The sample is loaded by the loading pump, the sample is injected from the initial loading inlet, and enters any chromatography component through the liquid inlet, and the loading flow-through is discharged through the final loading outlet;

[0033] c. When 1% of the sample flows through the first set of chromatography components, the second chromatography component is connected in series to the first chromatography component, and the sample flows through the first chromatography component to continue loading, and the sample flow-through is discharged through the final loading outlet;

[0034] d. After the first chromatography component reaches full load, the first chromatography component and the second chromatography component are kept in series, and the eluent is eluted by the loading pump. The eluent enters from the initial loading inlet, passes through the first chromatography component and the second chromatography component in sequence, and is discharged from the final loading outlet;

[0035] e. After the elution is completed, the first chromatography component and the second chromatography component end the series connection state, and the sample is loaded on the second chromatography component by the sample loading pump. At the same time, the first chromatography component is eluted, cleaned, and rebalanced by the elution pump through the initial elution inlet, and the eluent is collected from the elution final outlet. After the elution peak is collected, the first chromatography component is discharged through the elution final outlet;

[0036] f. After the second chromatography component is loaded with 1% of the sample flow-through, the third chromatography component begins to be connected in series with the second chromatography component, and the sample flow-through of the second chromatography component continues to be loaded, and the sample flow-through liquid is discharged through the final loading outlet;

[0037] g. After the second chromatography component reaches full load, the third chromatography component and the second chromatography component are kept in series, and the eluent is eluted by the loading pump. After the eluent passes through the second chromatography component and the third chromatography component in turn, it is discharged from the final loading outlet;

[0038] h. When the third chromatography component is loaded with 1% sample flow-through and the first chromatography component is re-equilibrated, the first chromatography component starts to be connected in series with the second chromatography component, and the sample flow-through of the third chromatography component continues to be loaded, and the sample flow-through is discharged through the final loading outlet;

[0039] i. After the third chromatography component is fully loaded, the third chromatography component and the first chromatography component are kept in series, and the eluent is eluted by the loading pump. The eluent passes through the third chromatography component and the first chromatography component in turn, and is discharged from the final loading outlet;

[0040] j. After the elution is completed, the third chromatography component and the first chromatography component end the series connection state, and the sample is loaded on the first chromatography component by the sample loading pump. At the same time, the elution pump elutes, cleans and rebalances the third chromatography component through the initial elution inlet, and the eluent is collected from the elution final outlet for elution peak collection. After the elution peak is collected, the third chromatography component is discharged through the elution final outlet;

[0041] k. Repeat the above steps c~j in sequence to achieve continuous flow chromatography.

[0042] Compared with the prior art, this application has at least the following beneficial effects:

[0043] First, the present invention is suitable for constructing a production-type continuous flow chromatography system. Through the structural design of the continuous flow valve, the numerous valves and switching components of the continuous flow chromatography system are formed into a whole, the number of flow paths and valves is reduced, and the composition architecture of the chromatography system is greatly optimized, making it simpler and more convenient to maintain the system. By combining the valves and switching components, only the continuous flow valve group needs to be replaced or repaired, and there is no need to store too many spare parts. The chromatography system is more convenient to maintain and move.

[0044] Secondly, the continuous flow chromatography system of the present invention does not need to add or reduce pipelines and valves when switching between a 2-column and a 3-column continuous flow chromatography system. Unlike traditional continuous chromatography systems that require redesign of pipeline and valve layouts when demand changes, the present invention can flexibly expand or adjust the number of chromatography components based on the existing structure, avoiding the tedious re-planning and layout of pipelines, which makes the system of the present invention more adaptable and can quickly respond to the needs of different production scales. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0046] Figure 1 This is a schematic structural diagram of one embodiment of the continuous flow valve of the present invention;

[0047] Figure 2 This is a schematic diagram of the internal structure of the continuous flow valve of the present invention;

[0048] Figure 3 This is a PID diagram of one embodiment of a two-column continuous flow chromatography system of the present invention;

[0049] Figure 4 This is a flow chart of the production-level continuous flow chromatography method of the present invention;

[0050] Figure 5 This is a PID diagram of one embodiment of a three-column continuous flow chromatography system of the present invention;

[0051] Markings in the figure: 100-inlet and outlet; 200-valve; 300-flow path; A-loading combination valve; B-elution combination valve; P1-loading pump; P2-elution pump; C1-first group of chromatography components; C2-second group of chromatography components; C3-third group of chromatography components; A1-initial inlet for loading; A2-first liquid inlet; A3-second liquid inlet; A4-third liquid inlet; A5-first front road connection port; A6-second front road connection port; A7-third front road connection port; A8-final outlet for elution; B1-final outlet for loading; B2-first liquid outlet; B3-second liquid outlet; B4-third liquid outlet; B5-first rear road connection port; B6-second rear road connection port; B7-third rear road connection port; B8-initial inlet for elution. DETAILED DESCRIPTION

[0052] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0053] In the description of the present invention, it should be noted that the terms "center", "up", "down", "left", "right", "vertical", "horizontal", "inside", "outside", etc. indicate directions or positional relationships based on the directions or positional relationships shown in the accompanying drawings, or are the directions or positional relationships in which the inventive product is usually placed when in use. They are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific direction, be constructed and operated in a specific direction, and therefore should not be understood as a limitation on the present invention.

[0054] In addition, the terms "horizontal", "vertical" and the like do not mean that the components are required to be absolutely horizontal or suspended, but can be slightly tilted. For example, "horizontal" only means that its direction is more horizontal than "vertical", and does not mean that the structure must be completely horizontal, but can be slightly tilted.

[0055] In the description of the present invention, it is also necessary to explain that, unless otherwise clearly specified and limited, the terms "set", "install", "connect", and "connect" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be the internal communication of two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0056] See also Figure 1 In order to solve the problems of numerous switching components, complex connections and complex controls in the current continuous flow chromatography system, the present application provides a continuous flow valve; the continuous flow valve includes a plurality of inlets and outlets 100, and these inlets and outlets 100 form independent flow paths 300 with adjacent inlets and outlets 100, wherein two inlets and outlets 100 serve as the initial liquid inlet and final liquid outlet of the continuous flow valve respectively, and the remaining inlets and outlets serve as connecting ports, and each flow path 300 is provided with a valve 200 for opening or cutting off the corresponding flow paths 300; the continuous flow valve can cooperate with a chromatography component to construct a continuous flow chromatography system, and the chromatography component includes at least one chromatography column, and the continuous flow valve can cooperate with the chromatography column to form a continuous flow chromatography system with 2 columns, 3 columns, 6 columns, or even more chromatography columns.

[0057] See also Figure 2-Figure 3When the continuous flow valve cooperates with the chromatography column to form a continuous flow chromatography system, at least two groups of continuous flow valves are configured at both ends of the chromatography unit, which are respectively used as a loading combination valve A and an elution combination valve B; the liquid initial inlet and the liquid final outlet of the loading combination valve A are respectively used as the loading initial inlet A1 and the elution final outlet A8, and the remaining inlets and outlets are used as connecting ports, which are divided into two groups, one group is used as the liquid inlet A2, A3, A4 of each chromatography component, and the other group is used as the front-end connecting ports A5, A6, A7 connected to other chromatography components, the loading initial inlet A1 can be selected to be connected to different liquid inlets A2, A3, A4 through the control valve 200, and the elution final outlet A8 can be selected to be connected to different front-end connecting ports A5, A6, A7 through the control valve 200;

[0058] The liquid initial inlet and liquid final outlet of the elution combination valve are respectively used as the elution initial inlet B8 and the sample loading final outlet B1, and the remaining inlets and outlets are used as connecting ports, which are divided into two groups, one group is used as the liquid outlets B2, B3, and B4 of each chromatography component, and the other group is used as the back-end connecting ports B5, B6, and B7 connected to other chromatography components. The elution initial inlet B8 can be selectively connected to different back-end connecting ports B5, B6, and B7 through the control valve 200, and the sample loading final outlet B1 can be selectively connected to different liquid outlets B2, B3, and B4 through the control valve 200;

[0059] Among them, any liquid inlet A2, A3, A4 is arranged adjacent to its corresponding front-path connecting port A5, A6, A7, any liquid outlet B2, B3, B4 is arranged adjacent to its corresponding rear-path connecting port B5, B6, B7, and any rear-path connecting port B5, B6, B7 is connected to the adjacent front-path connecting port, so that each chromatography component can be selectively connected in series with the remaining chromatography components; wherein each group of chromatography components is connected between any liquid inlet A2, A3, A4 and liquid outlet B2, B3, B4; the initial loading inlet A1 is connected to the loading pump P1, which is used for loading and eluting; the initial elution inlet B8 is connected to the elution pump P2, which is used for elution, cleaning and rebalancing.

[0060] In this way, the continuous flow valve of the present application can replace the numerous valves and switching components in the traditional continuous flow system to form a whole, reduce the number of pipes and valves in the continuous flow chromatography system, greatly optimize the composition architecture of the system, and make it simpler. During maintenance, only the continuous flow valve group needs to be replaced or repaired, and there is no need to store too many spare parts. At the same time, it is easier to maintain and move, and the reliability and flexibility of the system are greatly improved. These optimizations make the continuous flow chromatography system of the present application more suitable for industrial production.

[0061] In the valve body of the loading combination valve A and / or the elution combination valve B, each group of liquid inlets and / or liquid outlets includes N inlets and outlets, and each group of front-path connection ports and / or rear-path connection ports includes N inlets and outlets. N groups of chromatography components can be correspondingly arranged in the chromatography unit, or N-1 groups of chromatography components can be arranged. Compared with the traditional continuous flow system, when the system of the present application switches from N-1 groups to N groups of chromatography components, there is no need to add or reduce pipes and valves, so that the system of the present application can be better expanded or adjusted according to needs. The following takes the most commonly used 2-column and 3-column continuous flow chromatography systems in industrial production as an example of the switching and structure of the chromatography system of the present application. For example,

[0062] See also Figure 2 The continuous flow valve includes eight inlets and outlets 100, and these inlets and outlets 100 form nine independent flow paths 300 with adjacent inlets and outlets 100. Among them, two inlets and outlets 100 form flow paths 300 with three adjacent inlets and outlets 100, and these two inlets and outlets serve as the initial liquid inlet and final liquid outlet of the continuous flow valve, respectively. The remaining six inlets and outlets 100 serve as connecting ports, which are divided into two groups, so that each group of liquid inlets and liquid outlets includes three inlets and outlets 100, so that each group of front-path connecting ports and rear-path connecting ports includes three inlets and outlets 100;

[0063] See also Figure 3 In a two-column continuous flow chromatography system, the chromatography unit comprises a first group of chromatography components C1 and a second group of chromatography components C2, the liquid inlet and liquid outlet of the first group of chromatography components C1 are respectively a first liquid inlet A2 and a first liquid outlet B2, the liquid inlet and liquid outlet of the second group of chromatography components C2 are respectively a second liquid inlet A3 and a second liquid outlet B3, the front connection port and the rear connection port of the first group of chromatography components C1 are respectively a first front connection port A5 and a first rear connection port B5, the front connection port of the second group of chromatography components C2 are respectively a first front connection port A6 and a first rear connection port B7, The connection port and the rear connection port are respectively the second front connection port A6 and the second rear connection port B6; the first rear connection port B5 is connected with the second front connection port A6, so that the second group of chromatography components can be selectively connected in series after the first group of chromatography components; the second rear connection port B6 is connected with the third front connection port A7, the third liquid inlet A4 is connected with the third liquid outlet B4, and the third rear connection port B7 is connected with the first front connection port A5, so that the first group of chromatography components C1 can be selectively connected in series after the second group of chromatography components C2.

[0064] See also Figure 5In the three-column continuous flow chromatography system, the chromatography unit comprises a first group of chromatography components C1, a second group of chromatography components C2 and a third group of chromatography components C3, the liquid inlet and liquid outlet of the first group of chromatography components C1 are respectively a first liquid inlet A2 and a first liquid outlet B2, the liquid inlet and liquid outlet of the second group of chromatography components C2 are respectively a second liquid inlet A3 and a second liquid outlet B3, the liquid inlet and liquid outlet of the third group of chromatography components C3 are respectively a third liquid inlet A4 and a third liquid outlet B4; the front connection port and the rear connection port of the first group of chromatography components C1 are respectively a first front connection port A5 and a first rear connection port B5, the front connection port and the rear connection port of the second group of chromatography components C2 are respectively a first front connection port A6 and a first rear connection port B7, the front connection port and the rear connection port of the second group of chromatography components C2 are respectively a first front connection port A7 and a first rear connection port B6, the front connection port and the rear connection port of the second group of chromatography components C2 are respectively a first front connection port A8 and a first rear connection port B9, the front connection port and the rear connection port of the second group of chromatography components C2 are respectively a first front connection port A9 and a first rear connection port B10, the front connection port and the rear connection port of the second group of chromatography components C2 are respectively a first front connection port A10 and a first rear connection port B11, the front connection port and the rear connection port of the second group of chromatography components C2 are respectively a first front connection port A20 and a first rear connection port B11, the front connection port and the rear connection port of the second group of chromatography components C2 are respectively a first front connection port A30 and a first rear connection port B11, the front connection port and the rear connection port of the second group of chromatography components C2 are respectively a first front connection port A40 and a first rear connection port B11, the front connection port and the rear connection port of the second group of chromatography components C2 are respectively a first front connection port A50 and a first rear connection port B5 The interfaces are respectively the second front connection port A6 and the second rear connection port B6, the front connection port and the rear connection port of the third group of chromatography components C3 are respectively the third front connection port A7 and the third rear connection port B7; the first rear connection port B5 is connected with the second front connection port A6, so that the second group of chromatography components C2 can be selectively connected in series after the first group of chromatography components C1; the second rear connection port B6 is connected with the third front connection port A7, so that the third group of chromatography components C3 can be selectively connected in series after the second group of chromatography components C2; the third rear connection port B7 is connected with the first front connection port A5, so that the first group of chromatography components C1 can be selectively connected in series after the third group of chromatography components C3.

[0065] It can be seen from the above structure that when converting a 2-column continuous flow chromatography system into a 3-column continuous flow chromatography system, or converting a 3-column continuous flow chromatography system into a 2-column continuous flow chromatography system, the present application does not need to add or reduce pipes and valves. Unlike traditional continuous chromatography systems that require redesigning the layout of pipes and valves when demand changes, the system of the present application can more flexibly expand or adjust the number of chromatography components based on the existing structural foundation without the need to replan and arrange pipes; this makes the system of the present application more adaptable and able to quickly respond to the needs of different production scales.

[0066] In one embodiment of the present application, the valve 200 on the continuous flow valve for opening or cutting off the flow path 300 between the inlet and outlet is preferably a pneumatic diaphragm valve, so as to be suitable for fast flow path switching during the chromatography process. In order to optimize the operation and improve the reliability and accuracy of the continuous flow chromatography system of the present application, these pneumatic diaphragm valves are equipped with a feedback mechanism to monitor the status of the valve. The feedback information includes but is not limited to parameters such as position, pressure and flow rate. The present application does not impose specific restrictions on the specific feedback content;

[0067] The caliber and volume of the flow paths between the multiple connection ports (taking six connection ports as an example) of the continuous flow valve are designed to be the same, so that the dead volume of each branch pipeline drawn from each connection port is the same, ensuring that the retention time of each chromatographic liquid in each branch pipeline is consistent, and ensuring that the flow rate of the liquid in the chromatography system is balanced; further, the design of the continuous flow valve is symmetrical, and the arrangement of each connection port on the combination valve is uniform. By connecting the two inlets and outlets 100, the combination valve can be divided into 6 equal parts (taking six connection ports as an example) to ensure that the flow of the liquid in each pipeline is consistent, thereby enhancing the reliability of the chromatography system. In general, by designing the flow path caliber and volume of the connection port, ensuring the consistency of the dead volume, and using a pneumatic diaphragm valve with a feedback mechanism, the implementation scheme of the present application can effectively improve the separation efficiency, operational stability and reliability of the chromatography system.

[0068] In one embodiment of the present application, the flow paths 300 on the continuous flow valve are all independent passages that do not interfere with each other. The flow paths of various types of liquids on the continuous flow valve are completely separated without crossing or mixing. Each flow path can independently transport liquids, and there is no mixing of liquids in the combination valve to ensure the purity and separation effect of the sample; in the chromatography unit, the specifications, filler types, filling heights and column efficiencies of each chromatography column in each chromatography component are consistent to ensure that in the entire system, all chromatography columns have the same performance. When the chromatography columns are alternately loaded with samples, the separation results are not affected by the performance differences of different chromatography columns.

[0069] It should be noted that in the continuous flow chromatography system of the present application, in addition to the above-mentioned chromatography unit, loading combination valve and elution combination valve, the remaining components, such as conductivity sensor, pH sensor, flow meter, pressure sensor, etc., can be configured according to the specific production process, and the present application does not limit this;

[0070] See also Figure 4 The present application also provides a chromatography method based on a production-level continuous flow chromatography system. The production-level continuous flow chromatography system can be a continuous flow chromatography system with 2 columns, 3 columns, 6 columns, or even more chromatography columns. The chromatography method specifically comprises the following steps:

[0071] a. System balance, the sample pump P1 balances each chromatography component through the initial sample inlet A1, each time it selects to enter any chromatography component, the remaining chromatography components are connected in series in sequence, the fluid passes through all the chromatography components in sequence, and finally discharged from the final sample outlet B1;

[0072] b. Sample loading: the sample is loaded into each chromatography component through the loading initial inlet A1 by the loading pump P1, and each time it enters any chromatography component, the sample flow-through is directly discharged from the loading final outlet B1 before the loading;

[0073] c. Series operation, when the sample of one of the chromatography components flows through, another chromatography component is connected in series to the back of the chromatography component through which the sample flows, and the sample loading continues;

[0074] d. Lin washing operation, when one of the chromatography components reaches the full load state, the chromatography component is kept in series with the other chromatography component, and the two chromatography components are washed by the sample pump P1 through the initial sample inlet A1;

[0075] e. Continuous chromatography: when one of the fully loaded chromatography components has completed elution, it ends its serial connection with the other chromatography component, and the loading pump P1 continues to load the unloaded chromatography component; at the same time, the elution pump P2 elutes, cleans, and rebalances the fully loaded chromatography component through the elution initial inlet B8; the rebalanced chromatography component waits for serial loading with other chromatography components that have sample flow-through. In this way, the chromatography method based on the production-level continuous flow chromatography system ensures the continuity of sample loading, and through highly optimized steps, the chromatography operation can be made efficient and stable, which is particularly suitable for large-scale production and high-throughput separation processes.

[0076] In order to make the working principle and beneficial effects of the continuous flow chromatography system of the present application more clear to those skilled in the art, the following will take the most commonly used 2-column and 3-column continuous flow chromatography systems in industrial production as examples to illustrate the use of the continuous flow valve group;

[0077] A chromatography method of a two-column continuous flow chromatography system; the two-column continuous flow chromatography system involved in this embodiment, see Figure 3 , including the following components:

[0078] Sample loading combination valve A; elution combination valve B; sample loading pump P1, used for sample loading and elution; elution pump P2, used for elution, cleaning and rebalancing; first group of chromatography components C1; second group of chromatography components C2; sample loading initial inlet A1; elution initial inlet B8; elution final outlet A8; sample loading final outlet B1; first liquid inlet A2; second liquid inlet A3; first liquid outlet B2; second liquid outlet B3; third liquid inlet A4; third liquid outlet B4; first front road connection port A5; second front road connection port A6; third front road connection port A7; first rear road connection port B5; second rear road connection port B6; third rear road connection port B7, and connected by pipelines in the order shown in the figure;

[0079] The specific operation steps and liquid flow path of the continuous flow chromatography system of this embodiment are as follows:

[0080] (1) First, the first group of chromatography components C1 and the second group of chromatography components C2 are balanced by the sample loading pump P1, the inlet is the initial sample loading inlet A1, and the balanced liquid passes through the first liquid inlet A2, the first group of chromatography components C1, the first liquid outlet B2, the first rear connection port B5, the second front connection port A6, the second liquid inlet A3, the second group of chromatography components C2, the second liquid outlet B3, and is discharged from the final sample loading outlet B1;

[0081] (2) Then, the sample pump P1 loads the first group of chromatography components C1 through the initial sample inlet A1 and the first liquid inlet A2, and the sample flow-through is discharged through the first liquid outlet B2 and the final sample outlet B1;

[0082] (3) When 1% of the sample flows through the first group of chromatography components C1, the second group of chromatography components C2 starts to be connected in series with the first group of chromatography components C1, and continues to load the sample after the sample flows through the first group of chromatography components C1. The loaded flow-through liquid enters the second group of chromatography components C2 through the first liquid outlet B2, the first rear connection port B5, the second front connection port A6, and the second liquid inlet A3, and is then discharged through the second liquid outlet B3 and the final loading outlet B1;

[0083] (4) After the first group of chromatography components C1 is fully loaded, the first group of chromatography components C1 and the second group of chromatography components C2 remain in a series state, and the first group of chromatography components C1 and the second group of chromatography components C2 are eluted by the sample loading pump P1 through the sample loading initial inlet A1, the first liquid inlet A2, the first liquid outlet B2, the first rear connection port B5, the second front connection port A6, and the second liquid inlet A3, and the waste is discharged from the second liquid outlet B3 and the sample loading final outlet B1;

[0084] (5) After elution, the first group of chromatography components C1 and the second group of chromatography components C2 end the series connection state, and the sample pump P1 loads the second group of chromatography components C2 through the initial sample inlet A1 and the second liquid inlet A3, and the sample flow-through is discharged through the second liquid outlet B3 and the final sample outlet B1. At the same time, the elution pump P2 begins to elute, clean, and rebalance the first group of chromatography components C1 through the initial elution inlet B8, the third rear-path connection port B7, the first front-path connection port A5, and the first liquid inlet A2. The first group of chromatography components C1 collects the elution peak through the first liquid outlet B2, the first rear-path connection port B5, the second front-path connection port A6, and the final elution outlet A8. After the elution peak is collected, the first group of chromatography components C1 is discharged through the first liquid outlet B2, the first rear-path connection port B5, the second front-path connection port A6, and the final elution outlet A8;

[0085] (6) When the second group of chromatography components C2 is loaded with 1% sample flow-through and the first group of chromatography components C1 is rebalanced, the first group of chromatography components C1 starts to be connected in series with the second group of chromatography components C2, and continues to load the sample flow-through from the second group of chromatography components C2. The sample flow-through liquid enters the first group of chromatography components C1 through the second liquid outlet B3, the second rear connection port B6, the third front connection port A7, the third liquid inlet A4, the third liquid outlet B4, the third rear connection port B7, the first front connection port A5, and the first liquid inlet A2, and is discharged to waste through the first liquid outlet B2 and the final sample outlet B1;

[0086] (7) After the second group of chromatography components C2 reaches full load, the second group of chromatography components C2 and the first group of chromatography components C1 remain in a series state, and the second group of chromatography components C2 and the first group of chromatography components C1 are eluted by the sample loading pump P1 through the sample loading initial inlet A1, the second liquid inlet A3, the second liquid outlet B3, the second rear connection port B6, the third front connection port A7, the third liquid inlet A4, the third liquid outlet B4, the third rear connection port B7, the first front connection port A5, and the first liquid inlet A2, and the waste is discharged from the first liquid outlet B2 and the sample loading final outlet B1;

[0087] (8) After elution is completed, the first group of chromatography components C1 and the second group of chromatography components C2 end the series connection state, and then the sample pump P1 loads the first group of chromatography components C1 through the initial sample inlet A1 and the first liquid inlet A2, and the sample flow-through is discharged through the first liquid outlet B2 and the final sample outlet B1. At the same time, the elution pump P2 begins to elute, clean, and rebalance the second group of chromatography components C2 through the initial elution inlet B8, the first rear-path connection port B5, the second front-path connection port A6, and the second liquid inlet A3. The second group of chromatography components C2 collects the elution peak through the second liquid outlet B3, the second rear-path connection port B6, the third front-path connection port A7, and the final elution outlet A8. After the elution peak is collected, the second group of chromatography components C2 is discharged through the second liquid outlet B3, the second rear-path connection port B6, the third front-path connection port A7, and the final elution outlet A8;

[0088] (9) When the first chromatographic component C1 is loaded with sample until 1% of the sample flows through, and the second chromatographic component C2 is rebalanced, start again from step (3) above, and alternately load the two columns to achieve a two-column continuous flow chromatography system. During operation, the chromatographic column specifications, filler type, filling height and column efficiency of the first chromatographic component C1 and the second chromatographic component C2 must be consistent.

[0089] A chromatography method of a three-column continuous flow chromatography system; the three-column continuous flow chromatography system involved in this embodiment, see Figure 5 , including the following components:

[0090] Sample loading combination valve A; elution combination valve B; sample loading pump P1, used for sample loading and elution; elution pump P2, used for elution, cleaning and rebalancing; first group of chromatography components C1; second group of chromatography components C2; third group of chromatography components C3; sample loading initial inlet A1; elution initial inlet B8; elution final outlet A8; sample loading final outlet B1; first liquid inlet A2; second liquid inlet A3; third liquid inlet A4; first liquid outlet B2; second liquid outlet B3; third liquid outlet B4; first front road connection port A5; second front road connection port A6; third front road connection port A7; first rear road connection port B5; second rear road connection port B6; third rear road connection port B7; and connected by pipelines in the order shown in the figure;

[0091] The specific operation steps and liquid flow path of the continuous flow chromatography system of this embodiment are as follows:

[0092] (1) First, the elution pump P2 is used to balance the first group of chromatography components C1 to the third group of chromatography components C3. The inlet is the initial sample loading inlet A1. The balancing liquid passes through the first liquid inlet A2, the first group of chromatography components C1, the first liquid outlet B2, the first rear connection port B5, the second front connection port A6, the second liquid inlet A3, the second group of chromatography components C2, the second liquid outlet B3, the second rear connection port B6, the third front connection port A7, the third liquid inlet A4, the third group of chromatography components C3, and the third liquid outlet B4 in sequence, and is discharged from the final sample loading outlet B1;

[0093] (2) Then, the sample pump P1 loads the first group of chromatography components C1 through the initial sample inlet A1 and the first liquid inlet A2, and the sample flow-through is discharged through the first liquid outlet B2 and the final sample outlet B1;

[0094] (3) When 1% of the sample flows through the first group of chromatography components C1, the second group of chromatography components C2 starts to be connected in series with the first group of chromatography components C1, and continues to load the sample after the sample flows through the first group of chromatography components C1. The loaded flow-through liquid enters the second group of chromatography components C2 through the first liquid outlet B2, the first rear connection port B5, the second front connection port A6, and the second liquid inlet A3, and is then discharged through the second liquid outlet B3 and the final loading outlet B1;

[0095] (4) After the first group of chromatography components C1 is fully loaded, the first group of chromatography components C1 and the second group of chromatography components C2 remain in a series state, and the first group of chromatography components C1 and the second group of chromatography components C2 are eluted by the sample loading pump P1 through the sample loading initial inlet A1, the first liquid inlet A2, the first liquid outlet B2, the first rear connection port B5, the second front connection port A6, and the second liquid inlet A3, and the waste is discharged from the second liquid outlet B3 and the sample loading final outlet B1;

[0096] (5) After elution, the first group of chromatography components C1 and the second group of chromatography components C2 end the series connection state, and the sample pump P1 loads the second group of chromatography components C2 through the initial sample inlet A1 and the second liquid inlet A3, and the sample flow-through is discharged through the second liquid outlet B3 and the final sample outlet B1. At the same time, the elution pump P2 begins to elute, clean, and rebalance the first group of chromatography components C1 through the initial elution inlet B8, the third rear-path connection port B7, the first front-path connection port A5, and the first liquid inlet A2. The first group of chromatography components C1 collects the elution peak through the first liquid outlet B2, the first rear-path connection port B5, the second front-path connection port A6, and the final elution outlet A8. After the elution peak is collected, the first group of chromatography components C1 is discharged through the first liquid outlet B2, the first rear-path connection port B5, the second front-path connection port A6, and the final elution outlet A8;

[0097] (6) After the second group of chromatography components C2 is loaded with 1% of the sample flowing through, the third group of chromatography components C3 begins to be connected in series with the second group of chromatography components C2, and continues to load the sample by taking over the sample flow through the second group of chromatography components C2. The sample flow through enters the third group of chromatography components C3 through the second liquid outlet B3, the second rear connection port B6, the third front connection port A7, and the third liquid inlet A4, and is discharged to waste through the third liquid outlet B4 and the final sample outlet B1;

[0098] (7) After the second group of chromatography components C2 reaches full load, the second group of chromatography components C2 and the third group of chromatography components C3 remain in a series state, and the second group of chromatography components C2 and the third group of chromatography components C3 are eluted by the sample loading pump P1 through the sample loading initial inlet A1, the second liquid inlet A3, the second liquid outlet B3, the second rear connection port B6, the third front connection port A7, and the third liquid inlet A4, and discharged from the third liquid outlet B4 and the sample loading final outlet B1;

[0099] (8) After elution is completed, the second group of chromatography components C2 and the third group of chromatography components C3 end the series connection state, and the sample pump P1 loads the third group of chromatography components C3 through the initial sample inlet A1 and the third liquid inlet A4, and the sample flow-through is discharged through the third liquid outlet B4 and the final sample outlet B1. At the same time, the elution pump P2 begins to elute, clean, and rebalance the second group of chromatography components C2 through the initial elution inlet B8, the first rear-path connection port B5, the second front-path connection port A6, and the second liquid inlet A3. The second group of chromatography components C2 collects the elution peak through the second liquid outlet B3, the second rear-path connection port B6, the third front-path connection port A7, and the final elution outlet A8. After the elution peak is collected, the second group of chromatography components C2 is discharged through the second liquid outlet B3, the second rear-path connection port B6, the third front-path connection port A7, and the final elution outlet A8;

[0100] (9) When the third group of chromatography components C3 is loaded with 1% of the sample flow-through and the first group of chromatography components C1 is rebalanced, the first group of chromatography components C1 begins to be connected in series with the third group of chromatography components C3, and continues to load the sample flow-through from the third group of chromatography components C3. The sample flow-through enters the first group of chromatography components C1 through the third liquid outlet B4, the third rear connection port B7, the first front connection port A5, and the first liquid inlet A2, and is discharged to waste through the first liquid outlet B2 and the final sample outlet B1;

[0101] (10) After the third group of chromatography components C3 reaches full load, the third group of chromatography components C3 and the first group of chromatography components C1 remain in a series state, and the third group of chromatography components C3 and the first group of chromatography components C1 are eluted by the sample loading pump P1 through the sample loading initial inlet A1, the third liquid inlet A4, the third liquid outlet B4, the third rear connection port B7, the first front connection port A5, and the first liquid inlet A2, and the waste is discharged from the first liquid outlet B2 and the sample loading final outlet B1;

[0102] (11) After elution is completed, the third group of chromatography components C3 and the first group of chromatography components C1 end the series connection state, and the sample pump P1 loads the first group of chromatography components C1 through the initial sample inlet A1 and the first liquid inlet A2, and the sample flow-through is discharged through the first liquid outlet B2 and the final sample outlet B1. At the same time, the elution pump P2 begins to elute, clean, and rebalance the third group of chromatography components C3 through the initial elution inlet B8, the second rear-path connection port B6, the third front-path connection port A7, and the third liquid inlet A4. The third group of chromatography components C3 collects the elution peak through the third liquid outlet B4, the third rear-path connection port B7, the first front-path connection port A5, and the final elution outlet A8. After the elution peak is collected, the third group of chromatography components C3 is discharged through the third liquid outlet B4, the third rear-path connection port B7, the first front-path connection port A5, and the final elution outlet A8;

[0103] (12) When the first chromatographic component C1 is loaded with sample until 1% of the sample flows through, and the second chromatographic component C2 is rebalanced, start again from the above step (3) and alternately load the three columns to realize a three-column continuous flow chromatography system. During operation, the chromatographic column specifications, filler types, filling heights and column efficiencies of the first chromatographic component C1 to the third chromatographic component C3 must be consistent.

[0104] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A production-grade continuous flow chromatography system, characterized in that: The invention comprises a chromatography unit, a loading combination valve (A) and an elution combination valve (B), wherein the chromatography unit comprises a plurality of chromatography components, and the valve bodies of the loading combination valve (A) and the elution combination valve (B) are respectively provided with a plurality of inlets and outlets, wherein: Two of the inlets and outlets (100) of the sample loading combination valve (A) are respectively used as the initial sample loading inlet (A1) and the final elution outlet (A8), and the remaining inlets and outlets (100) are used as connection ports, which are divided into two groups, one group being used as the liquid inlet of each chromatography component, and the other group being used as the front connection ports connected to other chromatography components, the initial sample loading inlet (A1) can be selected to be connected to different liquid inlets, and the final elution outlet (A8) can be selected to be connected to different front connection ports; Two of the inlets and outlets (100) of the elution combination valve (B) are used as the initial elution inlet (B8) and the final sample loading outlet (B1), respectively, and the remaining inlets and outlets (100) are used as connection ports, which are divided into two groups, one group being used as the liquid outlet of each chromatography component, and the other group being used as the back-end connection ports connected to other chromatography components, the initial elution inlet (B8) can be selected to be connected to different back-end connection ports, and the final sample loading outlet (B1) can be selected to be connected to different liquid outlets; In the loading combination valve (A) and the elution combination valve (B), a valve (200) is provided between the inlet and outlet (100) forming the flow path (300), for opening or cutting off the corresponding flow path (300), and any rear-path connection port is connected to the adjacent front-path connection port, so that each chromatography component can be selectively connected in series with the remaining chromatography components, and the rear-path connection port of the last group of chromatography components is connected to the front-path connection port of the first group of chromatography components.

2. The production-grade continuous flow chromatography system according to claim 1, characterized in that: In the valve body of the loading combination valve (A) and / or the elution combination valve (B), each group of liquid inlets and / or liquid outlets includes N inlets and outlets, each group of front connection ports and / or rear connection ports includes N inlets and outlets, and the chromatography unit includes N-1 groups or N groups of chromatography components, where N is an integer ≥3.

3. The production-grade continuous flow chromatography system according to claim 2, characterized in that: In the chromatography unit, each chromatography component is cyclically connected via a loading combination valve (A) and an elution combination valve (B): the rear connection port of each chromatography component is connected to the front connection port of the next group of chromatography components.

4. The production-grade continuous flow chromatography system according to claim 3, characterized in that: The chromatography unit comprises N-1 groups of chromatography components, each group of chromatography components is connected between any liquid inlet and any liquid outlet, and the rear connection port of the N-2 group of chromatography components is connected to the front connection port of the N-1 group of chromatography components, so that the N-1 group of chromatography components can be selectively connected in series after the N-2 group of chromatography components; The rear connection port of the N-1 group of chromatography components is connected to the front connection port of the Nth group, the Nth liquid inlet is connected to the Nth liquid outlet, and the Nth rear connection port is connected to the front connection port of the first group of chromatography components, so that the N-2 group of chromatography components and / or the first group of chromatography components can be selectively connected in series after the N-1 group of chromatography components.

5. The production-level continuous flow chromatography system according to claim 3, characterized in that: The chromatography unit comprises N groups of chromatography components, each group of chromatography components is connected between any liquid inlet and any liquid outlet, and the rear connection port of the N-2 group of chromatography components is connected to the front connection port of the N-1 group of chromatography components, so that the N-1 group of chromatography components can be selectively connected in series after the N-2 group of chromatography components; The rear connection port of the N-1th group of chromatography components is connected to the front connection port of the Nth group of chromatography components, so that the Nth group of chromatography components can be selectively connected in series after the N-1th group of chromatography components; the rear connection port of the Nth group of chromatography components is connected to the front connection port of the first group of chromatography components, so that the first group of chromatography components can be selectively connected in series after the Nth group of chromatography components.

6. The production-level continuous flow chromatography system according to claim 1, characterized in that: The valves (200) used for opening or cutting off the flow path in the sample loading combination valve and the elution combination valve are both provided with a feedback mechanism; the diameter and volume of the flow paths between the connection ports in the sample loading combination valve (A) and the elution combination valve (B) are the same, so that the dead volume of the branch pipelines led out from each connection port is the same; the valve bodies of the sample loading combination valve (A) and the elution combination valve (B) are both symmetrical, and the valve bodies can be divided into a plurality of equal parts by connecting the two inlets and outlets (100).

7. The production-level continuous flow chromatography system according to claim 1, characterized in that: In the valve bodies of the loading combination valve (A) and the elution combination valve (B), the flow paths formed between the two inlets and outlets (100) are independent paths that do not interfere with each other, and there is no mixing point of liquid in the loading combination valve (A) and the elution combination valve (B); in the chromatography unit, the chromatography component includes at least one chromatography column, and the specifications, filler type, filling height and column efficiency of each chromatography column in each chromatography component are consistent.

8. A production-grade continuous flow chromatography method, characterized in that: The specific steps include: a. Providing a production-grade continuous flow chromatography system as described in any one of claims 1 to 7, wherein the initial loading inlet (A1) and the initial elution inlet (B8) are connected to the loading pump (P1) and the elution pump (P2), respectively; b. The sample loading pump (P1) balances each chromatographic component through the initial loading inlet (A1), and selects to enter any chromatographic component each time, and the remaining chromatographic components are connected in series in sequence, and the fluid passes through all the chromatographic components in sequence, and finally discharged from the final loading outlet (B1); c. The sample is loaded into each chromatographic component through the loading initial inlet (A1) by the loading pump (P1), and each time the sample enters any chromatographic component, the loading flow-through is directly discharged from the loading final outlet (B1); d. When the sample of one of the chromatography components flows through, another chromatography component is connected in series to the back of the chromatography component through which the sample flows, and the sample loading continues; e. When one of the chromatography components reaches a full load state, the chromatography component is kept in series with the other chromatography component, and the two chromatography components are eluted by the loading pump (P1) through the initial loading inlet (A1); f. When one of the fully loaded chromatography components has completed elution, its series connection with the other chromatography component ends, and the loading pump (P1) continues to load the partially loaded chromatography component; at the same time, the elution pump (P2) elutes, cleans, and rebalances the fully loaded chromatography component through the elution initial inlet (B8); the rebalanced chromatography component waits for series loading with other chromatography components that have sample flow-through.

9. The production-grade continuous flow chromatography method according to claim 8, characterized in that: The method includes: when a chromatography component has sample flow-through, another chromatography component is connected in series behind it; when a chromatography component is fully loaded, the chromatography component is eluted together with another chromatography component; when a chromatography component is eluted, cleaned and rebalanced, another chromatography component is loaded with samples; when a chromatography component has sample flow-through, a chromatography component completes rebalance and is connected in series behind the chromatography component through which the sample has flowed.

10. The production-grade continuous flow chromatography method according to claim 8, characterized in that: The method includes: when a chromatography component has sample flow-through, another chromatography component is connected in series behind it; when a chromatography component is fully loaded, the chromatography component is eluted together with another chromatography component; when a chromatography component is eluted, cleaned, and re-balanced, another chromatography component is loaded with samples; when a chromatography component has sample flow-through, a chromatography component is connected in series behind the chromatography component through which the sample has flowed, and another chromatography component is eluted, cleaned, and re-balanced.

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