CN114072216B - Modular chromatography device - Google Patents
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- CN114072216B CN114072216B CN201980097855.1A CN201980097855A CN114072216B CN 114072216 B CN114072216 B CN 114072216B CN 201980097855 A CN201980097855 A CN 201980097855A CN 114072216 B CN114072216 B CN 114072216B
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Abstract
A modular chromatography device comprising a plurality of basic chromatography modules (M1, M2, M3), each basic chromatography module (M1, M2, M3) comprising a chromatography column (C1, C2, C3), a sample selection valve (Vs) and an outlet valve (Vx), the sample selection valve (Vs) being connected upstream of the chromatography column (C1, C2, C3), the outlet valve (Vx) being connected downstream of the chromatography column (C1, C2, C3), the sample selection valve (Vs) and the outlet valve (Vx) each comprising at least three ports, the sample selection valve (Vs) of any one of the plurality of basic chromatography modules (M1, M2, M3) being connected to the outlet valve (Vx) of the other basic chromatography module (M1, M2, M3). Each module in the modularized chromatographic device can independently operate, and any several modules can be connected to realize continuous flow chromatography, seamless connection chromatography or seamless continuous flow chromatography.
Description
Citation of related application
The present invention claims priority from the patent application filed in china at 28, 6, 2019, entitled "modular chromatographic device", application number 201910574105.0, the entire contents of which are incorporated herein by reference.
Technical Field
The invention relates to the technical field of separation and purification, in particular to purification of biological agents, and particularly relates to a modularized chromatographic device.
Background
The continuous flow chromatography device in the prior art has low utilization rate when being used for single column chromatography; when the device is used for multi-column chromatography, an intermediate storage tube/tank is needed between the chromatography columns to store intermediate products, the process time is long, the volume of a solution storage tank is large, and the equipment cost is high. In addition, in the case of the optical fiber, existing chromatographic devices often fail to process samples on-line, dispense solutions or dilute solutions on-line.
Patent CN103562145B discloses a continuous processing method of biological products, which, although being able to selectively use one or more chromatographic columns, however, the parts of the device are not easily split, with low adaptability to various production environments.
Disclosure of Invention
The present invention aims to overcome or at least alleviate the above-mentioned disadvantages of the prior art and to provide a multi-module combined modular chromatographic device.
The invention provides a modularized chromatographic device, which comprises a plurality of basic chromatographic modules, wherein each basic chromatographic module comprises a chromatographic column, a sample injection selection valve and an outlet valve,
the sample injection selection valve is connected with the upstream of the chromatographic column, the outlet valve is connected with the downstream of the chromatographic column,
the sample injection selection valve and the outlet valve each comprise at least three ports, and the sample injection selection valve of any one of the base chromatography modules is connected to the outlet valve of another base chromatography module.
In at least one embodiment, the modular chromatographic apparatus further comprises at least one extended base chromatographic module further comprising a multi-channel connection valve and at least two pumps,
the multi-channel connecting valve is connected with the upstream of the sample injection selecting valve of the extended basic chromatography module,
the pumps are connected to the inlets of the multi-channel connection valves, and each pump is connected with at least one path of solution.
In at least one embodiment, the pump is connected to multiple solutions through a feed selection valve.
In at least one embodiment, the modular chromatographic apparatus comprises a plurality of expanded base chromatographic modules, the multi-channel connection valves of at least two of the expanded base chromatographic modules being connected together.
In at least one embodiment, the modular chromatographic device comprises a plurality of extended base chromatographic modules,
the outlet valve of the upstream expanded basic chromatography module is connected to the multi-channel connection valve of the downstream expanded basic chromatography module, or
The outlet valve of the upstream expanded base chromatography module is connected to the sample injection selection valve of the downstream expanded base chromatography module.
In at least one embodiment, the expanded base chromatography module is connected downstream of the base chromatography module.
In at least one embodiment, the elution times of the chromatography columns of the plurality of base chromatography modules are different, and there is no intermediate storage container between the expanded base chromatography module and the base chromatography module.
In at least one embodiment, an in-line mixer for assisting in mixing the solutions is connected upstream of the feed selection valve of each of the modules.
In at least one embodiment, the sample selection valve and the outlet valve of each of the modules include a port for discharging waste.
In at least one embodiment, the flow path of the modular chromatographic device is controlled manually or automatically by software.
The modularized chromatographic device adopts modularized design, each module can be independently operated, and any several modules can be connected to realize continuous flow chromatography, seamless connection chromatography or seamless continuous flow chromatography.
Drawings
FIG. 1 is a schematic diagram of a continuous flow chromatography apparatus including a base chromatography module according to one embodiment of the invention.
FIG. 2 is a schematic diagram of a seamless connection chromatography apparatus including an extended base chromatography module according to an embodiment of the invention.
Fig. 3 to 5 are chromatograms of three chromatographic columns of the seamless junction chromatographic apparatus shown in fig. 2.
FIG. 6 is a schematic diagram of a seamless continuous flow chromatography apparatus according to an embodiment of the invention.
Description of the reference numerals
M1 and M10 are the first modules; m2 and M20 modules II; m3, M30 module III;
pr products; s, sample;
c1, C2, C3 chromatographic columns;
ve liquid inlet selector valve; vm multi-channel connecting valve; vs sampling selection valve; vp column position valve; a Vx outlet valve;
an H pH detector; a D conductivity detector; a U ultraviolet detector;
a P pump; p1 a first pump; a P2 second pump;
mx in-line mixer; n pressure sensor.
Detailed Description
Exemplary embodiments of the present invention are described below with reference to the accompanying drawings. It should be understood that these specific illustrations are for the purpose of illustrating how one skilled in the art may practice the invention, and are not intended to be exhaustive of all of the possible ways of practicing the invention, nor to limit the scope of the invention.
The invention combines a single chromatographic column with fittings such as a valve, a pump and the like to form a chromatographic module. The chromatographic modules can be used singly or in combination to realize continuous flow chromatography, seamless connection chromatography or seamless continuous flow chromatography.
A basic chromatography module and a chromatography device constructed using the basic chromatography module according to the invention will first be described with reference to fig. 1.
(basic chromatography Module)
The chromatographic device shown in fig. 1 comprises three basic chromatographic modules, namely a first module M1, a second module M2 and a third module M3. The construction of the three basic chromatography modules described above is identical.
Taking a module M1 as an example, the basic chromatography module comprises: the chromatographic column C1, the pump P, the online mixer Mx, the pressure sensor N, the conductivity detector D, the Ultraviolet (UV) detector U, pH detector H, the liquid inlet selection valve Ve, the multi-channel connection valve Vm, the sample injection selection valve Vs, the column position valve Vp and the outlet valve Vx.
Each basic chromatography module can independently load a sample S, independently collect a product Pr and independently discharge waste liquid W.
Preferably, each base chromatography module is connected to a sample S and a plurality (four in this embodiment) of different solutions L by means of a feed selection valve Ve.
The outlet of the liquid inlet selection valve Ve is connected with the inlet of the pump P.
The outlet of the pump P is connected to one inlet of the multi-channel connection valve Vm.
The outlet of the multi-channel connection valve Vm is connected to an in-line mixer Mx to achieve mixing of multiple solutions.
The solution after completing the mixing by the in-line mixer Mx further flows to one inlet of the sample injection selection valve Vs. The other inlet of the feed selection valve Vs is used to connect to other modules from which the sample S is taken to achieve continuous flow chromatography or seamless connection chromatography between the modules. One outlet of the feed selection valve Vs is used for discharging the waste liquid W.
The solution flowing out from the other outlet of the sample injection selector valve Vs further flows to the column position valve Vp. The column position valve Vp is connected with the chromatographic column C1. By adjusting the open/close state of the column position valve Vp, the solution can be selectively introduced into the upper port of the column C1, flowed out of the lower port of the column C1, introduced into the lower port of the column C1, flowed out of the upper port of the column C1, or prevented from flowing through the column C1.
The solution flowing out through the outlet of the column position valve Vp flows through the ultraviolet detector U, the conductivity detector D, and the pH detector H in this order, and then flows to the outlet valve Vx.
The outlet valve Vx has three or more ports (two or more outlets). The outlet of the outlet valve Vx can be used for harvesting the product Pr, or connected to the feed selection valve Vs, or for discharging the waste liquid W.
Above, each basic chromatography module can realize the connection and the switching of the flow paths among the multiple modules through the multi-channel connecting valve Vm, the sample injection selecting valve Vs and the outlet valve Vx.
It should be understood that the conductivity detector D, the Ultraviolet (UV) detector U, and the pH detector H in the above-described embodiments may be selectively provided as needed, and the connection order of the three detectors is not limited by the present invention. The number and position of the pressure sensors N may be adjusted as needed, for example, the pressure sensors N may be disposed downstream of the chromatographic column.
For the liquid flow path control of the base chromatography module, the valve passage may be controlled manually or automatically in combination with control software. When automatically controlled using software, for example, multiple modules may be controlled simultaneously through one control interface; the control commands may be real-time or preprogrammed.
(expanded base chromatography Module)
An extended basic chromatography module according to the invention is described with reference to fig. 2. The chromatographic device shown in fig. 2 comprises three extended basic chromatographic modules, namely a first module M10, a second module M20 and a third module M30.
The extended basic chromatography module is a variant of the basic chromatography module, extended in that at least two ports of the multi-channel connection valve Vm are connected with one pump, respectively. I.e. the extended basic chromatography module comprises at least two pumps (P1, P2) for pumping the solution compared to the basic chromatography module. Each pump can be directly connected with one solution or connected with multiple solutions through a liquid inlet selection valve Ve.
For example, in module one M10, the multi-channel junction valve Vm includes a port to which the first pump P1 is connected, and a port to which the second pump P2 is connected. Each pump is connected with a liquid inlet selection valve Ve, and the liquid inlet selection valve Ve is connected with one or more paths of solutions according to the requirement of solution selection.
By supplying the solution to the multi-channel connection valve Vm by a plurality of pumps, it is possible to achieve, for example, a dual pumping gradient when dispensing the solution, or an on-line processing of the sample, such as on-line dilution and on-line pH adjustment, etc.
And when the multi-channel connection valves Vm of the two extended basic chromatography modules are connected together, the on-line solution preparation can be realized. For example, referring to the scheme of connecting the multi-channel connection valve Vm of the first module M10 and the second module M20 in fig. 2, the in-line mixer Mx can receive four solutions, such as one salt solution, one water solution, one acid solution, and one alkali solution, through the two pumps of the first module M10 and the two pumps of the second module M20, and the required solutions can be obtained in real time by controlling the flow rates of the four pumps without mixing the four solutions in the container in advance.
(continuous flow chromatography device)
Referring to fig. 1, three basic chromatography modules are connected together to form a chromatography apparatus capable of continuous flow chromatography. In the continuous flow chromatography apparatus, the feed selection valve Ve of each module includes a port for connecting the sample S, each feed selection valve Vs includes a port for discharging the waste liquid W, and each outlet valve Vx includes a port for harvesting the product Pr and a port for discharging the waste liquid W. The samples S of the three modules are identical, as are the packing of the three columns (C1, C2, C3).
In this embodiment, the outlet valve Vx of the first module M1 is connected to the sample injection selection valve Vs of the second module M2, the outlet valve Vx of the second module M2 is connected to the sample injection selection valve Vs of the third module M3, and the outlet valve Vx of the third module M3 is connected to the sample injection selection valve Vs of the first module M1. So that the sample S can flow in the three modules in the order of "module one M1-module two M2-module three M3-module one M1- …" according to the production arrangement requirement.
If the packing materials of three chromatographic columns (C1, C2 and C3) are put together to form a large (capacity) chromatographic column, continuous flow chromatography consisting of the three chromatographic columns can finish the purification operation of the large chromatographic column in a shorter time, and the volume of a solution storage container can be correspondingly reduced. This is because, by connecting a plurality of basic chromatography modules, chromatography of a large-batch preparation is distributed to different chromatography columns in small batches and dispersed, and the steps of equilibration, loading, re-equilibration, elution, etc. can be performed on different chromatography columns asynchronously without waiting for one large-capacity chromatography column to complete a certain step and then performing the next step. For example, in the continuous flow chromatography, any two of the three columns may be simultaneously loaded by the same pump while the other column is equilibrated or rebalanced.
Next, a method of continuous flow chromatography using the continuous flow chromatography apparatus will be described.
(i) Loading the chromatographic column C1, eluting C2, post-treating, loading, and re-balancing the chromatographic column C3
The sample injection selection valve Vs of the first module M1 selects the sample S of the first module M1 to be injected, and the sample S flows into the chromatographic column C1 to load the chromatographic column C1. The outlet valve Vx of module one M1 chooses to flow the exiting liquid to module two M2 before the chromatography column C1 loading is saturated.
The second module M2 elutes and post-processes the chromatographic column C2 through the solution L of the second module M2, and after the chromatographic column C2 is balanced, the sample S of the first module M1 is selected to be sampled through a sample sampling selection valve Vs of the second module M2, and the sample flows into the chromatographic column C2 to sample the chromatographic column C2. The outlet valve Vx of the second module M2 is connected to the waste liquid W.
The flow path was maintained until column C1 was overloaded (100% of filler utilization) while column C2 was not overloaded (less than 100% of filler utilization).
The sample injection selection valve Vs of the third M3 selects the solution L balancing chromatographic column C3 of the third M3. The outlet valve Vx of the third module M3 is connected to the waste liquid W.
In this step, the utilization of the packing of the column C1 can be up to 100% (in conventional single column chromatography, the utilization of the packing can generally be only up to about 70%), and the sample S flowing through the column C1 and exceeding the purification capacity of the column C1 is further loaded onto the column C2.
(ii) The chromatographic column C1 is rebalanced, the chromatographic column C2 is loaded, and C3 is eluted, post-treated and loaded
The sample injection selector valve Vs of module one M1 selects the solution L of module one M1 to rebalance the chromatographic column C1. The outlet valve Vx of the first module M1 selects the flow of the outgoing liquid to the second module M2, because there may be some sample falling off during the rebalancing of the chromatographic column C1, and by flowing the liquid to the second module M2, the loss of sample can be reduced. It should be appreciated that since the sample injection selector valve Vs of each module is connected to the outlet valve Vx of any other module, in other possible embodiments, it is also possible to select the partially detached sample from the chromatographic column C1 to flow to module three M3 while module two M2 is being loaded independently.
After a certain period of time (the length of the period of time can be controlled according to the arrangement of the production process), the longer the outlet valve Vx of the first module M1 is conducted to the second module M2, the less sample may be lost from the chromatographic column C1), the sample injection selection valve Vs of the second module M2 selects the sample S of the second module M2 to be injected, and the sample flows into the chromatographic column C2 to load the chromatographic column C2. The outlet valve Vx of module two M2 selects the flow of outgoing liquid to module three M3.
Eluting the chromatographic column C3 by the solution L of M3 in the second module M3 the post-treatment is carried out, after the chromatographic column C3 is balanced, the sample S of the second module M2 is selected to be sampled through the sample sampling selection valve Vs of the third module M3, and the sample S flows into the chromatographic column C3 to sample the chromatographic column C3. The outlet valve Vx of the third module M3 is connected to the waste liquid W.
The flow path is maintained until column C2 is overloaded and column C3 is not overloaded.
(iii) Eluting the chromatographic column C1, carrying out post-treatment and loading, rebalancing the chromatographic column C2, and loading the chromatographic column C3
The sample injection selector valve Vs of module one M1 selects elution, cleaning In Place (CIP) and equilibration of the chromatography column C1 by the solution L of module one M1. During elution, the outlet valve Vx of the first module M1 is connected to the collection product Pr. At the time of in-place cleaning and balancing, the outlet valve Vx of the first module M1 is conducted to the discharged waste liquid W.
The sample injection selection valve Vs of the second module M2 selects the solution L of the second module M2 to rebalance the chromatographic column C2. The outlet valve Vx of module two M2 selects the flow of outgoing liquid to module three M3.
After a period of time, the sample injection selection valve Vs of the third M3 selects the sample S of the third M3 to be injected, and the sample flows into the chromatographic column C3 to load the chromatographic column C3. The outlet valve Vx of module three M3 selects the flow of outgoing liquid to module one M1.
(iv) The three steps (i), (ii) and (iii) above are repeated in sequence.
(seamless connection chromatography apparatus)
Referring to fig. 2, three extended basic chromatography modules (M10, M20, M30) are connected together to form a chromatography apparatus capable of realizing seamless connection chromatography. In the seamless connection chromatographic apparatus, the packing materials of the three chromatographic columns (C1, C2 and C3) are different, the sample S is only arranged in one module (in the embodiment, the module one M10), and after the sample S is purified three times through the three chromatographic columns, the product Pr is collected by one module (in the embodiment, the module two M20).
In the present embodiment, the outlet valve Vx of the first module M10 is connected to the multi-channel connection valve Vm of the third module M30, and the outlet valve Vx of the third module M30 is connected to the sample injection selection valve Vs of the second module M20. The multi-channel connection valve Vm of the first module M10 is connected to the multi-channel connection valve Vm of the second module M20. Thus, the sample S can be purified by the chromatographic columns of the corresponding modules in the order of "module one M10-module three M30-module two M20" according to the production arrangement requirement.
Next, a method of performing seamless joining chromatography using the seamless joining chromatography apparatus will be described.
(i) Loading the chromatographic column C1, and balancing the chromatographic column C2 and C3
The sample injection selection valve Vs of the first module M10 selects the sample S of the first module M10 to be injected, and the sample S flows into the chromatographic column C1 to load the chromatographic column C1. The outlet valve Vx of module one M10 selects the waste water W to be discharged.
The sample injection selector valve Vs of the second module M20 selects the balancing of the chromatography column C2 by the solution from the in-line mixer Mx of the second module M20. The outlet valve Vx of the second module M20 selects the waste water W to be discharged.
The sample injection selector valve Vs of module three M30 selects the balancing of the chromatography column C3 by the solution from the in-line mixer Mx of module three M30. The outlet valve Vx of the third module M30 selects the waste water W to be discharged.
(ii) Eluting the chromatographic column C1, balancing the chromatographic column C3 after loading, and balancing the chromatographic column C2
The sample injection selector valve Vs of module one M10 selects elution of the chromatography column C1 from the solution from the in-line mixer Mx of module one M10. The outlet valve Vx of module one M10 is selected to flow eluent to module three M30 for loading column C3.
The multi-channel connection valve Vm of the third module M30 is first selected to be conducted to the outlet valve Vx of the first module M10, and the eluent from the first module M10 is applied to the chromatographic column C3. Thereafter, the multi-channel connection valve Vm of the third module M30 is conducted to the solution L of the third module M30 to rebalance the chromatographic column C3, and the outlet valve Vx of the third module M30 selects the waste liquid W to be discharged.
The sample injection selector valve Vs of the second module M20 selects the balancing of the chromatography column C2 by the solution from the in-line mixer Mx of the second module M20. The outlet valve Vx of the second module M20 selects the waste water W to be discharged.
(iii) The chromatographic column C1 is balanced after in-situ cleaning, the chromatographic column C3 is eluted, and the chromatographic column C2 is balanced after loading
The sample injection selector valve Vs of module one M10 selects the in-situ cleaning and equilibration of the chromatography column C1 by the solution from the in-line mixer Mx of module one M10. The outlet valve Vx of module one M10 selects the waste water W to be discharged.
The multi-channel connection valve Vm of module three M30 selects the elution of the chromatography column C3 by the solution L from module three M30. The outlet valve Vx of the third module M30 is selected to allow the eluent to flow to the second module M20 for loading the chromatographic column C2.
The sample injection selector valve Vs of the second module M20 first selects the outlet valve Vx which is conducted to the third module M30, and the eluent from the third module M30 is applied to the chromatographic column C2. Then, the sample injection selection valve Vs of the second module M20 is conducted to the solution L of the second module M20 to rebalance the chromatographic column C2, and the outlet valve Vx of the second module M20 is used for selecting the waste liquid W.
(iv) Loading the chromatographic column C1, balancing the chromatographic column C3 after in-situ cleaning, and eluting the chromatographic column C2
The sample injection selection valve Vs of the first module M10 selects the sample S of the first module M10 to be injected, and the sample S flows into the chromatographic column C1 to load the chromatographic column C1. The outlet valve Vx of module one M10 selects the waste water W to be discharged.
The multi-channel connection valve Vm of module three M30 selects the in-situ cleaning and equilibration of the chromatography column C3 by the solution L from module three M30. The outlet valve Vx of the third module M30 selects the waste water W to be discharged.
The sample injection selection valve Vs of the second module M20 is communicated to the solution L of the second module M20 to cause the chromatographic column C2 to elute. The outlet valve Vx of the second module M20 selects the waste water W to be discharged.
(v) The three steps (ii), (iii) and (iv) above are repeated in sequence.
Affinity chromatography (module one M10), cation chromatography (module three M30), and hydrophobic chromatography (module two M20) were performed sequentially using the seamless junction chromatography apparatus according to the present embodiment.
Fig. 3 to 5 are experimentally obtained chromatograms, wherein fig. 3 is a chromatogram of the chromatographic column C1, fig. 4 is a chromatogram of the chromatographic column C3, and fig. 5 is a chromatogram of the chromatographic column C2. In the figure, a solid line UV represents an ultraviolet absorption curve, a double-dot drawn line Cond represents a conductivity value curve, a long-dashed line Injection represents a node at which loading is started, and a short-dashed line represents a node at which a certain component is obtained.
Table 1 is a comparison of the quality detection results of the chromatographic product according to the present embodiment with those of the conventional single column chromatography.
TABLE 1 quality detection results of seamless connection chromatography products
According to the chromatographic spectrum and the quality detection result, the chromatographic device according to the embodiment can achieve the chromatographic quality of the traditional single-column chromatographic device.
(seamless continuous flow chromatography device)
Referring to fig. 6, when the continuous flow chromatography device(s) and the extended base chromatography module(s) are connected in series, a seamless continuous flow chromatography device is formed. Wherein a plurality of base chromatography modules may be connected to an expanded base chromatography module, for example, by a multi-way valve. The method comprises the steps that in a plurality of basic chromatographic modules, an outlet valve Vx of each module is connected with a sample injection selection valve Vs of another module; in the plurality of extended basic chromatography modules, each module outlet valve Vx is connected to the feed selection valve Vs of another module.
In the present embodiment, 3 basic chromatography modules (M1, M2, M3) are connected in series with 2 extended basic chromatography modules (M10, M20) to form a 5-column seamless continuous flow chromatography device. The 3 basic chromatographic modules and the extended basic chromatographic module M10 are connected through a four-way valve Vt.
The product captured by the chromatography column of either base chromatography module constitutes the sample S of the extended base chromatography module M10, and the product Pr is finally harvested by the extended base chromatography module M20.
The present invention has at least one of the following advantages:
(i) The chromatographic device adopts a modularized design, each module comprises a chromatographic column and a plurality of multi-channel valves, single-column chromatography can be realized by single-column operation, and a plurality of modules can be connected together through the valves to realize continuous flow chromatography, seamless connection chromatography or seamless continuous flow chromatography, and can also realize online solution preparation, online solution dilution and online sample treatment (such as pH adjustment, dilution, salt addition and the like).
(ii) When a plurality of modules are connected together, an intermediate storage tank is not needed to store intermediate samples among the modules, so that the equipment cost and the occupied space are saved.
(iii) The flexibility of combination among modules is strong, and the method can adapt to various production scales and different production processes.
Of course, the present invention is not limited to the above-described embodiments, and various modifications may be made to the above-described embodiments of the present invention by those skilled in the art in light of the present teachings without departing from the scope of the present invention. For example:
(i) The present invention is applicable to, but not limited to, purification of biological agents including, inter alia, antibodies, fusion proteins and cytokines, and unless otherwise indicated, the term "antibody" includes references to glycosylated and non-glycosylated immunoglobulins of any isotype or subclass or antigen-binding regions thereof that compete for specific binding with intact antibodies, including human antibodies, humanized antibodies, chimeric antibodies, multispecific antibodies, monoclonal antibodies, polyclonal antibodies, and oligomers or antigen-binding fragments thereof.
(ii) Although the embodiment of the present invention shows a case where one chromatography device is constituted by three chromatography modules, the present invention does not limit the number of chromatography modules used in the chromatography device, and preferably the number of chromatography modules of one chromatography device does not exceed 10.
Claims (6)
1. A modular chromatographic device comprising a plurality of basic chromatographic modules (M1/M2/M3 … …), each of which comprises a chromatographic column, a feed selection valve (Ve), a pump (P), a multi-channel connection valve (Vm), an on-line mixer (Mx), a feed selection valve (Vs) and an outlet valve (Vx),
the basic chromatography module is connected with a sample (S) and a plurality of different solutions (L) through the liquid inlet selection valve (Ve), the outlet of the liquid inlet selection valve (Ve) is connected with the inlet of the pump (P), the outlet of the pump (P) is connected with one inlet of the multi-channel connection valve (Vm), the outlet of the multi-channel connection valve (Vm) is connected with the online mixer (Mx) to realize the mixing of a plurality of solutions, the outlet of the online mixer (Mx) is connected with one inlet of the sample injection selection valve (Vs), the sample injection selection valve (Vs) is connected with the upstream of the chromatography column, the outlet valve (Vx) is connected with the downstream of the chromatography column,
said feed selection valve (Vs) and said outlet valve (Vx) each comprising at least three ports, said feed selection valve (Vs) of any one of said base chromatography modules of said plurality being connected to said outlet valve (Vx) of another of said base chromatography modules,
the modular chromatography device further comprises a plurality of expanded basic chromatography modules (M10/M20/M30), said expanded basic chromatography modules further comprising a multi-channel connection valve (Vm) and at least two pumps (P1, P2), said multi-channel connection valves (Vm) of at least two of said expanded basic chromatography modules being connected together, an outlet valve (Vx) of an upstream expanded basic chromatography module being connected to said multi-channel connection valve (Vm) of a downstream expanded basic chromatography module, or
The outlet valve (Vx) of the upstream expanded basic chromatography module is connected to the feed selection valve (Vs) of the downstream expanded basic chromatography module,
the multichannel connection valve (Vm) of the extended base chromatography module is connected upstream of the sample injection selection valve (Vs) of the extended base chromatography module,
the pumps (P1/P2) of the extended base chromatography module are connected to the inlets of the multi-channel connection valve (Vm) of the extended base chromatography module, each of the pumps (P1/P2) of the extended base chromatography module is connected to at least one path of solution (L), and the at least two pumps (P1, P2) are connected to different ones of the solutions (L).
2. Modular chromatographic device according to claim 1, characterized in that the pumps (P/P1/P2) of the basic chromatographic module and/or of the extended basic chromatographic module are connected to multiple solutions by means of a feed selection valve (Ve).
3. The modular chromatography device of claim 1, wherein the expanded base chromatography module is connected downstream of the base chromatography module.
4. A modular chromatography device according to claim 3, wherein the elution times of the chromatography columns of the plurality of base chromatography modules are different, there being no intermediate storage container between the expanded base chromatography module and the base chromatography module.
5. Modular chromatographic device according to any of claims 1 to 4, characterized in that the feed selection valve (Vs) and the outlet valve (Vx) of each of the modules (M1/M2/M3/M10/M20/M30 … …) each comprise one port for the drainage of waste liquid (W).
6. The modular chromatographic device of any of claims 1-4, wherein the flow path of the modular chromatographic device is controlled manually or automatically by software.
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