CN114392583A

CN114392583A - Chromatographic purification system and purification method

Info

Publication number: CN114392583A
Application number: CN202210105631.4A
Authority: CN
Inventors: 姜雪峰; 孟娇龙
Original assignee: Shanghai Quanhuan Technology Co ltd
Current assignee: Shanghai Quanhuan Technology Co ltd
Priority date: 2022-01-28
Filing date: 2022-01-28
Publication date: 2022-04-26

Abstract

The invention provides a chromatography purification system and a purification method, wherein the system comprises a liquid mixing module, a conveying module, a purification module and a collection module; the delivery module comprises a valve (22) and a delivery duct (21); the liquid mixing module comprises a liquid storage container (11) and a liquid mixing container (12); the liquid storage containers (11) are provided with a plurality of liquid storage containers and are connected with a valve (22) through independent conveying pipelines (21), the valve (22) is connected with the liquid mixing container (12), and the valve (22) is used for controlling the flow time of the solvent in different conveying pipelines (21) connected with the valve so that the solvents in different liquid storage containers (11) are mixed into a uniform blended solvent in the liquid mixing container (12); the chromatographic purification equipment and the purification method provided by the invention can realize continuous multiple chromatographic columns, and realize continuous separation and purification by different preset methods respectively, thereby realizing separation and purification of multiple systems.

Description

Chromatographic purification system and purification method

Technical Field

The invention relates to a chromatographic purification system and a purification method.

Background

In the current chemical field, most of the separated and purified compounds still adopt the traditional glass chromatographic column, which consumes a great deal of time of chemical researchers. At present, most of chemical researchers still carry out manual chromatography purification, manual plate spotting, column pressing, collection and eluent replacement at home. The cost of the chromatographic purification equipment on the market is too high at present, the popularization of most chemical scientific research workers is difficult to realize, the machine body is too large and heavy, the space of a laboratory is limited, and the machine body is difficult to put into a fume hood for operation. The existing chromatographic purification equipment has complicated operation system and too many unnecessary functions, which leads to overlong operation set time and does not save time cost. At present, the rapid automatic separation and purification system on the market can only separate and purify one chromatographic column at each time, can not be intelligently switched to the next chromatographic column, has limited wireless wifi operation distance and can not realize remote operation in the true sense.

Disclosure of Invention

In order to solve the above-mentioned deficiencies of the prior art, the present invention provides a chromatographic purification system and a purification method.

The technical problem to be solved by the invention is realized by the following technical scheme:

the invention provides a chromatographic purification system which comprises a liquid mixing module, a conveying module, a purification module and a collection module, wherein the liquid mixing module, the purification module and the collection module are connected through the conveying module; the delivery module comprises a valve 22 and a delivery pipe 21, the delivery pipe 21 is used for delivering the solvent, and the valve 22 controls the flow of the solvent in the delivery pipe 21;

the liquid mixing module comprises a liquid storage container 11 and a liquid mixing container 12, wherein the liquid storage container 11 is used for storing a solvent, and the liquid mixing container 12 is used for mixing the solvent;

the liquid storage container 11 has a plurality of liquid storage containers 11, and is connected with a valve 22 through a separate delivery pipe 21, the valve 22 is connected with the liquid mixing container 12, and the valve 22 is used for controlling the flow time of the solvent in the different delivery pipes 21 connected with the valve 22, so that the solvents in the different liquid storage containers 11 are mixed into the mixed solvent in the liquid mixing container 12.

Further, the delivery pipe 21 includes a first delivery pipe 211 and a second delivery pipe 212, the valve 22 includes a first valve 221, the first dredging pipe 211 is used for connecting the liquid storage container 11 and the first valve 221, the first delivery pipe 211 is connected to the first valve 221 through an input interface on the first valve 221, the second delivery pipe 212 is connected to the first valve 221 through an output interface on the first valve 221, and the second delivery pipe 212 is provided with the liquid mixing container 12.

Further, the conveying module comprises a pressurizing device 23, the conveying pipeline 21 comprises a third conveying pipeline 213, one end of the pressurizing device 23 is connected with the liquid mixing container 12 through a second conveying pipeline 212, and the other end of the pressurizing device 23 is connected with the third conveying pipeline 213.

Further, the purification module comprises at least two chromatography columns 31, the delivery pipe 21 comprises a fourth delivery pipe 214, the valve 22 comprises a second valve 222, one end of each chromatography column 31 is connected with the pressurization device 23 through a third delivery pipe 213, the other end of each chromatography column 31 is connected with the collection module through the fourth delivery pipe 214, and the third delivery pipe 213 is independently provided with second valves 222 matched with the third delivery pipes 213 in number.

Further, the third conveying pipe 213 and the fourth conveying pipe 214 each include a main pipe and a sub-pipe, the main pipeline of the third conveying pipeline 213 is connected out from the supercharging equipment 23 and is divided into a plurality of auxiliary pipelines of the third conveying pipeline 213, and is connected with a second valve 222 through a third delivery pipe 213 and a part of the third delivery pipe 213 and the sub-pipe are connected with one end of the chromatographic column 31 through a part of the second valve 222, the main pipe of the fourth conveying pipe 214 is connected out from the collecting module and is divided into a plurality of auxiliary pipes of the fourth conveying pipe 214, part of the auxiliary pipes of the fourth conveying pipe 214 are connected with the other end of the chromatographic column 31 to form a purification passage, and the other part of the auxiliary pipes of the third conveying pipe 213 and the other part of the auxiliary pipes of the fourth conveying pipe 214 are directly connected through the other part of the second valve 222 to form a flushing passage.

Further, the collection module includes a detection device 41 and a collection device 42, the delivery pipeline 21 includes a fifth delivery pipeline 215 and a sixth delivery pipeline 216, the valve 22 includes a third valve 23, one end of the detection device 41 is connected to the chromatography column 31 through a fourth delivery pipeline 214, the other end of the detection device 41 is connected to the collection device 42 through the fifth delivery pipeline 215, the fifth delivery pipeline 215 is provided with the third valve 23, and the sixth delivery pipeline 216 is connected to the detection device 41 and the collection device 42.

Further, the collecting device 42 comprises at least a first collecting device 421 and a second collecting device 422; the first collecting device 421 is a product collecting device for collecting a target product, and the second collecting device 422 is a waste liquid collecting device for collecting waste liquid;

the detection device 41 comprises at least one or more of a variable dual-wavelength detector, a fixed single-wavelength ultraviolet detector and an auxiliary evaporative light detection device, and the detection device 41 is used for detecting whether a target product appears in the blending solvent flowing through the detection device 41.

Further, the chromatography purification system comprises an automatic control module, wherein the automatic control module comprises a numerical control device, a circuit port and a PCB integrated circuit board; all be equipped with circuit port on valve 22, supercharging device 23, detection device 41, the collection device 42, circuit port connection PCB integrated circuit board is connected to numerical control equipment, realizes the control to all equipment through numerical control equipment.

Furthermore, the automatic control module comprises an intelligent terminal device, a cloud server and a local area network, the intelligent terminal device is connected with the numerical control device through the cloud server, and the chromatography purification system is connected to the local area network;

the intelligent terminal device is used for monitoring the purification process and controlling the purification system device to work, an instruction is sent to the cloud server through the intelligent terminal device, the cloud server transmits an instruction signal to each device of the chromatography purification system, and the corresponding device is controlled to start to work; the collection module in the chromatography purification system transmits the detection signal data to the cloud server through the local area network, and the cloud server transmits the detection signal data to the intelligent terminal device, so that the purification process is monitored.

A purification method comprising the following operating steps;

s1, mixing liquid: in the liquid mixing module, the solvent is mixed into uniform mixed solvent with different proportions by controlling different solvent flowing time according to requirements;

s2, purification: the purification equipment in the purification module works, the blended solvent flushing purification equipment realizes purification, after flushing of any layer of purification equipment is finished or reaches a preset time, the blended solvent flushing pipeline is switched for a plurality of minutes, and then the purification equipment is switched to work, and the purification equipment works alternately in sequence until all the purification equipment work;

s3, collecting: and a detection device is arranged in the collection module, whether a target product exists in the blending solvent flowing through the detection device is detected, the blending solvent with the detected target product enters the product collection device, and the blending solvent with the undetected target product enters the waste liquid collection device until the purification is finished.

Further, a purification process as described above, comprising the following operative steps:

s1, mixing liquid: the liquid mixing module comprises a plurality of liquid storage containers, a plurality of conveying pipelines, a plurality of valves and liquid mixing containers, wherein the liquid storage containers are filled with solvents, the passing time of the solvents in the conveying pipelines is controlled by the valves, and the solvents are mixed into uniform blending solvents in different proportions in the liquid mixing containers;

s2, purification: the purification module comprises purification equipment, valves and a conveying pipeline, wherein the purification equipment is a chromatographic column, the chromatographic column in the purification module works, after the flushing of any chromatographic column is finished or reaches a preset time, the corresponding valve is switched to flush the conveying pipeline for a plurality of minutes by using the blended solvent, and then the valve is switched to work on another chromatographic column, and the operation is alternated in sequence until all the chromatographic columns are flushed;

s3, collecting: the collection module comprises detection equipment and collection equipment, the collection equipment comprises product collection equipment and waste liquid collection equipment, the detection equipment detects the fluorescence reaction of the blending solvent flowing through, the blending solvent with the fluorescence reaction detected enters the product collection equipment, and the blending solvent without the fluorescence reaction detected enters the waste liquid collection equipment until the purification is finished.

The chromatography purification system provided by the invention has the advantages of cost reduction and highest cost performance. The requirements of most chemical workers are met. The operation system is simplified, the operation is foolproof, the training and fault maintenance cost is reduced, and gradient elution, liquid level early warning, pressure early warning, one-key termination and multiple collection modes can be set according to requirements.

By applying the purification mode of the chromatographic purification system, continuous multiple chromatographic columns can be realized, and continuous separation and purification can be realized by different preset methods respectively. The separation and purification of various systems are realized, and manual switching, starting or stopping can be controlled by a small program at a remote mobile phone mobile terminal, so that the separation and purification time is greatly reduced, and the efficiency of chemical workers is improved.

Drawings

FIG. 1 is a schematic diagram of a part of a chromatographic purification system;

FIG. 2 is a schematic view of a chromatographic purification system transport module;

FIG. 3, a partial schematic view of a purification system;

11. a reservoir; 111. a first reservoir; 112. a second reservoir; 12. a liquid mixing container; 21. a delivery conduit; 211. a first delivery conduit; 2111. a first delivery conduit; 2112. a first and second delivery conduits; 212. a second delivery conduit; 213. a third delivery conduit; 2131. a third delivery conduit; 2132. a third second delivery conduit; 2133. a third delivery conduit; 2134 a third and fourth delivery conduit; 214. a fourth delivery conduit; 2141. a fourth delivery conduit; 2142. a fourth second delivery conduit; 2143. a fourth, third delivery conduit; 2144. a fourth delivery conduit; 215. a fifth delivery conduit; 216. a sixth delivery conduit; 2161. a sixth transport conduit; 2162. a sixth second delivery conduit; 22. a valve; 221. a first valve; 222. a second valve; 2221. a second valve; 2222. a second valve; 2223. a second triple valve; 2224. a second four-way valve; 223. a third valve; 23. a pressure boosting device; 31. a chromatography column; 311. a first chromatography column; 312. a second chromatography column; 313. a third chromatography column; 41. a detection device; 42. a collection device; 421. a first collection device; 422. a second collection device; 51. a PLC controller; A. a liquid mixing module; B. a purification module; C. a collection module; D. a delivery module; E. and an automatic control module.

Detailed Description

It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict. The present invention will be described in detail below with reference to the embodiments with reference to the attached drawings.

It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.

It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments according to the present application. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof, unless the context clearly indicates otherwise.

The present invention will be described in detail below with reference to the accompanying drawings and examples.

A chromatography purification system, as shown in fig. 1, fig. 2 and fig. 3, the chromatography purification system comprises a liquid mixing module a, a conveying module D, a purification module B and a collection module C, and the liquid mixing module a, the purification module B and the collection module C are connected through the conveying module D; the delivery module D comprises a valve 22 and a delivery pipe 21, the delivery pipe 21 is used for delivering the solvent, and the valve 22 controls the flow of the solvent in the delivery pipe 21;

the liquid mixing module A comprises a liquid storage container 11 and a liquid mixing container 12, wherein the liquid storage container 11 is used for storing a solvent, and the liquid mixing container 12 is used for mixing the solvent;

the liquid storage container 11 has a plurality of liquid storage containers 11, and is connected with a valve 22 through a separate delivery pipe 21, the valve 22 is connected with the liquid mixing container 12, and the valve 22 is used for controlling the flow time of the solvent in the different delivery pipes 21 connected with the valve 22, so that the solvents in the different liquid storage containers 11 are mixed into a uniform blended solvent in the liquid mixing container 12.

Specifically, the conveying pipe 21 is at least one of a stainless steel pipe or a plastic hose, and is preferably a polytetrafluoroethylene hose having a diameter of 4mm from the viewpoint of experimental requirements (corrosion resistance). The number of the liquid storage containers 11 is preferably 2-3.

When the number of the liquid storage containers 11 is two, the number of the first delivery pipes 211 is also two, and the first delivery pipes 2111 and the second delivery pipes 2112 are respectively a first delivery pipe 2111 and a second delivery pipe 2112, the first delivery pipes 2111 and the second delivery pipes 2112 are respectively and independently connected with the first valve 221 through the input interface, and at this time, the first valve 221 is a two-position three-way electromagnetic valve, so that the time for the solvent to flow into the two input interfaces can be controlled. Certainly, when there are three liquid storage containers 111, there are three first delivery pipes 211, and the first valve 221 at this time has three input interfaces and one output interface, the first valve 221 controls on-off and circulation time of the first delivery pipes 211 connected at the three input interfaces, so as to ensure that the first delivery pipe 211 connected at only one input interface circulates at each time, and realize that the solvents in the three liquid storage containers 11 are mixed in the liquid mixing container 12, and so on, and ensure that the multi-component solvent flows into the first valve 221 and flows out from the second delivery pipe 221, and realize uniform mixing of the blending solvent through the liquid mixing container 12 arranged on the second delivery pipe 221, thereby realizing the technical effect of proportional mixing of the solvents.

Specifically, the first valve 221 controls the flow time of the solvent in the first delivery pipe 211, which means that a plurality of input interfaces are present on the first valve 221, and respectively correspond to the number of the first delivery pipes 211, and only the flow or the disconnection of a single first delivery pipe 211 is controlled each time, and the flow time of different first delivery pipes 211 is controlled, so as to control the ratio of the subsequent blending solvent, in a specific embodiment, as exemplified by the above-mentioned scheme that two liquid storage containers 11 are present, the first valve 221 first controls the first delivery pipe 2111 to flow for a plurality of times, at this time, the first and second delivery pipes 2112 are in a closed state, that is, the solvent in the first and second delivery pipes 2112 does not flow into the first valve 221, after a plurality of times, the first valve 221 controls the first and second delivery pipes 2112 to flow for a plurality of times, and the first delivery pipe 2111 is in a closed state, at this time, only the solvent in the second delivery pipe 2112 flows through the first valve 221, and the solvent flowing through the first valve 221 during the above time flows into the liquid mixing container 12 through the second delivery pipe 212, and is mixed into a uniform blended solvent in a certain proportion for the rinsing in the subsequent chromatography purification process. It should be noted that the ratio of the blending solvent may be continuously changed according to the requirement, that is, during the process of showering the single chromatographic column 31, the ratio of the blending solvent used is also changed, and is not the blending solvent with a fixed ratio.

Further, the conveying module D includes a pressurization device 23, the conveying pipeline 21 includes a third conveying pipeline 213, one end of the pressurization device 23 is connected to the liquid mixing container 12 through a second conveying pipeline 212, and the other end of the pressurization device 23 is connected to the third conveying pipeline 213.

The supercharging equipment 23 is any one of a plunger pump, an injection pump, an air pump, a peristaltic pump and an electromagnetic gear pump; the pressurizing means 23 is preferably an electromagnetic gear pump in view of cost and accuracy, and the flow rate of the solvent can be controlled by controlling the rotation speed of the electromagnetic gear pump.

Further, the purification module B includes at least two chromatography columns 31, the delivery line 21 includes a fourth delivery line 214, the valve 22 includes a second valve 222, one end of the chromatography column 31 is connected to the pressure boosting device 23 through a third delivery line 213, the other end of the chromatography column 31 is connected to the collection module C through the fourth delivery line 214, and the third delivery line 213 is independently provided with second valves 222, the number of which is matched with that of the third delivery lines 213.

Further, the number of the third delivery pipe 213, the fourth delivery pipe 214, and the second valve 222 is the same and matched with each other, and is at least one more than the number of the chromatography columns 31.

Specifically, the chromatographic column 31 is at least one selected from a glass chromatographic column, a high-performance silica gel column and a stainless steel high-pressure preparation column, and the chromatographic column 31 needs a preset filler, which is divided into: silica gel, C18, C4, functionalized amino filler and the like, wherein the setting of the chromatography 31 can be specifically selected according to the sample to be purified, and preferably, a high-performance silica gel column with a luer joint meeting the international standard is selected.

Preferably, the number of the chromatography columns 31 is not less than three. It should be noted that, each of the third conveying pipeline 213 and the fourth conveying pipeline 214 includes a main pipeline and a sub-pipeline, the main pipeline of the third conveying pipeline 213 is connected to the pressure boosting device 23 and is branched into a plurality of sub-pipelines of the third conveying pipeline 213, the blended solvent flowing out from the pressure boosting device 23 flows out through a single pipeline, that is, the main pipeline of the third conveying pipeline 213, that is, when the number of the chromatography columns 31 is three, the third conveying pipeline 213 is branched into four sub-pipelines of the third conveying pipeline 213, that is, a third conveying pipeline 2131, a third second conveying pipeline 2132, a third conveying pipeline 2133 and a third four conveying pipeline 2134, it can be understood that, corresponding to the sub-pipelines of the third conveying pipeline 213, four second valves 222 are disposed on the sub-pipelines of the third conveying pipeline 213, and are a second valve 2221 disposed on the third conveying pipeline 2131, a second valve 2222 disposed on the third conveying pipeline 2132, and a second valve 2222222 disposed on the third conveying pipeline 2131, A second three-way valve 2223 provided on the third delivery pipe 2133 and a second four-way valve 2224 provided on the third four delivery pipe 2134, it should be noted that the above-mentioned second valve 2221, second valve 2222, second three-way valve 2223 and second four-way valve 2224 merely represent a distinction of the second valve 222, and are not a limitation on the kind of valve 22, and it is preferable that the second valve 222 is provided as described above, and is a single open solenoid valve. Of course, a multi-way valve may be disposed on the main pipe of the third delivery pipe 213, and the flow direction of different and single solvents may be controlled by the multi-way valve, which is not described herein.

It can be understood that, like the third conveying pipeline 213, there are four sub-pipelines of the fourth conveying pipeline 214 and one main pipeline of the fourth conveying pipeline 214 matching with the number of the sub-pipelines of the third conveying pipeline 213, that is, when the number of the chromatography columns 31 is three, there are four sub-pipelines of the fourth conveying pipeline 214, that is, a fourth conveying pipeline 2141, a fourth conveying pipeline 2142, a fourth conveying pipeline 2143, and a fourth conveying pipeline 2144, and the sub-pipelines of the fourth conveying pipeline 214 are merged into one main pipeline of the fourth conveying pipeline 214 and connected to the detecting device 41.

The number of the third delivery pipe 213 secondary pipe, the fourth delivery pipe 214 secondary pipe and the second valve 222 is consistent and matched with each other, and is at least one more than that of the chromatographic column 31, and the third delivery pipe 213 secondary pipe, the second valve 222 and the fourth delivery pipe 214 secondary pipe which are directly connected with the chromatographic column 31 form a purification passage; the third delivery pipe 213, the second valve 222 and the fourth delivery pipe 214, which are not directly connected to the chromatographic column 31, are independently and sequentially connected to form a flushing passage, and the flushing passage is used for flushing the cross pipe of the chromatographic purification system, so that the product or impurities of the previous chromatographic column are prevented from remaining, contaminating the purification of the next chromatographic column, and affecting the purity analysis of the product. As one preferable example, it is known that the third transfer pipe 2131, the second valve 2221, the first chromatography column 311, and the fourth transfer pipe 2141 form a first purification passage; the third second delivery tube 2132, the second valve 2222, the second chromatography column 312, and the fourth second delivery tube 2142 form a second purification path; a third delivery conduit 2133, a second triple valve 2223, a third chromatography column 313, and a fourth delivery conduit 2143 form a third purification pathway; the third fourth delivery conduit 2134, the second fourth valve 2224, and the fourth delivery conduit 2144 form a first flush passage.

Further, the collecting device 42 comprises at least a first collecting device 421 and a second collecting device 422; the first collecting device 421 is a product collecting device for collecting a target product, and the second collecting device 422 is a waste liquid collecting device for collecting waste liquid.

Further, the detection device 41 preferably comprises at least one of a variable dual wavelength detector, a fixed single wavelength ultraviolet detector, optionally with an auxiliary evaporative light detection device.

Specifically, the detection device 41 distinguishes products and impurities through spectral properties of different substances to confirm the separation condition of a target product in the blending solvent, the detection device 41 judges the separation condition in the chromatographic column 31 by identifying the concentration of the solute in the blending solvent, specifically, the detection device 41 can output a solute concentration curve graph, a straight line appears when only the blending solvent exists, the concentration of the solute changes when the blending solvent carrying a sample enters the detection device 41 in the separation process, a peak appears, when the separation is finished, the concentration of the solute in the blending solvent is reduced, a straight line appears, and whether the separation is started or not and the separation is finished is judged by judging the appearance and disappearance time of the peak.

Specifically, a plurality of collecting containers are arranged in the collecting device 42, and the collecting device 42 can automatically switch to the next collecting container according to time, or solvent volume, and different fluorescence absorptions, so as to realize automatic collection and achieve separation and purification of the target product.

The first collecting device 421 is used for collecting the target product, and the second collecting device 422 is used for collecting the waste liquid. And the blending solvent flowing out of the purification module B enters the detection device 41, and if a target product is detected, the blending solvent enters the first collection device 421 through the third valve 223 to realize the collection of the target product, and the detected impurities enter the second collection device 422 through the third valve 223, so that the separation and purification of the mixed system are finally realized. Specifically, the third valve 223 is a two-position two-way solenoid valve. Of course, if there are three collection devices 42, the corresponding third valve 223 is a three-position, two-way solenoid valve, and so on. As an example, when the collecting means 42 includes two, a first collecting means 421 for collecting the target product and a second collecting means 422 for collecting the waste liquid, respectively, the first collecting means 421 is connected to the third valve 223 through a fifth transfer pipe 2151, and the second collecting means 422 is connected to the third valve 223 through a fifth transfer pipe 2152. An accurate and automatic collection function is achieved. In a specific embodiment, the detecting device 41 can detect whether a specific fluorescent compound passes through the blending solvent flowing through the detecting device 41, distinguish different fluorescence absorptions of the compounds, collect different fluorescence in the first collecting device 421 if a target product of a fluorescence reaction occurs, separately collect different fluorescence, that is, enter different collecting containers in the first collecting device 421, and enter the second collecting device 422 if no fluorescence is detected, thereby completing waste liquid collection.

Further, chromatography purification system includes automatic control module, automatic control module includes numerical control equipment, circuit port, PCB integrated circuit board, intelligent terminal equipment and high in the clouds treater, all be equipped with the circuit port on valve 22, supercharging device 23, detection device 41, the collection device 42, PCB integrated circuit board is connected to the circuit port to connect to numerical control equipment, realize the control to all equipment through numerical control equipment.

Specifically, each circuit port is independently integrated into the same PCB integrated circuit board and is controlled by a single numerical control device, or part of the circuit ports are integrated into the same PCB integrated circuit board, and the other part of the circuit ports are integrated into the other PCB integrated circuit board and are controlled by different numerical control devices, or each circuit port is independently integrated into the same PCB integrated circuit board and is controlled by an independent numerical control device; as a specific embodiment, for example, a part of the circuit ports are integrated into the same PCB, another part of the circuit ports are integrated into another PCB, and control is realized through different numerical control devices, the second valve 222 is connected to the PLC controller 51 through the circuit ports and directly controls the second valve 222 through the PLC controller 51, and the rest of the circuit ports are externally connected to the PCB and connected to the numerical control device, and the chromatography purification system is controlled through another numerical control device and controlled through an intelligent terminal device.

Specifically, the intelligent terminal device may be any one of a computer, a tablet computer, a mobile phone, and the like, and in order to implement remote control of the chromatography purification system, the intelligent terminal device is preferably a mobile phone, and the manual control finger of the program instruction of the intelligent terminal device may control the device connected to the circuit port through a remote program (for example, using a wechat applet on the mobile phone), and is not limited to the geographical limitation of the existing local area network plus terminal device system.

Specifically, the numerical control device is a controller, which has an effect of controlling the connection device, and as an option, the numerical control device may be selected as the PLC controller 51. As a specific embodiment, the second valves 222 are independently connected to a numerical control device, the numerical control device is a PLC controller 51, and the PLC controller 51 implements program-controllable opening and closing of the valves 22 corresponding to and independently connected to the chromatography column 31 at different times through pulse signals, that is, the opening and closing of each second valve 222 can be implemented by setting a timing program and/or using program instructions.

Specifically, in the chromatography purification system, the automatic control module includes a numerical control device, a circuit port, a PCB, a cloud server, and an intelligent terminal device, the collecting device 42, the detecting device 41, and the PLC controller 51 are connected to a local area network, the intelligent terminal device is connected to the chromatography purification system device in the local area network through the cloud server, taking the mobile phone using a WeChat small program control as an example, the WeChat small program sends a control instruction, the control instruction signal is transmitted to the cloud server, the cloud server transmits the control instruction signal to the PLC controller 51 in the local area network where the chromatography purification system is located, and controls the second valve 222 to open and close, so as to realize switching of different chromatography columns 31, and also can control a deuterium lamp switch provided in the detecting device; among the chromatography purification system, check out test set 41 is responsible for detecting the fluorescence reaction of the blending solvent that flows through check out test set 41 and the concentration of solute in the blending solvent, detects whether target product appears and the time that target product appears to the output detection signal, and is concrete, detection signal is solute concentration change curve, and through the time that concentration curve crest appears and disappears, whether the purification process is accomplished in certain layer analytical column 31 is judged, check out test signal and pass through the local area network and upload to the high in the clouds server to check out test signal that test set 41 output on the high in the clouds server transmits the cell-phone, and the purification condition is confirmed to the little procedure of accessible believe in the low in the accessible. Through to intelligent terminal equipment right chromatography purification system is to control and detect, can realize remote control's technological effect to can realize real-time supervision and even control, reduce the waste that has already been accomplished the separation by a certain chromatography column 31 and solvent idle flow causes.

A purification method comprising the following operating steps;

Further, a purification method as described above, comprising the following operating steps;

Concretely, a purification method using the chromatography purification system comprises the following operation steps;

s1, mixing liquid: setting the types of solvents in different liquid storage containers 11 according to actual requirements, presetting fillers and samples to be purified in different chromatographic columns 31, setting the same or different fillers and samples with purification between different chromatographic columns 31, and presetting the passing time of the solvents in the first conveying pipelines 211 at each input interface in the first valve 221;

s2, purification: controlling the first valve 22, the pressurization device 23 and the detection device 41, and the collection device 42 is opened to work, wherein the first valve 221 and the third valve 223 are in an open state, only one second valve 222 is in an open state, and the other second valves 222 are in a closed state; different solvents flow out of different liquid storage containers 11 through the first conveying pipeline 211, flow through the first valve 221 at different times, flow out of the first valve 221 through the blended solvent in a preset proportion, flow through the pressurizing device 23 through the second conveying pipeline 212, enter the third conveying pipeline 213, enter the corresponding chromatographic column 31 through the second valve 222 which is provided with the opened corresponding chromatographic column 31, flush the chromatographic column 31, flow out of the purification system through the corresponding fourth conveying pipeline 214 through the blended solvent of the chromatographic column 31, enter the detection device 41, and enter the collection device through the third valve 223; closing the second valve 222 of the corresponding chromatographic column 31 which is opened originally, controlling the second valve 222 corresponding to the flushing passage to be opened, flushing the pipeline for a plurality of minutes by using the blended solvent to prevent the sample in the previous chromatographic column 31 from being polluted, opening the second valve 222 of the other corresponding chromatographic column 31, and circulating the process to start the purification of the sample in the other chromatographic column 31;

specifically, the switching of the second valve 222 is controlled by a numerical control device, and the switching can be performed within a certain time according to the judgment that the target product does not appear in the program judgment, or can be performed at a fixed time, that is, after a certain time, the next chromatographic column 31 is automatically switched to perform the showering; when the automatic control module is arranged, the intelligent terminal equipment can be used for realizing remote control.

S3, collecting: the collection module comprises a detection device 41 and a collection device 42, the collection device 42 comprises a first collection device 421 and a second collection device 422, which correspond to the product collection device and the waste liquid collection device respectively, the detection device 41 detects the fluorescence reaction of the co-solvent flowing through, the co-solvent detecting the fluorescence reaction enters the product collection device, different fluorescence reactions occur, the co-solvent not detecting the fluorescence reaction enters the waste liquid collection device in another collection container of the product collection device, when the preset time is reached, or all samples in the chromatographic columns 31 are purified, all device switches are closed, and the purification process is finished.

Specifically, when an automatic control module is introduced, the purification method as described above includes the following operation steps:

s2, purification: the purification module comprises purification equipment, a valve and a conveying pipeline, the purification equipment is a chromatographic column, the chromatographic column in the purification module works, a detection signal output by the detection equipment is monitored through a mobile phone WeChat small program, whether the next purification equipment works is switched or not is judged, a control instruction is output through the mobile phone WeChat small program, the control instruction is transmitted to the numerical control equipment through a cloud server, the corresponding valve is controlled to be switched, the conveying pipeline is flushed by using a blending solvent for a plurality of minutes, the valve is switched to work on the other chromatographic column, and the steps are alternated in sequence until all the chromatographic columns are flushed;

Example 1

A chromatography purification system comprises two liquid storage containers 11 which are respectively a first liquid storage container 111 and a second liquid storage container 112, wherein two first conveying pipelines 211 which are respectively a first conveying pipeline 2111 and a second conveying pipeline 2112 are correspondingly arranged, the first conveying pipeline 2111 and the second conveying pipeline 2112 are respectively and independently connected with a first valve 221 through an input interface, the second valve 222 is a two-position three-way electromagnetic valve at the moment, the chromatography purification system also comprises a liquid mixing container 12, the liquid mixing container is arranged on the second conveying pipeline 212, the first valve 221 is connected with the liquid mixing container 12 through the second conveying pipeline 212 and then connected with a pressurizing device 23, the pressurizing device 23 is an electromagnetic gear pump and further comprises three chromatography columns 31 and corresponding third conveying pipelines 2131, 2132, 2133 and 2134, four second valves 222 are provided, respectively a second valve 2222 provided on the second valve 2221 of the third delivery pipe 2131, a second three valve 2223 provided on the third delivery pipe 2132, and a second four valve 2224 provided on the third delivery pipe 2134, said second valves 222 being single-way solenoid valves, four secondary pipes of the fourth delivery pipe 214 are provided, respectively a fourth delivery pipe 2141, a fourth second delivery pipe 2142, a fourth third delivery pipe 2143, and a fourth delivery pipe 2144, wherein the fourth delivery pipe 2144, the second four valve 2224, and the third delivery pipe 2134 are directly connected to form a first flushing passage, said fourth delivery pipe 214 is connected to the detection device 41, said detection device 41 comprises a variable dual wavelength detector, and an auxiliary evaporative light detection device, and further comprises a third valve 223, the third valve 223 is a two-position two-way electromagnetic valve, a fifth delivery pipeline 215 is arranged between the third valve 223 and the detection device 41, the collection device 43 is connected with the third valve 223 through a sixth delivery pipeline 216, the collection device 42 includes two first collection devices 421 for collecting the target product and a second collection device 422 for collecting the waste liquid, the first collection device 421 is connected with the third valve 223 through a sixth delivery pipeline 2161, and the second collection device 422 is connected with the third valve 223 through a sixth delivery pipeline 2162. All be equipped with the circuit port on above-mentioned first valve 221, second valve 222, third valve 223, supercharging device 23, detection device 41, the collection device 42, numerical control equipment is connected through the circuit port to second valve 222, numerical control equipment is PLC controller 51 promptly, the external PCB integrated circuit board of all the other circuit ports to integrated to a numerical control equipment, and be connected with intelligent control equipment through the cloud server, chromatography purification system passes through intelligent terminal equipment control, controls through cell-phone end little letter procedure promptly.

A purification method using the chromatography purification system,

s1, system presetting: according to actual requirements, putting a solvent into the liquid storage container 11, putting a sample to be purified into the purification module B, and setting the passing time of the solvent in the conveying pipeline 21 at each input interface in a valve 22 connected with the liquid storage container 11;

placing a solvent X in a first liquid storage container 111, placing a solvent Y in a second liquid storage container 112, wherein a first chromatographic column 311 is a high-performance silica gel column, a second chromatographic column 312 is a glass chromatographic column, a third chromatographic column 313 is a stainless steel high-pressure preparation column, and samples M1, M2 and M3 are respectively placed in the chromatographic columns; presetting blending solvents with different proportions required by corresponding three chromatographic columns 31, and respectively setting and controlling the passing time of the solvents in the first conveying pipelines 211 at the two input interfaces in the first valve 221;

s2, starting a system: the liquid mixing module A, the conveying module D, the purification module B and the collection module C are started to work:

controlling the first valve 22, the pressurization device 23 and the detection device 41, and the collection device 42 to be operated in an opening mode, wherein the first valve 221 and the third valve 223 are in an opening state, the second valve 2221 is in an opening state, and the other second valves 222 are in a closing state;

s3, purification process: purifying the samples in the purification module B in sequence;

the X solvent and the Y solvent flow out from different liquid storage containers 11 through a first delivery pipe 211, sequentially flow through a first valve 221 at a time preset by a program, enter a liquid mixing container 12 through a second delivery pipe 212 to be uniformly mixed, and flow out from the liquid mixing solvent 12 with a preset proportion of the blending solvent, so as to obtain the blending solvent 1 corresponding to the requirement of the first chromatographic column 311, the proportion of the blending solvent 1 is changed, flow through a pressurizing device 23 through the second delivery pipe 212 to enter a third delivery pipe 213, enter the first chromatographic column 311 through an opened second valve 2221, flush the first chromatographic column 311, flow out of the purification system from a corresponding fourth delivery pipe 2141 through the blending solvent of the first chromatographic column 311, and enter a detection device 41, the detection device 41 operates and recognizes that the fluorescence reaction and the output concentration change curve of the target product occur, and flow into a first collection device 421 through a third valve 223, after the target product is collected for a period of time, different fluorescence reactions occur, the fluorescence reactions enter different collection containers in the first collection device 421 through the third valve 223, and when the fluorescence reactions of the target product are not identified by the detection device 41, the blended solvent enters the second collection device 422 through controlling the third valve 223 and is used as waste liquid for subsequent treatment;

s4, switching chromatographic columns: the detection device 41 outputs a concentration change curve chart, the data of the concentration change curve chart is uploaded to a cloud server through a connected local area network and transmitted to the mobile phone, a mobile phone micro-communication small program is used for monitoring that the fluctuation of the concentration change curve chart tends to be stable and does not change any more, a control instruction is sent through the mobile phone micro-communication small program and transmitted to the PLC controller 51 through the cloud server, the PLC controller 51 is also connected to the local area network of the system, the PLC controller 51 responds to the received control instruction, the second valve 222 is controlled through the PLC controller 51, the second valve 2221 is closed, the second valve 2224 is opened at the same time, the second valve 2224 is flushed for 3 minutes, the second valve 2224 is closed, the second valve 2222 is opened at the same time, the time of controlling the two input interfaces by the first valve 221 is changed, the solvent blending ratio is changed, the blending solvent 2 adaptive to the second chromatographic column 312 is obtained, and flows through the pressurization device 23 through the second delivery pipe 212 and enters the third delivery pipe 213, the mixed solvent enters the second chromatographic column 312 through the opened second valve 2222, flows out of the purification system from the corresponding fourth delivery pipe 2142 through the second valve 2222, and enters the detection device 41, the detection device 41 works and recognizes that the target product appears, and enters the first collection device 421 through the third valve 223, the collection of the target product is completed, and after a while, when the target product is not recognized by the detection device 41, the mixed solvent enters the second collection device 422 through controlling the third valve 223, and is used as waste liquid for subsequent treatment;

the detection device 41 outputs a concentration change curve chart, data of the concentration change curve chart is uploaded to a cloud server through a connected local area network and transmitted to the mobile phone, a mobile phone micro-letter small program is used for monitoring that the fluctuation of the concentration change curve chart tends to be stable and does not change any more, a control instruction is sent through the mobile phone micro-letter small program and transmitted to the PLC controller 51 through the cloud server, the PLC controller 51 is also connected to the local area network of the system, the PLC controller 51 responds to the received control instruction, the second valve 222 is controlled through the PLC controller 51, the second valve 2222 is closed, the second valve 2224 is opened at the same time, flushing is carried out for 3 minutes, the second valve 2224 is closed, the second valve 2223 is opened at the same time, the time of controlling two input interfaces by the first valve 221 is changed, the solvent blending ratio is changed, and the blending solvent 3 suitable for the third chromatographic column 313 is obtained, flowing through the pressurization device 23 through the second delivery pipe 212, entering the third delivery pipe 213, entering the second chromatography column 313 through the opened second three valves 2223, showering the third chromatography column 313, flowing out of the purification system from the corresponding fourth delivery pipe 2143 through the blended solvent 3 of the third chromatography column 313, entering the detection device 41, working of the detection device 41, recognizing the occurrence of the target product, entering the first collection device 421 through the third valve 223, completing collection of the target product, and after a while, when the detection device 41 does not recognize the target product, controlling the third valve 223, allowing the blended solvent to enter the second collection device 422 as waste liquid for subsequent treatment, closing the second three valves 2223, and simultaneously opening the second four valves 2224, and flushing for 3 minutes;

s5, finishing purification: and (5) after all the samples in the chromatographic column 31 are purified and the washing is finished, closing all equipment switches and finishing the purification process.

The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and various modifications and changes will occur to those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A chromatography purification system is characterized by comprising a liquid mixing module, a conveying module, a purification module and a collection module, wherein the liquid mixing module, the purification module and the collection module are connected through the conveying module; the delivery module comprises a valve (22) and a delivery pipe (21), the delivery pipe (21) is used for delivering the solvent, and the valve (22) controls the flow of the solvent in the delivery pipe (21);

the liquid mixing module comprises a liquid storage container (11) and a liquid mixing container (12), wherein the liquid storage container (11) is used for storing a solvent, and the liquid mixing container (12) is used for mixing the solvent;

the liquid storage container (11) is provided with a plurality of liquid storage containers and is connected with a valve (22) through independent conveying pipelines (21), the valve (22) is connected with the liquid mixing container (12), and the valve (22) is used for controlling the flow time of the solvent in different conveying pipelines (21) connected with the valve so that the solvents in different liquid storage containers (11) are mixed into the blending solvent in the liquid mixing container (12).

2. Chromatographic purification system according to claim 1, wherein the delivery conduit (21) comprises a first delivery conduit (211) and a second delivery conduit (212), the valve (22) comprises a first valve (221), the first delivery conduit (211) is used for connecting the reservoir (11) and the first valve (221), the first delivery conduit (211) is connected with the first valve (221) through an input interface on the first valve (221), the second delivery conduit (212) is connected with the first valve (221) through an output interface on the first valve (221), and the second delivery conduit (212) is provided with a mixing container (12).

3. Chromatography purification system according to claim 2, wherein the delivery module comprises a pressurizing device (23), the delivery conduit (21) comprises a third delivery conduit (213), one end of the pressurizing device (23) is connected to the mixing container (12) through a second delivery conduit (212), and the other end of the pressurizing device (23) is connected to the third delivery conduit (213).

4. The chromatographic purification system according to claim 3, wherein the purification module comprises at least two chromatographic columns (31), the delivery pipeline (21) comprises a fourth delivery pipeline (214), the valve (22) comprises a second valve (222), one end of each chromatographic column (31) is connected with the pressure boosting device (23) through a third delivery pipeline (213), the other end of each chromatographic column (31) is connected with the collection module through the fourth delivery pipeline (214), and the third delivery pipeline (213) is independently provided with the second valves (222) with the number matched with that of the third delivery pipelines (213).

5. Chromatographic purification system according to claim 3, characterized in that the third and fourth transfer lines (213, 214) each comprise a primary line and a secondary line, the primary line of the third transfer line (213) being connected from the pressure boosting device (23), split into a number of secondary lines of the third transfer line (213), and connected to the second valve (222) via the secondary line of the third transfer line (213), part of the secondary lines of the third transfer line (213) being connected to one end of the chromatographic column (31) via part of the second valve (222), the primary line of the fourth transfer line (214) being connected from the collection module, split into a number of secondary lines of the fourth transfer line (214), part of the secondary lines of the fourth transfer line (214) being connected to the other end of the chromatographic column (31) to form a purification circuit, another part of the secondary lines of the third transfer line (213) and another part of the secondary lines of the fourth transfer line (214) being connected to the other end of the chromatographic column (31) via another secondary line Part of the second valves (222) are directly connected to form a flushing path.

6. Chromatographic purification system according to claim 5, wherein the collection module comprises a detection device (41) and a collection device (42), the delivery conduit (21) comprises a fifth delivery conduit (215) and a sixth delivery conduit (216), the valve (22) comprises a third valve (23), one end of the detection device (41) is connected with the chromatographic column (31) through a fourth delivery conduit (214), the other end of the detection device (41) is connected with the collection device (42) through a fifth delivery conduit (215), the fifth delivery conduit (215) is provided with the third valve (23), and the sixth delivery conduit (216) is connected with the detection device (41) and the collection device (42).

7. Chromatographic purification system according to claim 6, characterized in that the collecting device (42) comprises at least a first collecting device (421) and a second collecting device (422), the first collecting device (421) being a product collecting device for collecting the target product and the second collecting device (422) being a waste liquid collecting device for collecting waste liquid.

8. Chromatographic purification system according to claim 6, characterized in that the detection device (41) comprises at least one or more of a variable dual wavelength detector, a fixed single wavelength UV detector, and an auxiliary evaporative light detection device, the detection device (41) being adapted to detect the presence of the target product in the co-solvent flowing through the detection device (41).

9. The chromatographic purification system according to any of claims 1-8, comprising an automatic control module comprising a numerical control device, a circuit port, a PCB integrated circuit board; all be equipped with the circuit port on valve (22), supercharging device (23), detection device (41), the collection device (42), the circuit port is connected PCB integrated circuit board to be connected to numerical control equipment, realize the control to all equipment through numerical control equipment.

10. The chromatography purification system of claim 9, wherein the automatic control module comprises an intelligent terminal device, a cloud server and a local area network, the intelligent terminal device is connected with the numerical control device through the cloud server, and the chromatography purification system is connected to the local area network;

11. A purification method, characterized in that it comprises the following operative steps:

s1, mixing liquid: in the liquid mixing module, the solvent is mixed into the mixed solvent with different proportions by controlling the flowing time of the solvent to be different according to requirements;

s2, purification: the purification equipment in the purification module works, the blended solvent flushing purification equipment realizes the purification process, after flushing of any purification equipment is finished or reaches a preset time, the blended solvent flushing pipeline is switched for a plurality of minutes, and then the purification equipment is switched to work, and the purification equipment works alternately in sequence until all the purification equipment work;

12. A purification process according to claim 10, characterized in that it comprises the following operative steps:

s1, mixing liquid: the liquid mixing module comprises a plurality of liquid storage containers, a plurality of conveying pipelines, a plurality of valves and liquid mixing containers, wherein the liquid storage containers are filled with solvents, the passing time of the solvents in the conveying pipelines is controlled by the valves, and the solvents are mixed into uniform blending solvents with different proportions in the liquid mixing containers;

s2, purification: the purification module comprises purification equipment, valves and a conveying pipeline, wherein the purification equipment is a chromatographic column, the chromatographic column in the purification module works, any chromatographic column is flushed and/or reaches a specified time, the corresponding valve is switched to flush the conveying pipeline for a plurality of minutes by using the blended solvent, and then the valve is switched to work on another chromatographic column, and the steps are alternated in sequence until all the chromatographic columns are flushed and completed;

s3, collecting: the collection module comprises detection equipment and collection equipment, the collection equipment comprises product collection equipment and waste liquid collection equipment, the detection equipment detects the fluorescence reaction of the blending solvent flowing through, the blending solvent with the fluorescence reaction detected enters the product collection equipment, and the blending solvent with the fluorescence reaction undetected enters the waste liquid collection equipment until the purification is finished.