WO2020052511A1

WO2020052511A1 - Multi-dimensional liquid chromatographic separation system

Info

Publication number: WO2020052511A1
Application number: PCT/CN2019/104868
Authority: WO
Inventors: 李宜珊
Original assignee: 李宜珊
Priority date: 2018-09-11
Filing date: 2019-09-09
Publication date: 2020-03-19

Abstract

Disclosed is a multi-dimensional liquid chromatographic separation system, comprising a high-performance liquid chromatographic gradient pump A (1), a high-performance liquid chromatographic gradient pump B (2), a high-performance liquid diluting liquid pump (3), a gradient mixer A (4), a gradient mixer B (5), a sample valve (6), a fraction collector (9), a liquid chromatographic separation column array (10), a detector (11), a two way multi-port valve (12), one or two enrichment column array(s) (7, 8) and a connecting piping. Respective dimensional chromatographic separation columns are selected through the liquid chromatographic separation column array (10), thereby, based on the same gradient elution system and the same detector (11), realizing full on-line monitoring and control of multi-dimensional chromatographic separation, and realizing control of the degree of cleanliness of the enrichment columns (7, 8) and the separation column (10). Respective dimensional separations are connected through the enrichment columns (7, 8), and the diluting liquid pump (3) is used to assist the enrichment or trapping of a compound. The system achieves the efficient separation of monomer compounds in complex system samples with a high separation difficulty by selecting different combinations of chromatographic stationary phases and mobile phases.

Description

Multidimensional liquid chromatography separation system

Technical field

The invention belongs to the technical field of high-performance liquid chromatography separation, and relates to a multi-dimensional liquid chromatography separation system.

Background technique

With the development of separation technology, searching and separating components in complex sample systems has become a hot research area. Multidimensional liquid chromatography technology has effectively improved the resolution of complex sample components by increasing the peak capacity, and has become the development direction of fast chromatography. Multidimensional liquid chromatography is a liquid chromatography combined technique in which the eluent from the first-dimensional chromatographic column of a sample is sequentially injected into the subsequent-dimensional chromatographic columns for further separation. This separation technology can use two or more chromatographic columns with different separation mechanisms for orthogonal separation of samples. There are three kinds of most common multi-dimensional liquid chromatography interface technologies: interface technology based on sample loops; interface technology based on enrichment columns (also known as trapping columns); interface technology based on dwell mode.

Due to technical limitations, most common two-dimensional or multi-dimensional liquid chromatography systems currently use multiple gradient elution systems. They use the residence mode or continuous mode. They can only detect and control the last one-dimensional separation process. Process monitoring and automated transparent control, it is also difficult to monitor the cleanliness of all enrichment or separation columns, it is difficult to quickly repeat and meet the needs of sample preparation; in some multi-dimensional chromatography separation systems, each dimension separation system uses an independent detection And separate gradient elution system, the cost of the entire chromatographic separation system is relatively high.

At present, the multi-dimensional liquid chromatography separation system mainly includes a stop-flow two-dimensional liquid chromatography system, a continuous loop switching two-dimensional liquid chromatography system, and a serial mode multi-dimensional liquid chromatography system.

The operation mode of the stop-flow two-dimensional liquid chromatography system is: the first-dimensional separation system stops after a segment of the sample is separated, the separated sample is transferred to the second-dimensional separation system for separation, and the second-dimensional separation system stops after the completion, and continues to the first The operation of the one-dimensional separation system is repeated, and all separations are completed.

The operating mode of the continuous-loop switching type two-dimensional liquid chromatography system is: a section of the sample separated by the first-dimensional separation system is submitted to the second-dimensional separation system for separation, and the first-dimensional separation system continues the first-dimensional separation. Separation. The separation speed of the continuous-loop switched two-dimensional liquid chromatography system is extremely fast, but the separation of the second-dimensional liquid chromatography is severely restricted by the first-dimensional liquid chromatography, and the application field is limited. In addition, if a continuous-ring-switching two-dimensional liquid chromatography system is to achieve three-dimensional or higher-dimensional chromatographic separation, it must be cascaded to form a cascaded parallel multi-dimensional chromatographic separation system, which has a relatively high cost and complicated use control.

The operating mode of the serial mode multi-dimensional liquid chromatography system is: firstly run the first-dimensional separation system, and accurately cut and separate the separated sample components in order to enrich them in multiple enrichment columns. After the first-dimensional separation ends, the first Two-dimensional separation; so reciprocating to achieve multi-dimensional chromatographic separation. The serial mode multi-dimensional liquid chromatography system is represented by Sepiatec GmbH's full-automatic high-throughput preparative separation system sepbox series products, but this product can only perform two-dimensional chromatographic separation with limited separation capacity.

Summary of the Invention

The purpose of the present invention is to address the characteristics of the existing multidimensional liquid chromatography separation system, which are high in construction cost and complicated in operation, or take a long time and consume large mobile phases. On the basis of retaining the advantages of the existing multidimensional liquid chromatography separation system, Construct a multi-dimensional liquid chromatography separation system capable of performing three-dimensional or higher liquid chromatography separation at low cost.

In order to achieve the above object, the technical solution of the present invention is:

A multi-dimensional liquid chromatography separation system. The constituent elements of the multi-dimensional liquid chromatography separation system and the connection modes between the elements are any of the following devices A, B, C, D, E, F, H, I, and J. One type:

Due to the shortcomings of the existing technology, for example: Chinese patent application CN108037233A discloses a multi-dimensional liquid chromatography separation system based on the same detector for full online detection, which can realize the measurement and control of the entire separation process, and the cleanliness of the enrichment column and the separation column. Can be detected, suitable for difficult and repeated analysis, separation and preparation of complex sample systems, and facilitate the efficient preparation of monomer compounds. The system belongs to a serial mode multi-dimensional liquid chromatography system, which can provide three-dimensional or higher liquid chromatography separation capability, and facilitates the efficient preparation of monomer compounds. The inlet and outlet of the system's enrichment column array are fixed. When the enrichment column is used as the loading column, the flow direction of the eluent is the same as that of the mobile phase when the sample was originally enriched. Near the entrance of the enrichment column, it takes more mobile phase and more time to complete the sample loading in the enrichment column. In addition, the system cannot reverse elution after sample pretreatment. The invention aims at the characteristics of long time consumption and large mobile phase consumption of the existing multidimensional liquid chromatography separation system. On the basis of retaining the advantages of the existing multidimensional liquid chromatography separation system, the invention reduces the separation time and Consumption of mobile phase, the structure of device A is now proposed:

Corresponds to device A, a multi-dimensional liquid chromatography separation system, including HPLC gradient pump A, HPLC gradient pump B, diluent pump, gradient mixer A, gradient mixer B, injection valve, rich Column-column array A, enrichment-column array B, fraction collector, liquid chromatography separation column array, detector, two-position ten-way valve, and connecting pipeline. The ① position, ② position, ③ position, ④ position, ⑤ position, ⑥ position, ⑦ position, ⑧ position, ⑨ position, and ⑩ position of the two-position ten-way valve only indicate the positional adjacency relationship. Corresponding to the physical mark, its number is named and sorted from the arbitrary interface of the two-position ten-way valve, and named according to counterclockwise or clockwise from ①. The detector is used for detecting a chromatographic signal in a separation process.

The liquid chromatography separation column array is formed by a plurality of chromatographic separation columns connected in parallel through a multi-position selection valve, and only one chromatographic separation column can be turned on at the same time; there is a fixed inlet and a fixed outlet to the outside, and At least one bypass, the bypass and the separation column are connected in parallel through a multi-position selection valve; when the bypass is on, the chromatographic separation column will not be on, and when the chromatographic separation column is on, the bypass will not be on; the chromatographic separation column The number depends on the needs. If it is three-dimensional, it is recommended to be three separation columns. If it is four-dimensional, it is recommended to be four separation columns.

The enrichment column array A is formed by connecting a plurality of chromatographic enrichment columns in parallel through a multi-position selection valve, and at the same time, only one enrichment column can be conducted; at least one bypass, the bypass and the enrichment column pass through. Multi-position selector valves are connected in parallel; the enrichment column will not be conductive when the bypass is on, and the bypass will not be conductive when the enrichment column is on; there are two external interfaces, which are defined as interface X and interface Y, of which One acts as an inlet and the other acts as an outlet; the number of enrichment columns is determined as needed, and is mainly limited by the length of the pipeline and the installation space. Multiple enrichment column arrays can be connected in series, that is, the interface Y of the upper-level enrichment column array is connected to the interface X of the secondary enrichment column array to form a multi-stage enrichment column array. The operation control is the same as that of the single-stage enrichment column array. Only one enrichment column can be turned on at the same time; when the multi-stage enrichment column array is in the bypass conduction state, the enrichment column array in each stage is in bypass conduction.

The enrichment column array B is formed by connecting a plurality of chromatographic enrichment columns in parallel through a multi-position selection valve, and at the same time, only one enrichment column can be turned on; at least one bypass can pass through the enrichment column and the enrichment column. Multi-position selector valves are connected in parallel; the enrichment column will not be conductive when the bypass is on, and the bypass will not be conductive when the enrichment column is on; there are two external interfaces, which are defined as interface X and interface Y, of which One acts as an inlet and the other acts as an outlet; the number of enrichment columns is determined as needed, and is mainly limited by the length of the pipeline and the installation space. Multiple enrichment column arrays can be connected in series, that is, the interface Y of the upper-level enrichment column array is connected to the interface X of the secondary enrichment column array to form a multi-stage enrichment column array. The operation control is the same as that of the single-stage enrichment column array. Only one enrichment column can be turned on at the same time; when the multi-stage enrichment column array is in the bypass conduction state, the enrichment column array in each stage is in bypass conduction.

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the ten-position valve is connected; the ⑩ position of the two-position ten-port valve is connected to the interface X of the enrichment column array A, and the interface Y of the enrichment column array A is connected to the ⑦ position of the two-position ten-port valve; The position ⑥ of the two-position ten-way valve is connected to the inlet of the liquid chromatography separation column array. The outlet of the liquid chromatography separation column array is connected to the detector. The outlet of the detector is connected to the inlet of the gradient mixer B. The outlet is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the ⑧ position of the two-position ten-port valve; the ⑨ position of the two-position ten-port valve is connected to the ④ position; The number is connected to the Y interface of the enrichment column array B, and the X interface of the enrichment column array B is connected to the number ② of the two-position ten-way valve; the number ③ of the two-position ten-way valve is connected to the inlet of the fraction collector .

Based on the above-mentioned multi-dimensional liquid chromatography separation system's pipeline connection mode, by controlling the switching state of the two-position ten-way valve, the system is switched from the previous one-dimensional separation state to the next one-dimensional separation state, completing the cycle chromatography function, and achieving multi-dimensional full online Detection of chromatographic separation functions.

Due to the shortcomings of the existing technology, for example: Chinese patent application CN108037233A discloses a multi-dimensional liquid chromatography separation system based on the same detector for full online detection, which can realize the measurement and control of the entire separation process, and the cleanliness of the enrichment column and the separation column. Can be detected, suitable for difficult and repeated analysis, separation and preparation of complex sample systems, and facilitate the efficient preparation of monomer compounds. The system is a serial mode multidimensional liquid chromatography system. However, the system is based on a two-position ten-port valve. Due to the asymmetric flow path of the two-position ten-port valve, the application performance of the system is affected to some extent. The structure of device B is now proposed:

Corresponding to device B, a multi-dimensional liquid chromatography separation system based on double two-position four-way valves. A two-dimensional four-way valve with symmetrical flow paths is used to construct a multi-dimensional liquid chromatography separation system, which makes the flow paths completely symmetrical, providing more Good chromatographic separation and analysis ability.

A multi-dimensional liquid chromatography separation system includes a high-performance liquid chromatography gradient pump A, a high-performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array A, Enrichment column array B, fraction collector, liquid chromatography separation column array, detector, double two-position four-way valve, and connecting pipeline. The ①, ②, ③, ④, ⑤, ⑥, ⑦, and ⑧ positions of the double two-position four-way valve only indicate positional adjacency, and do not necessarily correspond to the physical marks of the double two-way four-way valve. . The detector is used for detecting a chromatographic signal in a separation process.

The enrichment column array A is formed by connecting a plurality of chromatographic enrichment columns in parallel through a multi-position selection valve, and at the same time, only one enrichment column can be conducted; at least one bypass, the bypass and the enrichment column pass through. The multi-position selector valve is connected in parallel; when the bypass is on, the other enrichment columns will not be on, and when the other enrichment columns are on, the bypass will not be on; there are two external interfaces, which are defined as interface X and interface Y. One is used as the inlet and the other as the outlet; the number of enrichment columns is determined according to the needs, which is mainly limited by the length of the pipeline and the installation space. Multiple enrichment column arrays can be connected in series, that is, the interface Y of the upper-level enrichment column array is connected to the interface X of the secondary enrichment column array to form a multi-stage enrichment column array. The operation control is the same as that of the single-stage enrichment column array. Only one enrichment column can be turned on at the same time; when the multi-stage enrichment column array is in the bypass conduction state, the enrichment column array in each stage is in bypass conduction.

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the injection valve, and the outlet of the injection valve and the double The ① position of the two-position four-way valve is connected; the ④ position of the two-position four-way valve is connected to the interface X of the enrichment column array A, and the interface Y of the enrichment column array A is connected to the ⑦ number of the two-position four-way valve. Position connection; the ⑧ position of the double two-position four-way valve is connected to the inlet of the liquid chromatography separation column array, the outlet of the liquid chromatography separation column array is connected to the detector, the outlet of the detector is connected to the inlet of the gradient mixer B, The outlet of the diluent pump is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the ③ position of the double two-position four-way valve; the ② position of the double two-position four-way valve is connected to the enrichment column array B. The Y interface is connected, and the X interface of the enrichment column array B is connected to the position ⑤ of the double two-position four-way valve; the position ⑥ of the double two-position four-way valve is connected to the inlet of the fraction collector.

Based on the above-mentioned multi-dimensional liquid chromatography separation system's pipeline connection mode, the system switches from the previous one-dimensional separation state to the next-dimensional separation state by controlling the switching state of the double two-position four-way valve, completing the cyclic chromatography separation function, and achieving multi-dimensional Fully online chromatographic separation.

Due to the shortcomings of the prior art, for example, Chinese patent application CN105938130A discloses a two-dimensional liquid chromatography separation system based on a two-position eight-way valve, which belongs to a serial mode multidimensional liquid chromatography system. This system has only two-dimensional chromatographic separation capabilities, and cannot fully meet the needs of difficult repeated analysis, separation, and preparation of complex sample systems. The structure of device C is now proposed:

Corresponding to device C, a multi-dimensional liquid chromatography separation system based on a two-position eight-way valve, which has three-dimensional or higher chromatographic separation capabilities.

A multi-dimensional liquid chromatography separation system includes a high-performance liquid chromatography gradient pump A, a high-performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array A, Enrichment column array B, fraction collector, liquid chromatography separation column array, detector, two-position eight-way valve, and connecting lines. The

positions

①, ②, ③, ④, ⑤, ⑥, ⑦, and ⑧ of the two-position eight-way valve only indicate positional adjacency, and do not necessarily correspond to the physical marks of the two-position eight-way valve. Nomenclature is named and sorted from any interface of the two-position eight-way valve, and named according to counterclockwise or clockwise from ①. The detector is used for detecting a chromatographic signal in a separation process.

The enrichment column array B is formed by multiple chromatographic enrichment columns connected in parallel through a multi-position selection valve, and only one enrichment column can be connected at the same time; at least one bypass, the bypass and the enrichment column Multi-position selector valves are connected in parallel; the enrichment column will not be conductive when the bypass is on, and the bypass will not be conductive when the enrichment column is on; there are two external interfaces, which are defined as interface X and interface Y, One is used as the inlet and the other as the outlet; the number of enrichment columns is determined according to the needs, which is mainly limited by the length of the pipeline and the installation space. Multiple enrichment column arrays can be connected in series, that is, the interface Y of the upper-level enrichment column array is connected to the interface X of the secondary enrichment column array to form a multi-stage enrichment column array. The operation control is the same as that of the single-stage enrichment column array. Only one enrichment column can be turned on at the same time; when the multi-stage enrichment column array is in the bypass conduction state, the enrichment column array in each stage is in bypass conduction.

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the eight-position valve is connected; the ② position of the two-position eight-way valve is connected to the interface X of the enrichment column array B, and the interface Y of the enrichment column array B is connected to the ⑥ position of the two-position eight-way valve; The position ⑤ of the two-position eight-way valve is connected to the inlet of the liquid chromatography separation column array. The outlet of the liquid chromatography separation column array is connected to the detector. The outlet of the detector is connected to the inlet of the gradient mixer B. The outlet is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the ⑦ position of the two-position eight-way valve; the ⑧ position of the two-position eight-way valve is connected to the X interface of the enrichment column array A to enrich The Y interface of column array A is connected to the ④ position of the two-position eight-way valve; the ③ position of the two-position eight-way valve is connected to the inlet of the fraction collector.

Based on the pipeline connection method of the above-mentioned multi-dimensional liquid chromatography separation system, by controlling the switching state of the two-position eight-way valve, the system is switched from the previous one-dimensional separation state to the next-dimensional separation state, completing the cyclic chromatography separation function, and realizing the multi-dimensional full-scale Chromatographic separation function for online detection.

Due to the shortcomings of the prior art, for example: Chinese patent application CN108037233A discloses a multi-dimensional liquid chromatography separation system based on the same detector for full-line detection. This system cannot reversely elute after the sample is pretreated. Structure of device D:

Corresponding to device D, a three-dimensional chromatographic separation system based on a two-position ten-way valve. In view of the characteristics of the long time consuming and mobile phase consumption of the existing multidimensional liquid chromatography separation system, the existing multidimensional liquid chromatography separation is retained. Based on the advantages of the system, it reduces the separation time and mobile phase consumption of the multi-dimensional liquid chromatography separation system, and provides an automated high-performance liquid chromatography separation system from sample pretreatment to sample separation to sample analysis.

A three-dimensional liquid chromatography separation system comprising a high-performance liquid chromatography gradient pump A, a high-performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array A, Enrichment column array B, fraction collector, liquid chromatography separation column array, detector, two-position ten-way valve, and connecting pipeline. The ① position, ② position, ③ position, ④ position, ⑤ position, ⑥ position, ⑦ position, ⑧ position, ⑨ position, and ⑩ position of the two-position ten-way valve only indicate the positional adjacency relationship. Corresponding to the physical mark, its number is named and sorted from the arbitrary interface of the two-position ten-way valve, and named according to counterclockwise or clockwise from ①. The detector is used for detecting a chromatographic signal in a separation process.

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the ten-position valve is connected; the ⑩ position of the two-position ten-way valve is connected to the interface X of the enrichment column array B, and the interface Y of the enrichment column array B is connected to the ③ position of the two-position ten-way valve; The ② position of the two-position ten-way valve is connected to the ⑦ position of the two-position ten-way valve; the ⑥ position of the two-position ten-way valve is connected to the inlet of the liquid chromatography separation column array, and the outlet of the liquid chromatography separation column array is connected to The detector is connected, the outlet of the detector is connected to the inlet of the gradient mixer B, the outlet of the diluent pump is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the ④ position of the two-position ten-way valve; The ⑤ position of the ten-position valve is connected to the Y interface of the enrichment column array A, and the X interface of the enrichment column array A is connected to the ⑧ position of the two-position ten-port valve; The inlet of the share collector is connected.

Based on the pipeline connection method of the above three-dimensional liquid chromatography separation system, by controlling the switching state of the two-position ten-way valve, the system is switched from the previous one-dimensional separation state to the next one-dimensional separation state, and the cycle chromatography function is completed to realize three-dimensional full online. Detection of chromatographic separation functions.

Due to the shortcomings of the prior art, for example, Chinese patent application CN109541090A discloses a multi-dimensional liquid chromatography separation system based on a two-position, two-position, four-way valve. Elution function, the structure of device E is now proposed:

Corresponding to device E, a multi-dimensional liquid chromatography separation system based on a two-two-position four-way valve, which retains the multi-dimensional liquid chromatography separation capability of a two-dimensional four-way valve based on a multi-dimensional liquid chromatography separation system, so that it has The reverse elution function of the enrichment column can save its separation time and mobile phase to a certain extent.

The enrichment column array A is formed by connecting a plurality of chromatographic enrichment columns in parallel through a multi-position selection valve, and at the same time, only one enrichment column can be conducted; at least one bypass, the bypass and the enrichment column pass through. The multi-position selector valve is connected in parallel; when the bypass is on, the other enrichment columns will not be on, and when the other enrichment columns are on, the bypass will not be on; there are two external interfaces, which are defined as interface X and interface Y. ; The number of enrichment columns depends on the needs, and is mainly limited by the length of the pipeline and the installation space. Multiple enrichment column arrays can be connected in series, that is, the interface Y of the upper-level enrichment column array is connected to the interface X of the secondary enrichment column array to form a multi-stage enrichment column array. The operation control is the same as that of the single-stage enrichment column array. Only one enrichment column can be turned on at the same time; when the multi-stage enrichment column array is in the bypass conduction state, the enrichment column array in each stage is in bypass conduction.

The enrichment column array B is formed by connecting a plurality of chromatographic enrichment columns in parallel through a multi-position selection valve, and at the same time, only one enrichment column can be turned on; at least one bypass can pass through the enrichment column and the enrichment column. The multi-position selector valve is connected in parallel; when the bypass is on, the other enrichment columns will not be on, and when the other enrichment columns are on, the bypass will not be on; there are two external interfaces, which are defined as interface X and interface Y. ; The number of enrichment columns depends on the needs, and is mainly limited by the length of the pipeline and the installation space. Multiple enrichment column arrays can be connected in series, that is, the interface Y of the upper-level enrichment column array is connected to the interface X of the secondary enrichment column array to form a multi-stage enrichment column array. The operation control is the same as that of the single-stage enrichment column array. Only one enrichment column can be turned on at the same time; when the multi-stage enrichment column array is in the bypass conduction state, the enrichment column array in each stage is in bypass conduction.

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the injection valve, and the outlet of the injection valve is double-digit The ① position of the four-way valve is connected; the ④ position of the double two-position four-way valve is connected to the interface X of the enrichment column array A, and the interface Y of the enrichment column array A is connected to the ⑦ position of the double two-position four-way valve. ; The ⑧ position of the double two-position four-way valve is connected to the inlet of the liquid chromatography separation column array, the outlet of the liquid chromatography separation column array is connected to the detector, the outlet of the detector is connected to the inlet of the gradient mixer B, and the diluent The pump is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the ⑥ position of the double two-position four-way valve; the ⑤ position of the double two-position four-way valve is connected to the interface X of the enrichment column array B, The interface Y of the enrichment column array B is connected to the position ② of the double two-position four-way valve; the position ③ of the double two-position four-way valve is connected to the inlet of the fraction collector.

Due to the shortcomings of the prior art, for example: Chinese patent application CN109655561A discloses a multi-dimensional liquid chromatography separation system based on a two-position ten-port valve. The system has only the reverse elution function of the enrichment column and no forward direction of the enrichment column. Elution function, the structure of device F is now proposed:

Corresponding to device F, a multi-dimensional liquid chromatography separation system based on a two-position ten-way valve is designed to solve the reverse elution of the enrichment column in some cases. It needs to be quickly changed to the forward elution of the enrichment column in the field. Provide a multi-dimensional liquid chromatography separation system with low cost and convenient to quickly switch the elution direction of the enrichment column.

A multi-dimensional liquid chromatography separation system includes a high-performance liquid chromatography gradient pump A, a high-performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array A, Enrichment column array B, fraction collector, liquid chromatography separation column array, detector, two-position ten-way valve, and connecting pipeline. The ① position, ② position, ③ position, ④ position, ⑤ position, ⑥ position, ⑦ position, ⑩ position, ⑨ position, ⑩ position of the two-position ten-way valve only indicate an adjacency relationship, and need not be related to the two-position ten-way valve. Corresponding to the physical mark, the number is named and sorted from any interface of the two-position ten-way valve, and named according to counterclockwise or clockwise from ①. The detector is used for detecting a chromatographic signal in a separation process.

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the ten-position valve is connected, the ⑩ position of the two-position ten-way valve is connected to the interface X of the enrichment column array B, and the interface Y of the enrichment column array B is connected to the ③ position of the two-position ten-way valve. The ② position of the two-position ten-way valve is connected to the ⑦ position, the ⑥ position of the two-position ten-way valve is connected to the inlet of the liquid chromatography separation column array, and the outlet of the liquid chromatography separation column array is connected to the detector. The outlet of is connected to the inlet of the gradient mixer B, the outlet of the diluent pump is connected to the inlet of the gradient mixer B, the outlet of the gradient mixer B is connected to the 两位 position of the two-position ten-way valve, and the 两位 of the two-position ten-way valve The number position is connected to the X interface of the enrichment column array A, the Y interface of the enrichment column array A is connected to the position ⑤ of the two-position ten-way valve, and the position ④ of the two-position ten-way valve is connected to the inlet of the fraction collector .

Based on the above-mentioned multi-dimensional liquid chromatography separation system's pipeline connection mode, by controlling the switching state of the two-position ten-way valve, the system is switched from the previous one-dimensional separation state to the next one-dimensional separation state, completing the cycle chromatography function, and achieving multi-dimensional full online. Detection of chromatographic separation functions.

Due to the shortcomings of the prior art, for example, Chinese patent application CN105938130A discloses a two-dimensional liquid chromatography separation system based on a two-position eight-way valve, which belongs to a serial mode multidimensional liquid chromatography system. This system has only two-dimensional chromatographic separation capabilities, and cannot fully meet the needs of difficult and difficult repeated analysis, separation, and preparation of complex sample systems. The structure of device H is now proposed:

Corresponding to the device H, a multi-dimensional liquid chromatography separation system based on a two-position eight-way valve, and a multi-dimensional liquid chromatography separation system based on a two-position eight-way valve, to meet the needs of three-dimensional or higher chromatographic separation.

positions

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the eight-position valve is connected, the ⑧ position of the two-position eight-way valve is connected to the interface X of the enrichment column array B, and the interface Y of the enrichment column array B is connected to the ④ position of the two-position eight-way valve; The position ⑤ of the two-position eight-way valve is connected to the inlet of the liquid chromatography separation column array. The outlet of the liquid chromatography separation column array is connected to the detector. The outlet of the detector is connected to the inlet of the gradient mixer B. The outlet is connected to the inlet of the gradient mixer B. The outlet of the gradient mixer B is connected to the ③ position of the two-position eight-way valve, and the ② position of the two-position eight-way valve is connected to the X interface of the enrichment column array A to enrich. The Y interface of the column array A is connected to the ⑥ position of the two-position eight-way valve, and the ⑦ position of the two-position eight-way valve is connected to the inlet of the fraction collector.

Due to the shortcomings of the prior art, such as: CN108037233A, CN109557219A, CN109655561A, CN109557221A, CN109541090A, the injection valves in the above patents are connected before the enrichment column array or in the bypass of the enrichment column array. The structure of the device H is now proposed :

Corresponding to device I, a multi-dimensional liquid chromatography separation system based on a two-position multi-port valve is a multi-dimensional liquid chromatography separation system in which the injection valve is connected to the enrichment column array and before the liquid chromatography separation column array. Chromatographic separation above 3D is required.

A multi-dimensional liquid chromatography separation system, characterized in that the multi-dimensional liquid chromatography separation system includes a high-performance liquid chromatography gradient pump A, a high-performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, and gradient mixing. Detector B, injection valve, enrichment column array A, enrichment column array B, fraction collector, liquid chromatography separation column array, detector, two-position multi-port valve, and connecting pipeline; the detector is used for detection Chromatographic signal during separation; the injection valve is used for injection.

The liquid chromatography separation column array is formed by connecting multiple chromatographic separation columns in parallel, and only one chromatographic separation column can be connected at a time; a fixed inlet and a fixed outlet are provided to the outside, and at least one bypass is provided. The bypass and the separation column are connected in parallel; the chromatographic separation column will not be conductive when the bypass is on, and the bypass will not be conductive when the chromatographic separation column is on; the number of chromatographic separation columns is determined as required.

The enrichment column array A is formed by connecting a plurality of chromatographic enrichment columns in parallel, and at the same time only one enrichment column can be turned on; at least one bypass, the bypass and the enrichment column are connected in parallel; when the bypass When conducting, the enrichment column will not be able to conduct, and when the enrichment column is conducting, the bypass will not be able to conduct; the number of enrichment columns is determined as needed; there are two external interfaces, which are defined as interface X and interface Y, of which One as an entrance and the other as an exit.

The enrichment column array B is formed by connecting a plurality of chromatographic enrichment columns in parallel, and only one enrichment column can be turned on at the same time; at least one bypass is connected in parallel with the enrichment column; When conducting, the enrichment column will not be able to conduct, and when the enrichment column is conducting, the bypass will not be able to conduct; the number of enrichment columns is determined as needed; there are two external interfaces, which are defined as interface X and interface Y, of which One as an entrance and the other as an exit.

The inlet of the sampling valve is connected to one port of a two-position multi-port valve, the outlet of the sampling valve is connected to the inlet of a liquid chromatography separation column array, and the outlet of the liquid chromatography separation column array is connected to an inlet of a detector to detect The outlet of the mixer is connected to the inlet of the gradient mixer B, the outlet of the diluent pump is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the other port of the two-position multi-way valve.

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, and the outlet of the gradient mixer A is connected to one port of a two-position multi-port valve; an enrichment column array The interface X of B is connected to one port of the two-position multiport valve, and the interface Y of the enrichment column array B is connected to the other port of the two-position multiport valve; the X interface of the enrichment column array A is connected to the two-port multiport valve. One port is connected, and the Y port of the enrichment column array A is connected to the other port of the two-position multi-port valve; the inlet of the fraction collector is connected to one port of the two-position multi-port valve.

By controlling the state switching of the two-position multi-way valve, the system is switched from the previous one-dimensional separation state to the next one-dimensional separation state, completes the cyclic chromatography function, and realizes the chromatographic separation function of multidimensional full-line detection.

Due to the shortcomings of the prior art, for example: Chinese patent application CN104713973A discloses a two-dimensional preparative chromatographic instrument system with online enrichment function and its application. The detector of this system is connected to the enrichment column array and then enriches the column. The switching is not performed under the real-time guidance of the chromatographic signal. The establishment of a chromatographic separation method is more complicated. The structure of the device J is now proposed:

Corresponding to device J, a multi-dimensional liquid chromatography separation system based on a two-position six-way valve is based on a two-position six-way valve, an enrichment column array, and a separation column array. Multi-dimensional liquid chromatography separation system with enrichment column switching to meet the needs of three-dimensional or higher chromatographic separation.

A multi-dimensional liquid chromatography separation system includes a high performance liquid chromatography gradient pump A, a high performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array, and a distillation column. Fraction collector, liquid chromatography separation column array, detector, two-position six-way valve, and connecting pipeline; the two-position six-way valve ① position, ② position, ③ position, ④ position, ⑤ position, ⑥ position are only Represents the positional adjacency relationship, which does not need to correspond to the physical mark of the two-position six-way valve. Its number is named and sorted from any interface of the two-position six-way valve, and named according to counterclockwise or clockwise from ①; the detector is used For detecting a chromatographic signal during a separation process; the sampling valve is used for sampling;

The liquid chromatography separation column array is formed by connecting a plurality of chromatographic separation columns in parallel, and only one chromatographic separation column can be turned on at the same time; at least one bypass is connected in parallel with the separation column; when the bypass is turned on When the chromatographic separation column is conductive, the bypass will not be conductive; a fixed inlet and a fixed outlet are provided to the outside;

The enrichment column array is formed by connecting a plurality of chromatographic enrichment columns in parallel, and only one enrichment column can be turned on at the same time; at least one bypass is connected in parallel with the enrichment column; The enrichment column will not be able to conduct when it is connected. When the enrichment column is conducting, the bypass will not be able to conduct. There are two external interfaces, which are defined as interface X and interface Y, one of which is used as the inlet and the other as the outlet;

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the six-position valve is connected, and the ⑥ position of the two-position six-way valve is connected to the inlet of the LC separation column array. The outlet of the LC separation column array is connected to the detector, and the outlet of the detector is mixed with the gradient. The inlet of the diluent pump is connected to the inlet of the gradient mixer B. The outlet of the gradient mixer B is connected to the ④ position of the two-position six-way valve, and the ⑤ position of the two-position six-way valve is to be enriched. The interface Y of the column array is connected, the interface X of the enriched column array is connected to the position ② of the two-position six-way valve, and the position ③ of the two-position six-way valve is connected to the inlet of the fraction collector. In this pipeline-connected system, the enrichment and elution directions of the enrichment columns are opposite. Called reverse elution, it can save a certain amount of mobile phase and separation time.

In the above-mentioned multi-dimensional liquid chromatography separation system, the outlet of the gradient mixer B can also be connected to the position ③ of the two-position six-way valve. At this time, the position ④ of the two-position six-way valve and the inlet of the fraction collector Connection, other connection lines remain unchanged. The enrichment and elution directions of the enrichment column in this pipeline-connected system are consistent, and they are called forward elution.

Based on the pipeline connection mode of the above multi-dimensional liquid chromatography separation system, by controlling the switching state of the two-position six-way valve, the system can be loaded and separated, the circulation chromatography separation function can be completed, and the multi-dimensional full-line detection chromatography function can be realized.

Corresponding to device A or D or F, the injection valve in the above multi-dimensional liquid chromatography separation system can also be connected to the bypass of enrichment column array A or enrichment column array B, or connected to enrichment column array A Or the connection line between the enrichment column array B and the two-position ten-port valve; at this time, the outlet of the gradient mixer A is connected to the position ① of the two-position ten-port valve; the above connection changes do not affect the use of the system, only Redefine the dimensions of the enrichment column during control.

Corresponding to device B or E, the injection valve in the above multi-dimensional liquid chromatography separation system can also be connected to the bypass of enrichment column array A or enrichment column array B, or connected to enrichment column array A or rich In the connecting pipeline between the column array B and the double two-way four-way valve; at this time, the outlet of the gradient mixer A is connected to the number ① of the double two-way four-way valve; the above connection changes do not affect the use of the system, but only in the Redefine the dimensions of the enrichment column during control.

Corresponding to the device C or H, the injection valve in the above-mentioned multi-dimensional liquid chromatography separation system may also be connected to the bypass of the enrichment column array A or the enrichment column array B, or connected to the enrichment column array A or the enrichment column. In the connecting pipeline between the column array B and the two-position eight-way valve; at this time, the outlet of the gradient mixer A is connected to the position ① of the two-position eight-way valve; the above connection changes do not affect the use of the system, but only during control Redefine the dimensions of the enrichment column.

Corresponding to device A or B or C or D or E or F or H, the enrichment column array may be composed of a plurality of enrichment column arrays in series to form a multi-stage enrichment column array, and the operation control is the same as that of a single-stage enrichment column array. Only one enrichment column can be turned on at the same time; when the multi-stage enrichment column array is in the bypass conduction state, the enrichment column array in each stage is in bypass conduction.

Corresponding to device A or D or F, the two-position ten-port valve is a valve or consists of multiple valves, and operates according to the principle of two-position ten-port valve switching valve.

Corresponding to the device B or E, the double two-position four-way valve is a valve or composed of multiple valves, and operates according to the principle of the double two-position four-way valve switching valve;

Corresponding to the device C or H, the two-position eight-way valve is a valve or composed of multiple valves, and operates according to the principle of the two-position eight-way valve switching valve;

Corresponding to device I, the two-position multi-port valve includes two-position ten-port valves, two-position eight-port valves or double two-position four-port valves, and includes a plurality of valves and Valves that operate on a one-way or two-position four-way valve principle.

Corresponding to device J, the injection valve in the multi-dimensional liquid chromatography separation system can also be connected in the bypass of the enrichment column array, or in the connection line between the enrichment column array and the two-position six-way valve, or Between the six position of the two-position six-way valve and the inlet of the liquid chromatography separation column array.

The sampling valve is a sampling device, which may be a two-position six-port switching sampling valve, or an injector; it may be another multi-position switching sampling valve for liquid or solid state loading; or it may be an implementation Column for solid loading.

The high-performance liquid chromatography gradient pump A and the high-performance liquid chromatography gradient pump B both consist of one or two or more unit pumps, or one or two or more multivariate gradient pumps. The diluent pump is a high-performance liquid diluent pump, a unit pump, or a multi-component pump. In the HPLC gradient pump A, the HPLC gradient pump B, and the diluent pump, the diluent may be water, salt solution, methanol, acetonitrile, acetone, ethanol, or n-alkane solvent, and the eluent may be Common solvents include methanol, acetonitrile, ethanol, water and mixtures thereof, and normal paraffins.

The detectors are various devices for detecting chromatographic signals in the separation process, including but not limited to ultraviolet detectors, diode array detectors, evaporative light scattering detectors, or mass spectrometer detectors, which can be one detector or composed of multiple detectors. The detector is a joint detection system.

The chromatographic columns of the separation column array, the enrichment column array A, and the enrichment column array B may use the same or different packing materials. The packing materials may be silica gel, with reverse phase of C18, Xion, C8, CN group or amino group. Silica gel matrix fillers or various macroporous adsorption resins and ion exchange resins.

The multi-position selector valve has a common inlet and a common outlet. The other interfaces of the multi-position selector valve are connected to the two ends of the flow path to be conducted in pairs. The common inlet and common outlet of the multi-position selection valve are connected to one or more flows. The multi-position selection valve can be connected to one column or multiple columns. At the same time, one column is selected to be connected or all of them are not connected. There are two external interfaces, one as an outlet and one as an outlet. Entrance. The multi-position selection switching valve is only an implementation form of a column array; when one column in a column array column is conducting, the other columns in the column array and the bypass will not be conducting, and when the column array bypass is conducting, the The other pillars in the pillar array are not conducting. Two-position four-way valve is a form of multi-position selection valve.

The gradient mixer B may be replaced with a tee fitting.

The present invention retains the advantages of the existing multidimensional liquid chromatography technology. Compared with the existing multidimensional liquid chromatography technology, the innovation and beneficial effects of the present invention are:

Corresponding to devices A, B, C, D, E, F, H, I, J, it can realize full online sample processing and sample separation, and sample enrichment and recovery; each dimension liquid chromatography separation process is independent, which can maximize the improvement Resolution of complex sample separation; By providing three-dimensional or higher liquid chromatography separation capabilities, the resolution of complex sample separation can be further improved; in each dimension separation process, multiple loading, separation and enrichment can be performed, and the target components are Enriched in the enrichment column, which can increase the sample loading amount for the next dimension separation, effectively avoid the problem of sample volume overload and solvent effect, the column efficiency loss is small, and the multi-dimensional separation effect is guaranteed; the one-dimensional liquid chromatography separation method can directly adopt one-dimensional The traditional liquid chromatography method is easy to operate and use, and is convenient for the rapid separation of monomer compounds. If the enrichment column in the enrichment column array is replaced with a chromatographic separation column, a dynamically switchable multi-column tandem chromatography guided by the chromatographic signal can be realized Separation.

Corresponding to devices A and D, the inlet and outlet of the enrichment column array are not fixed. When the enrichment column is used as the loading column, the flow direction of the eluent is opposite to that of the mobile phase when the sample was originally enriched, and Samples are generally concentrated near the entrance of the enrichment column, so less mobile phase and less time are required to complete the elution and loading of the sample in the enrichment column, which reduces the total separation time and improves the separation efficiency. Can be reverse eluted during sample pretreatment.

Corresponding to devices B and E, a two-dimensional four-way valve with symmetrical flow paths is used to construct a multi-dimensional liquid chromatography separation system, which makes the flow path of the multi-dimensional liquid chromatography separation system completely symmetrical, and provides better chromatographic separation and analysis capabilities. Flexible and convenient. Corresponding to device E, the inlet and outlet of the enrichment column array are not fixed. When the enrichment column is used as the loading column, the flow direction of the eluent is opposite to that of the mobile phase when the sample was originally enriched, and the sample is generally Enrichment is near the entrance of the enrichment column, so it takes less mobile phase and less time to load the sample from the enrichment column.

Corresponds to device C, retains the advantages of the original two-dimensional liquid chromatography separation system based on the two-position eight-way valve, and improves the chromatographic separation capability of the two-dimensional liquid chromatography separation system based on the two-position eight-way valve to three-dimensional or more High-dimensional, more widely used.

Corresponding to device F, there is no need to increase the cost of the flow direction switching valve, etc., and it is used in conjunction with the system structure in Chinese patent application CN109655561A, and only changes the ⑨ number on the two-position ten-way valve in the multi-dimensional liquid chromatography separation system provided by the present invention. The connection of the two ports with position ④ can change the elution method of the enrichment column array A and the enrichment column array B, which is convenient to meet various needs in practical applications.

Corresponding to device H, a multi-dimensional liquid chromatography separation system based on a two-position eight-way valve can perform three-dimensional or higher chromatographic separation; when a two-dimensional ten-way valve based multi-dimensional liquid chromatography separation system cannot meet the needs, based on this The invention can construct a multidimensional liquid chromatography separation system which can meet the needs of chromatographic separation at low cost.

Corresponding to device I, the inlet of the sampling valve is connected to one port of a two-position multi-port valve, the outlet of the sampling valve is connected to the inlet of a liquid chromatography separation column array, and the outlet of the liquid chromatography separation column array is connected to a detector. Based on the above connection, a cyclic serial multi-dimensional liquid chromatography separation system that can meet the needs of chromatographic separation can be constructed at low cost.

Corresponding to device J, a multi-dimensional liquid chromatography separation system based on a two-position six-way valve, an enrichment column array, and a separation column array can switch the enrichment column under the real-time guidance of the chromatographic signal, and accurately control the three-dimensional or Chromatographic separation process above 3D and multidimensional chromatography separation method development is simple and easy.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. A1 is a pipeline connection structure diagram of the first-dimensional and third-dimensional odd-dimensional separation states of the multi-dimensional liquid chromatography separation system provided by the device A of the present invention, and the two-position ten-way valve is in the A state;

FIG. A2 is a pipeline connection structure diagram of the even-dimensional separation state of the second and fourth dimensions of the multi-dimensional liquid chromatography separation system provided by the device A of the present invention, and the two-position ten-way valve is in the B state;

Figure A3 is a pipeline connection structure diagram of the liquid chromatography separation column array of device A;

Figure A4 is a pipeline connection structure diagram of the enrichment column array A and the enrichment column array B of the device A;

Figure A5 (a) is the pipe connection structure of the sample loading state (LOAD state, A state) of the two-position six-port injection valve of device A. In this state, the sample is loaded into the quantitative loop, where number ④ is defined as the injection The inlet of the valve, position ⑤ is defined as the outlet of the injection valve;

Figure A5 (b) is the pipeline connection structure of the sample loading state (INJECT state, B state) of the two-position six-port injection valve of device A. In this state, the sample will be injected from the quantitative loop into the flow path of the separation system for separation. Number ④ is defined as the inlet of the injection valve, and ⑤ is defined as the outlet of the injection valve;

FIG. A6 (a) is a structural diagram of a multi-dimensional high-performance liquid chromatography separation system according to an embodiment of the device A of the present invention, and the two-position ten-way valve is in the A state;

In Figure A6 (a): 1 HPLC gradient pump A, 2 HPLC gradient pump B, 3 diluent pump, 4 gradient mixer A, 5 gradient mixer B, 6 injection valve, 7 enrichment Column array A, 8 enrichment column array B, 9 fraction collector, 10 liquid chromatography separation column array, 11 detectors, 12 two-position ten-way valve;

FIG. A6 (b) is a structural diagram of a multi-dimensional high performance liquid chromatography separation system according to an embodiment of the device A of the present invention, and the two-position ten-way valve is in a B state.

FIG. B1 is a connection structure diagram of the first-dimensional, third-dimensional and other odd-dimensional separation states of the multi-dimensional liquid chromatography separation system provided by the device B of the present invention, and the double two-position four-way valve is in the A state;

FIG. B2 is a pipeline connection structure diagram of the even-dimensional separation state of the second and fourth dimensions of the multi-dimensional liquid chromatography separation system provided by the device B of the present invention, and the double two-position four-way valve is in a B state;

Figure B3 is a pipeline connection structure diagram of the liquid chromatography separation column array of device B;

Figure B4 is a pipeline connection structure diagram of the enrichment column array A and the enrichment column array B of the device B;

Figure B5 (a) is the pipeline connection structure of the sample loading state (LOAD state, A state) of the two-position six-port injection valve of device B. In this state, the sample is loaded into the quantitative loop, where number ④ is defined as the injection The inlet of the valve, position ⑤ is defined as the outlet of the injection valve;

Figure B5 (b) is the pipe connection structure of the sample loading state (INJECT state, state B) of the two-position six-port injection valve of device B. In this state, the sample will be injected from the quantitative loop into the separation system flow path for separation. Number ④ is defined as the inlet of the injection valve, and ⑤ is defined as the outlet of the injection valve;

FIG. B6 (a) is a structural diagram of a multi-dimensional high-performance liquid chromatography separation system according to an embodiment of the device B of the present invention, and the double two-position four-way valve is in the A state;

In Figure B6 (a): 1 HPLC gradient pump A, 2 HPLC gradient pump B, 3 diluent pump, 4 gradient mixer A, 5 gradient mixer B, 6 injection valve, 7 enrichment Column array A, 8 enrichment column array B, 9 fraction collector, 10 liquid chromatography separation column array, 11 detectors, 12 double two-position four-way valves;

FIG. B6 (b) is a structural diagram of a multi-dimensional high-performance liquid chromatography separation system according to an embodiment of the apparatus B of the present invention, and the double two-position four-way valve is in a B state.

FIG. C1 is a pipeline connection structure diagram of the first-dimensional and third-dimensional odd-dimensional separation states of the multidimensional liquid chromatography separation system provided by the device C of the present invention, and the two-position eight-way valve is in the A state;

FIG. C2 is a pipeline connection structure diagram of the even-dimensional separation state of the second and fourth dimensions of the multi-dimensional liquid chromatography separation system provided by the device C of the present invention, and the two-position eight-way valve is in a B state;

Figure C3 is a pipeline connection structure diagram of the liquid chromatography separation column array of device C;

Figure C4 is a pipeline connection structure diagram of the enrichment column array A and the enrichment column array B of the device C;

Figure C5 (a) is the pipeline connection structure of the sample loading state (LOAD state, A state) of the two-position six-port injection valve of device C. In this state, the sample is loaded into the quantitative loop, where number ④ is defined as the injection The inlet of the valve, position ⑤ is defined as the outlet of the injection valve;

Figure C5 (b) is the pipe connection structure of the sample loading state (INJECT state, B state) of the two-position six-port injection valve of device C. In this state, the sample will be injected from the quantitative loop into the flow path of the separation system for separation. Number ④ is defined as the inlet of the injection valve, and ⑤ is defined as the outlet of the injection valve;

FIG. C6 (a) is a structural diagram of a multi-dimensional high-performance liquid chromatography separation system according to an embodiment C of the device of the present invention, and the two-position eight-way valve is in the A state;

In Figure C6 (a): 1 HPLC gradient pump A, 2 HPLC gradient pump B, 3 diluent pump, 4 gradient mixer A, 5 gradient mixer B, 6 injection valve, 7 enrichment Column array A, 8 enrichment column array B, 9 fraction collector, 10 liquid chromatography separation column array, 11 detectors, 12 two-position eight-way valve;

FIG. C6 (b) is a structural diagram of a multi-dimensional high performance liquid chromatography separation system according to an embodiment C of the device of the present invention, and the two-position eight-way valve is in a B state.

FIG. D1 is a pipeline connection structure diagram of the first-dimensional and third-dimensional odd-dimensional separation states of the three-dimensional liquid chromatography separation system provided by the device D of the present invention, and the two-position ten-way valve is in the A state;

FIG. D2 is a pipeline connection structure diagram of the second-dimensional and even-dimensional separation state of the three-dimensional liquid chromatography separation system provided by the device D of the present invention, and the two-position ten-way valve is in a B state;

Figure D3 is a pipeline connection structure diagram of the liquid chromatography separation column array of device D;

Figure D4 is a pipeline connection structure diagram of the enrichment column array A and the enrichment column array B of the device D;

Figure D5 (a) is the pipe connection structure of the sample loading state (LOAD state, A state) of the two-position six-port injection valve of device D. In this state, the sample is loaded into the quantitative loop, where number ④ is defined as the injection The inlet of the valve, position ⑤ is defined as the outlet of the injection valve;

Figure D5 (b) is the pipe connection structure of the sample loading state (INJECT state, B state) of the two-position six-port injection valve of device D. In this state, the sample will be injected from the quantitative loop into the flow path of the separation system for separation. Number ④ is defined as the inlet of the injection valve, and ⑤ is defined as the outlet of the injection valve;

FIG. D6 (a) is a structural diagram of a three-dimensional high performance liquid chromatography separation system according to an embodiment D of the device of the present invention, and the two-position ten-way valve is in the A state;

In Figure D6 (a): 1 HPLC gradient pump A, 2 HPLC gradient pump B, 3 diluent pump, 4 gradient mixer A, 5 gradient mixer B, 6 injection valve, 7 enrichment Column array A, 8 enrichment column array B, 9 fraction collector, 10 liquid chromatography separation column array, 11 detectors, 12 two-position ten-way valve;

FIG. D6 (b) is a structural diagram of a three-dimensional high performance liquid chromatography separation system according to an embodiment D of the device of the present invention, and the two-position ten-way valve is in a B state.

FIG. E1 is a connection structure diagram of the first-dimensional, third-dimensional, and other odd-dimensional separation states of the multidimensional liquid chromatography separation system provided by the device E of the present invention, and the double two-position four-way valve is in the A state;

FIG. E2 is a pipeline connection structure diagram of the even-dimensional separation state of the second and fourth dimensions of the multi-dimensional liquid chromatography separation system provided by the device E of the present invention, and the double two-position four-way valve is in a B state;

Figure E3 is a pipeline connection structure diagram of the liquid chromatography separation column array of device E;

Figure E4 is a pipeline connection structure diagram of the enrichment column array A and the enrichment column array B of the device E;

Figure E5 (a) is the pipeline connection structure of the sample loading state (LOAD state, A state) of the two-position six-port injection valve of device E. In this state, the sample is loaded into the quantitative loop, where number ④ is defined as the injection The inlet of the valve, position ⑤ is defined as the outlet of the injection valve;

Figure E5 (b) is the pipe connection structure of the sample loading state (INJECT state, B state) of the two-position six-port injection valve of device E. In this state, the sample will be injected from the quantitative loop into the separation system flow path for separation. Number ④ is defined as the inlet of the injection valve, and ⑤ is defined as the outlet of the injection valve;

FIG. E6 (a) is a structural diagram of a multi-dimensional high-performance liquid chromatography separation system according to an embodiment E of the device of the present invention, and the double two-position four-way valve is in the A state;

In Figure E6 (a): 1 HPLC gradient pump A, 2 HPLC gradient pump B, 3 diluent pump, 4 gradient mixer A, 5 gradient mixer B, 6 injection valve, 7 enrichment Column array A, 8 enrichment column array B, 9 fraction collector, 10 liquid chromatography separation column array, 11 detectors, 12 double two-position four-way valves;

FIG. E6 (b) is a structural diagram of a multi-dimensional high-performance liquid chromatography separation system according to an embodiment E of the device of the present invention, and the double two-position four-way valve is in a B state.

FIG. F1 is a pipeline connection structure diagram of the first-dimensional and third-dimensional odd-dimensional separation states of the multidimensional liquid chromatography separation system provided by the device F of the present invention, and the two-position ten-way valve is in the A state;

FIG. F2 is a pipeline connection structure diagram of the even-dimensional separation state of the second and fourth dimensions of the multi-dimensional liquid chromatography separation system provided by the device F of the present invention, and the two-position ten-way valve is in the B state;

Figure F3 is a pipeline connection structure diagram of the liquid chromatography separation column array of the device F;

Figure F4 is a pipeline connection structure diagram of the enrichment column array A and the enrichment column array B of the device F;

Figure F5 (a) is the pipeline connection structure of the sample loading state (LOAD state, A state) of the two-position six-port injection valve of device F. In this state, the sample is loaded into the quantitative loop, where number ④ is defined as the injection The inlet of the valve, position ⑤ is defined as the outlet of the injection valve;

Figure F5 (b) is the pipeline connection structure of the sample loading state (INJECT state, B state) of the two-position six-port injection valve of device F. In this state, the sample will be injected from the quantitative loop into the flow path of the separation system for separation. Number ④ is defined as the inlet of the injection valve, and ⑤ is defined as the outlet of the injection valve;

FIG. F6 (a) is a structural diagram of a multi-dimensional high-performance liquid chromatography separation system according to an embodiment F of the device of the present invention, and the two-position ten-way valve is in the A state;

In Figure F6 (a): 1 HPLC gradient pump A, 2 HPLC gradient pump B, 3 diluent pump, 4 gradient mixer A, 5 gradient mixer B, 6 injection valve, 7 enrichment Column array A, 8 enrichment column array B, 9 fraction collector, 10 liquid chromatography separation column array, 11 detectors, 12 two-position ten-way valve;

FIG. F6 (b) is a structural diagram of a multi-dimensional high-performance liquid chromatography separation system according to an embodiment F of the device of the present invention, and the two-position ten-way valve is in a B state.

FIG. H1 is a connection structure diagram of the first-dimensional and third-dimensional odd-dimensional separation states of the multidimensional liquid chromatography separation system provided by the device H of the present invention, and the two-position eight-way valve is in the A state;

FIG. H2 is a pipeline connection structure diagram of the even-dimensional separation state of the second and fourth dimensions of the multi-dimensional liquid chromatography separation system provided by the device H of the present invention, and the two-position eight-way valve is in a B state;

Figure H3 is a pipeline connection structure diagram of the liquid chromatography column array of the device H;

FIG. H4 is a pipeline connection structure diagram of the enrichment column array A and the enrichment column array B of the device H;

Figure H5 (a) is the pipeline connection structure of the sample loading state (LOAD state, A state) of the two-position six-port injection valve of the device H. In this state, the sample is loaded into the quantitative loop, where number ④ is defined as the injection The inlet of the valve, position ⑤ is defined as the outlet of the injection valve;

Figure H5 (b) is the pipeline connection structure of the sample loading state (INJECT state, B state) of the two-position six-port injection valve of the device H. In this state, the sample will be injected from the quantitative loop into the flow path of the separation system for separation. Number ④ is defined as the inlet of the injection valve, and ⑤ is defined as the outlet of the injection valve;

FIG. H6 (a) is a structural diagram of a multi-dimensional high-performance liquid chromatography separation system according to an embodiment H of the device of the present invention, and the two-position eight-way valve is in the A state;

In Figure H6 (a): 1 HPLC gradient pump A, 2 HPLC gradient pump B, 3 diluent pump, 4 gradient mixer A, 5 gradient mixer B, 6 injection valve, 7 enrichment Column array A, 8 enrichment column array B, 9 fraction collector, 10 liquid chromatography separation column array, 11 detectors, 12 two-position eight-way valve;

FIG. H6 (b) is a structural diagram of a multi-dimensional high performance liquid chromatography separation system according to an embodiment H of the device of the present invention, and the two-position eight-way valve is in a B state.

FIG. 1 is a connection structure diagram of the first-dimensional, third-dimensional, and other odd-dimensional separation states of the multidimensional liquid chromatography separation system provided by the device I of the present invention. The two-position four-way valve A and the two-position four-way valve B are in the A state. ;

FIG. I2 is a connection structure diagram of the two-dimensional and fourth-dimensional even-dimensional separation states of the multi-dimensional liquid chromatography separation system provided by the device I of the present invention. status;

Figure I3 is a structural diagram of a liquid chromatography separation column array of the device I;

FIG. I4 is a structural diagram of the enrichment column array A and the enrichment column array B of the device I; FIG.

Figure I5 is the operation structure diagram of the column array unit in which the chromatographic separation column or the enrichment column of the device I is connected to the two-position four-way valve pipeline;

Figure I5 (a) is a structural diagram of a column array unit in which the chromatographic separation column or the enrichment column of the device I is connected to a two-position four-way valve pipeline, wherein the chromatographic separation column or the enrichment column is in a conducting state, ① the port and ④ The port is defined as the external interface of the pillar array unit;

Figure I5 (b) is a structural diagram of a column array unit in which the chromatographic separation column or the enrichment column of the device I is connected to a two-position four-way valve pipeline. The chromatographic separation column or the enrichment column is in a non-conducting state. ④ The port is defined as the external interface of the column array unit;

Figure I6 is the pipeline connection and operation structure diagram of the two-position six-port sampling valve of device I;

Figure I6 (a) is the pipeline connection structure of the sample loading state (LOAD state, A state) of the two-position six-port injection valve of device I. In this state, the sample is loaded into the quantitative loop, where ④ port is defined as the injection valve The inlet, ⑤ port is defined as the outlet of the injection valve;

Figure I6 (b) is the pipeline connection structure of the sample loading state (INJECT state, B state) of the two-position six-port injection valve of device I. In this state, the sample will be injected from the quantitative loop into the separation system flow path for separation. ④ port is defined as the inlet of the injection valve, and ⑤ port is defined as the outlet of the injection valve;

Figure I7 (a) is a structural diagram of a multi-dimensional high-performance liquid chromatography separation system according to an embodiment of the device I of the present invention. The two-position four-way valve A and the two-position four-way valve B are in the A state, and the first separation column is in the conducting state. The first enrichment column in the enrichment column array A is in an on state;

In Figure I7 (a): 1 HPLC gradient pump A, 2 HPLC gradient pump B, 3 diluent pump, 4 gradient mixer A, 5 gradient mixer B, 6 injection valve, 7 enrichment Column array A, 8 enrichment column array B, 9 fraction collector, 10 liquid chromatography separation column array, 11 detectors, 12 two-way four-way valve A, 13 two-way four-way valve B;

FIG. I7 (b) is a structural diagram of a multi-dimensional high-performance liquid chromatography separation system according to an embodiment of the device I of the present invention, and the two-position four-way valve A and the two-position four-way valve B are in a B state.

FIG. J1 is a connection structure diagram of a two-position six-way valve of the reverse elution multi-dimensional liquid chromatography separation system provided by the device J of the present invention in an A state;

Figure J2 is a pipeline connection structure diagram of a two-position six-way valve of a reverse elution multi-dimensional liquid chromatography separation system provided by the device J of the present invention in a state of B;

FIG. J3 is a pipeline connection structure diagram of a two-position six-way valve of the forward elution multi-dimensional liquid chromatography separation system provided by the device J of the present invention in an A state;

FIG. J4 is a pipeline connection structure diagram of the two-position six-way valve of the forward elution multi-dimensional liquid chromatography separation system provided by the device J of the present invention in a state of B;

Figure J5 is a pipeline connection structure diagram of the liquid chromatography separation column array of device J;

Figure J6 is a pipeline connection structure diagram of the device J enrichment column array;

Figure J7 (a) is the pipeline connection structure of the sample loading state (LOAD state, A state) of the two-position six-port injection valve of device J. In this state, the sample is loaded into the quantitative loop, where number ④ is defined as the injection The inlet of the valve, position ⑤ is defined as the outlet of the injection valve;

Figure J7 (b) is the pipe connection structure of the sample loading state (INJECT state, B state) of the two-position six-port injection valve of device J. In this state, the sample will be injected from the quantitative loop into the flow path of the separation system for separation. Number ④ is defined as the inlet of the injection valve, and ⑤ is defined as the outlet of the injection valve;

Figure J8 (a) is a structural diagram of a multi-dimensional high-performance liquid chromatography separation system according to an embodiment J of the device of the present invention, and the two-position six-way valve is in the A state;

In Figure J8 (a): 1 HPLC gradient pump A, 2 HPLC gradient pump B, 3 diluent pump, 4 gradient mixer A, 5 gradient mixer B, 6 injection valve, 7 enrichment Column array, 8 fraction collector, 9 liquid chromatography separation column array, 10 detectors, 11 two-position six-way valve;

FIG. J8 (b) is a structural diagram of a multi-dimensional high-performance liquid chromatography separation system according to an embodiment J of the device of the present invention, and a two-position six-way valve is in a B state.

detailed description

The embodiments described below are only a description of the patent application of the present invention, and do not limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications made by those skilled in the art to the solution of the present invention And improvements should fall into the protection scope determined by the claims of the present invention.

Corresponding to device A,

A multi-dimensional liquid chromatography separation system includes a high-performance liquid chromatography gradient pump A, a high-performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array A, Enrichment column array B, fraction collector, liquid chromatography separation column array, detector, two-position ten-way valve, and connecting pipeline. The diluent pump is a high-performance liquid diluent pump.

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the ten-position valve is connected, the ⑩ position of the two-position ten-port valve is connected to the X interface of the enrichment column array A, and the Y interface of the enrichment column array A is connected to the ⑦ position of the two-position ten-port valve. The position ⑥ of the two-position ten-way valve is connected to the inlet of the liquid chromatography separation column array. The outlet of the liquid chromatography separation column array is connected to the detector. The outlet of the detector is connected to the inlet of the gradient mixer B. The outlet is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the ⑧ position of the two-position ten-port valve; the ⑨ position of the two-position ten-port valve is connected to the ④ position; The number is connected to the Y interface of the enrichment column array B, and the X interface of the enrichment column array B is connected to the number ② of the two-position ten-way valve; the number ③ of the two-position ten-way valve is connected to the inlet of the fraction collector . The ①, ②, ③, ④, ⑤, ⑥, ⑦, ⑧, ⑨, ⑩, and ⑩ positions of the two-position ten-way valve only indicate the positional adjacency relationship. Correspondence.

In Figure A1, the two-position ten-way valve is in the A state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A constitute a chromatographic separation gradient elution mobile phase supply system. The gradient mixer A The outlet of the sample valve is connected to the inlet of the sample valve, and the outlet of the sample valve is connected to the ① position of the two-position ten-port valve; the ① position of the two-position ten-port valve is connected to the ⑩ position and is connected to the The interface X (the interface X of the enrichment column array A is its inlet at this time); the interface Y of the enrichment column array A (the interface Y of the enrichment column array A at this time is its outlet); The number is connected and connected to the inlet of the liquid chromatography separation column array through the number ⑥ of the two-position ten-way valve; any column in the separation column array is selected for separation; the outlet of the separation column array is connected to the detector, and the detector detects Chromatographic signal, the outlet of the detector is connected to the inlet of the gradient mixer B, the outlet of the diluent pump is connected to the inlet of the gradient mixer B, and the sample is flowed out after the gradient mixer B dilutes the column, and the outlet of the gradient mixer B is connected to two ten The ⑧ position of the two-way valve is connected; Conduction; the ⑨ position of the two-position ten-way valve is connected to the ④ position, the ④ position of the two-port ten-way valve is connected to the ⑤ position; the ⑤ position of the two-port ten-way valve is connected to the enrichment column array B The interface Y (the interface Y of the enrichment column array B is its inlet at this time), the interface X of the enrichment column array B (the interface X of the enrichment column array B at this time is its outlet) and the two-position ten-way valve② The number is connected to realize the enrichment of separated samples; the number ③ of the two-position ten-way valve is connected to the inlet of the fraction collector to realize the sample collection.

In Figure A2, the two-position ten-way valve is in the B state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A constitute a chromatographic separation gradient elution mobile phase supply system. The gradient mixer A The outlet of the sample valve is connected to the inlet of the sample valve. The outlet of the sample valve is connected to the ① position of the two-position ten-way valve, and the ① position of the two-position ten-port valve is in communication with the ② position; The number is connected to the interface X of the enrichment column array B (the interface X of the enrichment column array B is its entrance at this time); the interface Y of the enrichment column array B (the interface Y of the enrichment column array B is its exit at this time) ) Is connected to position ⑤ of the two-position ten-way valve; position ⑤ of the two-position ten-way valve is connected to position ⑥; position ⑥ of the two-position ten-way valve is connected to the inlet of the liquid chromatography separation column array; select Any column in the separation column array is used for separation; the outlet of the separation column array is connected to the detector, the detector detects the chromatographic signal, the outlet of the detector is connected to the inlet of the gradient mixer B, and the outlet of the diluent pump is connected to the gradient mixer B The inlet of the gradient mixer B is used to dilute the column and the sample flows out. The outlet of the gradient mixer B is connected to the sample.十 position of the ten-position valve is connected; ⑧ position of the two-position ten-way valve is connected to the ⑦ position; the ⑦ position of the two-position ten-way valve is connected to the interface Y of the enrichment column array A (the enrichment column at this time) The interface Y of the array A is its inlet); the interface X of the enrichment column array A (the interface X of the enrichment column array A is its exit at this time) is connected to the ⑩ position of the two-position ten-way valve to realize the enrichment of the separated sample The two-position ten-way valve is connected to the 通 position and the ⑨ position; the two-position ten-way valve is connected to the ④ position; the two-position ten-way valve is connected to the ④ position and the ③ position; two Position ③ of the ten-way valve is connected to the inlet of the fraction collector to realize sample collection.

Example: Structure of a multidimensional high performance liquid chromatography separation system

In this embodiment, the enrichment column array A has 9 enrichment columns, which are sequentially numbered as the first enrichment column, the second enrichment column, and the like of the enrichment column array A, and the last number is the enrichment column array A The 9th enrichment column; the enrichment column array B is a two-stage enrichment column array, and each stage of the enrichment column array has 9 enrichment columns, that is, the enrichment column array B is 18 enrichment columns, which are sequentially numbered as enrichment The first enrichment column of column array B, the second enrichment column, and so on. The last is the eighteenth enrichment column of enrichment column array B; the liquid chromatography separation column array has five separation columns, which are sequentially numbered as The first separation column, the second separation column, etc., the last one is the fifth separation column; the two-position ten-port valve in Fig. A6 (a) is in the A state, and the two-position ten-port valve in Fig. A6 (b). B state.

The following is the four-dimensional separation process control of the above-mentioned multi-dimensional high-performance liquid chromatography separation system structure:

The operation mode of the multi-dimensional liquid chromatography separation system mainly includes two types. The first is multiple cycles of separation-enrichment, which ends with separation. The second is multiple cycles of enrichment-separation, which ends with separation. . The following briefly describes a four-dimensional liquid chromatography separation control process.

First clean the enrichment column and separation column; switch each enrichment column and separation column to the flow path in turn, and observe the detector signal to determine the cleaning effect.

First-dimension separation process control: The two-position ten-way valve is in the A state, see Figure A1; the enrichment column array A is in the bypass state; the sample is loaded into the quantitative loop on the injection valve; the first-dimensional chromatographic separation column is selected, For example, the first separation column, the chromatographic separation column is manually turned on; when the injection valve is switched to the INJECT state, the first-dimensional separation is started; with the assistance of the diluent pump, the fractions are sequentially enriched according to the sample properties and detection signals. Enrichment is performed in the 1st to 9th enrichment columns of the concentrated column array B, and the 10th to 18th enrichment columns of the enriched column array B are reserved for the third dimension separation; this is repeated until the enrichment column array B Enough compounds in the 1st to 9th enrichment columns are transferred to the second-dimensional separation process control; if the second-dimensional separation is not required, the enrichment column array B is always in the bypass state, and a fraction collector is used 9 Collect multiple fractions directly.

Control of the second-dimensional separation process: After the control of the first-dimensional separation process is completed, the injection valve should be switched to the LOAD state, and the two-position ten-way valve is switched to the B state, see Figure A2. Select the second-dimensional chromatographic separation column. 2 separation column, the chromatographic separation column is manually turned on; one of the 1st to 9th enrichment columns of the enrichment column array B is selected as a sample column for the second-dimensional separation; when the enrichment column is turned on The second-dimensional separation process begins; with the assistance of the diluent pump, the fractions are sequentially switched to the 1st to 9th enrichment columns of the enrichment column array A for enrichment according to the sample properties and detection signals; if the first For three-dimensional separation, the first to ninth enrichment columns of the enrichment column array A can be sequentially eluted, and multiple fractions can be directly collected using the fraction collector; in this way, the second-dimensional separation is completed;

Control of the third-dimensional separation process: After the control of the second-dimensional separation process is completed, the two-position ten-way valve is switched to the A state, see FIG. A1; the injection valve remains in the LOAD state; and the third-dimensional chromatography separation column, for example, the third separation column, The chromatographic separation column was manually turned on; one of the first to ninth enrichment columns of the enrichment column array A was selected as a sample column for the third separation; when the enrichment column was turned on, the third separation process was performed Start; if a fourth-dimensional separation is required, with the assistance of a diluent pump, the fractions are sequentially switched to the 10th to 18th enrichment columns of the enrichment column array B for enrichment according to the sample properties and detection signals. The fraction is cut into 9 parts; if the fourth-dimensional separation is not required, the 1st to 9th enrichment columns of the enrichment column array A can be eluted and separated in sequence, and the fraction collector can be used to directly perform the distillation of multiple fractions. Collect; repeat this way to complete the third dimension separation.

Control of the fourth-dimensional separation process: After the control of the third-dimensional separation process, the two-position ten-way valve is switched to the B state, see Figure A2; the injection valve remains in the LOAD state; a fourth-dimensional chromatographic separation column is selected, for example, the fourth separation column The chromatographic separation column was manually turned on; one of the 10th to 18th enrichment columns of the enrichment column array B was selected as the fourth-dimensional separation sample column; when the enrichment column was turned on, the fourth The dimension separation process begins; under the action of the gradient eluent, the compounds in the enrichment column as the sample column can be eluted, and the fourth dimension separation is performed under the action of the fourth separation column; The fractions were collected; in this way, the fourth-dimensional separation was completed.

Corresponding to device B,

A multi-dimensional liquid chromatography separation system includes a high-performance liquid chromatography gradient pump A, a high-performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array A, Enrichment column array B, fraction collector, liquid chromatography separation column array, detector, double two-position four-way valve, and connecting pipeline. The diluent pump is a high-performance liquid diluent pump.

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the injection valve, and the outlet of the injection valve and the double The ① position of the two-position four-way valve is connected. The ④ position of the two-position four-way valve is connected to the X interface of the enrichment column array A. The Y interface of the enrichment column array A is connected to the ⑦ number of the two-position four-way valve. Position connection, the ⑧ position of the double two-position four-way valve is connected to the inlet of the liquid chromatography separation column array, the outlet of the liquid chromatography separation column array is connected to the detector, the outlet of the detector is connected to the inlet of the gradient mixer B, The outlet of the diluent pump is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the ③ position of the double two-position four-way valve; the ② position of the double two-position four-way valve is connected to the enrichment column array B. The Y interface is connected, and the X interface of the enrichment column array B is connected to the position ⑤ of the double two-position four-way valve; the position ⑥ of the double two-position four-way valve is connected to the inlet of the fraction collector. The ① position, ② position, ③ position, ④ position, ⑤ position, ⑥ position, ⑦ position, and ⑧ position of the double two-way four-way valve only indicate positional adjacency, and do not necessarily correspond to the physical marks of the double two-way four-way valve.

In Figure B1, the two-position two-position four-way valve is in the A state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A constitute a chromatographic separation gradient elution mobile phase supply system, and the gradient mixer The outlet of A is connected to the inlet of the injection valve. The outlet of the injection valve is connected to the ① position of the double two-position four-way valve; the ① position of the double two-position four-way valve is connected to the ④ position and is connected to the enrichment column. The interface X of the array A (the interface X of the enrichment column array A is its entrance at this time); the interface Y of the enrichment column array A (the interface Y of the enrichment column array A at this time is its exit); The ⑦ position of the on-off valve is connected and connected to the inlet of the liquid chromatography separation column array via the 两位 position of the double two-position four-way valve; select any column in the separation column array for separation; the outlet of the separation column array and the detector Connected, the detector detects the chromatographic signal, the outlet of the detector is connected to the inlet of the gradient mixer B, the outlet of the diluent pump is connected to the inlet of the gradient mixer B, and the sample flows out after the gradient mixer B dilutes the column, and the gradient mixer B The outlet is connected to the ③ position of the double two-position four-way valve; the double two-position four-way valve The ③ position is connected to the ② position; the ② position of the double two-position four-way valve is connected to the interface Y of the enrichment column array B (the interface Y of the enrichment column array B is its entrance at this time), and the enrichment column array The interface X of B (the interface X of the enrichment column array B is its outlet at this time) is connected to the position ⑤ of the double two-position four-way valve to realize the enrichment of the separated sample; the position ⑤ of the double two-position four-way valve is connected to The position ⑥ of the double two-position four-way valve is turned on, and the position ⑥ of the double two-position four-way valve is connected to the inlet of the fraction collector to realize sample collection.

In Figure B2, the two-position two-position four-way valve is in the B state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A constitute a chromatographic separation gradient elution mobile phase supply system. The gradient mixer The outlet of A is connected to the inlet of the injection valve. The outlet of the injection valve is connected to the ① position of the double two-position four-way valve, and the ① position of the double two-position four-way valve is connected to the ② position. The number ② of the valve is connected to the interface Y of the enrichment column array B (the interface Y of the enrichment column array B is its entrance at this time); the interface X of the enrichment column array B (the interface of the enrichment column array B at this time) X is its outlet) is connected to the ⑤ position of the double two-position four-way valve; the ⑤ position of the double two-position four-way valve is connected to the ⑧ position, and the ⑧ position of the double two-position four-way valve is separated from the liquid chromatography. The inlet of the column array is connected; any column in the separation column array is selected for separation; the outlet of the separation column array is connected to the detector, the detector detects the chromatographic signal, the outlet of the detector is connected to the inlet of the gradient mixer B, and the diluent pump The outlet of the gradient mixer B is connected to the inlet of the gradient mixer B. The outlet of mixer B is connected to the ③ position of the double two-position four-way valve; the ③ position of the double two-position four-way valve is connected to the ④ position; the ④ position of the double two-position four-way valve is connected to the enrichment column array A. Interface X is connected (at this time, interface X of enrichment column array A is its inlet); interface Y of enrichment column array A (at this time, interface Y of enrichment column array A is its outlet); The ⑦ position is connected to realize the enrichment of separated samples; the ⑦ position of the double two-position four-way valve is connected to the ⑥ position; the ⑥ position of the double two-position four-way valve is connected to the inlet of the fraction collector to realize the sample collect.

In this embodiment, the enrichment column array A has 9 enrichment columns, which are sequentially numbered as the first enrichment column, the second enrichment column, and the like of the enrichment column array A, and the last number is the enrichment column array A The 9th enrichment column; the enrichment column array B is a two-stage enrichment column array, and each stage of the enrichment column array has 9 enrichment columns, that is, the enrichment column array B is 18 enrichment columns, which are sequentially numbered as enrichment The first enrichment column of column array B, the second enrichment column, and so on. The last is the eighteenth enrichment column of enrichment column array B; the liquid chromatography separation column array has five separation columns, which are sequentially numbered as The first separation column, the second separation column, etc., the last one is the fifth separation column; the double two-position four-way valve in Fig. B6 (a) is in the A state, and the double two-position four in Figure B6 (b) The on-off valve is in the B state.

First-dimension separation process control: the double two-position four-way valve is in the A state, see Figure B1; the enrichment column array A is in the bypass state; the sample loop is loaded on the injection valve; the first-dimensional chromatographic separation column is selected For example, the first separation column, the chromatographic separation column is manually turned on; when the injection valve is switched to the INJECT state, the first-dimensional separation is started; with the assistance of the diluent pump, the fractions are sequentially used according to the nature of the sample and the detection signal. Enrichment is performed in the 1st to 9th enrichment columns of the enrichment column array B, and the 10th to 18th enrichment columns of the enrichment column array B are reserved for the third-dimensional separation; this is repeated until the enrichment column array B There are enough compounds in the 1st to 9th enrichment columns in the column to be transferred to the second-dimensional separation process control; if the second-dimensional separation is not required, the enrichment column array B is always in the bypass state and collected by fractions The device directly collects multiple fractions.

Control of the second two-dimensional separation process: After the control of the first two-dimensional separation process is completed, the injection valve should be switched to the LOAD state, and the two-position two-way four-way valve should be switched to the B state, see Figure B2; select the second-dimensional chromatography separation column, for example, The second separation column, the chromatographic separation column is manually turned on; one of the first to ninth enrichment columns of the enrichment column array B is selected as a sample column for the second-dimensional separation; when the enrichment column is turned on At the beginning, the second-dimensional separation process begins; with the assistance of the diluent pump, the fractions are sequentially switched to the 1st to 9th enrichment columns of enrichment column array A for enrichment according to the sample properties and detection signals; if not required, For the third dimension separation, the first to ninth enrichment columns of the enrichment column array A can be sequentially eluted, and the fraction collector can be used to directly collect multiple fractions; in this way, the second dimension separation is completed;

Control of the third-dimensional separation process: After the control of the second-dimensional separation process is completed, the double two-position four-way valve is switched to the A state, see FIG. B1; the injection valve remains in the LOAD state; and the third-dimensional chromatography separation column is selected, for example, the third separation column The chromatographic separation column is manually turned on; one of the first to ninth enrichment columns of the enrichment column array A is selected as a sample column for the third dimension separation; when the enrichment column is turned on, the third dimension separation is performed The process begins; if a fourth-dimensional separation is required, the fractions are sequentially switched to the 10th to 18th enrichment columns of enrichment column array B for enrichment with the assistance of the diluent pump according to the sample properties and detection signals. The fraction is cut into 9 parts; if the fourth-dimensional separation is not required, the 1st to 9th enrichment columns of the enrichment column array A can be sequentially eluted and separated, and a plurality of fractions can be directly performed by the fraction collector. Collection; repeat this step to complete the third separation.

Control of the fourth-dimensional separation process: After the control of the third-dimensional separation process, the double two-position four-way valve is switched to the B state, see Figure B2; the injection valve remains in the LOAD state; a fourth-dimensional chromatographic separation column is selected, for example, the fourth separation Column, the chromatographic separation column is manually turned on; one of the 10th to 18th enrichment columns of the enrichment column array B is selected as the fourth-dimensional separation sample column; when the enrichment column is turned on, the first The four-dimensional separation process begins; under the action of a gradient eluent, the compounds in the enrichment column as the sample column can be eluted, and the fourth-dimensional separation is performed under the action of the fourth separation column; The fractions were collected; in this way, the fourth-dimensional separation was completed.

Corresponding to device C,

A multi-dimensional liquid chromatography separation system includes a high-performance liquid chromatography gradient pump A, a high-performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array A, Enrichment column array B, fraction collector, liquid chromatography separation column array, detector, two-position eight-way valve, and connecting lines. The diluent pump is a high-performance liquid diluent pump.

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the two-position eight-way valve is connected, the ② position of the two-position eight-way valve is connected to the X interface of the enrichment column array B, and the Y interface of the enrichment column array B is connected to the ⑥ position of the two-position eight-way valve. The position ⑤ of the two-position eight-way valve is connected to the inlet of the liquid chromatography separation column array. The outlet of the liquid chromatography separation column array is connected to the detector. The outlet of the detector is connected to the inlet of the gradient mixer B. The outlet is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the ⑦ position of the two-position eight-way valve; the ⑧ position of the two-position eight-way valve is connected to the X interface of the enrichment column array A to enrich The Y interface of column array A is connected to the ④ position of the two-position eight-way valve; the ③ position of the two-position eight-way valve is connected to the inlet of the fraction collector. The

positions

①, ②, ③, ④, ⑤, ⑥, ⑦, and ⑧ of the two-position eight-way valve only indicate the positional adjacency and do not necessarily correspond to the physical marks of the two-position eight-way valve.

In Figure C1, the two-position eight-way valve is in the A state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A constitute a chromatographic separation gradient elution mobile phase supply system, and the gradient mixer A The outlet of the sample valve is connected to the inlet of the injection valve, and the outlet of the sample valve is connected to the ① position of the two-position eight-way valve; The interface X (the interface X of the enrichment column array B is its inlet at this time); the interface Y of the enrichment column array B (the interface Y of the enrichment column array B at this time is its outlet); The number is connected and connected to the inlet of the liquid chromatography separation column array through the number ⑤ of the two-position eight-way valve; any column in the separation column array is selected for separation; the outlet of the separation column array is connected to the detector, and the detector detects Chromatographic signal, the outlet of the detector is connected to the inlet of the gradient mixer B, the outlet of the diluent pump is connected to the inlet of the gradient mixer B, and the sample is flowed out after the gradient mixer B dilutes the column. The ⑦ position of the port valve is connected; the ⑦ position and the ⑧ position of the two-position eight-way valve Conduction; the ⑧ position of the two-position eight-way valve is connected to the interface X of the enrichment column array A (the interface X of the enrichment column array A is the entrance at this time), and the interface Y of the enrichment column array A (the rich at this time) The interface Y of the column array A is its outlet) and is connected to the ④ position of the two-position eight-way valve to realize the enrichment of separated samples; the ④ position of the two-position eight-way valve and the ③ position of the two-position eight-way valve The ③ position of the two-position eight-way valve is connected to the inlet of the fraction collector to realize sample collection.

In Figure C2, the two-position eight-way valve is in the B state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A constitute a chromatographic separation gradient elution mobile phase supply system, and the gradient mixer A The outlet of the two-port eight-way valve is connected to the ① position of the two-position eight-way valve, and the ① position of the two-position eight-way valve is connected to the ⑧ position; The number is connected to the interface X of the enrichment column array A (the interface X of the enrichment column array A is its entrance at this time); the interface Y of the enrichment column array A (the interface Y of the enrichment column array B is its exit at this time) ) Is connected to the ④ position of the two-position eight-way valve; the ④ position of the two-position eight-way valve is connected to the ⑤ position, and the ⑤ position of the two-position eight-way valve is connected to the inlet of the liquid chromatography separation column array; select Any column in the separation column array is used for separation; the outlet of the separation column array is connected to the detector, the detector detects the chromatographic signal, the outlet of the detector is connected to the inlet of the gradient mixer B, and the outlet of the diluent pump is connected to the gradient mixer B The inlet of the gradient mixer B is used to dilute the column and the sample flows out. The outlet of the gradient mixer B is connected to the sample.八 position of the two-position eight-way valve is connected; ⑦ position of the two-position eight-way valve is connected to ⑥ position; ⑥ position of the two-position eight-way valve is connected to the interface Y of the enrichment column array B (the enrichment column at this time) The interface Y of the array B is its inlet); the interface X of the enrichment column array B (the interface X of the enrichment column array A is its outlet at this time) is connected to the number ② of the two-position eight-way valve to realize the enrichment of the separated sample. The ② position and ③ position of the two-position eight-way valve are connected; the ③ position of the two-position eight-way valve is connected to the inlet of the fraction collector to realize sample collection.

Example: Structure of a multidimensional liquid chromatography separation system

In this embodiment, the enrichment column array B has 9 enrichment columns, which are sequentially numbered as the first enrichment column, the second enrichment column, and the like of the enrichment column array B, and the last number is the enrichment column array B. The 9th enrichment column; the enrichment column array A is a two-stage enrichment column array, and each stage of the enrichment column array has 9 enrichment columns, that is, the enrichment column array A is 18 enrichment columns, which are sequentially numbered as enrichment The first enrichment column of column array A, the second enrichment column, and so on. The last is the eighteenth enrichment column numbered as enrichment column array A; the liquid chromatography separation column array has five separation columns, numbered sequentially The first separation column, the second separation column, etc., the last one is the fifth separation column; the two-position eight-way valve in Figure C6 (a) is in the A state, and the two-position eight-way valve in Figure C6 (b) B state.

First-dimensional separation process control: the two-position eight-way valve is in the A state, see Figure C1; the enrichment column array B is in the bypass state; the sample is loaded on the quantitative loop on the injection valve; the first-dimensional chromatographic separation column is selected, For example, the first separation column, the chromatographic separation column is manually turned on; when the injection valve is switched to the INJECT state, the first-dimensional separation is started; with the assistance of the diluent pump, the fractions are sequentially enriched according to the sample properties and detection signals. Enrichment is performed in the 1st to 9th enrichment columns of the concentration column array A, and the 10th to 18th enrichment columns of the concentration column array A are reserved for the third dimension separation; this is repeated until the concentration of the enrichment column array A Enough compounds in the 1st to 9th enrichment columns are transferred to the second-dimensional separation process control; if the second-dimensional separation is not required, the enrichment column array A is always in the bypass state, and a fraction collector is used The collection of multiple fractions was performed directly.

Second-dimensional separation process control: After the first-dimensional separation process control is completed, the injection valve should be switched to the LOAD state, and the two-position eight-way valve should be switched to the B state, see Figure C2. Select the second-dimensional chromatographic separation column. 2 separation column, the chromatographic separation column is manually turned on; one of the 1st to 9th enrichment columns of the enrichment column array A is selected as a sample column for the second-dimensional separation; when the enrichment column is turned on The second-dimensional separation process begins; with the assistance of the diluent pump, the fractions are sequentially switched to the 1st to 9th enrichment columns of the enrichment column array B for enrichment according to the sample properties and detection signals; if the first For three-dimensional separation, the first to ninth enrichment columns of the enrichment column array B can be sequentially eluted, and the fraction collector can be used to directly collect multiple fractions; in this way, the second-dimensional separation is completed;

Control of the third-dimensional separation process: After the control of the second-dimensional separation process is completed, the two-position eight-way valve is switched to the A state, see Figure C1; the injection valve remains in the LOAD state; and the third-dimensional chromatographic separation column is selected, for example, the third separation column, The chromatographic separation column was manually turned on; one of the first to ninth enrichment columns of the enrichment column array B was selected as a sample column for the third separation; when the enrichment column was turned on, the third separation process was performed Start; if a fourth-dimensional separation is required, with the assistance of a diluent pump, the fractions are sequentially switched to the 10th to 18th enrichment columns of enrichment column array A for enrichment according to the sample properties and detection signals. The fraction is cut into 9 parts; if the fourth-dimensional separation is not required, the 1st to 9th enrichment columns of the enrichment column array B can be sequentially eluted and separated, and the fraction collector can be used to directly perform the distillation of multiple fractions. Collect; repeat this way to complete the third dimension separation.

Control of the fourth-dimensional separation process: After the control of the third-dimensional separation process, the two-position eight-way valve is switched to the B state, see Figure C2; the injection valve remains in the LOAD state; a fourth-dimensional chromatographic separation column is selected, for example, the fourth separation column The chromatographic separation column was manually turned on; one of the 10th to 18th enrichment columns of the enrichment column array A was selected as the fourth-dimensional separation sample column; when the enrichment column was turned on, the fourth The dimension separation process begins; under the action of the gradient eluent, the compounds in the enrichment column as the sample column can be eluted, and the fourth dimension separation is performed under the action of the fourth separation column; The fractions were collected; in this way, the fourth-dimensional separation was completed.

Corresponding to device D,

A three-dimensional liquid chromatography separation system comprising a high-performance liquid chromatography gradient pump A, a high-performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array A, Enrichment column array B, fraction collector, liquid chromatography separation column array, detector, two-position ten-way valve, and connecting pipeline. The diluent pump is a high-performance liquid diluent pump.

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the ten-position valve is connected, the ⑩ position of the two-position ten-way valve is connected to the X interface of the enrichment column array B, and the Y interface of the enrichment column array B is connected to the ③ position of the two-position ten-way valve. The ② position of the two-position ten-way valve and the ⑦ position of the two-position ten-way valve are connected; the ⑥ position of the two-position ten-way valve is connected to the inlet of the liquid chromatography separation column array, and the outlet of the liquid chromatography separation column array is connected to The detector is connected, the outlet of the detector is connected to the inlet of the gradient mixer B, the outlet of the diluent pump is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the ④ position of the two-position ten-way valve; The ⑤ position of the ten-position valve is connected to the Y interface of the enrichment column array A, and the X interface of the enrichment column array B is connected to the ⑧ position of the two-position ten-way valve; The inlet of the share collector is connected. The ①, ②, ③, ④, ⑤, ⑥, ⑦, ⑧, ⑨, ⑩, and ⑩ positions of the two-position ten-way valve only indicate the positional adjacency relationship. Correspondence.

In Figure D1, the two-position ten-way valve is in the A state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A constitute a chromatographic separation gradient elution mobile phase supply system, and the gradient mixer A The outlet of the sample valve is connected to the inlet of the sample valve, and the outlet of the sample valve is connected to the ① position of the two-position ten-port valve; the ① position of the two-position ten-port valve is connected to the ⑩ position and is connected to the Interface X (the interface X of the enrichment column array B is its inlet at this time); interface Y of the enrichment column array B (the interface Y of the enrichment column array B at this time is its outlet); Number position connection; position ③ of two-position ten-way valve is connected to position ② of two-position ten-port valve; position ② of two-position ten-port valve is connected to position ⑦ of two-position ten-port valve; two-position ten The ⑦ position of the on-way valve is in communication with the ⑥ position; the ⑥ position of the two ten-way valve is connected to the inlet of the liquid chromatography separation column array; any column in the separation column array is selected for separation; the outlet of the separation column array Connected to the detector, the detector detects the chromatographic signal, the outlet of the detector is connected to the inlet of the gradient mixer B, and the outlet of the diluent pump is connected to The inlet of the degree mixer B is connected, and the sample flows out after the gradient mixer B dilutes the column. The outlet of the gradient mixer B is connected to the position ④ of the two-position ten-way valve; the position ④ and the position ⑤ of the two-position ten-way valve are connected. The ⑤ position of the two-position ten-way valve is connected to the interface Y of the enrichment column array A (the interface Y of the enrichment column array A is the entrance at this time), and the interface X of the enrichment column array A (the enrichment at this time) The interface X of the column array A is its outlet) is connected to the ⑧ position of the two-position ten-port valve to realize the enrichment of the separated sample; the ⑧ position of the two-port ten-port valve is in communication with the ⑨ position; the two-position ten-port valve The ⑨ position is connected to the inlet of the fraction collector for sample collection.

In Figure D2, the two-position ten-way valve is in the B state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A constitute a chromatographic separation gradient elution mobile phase supply system, and the gradient mixer A The outlet of the sample valve is connected to the inlet of the sample valve. The outlet of the sample valve is connected to the ① position of the two-position ten-way valve, and the ① position of the two-position ten-port valve is in communication with the ② position; The position of the two-position ten-way valve is connected to the position of the position ⑧; the position of the two-position ten-way valve is connected to the interface X of the enrichment column array A (the enrichment column array at this time) The interface X of A is its inlet); the interface Y of the enrichment column array A (the interface Y of the enrichment column array A is its outlet at this time) is connected to the position ⑤ of the two-position ten-way valve; The ⑤ position is connected to the ⑥ position, and the ⑥ position of the two-position ten-way valve is connected to the inlet of the liquid chromatography separation column array; select any column in the separation column array for separation; the outlet of the separation column array and the detector Connected, the detector detects the chromatographic signal, the outlet of the detector is connected to the inlet of the gradient mixer B, and the outlet of the diluent pump is mixed with the gradient The inlet of the mixer B is connected, and the sample is flowed out after the gradient mixer B dilutes the column. The outlet of the gradient mixer B is connected to the ④ position of the two-position ten-way valve; the ④ position of the two-position ten-way valve is connected to the ③ position; The ③ position of the two-position ten-way valve is connected to the interface Y of the enrichment column array B (the interface Y of the enrichment column array B is its entrance at this time); the interface X of the enrichment column array B (the enrichment column array B at this time) The interface X is its outlet) is connected to the ⑩ position of the two-position ten-port valve to realize the enrichment of the separated sample; the ⑩ position of the two-port ten-port valve is in communication with the ⑨ position; The position is connected to the inlet of the fraction collector to realize sample collection.

Example: Structure of a three-dimensional high performance liquid chromatography separation system

In this embodiment, the enrichment column array B has 9 enrichment columns, which are sequentially numbered as the first enrichment column, the second enrichment column, and the like of the enrichment column array B, and the last number is the enrichment column array B. The 9th enrichment column; the enrichment column array A is a two-stage enrichment column array, and each stage of the enrichment column array has 9 enrichment columns, that is, the enrichment column array A is 18 enrichment columns, which are sequentially numbered as enrichment The first enrichment column of column array A, the second enrichment column, and so on. The last is the eighteenth enrichment column numbered as enrichment column array A; the liquid chromatography separation column array has five separation columns, numbered sequentially The first separation column, the second separation column, etc., the last one is the fifth separation column; the two-position ten-port valve in Figure D6 (a) is in the A state, and the two-port ten-port valve in Figure D6 (b). B state.

The following is the three-dimensional separation process control of the structure of the above three-dimensional high-performance liquid chromatography separation system:

The operation mode of the three-dimensional liquid chromatography separation system mainly includes two types, the first is multiple cycles of separation-enrichment, and finally ends with separation; the second is multiple cycles of enrichment-separation, and finally ends with separation . The following briefly describes a three-dimensional liquid chromatography separation control process.

First-dimension separation process control: The two-position ten-way valve is in the A state, see Figure D1; the enrichment column array B is in the bypass state; the sample is loaded into the quantitative loop on the injection valve; the first-dimensional chromatographic separation column is selected, For example, the first separation column, the chromatographic separation column is manually turned on; when the injection valve is switched to the INJECT state, the first-dimensional separation is started; with the assistance of the diluent pump, the fractions are sequentially enriched according to the sample properties and detection signals. Enrichment is performed in the 1st to 18th enrichment columns of the concentration column array A; this is repeated until enough compounds in the 1st to 18th enrichment columns of the concentration column array A are transferred to the second-dimensional separation Process control; if the second-dimensional separation is not required, the enrichment column array A is always in the bypass state, and a fraction collector is used to directly collect multiple fractions.

Control of the second two-dimensional separation process: After the control of the first two-dimensional separation process is completed, the injection valve should be switched to the LOAD state, and the two-position ten-way valve is switched to the B state, see Figure D2. Select the second-dimensional chromatographic separation column. 2 separation column, the chromatographic separation column is manually turned on; one of the first to 18th enrichment columns of the enrichment column array A is selected as a sample column for the second-dimensional separation; when the enrichment column is turned on The second-dimensional separation process begins; with the assistance of the diluent pump, the fractions are sequentially switched to the 1st to 9th enrichment columns of the enrichment column array B for enrichment according to the sample properties and detection signals; if the first For three-dimensional separation, the first to ninth enrichment columns of the enrichment column array B can be sequentially eluted, and the fraction collector can be used to directly collect multiple fractions; in this way, the second-dimensional separation is completed;

Control of the third-dimensional separation process: After the control of the second-dimensional separation process, the two-position ten-way valve is switched to the A state, see Figure D1; the injection valve remains in the LOAD state; the enrichment column array A is in the bypass state; the third-dimensional chromatography is selected A separation column, for example, a third separation column, the chromatographic separation column is manually turned on; one of the first to ninth enrichment columns of the enrichment column array B is selected as a sample column for the third separation; When the column is turned on, the third-dimensional separation process begins; a plurality of separated fractions are collected using a fraction collector; and the third-dimensional separation is completed by repeating this process.

The following is the two-dimensional separation process control of online sample processing and liquid chromatography combined with the above-mentioned three-dimensional high performance liquid chromatography separation system structure:

Sample pretreatment process: The separation object generally contains pre- impurities, target compounds and post- impurities. At the beginning of the sample preparation process, the two-position ten-way valve is in the A state, see Figure D1; the enrichment column array A is in the bypass state, and the chromatographic separation column array is in the bypass state; the sample is loaded when the injection valve is in the LOAD state To the loop on the injection valve; select the enrichment column in the enrichment column array B, for example, the first enrichment column, the enrichment column is turned on manually; when the injection valve is switched to the INJECT state, the sample starts at The first enrichment column is enriched and pre-eluted as needed; if reverse elution is required, the two-position ten-way valve is turned to the B state, see Figure D2. ; If multiple repetitions are required, other enrichment columns in the enrichment column array B can be selected and the sample pretreatment repeated in sequence.

First-dimension separation process control: After the sample pretreatment process is completed, the two-position ten-way valve is switched to the A state, see Figure D1; the injection valve remains in the LOAD state; the enrichment column array A is in the bypass state; the first-dimensional chromatography is selected A separation column, for example, the first separation column, the chromatographic separation column is manually turned on; one of the first to ninth enrichment columns of the enrichment column array B is selected as a sample column for the first-dimensional separation; when the When the enrichment column is turned on, the first-dimensional separation process starts; with the assistance of the diluent pump, the target fractions are sequentially carried out in the 1st to 18th enrichment columns of the enrichment column array A according to the nature of the target sample and the detection signal. Enrichment; this is repeated until there are enough target compounds in the 1st to 18th enrichment columns of the enrichment column array A. After the first-dimensional separation process control is completed, all the enrichment columns in the enrichment column array B are cleaned and balanced, and are reserved for the second-dimensional separation process.

Control of the second two-dimensional separation process: After the control of the first two-dimensional separation process, the injection valve remains in the LOAD state, and the two-position ten-way valve is switched to the B state, see Figure D2. Select the second-dimensional chromatographic separation column, for example, the second separation Column, the chromatographic separation column is manually turned on; one of the enrichment columns of the first to eighteenth enrichment columns of the enrichment column array A is selected as a sample column for the second-dimensional separation; when the enrichment column is turned on, the first The two-dimensional separation process begins; with the assistance of a diluent pump, the fractions are sequentially switched to the first to ninth enrichment columns of the enrichment column array B for enrichment and concentration according to the sample properties and detection signals.

Target sample elution process control: After the second-dimensional separation process control is completed, the injection valve remains in the LOAD state, the two-position ten-way valve is switched to the A state, the enrichment column array A is in the bypass state, and the chromatographic separation column array is in the bypass state. State, see Figure D1; select one of the 1st to 9th enrichment columns of the enrichment column array B as the target sample column; when the enrichment column is turned on, the target sample elution process begins, using distillation The collector collects the target sample.

Corresponding to device E,

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the injection valve, and the outlet of the injection valve and the double The ① position of the two-position four-way valve is connected. The ④ position of the two-position four-way valve is connected to the X interface of the enrichment column array A. The Y interface of the enrichment column array A is connected to the ⑦ number of the two-position four-way valve. Position connection, the ⑧ position of the double two-position four-way valve is connected to the inlet of the liquid chromatography separation column array, the outlet of the liquid chromatography separation column array is connected to the detector, the outlet of the detector is connected to the inlet of the gradient mixer B, The outlet of the diluent pump is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the ⑥ position of the double two-position four-way valve; the ⑤ position of the double two-position four-way valve is connected to the enrichment column array B. The interface X is connected, and the Y interface of the enrichment column array B is connected to the position ② of the double two-position four-way valve; the position ③ of the double two-position four-way valve is connected to the inlet of the fraction collector. The ① position, ② position, ③ position, ④ position, ⑤ position, ⑥ position, position, and ⑧ position of the double two-way four-way valve only indicate the adjacency relationship, and do not necessarily correspond to the physical marks of the double two-way four-way valve.

In Figure E1, the two-position two-position four-way valve is in the A state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A constitute a chromatographic separation gradient elution mobile phase supply system, and the gradient mixer The outlet of A is connected to the inlet of the injection valve. The outlet of the injection valve is connected to the ① position of the double two-position four-way valve; the ① position of the double two-position four-way valve is connected to the ④ position and is connected to the enrichment column. The interface X of the array A (the interface X of the enrichment column array A is its entrance at this time); the interface Y of the enrichment column array A (the interface Y of the enrichment column array A at this time is its exit); The ⑦ position of the on-off valve is connected and connected to the inlet of the liquid chromatography separation column array via the 两位 position of the double two-position four-way valve; select any column in the separation column array for separation; the outlet of the separation column array and the detector Connected, the detector detects the chromatographic signal, the outlet of the detector is connected to the inlet of the gradient mixer B, the outlet of the diluent pump is connected to the inlet of the gradient mixer B, and the sample flows out after the gradient mixer B dilutes the column, and the gradient mixer B The outlet is connected to the ⑥ position of the double two-position four-way valve; the double two-position four-way valve The ⑥ position is connected to the ⑤ position; the ⑤ position of the double two-position four-way valve is connected to the interface X of the enrichment column array B (the interface X of the enrichment column array B is its entrance at this time), and the enrichment column array The interface Y of B (the interface Y of the enrichment column array B is its outlet at this time) is connected to the ② position of the double two-position four-way valve to realize the enrichment of the separated sample; The position ③ of the double two-position four-way valve is turned on, and the position ③ of the double two-position four-way valve is connected to the inlet of the fraction collector to realize sample collection.

In Figure E2, the two-position two-position four-way valve is in the B state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A constitute a chromatographic separation gradient elution mobile phase supply system, and the gradient mixer The outlet of A is connected to the inlet of the injection valve. The outlet of the injection valve is connected to the ① position of the double two-position four-way valve, and the ① position of the double two-position four-way valve is connected to the ② position. The number ② of the valve is connected to the interface Y of the enrichment column array B (the interface Y of the enrichment column array B is its entrance at this time); the interface X of the enrichment column array B (the interface of the enrichment column array B at this time) X is its outlet) is connected to the ⑤ position of the double two-position four-way valve; the ⑤ position of the double two-position four-way valve is connected to the ⑧ position, and the ⑧ position of the double two-position four-way valve is separated from the liquid chromatography. The inlet of the column array is connected; any column in the separation column array is selected for separation; the outlet of the separation column array is connected to the detector, the detector detects the chromatographic signal, the outlet of the detector is connected to the inlet of the gradient mixer B, and the diluent pump The outlet of the gradient mixer B is connected to the inlet of the gradient mixer B. The outlet of the mixer B is connected to the ⑥ position of the double two-position four-way valve; the ⑥ position of the double two-position four-way valve is connected to the ⑦ position; the ⑦ position of the double two-position four-way valve is connected to the enrichment column array A. The interface Y is connected (the interface Y of the enrichment column array A is its inlet at this time); the interface X of the enrichment column array A (the interface X of the enrichment column array A is its outlet at this time) and the double two-position four-way valve ④ Number connection to realize the enrichment of separated samples; Number ④ of the double two-position four-way valve is connected to number ③; Number ③ of the double two-position four-way valve is connected to the inlet of the fraction collector to realize the sample collect.

In this embodiment, the enrichment column array A has 9 enrichment columns, which are sequentially numbered as the first enrichment column, the second enrichment column, and the like of the enrichment column array A, and the last number is the enrichment column array A The 9th enrichment column; the enrichment column array B is a two-stage enrichment column array, and each stage of the enrichment column array has 9 enrichment columns, that is, the enrichment column array B is 18 enrichment columns, which are sequentially numbered as enrichment The first enrichment column of column array B, the second enrichment column, and so on. The last is the eighteenth enrichment column of enrichment column array B; the liquid chromatography separation column array has five separation columns, which are sequentially numbered as The first separation column, the second separation column, etc., the last one is the fifth separation column; the double two-position four-way valve in Figure E6 (a) is in the A state, and the double two-position four in Figure E6 (b). The on-off valve is in the B state.

First-dimension separation process control: the double two-position four-way valve is in the A state, see Figure E1; the enrichment column array A is in the bypass state; the sample loop is loaded on the injection valve; the first-dimensional chromatographic separation column is selected For example, the first separation column, the chromatographic separation column is manually turned on; when the injection valve is switched to the INJECT state, the first-dimensional separation is started; with the assistance of the diluent pump, the fractions are sequentially used according to the nature of the sample and the detection signal. Enrichment is performed in the 1st to 9th enrichment columns of the enrichment column array B, and the 10th to 18th enrichment columns of the enrichment column array B are reserved for the third-dimensional separation; this is repeated until the enrichment column array B There are enough compounds in the 1st to 9th enrichment columns in the column to be transferred to the second-dimensional separation process control; if the second-dimensional separation is not required, the enrichment column array B is always in the bypass state and collected by fractions The device directly collects multiple fractions.

Control of the second two-dimensional separation process: After the control of the first two-dimensional separation process is completed, the injection valve should be switched to the LOAD state, and the two-position two-way four-way valve should be switched to the B state, see Figure E2; The second separation column, the chromatographic separation column is manually turned on; one of the first to ninth enrichment columns of the enrichment column array B is selected as a sample column for the second-dimensional separation; when the enrichment column is turned on At the beginning, the second-dimensional separation process begins; with the assistance of the diluent pump, the fractions are sequentially switched to the 1st to 9th enrichment columns of enrichment column array A for enrichment according to the sample properties and detection signals; if not required, For the third dimension separation, the first to ninth enrichment columns of the enrichment column array A can be sequentially eluted, and the fraction collector can be used to directly collect multiple fractions; in this way, the second dimension separation is completed;

Control of the third-dimensional separation process: After the control of the second-dimensional separation process is completed, the double two-position four-way valve is switched to the A state, see FIG. E1; the injection valve remains in the LOAD state; and the third-dimensional chromatography column is selected, for example, the third separation column The chromatographic separation column is manually turned on; one of the first to ninth enrichment columns of the enrichment column array A is selected as a sample column for the third dimension separation; when the enrichment column is turned on, the third dimension separation is performed The process begins; if a fourth-dimensional separation is required, the fractions are sequentially switched to the 10th to 18th enrichment columns of enrichment column array B for enrichment with the assistance of the diluent pump according to the sample properties and detection signals. The fraction is cut into 9 parts; if the fourth-dimensional separation is not required, the 1st to 9th enrichment columns of the enrichment column array A can be sequentially eluted and separated, and a plurality of fractions can be directly performed by the fraction collector. Collection; repeat this step to complete the third separation.

Control of the fourth-dimensional separation process: After the control of the third-dimensional separation process, the double two-position four-way valve is switched to the B state, see Figure E2; the injection valve remains in the LOAD state; a fourth-dimensional chromatographic separation column is selected, for example, the fourth separation Column, the chromatographic separation column is manually turned on; one of the 10th to 18th enrichment columns of the enrichment column array B is selected as the fourth-dimensional separation sample column; when the enrichment column is turned on, the first The four-dimensional separation process begins; under the action of a gradient eluent, the compounds in the enrichment column as the sample column can be eluted, and the fourth-dimensional separation is performed under the action of the fourth separation column; The fractions were collected; in this way, the fourth-dimensional separation was completed.

Corresponding to device F,

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the ten-position valve is connected, the ⑩ position of the two-position ten-way valve is connected to the X interface of the enrichment column array B, and the Y interface of the enrichment column array B is connected to the ③ position of the two-position ten-way valve. The ② position of the two-position ten-way valve is connected to the ⑦ position, the ⑥ position of the two-position ten-way valve is connected to the inlet of the liquid chromatography separation column array, and the outlet of the liquid chromatography separation column array is connected to the detector. The outlet of is connected to the inlet of the gradient mixer B, the outlet of the diluent pump is connected to the inlet of the gradient mixer B, the outlet of the gradient mixer B is connected to the 两位 position of the two-position ten-way valve, and the 两位 of the two-position ten-way valve The number position is connected to the X interface of the enrichment column array A, the Y interface of the enrichment column array A is connected to the position ⑤ of the two-position ten-way valve, and the position ④ of the two-position ten-way valve is connected to the inlet of the fraction collector . The ①, ②, ③, ④, ⑤, ⑥, ⑦, ⑧, ⑨, ⑩, and ⑩ positions of the two-position ten-way valve only indicate the positional adjacency relationship. Correspondence.

In Figure F1, the two-position ten-way valve is in the A state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A form a chromatographic separation gradient elution mobile phase supply system. The gradient mixer A The outlet of the sample valve is connected to the inlet of the sample valve, and the outlet of the sample valve is connected to the ① position of the two-position ten-port valve; the ① position of the two-position ten-port valve is connected to the ⑩ position and is connected to the Interface X (the interface X of the enrichment column array B is its inlet at this time); interface Y of the enrichment column array B (the interface Y of the enrichment column array B at this time is its outlet); The position is connected, and the ③ position of the two-position ten-way valve is connected to the ② position; the ② position of the two-position ten-way valve is connected to the ⑦ position, and the ⑦ position of the two-position ten-way valve is connected to the ⑥ position. ; The number ⑥ of the two-position ten-way valve is connected to the inlet of the liquid chromatography separation column array; any column in the separation column array is selected for separation; the outlet of the separation column array is connected to the detector, and the detector detects the chromatographic signal and detects The outlet of the mixer is connected to the inlet of the gradient mixer B, and the outlet of the diluent pump is connected to the inlet of the gradient mixer B. Mixer B dilutes the column and flows out of the sample. The outlet of the gradient mixer B is connected to the ⑨ position of the two-position ten-port valve; the ⑨ position of the two-port ten-port valve is in communication with the ⑧ position; Is connected to the interface X of the enrichment column array A (the interface X of the enrichment column array B is its entrance at this time), and the interface Y of the enrichment column array A (the interface Y of the enrichment column array A is its exit at this time) Connected to position ⑤ of the two-position ten-way valve to realize the enrichment of separated samples;

position

⑤ and ④ of the two-position ten-way valve are connected, and position ④ of the two-position ten-way valve is connected to the fraction collector. The inlet is connected for sample collection.

In Figure F2, the two-position ten-way valve is in the B state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A constitute a chromatographic separation gradient elution mobile phase supply system. The gradient mixer A The outlet of the sample valve is connected to the inlet of the sample valve. The outlet of the sample valve is connected to the ① position of the two-position ten-way valve, and the ① position of the two-position ten-port valve is in communication with the ② position; No. position is connected to No. position, and the No. position of the two-position ten-way valve is in communication with the No. position; the No. position of the two-position ten-way valve is connected to the interface X of the enrichment column array A (the enrichment column array at this time) The interface X of A is its inlet); the interface Y of the enrichment column array A (the interface Y of the enrichment column array A is its outlet at this time) is connected to the position ⑤ of the two-position ten-way valve; The ⑤ position is connected to the ⑥ position, and the ⑥ position of the two-position ten-way valve is connected to the inlet of the liquid chromatography separation column array; select any column in the separation column array for separation; the outlet of the separation column array and the detector Connected, the detector detects the chromatographic signal, the outlet of the detector is connected to the inlet of the gradient mixer B, and the outlet of the diluent pump is mixed with the gradient The inlet of device B is connected, and the sample flows out after the gradient mixer B dilutes the column. The outlet of the gradient mixer B is connected to the ⑨ position of the two-position ten-port valve; the ⑨ position of the two-position ten-port valve is in communication with the ⑩ position; The position of the two-position ten-way valve is connected to the interface X of the enrichment column array B (the interface X of the enrichment column array B is its entrance at this time); the interface Y of the enrichment column array B (the enrichment column array B is now The interface Y is its outlet) is connected to the number ③ of the two-position ten-way valve to realize the enrichment of separated samples; the

number

③ and ④ of the two-position ten-way valve are connected; the number ④ of the two-position ten-way valve is connected. The position is connected to the inlet of the fraction collector to realize sample collection.

In this embodiment, the enrichment column array B has 9 enrichment columns, which are sequentially numbered as the first enrichment column, the second enrichment column, and the like of the enrichment column array B, and the last number is the enrichment column array B. The 9th enrichment column; the enrichment column array A is a two-stage enrichment column array, and each stage of the enrichment column array has 9 enrichment columns, that is, the enrichment column array A is 18 enrichment columns, which are sequentially numbered as enrichment The first enrichment column of column array A, the second enrichment column, and so on. The last is the eighteenth enrichment column numbered as enrichment column array A; the liquid chromatography separation column array has five separation columns, numbered sequentially The first separation column, the second separation column, etc., the last one is the fifth separation column; the two-position ten-port valve in Fig. F6 (a) is in the A state, and the two-position ten-port valve in Fig. F6 (b). B state.

First-dimension separation process control: the two-position ten-way valve is in the A state, see Figure F1; the enrichment column array B is in the bypass state; the sample is loaded into the quantitative loop on the injection valve; the first-dimensional chromatographic separation column is selected, For example, the first separation column, the chromatographic separation column is manually turned on; when the injection valve is switched to the INJECT state, the first-dimensional separation is started; with the assistance of the diluent pump, the fractions are sequentially enriched according to the sample properties and detection signals. Enrichment is performed in the 1st to 18th enrichment columns of the concentration column array A; this is repeated until enough compounds in the 1st to 18th enrichment columns of the concentration column array A are transferred to the second-dimensional separation Process control; if the second-dimensional separation is not required, the enrichment column array A is always in the bypass state, and a fraction collector is used to directly collect multiple fractions.

Control of the second-dimensional separation process: After the control of the first-dimensional separation process is completed, the injection valve should be switched to the LOAD state, and the two-position ten-way valve is switched to the B state, see Figure F2; select the second-dimensional chromatographic separation column. 2 separation column, the chromatographic separation column is manually turned on; one of the first to 18th enrichment columns of the enrichment column array A is selected as a sample column for the second-dimensional separation; when the enrichment column is turned on The second-dimensional separation process begins; with the assistance of the diluent pump, the fractions are sequentially switched to the 1st to 9th enrichment columns of the enrichment column array B for enrichment according to the sample properties and detection signals; if the first For three-dimensional separation, the first to ninth enrichment columns of the enrichment column array B can be sequentially eluted, and the fraction collector can be used to directly collect multiple fractions; in this way, the second-dimensional separation is completed;

Control of the third-dimensional separation process: After the control of the second-dimensional separation process, the two-position ten-way valve is switched to the A state, see Figure F1; the injection valve remains in the LOAD state; the enrichment column array A is in the bypass state; the third-dimensional chromatography is selected A separation column, for example, a third separation column, the chromatographic separation column is manually turned on; one of the first to ninth enrichment columns of the enrichment column array B is selected as a sample column for the third separation; When the column is turned on, the third-dimensional separation process begins; a plurality of separated fractions are collected using a fraction collector; and the third-dimensional separation is completed by repeating this process.

Corresponds to device H, a multi-dimensional liquid chromatography separation system, including HPLC gradient pump A, HPLC gradient pump B, diluent pump, gradient mixer A, gradient mixer B, injection valve, rich Concentrated column array A, enriched column array B, fraction collector, liquid chromatography separation column array, detector, two-position eight-way valve, and connecting pipeline. The diluent pump is a high-performance liquid diluent pump.

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the 8-position valve is connected, the ⑧ position of the 2-position 8-way valve is connected to the X interface of the enrichment column array B, and the Y interface of the enrichment column array B is connected to the ④ position of the 2-position eight-way valve. The position ⑤ of the two-position eight-way valve is connected to the inlet of the liquid chromatography separation column array. The outlet of the liquid chromatography separation column array is connected to the detector. The outlet of the detector is connected to the inlet of the gradient mixer B. The outlet is connected to the inlet of the gradient mixer B. The outlet of the gradient mixer B is connected to the ③ position of the two-position eight-way valve, and the ② position of the two-position eight-way valve is connected to the X interface of the enrichment column array A to enrich. The Y interface of the column array A is connected to the ⑥ position of the two-position eight-way valve, and the ⑦ position of the two-position eight-way valve is connected to the inlet of the fraction collector. The

positions

In Figure H1, the two-position eight-way valve is in the A state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A form a chromatographic separation gradient elution mobile phase supply system. The gradient mixer A The outlet of the sample valve is connected to the inlet of the injection valve, and the outlet of the sample valve is connected to the ① position of the two-position eight-way valve; Interface X (the interface X of the enrichment column array B is its inlet at this time); interface Y of the enrichment column array B (the interface Y of the enrichment column array B at this time is its outlet); The number is connected and connected to the inlet of the liquid chromatography separation column array through the number ⑤ of the two-position eight-way valve; any column in the separation column array is selected for separation; the outlet of the separation column array is connected to the detector, and the detector detects Chromatographic signal, the outlet of the detector is connected to the inlet of the gradient mixer B, the outlet of the diluent pump is connected to the inlet of the gradient mixer B, and the sample is flowed out after the gradient mixer B dilutes the column. Number ③ of on-off valve is connected;

number

③ and ② of two-position eight-way valve Conduction; the number ② of the two-position eight-way valve is connected to the interface X of the enrichment column array A (the interface X of the enrichment column array A is its entrance at this time), and the interface Y of the enrichment column array A (the rich at this time) The interface Y of the column array A is its outlet) and is connected to the ⑥ position of the two-position eight-way valve to realize the enrichment of separated samples; the ⑥ position of the two-position eight-way valve and the ⑦ position of the two-position eight-way valve The ； position of the two-position eight-way valve is connected to the inlet of the fraction collector to realize sample collection.

In Figure H2, the two-position eight-way valve is in the B state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A form a chromatographic separation gradient elution mobile phase supply system. The gradient mixer A The outlet of the valve is connected to the inlet of the injection valve. The outlet of the injection valve is connected to the ① position of the two-position eight-way valve. The ① position of the two-position eight-way valve is in communication with the ② position; ② of the two-position eight-way valve. The number is connected to the interface X of the enrichment column array A (the interface X of the enrichment column array A is its entrance at this time); the interface Y of the enrichment column array A (the interface Y of the enrichment column array B is its exit at this time) ) Is connected to position ⑥ of two-position eight-way valve; position ⑥ of two-position eight-way valve is connected to position ⑤; position ⑤ of two-position eight-way valve is connected to the inlet of the liquid chromatography separation column array; select Any column in the separation column array is used for separation; the outlet of the separation column array is connected to the detector, the detector detects the chromatographic signal, the outlet of the detector is connected to the inlet of the gradient mixer B, and the outlet of the diluent pump is connected to the gradient mixer B The inlet of the gradient mixer B is used to dilute the column and the sample flows out. The outlet of the gradient mixer B is connected to the sample. The position ③ of the two-position eight-way valve is connected to the position ④ of the two-position eight-way valve; the position ④ of the two-position eight-way valve is connected to the interface Y of the enrichment column array B (the enrichment column at this time) The interface Y of the array B is its inlet); the interface X of the enrichment column array B (the interface X of the enrichment column array A is its outlet at this time) is connected to the ⑧ position of the two-position eight-way valve to realize the enrichment of the separated sample. The ⑧ position of the two-position eight-way valve is in communication with the ⑦ position, and the ⑦ position of the two-position eight-way valve is connected to the inlet of the fraction collector to realize sample collection.

In this embodiment, the enrichment column array B has 9 enrichment columns, which are sequentially numbered as the first enrichment column, the second enrichment column, and the like of the enrichment column array B, and the last number is the enrichment column array B. The 9th enrichment column; the enrichment column array A is a two-stage enrichment column array, and each stage of the enrichment column array has 9 enrichment columns, that is, the enrichment column array A is 18 enrichment columns, which are sequentially numbered as enrichment The first enrichment column of column array A, the second enrichment column, and so on. The last is the eighteenth enrichment column numbered as enrichment column array A; the liquid chromatography separation column array has five separation columns, numbered sequentially The first separation column, the second separation column, etc., the last one is the fifth separation column; the two-position eight-way valve in Fig. H6 (a) is in the A state, and the two-position eight-way valve in Fig. H6 (b) B state.

Control of the first-dimensional separation process: the two-position eight-way valve is in the A state, see Figure H1; the enrichment column array B is in the bypass state; the sample is loaded into the quantitative loop on the injection valve; the first-dimensional chromatographic separation column is selected, For example, the first separation column, the chromatographic separation column is manually turned on; when the injection valve is switched to the INJECT state, the first-dimensional separation is started; with the assistance of the diluent pump, the fractions are sequentially enriched according to the sample properties and detection signals. Enrichment is performed in the 1st to 9th enrichment columns of the concentration column array A, and the 10th to 18th enrichment columns of the concentration column array A are reserved for the third dimension separation; this is repeated until the concentration of the enrichment column array A Enough compounds in the 1st to 9th enrichment columns are transferred to the second-dimensional separation process control; if the second-dimensional separation is not required, the enrichment column array A is always in the bypass state, and a fraction collector is used The collection of multiple fractions was performed directly.

Second-dimensional separation process control: After the first-dimensional separation process control is completed, the injection valve should be switched to the LOAD state, and the two-position eight-way valve should be switched to the B state, see Figure H2. Select the second-dimensional chromatographic separation column. 2 separation column, the chromatographic separation column is manually turned on; one of the 1st to 9th enrichment columns of the enrichment column array A is selected as a sample column for the second-dimensional separation; when the enrichment column is turned on The second-dimensional separation process begins; with the assistance of the diluent pump, the fractions are sequentially switched to the 1st to 9th enrichment columns of the enrichment column array B for enrichment according to the sample properties and detection signals; if the first For three-dimensional separation, the first to ninth enrichment columns of the enrichment column array B can be sequentially eluted, and the fraction collector can be used to directly collect multiple fractions; in this way, the second-dimensional separation is completed;

Control of the third-dimensional separation process: After the control of the second-dimensional separation process is completed, the two-position eight-way valve is switched to the A state, see FIG. H1; the injection valve remains in the LOAD state; and the third-dimensional chromatography column is selected, for example, the third separation column, The chromatographic separation column was manually turned on; one of the first to ninth enrichment columns of the enrichment column array B was selected as a sample column for the third separation; when the enrichment column was turned on, the third separation process was performed Start; if a fourth-dimensional separation is required, with the assistance of a diluent pump, the fractions are sequentially switched to the 10th to 18th enrichment columns of enrichment column array A for enrichment according to the sample properties and detection signals. The fraction is cut into 9 parts; if the fourth-dimensional separation is not required, the 1st to 9th enrichment columns of the enrichment column array B can be sequentially eluted and separated, and the fraction collector can be used to directly perform the distillation of multiple fractions. Collect; repeat this way to complete the third dimension separation.

Fourth-dimensional separation process control: After the third-dimensional separation process control is completed, the two-position eight-way valve is switched to the B state, see Figure H2; the injection valve remains in the LOAD state; a fourth-dimensional chromatographic separation column is selected, for example, the fourth separation column The chromatographic separation column was manually turned on; one of the 10th to 18th enrichment columns of the enrichment column array A was selected as the fourth-dimensional separation sample column; when the enrichment column was turned on, the fourth The dimension separation process begins; under the action of the gradient eluent, the compounds in the enrichment column as the sample column can be eluted, and the fourth dimension separation is performed under the action of the fourth separation column; The fractions were collected; in this way, the fourth-dimensional separation was completed.

Corresponds to device I, a multi-dimensional liquid chromatography separation system, including high-performance liquid chromatography gradient pump A, high-performance liquid chromatography gradient pump B, diluent pump, gradient mixer A, gradient mixer B, injection valve, rich Concentrated column array A, enriched column array B, fraction collector, liquid chromatography separation column array, detector, double two-position four-way valve, and connecting pipeline. Among them, the two-position two-position four-way valve is a two-position multi-position valve in the technical solution of the present invention, which is composed of two-position four-way valve A and two-position four-way valve B and operates according to the principle of one two-position four-way valve; The column array A and the enrichment column array B are each composed of a series connection of a two-position four-way valve and an enrichment column. The liquid chromatography separation column array is a two-position four-way valve and a separation column. The connected units are connected in series; the diluent pump is a high-performance liquid diluent pump.

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, and the outlet of the gradient mixer A is connected to the ① port of the two-position four-way valve A, and the two-position four Port ② of port A is connected to the X port of the enrichment column array B, and port Y of the enrichment column array B is connected to the port ② of the two-position four-way valve B, and the port ① of the two-position four-way valve B is connected to the injection valve The inlet of the injection valve is connected to the inlet of the LC separation column array. The outlet of the LC separation column array is connected to the detector. The outlet of the detector is connected to the inlet of the gradient mixer B. The outlet is connected to the inlet of the gradient mixer B, the outlet of the gradient mixer B is connected to the ③ port of the two-position four-way valve B, and the ④ port of the two-position four-way valve B is connected to the Y interface of the enrichment column array A to enrich The X interface of the column array A is connected to the ④ port of the two-position four-way valve A, and the ③ port of the two-position ten-way valve is connected to the inlet of the fraction collector. The ①, ②, ③, and ④ ports of the two-position four-way valve A and the two-position four-way valve B only indicate the positional adjacency, and do not necessarily correspond to the physical marks of the two-position four-way valve A and the two-position four-way valve B. The ports The naming and ordering are named from any port of the two-position four-way valve A and the two-position four-way valve B in a counterclockwise or clockwise direction from ①.

In Figure I1, the two-position four-way valve A and the two-position four-way valve B are both in the A state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A constitute a chromatographic separation gradient elution. In the mobile phase supply system, the outlet of the gradient mixer A is connected to the ① port of the two-position four-way valve A; the ① port of the two-position four-way valve A is connected to the ② port and is connected to the interface X of the enrichment column array B (at this time The interface X of the enrichment column array B is the inlet thereof; the interface Y of the enrichment column array B (the interface Y of the enrichment column array B is its outlet at this time) is connected to the ② port of the two-position four-way valve B, two The ② port of the four-way valve B is connected to the ① port; the ① port of the two-way four-way valve B is connected to the inlet of the injection valve, and the outlet of the injection valve is connected to the inlet of the liquid chromatography separation column array; a separation column is selected Any column in the array is separated; the outlet of the separation column array is connected to the detector, the detector detects the chromatographic signal, the outlet of the detector is connected to the inlet of the gradient mixer B, and the outlet of the diluent pump is connected to the inlet of the gradient mixer B Connected, the sample is flowed out after the column is diluted by the gradient mixer B, and the outlet of the gradient mixer B and the two The ③ port of four-way valve B is connected; the ③ port of two-position four-way valve B is in communication with the ④ port; the ④ port of two-position four-way valve B is connected to interface Y of enrichment column array A (at this time, enrichment column array B Interface Y is its inlet), interface X of enrichment column array A (interface X of enrichment column array A is its outlet at this time) is connected to the ④ port of two-position four-way valve A to realize the enrichment of separated samples ; The ④ port of the two-position four-way valve A is in communication with the ③ port, and the ③ port of the two-position four-way valve A is connected to the inlet of the fraction collector to realize sample collection.

In Figure I2, the two-position four-way valve A and the two-position four-way valve B are in the B state. At this time, the HPLC gradient pump A, the HPLC gradient pump B and the gradient mixer A constitute a chromatographic separation gradient elution mobile phase supply system. The outlet of the gradient mixer A and the ① port of the two-position four-way valve A Connection, ① port of two-position four-way valve A is in communication with ④ port; ④ port of two-position four-way valve A is connected to interface X of enrichment column array A (at this time, interface X of enrichment column array A is its inlet ); The interface Y of the enrichment column array A (the interface Y of the enrichment column array A is its outlet at this time) is connected to the ④ port of the two-position four-way valve B; the ④ port of the two-position four-way valve B and the ① port guide The ① port of the two-position four-way valve B is connected to the inlet of the injection valve, and the outlet of the injection valve is connected to the inlet of the liquid chromatography separation column array; any column in the separation column array is selected for separation; the separation column array The outlet of the detector is connected to the detector. The detector detects the chromatographic signal. The outlet of the detector is connected to the inlet of the gradient mixer B. The outlet of the diluent pump is connected to the inlet of the gradient mixer B. After the gradient mixer B dilutes the column, the sample flows out. , The outlet of the gradient mixer B is connected to the ③ port of the two-position four-way valve B ; The ③ port of the two-position four-way valve B is in communication with the ② port; the ② port of the two-position four-way valve B is connected to the interface Y of the enrichment column array B (the interface Y of the enrichment column array B is its inlet at this time) ; The interface X of the enrichment column array B (the interface X of the enrichment column array B is its outlet at this time) is connected to the ② port of the two-position four-way valve A to realize the enrichment of the separated sample; ② The port is in communication with the ③ port; the ③ port of the two-position four-way valve A is connected to the inlet of the fraction collector to realize sample collection.

In this embodiment, the enrichment column array B has 9 enrichment columns, which are sequentially numbered as the first enrichment column, the second enrichment column, and the like of the enrichment column array B, and the last number is the enrichment column array B. 9th enrichment column; there are 18 enrichment columns in enrichment column array A, which are numbered as the 1st enrichment column, the 2nd enrichment column, and so on, and the last number is the enrichment column array The 18th enrichment column of A; the liquid chromatography separation column array has 4 separation columns, which are sequentially numbered as the 1st separation column, the 2nd separation column, etc., and the last is the 4th separation column; Figure I7 (a) The four-way valve A and two-position four-way valve B in the state are both in the A state, and the four-way valve A and two-position four-way valve B in Fig. I7 (b) are in the B state.

First-dimensional separation process control: the two-position four-way valve A and the two-position four-way valve B are in the A state, see Figure I1; the enrichment column array B is in the bypass state; the sample loop is loaded on the injection valve ; Select the first-dimensional chromatographic separation column, for example, the first separation column, the chromatographic separation column is turned on manually; when the injection valve is switched to the INJECT state, the first-dimensional separation is started; with the assistance of the diluent pump, according to the nature of the sample And the detection signal, the fractions are first enriched in the first to ninth enrichment columns of the enrichment column array A, and the tenth to eighteenth enrichment columns of the enrichment column array A are reserved for the third dimension separation; Repeat until there are enough compounds in the 1st to 9th enrichment columns of the enrichment column array A, and transfer to the second-dimensional separation process control; if the second-dimensional separation is not needed, the enrichment column array A is always in In the bypass state, multiple fractions are directly collected by the fraction collector.

Control of the second two-dimensional separation process: After the control of the first two-dimensional separation process is completed, the injection valve should be switched to the LOAD state, and the two-position four-way valve A and the two-position four-way valve B should be switched to the B state, see Figure I2; A two-dimensional chromatographic separation column, for example, a second separation column, which is manually turned on; one of the first to ninth enrichment columns of the enrichment column array A is selected as a sample column for the second-dimensional separation ; When the enrichment column is turned on, the second-dimensional separation process begins; with the assistance of the diluent pump, the fractions are sequentially switched to the 1st to 9th enrichment columns of the enrichment column array B according to the sample properties and detection signals. If the third-dimensional separation is not required, the first to ninth enrichment columns of the enrichment column array B can be eluted in sequence, and multiple fractions can be directly collected using the fraction collector; Complete the second dimension separation;

Control of the third-dimensional separation process: After the control of the second-dimensional separation process, the two-position four-way valve A and the two-position four-way valve B are switched to the A state, see FIG. I1; the injection valve remains in the LOAD state; the third-dimensional chromatographic separation is selected Column, for example, the third separation column, the chromatographic separation column is manually turned on; one of the first to ninth enrichment columns of the enrichment column array B is selected as the sample column for the third separation; when the enrichment When the column is turned on, the third-dimensional separation process begins; if a fourth-dimensional separation is required, the fractions are sequentially switched to the 10th to 18th columns of the enrichment column array A according to the sample properties and detection signals with the assistance of the diluent pump. The enrichment column is enriched, and the fraction is cut into 9 parts; if the fourth-dimensional separation is not required, the 1st to 9th enrichment columns of the enrichment column array B can be sequentially eluted and separated, and the fractions are used. The collector directly collects multiple fractions; in this way, the third-dimensional separation is completed.

Control of the fourth-dimensional separation process: After the control of the third-dimensional separation process, the two-position four-way valve A and the two-position four-way valve B are switched to the B state, see Figure I2; the injection valve remains in the LOAD state; the fourth-dimensional chromatography is selected Separation column, for example, the fourth separation column, the chromatographic separation column is manually turned on; one of the 10th to 18th enrichment columns of the enrichment column array A is selected as the fourth-dimensional separation sample column; when the When the enrichment column is turned on, the fourth-dimensional separation process begins; under the action of the gradient eluent, the compounds in the enrichment column as the sample column can be eluted, and the fourth-dimensional separation is performed by the fourth separation column ; Use a fraction collector to collect multiple fractions; repeat this to complete the fourth dimension.

Corresponds to device J, a multi-dimensional liquid chromatography separation system, including HPLC gradient pump A, HPLC gradient pump B, diluent pump, gradient mixer A, gradient mixer B, injection valve, rich Column array, fraction collector, liquid chromatography separation column array, detector, two-position six-way valve, and connecting pipeline. Among them, the enrichment column array and the liquid chromatography separation column array are constructed by a multi-position selection valve, and the diluent pump is a high-performance liquid diluent pump.

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the six-position valve is connected, and the ⑥ position of the two-position six-way valve is connected to the inlet of the LC separation column array. The outlet of the LC separation column array is connected to the detector, and the outlet of the detector is mixed with the gradient. The inlet of the diluent pump is connected to the inlet of the gradient mixer B. The outlet of the gradient mixer B is connected to the ④ position of the two-position six-way valve, and the ⑤ position of the two-position six-way valve is to be enriched. The interface Y of the column array is connected, the interface X of the enriched column array is connected to the position ② of the two-position six-way valve, and the position ③ of the two-position six-way valve is connected to the inlet of the fraction collector.

In the above-mentioned multi-dimensional liquid chromatography separation system, the outlet of the gradient mixer B can also be connected to the position ③ of the two-position six-way valve. At this time, the position ④ of the two-position six-way valve and the inlet of the fraction collector Connection, other connection lines remain unchanged.

In Figure J1, the two-position six-way valve is in the A state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A form a chromatographic separation gradient elution mobile phase supply system. The gradient mixer A The outlet of the valve is connected to the inlet of the injection valve. The outlet of the injection valve is connected to the ① position of the two-position six-way valve; the ① position of the two-position six-way valve is connected to the ⑥ position and is connected to the liquid chromatography separation column array. The inlet of the separation column is selected for separation; the outlet of the separation column array is connected to the detector, the detector detects the chromatographic signal, the outlet of the detector is connected to the inlet of the gradient mixer B, and the outlet of the diluent pump It is connected to the inlet of the gradient mixer B and flows out of the sample after the gradient mixer B dilutes the column. The outlet of the gradient mixer B is connected to the ④ position of the two-position six-way valve; The position ⑤ of the on-off valve is connected; the position ⑤ of the two-position six-way valve is connected to the interface Y of the enrichment column array (the interface Y of the enrichment column array is its entrance at this time), and the interface X of the enrichment column array (At this time, the interface X of the enrichment column array is its exit) The ② position of the valve is connected to realize the enrichment of separated samples; the ② position of the two-position six-way valve is connected to the ③ position of the two-position six-way valve; the ③ position of the two-position six-way valve is connected to the fraction collector The inlet is connected for sample collection.

In Figure J2, the two-position six-way valve is in the B state. At this time, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A constitute a chromatographic separation gradient elution mobile phase supply system, and the gradient mixer A The outlet of the injection valve is connected to the inlet of the injection valve. The outlet of the injection valve is connected to the ① position of the two-position six-way valve, and the ① position of the two-position six-way valve is in communication with the ② position; The number is connected to the interface X of the enrichment column array (the interface X of the enrichment column array is its entrance at this time); the interface Y of the enrichment column array (the interface Y of the enrichment column array is its exit at this time) and two bits The position ⑤ of the six-way valve is connected; the position ⑤ of the two-position six-way valve is connected to the position ⑥; the position ⑥ of the two-position six-way valve is connected to the inlet of the liquid chromatography separation column array; The separation column array is connected to the detector, the detector detects the chromatographic signal, the detector output is connected to the inlet of the gradient mixer B, the outlet of the diluent pump is connected to the inlet of the gradient mixer B, After the column was diluted by the gradient mixer B, the sample flowed out. No. ④ position six-way valve is connected; ④ number two position valve and the six-bit number ③ ON; ③ entry position number and fraction collector is connected to two six-way valve, the sample collection implement.

In this embodiment, the enrichment column array is composed of a two-stage enrichment column array and operates according to the principle of one enrichment column array. Each stage of the enrichment column array has 9 enrichment columns, that is, the enrichment column array is 18 enrichment columns. , The first enrichment column numbered as the enrichment column array, the second enrichment column, etc., the last 18th enrichment column numbered as the enrichment column array; the liquid chromatography separation column array has 5 separation columns , Numbered as the first separation column, the second separation column, etc., the last one is the fifth separation column; the two-position six-way valve in Figure J8 (a) is in the A state, and the two in Figure J8 (b) The six-position valve is in the B state.

The following is the three-dimensional separation process control of the structure of the above-mentioned multi-dimensional high-performance liquid chromatography separation system:

First-dimension separation process control: the two-position six-way valve is in the A state, see Figure J1; the sample is loaded into the sample valve; the first-dimensional chromatographic separation column, for example, the first separation column, is used for the chromatographic separation The column is manually turned on; when the injection valve is switched to the INJECT state, the first-dimensional separation is started; with the assistance of the diluent pump, the fractions are sequentially used in the first to ninth enrichment of the enrichment column array according to the sample properties and detection signals. The enrichment column is enriched, and the 10th to 18th enrichment columns of the enrichment column array are reserved for the third dimension separation; this is repeated until there are enough compounds in the 1st to 9th enrichment columns of the enrichment column array. , Transfer to the second-dimensional separation process control;

Second dimension loading process control: After the first dimension separation process control is completed, the injection valve should be switched to the LOAD state, the two-position six-way valve is switched to the B state, and the second dimension chromatography column is selected, for example, the second separation column. The chromatographic separation column is turned on manually, see FIG. J2. One of the enrichment columns from the 1st to 9th enrichment columns is selected as the second-dimensional separation sample column, and the target in the enrichment column is selected. The sample is eluted into the second separation column to complete the loading process of the second-dimensional separation;

Control of the second-dimension separation process: After completing the second-dimension loading process, the two-position six-way valve is switched to the A state for the second-dimension separation, see Figure J1; during the second-dimension separation process, the diluent pump assists Next, according to the sample properties and detection signals, the fractions are sequentially switched to the 10th to 18th enrichment columns of the enrichment column array for enrichment;

Control of the third-dimensional separation process: After the control of the second-dimensional separation process, the two-position six-way valve is switched to the B state, see FIG. J2; the injection valve remains in the LOAD state; and the third-dimensional chromatographic separation column is selected, for example, the third separation column. The chromatographic separation column was manually turned on; one of the 10th to 18th enrichment columns of the enrichment column array was selected as a sample column for the third separation; when the enrichment column was turned on, the third separation process started The fraction collector is used to directly collect multiple fractions; in this way, the third-dimensional separation is completed.

Claims

A multi-dimensional liquid chromatography separation system, characterized in that:

The constituent elements of the multi-dimensional liquid chromatography separation system and the connection modes between the elements are any of the following devices A, B, C, D, E, F, H, I, J:

Device A,

The multi-dimensional liquid chromatography separation system includes a high performance liquid chromatography gradient pump A, a high performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array A, Enrichment column array B, fraction collector, liquid chromatography separation column array, detector, two-position ten-way valve and connecting pipeline; positions ①, ②, ③, and ④ of the two-position ten-way valve , ⑤ position, ⑥ position, ⑦ position, ⑧ position, ⑩ position, ⑨ position, and ⑩ position only indicate the adjacency relationship, and do not need to correspond to the physical mark of the two-position ten-way valve. The interface begins to be named according to counterclockwise or clockwise from ①; the detector is used to detect the chromatographic signal during the separation process; the injection valve is used to inject;

The liquid chromatography separation column array is formed by a plurality of chromatographic separation columns connected in parallel through a multi-position selection valve, and only one chromatographic separation column can be connected at a time; a fixed inlet and a fixed outlet are provided to the outside, and At least one bypass, the bypass and the separation column are connected in parallel through a multi-position selection valve; when the bypass is on, other chromatographic separation columns will not be on, and when the other chromatographic separation column is on, the bypass will not be on; The number of separation columns is determined as required;

The enrichment column array A and the enrichment column array B are each formed by connecting multiple chromatographic enrichment columns in parallel through a multi-position selection valve, and only one enrichment column can be turned on at the same time; at least one by side The bypass and the enrichment column are connected in parallel through a multi-position selection valve; when the bypass is on, the other enrichment columns will not be on, and when the other enrichment columns are on, the bypass will not be on; The quantity is determined according to needs; there are two external interfaces, which are defined as interface X and interface Y respectively;

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the ten-position valve is connected, the ⑩ position of the two-position ten-port valve is connected to the interface X of the enrichment column array A, and the interface Y of the enrichment column array A is connected to the ⑦ position of the two-position ten-port valve. The position ⑥ of the two-position ten-way valve is connected to the inlet of the liquid chromatography separation column array. The outlet of the liquid chromatography separation column array is connected to the detector. The outlet of the detector is connected to the inlet of the gradient mixer B. The outlet is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the ⑧ position of the two-position ten-port valve; the ⑨ position of the two-position ten-port valve is connected to the ④ position; The number position is connected to the interface Y of the enrichment column array B, and the interface X of the enrichment column array B is connected to the position ② of the two-position ten-way valve; the position ③ of the two-position ten-way valve is connected to the inlet of the fraction collector. ;

By controlling the switching state of the two-position ten-way valve, the system is switched from the previous one-dimensional separation state to the next one-dimensional separation state, completes the cyclic chromatography function, and realizes the chromatographic separation function of multidimensional full-line detection;

Or device B,

The multi-dimensional liquid chromatography separation system includes a high performance liquid chromatography gradient pump A, a high performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array A, Enrichment column array B, fraction collector, liquid chromatography separation column array, detector, double two-position four-way valve and connecting pipeline; the two positions of the two-position four-way valve ①, ②, ③, The ④, ⑤, ⑥, ⑦, and ⑧ positions only indicate the adjacency relationship, and do not necessarily correspond to the physical marks of the double two-position four-way valve; the detector is used to detect the chromatographic signal during the separation process; the injection valve For injection

The liquid chromatography separation column array is formed by a plurality of chromatographic separation columns connected in parallel through a multi-position selection valve, and only one chromatographic separation column can be connected at a time; a fixed inlet and a fixed outlet are provided to the outside, and At least one bypass, the bypass and the separation column are connected in parallel through a multi-position selection valve; when the bypass is on, other chromatographic separation columns will not be on, and when the other chromatographic separation column is on, the bypass will not be on; The number of separation columns is determined as required;

The enrichment column array A and the enrichment column array B are formed by multiple chromatographic enrichment columns connected in parallel through a multi-position selection valve, and only one enrichment column can be turned on at the same time; at least one bypass, The bypass and the enrichment column are connected in parallel through a multi-position selection valve; when the bypass is on, the other enrichment columns will not be on, and when the other enrichment column is on, the bypass will not be on; the number of enrichment columns is based on Need to be determined; there are two external interfaces, which are defined as interface X and interface Y respectively;

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the injection valve, and the outlet of the injection valve and the double The ① position of the two-position four-way valve is connected, the ④ position of the two-position four-way valve is connected to the interface X of the enrichment column array A, and the interface Y of the enrichment column array A is connected to the ⑦ number of the two-position four-way valve. Position connection, the ⑧ position of the double two-position four-way valve is connected to the inlet of the liquid chromatography separation column array, the outlet of the liquid chromatography separation column array is connected to the detector, the outlet of the detector is connected to the inlet of the gradient mixer B, The outlet of the diluent pump is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the ③ position of the double two-position four-way valve; the ② position of the double two-position four-way valve is connected to the enrichment column array B. The interface Y is connected, and the interface X of the enrichment column array B is connected to the position ⑤ of the double two-position four-way valve; the position ⑥ of the double two-position four-way valve is connected to the inlet of the fraction collector;

By controlling the switching state of the two-position two-position four-way valve, the system is switched from the previous one-dimensional separation state to the next one-dimensional separation state, completes the cyclic chromatography function, and realizes the chromatographic separation function of multidimensional full-line detection;

Or device C,

The multi-dimensional liquid chromatography separation system includes a high performance liquid chromatography gradient pump A, a high performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array A, Enrichment column array B, fraction collector, liquid chromatography separation column array, detector, two-position eight-way valve, and connecting pipeline; positions ①, ②, ③, and ④ of the two-position eight-way valve , ⑤ position, ⑥ position, ⑧ position, ⑧ position only indicate the adjacency relationship, and do not need to correspond to the physical mark of the two-position eight-way valve. The numbers are named and sorted starting from any interface of the two-position eight-way valve in a counterclockwise or Clockwise from ① to sort and name; the detector is used to detect the chromatographic signal in the separation process; the injection valve is used to inject;

The liquid chromatography separation column array is formed by a plurality of chromatographic separation columns connected in parallel through a multi-position selection valve, and only one chromatographic separation column can be connected at a time; a fixed inlet and a fixed outlet are provided to the outside, and At least one bypass, the bypass and the separation column are connected in parallel through a multi-position selection valve; when the bypass is on, other chromatographic separation columns will not be on, and when the other chromatographic separation column is on, the bypass will not be on; The number of separation columns is determined as required;

The enrichment column array A and the enrichment column array B are formed by multiple chromatographic enrichment columns connected in parallel through a multi-position selection valve, and only one enrichment column can be turned on at the same time; at least one bypass, The bypass and the enrichment column are connected in parallel through a multi-position selection valve; when the bypass is on, the other enrichment columns will not be on, and when the other enrichment column is on, the bypass will not be on; the number of enrichment columns is based on Need to be determined; there are two external interfaces, which are defined as interface X and interface Y respectively;

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The position ① of the two-position eight-way valve is connected. The position ② of the two-position eight-way valve is connected to the interface X of the enrichment column array B. The interface Y of the enrichment column array B is connected to the position ⑥ of the two-position eight-way valve. The position ⑤ of the two-position eight-way valve is connected to the inlet of the liquid chromatography separation column array. The outlet of the liquid chromatography separation column array is connected to the detector. The outlet of the detector is connected to the inlet of the gradient mixer B. The outlet is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the ⑦ position of the two-position eight-way valve; the ⑧ position of the two-position eight-way valve is connected to the interface X of the enrichment column array A. The connector Y of the column array A is connected to the ④ position of the two-position eight-way valve; the ③ position of the two-position eight-way valve is connected to the inlet of the fraction collector;

By controlling the switching state of the two-position eight-way valve, the system is switched from the previous one-dimensional separation state to the next one-dimensional separation state, completes the cyclic chromatography function, and realizes the chromatographic separation function of multidimensional full-line detection;

Or device D,

The three-dimensional liquid chromatography separation system includes a high performance liquid chromatography gradient pump A, a high performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array A, Enrichment column array B, fraction collector, liquid chromatography separation column array, detector, two-position ten-way valve and connecting pipeline; positions ①, ②, ③, and ④ of the two-position ten-way valve , ⑤ position, ⑥ position, ⑦ position, ⑧ position, ⑩ position, ⑨ position, and ⑩ position only indicate the adjacency relationship, and do not need to correspond to the physical mark of the two-position ten-way valve. The interface begins to be named according to counterclockwise or clockwise from ①; the detector is used to detect the chromatographic signal during the separation process; the injection valve is used to inject;

The liquid chromatography separation column array is formed by a plurality of chromatographic separation columns connected in parallel through a multi-position selection valve, and only one chromatographic separation column can be connected at a time; a fixed inlet and a fixed outlet are provided to the outside, and At least one bypass, the bypass and the separation column are connected in parallel through a multi-position selection valve; when the bypass is on, other chromatographic separation columns will not be on, and when the other chromatographic separation column is on, the bypass will not be on; The number of separation columns is determined as required;

The enrichment column array A and the enrichment column array B are formed by multiple chromatographic enrichment columns connected in parallel through a multi-position selection valve, and only one enrichment column can be turned on at the same time; at least one bypass, The bypass and the enrichment column are connected in parallel through a multi-position selection valve; when the bypass is on, the other enrichment columns will not be on, and when the other enrichment column is on, the bypass will not be on; the number of enrichment columns is based on Need to be determined; there are two external interfaces, which are defined as interface X and interface Y respectively;

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the ten-position valve is connected, the ⑩ position of the two-position ten-port valve is connected to the interface X of the enrichment column array B, and the interface Y of the enrichment column array B is connected to the ③ position of the two-position ten-way valve. The ② position of the two-position ten-port valve is connected to the ⑦ position of the two-position ten-port valve, the ⑥ position of the two-position ten-port valve is connected to the inlet of the liquid chromatography separation column array, and the outlet of the liquid chromatography separation column array is connected to The detector is connected, the outlet of the detector is connected to the inlet of the gradient mixer B, the outlet of the diluent pump is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the ④ position of the two-position ten-way valve; The position ⑤ of the ten-way valve is connected to the interface Y of the enrichment column array A, and the interface X of the enrichment column array A is connected to the ⑧ position of the two-position ten-way valve; The inlet connection of the collector;

By controlling the switching state of the two-position ten-way valve, the system is switched from the previous one-dimensional separation state to the next one-dimensional separation state, completes the cyclic chromatography function, and realizes the three-dimensional full-line detection chromatographic separation function;

Or device E,

The multi-dimensional liquid chromatography separation system includes a high performance liquid chromatography gradient pump A, a high performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array A, Enrichment column array B, fraction collector, liquid chromatography separation column array, detector, double two-position four-way valve and connecting pipeline; the two positions of the two-position four-way valve ①, ②, ③, The ④, ⑤, ⑥, ⑦, and ⑧ positions only indicate the adjacency relationship, and do not necessarily correspond to the physical marks of the double two-position four-way valve; the detector is used to detect the chromatographic signal during the separation process; the injection valve For injection

The liquid chromatography separation column array is formed by a plurality of chromatographic separation columns connected in parallel through a multi-position selection valve, and only one chromatographic separation column can be connected at a time; a fixed inlet and a fixed outlet are provided to the outside, and At least one bypass, the bypass and the separation column are connected in parallel through a multi-position selection valve; when the bypass is on, other chromatographic separation columns will not be on, and when the other chromatographic separation column is on, the bypass will not be on; The number of separation columns is determined as required;

The enrichment column array A and the enrichment column array B are formed by multiple chromatographic enrichment columns connected in parallel through a multi-position selection valve, and only one enrichment column can be turned on at the same time; at least one bypass, The bypass and the enrichment column are connected in parallel through a multi-position selection valve; when the bypass is on, the other enrichment columns will not be on, and when the other enrichment column is on, the bypass will not be on; the number of enrichment columns is based on Need to be determined; there are two external interfaces, which are defined as interface X and interface Y respectively;

When the double two-position four-way valve is in the A state, through the double two-position four-way valve and the connecting pipeline, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A form a chromatographic separation gradient. The eluent mobile phase supply system, the outlet of the gradient mixer A is connected to the inlet of the injection valve, the outlet of the injection valve is connected to the interface X of the enrichment column array A, and the interface Y of the enrichment column array A is connected to the liquid chromatography separation column The inlet of the array is connected, the outlet of the separation column array is connected to the detector, the outlet of the detector is connected to the inlet of the gradient mixer B, the diluent pump is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the enrichment column array The interface X of B is connected, and the interface Y of the enrichment column array B is connected to the inlet of the fraction collector;

When the double two-position four-way valve is in the B state, through the double two-position four-way valve and the connecting pipeline, the HPLC gradient pump A, the HPLC gradient pump B, and the gradient mixer A form a chromatographic separation gradient. The eluent mobile phase supply system, the outlet of the gradient mixer A is connected to the inlet of the injection valve, and the outlet of the injection valve is connected to the interface Y of the enrichment column array B; the interface X of the enrichment column array B is connected to the liquid chromatography separation column The inlet of the array is connected, the outlet of the separation column array is connected to the detector, the outlet of the detector is connected to the inlet of the gradient mixer B, the diluent pump is connected to the inlet of the gradient mixer B, and the outlet of the gradient mixer B is connected to the enrichment column array The interface Y of A is connected; the interface X of the enrichment column array A is connected to the inlet of the fraction collector;

By controlling the state switching of the double two-position four-way valve, the system is switched from the previous one-dimensional separation state to the next one-dimensional separation state, completes the cyclic chromatography function, and realizes the chromatographic separation function of multidimensional full-line detection;

Or device F,

The multi-dimensional liquid chromatography separation system includes a high performance liquid chromatography gradient pump A, a high performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array A, Enrichment column array B, fraction collector, liquid chromatography separation column array, detector, two-position ten-way valve and connecting pipeline; positions ①, ②, ③, and ④ of the two-position ten-way valve , ⑤ position, ⑥ position, ⑦ position, ⑧ position, ⑩ position, ⑨ position, and ⑩ position only indicate the adjacency relationship, and do not need to correspond to the physical mark of the two-position ten-way valve. The interface begins to be named according to counterclockwise or clockwise from ①; the detector is used to detect the chromatographic signal during the separation process; the injection valve is used to inject;

The liquid chromatography separation column array is formed by a plurality of chromatographic separation columns connected in parallel through a multi-position selection valve, and only one chromatographic separation column can be connected at a time; a fixed inlet and a fixed outlet are provided to the outside, and At least one bypass, the bypass and the separation column are connected in parallel through a multi-position selection valve; when the bypass is on, other chromatographic separation columns will not be on, and when the other chromatographic separation column is on, the bypass will not be on; The number of separation columns is determined as required;

The enrichment column array A and the enrichment column array B are formed by multiple chromatographic enrichment columns connected in parallel through a multi-position selection valve, and only one enrichment column can be turned on at the same time; at least one bypass, The bypass and the enrichment column are connected in parallel through a multi-position selection valve; when the bypass is on, the other enrichment columns will not be on, and when the other enrichment column is on, the bypass will not be on; the number of enrichment columns is based on Need to be determined; there are two external interfaces, which are defined as interface X and interface Y respectively;

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the ten-position valve is connected, the ⑩ position of the two-position ten-port valve is connected to the interface X of the enrichment column array B, and the interface Y of the enrichment column array B is connected to the ③ position of the two-position ten-way valve. The ② position of the two-position ten-way valve is connected to the ⑦ position, the ⑥ position of the two-position ten-way valve is connected to the inlet of the liquid chromatography separation column array, and the outlet of the liquid chromatography separation column array is connected to the detector. The outlet of is connected to the inlet of the gradient mixer B, the outlet of the diluent pump is connected to the inlet of the gradient mixer B, the outlet of the gradient mixer B is connected to the 两位 position of the two-position ten-way valve, and the 两位 of the two-position ten-way valve The position is connected to the interface X of the enrichment column array A, the interface Y of the enrichment column array A is connected to the position ⑤ of the two-position ten-way valve, and the position ④ of the two-position ten-way valve is connected to the inlet of the fraction collector. ;

By controlling the switching state of the two-position ten-way valve, the system is switched from the previous one-dimensional separation state to the next one-dimensional separation state, completes the cyclic chromatography function, and realizes the chromatographic separation function of multidimensional full-line detection;

Or device H,

The multi-dimensional liquid chromatography separation system includes a high performance liquid chromatography gradient pump A, a high performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array A, Enrichment column array B, fraction collector, liquid chromatography separation column array, detector, two-position eight-way valve, and connecting pipeline; positions ①, ②, ③, and ④ of the two-position eight-way valve , ⑤ position, ⑥ position, ⑧ position, ⑧ position only indicate the adjacency relationship, and do not need to correspond to the physical mark of the two-position eight-way valve. The numbers are named and sorted starting from any interface of the two-position eight-way valve in a counterclockwise or Clockwise from ① to sort and name; the detector is used to detect the chromatographic signal in the separation process; the injection valve is used to inject;

The liquid chromatography separation column array is formed by a plurality of chromatographic separation columns connected in parallel through a multi-position selection valve, and only one chromatographic separation column can be connected at a time; a fixed inlet and a fixed outlet are provided to the outside, and At least one bypass, the bypass and the separation column are connected in parallel through a multi-position selection valve; when the bypass is on, other chromatographic separation columns will not be on, and when the other chromatographic separation column is on, the bypass will not be on; The number of separation columns is determined as required;

The enrichment column array A and the enrichment column array B are formed by multiple chromatographic enrichment columns connected in parallel through a multi-position selection valve, and only one enrichment column can be turned on at the same time; at least one bypass, The bypass and the enrichment column are connected in parallel through a multi-position selection valve; when the bypass is on, the other enrichment columns will not be on, and when the other enrichment column is on, the bypass will not be on; the number of enrichment columns is based on Need to be determined; there are two external interfaces, which are defined as interface X and interface Y respectively;

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the 8-position valve is connected, the ⑧ position of the 2-position 8-way valve is connected to the interface X of the enrichment column array B, and the interface Y of the enrichment column array B is connected to the ④ position of the 2-position eight-way valve. The position ⑤ of the two-position eight-way valve is connected to the inlet of the liquid chromatography separation column array. The outlet of the liquid chromatography separation column array is connected to the detector. The outlet of the detector is connected to the inlet of the gradient mixer B. The outlet is connected to the inlet of the gradient mixer B. The outlet of the gradient mixer B is connected to the ③ position of the two-position eight-way valve, and the ② position of the two-position eight-way valve is connected to the interface X of the enrichment column array A to enrich the The interface Y of the column array A is connected to the ⑥ position of the two-position eight-way valve, and the ⑦ position of the two-position eight-way valve is connected to the inlet of the fraction collector;

By controlling the switching state of the two-position eight-way valve, the system is switched from the previous one-dimensional separation state to the next one-dimensional separation state, completes the cyclic chromatography function, and realizes the chromatographic separation function of multidimensional full-line detection;

Or device I,

The multi-dimensional liquid chromatography separation system includes a high performance liquid chromatography gradient pump A, a high performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array A, Enrichment column array B, fraction collector, liquid chromatography separation column array, detector, two-position multi-port valve, and connecting pipeline; the detector is used to detect the chromatographic signal during the separation process; the injection valve is used for In injection

The liquid chromatography separation column array is formed by connecting multiple chromatographic separation columns in parallel, and only one chromatographic separation column can be connected at a time; a fixed inlet and a fixed outlet are provided to the outside, and at least one bypass is provided. , The bypass and the separation column are connected in parallel; when the bypass is on, other chromatographic separation columns will not be on, and when the other chromatographic separation column is on, the bypass will not be on; the number of chromatographic separation columns is determined according to need;

The enrichment column array A and the enrichment column array B are formed by connecting a plurality of chromatographic enrichment columns in parallel, and only one enrichment column can be turned on at the same time; at least one bypass, the bypass and enrichment columns The concentrated columns are connected in parallel; other enriched columns cannot be connected when the bypass is turned on, and the bypass cannot be connected when the other enriched columns are turned on; the number of enriched columns is determined according to need; there are two external interfaces, respectively Defined as interface X and interface Y;

The inlet of the sampling valve is connected to one port of a two-position multi-port valve, the outlet of the sampling valve is connected to the inlet of a liquid chromatography separation column array, and the outlet of the liquid chromatography separation column array is connected to a detector;

By controlling the state switching of the two-position multi-way valve, the system is switched from the previous one-dimensional separation state to the next one-dimensional separation state, and the cycle chromatography function is completed, and the multi-dimensional full-line detection chromatography function is realized;

Or device J,

The multi-dimensional liquid chromatography separation system includes a high-performance liquid chromatography gradient pump A, a high-performance liquid chromatography gradient pump B, a diluent pump, a gradient mixer A, a gradient mixer B, an injection valve, an enrichment column array, and a distillation column. Fraction collector, liquid chromatography separation column array, detector, two-position six-way valve, and connecting pipeline; the two-position six-way valve ① position, ② position, ③ position, ④ position, ⑤ position, ⑥ position are only Represents the adjacency relationship, which does not necessarily correspond to the physical mark of the two-position six-way valve. Its number is named and sorted from any interface of the two-position six-way valve, and named according to counterclockwise or clockwise from ①; the detector is used for Detecting a chromatographic signal during a separation process; the sampling valve is used for sampling;

The liquid chromatography separation column array is formed by connecting a plurality of chromatographic separation columns in parallel, and only one chromatographic separation column can be turned on at the same time; at least one bypass is connected in parallel with the separation column; when the bypass is turned on When other chromatographic separation columns are not conducting, the bypass will not be conducting when other chromatographic separation columns are conducting; a fixed inlet and a fixed outlet are provided to the outside;

The enrichment column array is formed by connecting a plurality of chromatographic enrichment columns in parallel, and only one enrichment column can be turned on at the same time; at least one bypass is connected in parallel with the enrichment column; The other enrichment columns will not be able to conduct when it is on, and the bypass will not be able to conduct when the other enrichment columns are on; there are two external interfaces, which are defined as interface X and interface Y, respectively;

The outlets of the HPLC gradient pump A and the HPLC gradient pump B are respectively connected to the inlet of the gradient mixer A, the outlet of the gradient mixer A is connected to the inlet of the sampling valve, and the outlet of the sampling valve is connected to two The ① position of the six-position valve is connected, and the ⑥ position of the two-position six-way valve is connected to the inlet of the LC separation column array. The outlet of the LC separation column array is connected to the detector, and the outlet of the detector is mixed with the gradient. The inlet of the diluent pump is connected to the inlet of the gradient mixer B. The outlet of the gradient mixer B is connected to the ④ position of the two-position six-way valve, and the ⑤ position of the two-position six-way valve is to be enriched. The interface Y of the column array is connected, the interface X of the enriched column array is connected to the position ② of the two-position six-way valve, and the position ③ of the two-position six-way valve is connected to the inlet of the fraction collector.
The multi-dimensional liquid chromatography separation system according to claim 1, wherein:

Corresponding to device A or D or F, the injection valve in the above multi-dimensional liquid chromatography separation system can also be connected to the bypass of enrichment column array A or enrichment column array B, or connected to enrichment column array A Or the connection line between the enrichment column array B and the two-position ten-port valve; at this time, the outlet of the gradient mixer A is connected to the position ① of the two-position ten-port valve; the above connection changes do not affect the use of the system, only Redefine the dimensions of the enrichment column during control;

Or, corresponding to the device B or E, the injection valve in the above-mentioned multi-dimensional liquid chromatography separation system can also be connected to the bypass column of the enrichment column array A or the enrichment column array B, or to the enrichment column array A. Or the connection line between the enrichment column array B and the double two-way four-way valve; at this time, the outlet of the gradient mixer A is connected to the number ① of the double two-way four-way valve; the above connection changes do not affect the use of the system. Just redefine the dimensions of the enrichment column during control;

Or, corresponding to the device C or H, the injection valve in the above multi-dimensional liquid chromatography separation system can also be connected to the bypass of the enrichment column array A or the enrichment column array B, or to the enrichment column array A. Or the connection line between the enrichment column array B and the two-position eight-way valve; at this time, the outlet of the gradient mixer A is connected to the position ① of the two-position eight-way valve; Redefine the dimensions of the enrichment column during control;

Or, corresponding to the device J, the injection valve in the multi-dimensional liquid chromatography separation system can be connected in the bypass of the enrichment column array, or in the connection line between the enrichment column array and the two-position six-way valve. , Or between the six position of the two-position six-way valve and the inlet of the LC separation column array.
The multi-dimensional liquid chromatography separation system according to claim 1 or 2, wherein:

Corresponding to device A or B or C or D or E or F or H, the enrichment column array may be composed of a plurality of enrichment column arrays in series to form a multi-stage enrichment column array, and the operation control is the same as that of a single-stage enrichment column array. Only one enrichment column can be turned on at the same time; when the multi-stage enrichment column array is in the bypass conduction state, the enrichment column array in each stage is in bypass conduction.
The multi-dimensional liquid chromatography separation system according to claim 1 or 2, wherein:

Corresponding to device A or D or F, the two-position ten-port valve is a valve or composed of multiple valves, and operates according to the principle of two-position ten-port valve switching valve;

Or, corresponding to the device B or E, the double two-position four-way valve is a valve or composed of multiple valves, and operates according to the double two-way four-way valve switching valve principle;

Or, corresponding to the device C or H, the two-position eight-way valve is a valve or composed of multiple valves, and operates according to the principle of the two-position eight-way valve switching valve;

Or, corresponding to device I, the two-position multi-port valve includes two-position ten-port valves, two-position eight-port valves or two two-position four-port valves, including one valve or consisting of multiple valves, and according to a two-position ten A two-position, eight-position valve or a two-position, four-position valve operates on the principle of a valve.
The multi-dimensional liquid chromatography separation system according to claim 3, wherein:

Corresponding to device A or D or F, the two-position ten-port valve is a valve or composed of multiple valves, and operates according to the principle of two-position ten-port valve switching valve;

Or, corresponding to the device B or E, the double two-position four-way valve is a valve or composed of multiple valves, and operates according to the double two-way four-way valve switching valve principle;

Or, corresponding to the device C or H, the two-position eight-way valve is a valve or composed of multiple valves, and operates according to the principle of the two-position eight-way valve switching valve.
The multi-dimensional liquid chromatography separation system according to claim 1 or 2 or 5, wherein:

Corresponding to device A or B or C or D or E or F or H, the HPLC gradient pump A and HPLC gradient pump B are each composed of one or two or more unit pumps, or one or It consists of two or more multivariate gradient pumps; the diluent pump is a unit pump or a multivariable pump.
The multi-dimensional liquid chromatography separation system according to claim 3, wherein:

Corresponding to device A or B or C or D or E or F or H, the HPLC gradient pump A and HPLC gradient pump B are each composed of one or two or more unit pumps, or one or It consists of two or more multivariate gradient pumps; the diluent pump is a unit pump or a multivariable pump.
The multi-dimensional liquid chromatography separation system according to claim 4, wherein:

Corresponding to device A or B or C or D or E or F or H, the HPLC gradient pump A and HPLC gradient pump B are each composed of one or two or more unit pumps, or one or It consists of two or more multivariate gradient pumps; the diluent pump is a unit pump or a multivariable pump.
The multi-dimensional liquid chromatography separation system according to claim 1 or 2 or 5 or 7 or 8, characterized in that:

Corresponding to devices A or B or C or D or E or F or H, the detectors are various devices for detecting chromatographic signals in the separation process, including but not limited to ultraviolet detectors, diode array detectors, evaporative light Scattering or mass spectrometry detectors, including a combined detection system consisting of multiple detectors.
The multi-dimensional liquid chromatography separation system according to claim 6, wherein:

Corresponding to devices A or B or C or D or E or F or H, the detectors are various devices for detecting chromatographic signals in the separation process, including but not limited to ultraviolet detectors, diode array detectors, evaporative light Scattering or mass spectrometry detectors, including a combined detection system consisting of multiple detectors.
The multi-dimensional liquid chromatography separation system according to claim 1 or 2, wherein:

Corresponding to device J, the outlet of the gradient mixer B in the multi-dimensional liquid chromatography separation system can also be connected to the position ③ of the two-position six-way valve. At this time, the position ④ of the two-position six-way valve and the fraction The inlet of the collector is connected, and other connecting pipes are unchanged.
The multi-dimensional liquid chromatography separation system according to claim 1 or 2, characterized in that, corresponding to any one of the devices A, B, C, D, E, F, H, I, the Any one of the two enrichment column arrays A and B can be directly replaced by a connecting pipe.