Circulating multi-dimensional liquid chromatography separation system

Abstract

The circulating multi-dimensional liquid chromatography separation system provided by the invention is a standardized and low-cost multi-center cutting circulating multi-dimensional liquid phase system, based on one separation column array and one quantitative loop array, the quantitative loop does not dilute and mix when storing a target sample, and when the target sample in the quantitative loop is loaded to the separation column, the quantitative loop is separated from the separation column array and the quantitative loop array. A target sample can be diluted and mixed by using a diluent, the operation is simple, and automatic control is convenient.

Description

Technical Field

[0001] The invention belongs to the technical field of high performance liquid chromatography separation and relates to a circulating multidimensional liquid chromatography separation system. Background Art

[0002] The transfer storage link of the two-dimensional liquid chromatography separation system includes a quantitative loop and an enrichment column. The two-dimensional liquid chromatography separation system based on the quantitative loop is often used for the separation and detection of trace components such as impurities. Through the online dilution and mixing of the diluent, the enrichment column can more efficiently enrich the target sample. When the quantitative loop stores the target sample, the target sample cannot be diluted and mixed by the diluent, otherwise it will cause the volume of the target sample to increase, the peak to expand, and the sample to be lost. In the two-dimensional liquid chromatography separation system, when the target sample of the quantitative loop or enrichment column in the transfer storage link is loaded onto the separation column, the target sample needs to be diluted and mixed with a diluent (sufficient mixing volume) so that the target sample can be enriched at the head of the separation column or focused at the head of the column to suppress the broadening or distortion of the chromatographic peak.

[0003] Based on the quantitative ring array and four three-way valves, Northwest University's 2009 master's thesis "Construction and Application of Online Protein Two-Dimensional Liquid Chromatograph" (author Zhang Huiqiang), CN103063753A, etc. disclose an online protein two-dimensional liquid chromatography separation system, which realizes that the quantitative ring does not dilute and mix when storing the target sample, and when the quantitative ring target sample is loaded onto the separation column, the target sample can be diluted and mixed with a diluent. However, the two-dimensional liquid chromatography separation system disclosed in CN103063753A, etc., has a complex structure and is not easy to operate and control automatically.

[0004] CN113607857 A Figure 5 , Figure 6 A circulating multidimensional liquid phase system is disclosed, which can realize double dilution and mixing when enriching the target sample and when the enrichment column is used as a loading column to load the sample on the separation column based on the same diluent pump. Figure 5 , Figure 6 The mixer in the separation column is replaced by a tee (mixing volume is very small, mixing effect is very small), and the enrichment column array is replaced by a quantitative loop array, so that the diluent pump does not run when the quantitative loop stores the target sample, and the target sample is not diluted and mixed by the diluent. However, the consequence of this is that since the mixing volume of the tee is very small, when the target sample in the quantitative loop is loaded onto the separation column, the target sample can only be diluted but not sufficiently mixed. Summary of the invention

[0005] In order to solve the technical problems of complex structure, numerous components and high cost of the existing two-dimensional liquid chromatography separation system based on quantitative ring array, and to compete with the Agilent 1290 Infinity multiple heart-cutting two-dimensional liquid chromatography solution based on quantitative ring array, a standardized and low-cost multiple heart-cutting cycle multidimensional liquid system is provided.

[0006] The purpose of the present invention is to construct a cyclic multidimensional liquid chromatography separation system based on a separation column array and a quantitative loop array, so as to achieve the quantitative loop without dilution and mixing when storing the target sample, and when the target sample in the quantitative loop is loaded onto the separation column, the target sample can be diluted and mixed with a diluent.

[0007] In order to achieve the above object, the technical solution 1 of the present invention is:

[0008] A circulating multidimensional liquid chromatography separation system, comprising an infusion unit, a sample injection unit, a detection unit, a separation column array, a quantitative loop array, a diluent pump, a mixer and a two-position multi-way valve; the number of ports of the two-position multi-way valve is greater than or equal to 8;

[0009] The infusion unit is used to complete the supply of mobile phase for liquid chromatography separation gradient elution;

[0010] The diluent pump is used to complete the supply of mobile phase and has an outlet;

[0011] The injection unit is used for injection and has an inlet and an outlet;

[0012] The detector is used to detect the chromatographic signal during the separation process and has an inlet;

[0013] The separation column array has an inlet and an outlet;

[0014] The quantitative ring array has two interfaces, one for the inlet and the other for the outlet;

[0015] The quantitative ring array is composed of a plurality of quantitative rings, and only one quantitative ring can be turned on at the same time; the quantitative ring array includes at least one bypass, and the bypass and the quantitative ring are connected in parallel; when the bypass is turned on, the quantitative ring will not be turned on, and when the quantitative ring is turned on, the bypass will not be turned on;

[0016] The mixer has a first interface, a second interface and a third interface;

[0017] Through the two-position multi-way valve and pipeline,

[0018] When the cyclic multidimensional liquid chromatography separation system performs chromatographic separation, when the two-position multi-way valve is in state A, the mobile phase output by the infusion unit flows into the inlet of the injection unit; the solution flowing out of the outlet of the injection unit flows into a port in the two-position multi-way valve connected to the outlet of the injection unit, passes through the two-position multi-way valve, and flows into the inlet of the separation column array connected to a port in the two-position multi-way valve; the solution flowing out of the outlet of the separation column array is detected by the detection unit, flows into a port of the two-position multi-way valve, passes through the two-position multi-way valve, and flows into the inlet of the quantitative ring array connected to a port of the two-position multi-way valve; the solution flowing out of the outlet of the quantitative ring array flows into a port in the two-position multi-way valve connected to the outlet of the quantitative ring array, passes through the two-position multi-way valve, and flows out from a port of the two-position multi-way valve;

[0019] When the cyclic multidimensional liquid chromatography separation system performs chromatographic separation, when the two-position multi-way valve is in state B, in the process of loading the target sample in the quantitative loop onto the separation column, if it is necessary to use a diluent to dilute and mix the sample solution flowing out of the quantitative loop, then the mobile phase output by the infusion unit flows into the inlet of the injection unit; the solution flowing out of the outlet of the injection unit flows into a port of the two-position multi-way valve connected to the outlet of the injection unit, passes through the two-position multi-way valve, and flows into the inlet of the quantitative loop array connected to a port of the two-position multi-way valve; the solution flowing out of the outlet of the quantitative loop array flows into the two-position multi-way valve connected to the quantitative loop array. A port connected to the ring array outlet passes through a two-position multi-way valve and flows into a first port of a mixer connected to a port of the two-position multi-way valve; a diluent output by a dilution pump flows into a second port of the mixer; a solution flowing out of a third port of the mixer flows into a port of the two-position multi-way valve connected to the third port of the mixer, passes through the two-position multi-way valve, and flows into an inlet of a separation column array connected to a port of the two-position multi-way valve; a solution flowing out of the separation column array outlet is detected by a detection unit, flows into a port of the two-position multi-way valve, passes through the two-position multi-way valve, and flows out from a port of the two-position multi-way valve;

[0020] When the cyclic multidimensional liquid chromatography separation system performs chromatographic separation, when the two-position multi-way valve is in state B, in the process of loading the target sample in the quantitative loop onto the separation column, if it is not necessary to use a diluent to dilute and mix the sample solution flowing out of the quantitative loop, then the mobile phase output by the infusion unit flows into the inlet of the injection unit; the solution flowing out of the outlet of the injection unit flows into a port of the two-position multi-way valve connected to the outlet of the injection unit, passes through the two-position multi-way valve, and flows into the inlet of the quantitative loop array connected to one port of the two-position multi-way valve; the solution flowing out of the outlet of the quantitative loop array flows into the two-position multi-way valve. A port in the multi-way valve connected to the outlet of the quantitative ring array flows into the first port of the mixer connected to a port of the two-way multi-way valve through the two-way multi-way valve, the dilution pump stops working, the solution flowing out of the third port of the mixer flows into a port of the two-way multi-way valve connected to the third port of the mixer, flows into the inlet of the separation column array connected to a port of the two-way multi-way valve through the two-way multi-way valve; the solution flowing out of the outlet of the separation column array is detected by the detection unit, flows into a port of the two-way multi-way valve, passes through the two-way multi-way valve, and flows out from a port of the two-way multi-way valve;

[0021] By controlling the switching between the two states of state A and state B of the two-position multi-way valve, a cyclic multi-dimensional liquid chromatography separation function with full online detection is realized.

[0022] Technical solution 2 is:

[0023] A circulating multidimensional liquid chromatography separation system, comprising an infusion unit, a sample injection unit, a detection unit, a separation column array, a quantitative loop array, a dilution pump, a mixer and a two-position multi-way valve; the number of ports of the two-position multi-way valve is greater than or equal to 6;

[0024] The infusion unit is used to complete the supply of mobile phase for liquid chromatography separation gradient elution;

[0025] The dilution pump is used to complete the supply of mobile phase and has an outlet;

[0026] The injection unit is used for injection and has an inlet and an outlet;

[0027] The detection unit is used to detect the chromatographic signal during the separation process and has an inlet;

[0028] The separation column array has an inlet and an outlet;

[0029] The quantitative ring array has two interfaces, one for the inlet and the other for the outlet;

[0030] The quantitative ring array is composed of a plurality of quantitative rings, and only one quantitative ring can be turned on at the same time; the quantitative ring array includes at least one bypass, and the bypass and the quantitative ring are connected in parallel; when the bypass is turned on, the quantitative ring will not be turned on, and when the quantitative ring is turned on, the bypass will not be turned on;

[0031] The mixer has a first interface, a second interface and a third interface;

[0032] When the cyclic multidimensional liquid chromatography separation system performs chromatographic separation, when the two-position multi-way valve is in state A, the mobile phase output by the infusion unit flows into the inlet of the injection unit; the solution flowing out of the outlet of the injection unit flows into a port in the two-position multi-way valve connected to the outlet of the injection unit, passes through the two-position multi-way valve, and flows into the first interface of the mixer connected to a port in the two-position multi-way valve; the solution flowing out of the third interface of the mixer flows into the inlet of the separation column array connected to the third interface of the mixer; the solution flowing out of the outlet of the separation column array is detected by the detection unit, flows into a port of the two-position multi-way valve, passes through the two-position multi-way valve, and flows into the inlet of the quantitative ring array connected to a port of the two-position multi-way valve; the solution flowing out of the outlet of the quantitative ring array flows into a port in the two-position multi-way valve connected to the outlet of the quantitative ring array, passes through the two-position multi-way valve, and flows out from a port of the two-position multi-way valve;

[0033] When the cyclic multidimensional liquid chromatography separation system performs chromatographic separation, when the two-position multi-way valve is in state B, in the process of loading the quantitative loop target sample onto the separation column, if it is necessary to use a diluent to dilute and mix the sample solution flowing out of the quantitative loop, then the mobile phase output by the infusion unit flows into the inlet of the injection unit; the solution flowing out of the injection unit outlet flows into a port in the two-position multi-way valve connected to the injection unit outlet, passes through the two-position multi-way valve, and flows into the inlet of the quantitative loop array connected to a port of the two-position multi-way valve; the solution flowing out of the quantitative loop array outlet flows into a port in the two-position multi-way valve connected to the quantitative loop array outlet, passes through the two-position multi-way valve, and flows into the first interface of the mixer connected to a port in the two-position multi-way valve, the diluent output by the dilution pump as needed flows into the second interface of the mixer, and the solution flowing out of the third interface of the mixer flows into the inlet of the separation column array; the solution flowing out of the separation column array outlet is detected by the detection unit, flows into a port of the two-position multi-way valve, passes through the two-position multi-way valve, and flows out from a port of the two-position multi-way valve;

[0034] When the cyclic multidimensional liquid chromatography separation system performs chromatographic separation, when the two-position multi-way valve is in state B, in the process of loading the quantitative loop target sample onto the separation column, if it is not necessary to use a diluent to dilute and mix the sample solution flowing out of the quantitative loop, then the mobile phase output by the infusion unit flows into the inlet of the injection unit; the solution flowing out of the injection unit outlet flows into a port in the two-position multi-way valve connected to the injection unit outlet, passes through the two-position multi-way valve, and flows into the inlet of the quantitative loop array connected to a port of the two-position multi-way valve; the solution flowing out of the quantitative loop array outlet flows into a port in the two-position multi-way valve connected to the quantitative loop array outlet, passes through the two-position multi-way valve, and flows into the first interface of the mixer connected to a port in the two-position multi-way valve, the dilution pump stops working, and the solution flowing out of the third interface of the mixer flows into the inlet of the separation column array; the solution flowing out of the separation column array outlet is detected by the detection unit, flows into a port of the two-position multi-way valve, passes through the two-position multi-way valve, and flows out from a port of the two-position multi-way valve;

[0035] By controlling the switching between the two states of state A and state B of the two-position multi-way valve, a cyclic multi-dimensional liquid chromatography separation function with full online detection is realized.

[0036] In technical solutions 1 and 2,

[0037] The injection unit can be connected to the connecting pipeline before the inlet of the separation column array.

[0038] The injection unit is an injection device, which can be in the form of an injection valve, an automatic injector or a sample pump, etc. It has two states, namely an injection state and a non-injection straight-through state, and has an inlet and an outlet for system flow connection.

[0039] The infusion unit may be composed of an HPLC gradient pump A, an HPLC gradient pump B and a gradient mixer. The diluent pump is an HPLC diluent pump, which is a unit pump or a multi-element pump. The diluent of the HPLC gradient pump A, the HPLC gradient pump B and the diluent pump may be water, saline solution, methanol, acetonitrile, acetone, ethanol or normal alkane solvent, and the eluent may be methanol, acetonitrile, ethanol, water and mixtures thereof, normal alkanes and other commonly used organic solvents.

[0040] The separation column array is formed by connecting multiple separation columns in parallel, and only one separation column can be turned on at the same time; there is at least one bypass, which is connected in parallel with the separation column; when the bypass is turned on, the separation column will not be turned on, and when the separation column is turned on, the bypass and other separation columns will not be turned on; there are two interfaces to the outside, one for the inlet and the other for the outlet. The separation column array can be constructed by a multi-position selector valve or a two-position four-way valve, or by a two-way valve.

[0041] The quantitative ring array can be constructed by a multi-position selection valve or a two-position four-way valve, or by a two-way valve.

[0042] The detection unit is a variety of devices used to detect chromatographic signals during the separation process, including but not limited to ultraviolet detectors, diode array detectors, evaporative light scattering detectors or mass spectrometry detectors, including a combined detection system consisting of multiple detectors.

[0043] If dilution and mixing are not required, the dilution pump and mixer can be removed.

[0044] Compared with the prior art, the invention has the following innovative features and beneficial effects:

[0045] The present invention provides a circulating multidimensional liquid chromatography separation system, which is a standardized, low-cost multi-heart-cutting circulating multidimensional liquid phase system, which realizes that the quantitative loop does not dilute and mix the target sample when storing it. When the target sample in the quantitative loop is loaded onto the separation column, the target sample can be diluted and mixed with a diluent, which is simple to operate and convenient for automated control. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 A system flow diagram of a circulating multidimensional liquid chromatography separation system with a two-position eight-way valve in state A provided for the connection mode (A) of the present invention, wherein the dotted line portion indicates a non-circulating state and the dilution pump does not work;

[0047] Figure 2 A system flow diagram of a circulating multidimensional liquid chromatography separation system with a two-position eight-way valve in state B provided for the connection mode (A) of the present invention, wherein the dilution pump can work;

[0048] Figure 3 A system flow diagram of a circulating multidimensional liquid chromatography separation system with a two-position eight-way valve in state A provided for the connection mode (B) of the present invention, wherein the dotted line portion indicates a non-circulating state and the dilution pump does not work;

[0049] Figure 4 A system flow diagram of a circulating multidimensional liquid chromatography separation system with a two-position eight-way valve in state B provided for the connection mode (B) of the present invention, and the dilution pump can work;

[0050] Figure 5 A system flow diagram of a circulating multidimensional liquid chromatography separation system with a two-position six-way valve in state A provided for the connection mode (C) of the present invention, and the dilution pump is not working;

[0051] Figure 6 A system flow diagram of a circulating multidimensional liquid chromatography separation system with a two-position six-way valve in state B provided by the connection mode (C) of the present invention, and the dilution pump can work;

[0052] Figure 7A system flow diagram of a circulating multidimensional liquid chromatography separation system with a two-position six-way valve in state A provided for the connection mode (D) of the present invention, and the dilution pump is not working;

[0053] Figure 8 A system flow diagram of a circulating multidimensional liquid chromatography separation system with a two-position six-way valve in state B provided for the connection mode (D) of the present invention, and the dilution pump can work;

[0054] Fig. 9 It is a pipe connection structure diagram of the separation column array;

[0055] Fig.10 This is the pipeline connection structure diagram of the quantitative ring array. Fig.10 Columns 1 to N in the column were replaced with a quantitative loop. DETAILED DESCRIPTION

[0056] The embodiments described below are merely a description of the application of the patent of the present invention and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the scheme of the present invention by ordinary technicians in this field should fall within the scope of protection determined by the claims of the present invention.

[0057] Technical solution 1 implementation method:

[0058] A cyclic multidimensional liquid chromatography separation system comprises an infusion unit, an injection unit, a detection unit, a separation column array, a quantitative loop array, a diluent pump, a mixer and a two-position multi-way valve; the number of ports of the two-position multi-way valve is greater than or equal to 8; for simplicity, the two-position multi-way valve is a two-position eight-way valve; the detection unit is a detector or an ultraviolet detector, having an inlet and an outlet; the injection unit is an injection valve or an automatic sampler, which illustrates the best implementation method.

[0059] A two-position twelve-way valve, or a valve group consisting of multiple valves, etc., connected to form a two-position eight-way valve can be implemented in this way; other connection methods can also be used to achieve the same technical effect.

[0060] The eight ports of the two-position eight-way valve are port ①, port ②, port ③, port ④, port ⑤, port ⑥, port ⑦, and port ⑧. These numbers only indicate the adjacency relationship and do not have to correspond to the physical markings of the two-position eight-way valve. The number positions are named and sorted in a counterclockwise or clockwise order starting from ① from any port of the two-position eight-way valve.

[0061] The system pipeline is connected in any of the following ways (A) or (B):

[0062] (A) Connection method: the outlet of the infusion unit is connected to the inlet of the injection unit, the outlet of the injection unit is connected to the port ① of the two-position eight-way valve, the port ⑧ of the two-position eight-way valve is connected to the inlet of the separation column array, the outlet of the separation column array is connected to the inlet of the detection unit, the outlet of the detection unit is connected to the port ④ of the two-position eight-way valve; the port ⑥ of the two-position eight-way valve is connected to the first interface of the mixer, the outlet of the dilution pump is connected to the second interface of the mixer, the third interface of the mixer is connected to the port ⑦ of the two-position eight-way valve; the port ⑤ of the two-position eight-way valve is connected to an interface of the quantitative ring array, the other interface of the quantitative ring array is connected to the port ② of the two-position eight-way valve; the port ③ of the two-position eight-way valve outputs the separated sample. Figure 1 and Figure 2 .

[0063] (B) Connection method: the outlet of the infusion unit is connected to the inlet of the injection unit, the outlet of the injection unit is connected to the port ① of the two-position eight-way valve, the port ⑧ of the two-position eight-way valve is connected to the inlet of the separation column array, the outlet of the separation column array is connected to the inlet of the detection unit, the outlet of the detection unit is connected to the port ③ of the two-position eight-way valve; the port ⑥ of the two-position eight-way valve is connected to the first interface of the mixer, the outlet of the dilution pump is connected to the second interface of the mixer, the third interface of the mixer is connected to the port ⑦ of the two-position eight-way valve; the port ⑤ of the two-position eight-way valve is connected to an interface of the quantitative ring array, the other interface of the quantitative ring array is connected to the port ② of the two-position eight-way valve; the port ④ of the two-position eight-way valve outputs the separated sample. Figure 3 and Figure 4 .

[0064] Technical solution 2 implementation method:

[0065] A cyclic multidimensional liquid chromatography separation system includes an infusion unit, an injection unit, a detection unit, a separation column array, a quantitative loop array, a dilution pump, a mixer and a two-position multi-way valve; the number of ports of the two-position multi-way valve is greater than or equal to 6; for simplicity, the two-position multi-way valve is a two-position six-way valve, the detection unit is a detector or an ultraviolet detector, and the injection unit is an injection valve or an automatic sampler, which illustrates the best implementation method.

[0066] A two-position twelve-way valve, or a valve group consisting of multiple valves, etc., connected to form a two-position six-way valve can be implemented in this way; other connection methods can also be used to achieve the same technical effect.

[0067] The six ports of the two-position six-way valve are port ①, port ②, port ③, port ④, port ⑤, and port ⑥. These numbers only indicate the adjacency relationship and do not have to correspond to the physical markings of the two-position six-way valve. The number positions are named and sorted in a counterclockwise or clockwise order starting from ① from any port of the two-position six-way valve.

[0068] The system pipeline is connected in any of the following (C) or (D) connection methods:

[0069] (C) Connection method: the outlet of the infusion unit is connected to the inlet of the injection unit, the outlet of the injection unit is connected to the port ① of the two-position six-way valve, the port ⑥ of the two-position six-way valve is connected to the first interface of the mixer, the outlet of the dilution pump is connected to the second interface of the mixer, the third interface of the mixer is connected to the inlet of the separation column array, the outlet of the separation column array is connected to the inlet of the detection unit, the outlet of the detection unit is connected to the port ③ of the two-position six-way valve; the port ② of the two-position six-way valve is connected to an interface of the quantitative ring array, the other interface of the quantitative ring array is connected to the port ⑤ of the two-position six-way valve; the port ④ of the two-position six-way valve outputs the separated sample. Figure 5 and Figure 6 .

[0070] (D) Connection mode, the outlet of the infusion unit is connected to the inlet of the injection unit, the outlet of the injection unit is connected to the port ① of the two-position six-way valve, the port ⑥ of the two-position six-way valve is connected to the first interface of the mixer, the outlet of the dilution pump is connected to the second interface of the mixer, the third interface of the mixer is connected to the inlet of the separation column array, the outlet of the separation column array is connected to the inlet of the detection unit, and the outlet of the detection unit is connected to the port ④ of the two-position six-way valve; the port ② of the two-position six-way valve is connected to an interface of the quantitative ring array, and the other interface of the quantitative ring array is connected to the port ⑤ of the two-position six-way valve; the port ③ of the two-position six-way valve outputs the separated sample.

Claims

1. A circulating multidimensional liquid chromatography separation system, characterized in that: It includes an infusion unit, a sample injection unit, a detection unit, a separation column array, a quantitative loop array, a dilution pump, a mixer and a two-position multi-way valve; the number of ports of the two-position multi-way valve is greater than or equal to 8; The infusion unit is used to complete the supply of mobile phase for liquid chromatography separation gradient elution; The dilution pump is used to complete the supply of mobile phase and has an outlet; The injection unit is used for injection and has an inlet and an outlet; The detection unit is used to detect the chromatographic signal during the separation process and has an inlet; The separation column array has an inlet and an outlet; The quantitative ring array has two interfaces, one for the inlet and the other for the outlet; The mixer has a first interface, a second interface and a third interface; When the cyclic multidimensional liquid chromatography separation system performs chromatographic separation, when the two-position multi-way valve is in state A, the mobile phase output by the infusion unit flows into the inlet of the injection unit; the solution flowing out of the outlet of the injection unit flows into a port in the two-position multi-way valve connected to the outlet of the injection unit, passes through the two-position multi-way valve, and flows into the inlet of the separation column array connected to a port in the two-position multi-way valve; the solution flowing out of the outlet of the separation column array is detected by the detection unit, flows into a port of the two-position multi-way valve, passes through the two-position multi-way valve, and flows into the inlet of the quantitative ring array connected to a port of the two-position multi-way valve; the solution flowing out of the outlet of the quantitative ring array flows into a port in the two-position multi-way valve connected to the outlet of the quantitative ring array, passes through the two-position multi-way valve, and flows out from a port of the two-position multi-way valve; When the cyclic multidimensional liquid chromatography separation system performs chromatographic separation, when the two-position multi-way valve is in state B, the mobile phase output by the infusion unit flows into the inlet of the injection unit; the solution flowing out of the outlet of the injection unit flows into a port in the two-position multi-way valve connected to the outlet of the injection unit, passes through the two-position multi-way valve, and flows into the inlet of the quantitative ring array connected to a port of the two-position multi-way valve; the solution flowing out of the outlet of the quantitative ring array flows into a port in the two-position multi-way valve connected to the outlet of the quantitative ring array, passes through the two-position multi-way valve, and flows into the first interface of the mixer connected to a port of the two-position multi-way valve, the diluent output by the dilution pump flows into the second interface of the mixer, the solution flowing out of the third interface of the mixer flows into a port of the two-position multi-way valve connected to the third interface of the mixer, passes through the two-position multi-way valve, and flows into the inlet of the separation column array connected to a port in the two-position multi-way valve; the solution flowing out of the outlet of the separation column array is detected by the detection unit, flows into a port of the two-position multi-way valve, passes through the two-position multi-way valve, and flows out from a port of the two-position multi-way valve; By controlling the switching between the two states of state A and state B of the two-position multi-way valve, a cyclic multi-dimensional liquid chromatography separation function with full online detection is realized.

2. A circulating multidimensional liquid chromatography separation system, characterized in that: It includes an infusion unit, a sample injection unit, a detection unit, a separation column array, a quantitative loop array, a dilution pump, a mixer and a two-position multi-way valve; the number of ports of the two-position multi-way valve is greater than or equal to 6; The infusion unit is used to complete the supply of mobile phase for liquid chromatography separation gradient elution; The dilution pump is used to complete the supply of mobile phase and has an outlet; The injection unit is used for injection and has an inlet and an outlet; The detection unit is used to detect the chromatographic signal during the separation process and has an inlet; The separation column array has an inlet and an outlet; The quantitative ring array has two interfaces, one for the inlet and the other for the outlet; The mixer has a first interface, a second interface and a third interface; When the cyclic multidimensional liquid chromatography separation system performs chromatographic separation, when the two-position multi-way valve is in state A, the mobile phase output by the infusion unit flows into the inlet of the injection unit; the solution flowing out of the outlet of the injection unit flows into a port in the two-position multi-way valve connected to the outlet of the injection unit, passes through the two-position multi-way valve, and flows into the first interface of the mixer connected to a port in the two-position multi-way valve; the solution flowing out of the third interface of the mixer flows into the inlet of the separation column array connected to the third interface of the mixer; the solution flowing out of the outlet of the separation column array is detected by the detection unit, flows into a port of the two-position multi-way valve, passes through the two-position multi-way valve, and flows into the inlet of the quantitative ring array connected to a port of the two-position multi-way valve; the solution flowing out of the outlet of the quantitative ring array flows into a port in the two-position multi-way valve connected to the outlet of the quantitative ring array, passes through the two-position multi-way valve, and flows out from a port of the two-position multi-way valve; When the cyclic multidimensional liquid chromatography separation system performs chromatographic separation, when the two-position multi-way valve is in state B, the mobile phase output by the infusion unit flows into the inlet of the injection unit; the solution flowing out of the outlet of the injection unit flows into a port in the two-position multi-way valve connected to the outlet of the injection unit, passes through the two-position multi-way valve, and flows into the inlet of the quantitative ring array connected to a port of the two-position multi-way valve; the solution flowing out of the outlet of the quantitative ring array flows into a port in the two-position multi-way valve connected to the outlet of the quantitative ring array, passes through the two-position multi-way valve, and flows into the first interface of the mixer connected to a port in the two-position multi-way valve, the dilution output by the dilution pump flows into the second interface of the mixer as needed, and the solution flowing out of the third interface of the mixer flows into the inlet of the separation column array; the solution flowing out of the outlet of the separation column array is detected by the detection unit, flows into a port of the two-position multi-way valve, passes through the two-position multi-way valve, and flows out from a port of the two-position multi-way valve; By controlling the switching between the two states of state A and state B of the two-position multi-way valve, a cyclic multi-dimensional liquid chromatography separation function with full online detection is realized.

3. A cyclic multidimensional liquid chromatography separation system according to claim 1 or 2, characterized in that: The sample injection unit is connected in the flow path before the separation column array.

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