CIRCULATING MULTIDIMENSIONAL LIQUID CHROMATOGRAPHY AND APPLICATION THEREOF

Abstract

The present invention discloses a circulating multidimensional liquid chromatography and application thereof. The liquid chromatography comprises an infusion device, a sampling device, a collecting-resampling device, a chromatographic column switching device and a detecting device which are connected sequentially, wherein the collecting-resampling device comprises a collecting valve and a sample ring, and the collecting valve is connected with the sample ring; the sampling device is successively connected with the collecting valve and the chromatographic column switching device; the detecting device is also connected with the collecting valve; and the collecting valve is a three-slot three-position multi-way valve. The present invention adopts the three-slot three-position multi-way valve as the collecting valve, and the creative rotor flow path design can simultaneously satisfy the requirements of collection and resampling of the circulating multidimensional liquid chromatography, and greatly simplifies the hardware configuration.

Claims

1. A circulating multidimensional liquid chromatography, comprising an infusion device, a sampling device, a collecting-resampling device, a chromatographic column switching device and a detecting device which are connected sequentially; wherein the collecting-resampling device comprises a collecting valve and a sample ring, and the collecting valve is connected with the sample ring; the sampling device is successively connected with the collecting valve and the chromatographic column switching device; the detecting device is also connected with the collecting valve; the collecting valve is a three-slot three-position ten-way valve; a valve of the collecting valve has three working rotation positions; 10 interfaces are evenly distributed annularly on a valve stator; a rotor surface is provided with three folded or curved flow slots adjacent to each other; and the coverage range of each flow slot comprises three contiguous stator interfaces; one end of the sample ring is connected with the stator interface not covered by the flow slots in the collecting valve, which is denoted as a first interface, and other interfaces are numbered in a clockwise direction; the other end of the sample ring is connected with a sixth interface; the sixth interface is radially corresponding to the first interface; a third interface is connected with a waste liquid outlet; a fourth interface is connected with the detecting device; an eighth interface is connected with the chromatographic column switching device; a ninth interface is connected with the sampling device; the other interfaces are closed with plugs; the chromatographic column switching device comprises a column switching valve and a plurality of chromatographic columns connected thereto; and the column switching valve is connected with the eighth interface and the detecting device respectively; the column switching valve is a double-multi-position multi-way valve; the center and the edge of a valve stator are respectively provided with an interface; an annular region between the interfaces at the center and the edge of the valve stator is evenly distributed with radial inner and outer double-layer annular interfaces used for connecting both ends of the chromatographic columns respectively; and the surface of a valve rotor is respectively provided with a flow slot having the same radial distribution and capable of communicating with the stator center, the inner layer interface, the outer layer interface and the edge interface respectively, and an annular flow slot capable of always covering the edge interface in a valve rotation process; the valve stator of the column switching valve is distributed with 8 interfaces; the interface at the center of the valve stator is denoted as interface I, the interface at the edge of the valve stator is denoted as interface II, and the other interfaces are denoted as interface III-interface VIII respectively; wherein the interface I in the column switching valve is connected with the eighth interface in the collecting valve; the interface II in the column switching valve is connected with the detecting device; and the other interfaces are connected with a plurality of chromatographic columns respectively.

2. The circulating multidimensional liquid chromatography according to claim 1, wherein the infusion device is composed of a plurality of connected liquid chromatographic pumps; and the liquid chromatographic pumps are multielement high pressure pumps, unit high pressure pumps or low pressure pumps.

3. The circulating multidimensional liquid chromatography according to claim 2, wherein the chromatographic columns are low pressure liquid chromatographic columns, normal pressure liquid chromatographic columns, high pressure liquid chromatographic columns or ultrahigh pressure liquid chromatographic columns.

4. The circulating multidimensional liquid chromatography according to claim 3, wherein the detecting device is an ultraviolet detecting device, a fluorescence detecting device, an evaporative light detecting device, a differential detecting device or a mass spectrometry detecting device.

5. An application of the circulating multidimensional liquid chromatography of claim 4 in detection of characteristic components and toxic and harmful substances.

Description

DESCRIPTION OF DRAWINGS

[0038] To more clearly describe the technical solutions in the embodiments of the present invention or in the prior art, the drawings required to be used in the description of the embodiments or the prior art will be simply presented below. Apparently, the drawings in the following description are merely the embodiments of the present invention, and for those ordinary skilled in the art, other drawings can also be obtained according to the provided drawings without contributing creative labor.

[0039] FIG. 1 shows the balance and elution states of chromatographic column X in embodiment 1;

[0040] FIG. 2 shows the collection state of outflow liquid of chromatographic column X in embodiment 1;

[0041] FIG. 3 shows the balance and elution states of chromatographic column Z in embodiment 1;

[0042] FIG. 4 shows the sampling state of chromatographic column Z in embodiment 1;

[0043] FIG. 5 shows the balance and elution states of chromatographic column X in embodiment 2;

[0044] FIG. 6 shows the collection state of outflow components of chromatographic column X in embodiment 2;

[0045] FIG. 7 shows the sampling state of chromatographic column Y in embodiment 2.

[0046] In the figures,

[0047] 111binary high pressure pump; 112sampling device; 113collecting valve; 114sample ring; 115double-three-position three-way valve; 116detecting device; 117waste liquid; 118chromatographic column X; 119chromatographic column Y; 120chromatographic column Z; 121three-slot three-position six-way valve; 122quaternary high pressure gradient pump; 123double-two-position two-way valve.

DETAILED DESCRIPTION

[0048] The technical solutions in the embodiments of the present invention will be clearly and fully described below in combination with the drawings in the embodiments of the present invention. Apparently, the described embodiments are merely part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments in the present invention, all other embodiments obtained by those ordinary skilled in the art without contributing creative labor will belong to the protection scope of the present invention.

Embodiment 1

[0049] A circulating multidimensional liquid chromatography that uses a three-slot three-position ten-way valve as a collecting-resampling device, as shown in FIG. 1-FIG. 4, comprises an infusion device, a sampling device, a collecting-resampling device, a chromatographic column switching device and a detecting device.

[0050] The infusion device is composed of a binary high pressure pump 111; the sampling device is an automatic sampling device 112; the collecting-resampling device is composed of a three-slot three-position ten-way valve 113 and a 500 L sample ring 114; the chromatographic column switching device is composed of three chromatographic columns (comprising chromatographic columns X118, Y119 and Z120) and a double-three-position three-way valve 115; and the detecting device is an ultraviolet detecting device. The implementation steps of multidimensional liquid chromatographic analysis are as follows: [0051] (1) As shown in FIG. 1, both ends of the sample ring 114 are respectively connected with the stator interface (position 1) not covered by the flow slot and the radial corresponding interface (position 6) in the three-slot three-position ten-way valve 113; positions 3 and 4 are respectively connected with an outlet pipe of waste liquid 7 and an outflow pipe of the detecting device 6; positions 8 and 9 are connected with position 1 of the double-three-position three-way valve 115 and an outlet pipe of the sampling device 112 respectively; other number positions (positions 2, 5, 7 and 10) of the three-slot three-position ten-way valve 113 are closed with plugs; position 12 of the double-three-position three-way valve 115 is connected with an inflow pipe of the detecting device, and the radial double-layer inner and outer interfaces, positions 13 and 14, positions 15 and 16 and positions 17 and 18 of the double-three-position three-way valve 115 are connected with both ends of the chromatographic columns X118, Y119 and Z120 respectively; [0052] when the system is in a first-dimensional chromatographic column X elution state after sampling (FIG. 1), the three-slot three-position ten-way valve 113 is in a standby working position; at this moment, the mobile phase is pumped through a binary high pressure pump 111, flows through the sampling device 112, position 9 and position 8 of the three-slot three-position ten-way valve 113, position 11 and position 13 of the double-three-position three-way valve 115, a first-dimensional chromatographic column, position 14 and position 12 of the double-three-position three-way valve 115, the detecting device 116, and position 4 and position 3 of the three-slot three-position ten-way valve 113, and finally flows to waste liquid 117; [0053] (2) when the system collects the outflow components of the chromatographic column X118, the three-slot three-position ten-way valve 113 is rotated counterclockwise to a collecting working position (FIG. 2); at this time, the outflow liquid of the detecting device 116 flows to the waste liquid 117 through positions 4, 5, 6, 1, 2 and 3 of the three-slot three-position ten-way valve 113 successively, and target components are cached and collected through the sample ring 114; after collection is completed, the three-slot three-position ten-way valve 113 is rotated clockwise to return to the standby working position, and then the double-three-position three-way valve 115 is rotated clockwise after the end of the current chromatographic column elution; at this time, the mobile phase flows through position 11 and position 17 of the double-three-position three-way valve 115 successively, then flows into position 18 of the double-three-position three-way valve 115 through the chromatographic column Z120, and flows out through position 12 to the detecting device 116; and the system enters a balance waiting state of the chromatographic column Z120 (FIG. 3); [0054] (3) when the chromatographic column Z120 is fully balanced, the three-slot three-position ten-way valve 113 is rotated clockwise to a resampling position (FIG. 4); at this time, the mobile phase at an outlet of the sampling device 112 passes through position 9, position 10, position 1, the sample ring, position 6, position 7 and position 8 of the three-slot three-position ten-way valve 113 successively; the target components cached in the sample ring 114 are transferred into the chromatographic column Z120 for second-dimensional chromatographic elution analysis; after the components in the sample ring 114 are completely transferred, the three-slot three-position ten-way valve 113 is rotated again counterclockwise to the standby working position (FIG. 3) to reduce a dead volume of the system and increase the elution efficiency of the system.

Embodiment 2

[0055] A circulating multidimensional liquid chromatography that uses a three-slot three-position six-way valve as a collecting-resampling device, as shown in FIG. 5-FIG. 7, comprises an infusion device, a sampling device, a collecting-resampling device, a chromatographic column switching device and a detecting device.

[0056] The infusion device is composed of a quaternary high pressure gradient pump 122; the sampling device is an automatic sampling device 112; the collecting-resampling device is composed of a three-slot three-position six-way valve 121 and a 500 L sample ring 114; the chromatographic column switching device is composed of two chromatographic columns (comprising chromatographic columns X: Protein BEH SEC 4.6150 mm and Y: BEH C18 2.150 mm) and a double-two-position two-way valve 123; and the detecting device is an ultraviolet detecting device 116 with wavelength set as 220 nm. The implementation steps of multidimensional liquid chromatographic analysis are as follows: [0057] (1) As shown in FIG. 5, both ends of the sample ring 114 in the collecting-resampling device of the chromatographic system are respectively connected with the stator interface (position 21) not covered by the flow slot and the radial corresponding interface (position 24) in the three-slot three-position six-way valve 121; positions 22 and 23 are respectively connected with an outlet pipe of waste liquid and an outflow pipe of the detecting device 6; positions 25 and 26 are connected with position 31 of the double-two-position two-way valve 123 and an outlet pipe of the sampling device 112 respectively; position 32 of the double-two-position two-way valve 123 is connected with an inflow pipe of the detecting device 116; and positions 33 and 34 and positions 35 and 36 of the radial double-layer inner and outer interfaces of the double-two-position two-way valve 123 are connected with both ends of the chromatographic columns X118 and Y119 respectively; [0058] when the system is in a first-dimensional chromatographic column X118 elution state after sampling (FIG. 5), the three-slot three-position six-way valve 121 is in a standby working position; at this moment, the mobile phase is pumped through the quaternary high pressure gradient pump 122, flows through the sampling device 112, position 26 and position 25 of the three-slot three-position six-way valve 121, position 31 and position 33 of the double-two-position two-way valve 123, a first-dimensional chromatographic column, position 34 and position 32 of the double-two-position two-way valve 123, the detecting device 116, and position 23 and position 22 of the three-slot three-position six-way valve 121, and finally flows to waste liquid 117; [0059] (2) when the system collects the outflow components of the chromatographic column X118, the three-slot three-position six-way valve 121 is rotated counterclockwise to a collecting working position (FIG. 6); at this time, the outflow liquid of the detecting device 116 flows to the waste liquid 117 through positions 24, 23, 21 and 22 of the three-slot three-position six-way valve 121 successively, and target components are cached and collected through the sample ring 114; after collection is completed, the three-slot three-position six-way valve 121 is rotated clockwise to return to the standby working position, and the double-two-position two-way valve 123 is rotated clockwise immediately; at this time, the mobile phase flows through position 31 and position 35 of the double-two-position two-way valve 123 successively, then flows into position 36 of the double-two-position two-way valve 123 through the chromatographic column Y119, and flows out through position 32 to the detecting device 116; and the system enters a balance waiting state of the chromatographic column Y119; [0060] (3) when the chromatographic column Y119 is fully balanced, the three-slot three-position six-way valve 121 is rotated clockwise to a resampling position (FIG. 7); at this time, the mobile phase at an outlet of the sampling device 112 passes through position 26, position 21, the sample ring 114, position 24 and position 25 of the three-slot three-position six-way valve 121 successively; the target components cached in the sample ring 114 are transferred into the chromatographic column Y119 for second-dimensional chromatographic elution analysis; after the components in the sample ring 114 are completely transferred, the three-slot three-position six-way valve 121 is rotated again counterclockwise to the standby working position to reduce a dead volume of the system and increase the elution efficiency of the system.

[0061] As shown in FIG. 1, in addition to the two-dimensional liquid chromatographic analysis of the target components, the system in embodiment 1 can also perform one-dimensional and three-dimensional liquid chromatographic analysis without any modification or supplement to the system hardware, with strong flexibility and compatibility and wide applicability, and meanwhile, the analysis time of the next dimension is not limited by the collection and transfer time of the components in the previous dimension so that separation efficiency is higher. On the basis of embodiment 1, embodiment 2 removes the stator interface closed by the plug in the three-slot three-position ten-way valve and uses the three-slot three-position six-way valve as the collecting valve. The implementation mode of the present invention is further described, and the innovation of the circulating two-dimensional liquid chromatography of the present invention and the broad application prospects in the separation and analysis of complex components are fully illustrated.

[0062] Each embodiment in the description is described in a progressive way. The difference of each embodiment from each other is the focus of explanation. The same and similar parts among all of the embodiments can be referred to each other. For a device disclosed by the embodiments, because the device corresponds to a method disclosed by the embodiments, the device is simply described. Refer to the description of the method part for the related part.

[0063] The above description of the disclosed embodiments enables those skilled in the art to realize or use the present invention. Many modifications to these embodiments will be apparent to those skilled in the art. The general principle defined herein can be realized in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments shown herein, but will conform to the widest scope consistent with the principle and novel features disclosed herein.