CN217060099U - Multi-mode liquid chromatography system - Google Patents

Abstract

The utility model discloses a multi-mode liquid chromatography system, include: the device comprises a sample tray for loading various samples, a sample adding needle for sucking and transferring the samples, a washing station for washing the sample adding needle, a liquid chromatography unit for separating or diluting the samples, a mass spectrometer for detecting and analyzing a target object after the samples are separated or diluted, and a control device; the liquid chromatography units are arranged at least two and are arranged at the rear end of the sampling needle in parallel and used for analyzing or diluting the sample transferred by the sampling needle to form a target object to be analyzed by the mass spectrometer, and the rear end of each liquid chromatography unit is connected with the sampling end of the mass spectrometer; the sample tray, the sample adding needle, the washing station, the mass spectrometer and the liquid chromatography unit are all connected with the control device. Through using the utility model provides a multi-mode liquid chromatography system can effectively improve the utilization ratio of mass spectrograph.

Description

Multi-mode liquid chromatography system

Technical Field

The utility model relates to a liquid chromatography mass spectrometry technical field that allies oneself with, more specifically says, relates to a multi-mode liquid chromatography system.

Background

In the prior art, a liquid chromatography-mass spectrometer (LC-MS) technology is a short-term LC-MS technology, that is, a chromatograph and a mass spectrometer are connected in series for use, and the LC-MS technology is increasingly emphasized in clinical application, and a chromatograph is used to separate an interested target and then is used together with the mass spectrometer, so that the LC-MS technology not only can effectively protect the mass spectrometer, but also can improve a final detection result.

The conventional LC-MS technology generally needs a sample pretreatment process, and common methods for sample pretreatment generally include methods such as protein precipitation, liquid-liquid extraction, solid-phase extraction, dilution, and the like, and these pretreatment methods often require professional personnel to operate, and each person has different operation methods, and there are human operation errors, which further seriously affects the consistency and accuracy of the detection result. In addition, different projects need to be matched with corresponding chromatographic columns (LC columns) after a complicated pretreatment process, and for a traditional single LC channel, when the same project is detected, a mass spectrum always waits for a complete detection period when detecting a first sample and a second sample, which can greatly reduce the utilization rate of a mass spectrometer, reduce the consistency and accuracy of detection results, and hardly realize the output of a high-quality and high-flux result. When different items are detected, laboratory personnel need to replace the corresponding chromatographic columns, and the utilization rate of the mass spectrum is also reduced.

In summary, how to improve the utilization rate of the mass spectrum is an urgent problem to be solved by those skilled in the art.

SUMMERY OF THE UTILITY MODEL

In view of this, the present invention provides a multi-mode liquid chromatography system, which can effectively improve the utilization rate of a mass spectrometer.

In order to achieve the above object, the present invention provides the following technical solutions:

a multi-modal liquid chromatography system, comprising: the device comprises a sample tray for loading various samples, a sample adding needle for sucking and transferring the samples, a washing station for washing the sample adding needle, a liquid chromatography unit for separating or diluting the samples, a mass spectrometer for detecting and analyzing a target object after the samples are separated or diluted, and a control device;

the liquid chromatography units are arranged at the rear end of the sample adding needle in parallel and used for separating or diluting the sample transferred by the sample adding needle to form a target object to be analyzed by the mass spectrometer, and the rear end of each liquid chromatography unit is connected with the sample inlet end of the mass spectrometer;

the sample tray, the sample adding needle, the washing station, the mass spectrometer and the liquid chromatography unit are all connected with the control device.

Preferably, the liquid chromatography unit comprises an analytical LC module for performing a separation operation on a conventional sample and a recovery device for collecting waste liquid after sample separation;

the analytical LC module comprises an LC channel, an LC injection valve for receiving a sample, an LC pump for driving liquid to flow and a three-way selection valve, wherein the LC channel comprises an LC chromatographic column and a pipeline for separating a required target;

the LC pump, the LC filling valve, the LC chromatographic column and the three-way selector valve pass through the pipeline communicates in proper order, the entry end and the mobile phase storage unit of LC pump are connected, the LC pump be used for transporting two at least different mobile phases, with make the sample be in through adjusting mobile phase concentration enrichment or elution on the LC chromatographic column, the entry end of three-way selector valve with the LC chromatographic column intercommunication, two exit ends of three-way selector valve respectively with recovery unit with the mass spectrograph intercommunication, recovery unit with controlling means connects.

Preferably, the liquid chromatography unit comprises an online SPE module for performing separation operation on a complex sample and a recovery device for collecting waste liquid after sample separation, the online SPE module comprises a first SPE injection valve, a SPE pump, an online SPE trapping/eluting valve, a SPE column arranged in the online SPE trapping/eluting valve, a second SPE injection valve, an LC pump, an LC chromatographic column and a three-way selection valve, the SPE pump and the LC pump are both used for driving liquid to flow, the SPE column and the LC chromatographic column are both used for performing substance separation on the sample, and the first SPE injection valve and the second SPE injection valve are both used for receiving the sample;

the system comprises an online SPE trapping/eluting valve, an LC pump, a first SPE injection valve, an LC chromatographic column, a three-way selection valve, a recovery device and a mass spectrometer, wherein one inlet ends of the SPE pump, the first SPE injection valve and the online SPE trapping/eluting valve are sequentially communicated, the other inlet ends of the LC pump, the second SPE injection valve and the online SPE trapping/eluting valve are sequentially communicated, the outlet ends of the online SPE trapping/eluting valve, the LC chromatographic column and the inlet end of the three-way selection valve are sequentially communicated, and the two outlet ends of the three-way selection valve are respectively communicated with the recovery device and the mass spectrometer;

the inlet end of the SPE pump is connected with the mobile phase storage unit, the SPE pump is used for conveying at least one mobile phase, the inlet end of the LC pump is connected with the mobile phase storage unit, the LC pump is used for conveying at least two different mobile phases, and the online SPE trapping/eluting valve is provided with a valve port for discharging waste liquid.

Preferably, the length of the SPE column is smaller than that of the LC chromatographic column, and the particle size of the SPE column packing is larger than that of the LC chromatographic column packing.

Preferably, the liquid chromatography unit comprises a dilution processing module for performing a separation operation on a simple sample, the dilution processing module comprising an LC pump for driving a liquid flow, a dilution injection valve for receiving the sample, and a dilution line;

the entry end and the mobile phase storage unit of LC pump are connected, the LC pump is used for transporting at least one different mobile phase, the LC pump dilute the filling valve dilute the pipeline and the mass spectrometer communicates in proper order.

Preferably, the liquid chromatography unit still include with dilute the SPE pipeline of the parallelly connected setting of pipeline, be connected with in the SPE pipeline and be used for carrying out the SPE post of enrichment to the sample, the SPE pipeline with the entry end that dilutes the pipeline all communicates through first distribution valve, first distribution valve with dilute the injection valve intercommunication, the SPE pipeline with the exit end that dilutes the pipeline all distributes the valve intercommunication through the second, the second distribute the valve pass through the tee bend selection valve with the introduction port intercommunication of mass spectrograph, the other end and the recovery unit of tee bend selection valve are connected.

Preferably, still including SPE elution pump and the bypass valve that is used for driving the eluent to flow, the bypass valve sets up dilute the injection valve with between the first distribution valve, SPE elution pump the bypass valve the tee bend selection valve the second distribute the valve the SPE post first distribution valve and the introduction end of mass spectrograph communicates in proper order, with will the target elution of SPE enrichment on the post extremely the mass spectrograph analyzes.

Preferably, each of the LC injection valves is provided with a dosing ring for receiving a sample and a valve port for discharging waste liquid.

Preferably, the recovery device comprises a waste liquid collector communicated with the plurality of three-way selector valves and a waste liquid bottle for containing waste liquid, and the waste liquid collector is communicated with the waste liquid bottle.

Preferably, the mass spectrometer further comprises a third distribution valve, a common valve port of the third distribution valve is communicated with a sample inlet port of the mass spectrometer, a rear end of each liquid chromatography unit is communicated with a distribution valve port of the third distribution valve, and the third distribution valve is connected with the control device.

When using the utility model provides a during multi-mode liquid chromatography system, conventional sample separates or dilutes in any liquid chromatography unit, by advancing a kind to appear the time of a peak for about 2.5 minutes, also be to single liquid chromatography unit, conventional sample begins to advance a kind from 0 minute moment, 0-2min carries out the enrichment of target useful thing and the analyte elution process of not being interested, the analyte of not being interested that the elution obtained is also the waste liquid, the waste liquid is mobile to be carried in the recovery unit, the analyte of interest is eluted 2-2.5 minutes time, target useful thing is mobile to be carried in the mass spectrograph and carries out analysis and detection. In order to improve the use efficiency of the mass spectrometer, an operator can perform sequential staggered switching work on a plurality of liquid chromatography units connected in parallel so as to maximize the efficient use of the mass spectrometer.

First, the control device can control the sample application needle to absorb the target sample in the sample tray, and then control the sample application needle to move to the sample receiving port of the liquid chromatography unit. Thereafter, the first liquid chromatography unit is operated, for example, by controlling the LC pump to deliver a mobile phase and adjusting the concentration of the mobile phase, which may carry the sample through the LC column, to complete the enrichment process for the analyte of interest. Meanwhile, the control device can control the sample adding needle to move to the position of the washing station for washing so as to prepare for sample introduction of the second liquid chromatography unit. Wherein, the work flow of the first liquid phase chromatographic unit is as follows: and (3) carrying out the enrichment of the target object and the elution process of the uninteresting analytes in 0-2min, then feeding the uninteresting analytes into a recovery device through a three-way selection valve, eluting the interesting analytes from the LC chromatographic column for 2-2.5min, and feeding the interesting analytes into a mass spectrometer to finish the analysis process of the interesting analytes.

Meanwhile, the target of the second liquid chromatography unit can start from 0.5 minute, the sample injection process of the first liquid chromatography unit can be repeated, namely, sample injection and sample transfer are sequentially carried out, the sample is transferred into the sample receiving port of the second liquid chromatography unit, the second liquid chromatography unit can carry out the enrichment of the target and the elution process of the analyte which is not interested in 0.5-2.5min, the analyte which is not interested in can enter the recovery device, the second liquid chromatography unit can carry out the elution process of the analyte which is interested in 2.5-3min, and the analyte which is interested in can flow into the mass spectrometer, so as to complete the analysis process of the analyte which is interested in. If the system is also connected with a third … liquid chromatographic unit and a fourth … liquid chromatographic unit in parallel, the liquid chromatographic units can be controlled to operate in sequence, alternately and in parallel according to the process, so that the mass spectrometer can continuously perform chromatographic analysis, and the efficiency of the mass spectrometer is maximized.

To sum up, the utility model provides a multi-mode liquid chromatography system can effectively improve the utilization ratio of mass spectrograph.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the embodiments or the prior art descriptions will be briefly described below, it is obvious that the drawings in the following description are only embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.

FIG. 1 is a schematic diagram of a multi-mode liquid chromatography system according to the present invention;

FIG. 2 is a schematic diagram of an analytical LC module during sample injection;

FIG. 3 is a schematic diagram of the sample transfer to the first LC injection valve;

FIG. 4 is a schematic diagram of the first LC channel during target enrichment;

FIG. 5 is a schematic diagram of the first and second LC channels in the target enrichment configuration;

FIG. 6 is a schematic diagram of the structure of the first LC channel when the target is transported to the mass spectrometer and the second LC channel when the target continues to be enriched;

FIG. 7 is a schematic diagram of the next target enrichment in the first LC channel and target delivery to the mass spectrometer in the second LC channel;

FIG. 8 is a schematic structural diagram of online SPE module sampling;

FIG. 9 is a schematic diagram of the structure of the sample transfer to the first SPE injection valve;

FIG. 10 is a schematic of the structure of a target enriched on the SPE column of the on-line SPE trap/elute valve;

FIG. 11 is a schematic diagram of the structure of the target eluted from the SPE column to the LC column and finally to the mass spectrometer;

FIG. 12 is a schematic diagram of a sample introduction structure of the dilution processing module;

FIG. 13 is a schematic diagram of the structure of the sample when it is transferred to the dilution injection valve;

FIG. 14 is a schematic diagram of a sample diluted by a dilution line and transported to a mass spectrometer;

FIG. 15 is a schematic of the structure of a target enriched on the SPE column of a SPE tube;

fig. 16 is a schematic diagram of the structure when the target is eluted to the mass spectrometer in reverse phase.

In fig. 1-16:

1 is a sample tray, 2 is a sample adding needle, 3 is a washing station, 4 is an analytical LC module, 5 is a mass spectrometer, 6 is a recovery device, 7 is an LC channel, 8 is an LC injection valve, 9 is a pipeline, 10 is an LC pump, 11 is an LC chromatographic column, 12 is a three-way selector valve, 13 is an online SPE module, 14 is a first SPE injection valve, 15 is an SPE pump, 16 is an online SPE trapping/eluting valve, 17 is an SPE column, 18 is a second SPE injection valve, 19 is a dilution processing module, 20 is a dilution injection valve, 21 is a bypass valve, 22 is a dilution pipeline, 23 is a SPE pipeline, 24 is a first distribution valve, 25 is a second distribution valve, 26 is an SPE eluting pump, 27 is a valve port, 28 is a waste liquid bottle collector, 29 is a waste liquid bottle, 30 is a third distribution valve, and 31 is a quantitative ring.

Detailed Description

The technical solutions in the embodiments of the present invention will be described clearly and completely with reference to the accompanying drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments in the present invention, all other embodiments obtained by a person skilled in the art without creative work belong to the protection scope of the present invention.

The core of the utility model is to provide a multi-mode liquid chromatography system, can effectively improve the utilization ratio of mass spectrograph.

Please refer to fig. 1 to fig. 16.

The present embodiment provides a multi-mode liquid chromatography system, comprising: the device comprises a sample tray 1 for loading various samples, a sample adding needle 2 for sucking and transferring the samples, a washing station 3 for washing the sample adding needle 2, a liquid chromatography unit for separating or diluting the samples, a mass spectrometer 5 for detecting and analyzing a target object after the samples are separated or diluted, and a control device; the liquid chromatography units are arranged at least two and are arranged at the rear end of the sampling needle in parallel and used for analyzing or diluting the sample transferred by the sampling needle to form a target object to be analyzed by the mass spectrometer 5, and the rear end of each liquid chromatography unit is connected with the sampling end of the mass spectrometer 5; the sample tray 1, the sample adding needle 2, the washing station 3, the mass spectrometer 5 and the liquid chromatography unit are all connected with a control device.

On the basis of the above embodiment, preferably, the liquid chromatography unit comprises an analytical LC module 4 for performing a separation operation on a conventional sample and a recovery device 6 for collecting waste liquid after sample separation; the analytical LC module 4 comprises an LC channel 7, an LC injection valve 8 for receiving a sample, an LC pump 10 for driving a liquid flow, and a three-way selector valve 12, the LC channel 7 comprising an LC chromatographic column 11 for separating a desired target and a conduit 9;

the LC pump 10, the LC injection valve 8, the LC chromatographic column 11 and the three-way selector valve 12 are sequentially communicated through a pipeline 9, the inlet end of the LC pump 10 is connected with the mobile phase storage unit, the LC pump 10 is used for conveying at least two different mobile phases so as to enable a sample to be enriched or eluted on the LC chromatographic column 11 by adjusting the concentration of the mobile phases, the inlet end of the three-way selector valve 12 is communicated with the LC chromatographic column 11, the two outlet ends of the three-way selector valve 12 are respectively communicated with the recovery device 6 and the mass spectrometer 5, and the recovery device 6 is connected with the control device.

It should be noted that the LC injection valve 8 of the present application may be set as a six-way selector valve, a rotor and a stator are arranged in the six-way selector valve, six valve ports of the six-way selector valve are named a, b, c, d, e, and f clockwise, when the rotor rotates, there are only two states, the first state is that the valve ports a and b are communicated, the valve ports c and d are communicated, the valve ports e and f are communicated, the second state is that the valve ports a and f are communicated, the valve ports b and c are communicated, and the valve ports d and e are communicated.

It should be noted that the sample tray 1 is mainly used for storing and transferring samples after pretreatment, the sample tray 1 can be set as a circular disc capable of rotating circumferentially, and various samples can be accommodated circumferentially on the circular disc, so that the sample adding needle 2 can accurately suck the samples through rotation and lifting operations. The LC filling valve 8 is provided with a dosing ring 31 to allow dosing control of the liquid by means of the dosing ring 31 and a dosing pump connected to the dosing ring 31. The sample addition needle 2 is mainly used for transferring a pretreated sample and injecting the sample into the quantitative loop 31 of the LC injection valve 8. Every time the sampling operation is accomplished to application of sample needle 2, then need remove and wash in the station 3 to avoid causing the pollution influence to the sampling operation next time.

The shape, structure, model and position of the sample tray 1, the sample adding needle 2, the washing station 3, the liquid chromatography unit, the mass spectrometer 5, the recovery device 6 and the control device can be determined in the actual application process according to the actual situation and the actual demand.

When the multi-mode liquid chromatography system provided by the present invention is used, the time from the sample injection to the peak discharge is about 2.5 minutes in any LC channel 7 of the analytical LC module 4 (fig. 1 shows 3 analytical LC modules 4 connected in parallel, in practical applications, the number of the analytical LC modules 4 can be reasonably set according to the separation speed of the analytical LC modules 4 and the processing speed of the mass spectrometer 5), that is, for a single analytical LC module 4, the conventional sample starts to sample from 0 minute, the enrichment of the target useful substance (also called target) and the elution process of the non-interesting analyte are performed in 0-2min, the non-interesting analyte obtained by the elution is also a waste liquid, the waste liquid can be flowed into the recovery device 6, the interesting analyte is eluted in 2-2.5min, and the target useful substance is delivered into the mass spectrometer 5 for analysis and detection. In order to improve the efficiency of use of the mass spectrometer 5, the operator may switch the plurality of analytical LC modules 4 in parallel alternately in sequence to maximize the efficiency of use of the mass spectrometer 5.

The staggered switching operation of analytical LC modules 4 will now be illustrated, as shown in fig. 2-7, with the arrows pointing in the direction of flow of the analyte of interest.

First, the control device can control the sample adding needle 2 to suck the target sample in the sample tray 1, then control the sample adding needle 2 to move to the LC injection valve 8, and inject the target sample into the quantitative ring 31 of the LC injection valve 8. Thereafter, the first analytical LC module 4 is operated, i.e., the LC pump 10 delivers the mobile phase and adjusts the concentration of the mobile phase, which carries the sample through the LC column 11 to complete the enrichment process for the analyte of interest. At the same time, the control device can control the sample adding needle 2 to move to the position of the washing station 3 for washing so as to prepare the sample adding of the second analysis type LC module 4. The work flow of the first analytical LC module 4 is as follows: and (3) carrying out the enrichment of the target object and the elution of the uninteresting analyte for 0-2min, then feeding the uninteresting analyte into the recovery device 6 through the three-way selector valve 12, eluting the interesting analyte from the LC chromatographic column 11 for 2-2.5min, and feeding the interesting analyte into the mass spectrometer 5 through the three-way selector valve 12 to finish the analysis process of the interesting analyte.

Meanwhile, the target of the second analytical LC module 4 may start from 0.5 minute, and the sample injection process of the first analytical LC module 4 may be repeated, that is, the sample is sequentially loaded and the sample is transferred to the quantitative loop 31 of the LC injection valve 8 of the second analytical LC module 4, the second analytical LC module 4 may perform the enrichment of the target and the elution of the analyte of no interest in 0.5-2.5 minutes, the analyte of no interest may enter the recovery device 6 through the three-way selection valve 12, and the second analytical LC module 4 may perform the elution of the analyte of interest in 2.5-3 minutes, and the analyte of interest may enter the mass spectrometer 5 through the three-way selection valve 12, so as to complete the analysis process of the analyte of interest.

In addition, if the third and fourth … analytical LC modules 4 are connected in parallel in the system, the channels can be controlled to operate alternately and in parallel according to the process, so that the mass spectrometer 5 can perform continuous chromatographic analysis, and the efficiency of the mass spectrometer 5 can be maximized.

To sum up, the utility model provides a multi-mode liquid chromatography system can effectively improve mass spectrograph 5's utilization ratio.

On the basis of the embodiment, preferably, the system further comprises an online SPE module 13 for performing separation operation on a complex sample and a recovery device 6 for collecting waste liquid after sample separation, wherein the online SPE module 13 comprises a first SPE injection valve 14, a SPE pump 15, an online SPE trapping/eluting valve 16, a SPE column 17, a second SPE injection valve 18, an LC pump 10, an LC chromatographic column 11 and a three-way selection valve 12, which are arranged in the online SPE trapping/eluting valve 16, the SPE column 17 and the LC chromatographic column 11 are used for performing substance separation on the sample, and the first SPE injection valve 14 and the second SPE injection valve 18 are used for receiving the sample; an SPE pump 15, a first SPE injection valve 14 and one inlet end of an online SPE trapping/eluting valve 16 are communicated in sequence, an LC pump 10, a second SPE injection valve 18 and the other inlet end of the online SPE trapping/eluting valve 16 are communicated in sequence, the outlet end of the online SPE trapping/eluting valve 16, the inlet ends of an LC chromatographic column 11 and a three-way selector valve 12 are communicated in sequence, and two outlet ends of the three-way selector valve 12 are communicated with a recovery device 6 and a mass spectrometer 5 respectively;

the inlet end of the SPE pump 15 is connected with the mobile phase storage unit, the SPE pump 15 is used for conveying at least one mobile phase, the inlet end of the LC pump 10 is connected with the mobile phase storage unit, the LC pump 10 is used for conveying at least two different mobile phases, and the online SPE trapping/eluting valve 16 is provided with a valve port 27 for discharging waste liquid.

It should be noted that the first SPE injection valve 14 has the same structure as the LC injection valve 8, and is a six-way selector valve, a rotor and a stator are provided in the valve, and the six valve ports of the valve are named a, b, c, d, e, and f clockwise. The structures of the second SPE injection valve 18, the LC injection valve 8, the first SPE injection valve 14, and the online SPE trapping/eluting valve 16 of the present application are the same, and thus are not described again. In addition, the LC pumps in the embodiments of the present application have the same structure, and the recovery device 6 in the embodiments has the same structure or the same recovery component, so the details are not repeated.

In addition, it should be noted that, for some complicated targets, the effect of performing enrichment and separation only by the LC column 11 of the analytical LC module 4 is not good. Therefore, more complex samples can be effectively separated by the on-line SPE module 13, that is, the analyte of interest is first enriched by the SPE column 17, and then the LC pump 10 drives the mobile phase to the LC chromatographic column 11, so as to complete the chromatographic separation process. Can increase SPE pump 15, first SPE on original LC channel 7 and pour into valve 14, online SPE entrapment/elution valve 16 and locate SPE post 17 in online SPE entrapment/elution valve 16, can obtain the online SPE module 13 that is used for carrying out effective separation detection to complicated sample.

It is further noted that SPE pump 15 delivers one mobile phase, LC pump 10 delivers at least two different mobile phases, and online SPE trap/elute valve 16 is provided with a valve port 27 for discharging waste liquid. The LC pump 10 may enrich or elute an analyte of interest (i.e., a target) of a sample on the LC chromatography column 11 by adjusting the concentration of various mobile phases. Since the SPE pump 15 carries a mobile phase that can transport the analyte of interest or the non-analyte of interest for enrichment on the SPE column 17, the non-analyte of interest can be directly discharged through the valve port 27 when the analyte of interest is enriched on the SPE column 17. The mobile phase here acts primarily to transport the target, pushing it through the SPE column 17 and enriching the desired target on the SPE column 17.

Preferably, the separation speed of the SPE column 17 is greater than the separation speed of the LC chromatographic column 11, specifically, the length of the SPE column 17 is smaller than the length of the LC chromatographic column 11, and the filler particle diameter of the SPE column 17 is greater than the filler particle diameter of the LC chromatographic column 11.

It should be noted that the SPE column 17 separates the extracted components, the sample matrix and other components according to the strength of the acting force on the stationary phase packing. Initially, the sample is placed on top of the stationary phase packing, enters the stationary phase with the extraction solvent, and is distributed between the stationary phase and the extraction solvent. The component with a small partition coefficient is not easy to be retained by the stationary phase and flows out earlier, while the component with a large partition coefficient is retained in the stationary phase for a longer time and flows out later. The target analyte then has a large partition coefficient and is retained in the stationary phase, which requires more or more polar extraction solvent to elute. Thus, the stationary Phase may be referred to as the Solid Phase extractant and the wash agent as the extraction solvent or eluent, and the column packed with the various packing materials is referred to as the SPE column 17(Solid Phase extraction Cartridges).

It should be noted that the LC column 11 and the SPE column 17 are made of the same material and have the same shape, but have different structural dimensions, for example, the length of the SPE column 17 is smaller than the length of the LC column 11, and the packing particle diameter of the SPE column 17 is larger than that of the LC column 11. Since the LC column 11 is longer and the packing particle size is smaller, the separation effect is better but the separation time is longer when the sample passes through the LC column 11, while the separation effect is relatively worse but the separation time is faster when the sample passes through the SPE column 17. Therefore, the LC column 11 and the SPE column 17 can be selected according to the sample. In addition, different mobile phases (solid phase extractants or eluents) may be provided within SPE pump 15 and LC pump 10 to enable enrichment or elution of the sample's analytes of interest on SPE column 17 or LC chromatography column 11.

To further illustrate the operation of online SPE module 13, an example is next provided, as shown in fig. 8-11, where the arrow flow direction is the direction of flow of the analyte of interest.

Firstly, the control device can control the sample adding needle 2 to absorb the complex sample in the sample tray 1, and then control the sample adding needle 2 to move to the first SPE injection valve 14, and inject the complex sample into the quantitative ring 31 of the first SPE injection valve 14. The SPE pump 15 is then controlled to operate to transport the mobile phase carrying the complex sample through the SPE column 17 of the on-line SPE trap/elute valve 16 so that the analyte of interest is enriched on the SPE column 17, whereas the analyte of no interest can be directly discharged with the mobile phase from the valve port 27 of the on-line SPE trap/elute valve 16.

The LC pump 10 can then be controlled to operate to carry the different mobile phases through the SPE column 17 of the in-line SPE trap/elute valve 16 and elute the analytes of interest enriched on the SPE column 17 into the LC chromatography column 11, wherein the analytes not of interest can pass through the three-way selector valve 12 with the mobile phase into the recovery device 6. Finally, the concentration of different mobile phases is adjusted, so that the analyte of interest enters the mass spectrometer 5 along with the mobile phases through the three-way selector valve 12, and the LC-MS analysis operation of the complex sample is completed. After the sampling and transferring operation of the complex sample is completed each time, the sampling needle 2 needs to be controlled to move into the washing station 3 for cleaning so as to prepare for the next sampling and transferring.

On the basis of the embodiment, preferably, the liquid chromatography unit comprises a dilution processing module 19 for performing a separation operation on a simple sample, the dilution processing module 19 comprises an LC pump 10 for driving a liquid to flow, a dilution injection valve 20 for receiving the sample, and a dilution pipeline 22, an inlet end of the LC pump 10 is connected with the mobile phase storage unit, the LC pump 10 is used for conveying at least one different mobile phase, and the LC pump 10, the dilution injection valve 20, the dilution pipeline 22, and the mass spectrometer 5 are sequentially communicated.

It should be noted that the structure of the dilution injection valve 20, the LC injection valve 8, the first SPE injection valve 14, the second SPE injection valve 18, and the on-line SPE trapping/eluting valve 16 are the same, and therefore, the description thereof is omitted. The dilution processing module 19 can be used for fast separation of some simple samples, the number of the dilution pipelines 22 can be freely set according to requirements, the SPE columns 17 are not arranged in the plurality of dilution pipelines 22, the dilution process of the samples in the dilution pipelines 22 is driven only by the mobile phase to complete the separation operation, and the separation process is fast.

To further illustrate the operation of the dilution processing module 19, an example will now be described, as shown in FIGS. 12-14, where the arrows indicate the direction of flow of the analyte of interest.

First, the control device can control the sample adding needle 2 to suck the simple sample in the sample tray 1, then control the sample adding needle 2 to move to the dilution injection valve 20, and inject the simple sample into the quantitative ring 31 of the dilution injection valve 20. Then, the LC pump 10 is controlled to operate to convey the mobile phase carrying the simple sample through the bypass valve 21, the dilution line 22 and the three-way selector valve 12, and finally into the mass spectrometer 5, so as to complete the LC-MS analysis operation of the simple sample. In this dilution mode, the simple sample is not passed through any SPE column 17, and the mobile phase pushes the simple sample through a long tube to be diluted so as to flow into the mass spectrometer 5 quickly to complete the dilution process analysis.

Preferably, the liquid chromatography unit further comprises a SPE pipeline 23 connected in parallel with the dilution pipeline 22, the SPE column 17 for enriching the sample is connected in the SPE pipeline 23, the inlet ends of the SPE pipeline 23 and the dilution pipeline 22 are both communicated through a first distribution valve 24, the first distribution valve 24 is communicated with the dilution injection valve 20, the outlet ends of the SPE pipeline 23 and the dilution pipeline 22 are both communicated through a second distribution valve 25, the second distribution valve 25 is communicated with the sample inlet port of the mass spectrometer through a three-way selector valve 12, and the other end of the three-way selector valve 12 is connected with the recovery device 6.

It should be noted that the SPE column 17 is a short column structure, which can realize the rapid enrichment and elution operations of the analyte of interest, and also, the number of SPE tubes 23 and SPE columns 17 can be freely set according to the requirement.

Preferably, in order to facilitate reverse elution of the SPE column 17, the SPE column further comprises an SPE elution pump 26 and a bypass valve 21 for driving eluent to flow, the bypass valve 21 is disposed between the dilution injection valve 20 and the first distribution valve 24, and the SPE elution pump 26, the bypass valve 21, the three-way selection valve 12, the second distribution valve 25, the SPE column 17, the first distribution valve 24 and the sample injection end of the mass spectrometer 5 are sequentially communicated to elute the target substance enriched on the SPE column 17 to the mass spectrometer 5 for analysis.

It should be noted that the bypass valve 21, the LC injection valve 8, the first SPE injection valve 14, the second SPE injection valve 18, the online SPE trap/elute valve 16, and the dilution injection valve 20 have the same structure, and therefore, the description thereof is omitted. In this embodiment, SPE elution pump 26, bypass valve 21, three-way selector valve 12, second distribution valve 25, SPE column 17, and first distribution valve 24 may be connected in sequence and connected to a distribution valve port of a third distribution valve 30 at the front end of mass spectrometer 5, and bypass valve 21 is provided with a valve port 27 for discharging waste liquid. The components described above including the LC pump 10 for driving the flow of liquid, the dilution injection valve 20 for receiving the sample, the SPE line 23, and the SPE elution pump 26 may be referred to as a SPE processing module, and 3 SPE lines 23 and one dilution line 22 may be provided.

To further illustrate the operation of the spe processing module, an example is next provided, as shown in FIGS. 15 and 16, where the direction of the arrows indicates the direction of flow of the analyte of interest.

First, the control device can control the sample adding needle 2 to suck the simple sample in the sample tray 1, then control the sample adding needle 2 to move to the dilution injection valve 20, and inject the simple sample into the quantitative ring 31 of the dilution injection valve 20. The LC pump 10 is then controlled to operate to deliver the mobile phase carrying the simple sample through the bypass valve 21, the SPE column 17 of the first SPE line 23 and the three-way selector valve 12, and finally to pass the waste liquid into valve port 27 of the bypass valve 21. Because of the shorter SPE column 17, the time for the enrichment of the analyte of interest on the SPE column 17 is short and the analyte of interest can be rapidly enriched on the SPE column 17 of the first SPE line 23.

The SPE elution pump 26 can then be controlled to operate to deliver the eluent through the three-way selector valve 12, the second distribution valve 25, and the first SPE line 23 to reverse the elution of the analyte of interest (also referred to as target) enriched before the SPE column 17 in the first SPE line 23, which can flow into the mass spectrometer 5 for LC-MS analysis as the eluent passes through the bypass valve 21 and the third distribution valve 30. Because SPE column 17 is short and can reverse elute the analyte of interest so that the analyte of interest does not need to pass through the entire bed of SPE column 17, the time taken for the analyte of interest to elute and flow to mass spectrometer 5 is also short.

On the basis of the described embodiment, it is preferred that each LC injection valve 8 is provided with a dosing ring 31 for containing a sample and a valve port 27 for discharging waste liquid. Therefore, it is possible to move the sample addition needle 2 to each LC injection valve 8 and inject the target sample into the quantitative loop 31 of the corresponding LC injection valve 8 to control the volume of the target sample. By providing the valve port 27 in the LC injection valve 8, the waste liquid can be recovered more conveniently. Similarly, a dosing ring 31 and a valve port 27 may be provided in the dilution injection valve 20, the first SPE injection valve 14, and the second SPE injection valve 18.

Preferably, the recovery device 6 comprises a waste liquid collector 28 communicating with the plurality of three-way selector valves 12 and a waste liquid bottle 29 for containing waste liquid, the waste liquid collector 28 communicating with the waste liquid bottle 29. Therefore, the waste liquid can enter the waste liquid collector 28 through the three-way selector valve 12, and then the waste liquid collector 28 discharges the waste liquid into the waste liquid bottle 29.

Preferably, the mass spectrometer further comprises a third distribution valve 30, a common valve port of the third distribution valve 30 is communicated with the sample inlet port of the mass spectrometer 5, a rear end of the liquid chromatography unit is communicated with a distribution valve port of the third distribution valve 30, and the third distribution valve 30 is connected with the control device. That is, the outlet end of each LC channel 7 is respectively communicated with the distributing valve port of the third distributing valve 30, the outlet end of each LC channel 7 is respectively communicated with the mass spectrometer 5 through the third distributing valve 30, and the third distributing valve 30 is connected with the control device. A third dispensing valve 30 is provided between the three-way selector valve 12 and the mass spectrometer 5 to allow further controlled adjustment of the analyte of interest to be introduced into the mass spectrometer 5.

It should also be said, the utility model provides a multi-mode liquid chromatography system has multiple separation detection mode, for example including carrying out the analysis type LC module 4 that separates the detection to conventional sample, the online SPE module 13 that separates the detection to complicated sample, the dilution processing module 19 that separates the detection to simple sample and the SPE processing module that separates the detection to comparatively simple sample, consequently, this system is applicable to the clinical detection project of multiple sample, can solve the problem that SPE post 17 frequently changed between the different detection projects, also can reduce complicated preceding processing procedure. Furthermore, a plurality of parallel LC channels 7 are provided in the analytical LC module 4, and the plurality of LC channels 7 are sequentially switched alternately, thereby maximizing the efficiency of the mass spectrometer 5.

It should be noted that the first SPE injection valve 14 and the second SPE injection valve 18, the first distribution valve 24 and the second distribution valve 25, and the third distribution valve 30 are mentioned in this document, wherein the first, the second, and the third are only for distinguishing the difference of the positions, and are not described in order.

The embodiments in the present description are described in a progressive manner, each embodiment focuses on differences from other embodiments, and the same and similar parts among the embodiments are referred to each other. The utility model provides an arbitrary compound mode of all embodiments all is in this utility model's a protection scope, does not do here and gives unnecessary details.

The multi-mode liquid chromatography system provided by the present invention has been described in detail above. The principles and embodiments of the present invention have been explained herein using specific examples, and the above descriptions of the embodiments are only used to help understand the method and its core ideas of the present invention. It should be noted that, for those skilled in the art, without departing from the principle of the present invention, the present invention can be further modified and modified, and such modifications and modifications also fall within the scope of the appended claims.

Claims (10)

1. A multi-modal liquid chromatography system, comprising: the device comprises a sample tray (1) for loading a sample, a sample adding needle (2) for sucking and transferring the sample, a washing station (3) for washing the sample adding needle (2), a liquid chromatography unit for separating or diluting the sample, a mass spectrometer (5) for detecting and analyzing a target object after the sample is separated or diluted, and a control device;

the number of the liquid chromatography units is at least two, the liquid chromatography units are arranged at the rear end of the sample adding needle in parallel and used for separating or diluting the sample transferred by the sample adding needle to form a target object to be analyzed by the mass spectrometer (5), and the rear end of the liquid chromatography unit is connected with the sample injection end of the mass spectrometer (5);

the sample tray (1), the sample adding needle (2), the washing station (3), the mass spectrometer (5) and the liquid chromatography unit are all connected with the control device.

2. The multimodal liquid chromatography system according to claim 1, wherein the liquid chromatography unit comprises an analytical LC module (4) for performing separation operations on regular samples and a recovery device (6) for collecting waste liquid after sample separation;

the analytical LC module (4) comprises an LC channel (7), an LC injection valve (8) for receiving a sample, an LC pump (10) for driving liquid flow and a three-way selection valve (12), wherein the LC channel (7) comprises an LC chromatographic column (11) and a pipeline (9) for separating a required target object;

the LC pump (10), the LC filling valve (8), the LC chromatographic column (11) and the three-way selector valve (12) pass through pipeline (9) communicate in proper order, the entry end and the mobile phase storage unit of LC pump (10) are connected, LC pump (10) are used for transporting at least two kinds of different mobile phases, in order to make the sample be in through adjusting mobile phase concentration enrichment or elution on LC chromatographic column (11), the entry end of three-way selector valve (12) with LC chromatographic column (11) intercommunication, two exit ends of three-way selector valve (12) respectively with recovery unit (6) with mass spectrometer (5) intercommunication, recovery unit (6) with controlling means connects.

3. A multi-mode liquid chromatography system according to claim 2, wherein the liquid chromatography unit comprises an online SPE module (13) for performing separation operation on complex samples and a recovery device (6) for collecting waste liquid after sample separation, the online SPE module (13) comprises a first SPE injection valve (14), a SPE pump (15), an online SPE trapping/eluting valve (16), a SPE column (17) arranged in the online SPE trapping/eluting valve (16), a second SPE injection valve (18), an LC pump (10), an LC chromatographic column (11) and a three-way selector valve (12), the SPE column (17) and the LC chromatographic column (11) are both used for performing substance separation on samples, and the first SPE injection valve (14) and the second SPE injection valve (18) are both used for receiving samples;

the system comprises an SPE pump (15), a first SPE injection valve (14) and an online SPE trapping/eluting valve (16), wherein one inlet end of the SPE pump (15), the other inlet end of the LC pump (10), the other inlet end of the second SPE injection valve (18) and the other inlet end of the online SPE trapping/eluting valve (16) are communicated in sequence, the outlet end of the online SPE trapping/eluting valve (16), the inlet ends of an LC chromatographic column (11) and a three-way selection valve (12) are communicated in sequence, and the two outlet ends of the three-way selection valve (12) are communicated with a recovery device (6) and a mass spectrometer (5) respectively;

the inlet end of the SPE pump (15) is connected with the mobile phase storage unit, the SPE pump (15) is used for conveying at least one mobile phase, the inlet end of the LC pump (10) is connected with the mobile phase storage unit, the LC pump (10) is used for conveying at least two different mobile phases, and the online SPE trapping/eluting valve (16) is provided with a valve port (27) used for discharging waste liquid.

4. A multi-mode liquid chromatography system according to claim 3, wherein the SPE column (17) has a length less than the LC column (11), the SPE column (17) having a packing particle size greater than the LC column (11).

5. The multimodal liquid chromatography system according to any of claims 1 to 4, wherein the liquid chromatography unit comprises a dilution processing module (19) for performing separation operations on simple samples, the dilution processing module (19) comprising an LC pump (10) for driving liquid flow, a dilution injection valve (20) for receiving a sample and a dilution line (22);

the inlet end of the LC pump (10) is connected with a mobile phase storage unit, the LC pump (10) is used for conveying at least one different mobile phase, and the LC pump (10), the dilution injection valve (20), the dilution pipeline (22) and the mass spectrometer (5) are communicated in sequence.

6. The multi-mode liquid chromatography system of claim 5, wherein the liquid chromatography unit further comprises a SPE line (23) arranged in parallel with the dilution line (22), the SPE column (17) for enriching the sample is connected in the SPE line (23), the inlet ends of the SPE line (23) and the dilution line (22) are communicated through a first distribution valve (24), the first distribution valve (24) is communicated with the dilution injection valve (20), the outlet ends of the SPE line (23) and the dilution line (22) are communicated through a second distribution valve (25), the second distribution valve (25) is communicated with the sample injection end of the mass spectrometer (5) through a three-way selection valve (12), and the other end of the three-way selection valve (12) is connected with a sample recovery device (6).

7. The multi-mode liquid chromatography system of claim 6, further comprising an SPE elution pump (26) and a bypass valve (21) for driving the flow of eluent, the bypass valve (21) being disposed between the dilution injection valve (20) and the first distribution valve (24), the SPE elution pump (26), the bypass valve (21), the three-way selection valve (12), the second distribution valve (25), the SPE column (17), the first distribution valve (24) and the sample inlet of the mass spectrometer (5) being in communication in sequence to elute the target enriched on the SPE column (17) to the mass spectrometer (5) for analysis.

8. Multimode liquid chromatography system according to any of claims 2 to 4, characterized in that each LC injection valve (8) is provided with a dosing ring (31) for containing a sample and a valve port (27) for draining waste liquid.

9. The multimodal liquid chromatography system according to any of claims 2 to 4, wherein the recovery device (6) comprises a waste liquid collector (28) in communication with a plurality of the three-way selector valves (12) and a waste liquid bottle (29) for containing waste liquid, the waste liquid collector (28) and the waste liquid bottle (29) being in communication.

10. The multimodal liquid chromatography system according to any of the claims 1 to 4, further comprising a third distribution valve (30), the common port of the third distribution valve (30) being in communication with the sample inlet port of the mass spectrometer (5), the rear end of each of the liquid chromatography units being in communication with the distribution port of the third distribution valve (30), the third distribution valve (30) being connected to the control device.

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