High-flux two-dimensional liquid chromatography-mass spectrometry system

Abstract

The utility model discloses a high-flux two-dimensional liquid chromatography-mass spectrometry system, which comprises n groups of two-dimensional liquid chromatography systems, n groups of high-flux liquid chromatography-mass spectrometry systems and n groups of high-flux liquid chromatography-mass spectrometry systems, wherein n is greater than or equal to 2; the control valve module is communicated with each group of two-dimensional liquid chromatography system and is used for switching and distributing the liquid phase in each group of two-dimensional liquid chromatography system into a mass spectrometer; and the control module is respectively connected with the two-dimensional liquid chromatography system and the control valve module and is used for sending a parameter regulation and control instruction to the two-dimensional liquid chromatography system and sending a switching distribution instruction to the control valve module. According to the two-dimensional liquid chromatography system disclosed by the utility model, the effect of high-throughput detection and analysis can be achieved through the cooperative work of the multiple groups of two-dimensional liquid chromatography systems, and the liquid phases of the multiple groups of two-dimensional liquid chromatography systems are switched and distributed, so that each group of two-dimensional liquid chromatography systems can sequentially and continuously perform chromatographic analysis; therefore, the problems of high vacancy rate, high pretreatment difficulty and the like of the mass spectrometer in the existing liquid chromatography-mass spectrometry equipment are solved, and the detection and analysis efficiency of liquid chromatography-mass spectrometry is improved.

Description

TECHNICAL FIELD

[0001] The utility model relates to liquid quality combined use technical field, concretely relates to a kind of high flux two-dimensional liquid quality combined use system. BACKGROUND

[0002] Mass spectrum (also called mass spectrometry) is a kind of spectrum method parallel with spectrum, when determining the molecular weight of known target compound, if impurity content is high or the concentration of measured substance is lower, then it will lead to the abundance and resolution of target compound corresponding peak are lower, the interference of impurity in this case can be particularly obvious, cause such sample cannot be accurately quantified.And the sample pretreatment time of mass spectrum is longer, and operation is more complex.

[0003] And for relatively complex sample, liquid quality combined use method has significant advantage compared with mass spectrum, liquid quality combined use (HPLC-MS) is also called liquid chromatography-mass spectrometry combined use technology, it is with liquid chromatography as separation system, mass spectrum as detection system.Sample is separated in mass spectrum part and mobile phase, after ionization, the ion fragments are separated according to mass number by mass analyzer of mass spectrum, and mass spectrum diagram is obtained by detector.Liquid quality combined use method can be detected by mass spectrum after obtaining relatively pure measured substance, so that the interference of impurity in sample can be avoided to a certain extent.But traditional liquid quality combined use equipment also has certain defects, for example, mass spectrometer needs to wait for once chromatographic separation analysis process to end, that is, the utilization rate of mass spectrometer is lower;Again, for example, the pretreatment difficulty of traditional liquid quality combined use equipment is greater, time process is longer, and there are also the shortcomings of difficult to realize high flux, automation etc..Therefore, how to improve the use efficiency of mass spectrometer in liquid quality combined use equipment and reduce the difficulty of pretreatment is the technical problem that the person skilled in the art needs to solve. UTILITY MODEL CONTENT

[0004] The utility model embodiment provides a kind of high flux two-dimensional liquid quality combined use system, to realize high flux analysis detection, and solve the idle rate of mass spectrometer in existing liquid quality combined use equipment is higher, and the pretreatment difficulty is greater etc., improve the detection analysis efficiency of liquid quality combined use.

[0005] The utility model embodiment provides a kind of high flux two-dimensional liquid quality combined use system, comprising:

[0006] Two-dimensional liquid chromatography system is provided with n groups;Wherein, n≥2;

[0007] Control valve module, with each group described two-dimensional liquid chromatography system intercommunication, for switching distribution liquid phase in each group described two-dimensional liquid chromatography system into mass spectrometer;

[0008] A control module is connected with the two-dimensional liquid chromatography system and the control valve module respectively, and is configured to send parameter control instructions to the two-dimensional liquid chromatography system and switching distribution instructions to the control valve module.

[0009] Further, the control valve module comprises a first control valve and a second control valve, and the first control valve and the second control valve are respectively connected with one or more groups of the two-dimensional liquid chromatography system.

[0010] Further, the first control valve and the second control valve each comprise a plurality of control valve positions, and the plurality of control valve positions comprise a control valve position connected with the two-dimensional liquid chromatography system, a control valve position connected with the mass spectrometer, and a control valve position connected with the waste liquid recovery device.

[0011] Further, the first control valve and the second control valve are each a six-way valve.

[0012] Further, the two-dimensional liquid chromatography system comprises:

[0013] A sample injector module is configured to extract a sample solution.

[0014] A constant flow pump module is connected with the sample injector module through a pipeline, and the constant flow pump module comprises a plurality of constant flow pumps configured to provide a mobile phase for chromatographic analysis.

[0015] A multi-way valve is connected with the sample injector module and the constant flow pump module through a pipeline, and the six-way valve is provided with a three-way valve between the sample injector module and the constant flow pump module, and is configured to switch the liquid path.

[0016] A column oven is connected with the multi-way valve through a pipeline, and the column oven is provided with a first chromatographic column, and is configured to control the temperature of chromatographic analysis.

[0017] A detection module is connected with the column oven module through a pipeline, and is configured to perform chromatographic analysis and detection on the sample solution.

[0018] Further, the control valve module is connected between the chromatographic column and the detection module through an adjustable flow type liquid distributor.

[0019] Further, the sample injector module in each two-dimensional liquid chromatography system extracts sample solutions in batches.

[0020] Further, the multi-way valve in each two-dimensional liquid chromatography system is in an output state when the sample solution is output, and is in an input state when the sample solution is input.

[0021] Further, the two-dimensional liquid chromatography systems share a mobile phase.

[0022] Further, a second chromatographic column is arranged between the three-way valve and the multi-way valve.

[0023] The utility model embodiment provides a kind of high flux two-dimensional liquid mass spectrometry system, the system includes: two-dimensional liquid chromatography system, is provided with n groups;Wherein, n≥2;Control valve module, with every group two-dimensional liquid chromatography system intercommunication, for switching distribution the liquid phase in each group two-dimensional liquid chromatography system into mass spectrometer;Control module is connected with two-dimensional liquid chromatography system and control valve module respectively, for sending parameter control instruction to two-dimensional liquid chromatography system and switching distribution instruction to control valve module.The utility model embodiment can reach the effect of high flux detection analysis by the cooperation of multiple two-dimensional liquid chromatography systems, and by control module and control valve module switching distribution to the liquid phase of multiple two-dimensional liquid chromatography systems, each group two-dimensional liquid chromatography system can successively carry out chromatographic analysis in turn, to solve the idle rate of mass spectrometer in the prior liquid mass spectrometry equipment is higher, and pretreatment difficulty is greater and so on Problem, improve the detection analysis efficiency of liquid mass spectrometry. BRIEF DESCRIPTION OF DRAWINGS

[0024] In order to more clearly illustrate the technical scheme of the utility model embodiment, the drawings needed to be used in the embodiment description will be simply introduced below, and obviously, the drawings in the following description are some embodiments of the utility model, and those skilled in the art can also obtain other drawings according to these drawings without creating labor.

[0025] Figure 1 A structure diagram of a high flux two-dimensional liquid mass spectrometry system provided by the utility model embodiment is provided;

[0026] Figure 2 Another structure diagram of a high flux two-dimensional liquid mass spectrometry system provided by the utility model embodiment is provided;

[0027] Figure 3 Still another structure diagram of a high flux two-dimensional liquid mass spectrometry system provided by the utility model embodiment is provided;

[0028] Figure 4 A structure diagram of two-dimensional liquid chromatography system in a high flux two-dimensional liquid mass spectrometry system provided by the utility model embodiment is provided;

[0029] Figure 5 Another structure diagram of two-dimensional liquid chromatography system in a high flux two-dimensional liquid mass spectrometry system provided by the utility model embodiment is provided;

[0030] Figure 6 A pipe connection diagram of a high flux two-dimensional liquid mass spectrometry system provided by the utility model embodiment is provided;

[0031] Figure 7Another pipe connection schematic view of the high-throughput two-dimensional liquid mass spectrometry system is provided in the utility model embodiment. DETAILED DESCRIPTION

[0032] The technical solutions in the utility model embodiments will be clearly and completely described below with reference to the drawings in the utility model embodiments. Obviously, the described embodiments are some but not all of the embodiments of the utility model. Based on the embodiments in the utility model, all other embodiments obtained by a person of ordinary skill in the art without creative work fall within the protection scope of the utility model.

[0033] It should be understood that, when used in the specification and the appended claims, the terms "comprise" and "include" indicate the presence of described features, integers, steps, operations, elements, and / or components, but do not exclude one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0034] It should also be understood that the terms used in the utility model specification are only for the purpose of describing specific embodiments and do not intend to limit the utility model. As used in the utility model specification and the appended claims, "a", "an", and "the" in singular form are intended to include plural forms unless the context clearly indicates otherwise.

[0035] It should be further understood that the term "and / or" used in the utility model specification and the appended claims means any combination of one or more of the associated listed items and all possible combinations, and includes these combinations.

[0036] Please see Figures 1 to 3 The utility model embodiment provides a kind of high-throughput two-dimensional liquid mass spectrometry system, comprising:

[0037] Two-dimensional liquid chromatography system is provided with n groups;Wherein, n≥2;

[0038] Control valve module, with each group described two-dimensional liquid chromatography system communication, for switching distribution liquid phase in each group described two-dimensional liquid chromatography system into mass spectrometer;

[0039] Control module, with described two-dimensional liquid chromatography system and control valve module are connected respectively, for sending parameter control instruction to described two-dimensional liquid chromatography system and switching distribution instruction to described control valve module.

[0040] In the embodiment, the high-throughput two-dimensional liquid chromatography-mass spectrometry system comprises a plurality of two-dimensional liquid chromatography systems, a control valve module connected with each two-dimensional liquid chromatography system, and a control module for controlling the operation parameters of the two-dimensional liquid chromatography system and for controlling the switching and distribution of the control valve module.

[0041] The plurality of two-dimensional liquid chromatography systems work cooperatively to achieve high-throughput detection and analysis, and the control module and the control valve module switch and distribute the liquid phases of the plurality of two-dimensional liquid chromatography systems, so that each two-dimensional liquid chromatography system can continuously perform chromatographic analysis in sequence, thereby solving the problems of high idle rate of the mass spectrometer and high pretreatment difficulty in the existing liquid chromatography-mass spectrometry equipment, and improving the detection and analysis efficiency of the liquid chromatography-mass spectrometry.

[0042] In combination Figures 1 to 3 In actual application scenarios, the two-dimensional liquid chromatography system is provided with three groups, and the three groups of two-dimensional liquid chromatography systems are respectively connected with the control valve module. Of course, in other application scenarios, the two-dimensional liquid chromatography system can also be provided with two groups or more than four groups, etc.

[0043] In an embodiment, the control valve module comprises a first control valve and a second control valve, and the first control valve and the second control valve are respectively connected with one or more two-dimensional liquid chromatography systems.

[0044] In the embodiment, the control valve module comprises two control valves, i.e., a first control valve and a second control valve, wherein the first control valve is connected with part of the plurality of two-dimensional liquid chromatography systems, and the second control valve is connected with the remaining part of the plurality of two-dimensional liquid chromatography systems. Here, the two-dimensional liquid chromatography system connected with the first control valve can be the same as or different from the two-dimensional liquid chromatography system connected with the second control valve, but it is necessary to ensure that all two-dimensional liquid chromatography systems can be connected with the control valve module, so as to achieve the final mass spectrometry purpose.

[0045] As shown in Figure 4 and Figure 5 , the two-dimensional liquid chromatography system is provided with three groups, i.e., two-dimensional liquid chromatography system 1, two-dimensional liquid chromatography system 2 and two-dimensional liquid chromatography system 3, wherein, in combination Figures 1 to 3 , the first control valve is connected with the two-dimensional liquid chromatography system 1 and the two-dimensional liquid chromatography system 2, and the second control valve is connected with the two-dimensional liquid chromatography system 3, so that the three groups of two-dimensional liquid chromatography systems are switched and distributed by the first control valve and the second control valve, and the liquid in the three groups of two-dimensional liquid chromatography systems enters the mass spectrometer for detection according to the switching and distribution of the first control valve and the second control valve.

[0046] In specific embodiments, the first and second control valves each comprise a plurality of control valve positions, including a control valve position in communication with the two-dimensional liquid chromatography system, a control valve position in communication with the mass spectrometer, and a control valve position in communication with the waste recovery device.

[0047] In the first and second control valves described in the embodiments, a portion of the control valve positions are connected to the two-dimensional liquid chromatography system, and another portion of the control valve positions are connected to the mass spectrometer or the waste recovery device. In this way, the connection and disconnection between the control valve positions can be used to control whether the liquid in the two-dimensional liquid chromatography system can pass through the first control valve or the second control valve to enter the mass spectrometer or the waste recovery device. In addition, the two control valves can also be connected through the respective control valve positions.

[0048] Specifically, the first and second control valves are each a six-way valve, such as the six-way valve A and the six-way valve B in Figures 1 to 3 As shown in Figure 1 , the control valve positions of the first control valve are A1, A2, A3, A4, A5, and A6 in sequence, and the control valve positions of the second control valve are B1, B2, B3, B4, B5, and B6 in sequence, wherein A1 is connected to the waste recovery device, A2 is connected to the two-dimensional liquid chromatography system 1, A3 is connected to A5 through a pipeline, A4 is connected to B2 of the second control valve, A6 is connected to the two-dimensional liquid chromatography system 2, B1 is connected to the waste recovery device, B3 is connected to B4 through a pipeline, B5 is connected to the mass spectrometer, and B6 is connected to the two-dimensional liquid chromatography system 3.

[0049] As shown in Figure 6 , in an embodiment, the two-dimensional liquid chromatography system comprises:

[0050] a sample injector module for extracting a sample solution;

[0051] a constant flow pump module connected to the sample injector module through a pipeline, the constant flow pump module comprising a plurality of constant flow pumps for providing a mobile phase for chromatographic analysis;

[0052] a multi-way valve connected to the sample injector module and the constant flow pump module through a pipeline, and a three-way valve is arranged between the sample injector module and the constant flow pump module, for liquid path switching;

[0053] a column oven connected to the multi-way valve through a pipeline, the column oven being provided with a first chromatographic column, and the column oven being used to control the temperature of chromatographic analysis;

[0054] a detection module connected to the column oven module through a pipeline, for chromatographic analysis and detection of the sample solution.

[0055] In combination with Figure 4 and Figure 5The two-dimensional liquid chromatography system described in the embodiment specifically comprises a sample injector module, a constant flow pump module, a multi-way valve, a column oven comprising a chromatographic column, and a detection module. In a specific embodiment, the multi-way valve is also a six-way valve. Based on the six-way valve, the constant flow pump P1 is connected to the sample injector module through a pipeline, the sample injector module is connected to a three-way valve through a pipeline and is connected to the constant flow pump P3, and the two are connected to the 6th position of the six-way valve through a pipeline. The constant flow pump P2 is connected to the 3rd position of the six-way valve through a pipeline. The chromatographic column is connected to the 1st and 4th positions of the six-way valve. The 2nd position of the six-way valve is connected to the chromatographic column in the column oven through a pipeline. The chromatographic column in the column oven is connected to the detection module through a pipeline.

[0056] In another specific embodiment, the sample injector module, the infusion pump module, the six-way valve, the column oven, and the detection module are all connected to the control module through a circuit. In this way, the sample injector module is used to extract sample solution according to the sampling control instruction of the control module and according to the preset volume. The constant flow pump module is used to provide the mobile phase required for chromatographic analysis to transmit the sample solution to the detection module according to the transmission control instruction of the control module.

[0057] In an embodiment, the control valve module is connected between the chromatographic column and the detection module through an adjustable flow type distributor.

[0058] In the embodiment, the sample solution enters the flow path through the sample injector module. The liquid flow in the flow path is driven by the constant flow pump. After analysis by the two-dimensional liquid chromatography system, the adjustable flow type distributor is used for distribution, so that part of the sample solution enters the detection module for liquid phase analysis and detection, and the other part enters the control valve module and is distributed into the mass spectrometer for detection through the switching and distribution of the control valve module.

[0059] In actual application scenarios, the sample injector module in each of the two-dimensional liquid chromatography systems extracts sample solution in batches.

[0060] By controlling the sample injection in batches, the substances separated by one group of two-dimensional liquid chromatography systems can be input into the mass spectrometer while the other group of two-dimensional liquid chromatography systems is still being processed, so as to avoid conflicts in detection time. Further, the time difference between different batches can be controlled to be equal to the time when the liquid chromatography is input into the mass spectrometer, so as to ensure that the six-way valves of all two-dimensional liquid chromatography systems are in the input state when they are not processed.

[0061] In a specific embodiment, the multi-way valve in each of the two-dimensional liquid chromatography systems is in an output state when the sample solution is output, and is in an input state when the sample solution is input.

[0062] In combination with Figure 1As shown, when the first control valve is in the 6-1 position and the second control valve is in the 6-1 position, the six-way valve in the two-dimensional liquid chromatography system 1 also changes to the output state, and the liquid in the two-dimensional liquid chromatography system 1 passes through A2 to A3, and then passes through the pipeline to A5 and A4 in turn, and then is connected to B2 through the pipeline and passes through B3, and then passes through the pipeline to B4 and B5 in turn, and finally enters the mass spectrometer from B5, at this time the substances in the two-dimensional liquid chromatography system 2 and the two-dimensional liquid chromatography system 3 are still being processed

[0063] When the liquid output in the two-dimensional liquid chromatography system 1 is completed, the substances in the two-dimensional liquid chromatography system 2 have also been processed and can be input, and the two-dimensional liquid chromatography system 3 is switched Figure 2 As shown, the first control valve A is in the 1-2 position and the second control valve is in the 6-1 position, the six-way valve of the two-dimensional liquid chromatography system 2 changes to the output state, the six-way valve of the two-dimensional liquid chromatography system 1 returns to the input state, the excess liquid in the two-dimensional liquid chromatography system 1 passes through A2 to A1 and enters the waste liquid recovery device, the liquid in the two-dimensional liquid chromatography system 2 passes through A6 to A5, and then passes through the pipeline to A3 and A4 in turn, and then is connected to B2 through the pipeline and passes through B3, and then passes through the pipeline to B4 and B5 in turn, and finally enters the mass spectrometer from B5, while the substances in the two-dimensional liquid chromatography system 3 are still being processed;

[0064] Similarly, when the liquid output in the two-dimensional liquid chromatography system 2 is completed, the two-dimensional liquid chromatography system 3 is switched, as shown in Figure 3 As shown, when the second control valve is in the 1-2 position, the six-way valve of the two-dimensional liquid chromatography system 3 changes to the output state, the six-way valve of the two-dimensional liquid chromatography system 2 returns to the input state, the excess liquid in the two-dimensional liquid chromatography system 2 enters the waste liquid, and the liquid in the two-dimensional liquid chromatography system 3 passes through B6 to B5 to enter the mass spectrometer.

[0065] In an embodiment, the flow phase is shared among the two-dimensional liquid chromatography systems.

[0066] The embodiment meets different two-dimensional liquid chromatography detection requirements by sharing the flow phase, which not only saves the flow phase and avoids resource waste, but also improves the application range of the two-dimensional liquid chromatography-mass spectrometry system.

[0067] In combination with Figure 7 , the three two-dimensional liquid chromatography systems share the flow phase, which can greatly save the flow phase, the inlet pipeline, the filter, the flow phase degassing device, etc. Figure 7 In the embodiment, the flow phase A and the flow phase B are organic solvents, the flow phase C1, the flow phase C2 and the flow phase C3 are buffer solutions or solutions for adjusting the pH of the flow phase, and the flow phase D is usually water.

[0068] In an embodiment, a second chromatographic column is arranged between the three-way valve and the multi-way valve.

[0069] In combination Figure 5 The embodiment can improve the separation effect of the sample solution and the detection effect of the liquid chromatography-mass spectrometry by arranging the chromatographic column between the tee and the multi-way valve.

[0070] The various embodiments are described in the specification by way of progressive development of an embodiment for the system and method, with each embodiment building on the previous one, so that the description can easily be understood. The same or similar reference numerals are used in different embodiments to represent the same or similar components. The embodiments disclosed in the specification are intended to be exemplary only, and the scope of the application is not limited to the embodiments disclosed in the specification. The skilled person in the art can make modifications and improvements to the embodiments disclosed in the specification without departing from the principles of the application, and these modifications and improvements also fall within the scope of protection of the claims of the application.

[0071] It should also be noted that the terms such as first and second in the specification are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between the entities or operations. Moreover, the terms "include", "contain" or any other variants thereof are intended to cover non-exclusive inclusion, so that the process, method, article or device including a series of elements not only includes those elements, but also includes other elements not explicitly listed or inherent to such process, method, article or device. Without further limitation, the element defined by the statement "including a" does not exclude the presence of other identical elements in the process, method, article or device including the element.

Claims

1. A high-throughput two-dimensional liquid chromatography-mass spectrometry system, characterized in that, The application relates to a two-dimensional liquid chromatography system. The two-dimensional liquid chromatography system comprises n groups, wherein n>=2. The control valve module is connected with each group of the two-dimensional liquid chromatography system and is used for switching and distributing liquid phase in each group of the two-dimensional liquid chromatography system into a mass spectrometer; the control valve module comprises a first control valve and a second control valve; and the first control valve and the second control valve are both six-way valves. A control module is connected with the two-dimensional liquid chromatography system and the control valve module respectively, and is used for sending parameter control instructions to the two-dimensional liquid chromatography system and sending switching and distributing instructions to the control valve module. The two-dimensional liquid chromatography system comprises: A sample injector module is used for extracting sample solution. A constant flow pump module is connected with the sample injector module through pipelines, and the constant flow pump module comprises a plurality of constant flow pumps and is used for providing a mobile phase for chromatographic analysis. A multi-way valve is connected with the sample injector module and the constant flow pump module through pipelines, and a three-way device is arranged between the six-way valve and the sample injector module and the constant flow pump module, and the multi-way valve is used for liquid path switching. A column oven is connected with the multi-way valve through pipelines, the column oven is provided with a first chromatographic column, and the column oven is used for controlling the temperature of chromatographic analysis. A detection module is connected with the column oven module through pipelines and is used for chromatographic analysis and detection of the sample solution.

2. The high-throughput two-dimensional liquid chromatography-mass spectrometry system of claim 1, wherein, The first control valve and the second control valve are respectively connected with one group or multiple groups of the two-dimensional liquid chromatography system.

3. The high-throughput two-dimensional liquid chromatography-mass spectrometry system of claim 2, wherein, The first control valve and the second control valve both comprise a plurality of control valve positions, the plurality of control valve positions comprise a control valve position connected with the two-dimensional liquid chromatography system, a control valve position connected with the mass spectrometer and a control valve position connected with a waste liquid recovery device.

4. The high-throughput two-dimensional liquid chromatography-mass spectrometry system of claim 1, wherein, The control valve module is connected between the chromatographic column and the detection module through an adjustable flow type liquid distributor.

5. The high-throughput two-dimensional LC-MS system of claim 1, wherein, The sample injector module in each group of the two-dimensional liquid chromatography system extracts sample solution in batches.

6. The high-throughput two-dimensional LC system of claim 1, wherein, The multi-way valve in each group of the two-dimensional liquid chromatography system is in an output state when sample solution is output and is in an input state when sample solution is input.

7. The high-throughput two-dimensional LC-MS system of claim 1, wherein, The mobile phase is shared between the two-dimensional liquid chromatography systems.

8. The high-throughput two-dimensional LC-MS system of claim 1, wherein, A second chromatographic column is arranged between the three-way device and the multi-way valve.

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