Liquid chromatography-mass spectrometry combined system and liquid chromatography-mass spectrometer

Abstract

The invention provides a liquid chromatography-mass spectrometry combined system and a liquid chromatography-mass spectrograph, and the combined system comprises at least two sets of liquid chromatography groups, at least one flow path distributor and a central control module, each set of liquid chromatography group comprises a sample injector module, a constant flow pump module, a switching valve, a first chromatographic column, a second chromatographic column, a column oven and a liquid phase detection module connected with an outlet of the second chromatographic column; the inlet end of the flow path distributor is selectively communicated with the outlet flow path of each second chromatographic column, and the flow path distributor is used for receiving the eluent from any liquid chromatogram group and selectively guiding the eluent to the mass spectrometer. A high-throughput, continuous and automatic on-line analysis process is realized by utilizing the combined system, the system can effectively improve the utilization rate of the mass spectrometer, simplify or replace tedious off-line pretreatment steps, and realize seamless connection of multi-sample parallel treatment and mass spectrum continuous detection through reasonable flow path design and intelligent control.

Description

Technical Field

[0001] This application relates to the technical field of analytical chemistry sample pretreatment and liquid chromatography analysis systems, and in particular to a liquid chromatography-mass spectrometry system and a liquid chromatography-mass spectrometer. Background Technology

[0002] For the analysis of trace target compounds in complex matrices, cumbersome sample pretreatment is usually required, including extraction, purification, and concentration steps, to reduce matrix interference and improve detection sensitivity and accuracy. These offline pretreatment operations are not only time-consuming and labor-intensive, and difficult to guarantee repeatability, but also severely restrict the improvement of analytical throughput, becoming a prominent bottleneck to achieving high-throughput and automated analysis.

[0003] To reduce reliance on offline sample preparation, liquid chromatography-mass spectrometry (LC-MS) combines the high separation efficiency of liquid chromatography with the high selectivity and sensitivity of mass spectrometry. This allows for online sample purification through chromatographic separation, simplifying the analytical process to some extent. In particular, liquid chromatography utilizes first-dimensional chromatography for initial separation and purification, then transfers the target fraction to second-dimensional chromatography for rapid and precise separation, further enhancing the ability to remove impurities online.

[0004] However, existing liquid chromatography-mass spectrometry (LC-MS) systems, even in two-dimensional chromatography mode, still suffer from significant efficiency bottlenecks: First, the mass spectrometer utilization rate is low. In conventional serial operation mode, only one sample can be analyzed at a time, and the mass spectrometer must wait for each complete chromatographic separation process to finish, resulting in a large amount of idle time for this expensive equipment. Second, the system throughput is limited. Although two-dimensional chromatography enables online purification, sample analysis is still a single-channel serial process with a long analysis cycle, making it difficult to meet the growing demand for high-throughput screening.

[0005] In view of this, it is necessary to design a liquid chromatography-mass spectrometry (LC-MS) system and a LC-MS instrument to solve one of the above problems. Summary of the Invention

[0006] This application provides a liquid chromatography-mass spectrometry (LC-MS) system and a LC-MS instrument. The system enables efficient and simplified offline sample pretreatment and achieves high-throughput, automated, and continuous analysis.

[0007] To achieve the above objectives, the technical solution provided in this application is as follows: This application provides a liquid chromatography-mass spectrometry (LC-MS) system for connection to a mass spectrometer, wherein the system includes: At least two sets of liquid chromatography sets, each set of liquid chromatography sets includes: an injector module, a constant flow pump module, a switching valve connected to the injector module and the constant flow pump module through a pipeline, a first chromatographic column and a second chromatographic column respectively connected to the switching valve, a column oven for housing the second chromatographic column, and a liquid chromatography detection module connected to the outlet of the second chromatographic column; At least one flow path distributor, the inlet of which is selectively connected to the outlet flow path of each of the second chromatographic columns, is used to receive eluent from any of the liquid chromatography groups and selectively guide the eluent to the mass spectrometer; The central control module is communicatively connected to each of the injector modules, constant flow pump modules, switching valves, column ovens, liquid phase detection modules, and flow path distributors, and is used to control the alternating operation of each module group and to control the flow path distributor to switch flow paths.

[0008] Furthermore, the number of liquid chromatography groups is M, and the number of flow path distributors is N, where ½M ≤ N < M. Furthermore, N flow path distributors are connected in series and configured to form at least M different valve position states under the control of the central control module. The M valve position states correspond to selectively switching and guiding the eluent from the M sets of liquid chromatography sets to the mass spectrometer.

[0009] Furthermore, the combined system includes a flow path distributor A, a flow path distributor B, a first liquid chromatography group, a second liquid chromatography group, and a third liquid chromatography group. The inlet end of the flow path distributor A is connected to the outlet flow paths of the first liquid chromatography group and the second liquid chromatography group. The inlet end of the flow path distributor B is connected to the outlet end of the flow path distributor A and the outlet flow path of the third liquid chromatography group. The outlet end of the flow path distributor B is used to connect to the mass spectrometer.

[0010] Furthermore, the flow path distributor is a six-way valve, wherein port A2 of the six-way valve A is connected to the outlet flow path of the first liquid chromatography group, port A6 is connected to the outlet flow path of the second liquid chromatography group, port A1 is connected to the waste liquid flow path, ports A3 and A5 are connected through a pipeline, and port A4 is connected to the six-way valve B2 through a pipeline; port B6 of the six-way valve B is connected to the outlet flow path of the third liquid chromatography group, port B1 is connected to the waste liquid flow path, and ports B3 and B4 are connected through a pipeline; port B5 is used to connect to the mass spectrometer; by controlling the valve position combination of the six-way valve A and the six-way valve B, the eluent from either liquid chromatography group can be selectively guided to the mass spectrometer.

[0011] Furthermore, it also includes an adjustable flow three-way valve located between the liquid chromatography group and the flow path distributor. The inlet end of the adjustable flow three-way valve is connected to the outlet flow path of the second chromatographic column, the first outlet end of the adjustable flow three-way valve is connected to the liquid chromatography detection module, and the second outlet end of the adjustable flow three-way valve is connected to the flow path distributor.

[0012] Furthermore, it also includes a mobile phase module, which is shared by at least two liquid chromatography systems.

[0013] Furthermore, each of the liquid chromatography units also includes a third chromatographic column, which is connected to the input end of the switching valve. Furthermore, the central control module is also used to receive and process data from the liquid phase detection module, and to trigger or adjust the control of the flow path distributor in real time according to the signal from the liquid phase detection module.

[0014] This application also provides a liquid chromatography-mass spectrometry (LC-MS) instrument, wherein the LC-MS instrument includes a mass spectrometer and the aforementioned LC-MS system connected to the injection port of the mass spectrometer, wherein the output port of the flow path distributor is connected to the injection port of the mass spectrometer.

[0015] Compared with related technologies, the beneficial effects of this application are as follows: By utilizing the liquid chromatography-mass spectrometry system of this application, through the cooperation of the flow path distributor and the liquid chromatography group, the flow path distributor selectively guides the eluent of any liquid chromatography group to the mass spectrometer, realizing a high-throughput, continuous and automated online analysis process. This system can effectively improve the utilization rate of the mass spectrometer, simplify or replace cumbersome offline pretreatment steps, and achieve seamless connection between parallel processing of multiple samples and continuous mass spectrometry detection through reasonable flow path design and intelligent control. Attached Figure Description

[0016] Figure 1 This is a schematic diagram of the structure of a liquid chromatography-mass spectrometry (LC-MS) system according to an embodiment of the LC-MS system of this application.

[0017] Figure 2 This is a flowchart of a detection method according to another embodiment of the liquid chromatography-mass spectrometry system of this application.

[0018] Figure 3 yes Figure 2 The flow path diagram of the eluent from the first liquid chromatography group entering the mass spectrometer.

[0019] Figure 4 yes Figure 2 The flow path diagram for the eluent from the second liquid chromatography group entering the mass spectrometer.

[0020] Figure 5 yes Figure 2The flow path diagram of the eluent from the third liquid chromatography group entering the mass spectrometer.

[0021] Among them, 10-Liquid Chromatography Group, 101-First Liquid Chromatography Group, 102-Second Liquid Chromatography Group, 103-Third Liquid Chromatography Group, 11-Injection Module, 12-Constant Flow Pump Module, 13-Switching Valve, 14-First Chromatographic Column, 15-Second Chromatographic Column, 16-Third Chromatographic Column, 17-Column Oven, 18-Liquid Chromatography Detection Module, 20-Flow Path Distributor, A-First Flow Path Distributor, B-Second Flow Path Distributor, 23-Connecting Pipeline, 30-Adjustable Flow Three-Way Valve, 40-Mobile Phase Module. Detailed Implementation

[0022] To enable those skilled in the art to better understand the technical solutions in this application, the technical solutions in the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments in this application, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of this application.

[0023] It should be noted that the terms "upper" and "lower," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the purpose of simplifying the description of this application and do not indicate or imply that the device referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limiting the scope of protection of this application. Specifically, in this application, the direction facing the ground is referred to as "lower," and conversely, the direction away from the ground is referred to as "upper." Other descriptions of orientation are defined based on "upper" and "lower."

[0024] In the various figures of this application, for ease of illustration, certain dimensions of structures or parts may be exaggerated relative to other structural parts; therefore, they are only used to illustrate the basic structure of the subject matter of this application.

[0025] This application provides a liquid chromatography-mass spectrometry (LC-MS) system for connection to a mass spectrometer. The solution to be tested is eluted by liquid chromatography and then detected in the mass spectrometer. Liquid chromatography can efficiently separate the components in complex mixtures, reduce matrix interference, and simultaneously complete the separation, identification, and quantification of the analyte in a single analysis, greatly improving the analytical capability and reliability of results for complex samples.

[0026] Among them, such as Figures 1 to 5As shown, the combined system includes at least two liquid chromatography arrays 10, at least one flow path distributor 20, and a central control module. The inlet of the flow path distributor 20 is selectively connected to the outlet flow path of the second chromatographic column 15 in each of the liquid chromatography arrays 10, and is used to receive the eluent from any of the liquid chromatography arrays 10. Under the control of the central control module, the flow path distributor 20 selectively guides the eluted solution of any liquid chromatography array 10 to the mass spectrometer, realizing online high-throughput, automated and continuous analysis, and improving the utilization rate of the mass spectrometer.

[0027] like Figures 1 to 5 As shown, each liquid chromatography array 10 includes an injector module 11, a constant flow pump module 12, a switching valve 13 connected to the injector module 11 and the constant flow pump module 12 via tubing, a first chromatographic column 14 and a second chromatographic column 15 connected to the switching valve 13, a column oven 17 for housing the second chromatographic column 15, and a liquid chromatography detection module 18 connected to the outlet of the second chromatographic column 15. That is, each liquid chromatography array 10 is based on the existing liquid chromatograph structure, and the flow path distributor 20 guides the solutions eluted from multiple liquid chromatography arrays 10 to the mass spectrometer in a preset order, reducing the waiting time of the mass spectrometer and realizing continuous automated online analysis of liquid chromatography-mass spectrometry.

[0028] The injector module 11 is used to extract sample solution according to a preset volume based on the sampling control command of the central control module; the constant flow pump module 12 is used to provide the mobile phase required for chromatographic analysis according to the transmission control command of the central control module, so as to transmit the sample solution to the liquid phase detection module 18; the switching valve 13 is a six-way valve used to switch the liquid path; and the column oven 17 is used to maintain the temperature for chromatographic analysis.

[0029] In this application, such as Figures 3 to 5 As shown, each of the liquid chromatography units 10 also includes a third chromatographic column 16, which is connected to the input end of the switching valve 13. The analyte is extracted once before the sample solution enters the switching valve 13, so that the sample separation effect is better.

[0030] If the number of liquid chromatography groups 10 is M, and the number of flow path distributors 20 is N, where ½M ≤ N < M, then each flow path distributor 20 can connect to a maximum of two liquid chromatography groups 10. The N flow path distributors 20 are connected in series and configured, under the control of the central control module, to form at least M different valve position states. Each of the M valve position states corresponds to selectively switching and guiding the eluent from the M liquid chromatography groups 10 to the mass spectrometer.

[0031] If there are two sets of liquid chromatography array 10, the minimum number of flow path distributors 20 is one; if there are three or four sets of liquid chromatography array 10, the minimum number of flow path distributors 20 is two. The above configuration is a relatively simple and reliable basic configuration, which can ensure the utilization rate of mass spectrometry without affecting the stability and reliability of the system.

[0032] In a preferred embodiment of this application, the number of liquid chromatography sets 10 is three, namely a first liquid chromatography set 101, a second liquid chromatography set 102, and a third liquid chromatography set 103; the number of flow path distributors 20 is two, namely a first flow path distributor A (hereinafter referred to as flow path distributor A) and a second flow path distributor B (hereinafter referred to as flow path distributor B). The inlet end of flow path distributor A is connected to the outlet flow path of the first liquid chromatography set 101 and the second liquid chromatography set 102, and the inlet end of flow path distributor B is connected to the outlet end of flow path distributor A and the outlet flow path of the third liquid chromatography set 103. The outlet end of flow path distributor B is used to connect to a mass spectrometer.

[0033] Specifically, the flow path distributor 20 is a six-way valve. Port A1 of the six-way valve A is connected to the waste liquid flow path, port A2 is connected to the outlet flow path of the first liquid chromatography group 101, port A6 is connected to the outlet flow path of the second liquid chromatography group 102, ports A3 and A5 are connected via a pipeline, and port A4 is connected to the six-way valve B2 via a pipeline. Port B6 of the six-way valve B is connected to the outlet flow path of the third liquid chromatography group 103, port B1 is connected to the waste liquid flow path, and ports B3 and B4 are connected via a pipeline. Port B5 is used to connect to the mass spectrometer. By controlling the valve position combination of the six-way valves A and B, the eluent from any liquid chromatography group 10 can be selectively guided to the mass spectrometer.

[0034] The following is a specific example of this embodiment.

[0035] like Figure 3 As shown, the eluent of the first liquid chromatography group 101 enters the mass spectrometer via the following path: At this time, the six-way valve A is in position 6-1 and the six-way valve B is in position 6-1. The eluent of the first liquid chromatography group 101 flows sequentially through port A2, port A3 of the six-way valve A, the external pipeline connecting port A3 and port A5, port A5, port A4, the external pipeline connecting A4 and B2, port B2, port B3 of the six-way valve B, the external pipeline connecting B3 and B4, port B4, and port B5 before entering the mass spectrometer. Simultaneously, the eluent of the second liquid chromatography group 102 flows sequentially through port A6 and port A1, and is discharged from the waste liquid path connected to port A1. The eluent of the third liquid chromatography group 103 flows sequentially through port B6 and port B1, and is discharged from the waste liquid path connected to port B1.

[0036] like Figure 4 As shown, the eluent of the second liquid chromatography group 102 enters the mass spectrometer via the following path: at this time, the six-way valve A is in position 1-2 and the six-way valve B is in position 6-1. The eluent of the second liquid chromatography group 102 flows sequentially through port A6 and port A5 of the six-way valve A, the external pipeline connecting A5 and A3, port A3, port A4, the external pipeline connecting A4 and B2, port B2 and port B3 of the six-way valve B, the external pipeline connecting B3 and B4, port B4, and port B5 before entering the mass spectrometer. At the same time, the eluent of the first liquid chromatography group 101 flows sequentially through port A2 and port A1, and is discharged from the waste liquid flow path connected to port A1. The eluent of the third liquid chromatography group 103 flows sequentially through port B6 and port B1 of the six-way valve B, and is discharged from the waste liquid flow path connected to port B1.

[0037] like Figure 5 As shown, the eluent of the third liquid chromatography group 103 enters the mass spectrometer via the following path: at this time, the six-way valve A is in position 6-1, the six-way valve B is in position 1-2, and the eluent of the third liquid chromatography group 103 flows sequentially through port B6 and port B5 of the six-way valve B before entering the mass spectrometer; simultaneously, the eluent of the first liquid chromatography group 101 flows sequentially through port A2, port A3, port A5, port A4, port B2, and port B1 of the six-way valve A before being discharged from the waste liquid path connected to port B1; the eluent of the second liquid chromatography group 102 flows sequentially through port A6 and port A1 of the six-way valve A before being discharged from the waste liquid path connected to port A1.

[0038] The central control module is communicatively connected to each of the injector modules 11, constant flow pump modules 12, switching valves 13, column ovens 17, liquid phase detection modules 18, and flow path distributors 20, and is used to control the alternating operation of each module group and to control the flow path distributors 20 to switch flow paths.

[0039] The central control module is also used to receive and process data from the liquid phase detection module 18, and to trigger or adjust the control of the flow path distributor 20 in real time according to the signal from the liquid phase detection module 18.

[0040] The combined system also includes an adjustable flow three-way valve 30 located between the liquid chromatography group 10 and the flow path distributor 20. Each liquid chromatography group 10 corresponds to one adjustable flow three-way valve 30. The inlet end of the adjustable flow three-way valve 30 is connected to the outlet flow path of the second chromatographic column 15. The first outlet end of the adjustable flow three-way valve 30 is connected to the liquid chromatography detection module 18, and the second outlet end of the adjustable flow three-way valve 30 is connected to the flow path distributor 20. When the eluent of any liquid chromatography group 10 is directed to the mass spectrometer, part of the eluent flowing through the liquid chromatography group 10 enters the liquid chromatography detection module 18, and part enters the flow path distributor 20.

[0041] The combined system also includes a mobile phase module 40. At least two sets of liquid chromatography units 10 share one mobile phase module 40. In an embodiment where the combined system includes three sets of liquid chromatography units 10, the three sets of liquid chromatography units 10 share the mobile phase module 40, which can greatly save mobile phase, inlet pipeline, filter, mobile phase degassing device, etc. Among them, mobile phase A and mobile phase B are organic solvents, mobile phase C1, mobile phase C2 and mobile phase C3 are buffer solutions or solutions for adjusting the pH of the mobile phase, and mobile phase D is usually water.

[0042] This application also provides a liquid chromatography-mass spectrometry (LC-MS) instrument, wherein the LC-MS instrument includes a mass spectrometer and the aforementioned LC-MS system connected to the injection port of the mass spectrometer, wherein the output port of the flow path distributor 20 is connected to the injection port of the mass spectrometer and is used to guide the eluent to be tested to the mass spectrometer.

[0043] In summary, the liquid chromatography-mass spectrometry (LC-MS) system of this application, through the cooperation of the flow path distributor and the liquid chromatography array, selectively guides the eluent of any liquid chromatography array 10 to the mass spectrometer via the flow path distributor 20, realizing a high-throughput, continuous, and automated online analysis process. This system can effectively improve the utilization rate of the mass spectrometer, simplify or replace cumbersome offline pretreatment steps, and achieve seamless integration of multi-sample parallel processing and continuous mass spectrometry detection through reasonable flow path design and intelligent control.

[0044] It should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This way of describing the specification is only for clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

[0045] The detailed descriptions listed above are merely specific illustrations of feasible embodiments of this application and are not intended to limit the scope of protection of this application. All equivalent embodiments or modifications made without departing from the spirit of the art of this application should be included within the scope of protection of this application.

Claims

1. A liquid chromatography-mass spectrometry (LC-MS) system for connection to a mass spectrometer, characterized in that, The combined system includes: At least two sets of liquid chromatography sets, each set of liquid chromatography sets includes: an injector module, a constant flow pump module, a switching valve connected to the injector module and the constant flow pump module through a pipeline, a first chromatographic column and a second chromatographic column respectively connected to the switching valve, a column oven for housing the second chromatographic column, and a liquid chromatography detection module connected to the outlet of the second chromatographic column; At least one flow path distributor, the inlet of which is selectively connected to the outlet flow path of each of the second chromatographic columns, is used to receive eluent from any of the liquid chromatography groups and selectively guide the eluent to the mass spectrometer; The central control module is communicatively connected to each of the injector modules, constant flow pump modules, switching valves, column ovens, liquid phase detection modules, and flow path distributors, and is used to control the alternating operation of each module group and to control the flow path distributor to switch flow paths.

2. The liquid chromatography-mass spectrometry system as described in claim 1, characterized in that, The number of liquid chromatography groups is M, and the number of flow path distributors is N, where ½M≤N<M.

3. The liquid chromatography-mass spectrometry system as described in claim 2, characterized in that, N flow path distributors are connected in series and configured to form at least M different valve position states under the control of the central control module. The M valve position states correspond to selectively switching and guiding the eluent from the M sets of liquid chromatography sets to the mass spectrometer.

4. The liquid chromatography-mass spectrometry system as described in claim 3, characterized in that, The combined system includes a flow path distributor A, a flow path distributor B, a first liquid chromatography group, a second liquid chromatography group, and a third liquid chromatography group. The inlet end of the flow path distributor A is connected to the outlet flow paths of the first liquid chromatography group and the second liquid chromatography group. The inlet end of the flow path distributor B is connected to the outlet end of the flow path distributor A and the outlet flow path of the third liquid chromatography group. The outlet end of the flow path distributor B is used to connect to the mass spectrometer.

5. The liquid chromatography-mass spectrometry system as described in claim 4, characterized in that, The flow path distributor is a six-way valve. Port A2 of the six-way valve A is connected to the outlet flow path of the first liquid chromatography group, port A6 is connected to the outlet flow path of the second liquid chromatography group, port A1 is connected to the waste liquid flow path, ports A3 and A5 are connected via a pipeline, and port A4 is connected to the six-way valve B2 via a pipeline. Port B6 of the six-way valve B is connected to the outlet flow path of the third liquid chromatography group, port B1 is connected to the waste liquid flow path, and ports B3 and B4 are connected via a pipeline. Port B5 is used to connect to the mass spectrometer. By controlling the valve position combination of six-way valves A and B, the eluent from either liquid chromatography group can be selectively guided to the mass spectrometer.

6. The liquid chromatography-mass spectrometry system as described in claim 1, characterized in that, It also includes an adjustable flow three-way valve located between the liquid chromatography group and the flow path distributor. The inlet end of the adjustable flow three-way valve is connected to the outlet flow path of the second chromatographic column, the first outlet end of the adjustable flow three-way valve is connected to the liquid chromatography detection module, and the second outlet end of the adjustable flow three-way valve is connected to the flow path distributor.

7. The liquid chromatography-mass spectrometry system according to any one of claims 1 to 6, characterized in that, It also includes a mobile phase module, which is shared by at least two liquid chromatography systems.

8. The liquid chromatography-mass spectrometry system according to any one of claims 1 to 6, characterized in that, Each of the liquid chromatography units also includes a third column, which is connected to the input of the switching valve.

9. The liquid chromatography-mass spectrometry system according to any one of claims 1 to 6, characterized in that, The central control module is also used to receive and process data from the liquid phase detection module, and to trigger or adjust the control of the flow path distributor in real time according to the signal from the liquid phase detection module.

10. A liquid chromatography-mass spectrometry instrument, characterized in that, The system includes a mass spectrometer and a liquid chromatography-mass spectrometry system as described in any one of claims 1 to 9, wherein the output of the flow path distributor is connected to the injection port of the mass spectrometer.

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