Capillary electrophoresis system used in combination with discontinuous sample introduction mass spectrometry, and method

Abstract

The present application relates to a capillary electrophoresis system used in combination with discontinuous sample introduction mass spectrometry, and a method. The system comprises: an electrophoresis separation-electrospray ionization module, which is used for separating components in a target analyte according to different electrophoretic mobilities; an adjustable-on-the-fly high-voltage power supply device, which is used for providing the voltage needed for capillary electrophoresis according to requirements on electroosmotic flow and the speed of electrophoresis in a capillary tube; a target component signal feedback module, which is used for evaluating the target analyte or a real-time electroosmotic flow speed; an electrophoresis current measurement and migration time correction module; a real-time feedback signal processing and control module; and a discontinuous sample introduction mass spectrometry system. Consequently, problems in the relevant prior art that occur when continuous capillary electrophoresis technology is used in combination with small-scale discontinuous sample introduction mass spectrometry systems are solved, such as reduced accuracy and poor analysis quality, as well as sampling frequency being greatly limited, which causes difficulty in ensuring that mass spectrum data having the highest points of chromatographic peaks can be collected, affecting measurement sensitivity, the accuracy of quantitative analysis, etc.

Description

Capillary electrophoresis system and method coupled with discontinuous injection mass spectrometry

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application is based on the Chinese patent application with application number 202310615069.4 and application date May 29, 2023, and claims the priority of the Chinese patent application. The entire content of the Chinese patent application is hereby introduced into this application as a reference. Technical Field

[0003] The present application relates to the technical field of mass spectrometry analysis, and in particular to a capillary electrophoresis system and method coupled with discontinuous injection mass spectrometry. Background Art

[0004] Mass spectrometry has the advantages of high sensitivity, fast analysis speed, and a wide range of applications. In particular, it has excellent qualitative and quantitative performance for low-concentration analytes in complex biological samples. Therefore, mass spectrometry technology has been widely used in clinical medicine, environmental monitoring, food safety and other fields. In particular, with the miniaturization of mass spectrometry and the rise of in situ ionization technology, the demand for mass spectrometry instruments in various scenarios has increased rapidly. Among them, a small mass spectrometer with a discontinuous inlet reduces the dependence of mass spectrometry on vacuum, the size can be reduced to 37×26.5×26.5cm, and the weight can be reduced to about 12kg (Anal.Chem.2021,93,47,15607-15616), which is the most widely used small mass spectrometry system.

[0005] Among the related technologies, first, to reduce the impact of matrix effects, chromatography-mass spectrometry is usually used to separate the various components of the sample, and then perform mass spectrometry detection on each component, which greatly improves the sensitivity of mass spectrometry detection. Chromatographic techniques commonly used in conjunction with mass spectrometry include liquid chromatography, gas chromatography, and capillary electrophoresis. Second, capillary electrophoresis technology is used, that is, a chromatographic separation technology using capillaries as separation channels and high-voltage direct current electric fields as the driving force. It separates the components in the sample according to their different charges, reducing matrix effects and charge competition, and improving analytical sensitivity. Compared with other chromatographic techniques, it has the advantages of short analysis time, simple structure and easy miniaturization, low sample consumption, and good separation effect, making it suitable for use with small mass spectrometry systems.

[0006] However, in the related art, when continuous capillary electrophoresis technology is used in conjunction with a discontinuous injection small mass spectrometry system, due to the low mass spectrometry sampling rate, problems such as reduced accuracy and poor analysis quality usually occur: due to the high number of capillary electrophoresis separation plates, the chromatographic peak width of each component is very narrow (several seconds to more than ten seconds), and the sampling frequency of discontinuous injection mass spectrometry is greatly limited due to its discontinuous injection characteristics (once every few seconds). Therefore, it is difficult to ensure that the mass spectrometry data of the highest point of the chromatographic peak can be collected, which affects the sensitivity of detection and the accuracy of quantitative analysis. In addition, the introduction of chromatography may lead to a long blank analysis time between the target analysis components, resulting in a waste of analysis time, which urgently needs to be improved.

[0007] Summary of the Invention

[0008] The present application provides a capillary electrophoresis system and method for use with a discontinuous injection mass spectrometer to address the problems in the related art where, when continuous capillary electrophoresis technology is used in conjunction with a discontinuous injection small mass spectrometer system, the mass spectrometer sampling rate is low, resulting in reduced accuracy and poor analysis quality. In addition, the sampling frequency is greatly limited, making it difficult to ensure that mass spectrometer data at the highest point of the chromatographic peak can be collected, thereby affecting the sensitivity of detection and the accuracy of quantitative analysis, and reducing the sensitivity and stability of quantitative analysis using discontinuous injection mass spectrometry.

[0009] The first embodiment of the present application provides a capillary electrophoresis system coupled with a discontinuous inlet mass spectrometer, comprising: an electrophoresis separation-electrospray ionization module, for separating the components in the target analyte according to different electrophoretic mobilities, and ionizing the separated components to form a charged spray; a real-time adjustable high-voltage power supply device, for providing the voltage required for capillary electrophoresis according to the requirements of electroosmotic flow and electrophoretic velocity in the capillary; a target component signal feedback module, for detecting the target analyte or the real-time electroosmotic flow velocity; an electrophoresis current measurement and migration time correction module, for monitoring and recording the current value during the electrophoresis process, and using the current value to correct the migration time of the target component to obtain a migration index; a real-time feedback signal processing and control module, for generating a corresponding voltage control signal according to the target analyte or the real-time electroosmotic flow velocity; and a discontinuous inlet mass spectrometer system, for detecting the mass-to-charge ratio and intensity of the target analyte, and obtaining qualitative or quantitative analysis results based on the charged spray.

[0010] Optionally, in one embodiment of the present application, the electrophoresis separation-electrospray ionization module includes: an injection device for injecting the target analyte into a separation device; the separation device is used to separate the components in the target analyte and send the separated components into a capillary electrophoresis-mass spectrometry interface; the capillary electrophoresis-mass spectrometry interface is used to ionize the separated components to generate charged ions.

[0011] Optionally, in one embodiment of the present application, the real-time adjustable high-voltage power supply device includes: a high-voltage power supply body, the high-voltage power supply body including a positive polarity power supply and a negative polarity power supply, for providing the voltage required for electrophoresis; a control system, for adjusting the output voltage of the high-voltage power supply body through timing programming, or adjusting the voltage according to the trigger signal of the target component signal feedback module.

[0012] Optionally, in one embodiment of the present application, the control system is further used to reduce the voltage when it is found that the target analyte is about to flow out of the electrophoresis separation-electrospray ionization module, and increase the output voltage after the target analyte has completely flowed out until the next target analyte flows out.

[0013] Optionally, in one embodiment of the present application, the target component signal feedback module includes at least one of an ultraviolet detector, a fluorescence detector, an electrochemical detector, a conductivity detector and a flow sensor.

[0014] Optionally, in one embodiment of the present application, the electrophoresis current measurement and migration time correction module includes: a sampling resistor, used to convert the current signal into a voltage signal to adjust the resistance value according to the current value during actual operation; a sampling microcontroller, used to convert the voltage signal into a digital signal and transmit the digital signal to a host computer; a communication interface, used to connect the sampling microcontroller and the host computer, and use an optical coupling isolator or a wireless connection between Bluetooth to achieve high-voltage isolation between the microcontroller and the host computer.

[0015] Optionally, in one embodiment of the present application, the real-time feedback signal processing and control module includes: a signal processing module, which uses the single-chip microcomputer or the host computer to perform real-time processing of the voltage control signal and electrophoresis current; and a control signal issuing module, which is used to generate the corresponding voltage control signal after determining that a valid target signal is detected.

[0016] The second aspect of the present application provides a capillary electrophoresis method coupled with a discontinuous injection mass spectrometer, comprising the following steps: separating the components in the target analyte according to different electrophoretic mobilities, and ionizing the separated components to form a charged spray; providing the voltage required for capillary electrophoresis according to the requirements of electroosmotic flow and electrophoretic velocity in the capillary; detecting the target analyte or the real-time electroosmotic flow velocity; monitoring and recording the current value during the electrophoresis process, and using the current value to correct the migration time of the target component to obtain a migration index; generating a corresponding voltage control signal according to the target analyte or the real-time electroosmotic flow velocity; and detecting the mass-to-charge ratio and intensity of the target analyte, and obtaining a qualitative or quantitative analysis result based on the charged spray.

[0017] Optionally, in one embodiment of the present application, separating the components in the target analyte according to different electrophoretic mobilities includes: injecting the target analyte into a separation device; separating the components in the target analyte, and sending the separated components into a capillary electrophoresis-mass spectrometry interface; ionizing the separated components to generate charged ions.

[0018] Optionally, in one embodiment of the present application, the voltage required for capillary electrophoresis is provided according to the requirements of electroosmotic flow and electrophoretic speed in the capillary, including: the high-voltage power supply body includes a positive polarity power supply and a negative polarity power supply, which are used to provide the voltage required for electrophoresis; the output voltage of the high-voltage power supply body is adjusted by timing programming, or the voltage is adjusted according to the trigger signal of the target component signal feedback module.

[0019] Optionally, in one embodiment of the present application, the output voltage of the high-voltage power supply body is adjusted by timing programming, or the voltage is adjusted according to the trigger signal of the target component signal feedback module, including: if it is found that the target analyte is about to flow out of the electrophoresis separation-electrospray ionization module, the voltage is lowered, and after the target analyte has completely flowed out, the output voltage is increased until the next target analyte flows out.

[0020] Optionally, in one embodiment of the present application, the target component signal feedback module includes at least one of an ultraviolet detector, a fluorescence detector, an electrochemical detector, a conductivity detector and a flow sensor.

[0021] Optionally, in one embodiment of the present application, the monitoring records the current value during the electrophoresis process and uses the current value to correct the migration time of the target component, including: converting the current signal into a voltage signal to adjust the resistance value according to the current value during actual operation; converting the voltage signal into a digital signal, and transmitting the digital signal to a host computer; connecting the sampling microcontroller and the host computer, and using an optical coupling isolator or a wireless connection between Bluetooth to achieve high-voltage isolation between the microcontroller and the host computer.

[0022] Optionally, in one embodiment of the present application, generating a corresponding voltage control signal based on the target analyte or the real-time electroosmotic flow velocity includes: using the single-chip microcomputer or the host computer to process the voltage control signal and the electrophoretic current in real time; and generating the corresponding voltage control signal after determining that a valid target signal is detected.

[0023] The third aspect of the present application provides an electronic device, comprising: a memory, a processor, and a computer program stored on the memory and executable on the processor, wherein the processor executes the program to implement the capillary electrophoresis method combined with discontinuous injection mass spectrometry as described in the above embodiment.

[0024] A fourth aspect of the present application provides a computer-readable storage medium storing a computer program, which, when executed by a processor, implements the capillary electrophoresis method combined with discontinuous injection mass spectrometry as described above.

[0025] The embodiment of the present application can improve the efficiency of capillary electrophoresis and discontinuous injection mass spectrometry analysis by adjusting the electrophoresis flow rate in real time as needed, and specifically increase the number of sampling points of the target analyte electrophoresis chromatographic peak, improve the sensitivity and stability of discontinuous injection mass spectrometry for quantitative analysis, and improve the stability of the migration time of the target component in capillary electrophoresis. Thus, it solves the problem in the related art that when continuous capillary electrophoresis technology is used in conjunction with a discontinuous injection small mass spectrometry system, the mass spectrometry sampling rate is low, which usually leads to problems such as reduced accuracy and poor analysis quality, and the sampling frequency is greatly limited, making it difficult to ensure that the mass spectrometry data at the highest point of the chromatographic peak can be collected, affecting the sensitivity of detection and the accuracy of quantitative analysis, and reducing the sensitivity and stability of discontinuous injection mass spectrometry for quantitative analysis.

[0026] Additional aspects and advantages of the present application will be given in part in the description below, and in part will become apparent from the description below, or will be learned through practice of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] The above and / or additional aspects and advantages of the present application will become apparent and easily understood from the following description of the embodiments in conjunction with the accompanying drawings, in which:

[0028] FIG1 is a schematic structural diagram of a capillary electrophoresis system coupled with a discontinuous injection mass spectrometer according to an embodiment of the present application;

[0029] FIG2 is a schematic diagram of the principle of a capillary electrophoresis system coupled with a discontinuous injection mass spectrometer according to one embodiment of the present application;

[0030] FIG3 is a graph showing the relationship between separation voltage and electroosmotic flow rate during electrophoretic separation in a capillary electrophoresis system coupled with a discontinuous injection mass spectrometer according to one embodiment of the present application;

[0031] FIG4 is a graph showing the relationship between the electrophoresis separation voltage and the number of chromatographic peak sampling points when a capillary electrophoresis system coupled with a discontinuous injection mass spectrometer is used to detect a single target according to one embodiment of the present application;

[0032] FIG5 is a schematic diagram of a capillary electrophoresis system coupled with a discontinuous injection mass spectrometer for performing target component migration time correction using electrophoresis current values ​​according to one embodiment of the present application;

[0033] FIG6 is a chromatogram comparison diagram of conventional analysis (left) and deceleration analysis of a target peak (right) using a capillary electrophoresis system coupled with a discontinuous injection mass spectrometer according to one embodiment of the present application;

[0034] FIG7 is a graph comparing the stability of decelerated analysis and conventional non-decelerated analysis in a capillary electrophoresis system coupled with a discontinuous injection mass spectrometer according to one embodiment of the present application;

[0035] FIG8 is a comparison chart of the detection sensitivity of a capillary electrophoresis system coupled with a discontinuous injection mass spectrometer and a conventional non-decelerated analysis according to one embodiment of the present application;

[0036] FIG9 is a chromatogram comparison diagram of conventional analysis (left) and accelerated analysis between target peaks (right) of a capillary electrophoresis system coupled with discontinuous injection mass spectrometry according to one embodiment of the present application;

[0037] FIG10 is a comparison chart of chromatograms of conventional analysis (left) and analysis with deceleration of target peaks and acceleration between targets (right) using a capillary electrophoresis system coupled with discontinuous injection mass spectrometry according to one embodiment of the present application;

[0038] FIG11 is a chromatogram and secondary mass spectrometer of verapamil and phosphatidylcholine (PC 34:1) in blood analyzed using a capillary electrophoresis system coupled with a discontinuous injection mass spectrometer according to one embodiment of the present application;

[0039] FIG12 is a comparison of target fragment ion intensities detected by a capillary electrophoresis system coupled with a discontinuous injection mass spectrometer and a nanoESI method for analyzing verapamil in blood according to one embodiment of the present application;

[0040] FIG13 is a flow chart of a capillary electrophoresis method coupled with discontinuous injection mass spectrometry according to an embodiment of the present application;

[0041] FIG14 is a schematic structural diagram of an electronic device provided according to an embodiment of the present application. DETAILED DESCRIPTION

[0042] The following describes in detail embodiments of the present application, examples of which are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are intended to be used to explain the present application, and should not be construed as limiting the present application.

[0043] The capillary electrophoresis system and method for use with a discontinuous injection mass spectrometry according to an embodiment of the present application are described below with reference to the accompanying drawings. In view of the related art mentioned in the above background technology, when the continuous capillary electrophoresis technology is used in conjunction with a discontinuous injection small mass spectrometry system, due to the low mass spectrometry sampling rate, problems such as reduced accuracy and poor analysis quality usually occur, and the sampling frequency is greatly limited, making it difficult to ensure that mass spectrometry data at the highest point of the chromatographic peak can be collected, affecting the sensitivity of detection and the accuracy of quantitative analysis, and reducing the sensitivity and stability of quantitative analysis by discontinuous injection mass spectrometry. The present application provides a capillary electrophoresis system for use with a discontinuous injection mass spectrometry, in which the efficiency of capillary electrophoresis and discontinuous injection mass spectrometry analysis can be improved by adjusting the electrophoresis flow rate in real time as needed, and the number of sampling points of the electrophoretic chromatographic peak of the target analyte is increased in a targeted manner, thereby improving the sensitivity and stability of quantitative analysis by discontinuous injection mass spectrometry and improving the stability of the migration time of the target component in capillary electrophoresis. This solves the problem in related technologies that, when continuous capillary electrophoresis technology is used in conjunction with a discontinuous injection small mass spectrometry system, the mass spectrometry sampling rate is low, which usually leads to problems such as reduced accuracy and poor analysis quality. In addition, the sampling frequency is greatly limited, making it difficult to ensure that mass spectrometry data at the highest point of the chromatographic peak can be collected, affecting the sensitivity of detection and the accuracy of quantitative analysis, and reducing the sensitivity and stability of quantitative analysis using discontinuous injection mass spectrometry.

[0044] Specifically, FIG1 is a schematic structural diagram of a capillary electrophoresis system coupled with a discontinuous injection mass spectrometer provided in an embodiment of the present application.

[0045] As shown in Figure 1, the capillary electrophoresis system 10 combined with the discontinuous injection mass spectrometry includes: an electrophoresis separation-electrospray ionization module 100, a real-time adjustable high-voltage power supply device 200, a target component signal feedback module 300, an electrophoresis current measurement and migration time correction module 400, a real-time feedback signal processing and control module 500 and a discontinuous injection mass spectrometry system 600.

[0046] Specifically, the electrophoresis separation-electrospray ionization module 100 is used to separate the components in the target analyte according to their different electrophoretic mobilities, and ionize the separated components to form a charged spray.

[0047] During the actual implementation process, the embodiment of the present application can separate the components in the target analyte according to their different electrophoretic mobilities through the electrophoresis separation-electrospray ionization module 100, and ionize the separated components to form a charged spray, thereby providing support for the use of on-demand variable speed capillary electrophoresis mode, realizing the combination of capillary electrophoresis and discontinuous injection mass spectrometry, reducing the separation voltage when the target analyte flows out, and improving the sensitivity of discontinuous injection mass spectrometry detection of complex samples and the stability of quantitative analysis.

[0048] Optionally, in one embodiment of the present application, the electrophoresis separation-electrospray ionization module 100 includes: an injection device for injecting the target analyte into the separation device; a separation device for separating the components in the target analyte and sending the separated components into the capillary electrophoresis-mass spectrometry interface; a capillary electrophoresis-mass spectrometry interface for ionizing the separated components to generate charged ions.

[0049] It can be understood that the electrophoresis separation-electrospray ionization module 100 in the embodiment of the present application is composed of three parts: a sample injection device, a separation device and a capillary electrophoresis-mass spectrometry interface.

[0050] As a possible implementation method, the embodiment of the present application can inject the target analyte into the separation device through the sampling device, wherein the sampling device adopts an electrical sampling method, transfers the capillary and the electrode to the sample bottle, applies voltage, and uses electroosmosis to inject the sample into the capillary. The embodiment of the present application can separate the components in the target analyte through the separation device, and send the separated components into the capillary electrophoresis-mass spectrometry interface, wherein the separation device includes but is not limited to capillary and chip electrophoresis. Specifically, the separation device is a quartz capillary with a polyimide coating treated with sodium hydroxide solution, with an inner diameter of 50μm, an outer diameter of 150μm, and a length of 40cm. The polyimide coating of about 1cm is removed by ablation or cutting at both ends to expose the internal quartz capillary to avoid the polyimide coating affecting the sampling process and interface connection. The embodiment of the present application can ionize the separated components through a capillary electrophoresis-mass spectrometry interface to generate charged ions, wherein the capillary electrophoresis-mass spectrometry interface adopts a sheath flow type interface, and the main body is a standard four-way connector with an inner diameter of 1 / 16 inch, which can be connected to the nanoTIP through a standard fastening head. The nanoTIP is a borosilicate glass tube with an inner diameter of 0.8 mm and an outer diameter of 1.5 mm, and a needle puller is used to pull the tip. After drawing, the tip opening diameter is about 5-10 μm, which can ensure normal spraying and avoid tip clogging. The capillary extends into the tip of the nanoTIP through the four-way, and the other two ends of the four-way are electrically connected to a 2kV power supply through a sheath flow liquid.

[0051] The embodiments of the present application achieve the coupling of capillary electrophoresis and discontinuous injection mass spectrometry by changing the operating mode of capillary electrophoresis, separate the components in the sample before mass spectrometry analysis, reduce the influence of matrix effects on mass spectrometry analysis, further reduce the separation voltage when the target analyte flows out, and improve the sensitivity of discontinuous injection mass spectrometry detection of complex samples and the stability of quantitative analysis.

[0052] The real-time adjustable high-voltage power supply device 200 is used to provide the voltage required for capillary electrophoresis according to the requirements of electroosmotic flow and electrophoresis speed in the capillary.

[0053] During the actual implementation process, the embodiment of the present application can provide the voltage required for capillary electrophoresis according to the requirements of electroosmotic flow and electrophoresis speed in the capillary through the real-time adjustable high-voltage power supply device 200. Through the on-demand variable speed capillary electrophoresis mode, the separation voltage is increased after the target analyte flows out, thereby shortening the blank analysis time between each target analyte and improving the analysis efficiency when capillary electrophoresis is combined with non-continuous injection mass spectrometry.

[0054] Optionally, in one embodiment of the present application, the real-time adjustable high-voltage power supply device 200 includes: a high-voltage power supply body, the high-voltage power supply body including a positive polarity power supply and a negative polarity power supply, for providing the voltage required for electrophoresis; a control system, for adjusting the output voltage of the high-voltage power supply body through timing programming, or adjusting the voltage according to the trigger signal of the target component signal feedback module.

[0055] Specifically, the real-time adjustable high-voltage power supply device 200 in the embodiment of the present application consists of two parts: a high-voltage power supply and a control program. The high-voltage power supply output voltage is 0-50kV, and has current measurement and display functions. The high-voltage power supply is connected to the computer via an RS232 interface. The control program on the computer can perform timing control on the high-voltage power supply output voltage, and can receive a trigger signal from a sensor. The high-voltage power supply body includes a positive polarity power supply and a negative polarity power supply, which can provide the voltage required for electrophoresis. The control system in the embodiment of the present application can adjust the output voltage of the high-voltage power supply body through timing programming, or adjust the voltage according to the trigger signal of the target component signal feedback module, thereby further changing the capillary electrophoresis mode on demand, increasing the separation voltage after the target analyte flows out, shortening the blank analysis time between each target analyte, and improving the analysis efficiency when capillary electrophoresis is combined with discontinuous injection mass spectrometry.

[0056] Optionally, in one embodiment of the present application, the control system is further configured to reduce the voltage when it is found that the target analyte is about to flow out of the electrophoresis separation-electrospray ionization module, and increase the output voltage after the target analyte has completely flowed out until the next target analyte flows out.

[0057] As a possible implementation method, the embodiment of the present application can reduce the voltage when it is found that the target analyte is about to flow out of the electrophoresis separation-electrospray ionization module, and increase the output voltage after the target analyte has completely flowed out until the next target analyte flows out, thereby further improving the analysis efficiency when capillary electrophoresis is combined with discontinuous injection mass spectrometry.

[0058] The target component signal feedback module 300 is used to detect target analytes or real-time electroosmotic flow velocity.

[0059] During the actual implementation process, the embodiment of the present application can detect the target analyte or real-time electroosmotic flow velocity through the target component signal feedback module 300, and reduce the separation voltage when the target analyte flows out through on-demand variable speed capillary electrophoresis, thereby extending the analyte flow time, increasing the number of sampling points of the non-continuous injection mass spectrometry for the target analyte, and improving the stability of quantitative analysis.

[0060] Optionally, in one embodiment of the present application, the target component signal feedback module 300 includes at least one of an ultraviolet detector, a fluorescence detector, an electrochemical detector, a conductivity detector, and a flow sensor.

[0061] Specifically, the target component signal feedback module 300 includes but is not limited to ultraviolet detectors, fluorescence detectors, electrochemical detectors, conductivity detectors and flow sensors, etc. Different sensors can be used to detect the migration time and real-time electroosmotic flow velocity of the target analyte according to the different properties of the target analyte. When the sensor detects that the target analyte begins to flow out of the separation device, the sensor sends a trigger signal to the signal processing and control module. The control module controls the high-voltage power supply to change the output voltage, thereby realizing automatic control of the output voltage of the entire process, simplifying the operating process, and improving the analysis efficiency. The on-demand variable speed capillary electrophoresis reduces the separation voltage when the target analyte flows out, prolongs the analyte flow time, increases the number of sampling points of the discontinuous injection mass spectrometry for the target analyte, and improves the stability of the quantitative analysis.

[0062] The electrophoresis current measurement and migration time correction module 400 is used to monitor and record the current value during the electrophoresis process, and use the current value to correct the migration time of the target component to obtain a migration index.

[0063] During the actual implementation process, the embodiment of the present application can monitor and record the current value during the electrophoresis process through the electrophoresis current measurement and migration time correction module 400, and use the current value to correct the migration time of the target component to obtain a migration index with better reproducibility. In addition, it can also be judged based on the migration index calculated in real time whether the target analyte begins to flow out of the separation device, and provide a trigger signal to the signal processing and control module to control the output voltage of the high-voltage power supply, so as to increase the separation voltage again after the previous target analyte flows out by the capillary electrophoresis on demand, shorten the blank analysis time between each target component, and improve the efficiency of the capillary electrophoresis and non-continuous injection mass spectrometry.

[0064] Optionally, in one embodiment of the present application, the electrophoresis current measurement and migration time correction module 400 includes: a sampling resistor, used to convert the current signal into a voltage signal to adjust the resistance value according to the current value during actual operation; a sampling microcontroller, used to convert the voltage signal into a digital signal and transmit the digital signal to a host computer; a communication interface, used to connect the sampling microcontroller and the host computer, and use an optical coupling isolator or a wireless connection between Bluetooth to achieve high-voltage isolation between the microcontroller and the host computer.

[0065] During the actual execution process, the embodiment of the present application can convert the current signal into a voltage signal through a sampling resistor to adjust the resistance value according to the current value during actual operation; the embodiment of the present application can convert the voltage signal into a digital signal through a sampling microcontroller, and transmit the digital signal to the host computer; the embodiment of the present application can connect the sampling microcontroller and the host computer through a communication interface, and use an optical coupling isolator or a wireless connection between Bluetooth to achieve high-voltage isolation between the microcontroller and the host computer, so as to further increase the separation voltage again after the previous target analyte flows out by changing the speed of capillary electrophoresis on demand, shorten the blank analysis time between each target component, and improve the efficiency of capillary electrophoresis combined with discontinuous injection mass spectrometry.

[0066] The real-time feedback signal processing and control module 500 is used to generate a corresponding voltage control signal according to the target analyte or the real-time electroosmotic flow velocity.

[0067] During actual implementation, the embodiment of the present application can generate a corresponding voltage control signal according to the target analyte or the real-time electroosmotic flow velocity through the real-time feedback signal processing and control module 500, thereby monitoring the electrophoresis process in real time, accurately determining the migration time of the target analyte, and solving the problem of unstable migration time of capillary electrophoresis through real-time current monitoring.

[0068] Optionally, in one embodiment of the present application, the real-time feedback signal processing and control module 500 includes: a signal processing module, which uses a single-chip microcomputer or a host computer to perform real-time processing of the voltage control signal and the electrophoresis current; and a control signal issuing module, which is used to generate a corresponding voltage control signal after determining that a valid target signal is detected.

[0069] In some embodiments, a single-chip microcomputer or a host computer can be used to perform real-time processing of the voltage control signal and the electrophoresis current to provide support for the subsequent generation of the corresponding voltage control signal; the embodiment of the present application can generate a corresponding voltage control signal after the control signal sending module determines that a valid target signal is detected, wherein the voltage control signal can be programmed and set as needed according to the actual analysis situation, thereby further monitoring the electrophoresis process in real time, accurately determining the migration time of the target analyte, and solving the problem of unstable migration time of capillary electrophoresis through real-time current monitoring.

[0070] The discontinuous injection mass spectrometry system 600 is used to detect the mass-to-charge ratio and intensity of target analytes and obtain qualitative or quantitative analysis results based on charged spray.

[0071] In the actual implementation process, the embodiment of the present application can detect the mass-to-charge ratio and intensity of the target analyte through the discontinuous injection mass spectrometry system 600, and obtain qualitative or quantitative analysis results based on the charged spray, thereby improving the sensitivity and stability of the discontinuous injection mass spectrometry for quantitative analysis. The discontinuous injection mass spectrometry in the embodiment of the present application is a small ion trap mass spectrometer using a discontinuous atmospheric pressure interface (DAPI). A solenoid valve can be used as an injection port to simplify the vacuum system. The solenoid valve is only opened for about 20ms during injection and remains normally closed for the rest of the time. It should be noted that this mode is limited by the pressure changes of the vacuum system, and the sampling frequency can reach 2-3 seconds / time at the fastest.

[0072] Specifically, in combination with Figures 2 to 12, the working principle of the capillary electrophoresis system combined with discontinuous injection mass spectrometry according to the embodiment of the present application is described in detail with reference to a specific embodiment.

[0073] As shown in Figure 2, an embodiment of the present application includes: an electrophoresis separation-electrospray ionization module 100, a real-time adjustable high-voltage power supply device 200, a target component signal feedback module 300, an electrophoresis current measurement and migration time correction module 400, a real-time feedback signal processing and control module 500 and a discontinuous injection mass spectrometry system 600.

[0074] In the actual implementation process, the electrophoresis separation-electrospray ionization module 100 consists of three parts: an injection device, a separation device, and a capillary electrophoresis-mass spectrometry interface. The injection device adopts an electric injection method. After the capillary and the electrode are transferred to the sample bottle, a voltage is applied and the sample is injected into the capillary by electroosmosis. The separation device is a quartz capillary with a polyimide coating treated with sodium hydroxide solution, with an inner diameter of 50 μm, an outer diameter of 150 μm, and a length of 40 cm. The polyimide coating of about 1 cm is removed at both ends by ablation or cutting to expose the internal quartz capillary to avoid the polyimide coating affecting the injection process and interface connection. The capillary electrophoresis-mass spectrometry interface adopts a sheath flow type interface. The main body is a standard four-way connector with an inner diameter of 1 / 16 inch, which can be connected to the nanoTIP through a standard fastening head. The nanoTIP is a borosilicate glass tube with an inner diameter of 0.8 mm and an outer diameter of 1.5 mm. The tip is pulled using a needle puller. After pulling, the tip opening has a diameter of approximately 5-10 μm, ensuring proper spraying while preventing tip clogging. The capillary extends into the nanoTIP tip through a crosspiece, the other ends of which are electrically connected to a 2 kV power supply via sheath fluid.

[0075] The real-time adjustable high-voltage power supply device 200 consists of a high-voltage power supply and a control program. The high-voltage power supply has an output voltage range of 0-50 kV and features current measurement and display capabilities. The high-voltage power supply connects to a computer via an RS232 interface. The control program on the computer controls the timing of the high-voltage power supply's output voltage and receives trigger signals from sensors.

[0076] The target component signal feedback module 300 can use different sensors, such as ultraviolet (UV) detectors, fluorescence detectors, electrochemical detectors, and conductivity detectors, to detect target analyte migration time and real-time electroosmotic flow velocity, depending on the properties of the target analyte. When a sensor detects that the target analyte begins to flow out of the separation device, it generates a trigger signal that is transmitted to the signal processing and control module. The control module then controls the high-voltage power supply to change its output voltage.

[0077] The electrophoretic current measurement and migration time correction module 400 measures the current during electrophoresis and corrects the migration time of the target component based on the change in current, resulting in a more reproducible migration index. Furthermore, the real-time calculated migration index can be used to determine whether the target analyte has begun to flow out of the separation device, providing a trigger signal to the signal processing and control module to control the output voltage of the high-voltage power supply.

[0078] The real-time feedback signal processing and control module 500 generates a corresponding voltage control signal according to the target analyte or the real-time electroosmotic flow velocity, and can use a single-chip microcomputer or a host computer to process the voltage control signal and the electrophoretic current in real time; after determining that a valid target signal is detected, a corresponding voltage control signal is generated.

[0079] In the discontinuous inlet mass spectrometry system 600, the discontinuous inlet mass spectrometer is a small ion trap mass spectrometer using a discontinuous atmospheric pressure interface (DAPI). It uses a solenoid valve as the inlet to simplify the vacuum system. The solenoid valve is only opened for about 20ms during injection and remains normally closed for the rest of the time. This mode is limited by the pressure changes of the vacuum system, and the sampling frequency can reach as fast as 2-3 seconds / time.

[0080] The working principle of the embodiment of the present application is shown in Figures 3 and 4. Specifically, Figure 3 is a graph showing the relationship between the electrophoresis separation voltage and the electroosmotic flow rate. It has been determined that during capillary electrophoresis, the electroosmotic flow rate is proportional to the separation voltage at both ends of the capillary. Therefore, the embodiment of the present application can achieve real-time control of the electroosmotic flow rate and electrophoretic velocity by changing the separation voltage at both ends of the capillary. Figure 4 is a graph showing the relationship between the electrophoresis separation voltage and the number of sampling points of a single target chromatographic peak. When detecting a single target, by reducing the voltage, the electroosmotic flow and the electrophoretic velocity are reduced, thereby increasing the number of sampling points on the chromatographic peak of a single target, which is of great help in improving the sensitivity and stability of the analysis.

[0081] How to use this application:

[0082] Example 1: Increasing the number of target peak sampling points by deceleration to improve analytical sensitivity and stability.

[0083] (1) The high-voltage power supply electrode and the capillary injection end are transferred to the container containing the sample to be tested. A 20 kV high voltage is applied to the sample bottle through the electrode. The sample is injected into the capillary under the action of electroosmotic flow. After 7 seconds, the high voltage is disconnected to complete the injection.

[0084] (2) The high-voltage power supply electrode and the capillary injection end are transferred to a container filled with buffer solution. A high voltage of 20 kV is applied to the buffer solution bottle through the electrode. Under the combined action of the electric field and electroosmotic flow, the sample migrates from the injection end to the electrophoresis-mass spectrometry interface. Since different molecules migrate at different speeds under the action of the electric field, the components of the sample are separated.

[0085] (3) During the electrophoresis process, the current measurement module monitors the changes in the electrophoretic current in real time and calculates the migration index, as shown in Figure 5, to correct the migration time of the target analyte. The current measurement module communicates with the host computer via a serial port via an optical coupling isolator or Bluetooth.

[0086] (4) The target analyte migrates to the electrophoresis-mass spectrometry interface, and after the sensor detects the outflow of the target analyte, a trigger signal is generated and transmitted to the signal processing and control module; or, when the migration index calculated in real time by the current measurement module reaches the migration index of the target analyte, the current measurement module generates a trigger signal and transmits it to the signal processing and control module.

[0087] (5) As shown in FIG6 , after the control program receives the trigger signal, it reduces the output voltage of the high-voltage power supply to 10 kV, and the migration speed of the target analyte is reduced. At the same time, the discontinuous injection mass spectrometer starts mass spectrometry analysis at a frequency of 2-3 seconds per time. The discontinuous injection mass spectrometer can have more time to sample the target analyte, thereby increasing the number of sampling points for the target object.

[0088] As shown in Figures 7 and 8, the mode of decelerating the analysis of the target peak significantly improved the stability of the quantitative analysis and the sensitivity of the detection.

[0089] Example 2: Improving analysis efficiency by reducing waiting time when analyzing two or more targets through acceleration.

[0090] In addition to single-target analysis, specific application scenarios such as drug monitoring and metabolite screening often involve the detection of multiple target analytes. However, in conventional chromatographic analysis, long blank analysis times may exist between target analyte components, resulting in wasted time and reduced analysis efficiency. In this embodiment, a method of increasing the electrophoresis speed during the blank analysis time is employed to address the issue of blank analysis time waste and improve the speed of multi-target analysis.

[0091] The injection procedure was performed similarly to that of Example 1, except that, as shown in Figure 8, the separation voltage was initially maintained at 20 kV. After the previous target analyte had completely eluted, the control program increased the high-voltage power supply output voltage to 30 kV, increasing the electroosmotic flow rate and electrophoresis speed until the next target analyte reached the electrophoresis-mass spectrometry interface. This process was repeated for two or more target analytes. This method reduced the blank analysis time between two adjacent target analytes and improved the analytical efficiency of the capillary electrophoresis-mass spectrometry system.

[0092] As shown in Figures 9 and 10, when performing multi-target analysis, the operating modes of Example 1 and Example 2 can also be combined. The separation voltage is lowered when the analyte flows out, and the separation voltage is increased during the blank analysis time between two adjacent target analytes. This can not only improve the stability and sensitivity of the quantitative analysis, but also improve the analysis efficiency.

[0093] Example 3: Rapid detection of drugs and metabolites in blood using a capillary electrophoresis-mass spectrometry interface system

[0094] (1) Drop 30 μL of blood supplemented with verapamil onto filter paper and quickly dry it using a hair dryer or oven to form a dried blood spot.

[0095] (2) Use a hole punch to cut the dried blood spot from the filter paper, immerse the dried blood spot in a centrifuge tube containing 200 μL of buffer, and let it stand for 3 minutes.

[0096] (3) The liquid in the centrifuge tube was injected and separated by electrophoresis in a similar manner to Example 2, and the separated verapamil and phosphatidylcholine (PC 34:1) were analyzed by secondary mass spectrometry. The chromatogram and secondary mass spectrum were shown in FIG11 .

[0097] (4) This method can significantly improve the sensitivity of mass spectrometry for detecting drugs or metabolites in complex matrices. As shown in Figure 12, the dried blood spot extract was subjected to mass spectrometry detection using nanoESI and this method, respectively, and the concentration of verapamil added to the blood was 10 ng / mL. This method can increase the intensity of the target fragment ion by about ten times. In addition, the use of field-enhanced injection can achieve online enrichment of the target analyte, further improving the sensitivity of the method. The specific operation method is: replace the buffer solution used to soak the dried blood spot with a buffer solution with a lower salt concentration (for example, the salt concentration is diluted 100 times), and at the same time increase the injection time during injection. As shown in Figure 12, the intensity of the target fragment ion can be further increased by 3-4 times.

[0098] The capillary electrophoresis system coupled with a discontinuous injection mass spectrometry system proposed in the embodiments of the present application improves the efficiency of capillary electrophoresis and discontinuous injection mass spectrometry analysis by changing the capillary electrophoresis operating mode, increases the number of sampling points for the electrophoretic chromatographic peak of the target analyte, and improves the sensitivity and stability of quantitative analysis by discontinuous injection mass spectrometry. This solves the problem in the related art that when continuous capillary electrophoresis technology is coupled with a discontinuous injection small mass spectrometry system, the accuracy is reduced and the analysis quality is poor due to the low mass spectrometry sampling rate. The sampling frequency is greatly limited, making it difficult to ensure that mass spectrometry data at the highest point of the chromatographic peak can be collected, affecting the sensitivity of detection and the accuracy of quantitative analysis, and reducing the sensitivity and stability of quantitative analysis by discontinuous injection mass spectrometry.

[0099] Next, a capillary electrophoresis method coupled with discontinuous injection mass spectrometry according to an embodiment of the present application will be described with reference to the accompanying drawings.

[0100] FIG13 is a flow chart of a capillary electrophoresis method coupled with discontinuous injection mass spectrometry according to an embodiment of the present application.

[0101] As shown in FIG13 , the capillary electrophoresis method coupled with discontinuous injection mass spectrometry comprises the following steps:

[0102] In step S1301 , the components of the target analyte are separated according to their electrophoretic mobility, and the separated components are ionized to form a charged spray.

[0103] In step S1302, the voltage required for capillary electrophoresis is provided according to the requirements of electroosmotic flow and electrophoretic velocity in the capillary.

[0104] In step S1303 , the target analyte or the real-time electroosmotic flow velocity is detected.

[0105] In step S1304, the current value during the electrophoresis process is monitored and recorded, and the migration time of the target component is corrected using the current value to obtain a migration index.

[0106] In step S1305 , a corresponding voltage control signal is generated according to the target analyte or the real-time electroosmotic flow velocity.

[0107] In step S1306 , the mass-to-charge ratio and intensity of the target analyte are detected, and a qualitative or quantitative analysis result is obtained based on the charged spray.

[0108] Optionally, in one embodiment of the present application, the components in the target analyte are separated according to different electrophoretic mobilities, including: injecting the target analyte into a separation device; separating the components in the target analyte, and sending the separated components into a capillary electrophoresis-mass spectrometry interface; ionizing the separated components to generate charged ions.

[0109] Optionally, in one embodiment of the present application, the voltage required for capillary electrophoresis is provided according to the requirements of electroosmotic flow and electrophoretic speed in the capillary, including: the high-voltage power supply body includes a positive polarity power supply and a negative polarity power supply, which are used to provide the voltage required for electrophoresis; the output voltage of the high-voltage power supply body is adjusted through timing programming, or the voltage is adjusted according to the trigger signal of the target component signal feedback module.

[0110] Optionally, in one embodiment of the present application, the output voltage of the high-voltage power supply body is adjusted by timing programming, or the voltage is adjusted according to the trigger signal of the target component signal feedback module, including: if it is found that the target analyte is about to flow out of the electrophoresis separation-electrospray ionization module, the voltage is reduced, and after the target analyte has completely flowed out, the output voltage is increased until the next target analyte flows out.

[0111] Optionally, in one embodiment of the present application, the target component signal feedback module includes at least one of an ultraviolet detector, a fluorescence detector, an electrochemical detector, a conductivity detector, and a flow sensor.

[0112] Optionally, in one embodiment of the present application, the current value during the electrophoresis process is monitored and recorded, and the migration time of the target component is corrected using the current value, including: converting the current signal into a voltage signal to adjust the resistance value according to the current value during actual operation; converting the voltage signal into a digital signal, and transmitting the digital signal to a host computer; connecting the sampling microcontroller and the host computer, and using an optical coupling isolator or a wireless connection between Bluetooth to achieve high-voltage isolation between the microcontroller and the host computer.

[0113] Optionally, in one embodiment of the present application, a corresponding voltage control signal is generated according to the target analyte or the real-time electroosmotic flow velocity, including: using a single-chip microcomputer or a host computer to process the voltage control signal and the electrophoretic current in real time; after determining that a valid target signal is detected, a corresponding voltage control signal is generated.

[0114] It should be noted that the above explanation of the embodiment of the capillary electrophoresis system coupled with discontinuous injection mass spectrometry is also applicable to the capillary electrophoresis method coupled with discontinuous injection mass spectrometry of this embodiment, and will not be repeated here.

[0115] According to the capillary electrophoresis method for use with a discontinuous injection mass spectrometry proposed in the embodiments of the present application, by changing the capillary electrophoresis operating mode, the efficiency of capillary electrophoresis combined with discontinuous injection mass spectrometry analysis is improved, the number of sampling points for the electrophoretic chromatographic peak of the target analyte is increased, and the sensitivity and stability of quantitative analysis by discontinuous injection mass spectrometry are improved. Thus, the problem in the related art that continuous capillary electrophoresis technology, when used in conjunction with a discontinuous injection small mass spectrometry system, usually suffers from reduced accuracy and poor analysis quality due to the low mass spectrometry sampling rate, and the sampling frequency is greatly limited, making it difficult to ensure that mass spectrometry data at the highest point of the chromatographic peak can be collected, affecting the sensitivity of detection and the accuracy of quantitative analysis, and reducing the sensitivity and stability of quantitative analysis by discontinuous injection mass spectrometry is solved.

[0116] FIG14 is a schematic diagram of the structure of an electronic device provided in an embodiment of the present application. The electronic device may include:

[0117] Memory 1401 , processor 1402 , and computer programs stored in the memory 1401 and executable on the processor 1402 .

[0118] When the processor 1402 executes the program, the capillary electrophoresis method combined with discontinuous injection mass spectrometry provided in the above embodiment is implemented.

[0119] Furthermore, the electronic device further includes:

[0120] The communication interface 1403 is used for communication between the memory 1401 and the processor 1402 .

[0121] The memory 1401 is used to store computer programs that can be run on the processor 1402 .

[0122] The memory 1401 may include a high-speed RAM memory, and may also include a non-volatile memory (non-volatile memory), such as at least one disk memory.

[0123] If the memory 1401, processor 1402, and communication interface 1403 are implemented independently, the communication interface 1403, memory 1401, and processor 1402 can be interconnected via a bus and communicate with each other. The bus can be an Industry Standard Architecture (ISA) bus, a Peripheral Component Interconnect (PCI) bus, or an Extended Industry Standard Architecture (EISA) bus. Buses can be divided into address buses, data buses, control buses, etc. For ease of illustration, FIG14 shows only one thick line, but this does not mean that there is only one bus or only one type of bus.

[0124] Optionally, in a specific implementation, if the memory 1401, the processor 1402 and the communication interface 1403 are integrated on a chip, the memory 1401, the processor 1402 and the communication interface 1403 can communicate with each other through an internal interface.

[0125] The processor 1402 may be a central processing unit (CPU), an application specific integrated circuit (ASIC), or one or more integrated circuits configured to implement the embodiments of the present application.

[0126] An embodiment of the present application further provides a computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, implements the above-mentioned capillary electrophoresis method combined with discontinuous injection mass spectrometry.

[0127] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present application. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or N embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification and features of different embodiments or examples without contradiction.

[0128] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be understood to indicate or imply relative importance or implicitly specify the number of technical features indicated. Thus, a feature specified as "first" or "second" may explicitly or implicitly include at least one such feature. In the description of this application, "N" means at least two, for example, two, three, etc., unless otherwise specifically defined.

[0129] Any process or method description in a flowchart or otherwise described herein may be understood to represent a module, fragment or portion of code comprising one or N executable instructions for implementing a custom logical function or process step, and the scope of the preferred embodiments of the present application includes alternative implementations in which functions may be performed in a different order than shown or discussed, including performing functions in a substantially simultaneous manner or in a reverse order depending on the functions involved, which should be understood by those skilled in the art to which the embodiments of the present application pertain.

[0130] The logic and / or steps represented in the flowcharts or otherwise described herein, for example, can be considered as a sequenced list of executable instructions for implementing the logical functions, and can be embodied in any computer-readable medium for use by, or in conjunction with, an instruction execution system, apparatus, or device (e.g., a computer-based system, a system including a processor, or other system that can fetch and execute instructions from an instruction execution system, apparatus, or device). For purposes of this specification, a "computer-readable medium" can be any device that can contain, store, communicate, propagate, or transport a program for use by, or in conjunction with, an instruction execution system, apparatus, or device. More specific examples (a non-exhaustive list) of computer-readable media include the following: an electrical connection with one or N wires (electronic devices), a portable computer disk cartridge (magnetic device), random access memory (RAM), read-only memory (ROM), erasable and programmable read-only memory (EPROM or flash memory), fiber optic devices, and a portable compact disc read-only memory (CDROM). In addition, the computer-readable medium may even be paper or other suitable medium on which the program is printed, since the program can be obtained electronically by optically scanning the paper or other medium and then editing, interpreting or processing it in other suitable ways as necessary, and then storing it in a computer memory.

[0131] It should be understood that various parts of the present application can be implemented using hardware, software, firmware, or a combination thereof. In the above embodiment, the N steps or methods can be implemented using software or firmware stored in a memory and executed by a suitable instruction execution system. If implemented using hardware, as in another embodiment, any one of the following technologies known in the art or a combination thereof can be used: a discrete logic circuit having a logic gate circuit for implementing a logic function on a data signal, an application-specific integrated circuit having a suitable combination of logic gate circuits, a programmable gate array (PGA), a field programmable gate array (FPGA), etc.

[0132] Those skilled in the art will understand that all or part of the steps in the method of the above embodiment can be completed by instructing related hardware through a program, and the program can be stored in a computer-readable storage medium. When the program is executed, it includes one or a combination of the steps of the method embodiment.

[0133] In addition, the functional units in the various embodiments of the present application may be integrated into a processing module, or each unit may exist physically separately, or two or more units may be integrated into a module. The above-mentioned integrated module may be implemented in the form of hardware or in the form of a software functional module. If the integrated module is implemented in the form of a software functional module and sold or used as an independent product, it may also be stored in a computer-readable storage medium.

[0134] The storage medium mentioned above may be a read-only memory, a magnetic disk, or an optical disk, etc. Although the embodiments of the present application have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present application. Persons skilled in the art may make changes, modifications, substitutions, and variations to the above embodiments within the scope of the present application.

Claims

1. A capillary electrophoresis system coupled with a discontinuous injection mass spectrometer, characterized in that: include: The electrophoretic separation-electrospray ionization module is used to separate the components in the target analyte according to their different electrophoretic mobilities, and ionize the separated components to form a charged spray; A real-time adjustable high-voltage power supply device is used to provide the voltage required for capillary electrophoresis according to the requirements of electroosmotic flow and electrophoresis speed in the capillary; A target component signal feedback module is used to detect target analytes or real-time electroosmotic flow velocity; The electrophoresis current measurement and migration time correction module is used to monitor and record the current value during the electrophoresis process, and use the current value to correct the migration time of the target component to obtain the migration index; A real-time feedback signal processing and control module, used to generate a corresponding voltage control signal according to the target analyte or the real-time electroosmotic flow velocity; as well as The discontinuous injection mass spectrometry system is used to detect the mass-to-charge ratio and intensity of the target analyte and obtain qualitative or quantitative analysis results based on the charged spray.

2. The capillary electrophoresis system coupled with a discontinuous injection mass spectrometer according to claim 1, characterized in that: The electrophoresis separation-electrospray ionization module comprises: an injection device, used to inject the target analyte into the separation device; The separation device is used to separate the components in the target analyte and send the separated components to the capillary electrophoresis-mass spectrometry interface; The capillary electrophoresis-mass spectrometry interface is used to ionize the separated components to generate charged ions.

3. The capillary electrophoresis system coupled with a discontinuous injection mass spectrometer according to claim 1, characterized in that: The real-time adjustable high-voltage power supply device comprises: A high-voltage power supply body, comprising a positive polarity power supply and a negative polarity power supply, for providing the voltage required for electrophoresis; A control system is used to adjust the output voltage of the high-voltage power supply body through timing programming, or to adjust the voltage according to the trigger signal of the target component signal feedback module.

4. The capillary electrophoresis system combined with discontinuous injection mass spectrometry according to claim 3, characterized in that: The control system is further used to reduce the voltage when it is found that the target analyte is about to flow out of the electrophoresis separation-electrospray ionization module, and increase the output voltage after the target analyte has completely flowed out until the next target analyte flows out.

5. The capillary electrophoresis system coupled with a discontinuous injection mass spectrometer according to claim 1, characterized in that: The target component signal feedback module includes at least one of an ultraviolet detector, a fluorescence detector, an electrochemical detector, a conductivity detector and a flow sensor.

6. The capillary electrophoresis system combined with discontinuous injection mass spectrometry according to claim 1, characterized in that: The electrophoresis current measurement and migration time correction module includes: The sampling resistor is used to convert the current signal into a voltage signal so as to adjust the resistance value according to the current value during actual operation; A sampling single chip microcomputer, used for converting the voltage signal into a digital signal and transmitting the digital signal to a host computer; The communication interface is used to connect the sampling single-chip microcomputer and the host computer, and to achieve high-voltage isolation between the single-chip microcomputer and the host computer by using an optical coupling isolator or a wireless connection between Bluetooth.

7. The capillary electrophoresis system combined with discontinuous injection mass spectrometry according to claim 6, characterized in that: The real-time feedback signal processing and control module includes: A signal processing module, utilizing the single chip microcomputer or the host computer to process the voltage control signal and the electrophoresis current in real time; The control signal issuing module is used to generate the corresponding voltage control signal after determining that a valid target signal is detected.

8. A capillary electrophoresis method coupled with discontinuous injection mass spectrometry, characterized in that: The following steps are involved: The components of the target analyte are separated according to their different electrophoretic mobilities, and the separated components are ionized to form a charged spray; Providing the voltage required for capillary electrophoresis according to the requirements of electroosmotic flow and electrophoretic velocity in the capillary; Detection of target analytes or real-time electroosmotic flow velocity; Monitoring and recording the current value during the electrophoresis process, and using the current value to correct the migration time of the target component to obtain a migration index; generating a corresponding voltage control signal according to the target analyte or the real-time electroosmotic flow velocity; as well as The mass-to-charge ratio and intensity of the target analyte are detected, and a qualitative or quantitative analysis result is obtained based on the charged spray.

9. An electronic device, characterized in that: include: A memory, a processor, and a computer program stored in the memory and executable on the processor, wherein the processor executes the program to implement the capillary electrophoresis method combined with discontinuous injection mass spectrometry as claimed in claim 8.

10. A computer-readable storage medium having a computer program stored thereon, characterized in that: The program is executed by a processor to implement the capillary electrophoresis method combined with discontinuous injection mass spectrometry as claimed in claim 8.

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