Capillary electrophoresis system and method coupled with non-continuous injection mass spectrometry

Abstract

The application relates to a capillary electrophoresis system and method combined with a non-continuous sample injection mass spectrum, wherein the system comprises: an electrophoretic separation-electrospray ionization module for separating components in a target analyte according to different electrophoretic mobilities; a real-time adjustable high-voltage power supply device for providing a voltage required by capillary electrophoresis according to the requirements of an electroosmotic flow and an electrophoretic speed in a capillary; a target component signal feedback module for detecting a target analyte or a real-time electroosmotic flow speed; an electrophoretic current measurement and migration time correction module; a real-time feedback signal processing and control module; and a non-continuous sample injection mass spectrum system. Thus, the problems in the prior art that, when a continuous capillary electrophoresis technology is combined with a non-continuous sample injection small mass spectrum system, the accuracy is reduced, the analysis quality is poor, the sampling frequency is greatly limited, it is difficult to ensure that mass spectrum data at the highest point of a chromatographic peak can be collected, and the sensitivity of detection and the accuracy of quantitative analysis are affected are solved.

Description

Technical Field

[0001] This application relates to the field of mass spectrometry analysis technology, and in particular to a capillary electrophoresis system and method coupled with discontinuous injection mass spectrometry. Background Technology

[0002] Mass spectrometry offers advantages such as high sensitivity, fast analysis speed, and wide application range. It is particularly effective for qualitative and quantitative analysis of low-concentration analytes in complex biological samples, leading to its widespread use in clinical medicine, environmental monitoring, and food safety. Especially with the rise of miniaturization and in-situ ionization techniques, the demand for mass spectrometry instruments in various scenarios has increased rapidly. Among these, miniature mass spectrometers with discontinuous injection ports reduce the dependence on vacuum, allowing for a size reduction to 37 × 26.5 × 26.5 cm and a weight reduction to approximately 12 kg (Anal. Chem. 2021, 93, 47, 15607–15616), making them the most widely used miniature mass spectrometry systems currently available.

[0003] Among related technologies, firstly, to reduce the influence of matrix effects, chromatography-mass spectrometry (GC-MS) is typically used to separate the components of the sample before mass spectrometry detection, significantly improving the sensitivity of mass spectrometry detection. Commonly used chromatographic techniques coupled with mass spectrometry include liquid chromatography, gas chromatography, and capillary electrophoresis. Secondly, capillary electrophoresis, a chromatographic separation technique that uses a capillary as the separation channel and a high-voltage DC electric field as the driving force, 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 advantages such as short analysis time, simple structure and easy miniaturization, small sample volume, and good separation effect, making it suitable for coupling with small mass spectrometry systems.

[0004] However, in related technologies, continuous capillary electrophoresis, when coupled with non-continuous injection small mass spectrometry systems, often suffers from reduced accuracy and poor analytical quality due to the low mass spectrometry sampling rate. Because capillary electrophoresis has a high plate number, the chromatographic peak width for each component is very narrow (a few seconds to tens of seconds). Furthermore, non-continuous injection mass spectrometry, due to its non-continuous injection characteristics, has a significantly limited sampling frequency (once every few seconds). Therefore, it is difficult to guarantee the acquisition of mass spectrometry data at the highest point of the chromatographic peak, affecting the sensitivity of detection and the accuracy of quantitative analysis. Moreover, the introduction of chromatography may lead to a long blank analysis time between target analytes, resulting in wasted analysis time, which urgently needs improvement. Summary of the Invention

[0005] This application provides a capillary electrophoresis system and method coupled with discontinuous injection mass spectrometry to solve the problems in related technologies, such as reduced accuracy and poor analytical quality when continuous capillary electrophoresis technology is coupled with discontinuous injection small mass spectrometry systems due to the low mass spectrometry sampling rate. 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, which affects the sensitivity of detection and the accuracy of quantitative analysis, and reduces the sensitivity and stability of quantitative analysis by discontinuous injection mass spectrometry.

[0006] The first aspect of this application provides a capillary electrophoresis system coupled with discontinuous injection mass spectrometry, comprising: an electrophoretic separation-electrospray ionization module for separating components in a target analyte according to their different electrophoretic mobilities, and ionizing the separated components to form a charged spray; a real-time adjustable high-voltage power supply for providing the voltage required for capillary electrophoresis according to the requirements of electroosmotic flow and electrophoresis velocity in the capillary; a target component signal feedback module for detecting the target analyte or the real-time electroosmotic flow velocity; an electrophoretic current measurement and migration time correction module for monitoring and recording the current value during electrophoresis, 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 injection mass spectrometry 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.

[0007] Optionally, in one embodiment of this application, the electrophoretic separation-electrospray ionization module includes: a sample introduction device for injecting the target analyte into a separation device; the separation device for separating the components in the target analyte and sending the separated components into a capillary electrophoresis-mass spectrometry interface; and the capillary electrophoresis-mass spectrometry interface for ionizing the separated components to generate charged ions.

[0008] Optionally, in one embodiment of this 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; and 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.

[0009] Optionally, in one embodiment of this application, the control system is further configured to reduce the voltage when it detects that the target analyte is about to flow out of the electrophoretic separation-electrospray ionization module, and increase the output voltage after the target analyte has completely flowed out, until the next target analyte flows out.

[0010] Optionally, in one embodiment of this 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.

[0011] Optionally, in one embodiment of this application, the electrophoretic current measurement and migration time correction module includes: a sampling resistor for converting a current signal into a voltage signal to adjust the resistance value according to the actual current value during operation; a sampling microcontroller for converting the voltage signal into a digital signal and transmitting the digital signal to a host computer; and a communication interface for connecting the sampling microcontroller and the host computer, and using a wireless connection between an optocoupler or Bluetooth to achieve high-voltage isolation between the microcontroller and the host computer.

[0012] Optionally, in one embodiment of this application, the real-time feedback signal processing and control module includes: a signal processing module, which uses the microcontroller or the host computer to process the voltage control signal and the electrophoretic current in real time; and a control signal issuing module, which generates the corresponding voltage control signal after determining that a valid target signal has been detected.

[0013] A second aspect of this application provides a capillary electrophoresis method coupled with discontinuous injection mass spectrometry, comprising the following steps: separating components in a target analyte according to their different electrophoretic mobilities, and ionizing the separated components to form a charged spray; providing the voltage required for capillary electrophoresis based on the requirements of electroosmotic flow and electrophoresis velocity in the capillary; detecting the target analyte or the real-time electroosmotic flow velocity; monitoring and recording the current value during electrophoresis, 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 based on 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 qualitative or quantitative analysis results based on the charged spray.

[0014] Optionally, in one embodiment of this application, separating the components in the target analyte according to their 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; and ionizing the separated components to generate charged ions.

[0015] Optionally, in one embodiment of this application, providing the voltage required for capillary electrophoresis according to the needs of electroosmotic flow and electrophoresis velocity in the capillary includes: the high-voltage power supply body includes a positive polarity power supply and a negative polarity power supply for providing the voltage required for electrophoresis; 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.

[0016] Optionally, in one embodiment of this application, 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, includes: if it is found that the target analyte is about to flow out of the electrophoretic separation-electrospray ionization module, then reducing the voltage, and after the target analyte has completely flowed out, increasing the output voltage until the next target analyte flows out.

[0017] Optionally, in one embodiment of this 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.

[0018] Optionally, in one embodiment of this application, the monitoring and recording of current values ​​during electrophoresis and the correction of the target component migration time using the current values ​​include: converting the current signal into a voltage signal to adjust the resistance value according to the actual current value during 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 a wireless connection between an optocoupler or Bluetooth to achieve high-voltage isolation between the microcontroller and the host computer.

[0019] Optionally, in one embodiment of this application, generating a corresponding voltage control signal based on the target analyte or the real-time electroosmotic flow velocity includes: using the microcontroller 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 has been detected.

[0020] A third aspect of this application provides an electronic device, including: 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 coupled with discontinuous injection mass spectrometry as described in the above embodiments.

[0021] A fourth aspect of this application provides a computer-readable storage medium storing a computer program that, when executed by a processor, implements the capillary electrophoresis method coupled with discontinuous injection mass spectrometry as described above.

[0022] This application's embodiments improve the efficiency of capillary electrophoresis coupled with discontinuous injection mass spectrometry by adjusting the electrophoresis flow rate in real time as needed. It also specifically increases the number of sampling points for the target analyte's electrophoretic peak, improving the sensitivity and stability of quantitative analysis using discontinuous injection mass spectrometry, and enhancing the stability of the target component migration time in capillary electrophoresis. Therefore, it solves the problems in related technologies where continuous capillary electrophoresis, when coupled with a discontinuous injection small-scale mass spectrometry system, typically suffers from reduced accuracy and poor analytical quality due to low mass spectrometry sampling rates. Furthermore, the sampling frequency is severely limited, making it difficult to guarantee the acquisition of mass spectrometry data at the highest point of the chromatographic peak, affecting detection sensitivity and quantitative analysis accuracy, and reducing the sensitivity and stability of quantitative analysis using discontinuous injection mass spectrometry.

[0023] Additional aspects and advantages of this application will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of this application. Attached Figure Description

[0024] The above and / or additional aspects and advantages of this application will become apparent and readily understood from the following description of the embodiments taken in conjunction with the accompanying drawings, wherein:

[0025] Figure 1 This is a schematic diagram of a capillary electrophoresis system coupled with discontinuous injection mass spectrometry according to an embodiment of this application;

[0026] Figure 2 This is a schematic diagram of a capillary electrophoresis system coupled with discontinuous injection mass spectrometry according to an embodiment of this application;

[0027] Figure 3 This is a graph showing the relationship between separation voltage and electroosmotic flow rate during electrophoretic separation, as determined by a capillary electrophoresis system coupled with discontinuous injection mass spectrometry according to an embodiment of this application.

[0028] Figure 4 This is a graph showing the relationship between electrophoretic separation voltage and the number of chromatographic peak sampling points when a capillary electrophoresis system coupled with discontinuous injection mass spectrometry is used to detect a single target analyte according to an embodiment of this application.

[0029] Figure 5 This is a schematic diagram of a capillary electrophoresis system coupled with discontinuous mass spectrometry according to an embodiment of this application, which uses electrophoretic current values ​​to correct the migration time of target components.

[0030] Figure 6 A chromatogram comparison of routine analysis (left) and target peak deceleration analysis (right) of a capillary electrophoresis system coupled with discontinuous injection mass spectrometry according to an embodiment of this application;

[0031] Figure 7A graph showing the stability comparison between decelerated analysis and conventional non-decelerated analysis of a capillary electrophoresis system coupled with discontinuous injection mass spectrometry according to an embodiment of this application.

[0032] Figure 8 A comparison of the detection sensitivity of decelerated analysis and conventional non-decelerated analysis using a capillary electrophoresis system coupled with discontinuous injection mass spectrometry according to an embodiment of this application;

[0033] Figure 9 A chromatogram comparison of conventional analysis (left) and accelerated analysis (right) between target peaks in a capillary electrophoresis system coupled with discontinuous injection mass spectrometry according to an embodiment of this application;

[0034] Figure 10 A chromatogram comparison of conventional analysis (left) and analysis that decelerates the target peak and accelerates the analysis between targets (right) using a capillary electrophoresis system coupled with discontinuous injection mass spectrometry according to an embodiment of this application;

[0035] Figure 11 To analyze the chromatograms and secondary mass spectra of verapamil and phosphatidylcholine (PC 34:1) in blood using a capillary electrophoresis system coupled with discontinuous injection mass spectrometry according to an embodiment of this application;

[0036] Figure 12 This is a comparison chart of the intensity of target fragment ions detected by verapamil in blood analyzed using a capillary electrophoresis system coupled with discontinuous injection mass spectrometry and a nanoESI method according to an embodiment of this application.

[0037] Figure 13 This is a flowchart of a capillary electrophoresis method coupled with discontinuous injection mass spectrometry according to an embodiment of this application;

[0038] Figure 14 This is a schematic diagram of the structure of an electronic device provided according to an embodiment of this application. Detailed Implementation

[0039] The embodiments of this application are described in detail below. Examples of these embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and intended to explain this application, and should not be construed as limiting this application.

[0040] The capillary electrophoresis system and method coupled with discontinuous injection mass spectrometry according to embodiments of this application are described below with reference to the accompanying drawings. In the related technologies mentioned in the background section, continuous capillary electrophoresis, when coupled with a small discontinuous injection mass spectrometry system, often suffers from reduced accuracy and poor analytical quality due to the low mass spectrometry sampling rate. Furthermore, the sampling frequency is greatly limited, making it difficult to guarantee the acquisition of mass spectrometry data at the highest point of the chromatographic peak, affecting the sensitivity of detection and the accuracy of quantitative analysis, thus reducing the sensitivity and stability of quantitative analysis using discontinuous injection mass spectrometry. This application provides a capillary electrophoresis system coupled with discontinuous injection mass spectrometry. In this system, the efficiency of capillary electrophoresis coupled with discontinuous injection mass spectrometry can be improved by adjusting the electrophoresis flow rate in real time as needed. It also specifically increases the number of sampling points for the electrophoretic peaks of the target analyte, improving the sensitivity and stability of quantitative analysis using discontinuous injection mass spectrometry, and enhancing the stability of the migration time of the target component in capillary electrophoresis. This solves the problems in related technologies, such as reduced accuracy and poor analytical quality when continuous capillary electrophoresis is coupled with non-continuous injection small mass spectrometry systems due to low mass spectrometry sampling rate. Furthermore, the sampling frequency is greatly limited, making it difficult to guarantee the acquisition of mass spectrometry data at the highest point of the chromatographic peak, which affects the sensitivity of detection and the accuracy of quantitative analysis, and reduces the sensitivity and stability of quantitative analysis by non-continuous injection mass spectrometry.

[0041] Specifically, Figure 1 This is a schematic diagram of a capillary electrophoresis system coupled with discontinuous sample injection mass spectrometry, provided as an embodiment of this application.

[0042] like Figure 1 As shown, the capillary electrophoresis system 10 coupled with discontinuous injection mass spectrometry includes: an electrophoretic separation-electrospray ionization module 100, a real-time adjustable high-voltage power supply device 200, a target component signal feedback module 300, an electrophoretic 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.

[0043] Specifically, the electrophoretic separation-electrospray ionization module 100 is used to separate the components in the target analyte according to their different electrophoretic mobilities, and to ionize the separated components to form an charged spray.

[0044] In actual implementation, the embodiments of this application can separate the components in the target analyte according to their different electrophoretic mobilities through the electrophoretic 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 in detecting complex samples and the stability of quantitative analysis.

[0045] Optionally, in one embodiment of this application, the electrophoretic separation-electrospray ionization module 100 includes: a sample introduction 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 a capillary electrophoresis-mass spectrometry interface; and a capillary electrophoresis-mass spectrometry interface for ionizing the separated components to generate charged ions.

[0046] It is understood that the electrophoretic separation-electrospray ionization module 100 in this embodiment consists of three parts: a sample introduction device, a separation device, and a capillary electrophoresis-mass spectrometry interface.

[0047] As one possible implementation method, embodiments of this application can inject the target analyte into the separation device via a sample introduction device. The sample introduction device employs an electro-injection method, whereby after transferring the capillary and electrode to the sample vial, a voltage is applied, and the sample is injected into the capillary using electroosmosis. Embodiments of this application can separate the components of the target analyte using the separation device, and then send the separated components to a capillary electrophoresis-mass spectrometry interface. The separation device includes, but is not limited to, capillary and chip-based electrophoresis. Specifically, 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. Approximately 1 cm of the polyimide coating is removed from both ends by ablation or cutting to expose the internal quartz capillary, preventing the polyimide coating from affecting the sample introduction process and interface connection. This embodiment of the application utilizes a capillary electrophoresis-mass spectrometry interface to ionize the separated components, generating charged ions. The capillary electrophoresis-mass spectrometry interface employs a sheath flow type interface, with the main body being a standard four-way connector with an inner diameter of 1 / 16 inch, which connects to the nanoTIP via 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 its tip is drawn using a needle puller. After drawing, its tip opening diameter is approximately 5-10 μm, ensuring normal spraying while preventing tip clogging. The capillary extends into the nanoTIP tip through the four-way connector, and the other two ends of the four-way connector are electrically connected to a 2 kV power supply via the sheath flow liquid.

[0048] This application embodiment achieves the combined use of capillary electrophoresis and discontinuous injection mass spectrometry by changing the capillary electrophoresis working mode. It separates the components in the sample before mass spectrometry analysis, reduces the influence of matrix effect on mass spectrometry analysis, and further reduces the separation voltage when the target analyte flows out, thereby improving the sensitivity of discontinuous injection mass spectrometry in detecting complex samples and the stability of quantitative analysis.

[0049] The real-time adjustable high-voltage power supply device 200 is used to provide the voltage required for capillary electrophoresis according to the needs of electroosmotic flow and electrophoresis velocity in the capillary.

[0050] In actual implementation, the embodiments of this application can provide the voltage required for capillary electrophoresis according to the needs of electroosmotic flow and electrophoresis speed in the capillary through the real-time adjustable high-voltage power supply device 200. By using the on-demand variable speed capillary electrophoresis mode, the separation voltage is increased after the target analyte flows out, which shortens the blank analysis time between each target analyte and improves the analysis efficiency when capillary electrophoresis is coupled with discontinuous injection mass spectrometry.

[0051] Optionally, in one embodiment of this application, the real-time adjustable high-voltage power supply device 200 includes: a high-voltage power supply body, which includes a positive polarity power supply and a negative polarity power supply for providing the voltage required for electrophoresis; and 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.

[0052] Specifically, the real-time adjustable high-voltage power supply device 200 in this embodiment consists of two parts: a high-voltage power supply and a control program. The high-voltage power supply outputs a voltage of 0-50kV and has current measurement and display functions. It is connected to a computer via an RS232 interface. The control program on the computer can perform timing control on the high-voltage power supply output voltage and receive trigger signals from sensors. The high-voltage power supply includes a positive polarity power supply and a negative polarity power supply, providing the voltage required for electrophoresis. The control system in this embodiment can adjust the output voltage of the high-voltage power supply through timing programming or adjust the voltage according to the trigger signal from the target component signal feedback module. This further enables on-demand variable-speed capillary electrophoresis mode, increasing the separation voltage after the target analyte flows out, shortening the blank analysis time between different target analytes, and improving the analytical efficiency when capillary electrophoresis is coupled with discontinuous injection mass spectrometry.

[0053] Optionally, in one embodiment of this application, the control system is further configured to reduce the voltage when it detects that the target analyte is about to flow out of the electrophoretic separation-electrospray ionization module, and increase the output voltage after the target analyte has completely flowed out, until the next target analyte flows out.

[0054] As one possible implementation, embodiments of this application can reduce the voltage when the target analyte is detected to be about to flow out of the electrophoretic 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 analytical efficiency when capillary electrophoresis is coupled with discontinuous injection mass spectrometry.

[0055] The target component signal feedback module 300 is used to detect the target analyte or the real-time electroosmotic flow rate.

[0056] In actual implementation, the embodiments of this application can detect the target analyte or the real-time electroosmotic flow rate 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 out time, increasing the number of sampling points for the target analyte by the non-continuous injection mass spectrometer, and improving the stability of quantitative analysis.

[0057] Optionally, in one embodiment of this 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.

[0058] 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. Different sensors can be used to detect the migration time and real-time electroosmotic flow rate of the target analyte according to its properties. 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, realizing automatic control of the output voltage throughout the process, simplifying the operation process, improving analysis efficiency, and further reducing the separation voltage during target analyte flow in variable-speed capillary electrophoresis, extending the analyte flow time, increasing the number of sampling points for the target analyte in discontinuous injection mass spectrometry, and improving the stability of quantitative analysis.

[0059] The electrophoresis current measurement and migration time correction module 400 is used to monitor and record the current value during electrophoresis, and to use the current value to correct the migration time of the target component to obtain the migration index.

[0060] In actual implementation, the embodiments of this application can monitor and record the current value during electrophoresis 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, the migration index calculated in real time can be used to determine whether the target analyte has started to flow out of the separation device, provide a trigger signal to the signal processing and control module, control the output voltage of the high voltage power supply, and thus raise the separation voltage again after the previous target analyte flows out in the variable-speed capillary electrophoresis, shorten the blank analysis time between each target component, and improve the efficiency of capillary electrophoresis coupled with discontinuous sample injection mass spectrometry.

[0061] Optionally, in one embodiment of this application, the electrophoretic current measurement and migration time correction module 400 includes: a sampling resistor for converting the current signal into a voltage signal to adjust the resistance value according to the actual current value during operation; a sampling microcontroller for converting the voltage signal into a digital signal and transmitting the digital signal to a host computer; and a communication interface for connecting the sampling microcontroller and the host computer, and using a wireless connection between an optocoupler or Bluetooth to achieve high-voltage isolation between the microcontroller and the host computer.

[0062] In actual implementation, this embodiment can convert the current signal into a voltage signal through a sampling resistor, and adjust the resistance value according to the actual current value during operation; this embodiment can convert the voltage signal into a digital signal through a sampling microcontroller, and transmit the digital signal to the host computer; this embodiment can connect the sampling microcontroller and the host computer through a communication interface, and use a wireless connection between an optical coupler or Bluetooth to achieve high-voltage isolation between the microcontroller and the host computer, thereby further increasing the separation voltage again after the previous target analyte flows out in the variable-speed capillary electrophoresis, shortening the blank analysis time between each target component, and improving the efficiency of capillary electrophoresis coupled with discontinuous injection mass spectrometry.

[0063] The real-time feedback signal processing and control module 500 is used to generate corresponding voltage control signals based on the target analyte or real-time electroosmotic flow velocity.

[0064] In actual implementation, the embodiments of this application can generate a corresponding voltage control signal based on the target analyte or real-time electroosmotic flow rate 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 capillary electrophoresis migration time through real-time current monitoring.

[0065] Optionally, in one embodiment of this application, the real-time feedback signal processing and control module 500 includes: a signal processing module, which uses a microcontroller or a host computer to process the voltage control signal and the electrophoretic current in real time; and a control signal issuing module, which generates a corresponding voltage control signal after determining that a valid target signal has been detected.

[0066] In some embodiments, a microcontroller or host computer can be used to process the voltage control signal and electrophoresis current in real time, providing support for the subsequent generation of the corresponding voltage control signal. In the embodiments of this application, after the control signal issuing module determines that a valid target signal has been detected, a corresponding voltage control signal is generated. 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 capillary electrophoresis migration time by real-time current monitoring.

[0067] 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 spraying.

[0068] In practical implementation, the embodiments of this application can detect the mass-to-charge ratio and intensity of the target analyte using a discontinuous injection mass spectrometry system 600, and obtain qualitative or quantitative analysis results based on charged spraying, thereby improving the sensitivity and stability of quantitative analysis using discontinuous injection mass spectrometry. The discontinuous injection mass spectrometer in this embodiment is a small ion trap mass spectrometer using a discontinuous atmospheric pressure interface (DAPI). A solenoid valve can be used as the 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 changes in vacuum system pressure, and the fastest sampling frequency can reach 2-3 seconds per cycle.

[0069] Specifically, in combination Figures 2 to 12 As shown, a specific embodiment is used to illustrate in detail the working principle of the capillary electrophoresis system coupled with discontinuous sample injection mass spectrometry in this application.

[0070] like Figure 2 As shown, the embodiments of this application include: an electrophoretic separation-electrospray ionization module 100, a real-time adjustable high-voltage power supply device 200, a target component signal feedback module 300, an electrophoretic current measurement and migration time correction module 400, a real-time feedback signal processing and control module 500, and a discontinuous sample injection mass spectrometry system 600.

[0071] In actual operation, the electrophoresis separation-electrospray ionization module 100 consists of three parts: a sample introduction device, a separation device, and a capillary electrophoresis-mass spectrometry interface. The sample introduction device uses an electroinjection method. After transferring the capillary and electrode to the sample vial, a voltage is applied, and the sample is injected into the capillary using 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. Approximately 1 cm of the polyimide coating is removed from both ends by ablation or cutting to expose the internal quartz capillary, preventing the polyimide coating from affecting the sample introduction process and interface connection. The capillary electrophoresis-mass spectrometry interface uses 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 via 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 drawn using a needle-pulling device, resulting in an opening diameter of approximately 5-10 μm at the tip. This design ensures proper spraying while preventing tip clogging. A capillary tube extends into the nanoTIP tip via a four-way connector, and the other two ends of the four-way connector are electrically connected to a 2 kV power supply via sheath fluid.

[0072] The real-time adjustable high-voltage power supply device 200 consists of two parts: a high-voltage power supply and a control program. The high-voltage power supply outputs a voltage of 0-50kV and has current measurement and display functions. The high-voltage power supply is connected to a computer via an RS232 interface. The control program on the computer can perform timing control on the output voltage of the high-voltage power supply and can receive trigger signals from sensors.

[0073] The target component signal feedback module 300 can use different sensors to detect the migration time and real-time electroosmotic flow rate of the target analyte, depending on its properties, such as ultraviolet detectors, fluorescence detectors, electrochemical detectors, and conductivity detectors. 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, which then controls the high-voltage power supply to change the output voltage.

[0074] The electrophoresis current measurement and migration time correction module 400 can measure the current value during the electrophoresis process and correct the migration time of the target component based on the change in the current value, thus obtaining a migration index with better reproducibility. Additionally, it can determine whether the target analyte has begun to flow out of the separation device based on the real-time calculated migration index, providing a trigger signal to the signal processing and control module to control the output voltage of the high-voltage power supply.

[0075] The real-time feedback signal processing and control module 500 generates a corresponding voltage control signal based on the target analyte or the real-time electroosmotic flow velocity. The voltage control signal and electrophoretic current can be processed in real time using a microcontroller or a host computer. It can generate a corresponding voltage control signal after determining that a valid target signal has been detected.

[0076] In the discontinuous injection mass spectrometry system 600, the discontinuous injection mass spectrometer is a small ion trap mass spectrometer that uses a discontinuous atmospheric pressure interface (DAPI). It uses a solenoid valve as the 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. This mode is limited by the pressure changes of the vacuum system, and the sampling frequency can reach up to 2-3 seconds / sample.

[0077] The working principle of the embodiments of this application is as follows: Figure 3 and Figure 4 shown, specifically, Figure 3 The graph shows the relationship between electrophoretic separation voltage and electroosmotic flow rate. It has been determined that during capillary electrophoresis, the electroosmotic flow rate is directly proportional to the separation voltage at both ends of the capillary. Therefore, in this embodiment, the electroosmotic flow rate and electrophoresis rate can be controlled in real time by changing the separation voltage at both ends of the capillary. Figure 4 The graph shows the relationship between electrophoretic separation voltage and the number of sampling points for a single target analyte chromatographic peak. When detecting a single target analyte, reducing the voltage decreases the electroosmotic flow and electrophoresis rate, thereby increasing the number of sampling points on the chromatographic peak of the single target analyte. This greatly helps to improve the sensitivity and stability of the analysis.

[0078] The method of using this application is as follows:

[0079] Example 1: Increasing the number of target peak sampling points by slowing down the process to improve analysis sensitivity and stability.

[0080] (1) Transfer the high voltage power supply electrode and the capillary injection end to the container containing the sample to be tested. Apply 20kV high voltage to the sample vial through the electrode. The sample is injected into the capillary under the action of electroosmosis. After 7s, disconnect the high voltage to complete the injection.

[0081] (2) Transfer the high voltage power supply electrode and capillary injection end to a container containing buffer solution. Apply 20kV high voltage to the buffer solution via the electrode. Under the combined action of 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 electric field, the components of the sample are separated.

[0082] (3) During electrophoresis, the current measurement module monitors the changes in the electrophoretic current in real time and calculates the migration index, such as... Figure 5 As shown, the migration time of the target analyte is corrected, and the current measurement module communicates with the host computer via serial port through an optical coupler or Bluetooth.

[0083] (4) When the target analyte migrates to the electrophoresis-mass spectrometry interface, the sensor detects the outflow of the target analyte and generates a trigger signal that is 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 that is transmitted to the signal processing and control module.

[0084] (5) Figure 6 As shown, after receiving the trigger signal, the control program reduces the output voltage of the high-voltage power supply to 10kV, which slows down the migration speed of the target analyte. At the same time, the discontinuous injection mass spectrometer starts mass spectrometry analysis at a frequency of 2-3 seconds / time. The discontinuous injection mass spectrometer has more time to sample the target analyte, increasing the number of sampling points for the target analyte.

[0085] like Figure 7 and Figure 8 As shown, the target peak deceleration analysis mode significantly improves the stability of quantitative analysis and the sensitivity of detection.

[0086] Example 2: Improving analysis efficiency by reducing waiting time when analyzing two or more targets through acceleration methods.

[0087] Besides single-analyte analysis, specific applications such as drug monitoring and metabolite screening often involve the detection of multiple target analytes. However, in conventional chromatographic analysis, there may be a long blank analysis time between target analytes, resulting in wasted time and reduced analytical efficiency. In this embodiment, the electrophoresis speed is increased during the blank analysis time, solving the problem of wasted blank time and improving the speed of multi-target analyte analysis.

[0088] The injection operation was performed using a method similar to that in Example 1, except that, as Figure 8 As shown, the separation voltage is initially kept constant at 20kV. After the previous target analyte has completely flowed out, the control program increases the high-voltage power supply output voltage to 30kV, thereby increasing the electroosmotic flow rate and electrophoresis rate until the next target analyte reaches the electrophoresis-mass spectrometry interface. This process is repeated for more than two target analytes. This method reduces the blank analysis time between two adjacent target analytes, improving the analytical efficiency of the capillary electrophoresis-mass spectrometry system.

[0089] like Figure 9 and Figure 10 As shown, when performing multi-target analysis, the operating modes of Example 1 and Example 2 can be combined. The separation voltage is reduced when the analyte flows out, while the separation voltage is increased during the blank analysis time between two adjacent target analytes. This can improve the stability and sensitivity of quantitative analysis, as well as the analysis efficiency.

[0090] Example 3: Rapid detection of drugs and metabolites in blood using a capillary electrophoresis-mass spectrometry interface system

[0091] (1) Drop 30 μL of blood containing verapamil onto filter paper and dry it quickly with a hair dryer or oven to form dried blood spots.

[0092] (2) Use a punch to cut the dried blood spot off the filter paper, immerse the dried blood spot in a centrifuge tube containing 200 μL of buffer, and let it stand for 3 minutes.

[0093] (3) The liquid in the centrifuge tube was injected and separated by electrophoresis in a manner similar to that in Example 2. The separated verapamil and phosphatidylcholine (PC 34:1) were then analyzed by secondary mass spectrometry to obtain the chromatogram and secondary mass spectrum as shown below. Figure 11 As shown.

[0094] (4) This method can significantly improve the detection sensitivity of mass spectrometry for drugs or metabolites in complex matrices. For example... Figure 12 As shown, nanoESI and this method were used to perform mass spectrometry detection on the dried blood spot extract, with verapamil added to the blood at a concentration of 10 ng / mL. This method can increase the intensity of target fragment ions by about ten times. Furthermore, field-enhanced injection can achieve online enrichment of the target analyte, further improving the sensitivity of the method. Specifically, the buffer solution used to soak the dried blood spots is replaced with a buffer solution with a lower salt concentration (e.g., diluted 100 times), and the injection time is increased during injection. Figure 12 As shown, the intensity of the target fragment ions can be further increased by 3-4 times.

[0095] The capillary electrophoresis system coupled with discontinuous injection mass spectrometry proposed in the embodiments of this application improves the efficiency of capillary electrophoresis and discontinuous injection mass spectrometry analysis by changing the capillary electrophoresis working mode, and increases the number of sampling points for the electrophoretic chromatographic peaks of the target analyte, thereby improving the sensitivity and stability of quantitative analysis by discontinuous injection mass spectrometry. This solves the problems in related technologies where continuous capillary electrophoresis technology, when coupled with discontinuous injection small-scale mass spectrometry systems, often suffers from reduced accuracy and poor analytical quality due to low mass spectrometry sampling rates. Furthermore, the sampling frequency is greatly limited, making it difficult to guarantee the acquisition of mass spectrometry data at the highest point of the chromatographic peak, 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.

[0096] Next, referring to the accompanying drawings, a capillary electrophoresis method coupled with discontinuous injection mass spectrometry proposed according to embodiments of this application is described.

[0097] Figure 13 This is a flowchart of a capillary electrophoresis method coupled with discontinuous injection mass spectrometry according to an embodiment of this application.

[0098] like Figure 13 As shown, this capillary electrophoresis method coupled with discontinuous injection mass spectrometry includes the following steps:

[0099] In step S1301, the components in the target analyte are separated according to their different electrophoretic mobilities, and the separated components are ionized to form an charged spray.

[0100] In step S1302, the voltage required for capillary electrophoresis is provided according to the needs of electroosmotic flow and electrophoresis velocity in the capillary.

[0101] In step S1303, the target analyte or real-time electroosmotic flow rate is detected.

[0102] In step S1304, the current value during electrophoresis is monitored and recorded, and the migration time of the target component is corrected using the current value to obtain the migration index.

[0103] In step S1305, a corresponding voltage control signal is generated based on the target analyte or the real-time electroosmotic flow rate.

[0104] In step S1306, the mass-to-charge ratio and intensity of the target analyte are detected, and qualitative or quantitative analysis results are obtained based on charged spraying.

[0105] Optionally, in one embodiment of this application, separating the components in the target analyte according to their 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; and ionizing the separated components to generate charged ions.

[0106] Optionally, in one embodiment of this application, providing the voltage required for capillary electrophoresis according to the needs of electroosmotic flow and electrophoresis velocity in the capillary includes: a high-voltage power supply body including a positive polarity power supply and a negative polarity power supply for providing the voltage required for electrophoresis; 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.

[0107] Optionally, in one embodiment of this application, adjusting the output voltage of the high-voltage power supply body by timing programming, or adjusting the voltage according to the trigger signal of the target component signal feedback module, includes: if it is found that the target analyte is about to flow out of the electrophoretic separation-electrospray ionization module, reducing the voltage, and increasing the output voltage after the target analyte has completely flowed out, until the next target analyte flows out.

[0108] Optionally, in one embodiment of this 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.

[0109] Optionally, in one embodiment of this application, monitoring and recording the current value during electrophoresis and using the current value to correct the migration time of the target component includes: converting the current signal into a voltage signal to adjust the resistance value according to the actual current value during 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 a wireless connection between an optocoupler or Bluetooth to achieve high-voltage isolation between the microcontroller and the host computer.

[0110] Optionally, in one embodiment of this application, generating a corresponding voltage control signal based on the target analyte or real-time electroosmotic flow rate includes: using a microcontroller or host computer to process the voltage control signal and electrophoretic current in real time; and generating the corresponding voltage control signal after determining that a valid target signal has been detected.

[0111] It should be noted that the foregoing explanation of the capillary electrophoresis system coupled with discontinuous injection mass spectrometry also applies to the capillary electrophoresis method coupled with discontinuous injection mass spectrometry in this embodiment, and will not be repeated here.

[0112] The capillary electrophoresis method coupled with discontinuous injection mass spectrometry proposed in the embodiments of this application improves the efficiency of capillary electrophoresis analysis coupled with discontinuous injection mass spectrometry by changing the capillary electrophoresis working mode. It also increases the number of sampling points for the electrophoretic peaks of the target analyte, thereby improving the sensitivity and stability of quantitative analysis using discontinuous injection mass spectrometry. This solves the problems in related technologies where continuous capillary electrophoresis, when coupled with a small discontinuous injection mass spectrometry system, typically suffers from reduced accuracy and poor analytical quality due to low mass spectrometry sampling rates. Furthermore, the sampling frequency is greatly limited, making it difficult to guarantee the acquisition of mass spectrometry data at the highest point of the chromatographic peak, thus affecting the detection sensitivity and accuracy of quantitative analysis, and reducing the sensitivity and stability of quantitative analysis using discontinuous injection mass spectrometry.

[0113] Figure 14 A schematic diagram of the structure of an electronic device provided in an embodiment of this application. The electronic device may include:

[0114] The memory 1401, the processor 1402, and the computer program stored on the memory 1401 and executable on the processor 1402.

[0115] When the processor 1402 executes the program, it implements the capillary electrophoresis method coupled with discontinuous sample injection mass spectrometry provided in the above embodiments.

[0116] Furthermore, electronic devices also include:

[0117] Communication interface 1403 is used for communication between memory 1401 and processor 1402.

[0118] The memory 1401 is used to store computer programs that can run on the processor 1402.

[0119] The memory 1401 may include high-speed RAM memory, and may also include non-volatile memory, such as at least one disk storage device.

[0120] If the memory 1401, processor 1402, and communication interface 1403 are implemented independently, then the communication interface 1403, memory 1401, and processor 1402 can be interconnected via a bus to complete communication between them. The bus can be an Industry Standard Architecture (ISA) bus, a Peripheral Component Interconnect (PCI) bus, or an Extended Industry Standard Architecture (EISA) bus, etc. Buses can be divided into address buses, data buses, control buses, etc. For ease of representation, Figure 14 The bus is represented by a single thick line, but this does not mean that there is only one bus or one type of bus.

[0121] Optionally, in a specific implementation, if the memory 1401, processor 1402, and communication interface 1403 are integrated on a single chip, then the memory 1401, processor 1402, and communication interface 1403 can communicate with each other through an internal interface.

[0122] 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 this application.

[0123] This application also provides a computer-readable storage medium storing a computer program that, when executed by a processor, implements the capillary electrophoresis method coupled with discontinuous injection mass spectrometry as described above.

[0124] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0125] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this application, "N" means at least two, such as two, three, etc., unless otherwise explicitly specified.

[0126] Any process or method described in the flowchart or otherwise herein can be understood as representing a module, segment, or portion of code comprising one or N executable instructions for implementing custom logic functions or processes, and the scope of the preferred embodiments of this application includes additional implementations in which functions may be performed not in the order shown or discussed, including substantially simultaneously or in reverse order depending on the functions involved, as should be understood by those skilled in the art to which embodiments of this application pertain.

[0127] The logic and / or steps represented in the flowchart or otherwise described herein, for example, can be considered as a sequenced list of executable instructions for implementing 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 (such as a computer-based system, a processor-included system, or other system that can fetch and execute instructions from, an instruction execution system, apparatus, or device). For the purposes of this specification, "computer-readable medium" can be any means that can contain, store, communicate, propagate, or transmit programs 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: an electrical connection having one or more wires (electronic device), a portable computer disk drive (magnetic device), random access memory (RAM), read-only memory (ROM), erasable and editable read-only memory (EPROM or flash memory), fiber optic devices, and portable optical disc read-only memory (CDROM). Alternatively, the computer-readable medium may be paper or other suitable media on which the program can be printed, since the program can be obtained electronically by optically scanning the paper or other medium, followed by editing, interpreting, or otherwise processing as necessary, and then stored in a computer memory.

[0128] It should be understood that the various parts of this application can be implemented using hardware, software, firmware, or a combination thereof. In the above embodiments, the N steps or methods can be implemented using software or firmware stored in memory and executed by a suitable instruction execution system. If implemented in hardware, as in another embodiment, it can be implemented using any one or a combination of the following techniques known in the art: discrete logic circuits having logic gates for implementing logical functions on data signals, application-specific integrated circuits (ASICs) having suitable combinational logic gates, programmable gate arrays (PGAs), field-programmable gate arrays (FPGAs), etc.

[0129] Those skilled in the art will understand that all or part of the steps of the methods described in the above embodiments can be implemented by a program instructing related hardware. The program can be stored in a computer-readable storage medium, and when executed, it includes one or a combination of the steps of the method embodiments.

[0130] Furthermore, the functional units in the various embodiments of this application can be integrated into a processing module, or each unit can exist physically separately, or two or more units can be integrated into a module. The integrated module can be implemented in hardware or as a software functional module. If the integrated module is implemented as a software functional module and sold or used as an independent product, it can also be stored in a computer-readable storage medium.

[0131] The storage medium mentioned above can be a read-only memory, a disk, or an optical disk, etc. Although embodiments of this application have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting this application. Those skilled in the art can make changes, modifications, substitutions, and variations to the above embodiments within the scope of this application.

Claims

1. A capillary electrophoresis system coupled with discontinuous injection mass spectrometry, 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 to ionize the separated components to form an charged spray; A real-time adjustable high-voltage power supply device is used to provide the voltage required for capillary electrophoresis according to the needs of electroosmotic flow and electrophoresis velocity in the capillary. The target component signal feedback module is used to detect the target analyte or the real-time electroosmotic flow rate; The electrophoresis current measurement and migration time correction module is used to monitor and record the current value during electrophoresis, and to 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 is used to generate a corresponding voltage control signal based on the target analyte or the real-time electroosmotic flow velocity. as well as A discontinuous injection mass spectrometry system is used to detect the mass-to-charge ratio and intensity of the target analyte, and to obtain qualitative or quantitative analysis results based on the charged spray. The real-time adjustable high-voltage power supply device includes: 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; The 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. The control system is further used to reduce the voltage when it detects that the target analyte is about to flow out of the electrophoretic separation-electrospray ionization module, and to increase the output voltage after the target analyte has completely flowed out, until the next target analyte flows out. During the flow of the target analyte through the electrophoretic separation-electrospray ionization module, the number of target peak sampling points is increased by deceleration, and the waiting time for analyzing two or more targets is reduced by acceleration.

2. The system according to claim 1, characterized in that, The electrophoretic separation-electrospray ionization module includes: A sample introduction device is 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 into a capillary electrophoresis-mass spectrometry interface. The capillary electrophoresis-mass spectrometry interface is used to ionize the separated components to generate charged ions.

3. The system 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.

4. The system according to claim 1, characterized in that, The electrophoretic current measurement and migration time correction module includes: A sampling resistor is used to convert a current signal into a voltage signal so that its resistance value can be adjusted according to the actual current value during operation. A sampling microcontroller is used to convert the voltage signal into a digital signal and transmit the digital signal to a host computer. A communication interface is provided for connecting the sampling microcontroller and the host computer, and high-voltage isolation between the microcontroller and the host computer is achieved through a wireless connection via an optical coupler or Bluetooth.

5. The system according to claim 4, characterized in that, The real-time feedback signal processing and control module includes: The signal processing module uses the microcontroller 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 has been detected.

6. A capillary electrophoresis method coupled with discontinuous injection mass spectrometry, characterized in that, Includes the following steps: The components in the target analyte are separated according to their different electrophoretic mobilities, and the separated components are ionized to form an charged spray. Provide the voltage required for capillary electrophoresis based on the needs of electroosmotic flow and electrophoresis velocity in the capillary; Detect target analytes or real-time electroosmotic flow velocity; The current value during electrophoresis is monitored and recorded, and the migration time of the target component is corrected using the current value to obtain the migration index; A corresponding voltage control signal is generated based on 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 qualitative or quantitative analysis results are obtained based on the charged spray. The real-time adjustable high-voltage power supply device includes: 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; The 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. The control system is further used to reduce the voltage when it detects that the target analyte is about to flow out of the electrophoretic separation-electrospray ionization module, and to increase the output voltage after the target analyte has completely flowed out, until the next target analyte flows out. During the flow of the target analyte through the electrophoretic separation-electrospray ionization module, the number of target peak sampling points is increased by deceleration, and the waiting time for analyzing two or more targets is reduced by acceleration.

7. An electronic device, characterized in that, include: The memory, the processor, and the computer program stored in the memory and executable on the processor, the processor executing the program to implement the capillary electrophoresis method coupled with discontinuous injection mass spectrometry as described in claim 6.

8. A computer-readable storage medium having a computer program stored thereon, characterized in that, The program is executed by the processor to implement the capillary electrophoresis method coupled with discontinuous injection mass spectrometry as described in claim 6.

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