Plasma ion source device having digital energy level control function and controlled ionization method

Abstract

A plasma ion source device having a digital energy level control function and a controlled ionization method. A plasma main module and a sample injector (11) face a plasma beam region, and a numerical control module is located beside the plasma main module and controls the plasma main module. The method comprises: adding a prepared solution or a gas sample into the sample injector (11) and then spraying out a gas-phase substance thereby; and inputting a control waveform into a plasma torch tube (4) by an arbitrary wave generator control board (5) to eject plasma to the plasma beam region, so that the gas-phase substance collides with electrons / ions in plasma to form gas-phase ions, thereby carrying out mass spectrometry detection. By using an arbitrary waveform controller to input the energy level of the plasma, the energy is flexible and controllable, and energy-dimensional scanning ionization is completed within seconds, greatly improving the detection throughput, and accelerating waveform scanning to match liquid chromatography retention time and mass spectrometry scanning time, achieving coverage analysis of a wide ionization range.

Description

Digital energy level controlled plasma ion source device and controlled ionization method Technical Field

[0001] The present invention relates to an atmospheric pressure ionization mass spectrometry technology, in particular to a plasma ion source controlled by digital energy levels and a controlled ionization method. Background Art

[0002] Atmospheric pressure ionization mass spectrometry (AMS) allows the ionization of untreated or minimally modified samples at atmospheric pressure. Over the past two decades, dozens of new AMS techniques and their variants have been developed, using various means such as electrospray, laser ablation, plasma, thermal desorption, and vibrational excitation to directly detect a variety of compounds. However, due to the wide variation in the chemical properties of analytes, it is difficult for a single AMS technique to cover all samples. For example, AMS techniques based on the electrospray mechanism are generally used for non-volatile polar compounds in a large mass range, while AMS techniques based on the atmospheric pressure chemical ionization (APCI) mechanism can characterize non-polar or low-polarity compounds.

[0003] To expand the range of detectable analyte molecules, researchers have combined different ionization techniques in a single device. By adjusting parameters, single and combined ionization modes can be obtained, enabling the simultaneous detection of polar and non-polar compounds. However, the combination and conversion of different ionization techniques is often complex, so the development of energy-flexible and controllable AMS technology to achieve coverage analysis of a wide ionization range is an important issue for many analytical chemists. Summary of the Invention

[0004] In order to solve the problems existing in the background technology, the present invention proposes a plasma ion source device with digital energy level control and a digital graded control ionization method, which uses an arbitrary waveform controller to input the plasma power supply to realize digital regulation of the plasma energy power, and a fast digital function waveform to perform energy control, greatly improving the detection flux, and completing the scanning ionization of the energy dimension within the time of s level; when using liquid chromatography-mass spectrometry, all different samples in a single peak package are analyzed, solving the problem of the coverage range of molecular species detected when using commercial ion source liquid chromatography-mass spectrometry, and realizing high-throughput full analysis of atmospheric pressure ion source.

[0005] The technical solutions of the present invention are as follows:

[0006] 1. A digital energy level controlled plasma ion source device:

[0007] The device includes a plasma beam area, an injector, a plasma main module, a numerical control module and a support and adjustment module; the injector, the numerical control module and the plasma main module are installed on the support and adjustment module, the plasma main module and the injector are arranged toward the plasma beam area, and the numerical control module is located beside the plasma main module. The numerical control module is electrically connected to the plasma main module through a signal transmission line and controls the plasma main module.

[0008] The support and adjustment module includes a mass spectrometry connector, a base, a three-axis movable platform and a plasma support plate; a mass spectrometry connector is fixed to the upper surface of one end of the base by bolts, a normal-pressure mass spectrometry inlet is provided on one side of the mass spectrometry connector, the normal-pressure mass spectrometry inlet faces the plasma beam area, and the normal-pressure mass spectrometry inlet is located directly above the base; a three-axis movable platform is installed on the upper surface of the base, a plasma support plate is fixedly connected to the three-axis movable platform, a plasma main module and an injector are installed on the plasma support plate by bolts, the injector is horizontally movably mounted on the plasma support plate through a slider bracket, the three-axis movable platform is used to drive the plasma main module and the injector to move three-dimensionally, the slider bracket and the plasma support plate are clamped by two slot structures, the slider bracket can slide along the slot direction to adjust the front and rear position, thereby ensuring that the injection position of the injector mounted on the slider bracket is appropriate, and the target compound is atomized into spray droplets or gaseous samples through the injector.

[0009] The plasma main module includes a plasma torch, a circuit interface and a gas path interface; the plasma torch is electrically connected to a numerical control module, one end of the plasma torch is connected to an external plasma working gas source via the gas path interface, the gas path interface is used to add plasma working gas, the other end of the plasma torch is provided with a plasma beam outlet, the plasma beam outlet faces the plasma beam area, the plasma main module is activated by the microwave energy generated by the numerical control module, and argon gas needs to be added for stability during operation, and the plasma torch is connected to a numerical control power supply via the circuit interface.

[0010] The numerical control module includes an arbitrary wave generator control board and a microwave power supply box; the arbitrary wave generator control board is connected to the plasma torch tube through a signal transmission line, and the microwave power supply box is electrically connected to the arbitrary wave generator control board through a signal transmission line. The arbitrary wave generator control board is used to quickly control plasma energy.

[0011] 2. A digital graded ionization control method for a digital energy level controlled plasma ion source device comprises the following steps:

[0012] 1) Prepare the chemical solution sample or gas sample to be tested;

[0013] 2) connecting the plasma ion source device to the mass spectrometer, connecting and opening the circuit interface and the gas path interface, setting and controlling the waveform energy through the arbitrary wave generator control panel, and the arbitrary wave generator control panel generating the ionization energy range of the desired waveform energy level for the target analyte and selecting the corresponding waveform signal;

[0014] 3) Open the injector and add the prepared chemical solution sample or gas sample into the injector;

[0015] 4) The gaseous material is ejected from the injector, and the arbitrary wave generator control board simultaneously inputs a control waveform into the plasma torch. The plasma main power of the plasma torch is controlled by a digitally controlled power supply, which adjusts the gas path. The plasma torch activates the plasma, irradiating the plasma beam from the plasma beam outlet to the plasma beam area. The gaseous material collides with the electrons / ions in the plasma, removing the solvent and forming gaseous ions. Due to the digital power control, the scanned ionization energy varies, allowing samples of different forms to be fully charged.

[0016] 5) The obtained gas phase ions enter the mass spectrometer through the atmospheric pressure mass spectrometer inlet for mass spectrometry detection.

[0017] In the step 4), the electrons / ions include metastable high-energy electrons, primary gas-phase ions and high-energy positive ions.

[0018] In the step 3), when the chemical solution sample is added to the injector, the chemical solution sample is atomized into spray droplets as a gas phase substance; when the gas sample is added to the injector, the gaseous sample is directly used as a gas phase substance.

[0019] In step 1), the solvent of the solution includes a mixture of one or more of methanol, water, and acetonitrile.

[0020] In the step 2), the waveform energy level set by the arbitrary wave generator control board can achieve rapid adjustment of the plasma energy from 100W to 200W within 0.5-5s.

[0021] In step 4), when the chemical solution sample or the gas sample to be tested is a compound requiring soft ionization, the plasma main power of the plasma torch is adjusted to be lower than 140W, and the compound requiring soft ionization includes peptides, drugs or amino acids;

[0022] When the chemical solution sample or the gas sample to be tested is a compound requiring hard ionization, the plasma main power of the plasma torch is adjusted to 140W-160W, and the compound requiring hard ionization includes polycyclic aromatic hydrocarbons, halogenated hydrocarbons or ferrocene;

[0023] When the chemical solution sample or the gas sample to be tested is a substance requiring high energy for desorption, the plasma main power of the plasma torch is adjusted to 160W-200W, and the substance requiring high energy for desorption includes metal elements, inorganic lead or inorganic mercury.

[0024] The sample injector can be connected to the liquid phase to realize plasma liquid chromatography-mass spectrometry of digital energy.

[0025] In the step 5), the detection mode of the ion detector used in the mass spectrometer analysis is positive ion mode or negative ion mode.

[0026] In the step 5), the ion detector used in the mass spectrometer analysis includes an ion trap, an orbital trap or a time-of-flight mass spectrometer, and the single scan time thereof shall not exceed 500 ms.

[0027] The beneficial effects of the present invention are:

[0028] The present invention uses an arbitrary waveform controller to input the energy level of the plasma. The energy is flexible and controllable, and scanning ionization in the energy dimension is completed within the time of s level, which greatly improves the detection flux and speeds up the waveform scanning to match the liquid phase peak time and the mass spectrometry scanning time. When using liquid chromatography-mass spectrometry, all different samples in a single peak package can be analyzed, realizing coverage analysis of a wide ionization range.

[0029] It has strong innovative and practical value and is suitable for mass spectrometry analysis in various fields such as laboratories, industrial production, medical research, and public security management. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] FIG1 is a schematic diagram of a plasma ion source device with digital energy level control.

[0031] Figure 2 is an energy diagram of a digitized triangle wave as an input control function.

[0032] FIG3 is a mass spectrum of L-tyrosine measured under digital triangle wave energy control.

[0033] FIG4 is the mass spectrum of perylene measured under digital triangle wave energy control.

[0034] FIG5 is a mass spectrum of divalent lead measured under digital triangle wave energy control.

[0035] FIG6 is a graph showing the extracted ion current of divalent lead measured under digital triangle wave energy control.

[0036] FIG7 is the extracted ion current of perylene measured under digital triangle wave energy control.

[0037] FIG8 is an extracted ion chromatogram of L-tyrosine measured under digital triangle wave energy control.

[0038] FIG9 is a mass spectrum of divalent lead and reserpine measured under digital rectangular energy rapid scanning.

[0039] Figure 10 shows the extracted ion chromatogram of the two substances superimposed under 1 Hz rectangular wave conditions.

[0040] Figure 11 shows the superimposed extracted ion chromatogram of the two substances under 0.5 Hz rectangular wave conditions.

[0041] Figure 12 shows the superimposed extracted ion chromatogram of the two substances under 0.2 Hz rectangular wave conditions.

[0042] FIG13 is an extracted ion chromatogram of two substances superimposed under 0.2 Hz sawtooth wave conditions.

[0043] FIG14 is an extracted ion chromatogram of two substances superimposed under 0.2 Hz triangle wave conditions.

[0044] FIG15 is an extracted ion chromatogram of reserpine, perylene, L-Phe-L-Phe, cortisone, and triphenyltin hydride at different retention times in the liquid phase when coupled with the liquid phase.

[0045] Figure 16 shows the superimposed mass spectra of spiked serum (including benzo[a]pyrene, anthracene, sulphos, sulpiride, midecamycin, prochlorperazine, triphenyltin chloride, reserpine, and divalent lead) after energy scanning ionization.

[0046] FIG17 shows that different analytes (benzo[a]pyrene, anthracene, sulpiride, sulpiride, midecamycin, reserpine and divalent lead) reach maximum signal response at different energy step positions.

[0047] FIG18 is an extracted ion chromatogram of serum samples analyzed using the method coupled with liquid chromatography, where multiple energy scans were performed within a single liquid chromatography peak. The inset is an enlarged extracted ion chromatogram of safranfos near 1.6-3.0 minutes.

[0048] In the figure: 1. Support and adjustment module, 2. Three-axis moving platform, 3. Plasma support plate, 4. Plasma torch, 5. Arbitrary wave generator control board, 6. Gas line interface, 7. Mass spectrometer connector, 8. Atmospheric pressure mass spectrometer inlet, 9. Plasma beam outlet, 10. Slider bracket, 11. Injector, 12. Base, 13. Microwave power box. DETAILED DESCRIPTION

[0049] To facilitate understanding of the present invention, the present invention will be described in more comprehensive and detailed form below in conjunction with the accompanying drawings and preferred embodiments. However, the protection scope of the present invention is not limited to the following specific embodiments.

[0050] Unless otherwise defined, all technical terms used hereinafter have the same meanings as those generally understood by those skilled in the art. The technical terms used herein are only for the purpose of describing specific embodiments and are not intended to limit the scope of protection of the present invention.

[0051] In the description of the present invention, it should be noted that the terms "up", "down", "left", "right", "inside", "outside", "middle", "vertical", "horizontal", etc. indicating directions or positional relationships are based on the directions or positional relationships shown in the accompanying drawings. They are only for the convenience of describing the invention and simplifying the description, and do not indicate or imply that the device or component referred to must have a specific direction, be constructed and operated in a specific direction. Therefore, they cannot be understood as limiting the invention.

[0052] As shown in Figure 1, the device includes a plasma beam area, an injector 11, a plasma main module, a numerical control module and a support and adjustment module 1; the injector 11, the numerical control module and the plasma main module are installed on the support and adjustment module 1, the plasma main module and the injector 11 are arranged toward the plasma beam area, and the numerical control module is located on the side of the plasma main module. The numerical control module is electrically connected to the plasma main module through a signal transmission line and controls the plasma main module.

[0053] The support and adjustment module 1 includes a mass spectrometer connector 7, a base 12, a three-axis movable platform 2 and a plasma support plate 3; the mass spectrometer connector 7 is fixed to the upper surface of one end of the base 12 by bolts, and a normal pressure mass spectrometer inlet 8 is provided on one side of the mass spectrometer connector 7. The normal pressure mass spectrometer inlet 8 faces the plasma beam area and is located directly above the base 12. The three-axis movable platform 2 is installed on the upper surface of the base 12, and the plasma support plate 3 is fixedly connected to the three-axis movable platform 2. The plasma main module and the injector 11 are installed on the plasma support plate 3 by bolts. The injector 11 is horizontally movably installed on the plasma support plate 3 through a slider bracket 10. The slider bracket 10 and the plasma support plate 3 are clamped by two groove structures. The slider bracket 10 can slide along the groove direction to realize the adjustment of the front and rear position to ensure that the injection position of the injector 11 installed on the slider bracket 10 is appropriate, and the target compound is atomized into spray droplets or gaseous samples through the injector 11.

[0054] The plasma main module includes a plasma torch tube 4, a circuit interface and a gas path interface 6; the plasma torch tube 4 is electrically connected to the numerical control module, one end of the plasma torch tube 4 is connected to the external plasma working gas source through the gas path interface 6, the gas path interface 6 is used to add plasma working gas, and the other end of the plasma torch tube 4 is provided with a plasma beam outlet 9, the plasma beam outlet 9 faces the plasma beam area, the plasma main module relies on the microwave energy generated by the numerical control module to be activated, and argon gas needs to be added for stability during operation, and the plasma torch tube 4 is connected to the numerical control power supply through the circuit interface.

[0055] The numerical control module includes an arbitrary wave generator control board 5 and a microwave power supply box 13; the arbitrary wave generator control board 5 is connected to the plasma torch tube 4 through a signal transmission line, and the microwave power supply box 13 is electrically connected to the arbitrary wave generator control board 5 through a signal transmission line. The arbitrary wave generator control board 5 is used to quickly control the plasma energy.

[0056] The sample injector can be a nebulizer, a gas delivery tube, etc., and a nebulizer is used in the embodiment. By adding an adapter to the sample injector 11, the device can be directly coupled to the liquid phase.

[0057] The gas path interface 6 is connected to an external plasma working gas source. The plasma working gas in the embodiment is argon.

[0058] The arbitrary wave generator control board 5 generates arbitrary wave signals for rapid regulation of plasma energy. Arbitrary waves include sawtooth waves, sine waves, rectangular waves or triangle waves. The frequency range is 0.1-5 Hz. The voltage amplitude is determined by the microwave power box. The overall output power can be precisely controlled within the range of 100-200 W.

[0059] There are no specific requirements for the liquid phase and mass spectrometry that are compatible with the device. The mass spectrometry can replace the ion source, including ion trap mass spectrometry, time-of-flight mass spectrometry, orbital trap mass spectrometry and magnetic mass spectrometry, and try to ensure that the mass spectrometry word scanning time is less than 500ms.

[0060] The specific operation process is as follows:

[0061] 1) Prepare the chemical solution sample or gas sample to be tested;

[0062] 2) Connecting the plasma ion source device to the mass spectrometer, connecting and opening the circuit interface and gas line interface 6, and setting the control waveform energy through the arbitrary wave generator control board 5. The arbitrary wave generator control board 5 generates the ionization energy range of the desired waveform energy level for the target analyte and selects the corresponding waveform signal;

[0063] 3) Open the sample injector 11 and add the configured chemical solution sample or gas sample into the sample injector 11;

[0064] 4) The gaseous material is ejected from the sample injector 11, and the arbitrary wave generator control board 5 simultaneously inputs a control waveform into the plasma torch 4. The plasma main power of the plasma torch 4 is controlled by a digitally controlled power supply, and the gas path is adjusted. The plasma torch 4 activates the plasma and irradiates the plasma from the plasma beam outlet 9 to the plasma beam area. The gaseous material collides with the electrons / ions in the plasma, removing the solvent and forming gaseous ions. Due to the digital power control, the scanned ionization energy varies, so that samples of different forms can be fully charged.

[0065] 5) The obtained gas phase ions enter the mass spectrometer through the atmospheric pressure mass spectrometer inlet 8 for mass spectrometry detection.

[0066] In step 4), the electrons / ions include metastable high-energy electrons, primary gas-phase ions and high-energy positive ions.

[0067] In step 3), when the chemical solution sample is added to the injector 11, the chemical solution sample is atomized into spray droplets as a gas phase substance; when the gas sample is added to the injector 11, the gaseous sample is directly used as a gas phase substance.

[0068] In step 1), the solvent of the solution includes a mixture of one or more of methanol, water, and acetonitrile.

[0069] In step 2), the waveform energy level set by the arbitrary wave generator control board 5 can achieve rapid adjustment of the plasma energy from 100W to 200W within 0.5-5s.

[0070] In step 4), when the chemical solution sample or the gas sample to be tested is a compound requiring soft ionization, the plasma main power of the plasma torch 4 is adjusted to be lower than 140W, and the compound requiring soft ionization includes peptides, drugs or amino acids;

[0071] When the chemical solution sample or the gas sample to be measured is a compound requiring hard ionization, the plasma main power of the plasma torch tube 4 is adjusted to 140W-160W, and the compound requiring hard ionization includes polycyclic aromatic hydrocarbons, halogenated hydrocarbons or ferrocene;

[0072] When the chemical solution sample or the gas sample to be tested is a substance requiring high energy for desorption, the plasma main power of the plasma torch 4 is adjusted to 160W-200W. The substances requiring high energy for desorption include metal elements, inorganic lead or inorganic mercury.

[0073] In order to make the objectives, technical solutions and advantages of the present invention more clear, the present invention will be further described in detail below with reference to embodiments.

[0074] The embodiments of the present invention are as follows:

[0075] Example 1:

[0076] The plasma ion source device with digital energy level control designed in the present invention and the ultimate UPLC / LTQ Orbitrap mass spectrometer (Thermo Fisher Scientific, USA, the same below) were used to test the small molecule L-tyrosine (mass number 182), the polycyclic aromatic hydrocarbon perylene (mass number 252), and the secondary lead element (mass number 208) in the solvent.

[0077] 1. Experimental Materials

[0078] L-tyrosine, perylene, and lead chloride standards (analytical grade, Shanghai Naicheng Biotechnology Co., Ltd., similarly hereinafter) were stored in a refrigerator for experimental use. During the experiment, the corresponding mass of sample was weighed and ultrasonicated for 5 minutes using acetonitrile:water (1:1) as the solvent. A mixed standard solution of the same concentration (10 mg / L) was prepared and ultrasonicated for 5 minutes.

[0079] 2. Experimental Parameters

[0080] Injection conditions: acetonitrile: water (1:1), flow rate 0.1 mL / min;

[0081] CNC module: A triangle wave with a frequency of 0.2-2 Hz is used as the input control function, the energy amplitude is 100 W, and the energy bias is 150 W, thereby generating a plasma beam with an energy scan of 100-200 W, as shown in Figure 2.

[0082] Injector: Concentric nebulizer, nebulizing gas: organic solvent spray module flow rate: 3 L / min; sample spray module flow rate: 3 L / min

[0083] Mass spectrometry conditions: positive ion detection mode, full scan mode

[0084] Ion source parameters: ion transfer tube: 300 °C; ion transfer tube voltage: 30 V; Lens voltage: 100 V.

[0085] 3. Experimental Results

[0086] The three compounds tested can all be successfully detected during the numerically controlled plasma energy scanning process. The energy range of the present invention can achieve soft ionization, hard ionization and rapid scanning of metal element ions.

[0087] As shown in Figures 3-5, L-tyrosine appears as a protonated ion, perylene as a molecular ion peak, and lead chloride as an elemental peak. The entire spectrum scans within 0.5-5 seconds, demonstrating the rationality of the method's numerically controlled energy mode for regulating ionization energy. Ion currents were then extracted for these three ions; as shown in Figures 6-8, significant differences in the highest ion signal intensities are observed among the three ions. Metal elements require the highest ionization energy for desorption, resulting in a sharper ion current peak for lead, which appears only at its highest energy point. Perylene, as a non-polar compound, relies on electron bombardment ionization energy for its ionization mechanism, requiring higher plasma energy than amino acids but lower than that of lead ions. The ionization mechanism of L-tyrosine acid, on the other hand, relies on proton affinity, resulting in soft ionization at low energies, producing a protonated ion peak. The ionization energies of the three types of compounds are 140W, 160W, and 200W respectively; on this basis, three energy levels are defined: soft ionization mode: 100W-140W; hard ionization mode: 140-180W; elemental analysis mode (high energy mode): 180W-200W.

[0088] Example 2:

[0089] To illustrate that the energy range of the present invention can achieve soft ionization and rapid scanning of metal element ions, the plasma ion source device designed with digital energy level control of the present invention was used to set energy waveforms with different scanning frequencies. In combination with an ultimate UPLC / LTQ Orbitrap mass spectrometer, reserpine (mass number 609), secondary lead elements (mass number 208), perylene (mass number 252), L-Phe-L-Phe (mass number 313), cortisone (mass number 361), and triphenyltin hydride (mass number 351) in the solvent were tested.

[0090] 1. Experimental Materials

[0091] Reserpine, lead chloride, perylene, L-Phe-L-Phe, cortisone, and triphenyltin hydride standards (analytical grade, Shanghai Naicheng Biotechnology Co., Ltd., the same below) were stored in a refrigerator for experimental use. During the experiment, the corresponding mass of the sample was weighed and ultrasonically infused for 5 minutes using a methanol:water (1:1) solvent to prepare a mixed standard solution of the same concentration (10 mg / L), which was then ultrasonically infused for 5 minutes.

[0092] 2. Experimental Parameters

[0093] Injection conditions: methanol: water (1:1), flow rate 0.1 mL / min;

[0094] CNC module: A rectangular wave with a frequency of 0.2-2 Hz and a triangle wave and a sawtooth wave with the same frequency are used as input control functions, with an energy amplitude of 100 W and an energy bias of 150 W, thereby generating a plasma beam with an energy scan of 100-200 W.

[0095] Injector: Concentric nebulizer, nebulizing gas: organic solvent spray module flow rate: 3 L / min; sample spray module flow rate: 3 L / min

[0096] Mass spectrometry conditions: positive ion detection mode, full scan mode

[0097] Ion source parameters: ion transfer tube: 300 °C; ion transfer tube voltage: 30 V; Lens voltage: 100 V.

[0098] 3. Experimental Results

[0099] First, the effectiveness of the rapid scanning of the CNC waveform was verified. Figure 9 shows the superimposed mass spectra of the metallic elements lead (m / z 208.98) and reserpine (m / z 609.28). High ion signal intensities are observed for both targets. Figure 10 shows the superimposed extracted ion chromatograms of the two compounds under a 1Hz rectangular wave. Within a scan time of s, the two compounds sequentially emit peaks according to the scan energy level, forming a staggered line graph, validating the rapid energy scanning capability. The effect of different operating frequencies on the results was then verified. Figure 11 shows the superimposed extracted ion chromatograms of the two compounds under a 0.5Hz rectangular wave, and Figure 12 shows the superimposed extracted ion chromatograms of the two compounds under a 0.2Hz rectangular wave. Stable particle current intensity is achieved within 1s, demonstrating that the rapid scanning frequency can be achieved within 0.5s, fully meeting the time-resolved analysis requirements of LC / MS. The ionization energy was then manipulated using different types of control waveforms. Figure 13 shows the superimposed extracted ion currents of the two substances under a 0.2 Hz triangle wave, and Figure 14 shows the superimposed extracted ion currents of the two substances under a 0.2 Hz sawtooth wave. The results show corresponding differences.

[0100] The sample was then subjected to liquid chromatography-mass spectrometry (LC-MS). Figure 15 shows the extracted ion chromatograms of reserpine, perylene, L-Phe-L-Phe, cortisone, and triphenyltin hydride at different retention times during coupled liquid chromatography. Approximately ten rapid ionization energy scans can be completed within a single liquid phase peak packet, appearing as dense peak packets in the liquid phase ion chromatogram, demonstrating the effectiveness of this method's digitally controlled ionization energy scanning.

[0101] Example 3:

[0102] To explore the applicability of the method described in the present invention to actual samples, a digital energy level controlled plasma ion source device designed in the present invention was coupled with an ultimate UPLC / LTQ Orbitrap mass spectrometer (Thermo Fisher Scientific, USA, the same below) to test nine toxicological samples in serum. The samples included pesticides (anthracene, polycyclic aromatic hydrocarbons (anthracene, benzo[a]pyrene), inorganic heavy metals (lead chloride), organometallics (triphenyltin chloride), and psychotropic and conventional drugs (sulpiride, midecamycin, prochlorperazine, and reserpine).

[0103] 1. Experimental Materials

[0104] Standards of sulpiride, anthracene, benzo[a]pyrene, lead chloride, triphenyltin chloride, sulpiride, midecamycin, prochlorperazine, and reserpine (analytical grade) were stored in a refrigerator for experimental use. Chicken serum was purchased from Genom Bio (Hangzhou, China) and prepared as follows. 200 μL of chicken serum and 10 μL of each of the nine standards (1 mg mL -1 ) were mixed, and 800 μL of acetonitrile was added to precipitate the protein. The solution was then sonicated for 5 minutes, centrifuged at 4193 × g for 3 minutes, and precipitated at 4°C for 10 minutes. The supernatant was filtered and stored at -20°C until use. The spiked concentration of the serum extract to be tested was 10 mg L -1 The blank serum was treated in the same way. -1 quantified by the concentration gradient.

[0105] 2. Experimental Parameters

[0106] Injection conditions: acetonitrile: water (1:1), flow rate 0.4 mL / min;

[0107] CNC module: A custom-programmed step wave is used as the input control function. The energy is initially 100 W and is increased in steps of 20 W, reaching 200 W within 2 seconds and repeating the cycle, thereby generating a plasma beam with an energy scan of 100-200 W.

[0108] Injector: concentric nebulizer, nebulizing gas flow rate: 3 L / min;

[0109] Mass spectrometry conditions: positive ion detection mode, full scan mode

[0110] Liquid chromatography conditions: The liquid chromatograph was a Thermo Fisher UltiMate 3000 UPLC. The chromatographic column was a HYPERSIL GOLD C18 column (2.1 mm × 100 mm, 3.0 μm). Mobile phase A (1‰ formic acid in water) and mobile phase B (acetonitrile) were used for gradient elution. Flow rate: 0.4 mL min-1; injection volume: 3 μL; column temperature: 30°C; gradient elution: 1 μL min-1. -1 : 30 ℃; elution gradient program: 0.0 min, 10%B (10% acetonitrile in water); 0.0-20.0 min, 10%-100%B; 20.0-30.0 min, 100%B; 30.0-31.0 min, 100%-10%B; 31.0-35.0 min, 10%B.

[0111] Ion source parameters: ion transfer tube: 300 °C; ion transfer tube voltage: 30 V; Lens voltage: 100 V.

[0112] 3. Experimental Results

[0113] The nine compounds tested were all successfully detected during the digitally controlled plasma energy scanning process. The 100-200 W step wave scanning mode can be used to directly ionize these nine compounds with different physical and chemical properties, as shown in Figure 16. During this scanning process, the analytes can reach their optimal energy positions respectively; therefore, during the scanning process, the signal response of each compound on an energy step is the highest (Figure 17). In other practical applications, the energy scanning range can also be adjusted according to the characteristics of the sample. Using digital scanning ionization technology to directly quantify these nine analytes in serum, the concentration of the analytes in the range of 10-5000 μg L -1 The linear range showed good R 2 The limits of detection (LOD) and quantification (LOQ) were 0.88–14.49 μg L -1 and 2.94-48.31 μg L -1 Furthermore, since the scan time described in this invention is between 0.5 and 5 seconds, the device can be rapidly coupled to liquid chromatography to ensure high ionization of compounds within the liquid phase peak. This method can complete multiple energy scans within the peak retention time, generating densely packed small peaks in the EIC plot (Figure 18). Quantitative analysis can be performed by fitting the highest point of each peak and calculating the area.

[0114] Therefore, the digital energy level controlled plasma ion source and digital graded controlled ionization method provided by the present invention form a fast scanning mode of ionization energy through digital control of the plasma ion source control input, which can achieve high coverage ionization energy ionization from drug molecules to metal elements, and the analysis time of the entire single scan can be shortened to less than 0.5. Compared with other ionization methods, there is currently no ion source that can achieve soft ionization and metal element analysis simultaneously and quickly, which is very innovative. In addition, the method can be directly coupled with the liquid phase under normal pressure conditions, completely matching the single peak retention time of the liquid phase, and completely matching the order of magnitude of the liquid phase peak time and mass spectrometry scanning time. Therefore, the method provided by the present invention has strong innovative and practical value and is suitable for mass spectrometry analysis in various fields such as laboratories, industrial production, medical research, and public security management.

[0115] The above is a further detailed description of the present invention in conjunction with specific preferred embodiments, and the specific implementation of the present invention should not be considered to be limited to these descriptions. For those skilled in the art of the present invention, without departing from the concept, several simple deductions or substitutions can be made, which should be considered to fall within the scope of protection of the present invention.

Claims

1. A plasma ion source device with digital energy level control, characterized in that: The invention comprises a plasma beam region, an injector (11), a plasma main body module, a numerical control module and a support adjustment module (1); the injector (11), the numerical control module and the plasma main body module are mounted on the support adjustment module (1), the plasma main body module and the injector (11) are arranged toward the plasma beam region, the numerical control module is located beside the plasma main body module, and the numerical control module is electrically connected to the plasma main body module via a signal transmission line and controls the plasma main body module.

2. A plasma ion source device with digital energy level control according to claim 1, characterized in that: The support and adjustment module (1) comprises a mass spectrometer connecting member (7), a base (12), a three-axis movable platform (2) and a plasma support plate (3); a mass spectrometer connecting member (7) is fixed to the upper surface of one end of the base (12); a normal-pressure mass spectrometer inlet (8) is provided on one side of the mass spectrometer connecting member (7); the normal-pressure mass spectrometer inlet (8) faces the plasma beam region; the normal-pressure mass spectrometer inlet (8) is located directly above the base (12); a three-axis movable platform (2) is installed on the upper surface of the base (12); a plasma support plate (3) is fixedly connected to the three-axis movable platform (2); a plasma main body module and an injector (11) are installed on the plasma support plate (3); and the injector (11) is horizontally movably installed on the plasma support plate (3) via a slider bracket (10).

3. The plasma ion source device with digital energy level control according to claim 1, characterized in that: The plasma main module comprises a plasma torch tube (4), a circuit interface and a gas path interface (6); the plasma torch tube (4) is electrically connected to a numerical control module; one end of the plasma torch tube (4) is connected to an external plasma working gas source via the gas path interface (6); the other end of the plasma torch tube (4) is provided with a plasma beam outlet (9), the plasma beam outlet (9) faces a plasma beam region, and the plasma torch tube (4) is connected to a numerical control power supply via the circuit interface.

4. The plasma ion source device with digital energy level control according to claim 1, characterized in that: The numerical control module comprises an arbitrary wave generator control board (5) and a microwave power supply box (13); the arbitrary wave generator control board (5) is connected to the plasma torch tube (4) via a signal transmission line, and the microwave power supply box (13) is electrically connected to the arbitrary wave generator control board (5) via the signal transmission line.

5. A digital hierarchical controlled ionization method applied to the device of claim 1, characterized in that: The method comprises the following steps: 1) Prepare the chemical solution sample or gas sample to be tested; 2) connecting the plasma ion source device to a mass spectrometer, and setting the control waveform energy through an arbitrary wave generator control board (5); 3) opening the sample injector (11) and adding the configured chemical solution sample or gas sample into the sample injector (11); 4) The gas phase material is ejected from the injector (11), and the control waveform is input into the plasma torch (4) by the arbitrary wave generator control board (5). The plasma main power of the plasma torch (4) is controlled by the digital control power supply, and the gas path is adjusted. The plasma torch (4) activates the plasma and irradiates the plasma from the plasma beam outlet (9) to the plasma beam area. The gas phase material collides with the electrons / ions in the plasma, and the solvent is removed to form gas phase ions. 5) The obtained gas phase ions enter the mass spectrometer through the atmospheric pressure mass spectrometer inlet (8) for mass spectrometry detection.

6. A digital hierarchical controlled ionization method according to claim 5, characterized in that: In the step 4), the electrons / ions include metastable high-energy electrons, primary gas-phase ions and high-energy positive ions.

7. A digital hierarchical controlled ionization method according to claim 5, characterized in that: In the step 3), when the chemical solution sample is added to the injector (11), the chemical solution sample is atomized into spray droplets as a gas phase substance; when the gas sample is added to the injector (11), the gaseous sample is directly used as a gas phase substance.

8. A digital hierarchical controlled ionization method according to claim 5, characterized in that: In the step 1), the solvent of the solution includes a mixture of one or more of methanol, water and acetonitrile.

9. A digital hierarchical controlled ionization method according to claim 5, characterized in that: In the step 2), the waveform energy level set by the arbitrary wave generator control board (5) can achieve rapid adjustment of the plasma energy from 100 W to 200 W within 0.5 to 5 seconds.

10. A digital hierarchical controlled ionization method according to claim 5, characterized in that: In the step 4), when the chemical solution sample or the gas sample to be tested is a compound requiring soft ionization, the plasma main power of the plasma torch (4) is lower than 140W, and the compound requiring soft ionization includes peptides, drugs or amino acids; When the chemical solution sample or the gas sample to be tested is a compound requiring hard ionization, the plasma main power of the plasma torch (4) is 140W-160W, and the compound requiring hard ionization includes polycyclic aromatic hydrocarbons, halogenated hydrocarbons or ferrocene; When the chemical solution sample or the gas sample to be tested requires desorption of organic elements and inorganic metal elements, the plasma main power of the plasma torch (4) is 160W-200W, and the sample includes metal elements, inorganic lead or inorganic mercury.

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