Mass spectrometry combined desorption ionization source device and its application

Abstract

This invention provides a novel mass spectrometry composite desorption-ionization source device and its application. The device includes a microwave plasma ionization source and an electrospray ionization source. In the microwave plasma ionization source, the variable-diameter dielectric tube in the T-shaped insulating dielectric tube and the electrospray capillary are coaxially arranged and simultaneously introduced with a working coil. One end of the working coil is connected to a microwave introduction unit, and the other end is wound around the thin section of the dielectric tube and back to the microwave introduction unit, and positioned close to the sample to be tested. Thus, in the same spacetime, the electrospray ionization source provides relatively stable initial ionization, and the microwave plasma ionization source further enhances the analytical signal through secondary ionization. Combining the two solves the problem of Coulomb interference, and under the action of the working coil, the ionization region is more concentrated, greatly improving the detection signal by up to 100 times.

Description

Technical Field

[0001] This invention belongs to the fields of analytical chemistry and ion sources for mass spectrometers, specifically relating to a novel device and application of a desorption electrospray / microwave-induced plasma desorption composite ionization source. Background Technology

[0002] Mass spectrometry, with its advantages of high sensitivity, high analytical throughput, high resolution, and high compatibility with chromatographs, has a wide range of applications in various fields such as biology, food, and atmosphere. Ionization methods play a crucial role in mass spectrometry because ionization efficiency directly affects the sensitivity and detection limit of the technique. Desorption-electrospray ionization (DESI) sources can ionize samples without destroying their molecular structure and have become the most widely used atmospheric pressure soft ionization source. With the continuous development of analytical techniques, single ionization sources often cannot perform optimally in all scenarios, especially in the analysis of complex samples. Improving signal intensity and sensitivity has always been a key research goal. Therefore, researchers have been searching for new ionization techniques to overcome these challenges and improve analytical efficiency.

[0003] Combining different ionization techniques to construct composite ionization sources has been proven by previous research to improve the ionization efficiency of sample detection. Plasma-based ionization sources have attracted widespread attention due to their excellent sample ionization efficiency. However, ionization sources that induce plasma using high-voltage direct current and radio frequency power supplies suffer from high-voltage limitations and electrode contamination, restricting their application. Microwave-induced plasma desorption ionization (MIPDI) avoids these problems. Its basic principle is that microwaves are typically used to excite gases (such as helium or argon) to form high-energy plasma, in which the sample is excited, decomposed, and ionized.

[0004] Mattra Corporation disclosed in its Taiwan patent application TW200703412A, entitled "Plasma Source Sprayer," a combination of an electro-fogging / microwave-induced plasma (MIP) ion source for use as an ion source in a mass spectrometer. The electro-fogging can operate in positive or negative modes, or it can be turned off. The microwave-induced plasma can also be turned on or off. This allows the device to operate in multiple modes. The device generally has the highest elemental sensitivity when the electro-fogging is off and the microwave-induced plasma is on. Mixed-mode operation may allow for the determination of additional information about the existing chemical components in the analyte. In pure electro-fogging mode, it is possible to obtain molecular information and analyze organic compounds. Therefore, this patent application aims to combine two ionization methods, electro-fogging and microwave-induced plasma, to improve ionization through multi-mode operation; however, it does not explicitly propose a specific structural design, while the structural design of the ionization source device is crucial to its detection effect; the aforementioned patent application also does not explicitly disclose the detection effect on local anesthetic samples. Summary of the Invention

[0005] In view of this, the main objective of this invention is to provide a novel mass spectrometry-based desorption / ionization source device and its application. The device primarily combines two ion sources: a desorption electrospray ionization source (DESI) and a microwave-induced plasma desorption / ionization source (MIPDI), while simultaneously introducing a working coil. Thus, in the same spacetime, the DESI ionization source provides relatively stable initial ionization, and the MIPDI further enhances the analytical signal through secondary ionization. Combining these two sources solves the problem of Coulomb interference, and the working coil further concentrates the ionization region, significantly improving the detection signal by up to 100 times.

[0006] The specific technical solution is as follows:

[0007] A mass spectrometry combined desorption ionization source device, comprising:

[0008] A microwave plasma ionization source includes a T-shaped insulating dielectric tube, a gas introduction unit, a microwave introduction unit, and a working coil. The T-shaped insulating dielectric tube comprises a variable-diameter dielectric tube and a dielectric branch tube. The variable-diameter dielectric tube mainly consists of a thicker section of the dielectric tube and a thinner section extending from the thicker section. The dielectric branch tube is located on one side of the thicker section of the dielectric tube and connected to the gas introduction unit. One end of the working coil is connected to the microwave introduction unit, and the other end is wound around the thinner section of the dielectric tube and then back to the microwave introduction unit, and is positioned close to the sample to be tested.

[0009] An electrospray ionization source includes an electrospray capillary, a desorption solvent introduction unit, and a DC voltage. The electrospray capillary is coaxially arranged with the variable diameter medium tube and passes through the variable diameter medium tube. The electrospray capillary extends from the thicker section of the medium tube and is connected to the desorption solvent introduction unit and the DC voltage, respectively. The electrospray capillary extends from the thinner section of the medium tube or is inside the thinner section of the medium tube and faces the sample to be tested.

[0010] In this invention, "sample" refers to liquid or solid materials.

[0011] Based on the above, the length of the working coil is an integer multiple of the microwave wavelength. Thus, the working coil is used to induce the generation of plasma, and its working state is close to the resonant state. This state can form a relatively uniform and widespread radiation pattern, effectively radiating microwave energy into space. The microwave can propagate without distortion on the working coil, avoiding microwave attenuation and maximizing the transmitted energy.

[0012] Based on the above, the microwave introduction unit includes a solid-state microwave source and a coaxial line, which is connected to the solid-state microwave source and the working coil respectively.

[0013] The device described above also includes an XYZ three-dimensional displacement slide stage, used to precisely adjust the relative position and angle between the T-shaped insulating dielectric tube, the surface of the sample to be tested, and the mass analyzer integrated in the mass spectrometer; this makes the ionization region more concentrated, the ionization efficiency higher, and the sample ions can smoothly enter the inlet of the mass analyzer.

[0014] The aforementioned device further includes an ion source support for fixing the T-shaped insulating dielectric tube.

[0015] An application of a mass spectrometry-desorption-ionization source device combined with a mass spectrometer in the analysis of compound structures, wherein the device operates in the following modes: independent operation of microwave plasma ionization source, independent operation of electrospray ionization source, and combined operation of microwave plasma ionization source and electrospray ionization source.

[0016] The microwave plasma ionization source and the electrospray ionization source, when used in combination, can be used to detect and analyze substances containing α,β-unsaturated ketones.

[0017] Compared with the prior art, the mass spectrometry composite desorption ionization source device provided by the present invention has the following characteristics:

[0018] 1) With the combined action of microwave and working coil, turning on the DC high voltage of the DESI ionization source can automatically initiate a plasma jet without the need for an additional igniter to provide electrons to generate plasma, thus simplifying the device.

[0019] 2) Under the induction of the working coil, the ionization region is more concentrated, and the ionization region can be as small as 0.375 cm. 3 ;

[0020] 3) The device described above by the present invention can not only realize the single function of DESI ionization source and MID ionization source, but also combine the two to greatly improve the detection signal by 100 times. In particular, it can be applied to the detection of complex compound samples containing α,β unsaturated ketones.

[0021] Therefore, the mass spectrometry composite desorption ionization source device provided by the present invention has the advantages of high ionization, concentrated ionization region, miniaturization, integration, simple structure, easy processing, convenient operation, and low price. Attached Figure Description

[0022] Figure 1 This is a schematic diagram of the mass spectrometry composite desorption ionization source device provided in Embodiment 1 of the present invention;

[0023] Figure 2 A schematic diagram of the ion source body generated by the mass spectrometry combined desorption ionization source device provided in Example 1;

[0024] Figure 3 (A) is a DESI experimental diagram showing the phenomena observed using the mass spectrometry combined desorption ionization source device provided in Example 1 alone. Figure 3 (B) A diagram showing the experimental phenomena of the mass spectrometry combined desorption ionization source device provided in Example 1 using DESI+MIPDI, wherein, because Figure 3 (B) Due to the influence of the background, the electrospray ion flow generated from the narrow section of the T-shaped glass tube is not easily observed with the naked eye;

[0025] Figure 4 The mass spectrum of a tricaine mixed sample in DESI mode of the mass spectrometry composite desorption ionization source device provided in Example 1;

[0026] Figure 5 The mass spectrum of a tricaine mixed sample in MIPDI mode of the mass spectrometry composite desorption ionization source device provided in Example 1;

[0027] Figure 6 The mass spectrum of a tricaine mixed sample in DESI+MIPDI mode of the mass spectrometry combined desorption ionization source device provided in Example 1;

[0028] In the above figures: 1. Injector; 2. Delivery tube; 3. Gas cylinder; 4. Gas tubing; 5. Mass flow controller; 6. T-shaped quartz glass tube; 7. Electrospray capillary; 8. DC high voltage; 9. Working coil; 10. Solid-state microwave source; 11. Coaxial cable; 12. Microwave interface; 13. Template; 14. Sample; 15. Mass analyzer; 16. Electrospray ion flow; 17. Plasma jet; 18. Ion source support; 19. Detailed Implementation

[0029] Unless otherwise specified, the terminology used in this invention is a common term in the relevant field. Unless otherwise specified, the preparation processes and testing methods used in each embodiment are conventional means well known to those skilled in the art, and the raw materials and equipment used can be obtained from publicly available commercial channels.

[0030] This invention primarily combines two ion sources: desorption electrospray ionization (DESI) and microwave-induced plasma desorption ionization (MIPDI), providing a novel mass spectrometry-based composite desorption ionization source. This device integrates DESI and MIPDI, and, under the induction effect of the working coil, solves the problem of coulomb interference, resulting in a more concentrated ionization region and significantly improving the detection signal, particularly enhancing the detection signal of anesthetic drugs by up to 100 times.

[0031] Specifically, one aspect of the present invention provides a mass spectrometry composite desorption ionization source device, comprising:

[0032] A microwave plasma ionization source includes a T-shaped insulating dielectric tube, a gas introduction unit, a microwave introduction unit, and a working coil. The T-shaped insulating dielectric tube comprises a variable-diameter dielectric tube and a dielectric branch tube. The variable-diameter dielectric tube mainly consists of a thicker section of the dielectric tube and a thinner section extending from the thicker section. The dielectric branch tube is located on one side of the thicker section of the dielectric tube and connected to the gas introduction unit. One end of the working coil is connected to the microwave introduction unit, and the other end is wound around the thinner section of the dielectric tube and then back to the microwave introduction unit, and is positioned close to the sample to be tested.

[0033] An electrospray ionization source includes an electrospray capillary, a desorption solvent introduction unit, and a DC voltage. The electrospray capillary is coaxially arranged with the variable diameter medium tube and passes through the variable diameter medium tube. The electrospray capillary extends from the thicker section of the medium tube and is connected to the desorption solvent introduction unit and the DC voltage, respectively. The electrospray capillary extends from the thinner section of the medium tube or is inside the thinner section of the medium tube and faces the sample to be tested.

[0034] The desorption solvent introduction unit is used to provide a desorption solvent to the electrospray capillary. This desorption solvent can be methanol, acetonitrile, isopropanol, acetone, etc. The desorption solvent introduction unit is a conventional structure and may include an injection pump, a syringe, and a delivery tube connected to one end of the electrospray capillary. The syringe is connected to the injection pump and the delivery tube at its two ends, respectively. The desorption solvent is placed in the syringe, and the injection pump injects the desorption solvent into the delivery tube at a predetermined rate. The other end of the delivery tube is connected to the electrospray capillary. Under the action of a DC high voltage, the desorption solvent generates charged droplets, forming an electrospray ion stream that is ejected from the tip of the electrospray capillary (the end closest to the sample to be tested), thus enabling the independent operation of the electrospray ion source. The delivery tube is an insulated hollow tube, and the diameter of the electrospray capillary is preferably 0.1-0.3 mm.

[0035] The T-shaped insulating dielectric tube is made of glass, quartz, or ceramic. The diameter of the thicker section of the dielectric tube is preferably 5-10 mm and the length 50-80 mm, while the diameter of the thinner section is preferably 1-5 mm and the length 50-80 mm. The dielectric branch tube is preferably perpendicular to the thicker section of the dielectric tube, and its specific location on that section is not limited; the diameter of the dielectric branch tube is preferably 5-10 mm and the length 20-50 mm.

[0036] The mass spectrometry combined desorption ionization source device also includes a gas introduction unit for supplying gas. This is an existing structure and may include a gas cylinder for supplying gas, a gas pipe for connecting the gas cylinder and the medium branch pipe, and a mass flow controller installed on the gas pipe. The gas flow rate is adjusted by the mass flow controller. The gas is an inert gas such as argon or helium.

[0037] The microwave introduction unit is mainly used to generate microwaves and has an existing structure. It may include a solid-state microwave source and a coaxial line, which is connected to both the solid-state microwave source and the working coil. The coaxial line is straight and cannot be bent to avoid affecting the microwave transmission efficiency. The coaxial line can be connected to the working coil via a microwave interface. The length of the coaxial line is preferably 40-60 cm, and the end of the coaxial line has a perforated microwave interface made of metal.

[0038] One end of the working coil is inserted into the hole of the microwave interface, and the other end is wound back and connected to the microwave interface to form a closed loop to complete the transmission of microwaves. The microwaves are emitted by a solid-state microwave source, which excites the gas to generate plasma and ejects it from the nozzle of the thin section of the dielectric tube; thereby realizing the independent operation of the microwave plasma ionization source.

[0039] The microwave plasma ionization source and the electrospray ionization source operate in combination: a solid-state microwave source generates high-frequency microwaves, which are transmitted to the working coil via a coaxial line, generating an electromagnetic field inside the working coil. The DC high voltage of the electrospray ionization source provides electrons. These electrons absorb magnetic field energy and collide with ground-state gas atoms, ionizing them and generating new electrons. These new electrons continue to collide with ground-state gas atoms, and this process continues in a cycle. When the generated electrons and ions fill the internal space of the working coil, a connected discharge channel is formed, resulting in gas breakdown discharge and the formation of plasma. Therefore, under the combined action of the microwave and the electrons provided by the DC high voltage, electrons absorb magnetic field energy and thermal energy and are accelerated by the electric field, colliding with ground-state gas atoms and ionizing them. When the generated electrons and ions fill the internal space of the working coil, a connected discharge channel is formed, resulting in gas breakdown discharge and the formation of a plasma jet. Driven by the airflow, the plasma jet is ejected through the nozzle of the narrow section of the dielectric tube in the T-shaped insulating dielectric tube; simultaneously, the desorption solvent forms an electrospray ion flow at the tip of the electrospray capillary. The plasma jet and the electrospray ion flow constitute the main body of the ion source.

[0040] When a microwave plasma ionization source and an electrospray ionization source operate in combination, the desorbed solvent is ejected through the electrospray capillary under the action of a DC high voltage, generating charged droplets. Induced by the microwaves generated during the operation of the microwave plasma ionization source and the working coil, a plasma jet can be automatically initiated to form an electrospray ion stream without the need for an additional igniter. Preferably, the length of the working coil is an integer multiple of the microwave wavelength. Thus, the working coil is used to induce plasma generation, and its operating state is close to a resonant state. This state can form a relatively uniform and widespread radiation pattern, effectively radiating microwave energy into space. The microwaves can propagate without distortion on the working coil, avoiding microwave attenuation and maximizing the transmitted energy. Therefore, the working coil is a helical coil wound with enameled wire, and the single-layer coils must not touch each other, otherwise a short circuit will occur. Preferably, the length of the working coil is one wavelength of the microwave, which further achieves impedance matching, reduces reflected waves, and minimizes the standing wave ratio. The output signal is in phase with the input signal, resulting in optimal microwave transmission.

[0041] The mass spectrometry combined desorption ionization source device further includes a sample plate for supporting and positioning the sample to be tested. The sample to be tested is placed on the surface of the sample plate. The samples suitable for analysis in this invention are solid or liquid. The sample plate is made of materials such as glass, silicon wafer, stainless steel, and polytetrafluoroethylene.

[0042] Furthermore, the mass spectrometry combined desorption ionization source device also includes an ion source support for fixing the T-shaped insulating dielectric tube, positioning the relative position and angle between the T-shaped insulating dielectric tube, the surface of the sample to be tested, and the mass analyzer integrated in the mass spectrometer, thereby determining the relative position between the ion source body, the sample point, and the mass analyzer inlet, ensuring that sample ions can smoothly enter the mass analyzer inlet. The mass analyzer is used to analyze the ions generated by the sample to be tested. Specifically, the ion source support is fixed on an XYZ three-dimensional displacement slide, which includes an X-axis, a Y-axis, and a Z-axis. The X-axis can be used to adjust the lateral distance between the T-shaped insulating dielectric tube, the surface of the sample to be tested, and the mass analyzer inlet; the Y-axis can be used to adjust the longitudinal distance between the T-shaped insulating dielectric tube, the surface of the sample to be tested, and the mass analyzer inlet; the Z-axis is used to adjust the vertical distance between the T-shaped insulating dielectric tube, the surface of the sample to be tested, and the mass analyzer inlet. The ion source support is fixed to the circular R-axis of the Z-axis and can rotate 360°. In this way, the positional relationship between the T-shaped insulating dielectric tube, the sample to be tested, and the mass analyzer can be effectively adjusted, thereby ensuring a more concentrated ionization region, higher ionization efficiency, and smooth entry of sample ions into the inlet of the mass analyzer. Here, the "sample point" in this invention refers to the position of the sample to be tested closest to the tip of the ion source body.

[0043] Another aspect of the present invention provides an application of a mass spectrometry-based desorption-ionization source device combined with a mass spectrometer in the analysis of compound structures. The device has operating modes including independent operation of the microwave plasma ionization source, independent operation of the electrospray ionization source, and joint operation of the microwave plasma ionization source and the electrospray ionization source. This makes the mass spectrometry-based desorption-ionization source device provided by the present invention suitable for the detection of complex compounds and has a wide range of applications.

[0044] Another aspect of the present invention provides a method for mass spectrometry analysis using a mass spectrometry combined with a desorption ionization source device and a mass spectrometer, comprising the steps of:

[0045] Adjusting the positional relationship: Adjusting and determining the relative positions of the T-shaped insulating dielectric tube, the sample to be tested, and the inlet of the mass analyzer;

[0046] Forming the ion source body: The microwave plasma ionization source is operated alone to eject a plasma jet from the opening of the thin segment of the dielectric tube; or, the electrospray ionization source is operated alone to form an electrospray ion flow from the tip of the electrospray capillary; or, the microwave plasma ionization source and the electrospray ionization source are operated in combination. This combined operation method includes turning on the gas introduction unit to deliver gas to the T-shaped insulating dielectric tube, turning on the desorption solvent introduction unit to deliver desorption solvent, applying the DC high voltage to the electrospray capillary, and starting the microwave introduction unit to deliver microwaves to the thin segment of the dielectric tube; under the action of the airflow, the desorption solvent forms an electrospray ion flow at the tip of the electrospray capillary, and the plasma jet is ejected through the opening of the thin segment of the dielectric tube.

[0047] Sample placement: Place the sample to be tested under the ion source body. Depending on the operating mode, the ion source body may be a plasma jet, an electrospray ion stream, or a combination of both.

[0048] Mass spectrometry detection: Open the mass spectrometer detection software to obtain the detection results.

[0049] Furthermore, the sample to be tested is a substance containing α,β-unsaturated ketones, and the microwave plasma ionization source and the electrospray ionization source operate in combination. The substance containing α,β-unsaturated ketones includes complex compounds such as anesthetics and hormones, including procaine, tetracaine, debucaine, dimethicone, lidocaine, etc.

[0050] Furthermore, in the step of adjusting the positional relationship, the distance from the tip of the ion source body to the surface of the sample to be tested is controlled to be <2 mm by the XYZ three-dimensional displacement slide, the angle between the ion source body and the sample point is 30°-90°, and the horizontal distance between the sample point and the mass analyzer inlet is about 2-10 mm, and the vertical distance is about 1-3 mm; thus, efficient detection of substances containing α,β unsaturated ketones can be achieved.

[0051] Compared with the prior art, the mass spectrometry composite desorption ionization source device provided by the present invention has the following characteristics:

[0052] 1) Under the induction of microwaves and working coils, turning on the DC high voltage of the DESI ionization source can automatically initiate a plasma jet without the need for an additional igniter to provide electrons to generate plasma, thus simplifying the device.

[0053] 2) In the same spacetime, the electromagnetic field generated in the MIPDI ionization source mainly acts on the excitation and maintenance of the plasma, without affecting the ionization efficiency of the DESI ionization source. Therefore, DESI provides a relatively stable initial ionization, and MIPDI further enhances the analysis signal through secondary ionization, combining the two and solving the Coulomb interference problem. Thus, under the induction of the working coil, the ionization region is more concentrated, and the ionization region can be as small as 0.375 cm. 3 ;

[0054] 3) The device described above by the present invention can not only realize the single function of DESI ionization source and MID ionization source, but also combine the two for use in the detection of compound samples containing α,β unsaturated ketones, which can greatly improve the detection signal by 100 times.

[0055] Therefore, the mass spectrometry composite desorption ionization source device provided by the present invention has the advantages of high ionization, concentrated ionization region, miniaturization, integration, simple structure, easy processing, convenient operation, and low price.

[0056] The technical solution of the present invention will be further described in detail below through specific embodiments.

[0057] Example 1

[0058] Please see Figure 1 and Figure 2 This embodiment provides a novel mass spectrometry composite desorption ionization source device, including: an injection pump 1, a syringe 2, a delivery tube 3, a gas cylinder 4, a gas tube 5, a mass flow controller 6, a T-shaped quartz glass tube 7, an electrospray capillary 8, a DC high voltage 9, a working coil 10, a solid-state microwave source 11, a coaxial linear device 12, a microwave interface 13, and a sample 14.

[0059] The gas cylinder 4, gas pipe 5, and mass flow controller 6 constitute a gas introduction unit, used to provide gas for the generation of the electrospray ionization source. The gas pipe 5 connects the gas cylinder 4 and the T-shaped quartz glass tube 7. The mass flow controller 6, installed on the gas pipe 5, controls the flow rate of the gas released from the gas cylinder 4. In this embodiment, the gas is argon, and the flow rate is 0.6 L / min.

[0060] The injection pump 1, syringe 2, and delivery tube 3 constitute a desorption solvent introduction unit, providing desorption solvent to the electrospray ionization source. The desorption solvent can be placed in syringe 2, and the injection pump 1 injects the desorption solvent into the delivery tube 3 at a preset rate. The other end of the delivery tube 3 is connected to the electrospray capillary 8. Under the action of the DC high voltage 9, the desorption solvent is ejected through the electrospray capillary 8, generating charged droplets, which, driven by the gas, form a charged spray ion stream 17, such as... Figure 3As shown in (A). In this embodiment, the desorption solvent is methanol, and its delivery rate is 5 μL / min. The delivery tube 3 is an insulated hollow tube, and the electrospray capillary 8 is a stainless steel capillary with a diameter of 0.3 mm.

[0061] The T-shaped quartz glass tube 7 includes a variable-diameter medium tube, which mainly consists of a thicker section and a thinner section extending from the thicker section. A medium branch pipe is provided on one side of the thicker section, and this medium branch pipe is connected to the air pipe 5. The electrospray capillary tube 8 is inserted into the axial center of the variable-diameter medium tube and extends from both ends of the variable-diameter medium tube. In this embodiment, the thicker section of the variable-diameter medium tube has a diameter of 7 mm and a length of 40 mm, the thinner section has a diameter of 4 mm and a length of 50 mm, and the medium branch pipe has a diameter of 7 mm and a length of 50 mm.

[0062] The electrospray capillary 8 extending from the thicker section of the dielectric tube is connected to the delivery tube 3 and the DC high voltage 9, respectively. The opening of the electrospray capillary 8 extending from the thinner section of the dielectric tube faces the sample 15 to be tested. A working coil 10 is wound around the tip of the thinner section of the dielectric tube. The working coil 10 is a helical coil made of enameled wire, used to induce the generation of microwave plasma. The length of the working coil is 12.2 cm, which is one wavelength of the microwave generated by the solid-state microwave source 11.

[0063] The solid-state microwave source 11, coaxial line 12, and microwave interface 13 constitute a microwave introduction unit for generating microwaves. The microwaves generated by the solid-state microwave source 11 are transmitted to the working coil 10 via the coaxial line 12, which is straight and inflexible. The coaxial line 12 is 50 cm long, and its end has a perforated microwave interface 13. The end of the working coil 10 is inserted into the hole of the microwave interface 13 to complete the microwave transmission. Gas is excited under the action of the microwaves, forming a plasma jet 18. In this embodiment, the solid-state microwave source 11 generates microwaves at a frequency of 2.45 GHz, and the microwave interface 13 is made of platinum.

[0064] Please see Figure 2 and Figure 3 (B) Under the combined action of microwave and DC high voltage provided by electrons, electrons absorb magnetic field energy and thermal energy and are accelerated by electric field to collide with ground state gas atoms and ionize. When the generated electrons and ions fill the interior of the working coil, a connected discharge channel is formed, generating gas breakdown discharge and forming plasma jet 18. Driven by the airflow, plasma jet 18 is ejected through the nozzle of the dielectric tube in the T-shaped quartz glass tube 7; at the same time, the desorption solvent will form an electrospray ion flow 17 at the tip of the electrospray capillary. Figure 3The purple light emitted from the end of the T-shaped quartz glass tube in (B) indicates the formation of the plasma jet 18, thus proving that, under the induction of the working coil, the plasma jet can be automatically initiated simply by turning on the DC high voltage of the DESI ionization source, without the need for an additional igniter to provide electrons to generate plasma, making the device structure simple. The plasma jet 18 and the electrospray ion stream 17 together constitute the main body of the ion source.

[0065] The template 14 is used to support and position the sample 15 to be tested. The sample 15 is placed on the surface of the template 14 and can be a solid or a liquid. In this embodiment, the template 15 is made of glass.

[0066] Furthermore, the novel mass spectrometry-based desorption-ionization source device provided in this embodiment also includes an ion source support 19. This ion source support 19 has a groove with the same outer diameter as the variable-diameter medium tube, used to fix the T-shaped quartz glass tube 7 and position the relative position and azimuth angle between the inlet of the electrospray capillary 8, the surface of the sample to be tested, and the inlet of the mass analyzer 16 integrated in the mass spectrometer. The mass analyzer 16 is used to analyze the ions generated by the sample to be tested. The ion source support 19 is fixed on an XYZ three-dimensional displacement slide, and the relative position and azimuth angle between the inlet of the electrospray capillary, the surface of the sample to be tested, and the inlet of the mass analyzer can be adjusted via the XYZ three-dimensional displacement slide. Specifically, the ion source support 19 is fixed on the circular R-axis of the Z-axis in the XYZ three-dimensional displacement slide and can rotate 360°. The XYZ three-dimensional displacement slide is made of aluminum alloy and is operated by a knob. The X-axis travel is 100 mm, used to adjust the lateral distance between the electrospray capillary inlet, the sample surface, and the mass analyzer inlet; the Y-axis travel is 100 mm, used to adjust the longitudinal distance between the electrospray capillary inlet, the sample surface, and the mass analyzer inlet; and the Z-axis travel is 100 mm, used to adjust the vertical distance between the electrospray capillary inlet, the sample surface, and the mass analyzer inlet. This effectively adjusts the positional relationship between the ion source body, the sample point, and the mass analyzer inlet 16. In this embodiment, the ion source support is 3D printed, rectangular, 13 cm long and 4 cm wide, and made of rigid polylactic acid. The distance from the tip of the ion source body (the tip of the plasma jet 18) to the sample surface is 1 mm. The contact angle between the plasma jet 18 generated by MIPDI and the sample point is 45°. The horizontal distance between the sample point and the mass analyzer inlet 16 is 5 mm, and the vertical distance is 2 mm.

[0067] The specific steps for mass spectrometry analysis using this embodiment include:

[0068] (1) Connect and adjust the air and electrical circuits of DESI and MIPDI using the XYZ three-dimensional displacement slide;

[0069] (2) The relative positions of the inlet of the electrospray capillary 8, the sample 15 to be tested, and the inlet of the mass analyzer 16 are determined by the XYZ three-dimensional displacement slide to ensure that the obtained sample ions can smoothly enter the mass analyzer.

[0070] (3) Turn on the gas cylinder 4 and the mass flow controller 6 to deliver gas to the T-shaped quartz glass tube 7; turn on the injection pump 1 to deliver the desorption solvent; turn on the DC high voltage power supply and apply the DC high voltage 9 to the electrospray capillary 8; turn on the solid microwave source 11 to start delivering microwaves; under the action of the airflow, the desorption solvent will form an electrospray ion flow 17 at the tip of the electrospray capillary 8, and the plasma jet 18 will be ejected through the thin tube opening of the T-shaped quartz glass tube.

[0071] (4) Place the sample to be tested 15 under the electrospray ion flow 17 and the plasma jet 18;

[0072] (5) Open the mass spectrometer detection software and obtain the detection results.

[0073] Example 2

[0074] This embodiment provides an application of the novel mass spectrometry-based desorption / ionization source device provided in Example 1, combined with a mass spectrometer, in the detection of anesthetic drugs. Specifically, this embodiment combines the novel mass spectrometry-based desorption / ionization source device with a Bruker high-resolution time-of-flight mass spectrometer (Bruker microOTOF-Q) to perform qualitative mass spectrometry analysis on a mixed standard solution of three local anesthetics: procaine, tetracaine, and debucaine.

[0075] (1) Experimental materials:

[0076] The sample solution was procaine C. 13 H 20 N2O2, tetracaine C 15 H 24 N2O2, debucaine C 20 H 29 The N3O2 mixed standard solution, the concentration of each of the three solutions is 10. -3 mg / mL, when not in use for testing, store properly in a refrigerator.

[0077] (2) Experimental conditions:

[0078] In this example, the DC high voltage used is 2 kV, the microwave power is 52 W, the gas is argon with a flow rate of 0.6 L / min, the solvent is methanol with a flow rate of 5 μL / min.

[0079] In this embodiment, data acquisition was performed using the microOTOF control software integrated into the mass spectrometer. The mass analyzer parameters were set as follows: positive ion acquisition mode; endplate voltage: 500V; capillary voltage: 4500V; drying gas temperature: 200℃; drying gas flow rate: 3.0 L / min; scan range: m / z 40-400; scan frequency: 3 Hz; transfer time: 30 μs; TIC mode was used to determine the molecular ion peak. Mass spectrometry data were acquired for 1 min using DESI, 1 min using MIPDI, and 1 min using DESI+MIPDI. The results are shown below. Figure 4-6 As shown.

[0080] 2. Analysis of experimental results:

[0081] The molecular formula of procaine [M+H] was calculated using the instrument's built-in software, Compass Isotope Pattern. + The theoretical value is 237.159754, for tetracaine [M+H]. + The theoretical value is 265.191054, for debucaine [M+H]. + The theoretical value is 344.233254. According to... Figure 4 , Figure 5 and Figure 6 Mass spectrometry analysis revealed a mixture of tricaine and [M+H]. + The values ​​are respectively compared with the theoretical [M+H] + The values ​​differ by ∆0.000546, ∆0.000246, and ∆0.002146, which are basically consistent with the computer calculation values, with minimal error. Furthermore, the mass spectra clearly show that the signal intensities of the three target analytes in both DESI and MIPDI modes are ~10. 5 In DESI and MIPDI modes (DESI+MIPDI), the signal strength of the three targets jumped to ~10. 7 The signal strength was significantly enhanced by 100 times compared to a single ionization source, verifying the excellent performance of the DESI and MIPDI composite ionization source.

[0082] The reason why the DESI and MIPDI combined ionization source can significantly improve the detection signal intensity is likely that: molecules in the excited state are more likely to be protonated to form protonated ions; the high temperature of MIPDI means that excited-state molecules have higher internal energy (more thermal energy than ground-state molecules), making it easier to overcome the energy barrier of the protonation reaction. Combining the DESI and MIPDI ionization sources makes it easier for molecules to transition from the ground state to the excited state.

[0083] In summary, the present invention provides a novel mass spectrometry-based desorption / ionization source device that combines DESI and MIPDI ion sources and incorporates a working coil. One end of the working coil is connected to a microwave introduction unit, and the other end is wound around a thin segment of the dielectric tube and then back to the microwave introduction unit, positioned close to the sample to be tested. Through the interaction of MIPDI and the working coil, DESI can automatically induce plasma generation without requiring additional electrons, and the ionization region can be made more concentrated, measuring only 0.375 cm⁻¹. 3 This allows the combination of the DESI ionization source and the MIPDI ionization source to significantly improve the detection signal intensity of the mass spectrometer, especially increasing the detection signal of anesthetic samples with complex structures by 100 times.

[0084] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them; although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications can still be made to the specific implementation of the present invention or equivalent substitutions can be made to some technical features without departing from the spirit of the technical solutions of the present invention, and all such modifications and substitutions should be covered within the scope of the technical solutions claimed in the present invention.

Claims

1. A mass spectrometry combined desorption ionization source device, comprising: A microwave plasma ionization source includes a T-shaped insulating dielectric tube, a gas introduction unit, a microwave introduction unit, and a working coil. The T-shaped insulating dielectric tube comprises a variable-diameter dielectric tube and a dielectric branch tube, the variable-diameter dielectric tube consisting of a thicker section and a thinner section extending from the thicker section. The dielectric branch tube is disposed on one side of the thicker section and connected to the gas introduction unit. One end of the working coil is connected to the microwave introduction unit, and the other end is wound around the thinner section of the dielectric tube and back to the microwave introduction unit, positioned close to the sample to be tested. The length of the working coil is an integer multiple of the microwave wavelength. The microwave introduction unit includes a solid-state microwave source and a coaxial line, the coaxial line being connected to both the solid-state microwave source and the working coil. An electrospray ionization source includes an electrospray capillary, a desorption solvent introduction unit, and a DC voltage. The electrospray capillary is coaxially arranged with the variable diameter medium tube and passes through the variable diameter medium tube. The electrospray capillary extends into the thicker section of the medium tube and is connected to the desorption solvent introduction unit and the DC voltage, respectively. The electrospray capillary extends out of the thinner section of the medium tube or is inside the thinner section of the medium tube and faces the sample to be tested.

2. The apparatus according to claim 1, characterized in that, It also includes an XYZ three-dimensional displacement slide stage, used to precisely adjust the relative position and angle between the T-shaped insulating dielectric tube, the surface of the sample to be tested, and the mass analyzer integrated in the mass spectrometer.

3. The apparatus according to claim 2, characterized in that, It also includes an ion source support for fixing the T-shaped insulating dielectric tube.

4. The application of the device according to any one of claims 1-3 in combination with a mass spectrometer in the analysis of compound structures, wherein the operating modes of the device include independent operation of the microwave plasma ionization source, independent operation of the electrospray ionization source, and joint operation of the microwave plasma ionization source and the electrospray ionization source.

5. A method for mass spectrometry analysis using the apparatus according to any one of claims 1-3 in conjunction with a mass spectrometer, wherein the mass analyzer is integrated into the mass spectrometer, comprising the steps of: Adjusting the positional relationship: Adjusting and determining the relative positions of the T-shaped insulating dielectric tube, the sample to be tested, and the inlet of the mass analyzer; Forming the ion source body: The microwave plasma ionization source is operated alone to eject a plasma jet from the opening of the thin segment of the dielectric tube; or, the electrospray ionization source is operated alone to form an electrospray ion flow from the tip of the electrospray capillary; or, the microwave plasma ionization source and the electrospray ionization source are operated in combination. This combined operation method includes turning on the gas introduction unit to deliver gas to the T-shaped insulating dielectric tube, turning on the desorption solvent introduction unit to deliver desorption solvent, applying the DC voltage to the electrospray capillary, and starting the microwave introduction unit to deliver microwaves to the thin segment of the dielectric tube; under the action of the airflow, the desorption solvent forms an electrospray ion flow at the tip of the electrospray capillary, and the plasma jet is ejected through the opening of the thin segment of the dielectric tube. Sample placement: The sample to be tested is placed under the ion source body. Depending on the operating mode, the ion source body may be a plasma jet, an electrospray ion stream, or a combination of both. Mass spectrometry detection: Open the mass spectrometer detection software to obtain the detection results.

6. The method according to claim 5, characterized in that, The sample to be tested is a substance containing α,β unsaturated ketones, and the microwave plasma ionization source and the electrospray ionization source are operated in combination.

7. The method according to claim 5 or 6, characterized in that, In the step of adjusting the positional relationship, the distance from the tip of the ion source body to the surface of the sample to be tested is controlled to be <2 mm by the XYZ three-dimensional displacement slide. The angle between the ion source body and the sample point is 30°-90°. The horizontal distance between the sample point and the mass analyzer inlet is 2-10 mm, and the vertical distance is 1-3 mm.

Images