Mass spectrum composite desorption ionization source device and application thereof

Abstract

The invention provides a novel mass spectrum composite desorption ionization source device and application thereof. The device comprises a microwave plasma ionization source and an electrospray ion source, a reducing medium tube in a T-shaped insulating medium tube in the microwave plasma ionization source and an electrospray capillary tube are coaxially arranged, meanwhile, a working coil is introduced, one end of the working coil is connected with a microwave introduction unit, and the other end of the working coil is connected with a power supply unit. The other end of the microwave induction unit is wound on the thin section of the medium tube, is wound back to the microwave induction unit and is arranged close to the sample to be detected; thus, in the same time space, the electrospray ion source provides stable initial ionization, the microwave plasma ionization source further enhances analysis signals through secondary ionization, the electrospray ion source and the microwave plasma ionization source are compounded together, the coulomb interference problem is solved, the ionization area is more concentrated under the action of the working coil, and the ionization efficiency is improved. The detection signal is improved to a great extent, and the detection signal can be improved by 100 times.

Description

Technical Field

[0001] The invention belongs to the field of analytical chemistry and the field of ion sources of mass spectrometers, and in particular relates to a novel device of a desorption electrospray / microwave-induced plasma desorption composite ionization source and an application thereof. Background Art

[0002] Mass spectrometry has been widely used in many fields such as biology, food, and atmosphere due to its advantages of high sensitivity, high analytical throughput, high resolution, and high compatibility with chromatographs. Ionization methods play a vital role in the field of mass spectrometry, because the ionization efficiency directly affects the sensitivity and detection limit of the technology. The desorption electrospray ionization source (DESI) can ionize samples without destroying the molecular structure, and has become the most widely used atmospheric pressure soft ionization source. With the continuous development of analytical technology, a single ionization source often cannot perform optimally in all scenarios. Especially in the analysis of complex samples, the improvement of signal strength and sensitivity has always been a key research goal. Therefore, researchers have been looking for new ionization technologies to overcome these challenges and improve analytical efficiency.

[0003] Combining different ionization technologies to construct a composite ionization source has been proven by previous studies to improve the ionization efficiency of sample detection. Plasma-based ionization sources have received widespread attention due to their good sample ionization efficiency, but ionization sources that induce plasma through high-voltage direct current and radio frequency power have problems such as high-voltage limitations and electrode contamination, which limit their application. Microwave-induced plasma ionization sources (MIPDI, Microplasma-Induced Plasma Desorption Ionization) avoid the problems of high-voltage limitations and electrode contamination. The basic principle is that microwaves are usually used to excite gases (such as helium and argon) to form high-energy plasma, and samples are excited, decomposed and ionized in this environment.

[0004] In the Taiwan invention patent application TW200703412A entitled "Nebulizer with Plasma Source", Matra Co., Ltd. disclosed a combination of an electrospray / microwave induced plasma (MIP) ion source for use as an ion source for a mass spectrometer. The electrospray can be operated in a positive mode, a negative mode, 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. When the electrospray is turned off and the microwave induced plasma is turned on, the device will generally have the greatest elemental sensitivity. Mixed mode operation may allow other information about the existing chemical components in the analyte to be determined. In a pure electrospray mode, it is possible to obtain molecular information and analyze organic compounds. It can be seen that the invention patent application aims to combine the two ionization methods of electrospray and microwave induced plasma to improve the ionization effect through multi-mode operation; but it does not clearly propose a specific structural design, and the structural design of the ionization source device is crucial to its detection effect; the above invention patent application also does not clearly disclose the detection effect on local anesthetic samples. Summary of the invention

[0005] In view of this, the main purpose of the present invention is to provide a new type of mass spectrometry composite desorption ionization source device and its application. The device mainly combines two ion sources, desorption electrospray ionization source (DESI) and microwave induced plasma desorption ionization source (MIPDI), and introduces a working coil at the same time; thus, in the same time and space, the DESI ionization source provides a relatively stable initial ionization, and the MIPDI further enhances the analysis signal through secondary ionization. The two are combined together to solve the problem of Coulomb interference, and the ionization area is more concentrated under the action of the working coil, which greatly improves the detection signal, and can increase the detection signal by 100 times.

[0006] The specific technical solutions are as follows: A mass spectrometry composite desorption ionization source device, comprising: A microwave plasma ionization source comprises a T-shaped insulating dielectric tube, a gas introduction unit, a microwave introduction unit and a working coil, wherein the T-shaped insulating dielectric tube comprises a variable diameter dielectric tube and a dielectric branch tube, the variable diameter dielectric tube mainly comprises a dielectric tube thick section and a dielectric tube thin section extending from the dielectric tube thick section; the dielectric branch tube is arranged on one side of the dielectric tube thick 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 dielectric tube thin section and wound back to the microwave introduction unit, and is arranged close to the sample to be tested; The electrospray ion source comprises an electrospray capillary, a desorption solvent introduction unit and a direct current voltage. The electrospray capillary is coaxially arranged with the variable diameter medium tube and penetrates the variable diameter medium tube. The electrospray capillary extends from the thick section of the medium tube and is respectively connected to the desorption solvent introduction unit and the direct current voltage; the electrospray capillary extends from the thin section of the medium tube or is in the thin section of the medium tube and faces the sample to be detected.

[0007] The "sample" mentioned in the present invention refers to a liquid material or a solid material.

[0008] Based on the above, the length of the working coil is an integer multiple of the microwave wavelength. In this way, the working coil is used to induce the generation of plasma, and its working state is close to the resonant state, which can form a relatively uniform and extensive radiation pattern, effectively radiating microwave energy into space. Microwaves can propagate on the working coil without distortion, avoiding microwave attenuation, so that the transmitted energy is maximized.

[0009] Based on the above, the microwave introduction unit includes a solid microwave source and a coaxial line, and the coaxial line is connected to the solid microwave source and the working coil respectively.

[0010] Based on the above device, it also includes an XYZ three-dimensional displacement slide for accurately adjusting the relative position and angle between the T-shaped insulating medium tube, the surface of the sample to be tested and the mass analyzer integrated in the mass spectrometer; this makes the ionization area more concentrated, the ionization efficiency higher, and the sample ions can smoothly enter the entrance of the mass analyzer.

[0011] The device further comprises an ion source bracket for fixing the T-shaped insulating medium tube.

[0012] A mass spectrometry composite desorption ionization source device is used in combination with a mass spectrometer in analyzing compound structures. The operation modes of the device include independent operation of a microwave plasma ionization source, independent operation of an electrospray ionization source, and combined operation of a microwave plasma ionization source and an electrospray ionization source.

[0013] The microwave plasma ionization source and the electrospray ionization source can be used in combination to detect and analyze substances containing α, β unsaturated ketones.

[0014] Compared with the prior art, the mass spectrometry composite desorption ionization source device provided by the present invention has the following characteristics: 1) Under the combined action of microwaves and the working coil, the plasma jet can be automatically triggered 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, thus simplifying the device; 2) Under the induction of the working coil, the ionization area is more concentrated, and the ionization area can be only 0.375 cm3 ; 3) The device of the present invention can not only realize the single functions of DESI ionization source and MID ionization source, but also can use the two together, which can greatly increase the detection signal by 100 times, especially can be applied to the detection of complex compound samples containing α, β unsaturated ketones.

[0015] Therefore, the mass spectrometry composite desorption ionization source device provided by the present invention has the advantages of high ionization, concentrated ionization area, miniaturization, integration, simple structure, easy processing, convenient operation, low price, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 A schematic diagram of the structure of a mass spectrometry composite desorption ionization source device provided in Example 1 of the present invention; Figure 2 A schematic diagram of the ion source body generated by the mass spectrometry composite desorption ionization source device provided in Example 1; Figure 3 (A) is a diagram of the experimental phenomenon of the mass spectrometry composite desorption ionization source device provided in Example 1 using DESI alone, Figure 3 (B) is a diagram of the experimental phenomenon of the mass spectrometry composite desorption ionization source device provided in Example 1 using DESI+MIPDI at the same time, where Figure 3 (B) The influence of background. The electrospray ion flow generated from the thin section of the T-shaped glass tube is not easy to observe with the naked eye. Figure 4 The mass spectrometry composite desorption ionization source device provided in Example 1 is a mass spectrum of a tricaine mixed sample in DESI mode; Figure 5 The mass spectrometry composite desorption ionization source device provided in Example 1 is a mass spectrum of a tricaine mixed sample in MIPDI mode; Figure 6 The mass spectrometry composite desorption ionization source device provided in Example 1 is a mass spectrum of a tricaine mixed sample in DESI+MIPDI mode; Among them, in the above figures: injection pump 1; syringe 2; delivery tube 3; gas cylinder 4; gas tube 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 line 12; microwave interface 13; sample 14; sample 15; mass analyzer 16; electrospray ion flow 17; plasma jet 18; ion source bracket 19. DETAILED DESCRIPTION

[0017] Unless otherwise specified, the terms used in the present invention are commonly used terms in the relevant field. The preparation processes, testing methods, etc. used in each embodiment are conventional means well known to those skilled in the art unless otherwise specified. The raw materials and equipment used can be obtained from public commercial channels.

[0018] The present invention is mainly based on the combination of two ion sources, desorption electrospray ionization source (DESI) and microwave induced plasma desorption ionization source (MIPDI), to provide a new type of mass spectrometry composite desorption ionization source device. The device combines DESI and MIPDI, and under the induction of the working coil, solves the problem of Coulomb interference, makes the ionization area more concentrated, and greatly improves the detection signal, especially the detection signal of anesthetic drugs can be increased by 100 times.

[0019] Specifically, the present invention provides a mass spectrometry composite desorption ionization source device, comprising: A microwave plasma ionization source comprises a T-shaped insulating dielectric tube, a gas introduction unit, a microwave introduction unit and a working coil, wherein the T-shaped insulating dielectric tube comprises a variable diameter dielectric tube and a dielectric branch tube, the variable diameter dielectric tube mainly comprises a dielectric tube thick section and a dielectric tube thin section extending from the dielectric tube thick section; the dielectric branch tube is arranged on one side of the dielectric tube thick 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 dielectric tube thin section and wound back to the microwave introduction unit, and is arranged close to the sample to be tested; The electrospray ion source comprises an electrospray capillary, a desorption solvent introduction unit and a direct current voltage. The electrospray capillary is coaxially arranged with the variable diameter medium tube and penetrates the variable diameter medium tube. The electrospray capillary extends from the thick section of the medium tube and is respectively connected to the desorption solvent introduction unit and the direct current voltage; the electrospray capillary extends from the thin section of the medium tube or is in the thin section of the medium tube and faces the sample to be detected.

[0020] The desorption solvent introduction unit is used to provide a desorption solvent to the electrospray capillary, and the desorption solvent may be methanol, acetonitrile, isopropanol, acetone, etc. The desorption solvent introduction unit is an existing structure, and may include a syringe pump, a syringe, and a delivery tube connected to one end of the electrospray capillary, and the two ends of the syringe are respectively connected to the syringe pump and the delivery tube. The desorption solvent is placed in the syringe, and the desorption solvent is injected into the delivery tube at a predetermined rate by the syringe pump. The other end of the delivery tube is connected to the electrospray capillary. Under the action of DC high voltage, the desorption solvent generates charged droplets, forming an electrospray ion flow that is ejected from the tip of the electrospray capillary (the end close to the sample to be tested), thereby realizing the independent operation of the electrospray ion source. Among them, the delivery tube is an insulating hollow tube, and the diameter of the electrospray capillary is preferably 0.1-0.3mm.

[0021] The T-shaped insulating dielectric tube is made of glass, quartz or ceramic. The diameter of the thick section of the dielectric tube is preferably 5-10 mm and the length is 50-80 mm, and the diameter of the thin section of the dielectric tube is preferably 1-5 mm and the length is 50-80 mm. The dielectric branch pipe is preferably perpendicular to the thick section of the dielectric tube, and the specific position on the thick section of the dielectric tube is not limited; the diameter of the dielectric branch pipe is preferably 5-10 mm and the length is 20-50 mm.

[0022] The mass spectrometry composite desorption ionization source device also includes a gas introduction unit for providing gas, which is an existing structure and can include a gas cylinder for providing gas, a gas pipe for connecting the gas cylinder and the medium branch pipe, and a mass flow controller installed on the gas pipe, and the flow rate of the gas is adjusted by the mass flow controller. The gas is an inert gas such as argon or helium.

[0023] The microwave introduction unit is mainly used to generate microwaves. It is an existing structure and may include a solid microwave source and a coaxial line, which is connected to the solid microwave source and the working coil respectively. The coaxial line is straight and cannot be bent so as to affect the transmission efficiency of the microwave. The coaxial line can be connected to the working coil through a microwave interface. The length of the coaxial line is preferably 40-60 cm, and a microwave interface with a hole is provided at the end of the coaxial line, and the microwave interface is made of metal.

[0024] 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. Microwaves are emitted by a solid-state microwave source, excite gas to generate plasma, and are ejected from the pipe mouth of the thin section of the dielectric pipe; thereby realizing the independent operation of the microwave plasma ionization source.

[0025] The microwave plasma ionization source and the electrospray ionization source operate jointly: the solid-state microwave source generates high-frequency microwaves which are transmitted to the working coil via the coaxial line, and an electromagnetic field is generated inside the working coil. The DC high voltage of the electrospray ionization source provides electrons, and the electrons absorb the magnetic field energy and collide with the ground-state gas atoms to generate new electrons. The new electrons will continue to collide with the ground-state gas atoms, and the process will continue to cycle. When the generated electrons and ions fill the internal space of the working coil, a connected discharge channel is formed, gas breakdown discharge is generated, and plasma is formed. Therefore, under the joint action of the electrons provided by the microwave and the DC high voltage, the electrons absorb the magnetic field energy and thermal energy and are accelerated by the electric field to collide with the ground-state gas atoms to generate plasma jets. Driven by the airflow, the plasma jets will be ejected through the orifice of the thin section of the dielectric tube in the T-shaped insulating dielectric tube; at the same time, the desorption solvent will form 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.

[0026] When the microwave plasma ionization source and the electrospray ionization source are operated together, the desorption solvent is ejected through the electrospray capillary only under the action of the DC high voltage to produce charged droplets. Under the induction of the microwaves generated during the operation of the microwave plasma ionization source and the working coil, the plasma jet can be automatically triggered without the need for an additional igniter to form an electrospray ion flow. Preferably, the length of the working coil is an integer multiple of the wavelength of the microwave. In this way, 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 extensive radiation mode, effectively radiating microwave energy into space, and the microwave can be transmitted on the working coil without distortion, avoiding microwave attenuation, so that the transmitted energy reaches the maximum. Therefore, the working coil is a spiral coil wound by enameled wire, and the single-layer coils cannot be connected or touched, otherwise a short circuit will occur. Preferably, the length of the working coil is one wavelength of the microwave, so that impedance matching is further achieved, reflected waves are reduced, and the output signal with the minimum standing wave ratio is consistent with the input signal in phase, so that the microwave transmission effect is optimal.

[0027] The mass spectrometry composite desorption ionization source device further includes a sample plate for carrying and positioning the sample to be tested, the sample to be tested is placed on the surface of the sample plate, and the sample suitable for analysis in the present invention is solid or liquid. The material of the sample plate is glass, silicon wafer, stainless steel, polytetrafluoroethylene, etc.

[0028] Further, the mass spectrometry composite desorption ionization source device also includes an ion source bracket, which is used to fix the T-shaped insulating medium tube, locate the relative position relationship and angle between the T-shaped insulating medium tube, the surface of the sample to be tested and the mass analyzer integrated in the mass spectrometer, so as to determine the relative position between the ion source body, the sample point and the entrance of the mass analyzer, and ensure that the sample ions can smoothly enter the entrance of the mass analyzer. The mass analyzer is used to analyze the ions generated by the sample to be tested. Specifically, the ion source bracket is fixed on the XYZ three-dimensional displacement slide, and the XYZ three-dimensional displacement slide includes an X-axis, a Y-axis and a Z-axis. The X-axis can be used to adjust the left and right distances between the T-shaped insulating medium tube, the surface of the sample to be tested and the entrance of the mass analyzer; the Y-axis can be used to adjust the front and back distances between the T-shaped insulating medium tube, the surface of the sample to be tested and the entrance of the mass analyzer; the Z-axis is used to adjust the upper and lower distances between the T-shaped insulating medium tube, the surface of the sample to be tested and the entrance of the mass analyzer. The ion source bracket is fixed on the circular R axis of the Z axis and can rotate 360°. In this way, the positional relationship between the T-shaped insulating medium tube, the sample to be tested and the mass analyzer can be effectively adjusted, thereby ensuring that the ionization area is more concentrated, the ionization efficiency is higher, and the sample ions can smoothly enter the entrance of the mass analyzer. Among them, the "sample point" in the present invention is the position where the sample to be tested is closest to the tip of the ion source body.

[0029] Another aspect of the present invention provides an application of a mass spectrometry composite desorption ionization source device combined with a mass spectrometer in analyzing the structure of a compound. The operating modes of the device include independent operation of a microwave plasma ionization source, independent operation of an electrospray ionization source, and combined operation of a microwave plasma ionization source and an electrospray ionization source, thereby making the mass spectrometry composite desorption ionization source device provided by the present invention suitable for the detection of complex compounds and having a wide range of applications.

[0030] Another aspect of the present invention provides a method for mass spectrometry analysis using a mass spectrometry composite desorption ionization source device in combination with a mass spectrometer, comprising the steps of: Adjusting the positional relationship: adjusting and determining the relative positions of the T-shaped insulating medium tube, the sample to be tested and the inlet of the mass analyzer; Forming an ion source body: operating the microwave plasma ionization source alone to eject a plasma jet from the orifice of the thin section of the dielectric tube; or operating the electrospray ion source alone to form an electrospray ion flow from the tip of the electrospray capillary; or operating the microwave plasma ionization source and the electrospray ion source jointly, the joint operation method comprising starting the gas introduction unit to deliver gas to the T-shaped insulating dielectric tube, starting 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 section of the dielectric tube; under the action of the gas flow, the desorption solvent forms an electrospray ion flow at the tip of the electrospray capillary, and the plasma jet is ejected from the orifice of the thin section of the dielectric tube; Placing the sample: placing the sample to be tested under the ion source body. Depending on the operation mode, the ion source body is a plasma jet, an electrospray ion flow, or a combination of the two; Mass spectrometry detection: Open the mass spectrometer detection software and obtain the detection results.

[0031] 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 are operated in combination. The substance containing α,β-unsaturated ketones includes complex compounds such as anesthetics and hormone drugs, such as procaine, tetracaine, dibucaine, dimethocaine, lidocaine, and the like.

[0032] 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 contact angle between the ion source body and the sample point is 30°-90°, the horizontal distance between the sample point and the entrance of the mass analyzer is about 2-10 mm, and the vertical distance is about 1-3 mm; in this way, efficient detection of substances containing α, β unsaturated ketones can be achieved.

[0033] Compared with the prior art, the mass spectrometry composite desorption ionization source device provided by the present invention has the following characteristics: 1) Under the induction of microwaves and working coils, the plasma jet can be automatically triggered 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, thus simplifying the device; 2) In the same space and time, the electromagnetic field generated in the MIPDI ionization source mainly acts on the excitation and maintenance of the plasma, and will not affect the ionization efficiency of the DESI ionization source. Therefore, DESI provides a relatively stable initial ionization, and MIPDI further enhances the analytical signal through secondary ionization. The two are combined together to solve the problem of Coulomb interference. Therefore, under the induction of the working coil, the ionization area is more concentrated, and the ionization area can be only 0.375 cm 3 ; 3) The device of the present invention can not only realize the single function of DESI ionization source and MID ionization source, but also can use the two together for the detection of compound samples containing α, β unsaturated ketones, which can greatly increase the detection signal by 100 times.

[0034] Therefore, the mass spectrometry composite desorption ionization source device provided by the present invention has the advantages of high ionization, concentrated ionization area, miniaturization, integration, simple structure, easy processing, convenient operation, low price, etc.

[0035] The technical solution of the present invention is further described in detail below through specific implementation methods.

[0036] Example 1 See also Figure 1 and Figure 2 The present 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 line 12, a microwave interface 13 and a sample 14.

[0037] The gas cylinder 4, gas pipe 5 and mass flow controller 6 constitute a gas introduction unit for providing gas for the generation of an electrospray ionization source. The gas pipe 5 connects the gas cylinder 4 and a T-shaped quartz glass tube 7. The mass flow controller 6 is installed on the gas pipe 5 to control the flow rate of the gas released from the gas cylinder 4. In this embodiment, the gas is argon gas with a flow rate of 0.6 L / min.

[0038] The injection pump 1, the syringe 2 and the delivery tube 3 constitute a desorption solvent introduction unit, which provides the desorption solvent for the electrospray ionization source. The desorption solvent can be placed in the syringe 2, and the desorption solvent is injected into the delivery tube 3 at a preset rate through the injection pump 1. The other end of the delivery tube 3 is connected to the electrospray capillary 8. The desorption solvent is sprayed through the electrospray capillary 8 under the action of the DC high voltage 9 to generate charged droplets, which are driven by the gas to form a charged spray ion flow 17, such as Figure 3 In this embodiment, the desorption solvent is methanol, and its delivery rate is 5 μL / min. The delivery tube 3 is an insulating hollow tube, and the electrospray capillary 8 is a stainless steel capillary with a diameter of 0.3 mm.

[0039] The T-shaped quartz glass tube 7 includes a variable diameter medium tube, which is mainly composed of a medium tube thick section and a medium tube thin section extending from the medium tube thick section. A medium branch pipe is arranged on one side of the medium tube thick section, and the medium branch pipe is connected to the air pipe 5. The electrospray capillary 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 diameter of the variable diameter medium tube thick section is 7 mm and the length is 40 mm, the diameter of the variable diameter medium tube thin section is 4 mm and the length is 50 mm, and the diameter of the medium branch pipe is 7 mm and the length is 50 mm.

[0040] The electrospray capillary 8 extending from the thick section of the medium tube is respectively connected to the delivery tube 3 and the DC high voltage 9. The tube mouth of the electrospray capillary 8 extending from the thin section of the medium tube faces the sample to be tested 15. The tip of the thin section of the medium tube is wound with a working coil 10, which is a spiral coil wound by enameled wire and is used to induce microwave plasma generation. The length of the working coil is one wavelength of the microwave generated by the solid-state microwave source 11, 12.2 cm.

[0041] The solid-state microwave source 11, the coaxial line 12 and the 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 through the coaxial line 12, and the coaxial line 12 is straight and cannot be bent. The length of the coaxial line 12 is 50 cm, and a microwave interface 13 with a hole is provided at the end of the coaxial line 12. The end of the working coil 10 is inserted into the hole of the microwave interface 13 to complete the transmission of the entire microwave, and the gas is excited under the action of the microwave to form a plasma jet 18. In this embodiment, the microwave frequency generated by the solid-state microwave source 11 is 2.45 GHz, and the microwave interface 13 is metal platinum.

[0042] See also Figure 2 and Figure 3 (B), under the combined action of microwaves and electrons provided by DC high voltage, the electrons absorb magnetic field energy and thermal energy and are accelerated by the electric field to collide and ionize with ground state gas atoms. 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 a plasma jet 18. Driven by the airflow, the plasma jet 18 is ejected through the orifice of the thin section of the dielectric tube in the T-shaped quartz glass tube 7; at the same time, the desorption solvent forms 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, which proves that under the induction of the working coil, the plasma jet can be automatically triggered by simply 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 flow 17 together constitute the main body of the ion source.

[0043] The sample 14 is used to carry and position the sample 15 to be tested. The sample 15 to be tested is placed on the surface of the sample 14. The sample 15 to be tested can be solid or liquid. In this embodiment, the sample 15 is made of glass.

[0044] Furthermore, the novel mass spectrometry composite desorption ionization source device provided in this embodiment also includes an ion source bracket 19, on which a groove having the same diameter as the outer diameter of the variable diameter medium tube is provided, which is used to fix the T-shaped quartz glass tube 7, and to locate the relative position and angle between the orifice 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. Among them, the mass analyzer 16 is used to analyze the ions generated by the sample to be tested. The ion source bracket 19 is fixed on the XYZ three-dimensional displacement slide, and the relative position and angle between the orifice of the electrospray capillary, the surface of the sample to be tested, and the inlet of the mass analyzer can be adjusted by the XYZ three-dimensional displacement slide. Specifically, the ion source bracket 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, knob-operated, and has an X-axis stroke of 100 mm, which can be used to adjust the left and right distance between the nozzle of the electrospray capillary, the surface of the sample to be tested, and the entrance of the mass analyzer; the Y-axis stroke is 100 mm, which can be used to adjust the front and back distance between the nozzle of the electrospray capillary, the surface of the sample to be tested, and the entrance of the mass analyzer; the Z-axis stroke is 100 mm, which can be used for the upper and lower distances between the nozzle of the electrospray capillary, the surface of the sample to be tested, and the entrance of the mass analyzer. In this way, the positional relationship between the ion source body, the sample point, and the entrance of the mass analyzer 16 can be effectively adjusted. In this embodiment, the ion source bracket is made by 3D printing, rectangular, 13 cm long and 4 cm wide, and is made of polylactic acid with strong rigidity; the distance from the tip of the ion source body (the tip of the plasma jet 18) to the surface of the sample to be tested is 1 mm, the angle of contact between the plasma jet 18 generated by MIPDI and the sample point is 45°, and the horizontal distance between the sample point and the entrance of the mass analyzer 16 is 5 mm and the vertical distance is 2 mm.

[0045] The specific steps of performing mass spectrometry analysis using this embodiment include: (1) Connect and adjust the gas and electrical circuits of DESI and MIPDI through the XYZ three-dimensional displacement slide; (2) Determine the relative positions of the orifice of the electrospray capillary 8, the sample 15 to be tested, and the entrance of the mass analyzer 16 by means of an XYZ three-dimensional displacement slide to ensure that the obtained sample ions can smoothly enter the mass analyzer; (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 syringe 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-state 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 narrow tube mouth of the T-shaped quartz glass tube; (4) placing the sample 15 to be tested under the electrospray ion flow 17 and the plasma jet 18; (5) Open the mass spectrometer detection software to obtain the detection results.

[0046] Example 2 This embodiment provides an application of the novel mass spectrometry composite desorption ionization source device provided in Example 1 combined with a mass spectrometer in the detection of anesthetics. Specifically, this embodiment combines the novel mass spectrometry composite desorption ionization source device with a Bruker high-resolution time-of-flight mass spectrometer (Bruker micrOTOF-Q) to perform mass spectrometry qualitative analysis on a mixed standard solution of three local anesthetics, procaine, tetracaine, and dibucaine.

[0047] (1) Experimental materials: The sample solution is procaine C 13 H 20 N2O2, tetracaine C 15 H 24 N2O2, dibucaine C 20 H 29 N3O2 mixed standard solution, the concentration of the three solutions is 10 -3 mg / mL, and should be kept in a refrigerator when not being tested.

[0048] (2) Experimental conditions: The DC high voltage used in this example is 2 kV, the microwave power is 52 W, the gas is argon, the argon flow rate is 0.6 L / min, and the solvent is methanol, and the methanol flow rate is 5 μL / min.

[0049] The data acquisition in this embodiment uses the software micrOTOF control that comes with the mass spectrometer. The mass analyzer parameters are set as follows: positive ion acquisition mode; end plate voltage: 500V; capillary voltage: 4500V; drying gas temperature: 200°C; drying gas flow rate: 3.0 L / min; scanning range: m / z 40-400; scanning frequency: 3 Hz; transmission time: 30 μs; TIC mode is used to determine the molecular ion peak, DESI collects mass spectrometry data for 1 min, MIPDI collects mass spectrometry data for 1 min, and DESI+MIPDI collects mass spectrometry data for 1 min. The results are as follows: Figure 4-6 shown.

[0050] 2. Experimental results analysis: The molecular formula was calculated based on the instrument's own software Compass Isotope Pattern, procaine [M+H] + The theoretical value is 237.159754, tetracaine [M+H] + The theoretical value is 265.191054, dibucaine [M+H] + The theoretical value is 344.233254. Figure 4 , Figure 5 and Figure 6 Mass spectrometry analysis revealed that the [M+H] + The values ​​are respectively the same as the theoretical [M+H] + The values ​​differ by ∆0.000546, ∆0.000246, and ∆0.002146, which are basically consistent with the values ​​calculated by computer, with little error. It can be clearly seen from the mass spectra that the signal intensities of the three targets in both DESI and MIPDI modes are all ~10 5 The signal intensity of the three targets in DESI and MIPDI mode (DESI+MIPDI) jumped to ~10 7 The signal intensity was significantly enhanced by 100 times compared with that of a single ionization source, verifying the excellent performance of the DESI and MIPDI composite ionization source.

[0051] The main reason why the DESI and MIPDI composite ionization source can greatly improve the detection signal intensity may be that: molecules in the excited state are more easily protonated to form protonated ions; due to the high temperature of MIPDI, the excited state molecules have higher internal energy (more thermal energy than ground state molecules), which can more easily overcome the energy barrier of the protonation reaction. Combining the DESI ionization source and the MIDI ionization source together makes it easier for molecules to transition from the ground state to the excited state.

[0052] In summary, the embodiment of the present invention provides a novel mass spectrometry composite desorption ionization source device, which mainly combines two ion sources, DESI and MIPDI, and introduces a working coil, one end of which is connected to a microwave introduction unit, and the other end is wound around the thin section of the medium tube and back to the microwave introduction unit, and is arranged close to the sample to be tested; through the action of MIPDI and the working coil, not only can DESI automatically induce the generation of plasma without the need for additional electrons; but also the ionization area can be more concentrated, only 0.375 cm 3 , the combination of DESI ionization source and MIPDI ionization source can greatly improve the detection signal intensity of the mass spectrometer, especially the detection signal of anesthetic samples with complex structure can be increased by 100 times.

[0053] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, ordinary technicians in the field should understand that the specific implementation methods of the present invention can still be modified or some technical features can be replaced by equivalents without departing from the spirit of the technical solution of the present invention, which should be included in the scope of the technical solution for protection of the present invention.

Claims

1. A mass spectrometry composite desorption ionization source device, comprising: A microwave plasma ionization source comprises a T-shaped insulating dielectric tube, a gas introduction unit, a microwave introduction unit and a working coil, wherein the T-shaped insulating dielectric tube comprises a variable diameter dielectric tube and a dielectric branch tube, the variable diameter dielectric tube mainly comprises a dielectric tube thick section and a dielectric tube thin section extending from the dielectric tube thick section; the dielectric branch tube is arranged on one side of the dielectric tube thick 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 dielectric tube thin section and wound back to the microwave introduction unit, and is arranged close to the sample to be tested; The electrospray ion source comprises an electrospray capillary, a desorption solvent introduction unit and a direct current voltage. The electrospray capillary is coaxially arranged with the variable diameter medium tube and penetrates the variable diameter medium tube. The electrospray capillary extends from the thick section of the medium tube and is respectively connected to the desorption solvent introduction unit and the direct current voltage; the electrospray capillary extends from the thin section of the medium tube or is in the thin section of the medium tube and faces the sample to be detected.

2. The device according to claim 1, characterized in that The length of the working coil is an integral multiple of the microwave wavelength.

3. The device according to claim 2, characterized in that The microwave introduction unit comprises a solid microwave source and a coaxial line, and the coaxial line is connected to the solid microwave source and the working coil respectively.

4. The device according to any one of claims 1 to 3, characterized in that: It also includes an XYZ three-dimensional displacement slide table for precisely adjusting the relative position and angle between the T-shaped insulating medium tube, the surface of the sample to be tested and the mass analyzer integrated in the mass spectrometer.

5. The device according to claim 4, characterized in that: Also included is an ion source bracket for fixing the T-shaped insulating medium tube.

6. Use of the device according to any one of claims 1 to 5 in combination with a mass spectrometer in analyzing compound structure, wherein the operating modes of the device include independent operation of a microwave plasma ionization source, independent operation of an electrospray ionization source, and combined operation of a microwave plasma ionization source and an electrospray ionization source.

7. A method for performing mass spectrometry analysis using the device according to any one of claims 1 to 5 in combination 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 medium tube, the sample to be tested and the inlet of the mass analyzer; Forming an ion source body: operating the microwave plasma ionization source alone to eject a plasma jet from the orifice of the thin section of the dielectric tube; or operating the electrospray ion source alone to form an electrospray ion flow from the tip of the electrospray capillary; or operating the microwave plasma ionization source and the electrospray ion source jointly, the joint operation method comprising starting the gas introduction unit to deliver gas to the T-shaped insulating dielectric tube, starting 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 section of the dielectric tube; under the action of the gas flow, the desorption solvent forms an electrospray ion flow at the tip of the electrospray capillary, and the plasma jet is ejected from the orifice of the thin section of the dielectric tube; Placing the sample: placing the sample to be tested under the ion source body. Depending on the operation mode, the ion source body is a plasma jet, an electrospray ion flow, or a combination of the two; Mass spectrometry detection: Open the mass spectrometer detection software and obtain the detection results.

8. The use according to claim 7, characterized in that: The sample to be tested is a substance containing α, β unsaturated ketone, and the microwave plasma ionization source and the electrospray ionization source are operated jointly.

9. The use according to claim 7, characterized in that: The substance containing α,β-unsaturated ketone includes anesthetics or hormone drugs.

10. The use according to any one of claims 7 to 9, 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 measured is controlled to be <2 mm by the XYZ three-dimensional displacement slide, the contact angle between the ion source body and the sample point is 30°-90°, the horizontal distance between the sample point and the entrance of the mass analyzer is about 2-10 mm, and the vertical distance is about 1-3 mm.

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