A paper-based electrospray ionization source integrated device and method for mass spectrometry analysis

Abstract

The application belongs to the technical field of mass spectrometric detection and analysis, and particularly relates to a paper-based electro-spray ionization source integrated device and method for mass spectrometric analysis. The device comprises a bearing platform, a rotating to-be-detected sample table, a plurality of conical sample tubes carried on the to-be-detected sample table, a solvent tank arranged above the bearing platform and located at the side of the to-be-detected sample table, an electrode clamping groove arranged above the bearing platform, a grabbing mechanism arranged above the bearing platform and located above the to-be-detected sample table, and a waste tube discarding channel arranged above the bearing platform. The application is based on the complex to-be-detected sample pretreatment-ionization integrated high-throughput technology of the paper-based electro-spray ionization source. The conical sample tube is grabbed by the grabbing mechanism, the tip of the conical sample tube is immersed in the solvent bottle, the solvent is loaded into the conical sample tube, and the conical sample tube is introduced into the electrode clamping groove for electro-spray ionization. The device can be used for rapid and high-sensitivity analysis of target compounds in complex to-be-detected samples.

Description

Technical Field

[0001] This invention belongs to the field of mass spectrometry detection and analysis technology, specifically relating to an integrated device and method for a paper-based electrospray ionization source used in mass spectrometry analysis. Background Technology

[0002] The most authoritative method for detecting target compounds in complex biological samples such as blood and urine is high-performance liquid chromatography-tandem mass spectrometry. Although this method has the characteristics of high sensitivity and low detection limit and plays a huge role in the detection and analysis of various compounds, it requires complex sample pretreatment steps such as digestion and pre-purification before the analysis of the sample. These steps are cumbersome and the analysis cost is high. It cannot detect the target compounds in the sample in a short time, thus delaying the evaluation and analysis.

[0003] Paper spray ionization (PSI) is an atmospheric pressure ionization source developed by Purdue University in 2010. The method involves cutting traditional chromatographic paper into triangles 10 mm high and 5 mm wide at the base. The sample to be analyzed, such as blood or urine, is then dropped into the center of the paper matrix. A solvent and spray voltage are applied, resulting in an electrospray at the tip of the triangular paper matrix. This ionization mode can be directly coupled to a mass spectrometer with an atmospheric pressure interface for the direct analysis of target compounds in complex samples. Compared to other types of atmospheric pressure ionization sources, PSI not only possesses the simple separation characteristics of paper chromatography but also allows for the differentiation and quantification of different compounds during mass spectrometry analysis. Currently, PSI coupled with tandem mass spectrometry has successfully analyzed target compounds in various complex samples, such as multiple diagnostic drugs in blood samples, hormonal compounds and lipids in biological tissue samples, and studies of chemical reaction mechanisms.

[0004] Currently, research on paper spray ionization-mass spectrometry (PSI) has evolved from simple compound analysis to high-sensitivity, high-throughput, and automated analysis of target compounds in complex analyte samples, particularly drug compounds and related metabolites in biological samples. To improve the throughput of mass spectrometry, existing techniques involve fixing multiple triangular paper matrices within a sliding plate, then applying solvent and voltage separately to perform high-throughput analysis of drug compounds in dried blood samples on the paper matrix surface. However, this approach still cannot achieve fully automated operation. Thermo Fisher Scientific subsequently developed an automated device where each triangular paper matrix is ​​fixed in a cartridge. When analyzing a sample, the sprayed solvent is loaded from a solvent storage bottle onto the paper matrix surface, and then a voltage is applied to the paper matrix through metal electrodes in the cartridge, thus realizing the paper spray ionization-mass spectrometry analysis process. This automated paper spray ionization device has been applied to the quantitative analysis of various drug compounds. Although the paper spray ionization device described above has advantages such as high analytical throughput, it does not take the adsorbent into account. The sample carrier still uses an unmodified paper matrix, which cannot effectively remove interference from complex sample matrices and improve the analytical sensitivity of target compounds. Its limit of quantitation is between 3 ng / mL. -1 ~68ng·mL -1 On the other hand, when the spray solvent is loaded onto the paper matrix surface, the solvent remains largely exposed to the air, increasing the evaporation rate and reducing spray time and stability. Typically, for 25µL of spray solvent, the spray time is less than 30 seconds, and the spray flow stability is poor. Furthermore, this automated device requires an additional flow pump to load the spray solvent, increasing instrument costs. Additionally, the electrode applying the spray voltage needs to be in contact with the paper matrix, increasing the risk of sample contamination and the possibility of sample dissociation. Summary of the Invention

[0005] To address the aforementioned problems, this invention provides an integrated device and method for a paper-based electrospray ionization source for mass spectrometry analysis. This achieves a high-throughput technique integrating pretreatment and ionization of complex analyte samples based on a paper-based electrospray ionization source. It not only considers the characteristics of adsorbent pretreatment for complex analyte samples but also effectively removes matrix interference from the analyte sample, improving the analytical sensitivity of mass spectrometry to 0.01 ng·mL⁻¹. -1 The establishment of an intelligent high-throughput ionization system not only lays a solid foundation for the high-throughput automated analysis of target compounds in complex test samples, but also provides a good platform for the rapid analysis of test samples such as food, environment, and biology. This, in turn, promotes the establishment and development of efficient, simple, and accurate analytical detection methods for related compounds in complex test samples.

[0006] The present invention solves the above-mentioned technical problems through the following technical solutions.

[0007] One objective of this invention is to provide an integrated paper-based electrospray ionization source device for mass spectrometry analysis, comprising:

[0008] The carrier platform has a rotating sample stage, on which multiple conical sample tubes are supported. All conical sample tubes contain paper matrix and adsorbent, with the adsorbent used to support the sample to be tested.

[0009] The solvent tank is located above the support platform and to the side of the sample stage. The solvent tank contains a solvent bottle, which is used to hold the solvent required for electrospray ionization.

[0010] The electrode slot, located above the support platform, is used to receive the conical sample tube and apply an induced voltage to electrospray ionize the solvent inside the conical sample tube before introducing it into the mass spectrometer inlet for mass spectrometry analysis.

[0011] The gripping mechanism, positioned above the support platform and above the sample stage, grips the conical sample tube, immerses its tip in the solvent bottle, and loads the solvent into the conical polymer tube using a self-priming method. The sample is then loaded into the solvent through liquid-solid extraction, and finally, the conical sample tube is guided into the electrode slot.

[0012] The waste tube disposal channel is located above the support platform and is used to recycle and process the conical sample tubes after the electrospray ionization is completed.

[0013] Furthermore, the conical sample tube has an open tip and an open rear end, with an inner diameter of 0.5 mm to 3 mm at the tip and 4 mm to 8 mm at the rear end, and a length of 15 mm to 30 mm.

[0014] Furthermore, the test sample stage includes a test sample tray and a base. The test sample tray has multiple bearing holes distributed around the circumference of the test sample tray. The test sample tray and the base are connected by multiple support columns. The base is rotatably mounted on a fixed frame, which is mounted on a bearing platform. A rotating shaft is rotatably mounted below the fixed frame. The rotating shaft passes through the fixed frame and connects to the base. The rotating shaft is rotatably connected to a drive mechanism.

[0015] Furthermore, a drive box is provided on the support platform, and a first driver is provided at the upper end of the drive box. The first driver is connected to the drive mechanism, which includes a drive driving wheel, a drive driven wheel, and a drive pulley. The output end of the first driver is connected to the drive driving wheel, and the lower end of the rotating shaft is connected to the drive driven wheel. The drive driving wheel and the drive pulley are connected by meshing with the drive pulley.

[0016] Furthermore, the gripping mechanism includes a support plate fixed on a support platform. A robotic arm is mounted on the support plate, and a rotating mechanism is mounted on the robotic arm. The rotating mechanism has a linkage shaft that slides up and down, and a linkage rod is mounted on the linkage shaft. The upper end of the linkage rod has a gripper for gripping the conical sample tube, and the lower end of the linkage rod passes through the rotating mechanism and is fixed to a reciprocating motion mechanism. The reciprocating motion mechanism is used for the linkage rod to move up and down, and the reciprocating motion mechanism is located below the robotic arm.

[0017] Furthermore, the rotating mechanism includes a rotating driving wheel, a rotating driven wheel, and a rotating pulley. The lower end of the rotating driving wheel passes through the robotic arm and is connected to the output end of the second driver. The rotating driven wheel is rotatably mounted on the robotic arm. A linkage shaft is provided inside the rotating driven wheel. The lower end of the linkage rod passes through the linkage shaft and is fixed to the up-and-down reciprocating motion mechanism. The rotating driving wheel and the rotating driven wheel are meshed and connected by the rotating pulley.

[0018] Furthermore, the reciprocating motion mechanism includes a reciprocating drive wheel, a reciprocating driven wheel, a reciprocating pulley, and a fixed shaft. A fixed plate is provided below the robotic arm. The reciprocating driven wheel is rotatably mounted on the fixed plate. One end of the reciprocating drive wheel passes through the fixed plate and is connected to the output end of the third driver. The reciprocating drive wheel and the reciprocating driven wheel are the same size and located at the same height line. The reciprocating drive wheel and the reciprocating driven wheel are connected by meshing with a rotating pulley. The fixed shaft is fixed on the rotating pulley. The linkage rod passes through the linkage shaft and is fixed on the fixed shaft.

[0019] Furthermore, the electrode slot includes a sample receiving slot and a high-voltage connector. The sample receiving slot is used to receive the conical sample tube and guide it into the mass spectrometer's inlet. The high-voltage connector is used to generate electrospray ionization of the sample to be tested in the conical sample tube. The sample receiving slot is located on a fixed block, which is rotatably mounted on a positioning plate. The positioning plate is fixed on a support platform. The fixed block is connected to the output end of the fourth driver, and the high-voltage connector is fixed on the support platform.

[0020] The second objective of this invention is to provide an integrated paper-based electrospray ionization source method for mass spectrometry analysis, utilizing the aforementioned integrated paper-based electrospray ionization source device, comprising the following steps:

[0021] S1. Install the paper-based electrospray ionization source integrated device at the sample inlet of the mass spectrometer.

[0022] S2. Place the paper matrix into the conical sample tube, then add the adsorbent solution. After drying, add the sample to be tested to the adsorbent, place the conical sample tube in the sample stage, and the gripping mechanism grips a conical sample tube. Then, immerse the tip of the conical sample tube into the solvent bottle and use self-absorption to load the solvent in the solvent bottle into the conical polymer tube. After liquid-solid extraction, the target compound in the sample is transferred from the surface of the adsorbent to the solvent in the conical polymer tube.

[0023] S3. Then, the gripping mechanism guides the conical polymer tube into the electrode slot, and the tip of the conical polymer tube is guided into the mass spectrometer's inlet. The electrode slot transmits the high voltage inside to the inside of the conical sample tube through induction. The solvent inside the tip of the conical sample tube is electrosprayed and ionized for mass spectrometry analysis.

[0024] Furthermore, the immersion time in the solvent bottle is 5s to 40s, the electrospray ionization time is 20s to 360s, and the electrospray ionization voltage is 3000V to 4500V.

[0025] Compared with the prior art, the present invention has the following advantages:

[0026] This invention provides an integrated paper-based electrospray ionization source device for mass spectrometry analysis. A conical sample tube serves as a carrier, loading a paper matrix and adsorbent. The adsorbent carries the sample to be analyzed. A gripping mechanism grasps the conical sample tube and immerses its tip into a solvent bottle in a solvent bath. Due to the unique structure of the conical sample tube tip, the tip self-absorbs the solvent into the conical polymer tube. The sample is then loaded into the solvent through liquid-solid extraction, eliminating the need for any flow pump to load the sprayed solvent, significantly reducing costs. The conical sample tube is then guided into an electrode holder, which induces the high voltage... The solvent inside the conical sample tube undergoes electrospray ionization at its tip and is then fed into the mass spectrometer inlet for mass spectrometry analysis. This allows for rapid and highly sensitive analysis of target compounds in complex samples. Simultaneously, after electrospray ionization, the electrode slot guides the deionized conical sample tube into a waste tube disposal channel for recycling. When the gripping mechanism picks up the previous conical sample tube from the sample stage, the stage rotates, positioning the next conical sample tube in the position of the previous one for the next pick. This invention enables continuous mass spectrometry analysis from the gripping of the conical sample tube and the self-absorption of the sprayed solvent to the application of power for complete spraying. The device is simple in structure, easy to assemble and operate. It not only considers the pretreatment characteristics of adsorbents for complex samples but also effectively removes matrix interference, increasing the analytical sensitivity of mass spectrometry to 0.01 ng·mL. -1 The establishment of an intelligent high-throughput ionization system not only lays a solid foundation for the high-throughput automated analysis of target compounds in complex test samples, but also provides a good platform for the rapid analysis of test samples such as food, environment, and biology. This, in turn, promotes the establishment and development of efficient, simple, and accurate analytical detection methods for related compounds in complex test samples. Attached Figure Description

[0027] Figure 1This is a schematic diagram of the integrated paper-based electrospray ionization source device for mass spectrometry analysis according to the present invention.

[0028] Figure 2 This is a schematic diagram of the gripping mechanism of the present invention.

[0029] Illustration:

[0030] 1. Support platform; 2. Sample stage; 3. Gripping mechanism; 4. Solvent tank; 5. Electrode slot; 6. Waste tube disposal channel; 21. Conical sample tube; 22. Sample tray; 23. Base; 24. Fixing frame; 25. Drive box; 26. First driver; 27. Drive mechanism; 31. Support plate; 32. Robotic arm; 33. Rotation mechanism; 34. Linkage shaft; 35. Linkage rod; 351. Connecting plate; 36. Clamp; 361. Fifth driver; 37. Up-down reciprocating motion mechanism; 38. Fixed shaft; 39. Limiting post; 41. Solvent bottle; 51. Sample receiving slot; 52. High-pressure connector.

[0031] Figure 3 This invention utilizes the aforementioned integrated paper-based electrospray ionization source device for mass spectrometry analysis of serum test samples, specifically targeting serum samples with concentrations of 1 μg·mL⁻¹. -1 Mass spectrometry ion chromatograms of 10 parallel experiments with amitriptyline, clozapine, amisulpride, quetiapine, risperidone, and aripiprazole.

[0032] Figure 4 This invention utilizes the aforementioned integrated paper-based electrospray ionization source device for mass spectrometry analysis of serum test samples, specifically targeting serum samples with concentrations of 1 μg·mL⁻¹. -1 The mass ion chromatograms obtained when amitriptyline, clozapine, amisulpride, quetiapine, risperidone and aripiprazole are ionized.

[0033] Figure 5 This invention utilizes the aforementioned integrated paper-based electrospray ionization source device for mass spectrometry analysis of serum test samples, specifically for serum samples with concentrations of 0.01 ng·mL⁻¹. -1 ~1000ng·mL -1 Quantitative analysis curves of amitriptyline, clozapine, amisulpride, quetiapine, risperidone, and aripiprazole. Detailed Implementation

[0034] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0035] It should be noted that the technical terms used in this invention are for the purpose of describing specific embodiments only and are not intended to limit the scope of protection of this invention. Unless otherwise specified, all raw materials, reagents, and equipment used in the following embodiments of this invention can be purchased commercially or prepared by existing methods. Certain terms are used in this invention to refer to specific components. Those skilled in the art will understand that different terms may be used to refer to the same component.

[0036] The following specific examples will provide further explanation.

[0037] An integrated paper-based electrospray ionization source device for mass spectrometry analysis, such as Figure 1 As shown, it includes:

[0038] A support platform 1 is provided, on which a sample stage 2 is rotatably mounted. The sample stage 2 supports multiple conical sample tubes 21, each containing a paper matrix and an adsorbent. The adsorbent is used to hold the sample to be tested. A solvent tank 4 is positioned above the support platform 1 and to the side of the sample stage 2. The solvent tank 4 contains a solvent bottle 41, which holds the solvent required for electrospray ionization. An electrode slot 5 is positioned above the support platform 1 to receive the conical sample tubes 21 and apply an induced voltage to the solvent inside the conical sample tubes 21. Electrospray ionization is performed, and the sample is then introduced into the mass spectrometer inlet for mass spectrometry analysis. The gripping mechanism 3, located above the support platform 1 and above the sample stage 2, is used to grip the conical sample tube 21, immerse the tip of the conical sample tube 21 into the solvent bottle 41, and load the solvent into the conical polymer tube 21 by self-absorption. The sample is loaded into the solvent through liquid-solid extraction, and then the conical sample tube 21 is guided into the electrode slot 5. The waste tube disposal channel 6, located above the support platform 1, is used to recycle and process the conical sample tube 21 after electrospray ionization.

[0039] This invention relates to a high-throughput integrated pretreatment and ionization technology for complex samples based on a paper-based electrospray ionization source. One side of the support platform 1 is connected to the positioning plate of the mass spectrometer, and multiple fixing seats are evenly distributed at the lower end of the support platform 1 to support it and ensure the stability of the integrated paper-based electrospray ionization source device. The invention uses a gripping mechanism 3 to grip a conical sample tube 21, immersing the tip of the conical sample tube 21 into the solvent bottle 41 in the solvent tank 4. After the tip of the conical sample tube 21 absorbs solvent, the sample to be tested is loaded into the solvent. Then, the conical sample tube 21 is guided into the electrode slot 5. The electrode slot 5 transmits high voltage to the interior of the conical sample tube 21 through induction, causing electrospray ionization of the solvent at the tip of the conical sample tube 21. The ionized sample is then sent to the mass spectrometer inlet for mass spectrometry analysis. This invention enables rapid and highly sensitive analysis of target compounds in complex samples. After electrospray ionization (ESI), the electrode slot 5 guides the conical sample tube 21 from the ESI to the waste tube disposal channel 65, where it is recycled. After the grasping mechanism 3 grasps the previous conical sample tube 21 in the sample stage 2, the sample stage 2 rotates, moving the next conical sample tube 21 to the position of the previous one for the next grasp. From the grasping of the conical sample tube 21 and the self-absorption of the sprayed solvent to the completion of the spray with power, this invention achieves continuous mass spectrometry analysis. The device is simple in structure, easy to assemble and operate. It not only considers the pretreatment characteristics of the adsorbent for complex samples but also effectively removes matrix interference, increasing the analytical sensitivity of the mass spectrometry to 0.01 ng·mL. -1 The establishment of an intelligent high-throughput ionization system not only lays a solid foundation for the high-throughput automated analysis of target compounds in complex test samples, but also provides a good platform for the rapid analysis of test samples such as food, environment, and biology. This, in turn, promotes the establishment and development of efficient, simple, and accurate analytical detection methods for related compounds in complex test samples.

[0040] In one specific embodiment, the test sample stage 2 includes a test sample tray 22 and a base 23. The test sample tray 22 is provided with multiple bearing holes, which are distributed circumferentially along the test sample tray 22. The test sample tray 22 and the base 23 are connected by multiple support columns. The base 23 is rotatably mounted on a fixed frame 24, which is mounted on a support platform 1. A rotating shaft is rotatably mounted below the fixed frame 24. The rotating shaft passes through the fixed frame 24 and connects to the base 23. The rotating shaft is rotatably connected to a drive mechanism 27.

[0041] The base 23 is provided with multiple bearing grooves, one bearing groove and one bearing hole correspond one to one and are on the same horizontal line along the height direction. One bearing groove and one bearing hole correspond to one conical sample tube 21, so that the conical sample tube 21 is perpendicular to the sample plate 22 to be tested along the height direction, which is convenient for the gripping mechanism 3 to grip.

[0042] In one specific embodiment, the support platform 1 is provided with a drive box 25, and the upper end of the drive box 25 is provided with a first driver 26. The first driver 26 is connected to a drive mechanism 27. The drive mechanism 27 includes a drive driving wheel, a drive driven wheel and a drive pulley. The output end of the first driver 26 is connected to the drive driving wheel, and the lower end of the rotating shaft is connected to the drive driven wheel. The drive driving wheel and the drive pulley are connected by the drive pulley meshing.

[0043] The first driver 26 is a motor. After the gripping mechanism 3 grips the previous conical sample tube 21 in the sample stage 2, the driving mechanism 27 drives the driving wheel and then drives the driven wheel to rotate through the engagement of the driving pulley. This causes the rotating shaft to rotate and drive the sample disk 22 to rotate, rotating the next conical sample tube 21 to the position of the previous conical sample tube 21 so that it can be gripped again, thereby realizing continuous mass spectrometry analysis.

[0044] In a specific embodiment, such as Figure 2 As shown, the gripping mechanism 3 includes a support plate 31, which is fixed on the support platform 1. A robotic arm 32 is mounted on the support plate 31. A rotating mechanism 33 is rotatably mounted on the robotic arm 32. A linkage shaft 34 that slides up and down is mounted on the rotating mechanism 33. A gripper 36 for gripping the conical sample tube 21 is mounted on the upper end of the linkage rod 35. The lower end of the linkage rod 35 passes through the rotating mechanism 33 and is fixed on the reciprocating motion mechanism 37. The reciprocating motion mechanism 37 is used for the linkage rod 35 to move up and down. The reciprocating motion mechanism 37 is located below the robotic arm 32.

[0045] In a specific embodiment, such as Figure 2 As shown, the rotating mechanism 33 includes a rotating driving wheel, a rotating driven wheel, and a rotating pulley. The lower end of the rotating driving wheel passes through the robotic arm 32 and is connected to the output end of the second driver. The rotating driven wheel is rotatably mounted on the robotic arm 32. A linkage shaft 34 is provided inside the rotating driven wheel. The lower end of the linkage rod 35 passes through the linkage shaft 34 and is fixed on the up-and-down reciprocating motion mechanism 37. The rotating driving wheel and the rotating driven wheel are connected by meshing with the rotating pulley.

[0046] The second actuator is a motor, which is bolted to the lower end of the robotic arm 32. The robotic arm 32 has a through hole, through which the lower end of the rotating drive wheel passes and connects to the motor's output. The drive wheel and driven wheel rotate on the same horizontal line. After the gripper 36 grasps the previous conical sample tube 21, the second actuator drives the drive wheel to rotate, which in turn drives the pulley to rotate, causing the linkage shaft 34 to rotate the linkage rod 35, rotating the gripper 36 directly above the conical sample tube 21. Then, the reciprocating motion mechanism 37 drives the linkage rod 35 to move towards the conical sample tube 21, gripping the sample tube 21. Then, the reciprocating motion mechanism 37 reverses the motion, moving the linkage rod 35 away from the conical sample tube 21, restoring the gripper 36 to its original height position. The second actuator then reverses the motion of the drive wheel. The rotating wheel rotates the clamp 36 to be directly above the solvent bottle 41. The reciprocating motion mechanism 37 drives the linkage rod 35 to move toward the solvent bottle 41, so that the tip of the conical sample tube 21 held by the clamp 36 is immersed in the solvent bottle 41 in the solvent tank 4. After the tip of the conical sample tube 21 absorbs the solvent, the sample to be tested in the conical sample tube 21 is loaded into the solvent. After the solvent and the sample to be tested in the tip of the conical sample tube 21 undergo liquid-solid extraction, the reciprocating motion mechanism 37 drives the linkage rod 35 away from the solvent bottle 41 to the original height position. Furthermore, the second driver drives the driven wheel to rotate so that the clamp 36 is directly above the electrode slot 5. The reciprocating motion mechanism 37 drives the linkage rod 35 to move toward the sample receiving slot 51 of the electrode slot 5, placing the conical sample tube 21 in the sample receiving slot 51.

[0047] In a specific embodiment, such as Figure 2 As shown, the clamp 36 is rotatably connected to the upper end of the linkage rod 35 via a connecting plate 351. The upper end of the connecting plate 351 is connected to the fifth driver 361, which is a stepper motor. The clamp 36 is a conventional scissor-type opening and closing clamp 36, therefore, this invention will not be described in further detail. The fourth driver pushes the two clamping arms of the clamp 36 to move up and down, and the two clamping arms open and close to hold the conical sample tube 21.

[0048] In a specific embodiment, such as Figure 2 As shown, the reciprocating motion mechanism 37 includes a reciprocating drive wheel, a reciprocating driven wheel, a reciprocating belt pulley, and a fixed shaft 38. A fixed plate is provided below the robotic arm 32. The reciprocating driven wheel is rotatably mounted on the fixed plate. One end of the reciprocating drive wheel passes through the fixed plate and is connected to the output end of the third driver. The reciprocating drive wheel and the reciprocating driven wheel are the same size and located at the same height line. The reciprocating drive wheel and the reciprocating driven wheel are connected by meshing with a rotating belt pulley. The fixed shaft 38 is fixed on the rotating belt pulley. The linkage rod 35 passes through the linkage shaft 34 and is fixed on the fixed shaft 38.

[0049] The fixed shaft 38 is connected to the inner side of the rotating pulley via a connecting rod. When the reciprocating motion mechanism 37 drives the linkage rod 35 to move up and down, the third driver drives the reciprocating drive wheel to rotate. After the rotating pulley rotates, it drives the fixed shaft 38 to move up and down, causing the gripper 36 to move up and down. The third driver is a motor, which is fixed to the fixed plate with bolts. The fixed plate has a through hole, and the output end of the third driver passes through the through hole and connects to the reciprocating drive wheel. The lower end of the robotic arm 32 is also provided with a limiting post 39. The fixed shaft 38 is slidably mounted on the limiting post 39, which is used to limit the fixed shaft 38 to move up and down.

[0050] In a specific embodiment, such as Figure 1 As shown, the electrode slot 5 includes a sample receiving slot 51 and a high-voltage connector 52. The sample receiving slot 51 is used to receive the conical sample tube 21 and introduce it into the sample inlet of the mass spectrometer. The high-voltage connector 52 is used to generate electrospray ionization of the sample to be tested in the conical sample tube 21. The sample receiving slot 51 is set on a fixed block, and the fixed block is rotatably set on a positioning plate. The positioning plate is fixed on the support platform 1. The fixed block is connected to the output end of the fourth driver, and the high-voltage connector 52 is fixed on the support platform 1.

[0051] The fourth actuator is a motor. When the conical sample tube 21 enters the sample receiving groove 51, the structure of the sample receiving groove 51 is the same as that of the conical sample tube 21. The lower end of the sample receiving groove 51 is open. When the conical sample tube 21 is supported, the tip of the conical sample tube 21 is only outside the lower end of the sample receiving groove 51. After the sample receiving groove 51 supports the conical sample tube 21, the fourth actuator rotates, causing the sample receiving groove 51 to rotate to a horizontal position. The tip of the conical sample tube 21 rotates to the sample inlet of the mass spectrometer. The high-voltage connector 52 is connected to a high-voltage power supply. The electrode slot 5 transmits high voltage to the inside of the conical sample tube 21 through the high-voltage connector 52 in an induced manner. The solvent inside the tip of the conical sample tube 21 is electrosprayed and ionized for mass spectrometry analysis.

[0052] In one specific embodiment, the control system connects the first driver 26, the second driver, the third driver, the fourth driver, and the fifth driver 361 respectively through multiple drive modules, and controls the first driver 26, the second driver, the third driver, the fourth driver, and the fifth driver 361 in sequence to achieve automated analysis.

[0053] The method for using the above-mentioned integrated paper-based electrospray ionization source for mass spectrometry analysis includes the following steps:

[0054] S1. Install the paper-based electrospray ionization source integrated device at the sample inlet of the mass spectrometer.

[0055] S2. Load the sample to be tested into the conical sample tube 21 containing the adsorbent. Distribute all the conical sample tubes 21 around the sample tray 22 in the bearing hole. Through the control system, the rotating mechanism 33 and the up-and-down reciprocating motion mechanism 37 are used to make the clamp 36 grasp and hold the conical sample tube 21 and rotate it above the solvent tank 4. The up-and-down reciprocating motion mechanism 37 moves the conical sample tube 21 on the clamp 36 toward the solvent bottle 41 and immerses the tip of the conical sample tube 21 into the solvent in the solvent bottle 41 and holds it for 5s to 40s. The solvent in the solvent bottle 41 is loaded into the conical polymer tube by self-absorption. After liquid-solid extraction, the target compound in the sample to be tested is transferred from the surface of the adsorbent to the spray solvent.

[0056] The process involves first adding the adsorbent solution into a conical sample tube 21. After the solvent evaporates in the air, a hollow conical sample tube 21 for loading the test sample is prepared. Finally, 1 μL to 5 μL of the test sample is added. The conical sample tube 21 can be a polyethylene conical sample tube, etc. Both the tip and the rear end of the conical sample tube 21 are open. The inner diameter of the tip is 0.5 mm to 3 mm, and the inner diameter of the rear end is 4 mm to 8 mm. The length of the conical sample tube 21 is 15 mm to 30 mm. This is to achieve spraying after liquid-solid extraction. The solvent is directly electrosprayed. The conical sample tube 21 contains a triangular paper matrix and an adsorbent. The triangular paper matrix has a base width of 5 mm and a length of 10 mm. The triangular paper can also be made of other fibrous materials, such as fiber rope, toothpick or other fibrous materials, or microporous materials such as capillaries. The adsorbent can be metal oxide, silica gel, carbon materials, etc. The triangular paper matrix is ​​rolled into a structure that matches the shape of the conical sample tube 21 and placed inside the conical sample tube 21, so that one end of the triangular paper matrix is ​​located at the tip of the conical sample tube 21.

[0057] When the tip of the conical sample tube 21 is immersed in the spray solvent reservoir, due to the unique structure of the tip, 20µL of spray solvent can be automatically introduced into the conical polymer tube. This eliminates the need for cumbersome flow injection pumps, pipettes, or other devices to transfer a fixed amount of spray solvent. Therefore, complex test samples can be directly loaded into the conical sample tube 21 containing the adsorbent. After loading the spray solvent, the tip of the conical polymer tube can be directly introduced into the solvent reservoir 4 for 5s to 40s. The target compounds in the complex test sample can be directly transferred from the surface of the solid adsorbent to the spray solvent via liquid-solid extraction. In this procedure, the volume of the spray solvent is only 20µL, allowing for direct electrospray ionization analysis without further concentration. This avoids the drawbacks of large solvent volumes and sample dilution in conventional liquid-solid extraction, as well as the cumbersome sample concentration steps after conventional liquid-solid extraction. It also eliminates the need for cumbersome flow injection pumps, pipettes, or other devices to transfer a fixed amount of spray solvent.

[0058] This invention enables high-throughput analysis of target compounds in complex samples. It combines liquid-solid extraction and direct electrospray ionization in situ for complex samples, eliminating the need for cumbersome sample preparation or pretreatment, and providing a powerful technical platform for high-throughput analysis of various complex samples.

[0059] S3. Then, the control system controls the rotating mechanism 33 and the up-and-down reciprocating motion mechanism 37 to move the clamp 36 to directly above the sample receiving slot 51 of the electrode slot 5. The clamp 36 guides the conical sample tube 21 into the sample receiving slot 51 where a high voltage power supply is applied. The sample receiving slot 51 rotates to a horizontal position, and the tip of the conical sample tube 21 rotates to the sample inlet of the mass spectrometer. The high voltage connector 52 transmits the high voltage in the electrode slot 5 to the inside of the conical sample tube 21 through induction, generating electrospray ionization at the tip of the conical sample tube 21. The voltage of the electrospray ionization is 3000V to 4500V, and mass spectrometry analysis is performed.

[0060] When the conical sample tube 21 containing the sample to be tested and the spray solvent is introduced into the electrode slot 5, the unique structure of the tip of the conical sample tube 21 allows the high voltage within the electrode slot 5 to be directly transmitted to the interior of the conical polymer tube through induction, thereby generating an electrospray phenomenon at the tip of the conical polymer tube. Mass spectrometry analysis can then be performed directly. This process avoids the drawback of contact between the sample solution and the high-voltage electrode in conventional paper-based electrospray processes, preventing contamination of the sample solution and improving analytical efficiency.

[0061] This invention not only considers the characteristics of adsorbent pretreatment for complex analyte samples, but also effectively removes matrix interference from the analyte sample, increasing the sensitivity of direct mass spectrometry analysis of target compounds in complex analyte samples to 0.01 ng·mL. -1 The method achieves high efficiency and low performance. Simultaneously, using an improved polymer tube as a carrier for the paper matrix, adsorbent, and spray solvent effectively suppresses solvent volatilization. For 20µL of spray solvent, a very stable electrospray flow is obtained, and the electrospray time can be extended to over 6 minutes. More importantly, this method uses a self-priming method to load the spray solvent into the polymer tube, eliminating the need for any flow pump and significantly reducing costs. Furthermore, this method uses an induced method to load the spray power onto the polymer tube, eliminating the need for contact between the sample and the electrode, thus reducing sample contamination and dissociation. From the grasping of the conical sample tube 21, the self-priming of the spray solvent, to the completion of the spray cycle, the time is less than 50 seconds, allowing for continuous analysis of over 1700 samples per day.

[0062] The following specific examples will provide further explanation.

[0063] Example 1

[0064] The paper-based electrospray ionization source integrated device for mass spectrometry analysis of serum test samples includes the following steps:

[0065] First, a conical sample tube 21 is prepared, with an inner diameter of 0.5 mm at the tip outlet, an inner diameter of 4 mm at the rear end, and a length of 15 mm. Then, a triangular paper matrix with a bottom width of 5 mm and a length of 10 mm is placed inside, with one end of the triangular paper matrix positioned at the tip of the conical sample tube 21. Next, an adsorbent solution of a certain concentration is added. After the solvent in the adsorbent solution evaporates in the air, a hollow conical sample tube 21 for loading the test sample is prepared. Finally, 2 μL of serum test sample containing a diagnostic drug compound is added.

[0066] The conical sample tube 21 containing the sample to be tested, prepared as described above, is then loaded onto the sample stage 2. The control system is activated, and the gripping mechanism 3 moves the conical sample tube 21 to the solvent tank 4 and holds it for 5 seconds. Then, the conical sample tube 21 is moved to the electrode slot 5 and held for 30 seconds. When the tip of the conical sample tube 21 contacts the high-voltage low-level slot, electrospraying behavior at the polymer tube tip is induced. Figure 2 As shown, the above method was used to continuously test 10 groups containing 1 μg·mL⁻¹ -1 Parallel experiments using serum samples of amitriptyline, clozapine, amisulpride, quetiapine, risperidone, and aripiprazole yielded very stable results.

[0067] Example 2

[0068] The paper-based electrospray ionization source integrated device for mass spectrometry analysis of serum test samples includes the following steps:

[0069] First, a conical sample tube 21 is prepared, with an inner diameter of 1.5 mm at the tip outlet, an inner diameter of 8 mm at the rear end, and a length of 15 mm. Then, a triangular paper matrix with a bottom width of 5 mm and a length of 10 mm is placed inside, with one end of the triangular paper matrix positioned at the tip of the conical sample tube 21. Next, an adsorbent solution of a certain concentration is added. After the solvent in the adsorbent solution evaporates in the air, a hollow conical sample tube 21 for loading the test sample is prepared. Finally, 2 μL of serum test sample containing a diagnostic drug compound is added.

[0070] The conical sample tube 21 containing the sample to be tested, prepared as described above, is then loaded onto the sample stage 2. The control system is activated, and the gripping mechanism 3 moves the conical sample tube 21 to the solvent tank 4 and holds it for 5 seconds. Then, the conical sample tube 21 is moved to the electrode slot 5 and held for 30 seconds. When the tip of the conical sample tube 21 contacts the high-voltage low-level slot, electrospraying behavior at the polymer tube tip is induced. Using the above mode, a sample containing 1 μg·mL⁻¹ of sample is tested. -1 Parallel experiments using serum samples of amitriptyline, clozapine, amisulpride, quetiapine, risperidone, and aripiprazole yielded very stable results.

[0071] Example 3

[0072] The paper-based electrospray ionization source integrated device for mass spectrometry analysis of serum test samples includes the following steps:

[0073] First, a conical sample tube 21 is prepared, with an inner diameter of 1.5 mm at the tip outlet, an inner diameter of 8 mm at the rear end, and a length of 25 mm. Then, a triangular paper matrix with a base width of 5 mm and a length of 10 mm is placed inside, with one end of the triangular paper matrix positioned at the tip of the conical sample tube 21. Next, an adsorbent solution of a certain concentration is added. After the solvent in the adsorbent solution evaporates in the air, a hollow conical sample tube 21 for loading the test sample is prepared. Finally, 2 μL of serum test sample containing a diagnostic drug compound is added.

[0074] The prepared conical sample tube 21 containing the sample to be tested is then loaded onto the sample stage 2. The control system is activated, and the gripping mechanism 3 moves the conical sample tube 21 to the solvent tank 4 and holds it for 10 seconds. Then, the conical sample tube 21 is moved to the electrode slot 5 and held for 40 seconds. When the tip of the conical sample tube 21 contacts the high-voltage low-level slot, electrospraying behavior at the tip of the conical sample tube 21 is induced. Using the above mode, a sample containing 1 μg·mL⁻¹ is tested. -1 Parallel experiments using serum samples of amitriptyline, clozapine, amisulpride, quetiapine, risperidone, and aripiprazole yielded very stable results.

[0075] Example 4

[0076] The paper-based electrospray ionization source integrated device for mass spectrometry analysis of serum test samples includes the following steps:

[0077] First, a conical sample tube 21 is prepared, with an inner diameter of 1.5 mm at the tip outlet, an inner diameter of 8 mm at the rear end, and a length of 25 mm. Then, a triangular paper matrix with a base width of 5 mm and a length of 10 mm is placed inside, with one end of the triangular paper matrix positioned at the tip of the conical sample tube 21. Next, an adsorbent solution of a certain concentration is added. After the solvent in the adsorbent solution evaporates in the air, the conical sample tube 21 for loading the test sample is prepared. Finally, 2 μL of serum test sample containing a diagnostic drug compound is added.

[0078] The conical sample tube 21 containing the sample to be tested, prepared as described above, is then loaded onto the sample stage 2. The control system is activated, and the robotic arm 32 moves the conical sample tube 21 to the solvent tank 4 and holds it for 20 seconds. Then, the conical sample tube 21 is moved to the electrode slot 5 and held for 320 seconds. When the outer end of the conical sample tube 21 contacts the high-voltage low-level slot, tip electrospraying behavior is induced. Using the above method, a sample containing 1 μg·mL⁻¹ is tested. -1 The serum samples of amitriptyline, clozapine, amisulpride, quetiapine, risperidone, and aripiprazole were used in the experiment. Figure 3 As can be seen, the above compounds can produce very stable mass spectrometry ion currents in this process, indicating that the technology developed in this invention can obtain convincing experimental results.

[0079] Example 5

[0080] The paper-based electrospray ionization source integrated device for mass spectrometry analysis of serum test samples includes the following steps:

[0081] First, a conical sample tube 21 is prepared, with an inner diameter of 3 mm at the tip outlet, an inner diameter of 6 mm at the rear end, and a length of 30 mm. Then, a triangular paper matrix with a base width of 5 mm and a length of 10 mm is placed inside, with one end of the triangular paper matrix positioned at the tip of the conical sample tube 21. Next, an adsorbent solution of a certain concentration is added. After the solvent in the adsorbent solution evaporates in the air, the conical sample tube 21 for loading the test sample is prepared. Finally, 2 μL of serum test samples containing different concentrations of diagnostic drug compounds are added to different conical sample tubes 21.

[0082] The prepared conical sample tube 21 containing the sample to be tested is then loaded onto the sample stage 2. The system control system is activated, and the gripping mechanism 3 moves the conical sample tube 21 to the solvent tank 4 and holds for 15 seconds. Then, the conical sample tube 21 is moved to the electrode slot 5 and held for 30 seconds. When the tip of the conical sample tube 21 contacts the high-voltage low-level slot, electrospraying behavior at the tip of the conical sample tube 21 is induced. Using the above mode, a sample containing 0.01 μg·mL⁻¹ is tested. -1 ~1000μg·mL-1 The serum samples of amitriptyline, clozapine, amisulpride, quetiapine, risperidone, and aripiprazole were used in the experiment. Figure 4 As can be seen, the above compounds exhibit excellent quantitative relationship curves in serum, with a detection limit as low as 0.003 ng / mL. -1 ~0.032 ng·mL -1 The scope of this invention demonstrates that the technology developed in this invention can be used for rapid and highly sensitive analysis of target compounds in complex test samples.

[0083] Example 6

[0084] The paper-based electrospray ionization source integrated device for mass spectrometry analysis of serum test samples includes the following steps:

[0085] First, a conical sample tube 21 is prepared, with an inner diameter of 2.0 mm at the tip outlet, an inner diameter of 6 mm at the rear end, and a length of 20 mm. Then, a triangular paper matrix with a base width of 5 mm and a length of 10 mm is placed inside, with one end of the triangular paper matrix positioned at the tip of the conical sample tube 21. Next, an adsorbent solution of a certain concentration is added. After the solvent in the adsorbent solution evaporates in the air, the conical sample tube 21 for loading the test sample is prepared. Finally, 2 μL of serum test sample containing a diagnostic drug compound is added.

[0086] The conical sample tube 21 containing the sample to be tested, prepared as described above, is then loaded onto the sample stage 2. The control system is activated, and the gripping mechanism 3 moves the conical sample tube 21 to the solvent tank 4 and holds it for 5 seconds. Then, the conical sample tube 21 is moved to the electrode slot 5 and held for 30 seconds. When the tip of the conical sample tube 21 contacts the high-voltage low-level slot, electrospraying behavior at the polymer tube tip is induced. Using the above mode, a sample containing 1 μg·mL⁻¹ of sample is tested. -1 The serum samples of amitriptyline, clozapine, amisulpride, quetiapine, risperidone, and aripiprazole were continuously tested. One sample could be analyzed every 50 seconds, and 1728 samples could be analyzed per day, demonstrating that the technology developed in this invention has high-throughput analysis performance.

[0087] Example 7

[0088] The paper-based electrospray ionization source integrated device for mass spectrometry analysis of urine samples using the above-mentioned paper-based electrospray ionization source integrated device includes the following steps:

[0089] First, a conical sample tube 21 is prepared, with an inner diameter of 2.0 mm at the tip outlet, an inner diameter of 6 mm at the rear end, and a length of 20 mm. Then, a triangular paper matrix with a base width of 5 mm and a length of 10 mm is placed inside, with one end of the triangular paper matrix positioned at the tip of the conical sample tube 21. Next, an adsorbent solution of a certain concentration is added. After the solvent in the adsorbent solution evaporates in the air, the conical sample tube 21 for loading the test sample is prepared. Finally, 2 μL of urine test sample containing diagnostic drug compounds is added.

[0090] The conical sample tube 21 containing the sample to be tested, prepared as described above, is then loaded onto the sample stage 2. Control is activated, and the gripping mechanism 3 moves the conical sample tube 21 to the solvent tank 4 and holds it for 5 seconds. Then, the conical sample tube 21 is moved to the electrode slot 5 and held for 30 seconds. When the tip of the conical sample tube 21 contacts the high-voltage low-level slot, electrospraying behavior at the polymer tube tip is induced. Using the above mode, a sample containing 1 μg·mL⁻¹ of sample is tested. -1 Satisfactory experimental results can be obtained by continuously testing urine samples containing amitriptyline, clozapine, amisulpride, quetiapine, risperidone, and aripiprazole.

[0091] Example 8

[0092] The paper-based electrospray ionization source integrated device for mass spectrometry analysis of serum test samples includes the following steps:

[0093] First, a conical sample tube 21 is prepared, with an inner diameter of 2.0 mm at the tip outlet, an inner diameter of 6 mm at the rear end, and a length of 20 mm. Then, a triangular paper matrix with a base width of 5 mm and a length of 10 mm is placed inside, with one end of the triangular paper matrix positioned at the tip of the conical sample tube 21. Next, an adsorbent solution of a certain concentration is added. After the solvent in the adsorbent solution evaporates in the air, the conical sample tube 21 for loading the test sample is prepared. Finally, 2 μL of whole blood test sample containing a diagnostic drug compound is added.

[0094] The conical sample tube 21 containing the sample to be tested, prepared as described above, is then loaded onto the sample stage 2. The control system is activated, and the gripping mechanism 3 moves the conical sample tube 21 to the solvent tank 4 and holds it for 5 seconds. Then, the conical sample tube 21 is moved to the electrode slot 5 and held for 30 seconds. When the tip of the conical sample tube 21 contacts the high-voltage low-level slot, electrospraying behavior at the tip of the conical sample tube 21 is induced. Using the above mode, a sample containing 1 μg·mL⁻¹ of solvent is tested. -1 Satisfactory experimental results can be obtained by continuously testing whole blood samples for amitriptyline, clozapine, amisulpride, quetiapine, risperidone, and aripiprazole.

[0095] It should be noted that when numerical ranges are involved in this invention, it should be understood that both endpoints of each numerical range and any value between the two endpoints can be selected. Since the steps and methods used are the same as in the embodiments, preferred embodiments are described here to avoid redundancy. Although preferred embodiments of the invention have been described, those skilled in the art, once they understand the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments as well as all changes and modifications falling within the scope of this invention.

[0096] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. An integrated paper-based electrospray ionization source device for mass spectrometry analysis, characterized in that, include: The carrier platform has a rotating sample stage, on which multiple conical sample tubes are supported. All conical sample tubes contain paper matrix and adsorbent, with the adsorbent used to support the sample to be tested. The solvent tank is located above the support platform and to the side of the sample stage. The solvent tank contains a solvent bottle, which is used to hold the solvent required for electrospray ionization. The electrode slot, located above the support platform, is used to receive the conical sample tube and apply an induced voltage to electrospray ionize the solvent inside the conical sample tube before introducing it into the mass spectrometer inlet for mass spectrometry analysis. The gripping mechanism, positioned above the support platform and above the sample stage, grips the conical sample tube. It immerses the tip of the conical sample tube into a solvent bottle, using a self-priming method to load the solvent into the conical polymer tube. Liquid-solid extraction is then used to load the sample into the solvent. Finally, the conical sample tube is guided into the electrode slot. The conical sample tube has open tips and open ends; the inner diameter of the tip is 0.5mm–3mm, the inner diameter of the rear end is 4mm–8mm, and the length is 15mm–30mm. The waste tube disposal channel is located above the support platform and is used to recycle and process the conical sample tubes after the electrospray ionization is completed. A paper-based electrospray ionization source integrated method for mass spectrometry analysis using a paper-based electrospray ionization source integrated device includes the following steps: The paper-based electrospray ionization source integrated device was installed at the sample inlet of the mass spectrometer; The paper matrix is ​​placed into a conical sample tube, then the adsorbent solution is added. After drying, the sample to be tested is added to the adsorbent, and the conical sample tube is placed in the sample stage. The gripping mechanism grips a conical sample tube, and then the tip of the conical sample tube is immersed in the solvent bottle. The solvent in the solvent bottle is loaded into the conical polymer tube by self-absorption. After liquid-solid extraction, the target compound in the sample is transferred from the surface of the adsorbent to the solvent in the conical polymer tube. Then, the gripping mechanism guides the conical polymer tube into the electrode slot, and the electrode slot guides the tip of the conical polymer tube into the mass spectrometer's inlet. The electrode slot transmits the high voltage inside to the inside of the conical sample tube through induction, and the solvent inside the tip of the conical sample tube is electrosprayed and ionized for mass spectrometry analysis. The immersion time in the solvent bottle is 5s to 40s, the electrospray ionization time is 20s to 360s, and the electrospray ionization voltage is 3000V to 4500V.

2. The integrated paper-based electrospray ionization source device for mass spectrometry analysis according to claim 1, characterized in that, The test sample stage includes a test sample tray and a base. The test sample tray has multiple bearing holes distributed around the circumference of the test sample tray. The test sample tray and the base are connected by multiple support columns. The base is rotatably mounted on a fixed frame, which is mounted on a bearing platform. A rotating shaft is rotatably mounted below the fixed frame. The rotating shaft passes through the fixed frame and connects to the base. The rotating shaft is rotatably connected to a drive mechanism.

3. The integrated paper-based electrospray ionization source device for mass spectrometry analysis according to claim 2, characterized in that, The platform is equipped with a drive box, and the upper end of the drive box is equipped with a first driver. The first driver is connected to the drive mechanism, which includes a drive drive wheel, a drive driven wheel, and a drive pulley. The output end of the first driver is connected to the drive drive wheel, and the lower end of the rotating shaft is connected to the drive driven wheel. The drive drive wheel and the drive pulley are connected by the drive pulley meshing.

4. The integrated paper-based electrospray ionization source device for mass spectrometry analysis according to claim 1, characterized in that, The gripping mechanism includes a support plate fixed on a support platform. A robotic arm is mounted on the support plate, and a rotating mechanism is mounted on the robotic arm. The rotating mechanism has a linkage shaft that slides up and down. The upper end of the linkage rod is equipped with a gripper for gripping a conical sample tube. The lower end of the linkage rod passes through the rotating mechanism and is fixed to a reciprocating motion mechanism. The reciprocating motion mechanism is used for the linkage rod to move up and down and is located below the robotic arm.

5. The integrated paper-based electrospray ionization source device for mass spectrometry analysis according to claim 4, characterized in that, The rotating mechanism includes a rotating drive wheel, a rotating driven wheel, and a rotating pulley. The lower end of the rotating drive wheel passes through the robotic arm and is connected to the output end of the second driver. The rotating driven wheel is rotatably mounted on the robotic arm. A linkage shaft is provided inside the rotating driven wheel. The lower end of the linkage rod passes through the linkage shaft and is fixed to the up-and-down reciprocating motion mechanism. The rotating drive wheel and the rotating driven wheel are connected by meshing with the rotating pulley.

6. The integrated paper-based electrospray ionization source device for mass spectrometry analysis according to claim 5, characterized in that, The reciprocating motion mechanism includes a reciprocating drive wheel, a reciprocating driven wheel, a reciprocating pulley, and a fixed shaft. A fixed plate is provided below the robotic arm. The reciprocating driven wheel is rotatably mounted on the fixed plate. One end of the reciprocating drive wheel passes through the fixed plate and is connected to the output end of the third driver. The reciprocating drive wheel and the reciprocating driven wheel are the same size and located at the same height line. The reciprocating drive wheel and the reciprocating driven wheel are connected by meshing with a rotating pulley. The fixed shaft is fixed on the rotating pulley. The linkage rod passes through the linkage shaft and is fixed on the fixed shaft.

7. The integrated paper-based electrospray ionization source device for mass spectrometry analysis according to claim 1, characterized in that, The electrode slot includes a sample receiving slot and a high-voltage connector. The sample receiving slot is used to receive a conical sample tube and guide it into the mass spectrometer's inlet. The high-voltage connector is used to generate electrospray ionization of the sample to be tested in the conical sample tube. The sample receiving slot is located on a fixed block, which is rotatably mounted on a positioning plate. The positioning plate is fixed on a support platform. The fixed block is connected to the output end of the fourth driver, and the high-voltage connector is fixed on the support platform.

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