Paper-based electrospray ionization mass spectrometry ion source and preparation method and application thereof

Abstract

The invention discloses a paper-based electrospray ionization mass spectrometry ion source and a preparation method and application thereof. The paper-based electrospray ionization mass spectrometry ion source comprises enrichment paper, an eluent and a high-voltage power supply, the enrichment paper is a triangular paper base modified by p-mercaptobenzohydrazide encapsulated nano-silver particles, the eluent is a methanol solution of 1-dodecanethiol, and the high-voltage power supply is direct-current voltage + 3-5kV. The enrichment paper can efficiently enrich aldehyde ketone compounds in gas, p-mercaptobenzoyl hydrazine is selected as an enrichment reagent, the enrichment time is shortened, and the enrichment efficiency is effectively improved; the detection limit of an ion trap mass spectrometer loaded with the paper-based electrospray ionization mass spectrometry ion source is lower than 0.1 ppt, the detection sensitivity and accuracy of the mass spectrometer are improved, and the paper-based electrospray ionization mass spectrometry ion source has performance advantages in qualitative and trace analysis aspects.

Description

Technical Field

[0001] The present invention relates to the field of clinical diagnostic instruments, and in particular to a paper-based electrospray mass spectrometry ion source device and a preparation method and application thereof. Background Art

[0002] In recent years, people have gradually realized that it is feasible to determine whether there is a disease state or metabolic change by detecting characteristic volatile organic compounds (VOCs) in exhaled breath. Exhaled breath diagnosis has the advantages of being non-invasive and painless, and the frequency and amount of sample collection are not limited. It is convenient for multiple tests to improve the accuracy of detection, and it is safer for patients, and there is no physical burden caused by exhaled breath examination. With the development of measuring instruments and the improvement of analytical methodology, VOCs in human exhaled breath have been better and better qualitatively and quantitatively analyzed. Characteristic VOCs in exhaled breath are also increasingly widely used in disease diagnosis, such as lung disease, stomach disease, liver disease, kidney disease, etc. In existing studies, there are a lot of reports on the use of conventional analytical instruments such as gas chromatography-mass spectrometry (GC-MS) to analyze VOCs in patients' exhaled breath for auxiliary diagnosis.

[0003] Mass spectrometry can achieve high-sensitivity and high-throughput analysis of biochemical components in complex samples and has been widely used in medical testing. While having the advantages of high specificity of mass spectrometry analysis, small mass spectrometers overcome the problems of large size and complex operation of traditional mass spectrometers, and have the advantages of portability, simple operation, and fast detection speed. The research on miniaturization of mass spectrometers originated in the late 20th century. The ionization of the molecules of the substance to be tested is a prerequisite for the mass spectrometer to generate signals. Therefore, people first realized that ion source technology is a bottleneck problem that needs to be solved urgently. Portable mass spectrometers are subject to many limitations of miniaturization, and the vacuum degree is usually not as good as that of conventional commercial large-scale mass spectrometers. Mature ionization sources such as electron bombardment (electron ionization, EI) have high requirements for vacuum degree and must be matched with a membrane injection interface, otherwise high vacuum inside the instrument cannot be achieved. However, for VOCs analysis, semi-volatile samples are difficult to pass through the membrane, which will limit high-precision exhaled breath detection. The atmospheric pressure open ionization mass spectrometry (ambientionization mass spectrometry, AI-MS) introduced in 2004 provides a solution. AI-MS is different from the previous method of ionizing the molecules to be tested in a high vacuum. Its advantage is that it can produce ions in any atmospheric environment, greatly expanding the application range of mass spectrometry, and greatly shortening the pre-treatment process of complex samples, making it possible to quickly detect trace complex samples. The open atmospheric pressure ionization technologies that have been reported include: desorption electrospray ionization (DESI), direct analysis in real-time (DART), paper spray ionization (PSI), etc.

[0004] Existing studies in the field have confirmed that micro-mass spectrometry has the ability to quickly analyze and detect exhaled breath components. By comparing the differences in exhaled breath components between virus-infected and healthy people through clinical samples, the exhaled VOCs markers of infected people can be found. Using a micro-mass spectrometer to measure exhaled VOCs as a biomarker can not only quickly determine whether a person is in a healthy or diseased state, but in the future it is also expected to achieve rapid screening of people in crowded areas such as hospitals, railway stations, and airports to prevent cross-infection among people, which is of great significance for effectively controlling the spread of pathogens. In addition, it can also be used as a bedside test to evaluate the efficacy of drugs in a timely manner.

[0005] However, the concentration of VOCs in exhaled breath samples is extremely low, about 10 -12 ~10 -9mol / L, the sample needs to be enriched before treatment to increase the sample concentration. The conventional sample pretreatment method is mainly solid-phase microextraction (SPME), the principle of which is to coat micron-sized adsorbent materials on millimeter-sized columnar fibers. Since the adsorption coating is thin, the analyte can quickly reach adsorption equilibrium, thereby reducing the time used for sample enrichment. SPME has become one of the most widely used sample pretreatment technologies because of its simple operation, rapidity, effectiveness, and ease of automation. However, SPME enrichment is currently commonly used in GC-MS analysis, and there are few types of SPME coatings on the market, which makes it difficult to cover all target analytes, especially for low-concentration compounds in complex matrices. In addition, the coating has a limited lifespan, and may wear and fall off during use, resulting in reduced stability and repeatability of the analysis results. Therefore, it is urgent to develop a new mass spectrometry ion source that can quickly enrich VOCs in gas samples (such as exhaled breath) according to the needs of micro-mass spectrometry analysis. Summary of the invention

[0006] In order to solve the problems in the prior art, the present invention provides a paper-based electrospray ionization mass spectrometry ion source device that can quickly enrich aldehyde and ketone volatile organic compounds in gas, as well as a preparation method and application thereof, which solves the problem that the volatile organic compounds (VOCs) contained in human exhaled breath are extremely low and difficult to be detected by instruments.

[0007] A paper-based electrospray mass spectrometry ion source comprises enrichment paper, an eluent and a high-voltage power supply. The enrichment paper is a triangular paper base modified by p-mercaptobenzoylhydrazide encapsulated nanosilver particles, the eluent is a methanol solution of 1-dodecanethiol, and the high-voltage power supply is a DC voltage of +3-5kV.

[0008] The high voltage power supply has a DC voltage of 3.5 kV.

[0009] A method for preparing a paper-based electrospray mass spectrometry ion source comprises the following steps:

[0010] Step 1: Preparation of p-mercaptobenzoyl hydrazide: 4-mercaptobenzoic acid is subjected to an esterification reaction to generate 4-mercaptobenzoic acid methyl ester, and the ester is subjected to a hydrazinolysis reaction to generate p-mercaptobenzoyl hydrazide;

[0011] Step 2: Preparation of enrichment paper: modifying chromatographic paper by encapsulating silver nanoparticles with p-mercaptobenzoyl hydrazide;

[0012] Step 3: Enrichment of sample gas: Pre-wet the dried enrichment paper with methanol, put it into a clean glass syringe, extract the sample gas from the sample container with the syringe, and culture it in a constant temperature incubator;

[0013] Step 4 Sample gas elution: Take out the enrichment paper and align its tip with the injection port of the mass spectrometer. Clamp it with a copper clip 5 mm away from the front end of the injection port. Add a methanol solution of 1-dodecanethiol as an eluent to the tail end of the enrichment paper.

[0014] Step 5: Apply a DC voltage of +3 to 5 kV to the copper clip for ionization.

[0015] The preparation method of the enrichment paper in step 2 is as follows: under vigorous stirring, a 50% methanol solution of p-mercaptobenzohydrazide is added to a silver nitrate solution, and a newly prepared sodium borohydride aqueous solution is then added dropwise to the solution for reaction, the obtained colloidal solution is transferred into an ultrafiltration tube for centrifugation, the suspension is removed, the p-mercaptobenzohydrazide-encapsulated nanosilver particles are resuspended in water for concentration, the chromatographic paper is cut into a triangle, and the concentrated p-mercaptobenzohydrazide-encapsulated nanosilver particles solution is dropped in the center of the triangular chromatographic paper, and the triangular enrichment paper is obtained after drying.

[0016] The concentration of the p-mercaptobenzoyl hydrazide solution is 5 mM and the volume is 2 mL, the concentration of the silver nitrate solution is 0.5 mM and the volume is 20 mL, the concentration of the sodium borohydride aqueous solution is 20 mM and the volume is 400 μL, the ultrafiltration tube molecular weight cutoff is 100 kDa, and the centrifugation parameter is centrifugation at 1500×g for 3 min.

[0017] The triangle has a height of 2 cm and a base of 1.5 cm.

[0018] The solution of the p-mercaptobenzoyl hydrazide encapsulating the nano-silver particles was dropped 5 μL each time, for a total of two drops.

[0019] Application of the paper-based electrospray mass spectrometry ion source in preparing a traditional Chinese medicine olfaction instrument.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] 1. The enrichment paper of the present invention can efficiently enrich aldehyde and ketone compounds in gas, selects p-thiobenzoylhydrazide as the enrichment reagent, shortens the enrichment time, effectively improves the enrichment efficiency, has good stability and reproducibility, and has low material cost, and is economical and easy to implement.

[0022] 2. The paper-based electrospray ionization mass spectrometry ion source device of the present invention can be used with a variety of mass spectrometers. The detection limit of the ion trap mass spectrometer equipped with the paper-based electrospray ionization mass spectrometry ion source of the present invention is lower than 0.1ppt, which improves the detection sensitivity and accuracy of the mass spectrometer and has performance advantages in qualitative and trace analysis. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1This is a liquid chromatography-mass spectrometry (LC-MS) result diagram of p-mercaptobenzoyl hydrazide;

[0024] Figure 1 A is the chromatogram of the product, B is the mass spectrum of the product in positive ion mode, and C is the mass spectrum of the product in negative ion mode;

[0025] Figure 2 This is the result of H NMR spectrum of 4-mercaptobenzoyl hydrazide;

[0026] Figure 3 This is a transmission electron microscopy image of a colloidal solution of silver nanoparticles encapsulated by p-mercaptobenzoylhydrazide;

[0027] Figure 4 A is the Ag 3d X-ray photoelectron spectrum of nanosilver particles and nanosilver particles encapsulated by mercaptobenzoyl hydrazide; B is the S2p X-ray photoelectron spectrum of nanosilver particles encapsulated by p-mercaptobenzoyl hydrazide and p-mercaptobenzoyl hydrazide;

[0028] Figure 5 is a scanning electron micrograph of a colloidal solution of silver nanoparticles encapsulated with p-mercaptobenzoylhydrazide;

[0029] Figure 6 It is a structural diagram of a paper-based electrospray mass spectrometry ion source device;

[0030] Figure 6 The marks in the figure represent: 1-enrichment paper, 2-elution solution, 3-high voltage power supply.

[0031] Figure 7 It is the result of detecting 1 ppm benzaldehyde gas in the multiple reaction monitoring (MRM) mode using a micro ion trap mass spectrometer equipped with a paper-based electrospray mass spectrometry ion source;

[0032] Figure 8 It is the result of detecting 0.1ppt benzaldehyde gas in MRM mode using a micro ion trap mass spectrometer equipped with a paper-based electrospray mass spectrometer ion source;

[0033] Fig. 9 Schematic diagram of the structure of a traditional Chinese medicine olfactometry device according to embodiment 4 of the present invention;

[0034] Fig. 9 The symbols in the figure represent: 4-paper-based electrospray mass spectrometer ion source, 5-ion trap mass spectrometer, 6-data processor display, 7-high voltage power supply, 8-lead wire, 9-injection tube, 10-ion funnel, 11-ion trap, 12-cooling fan, 13-circuit board;

[0035] Fig.10 is a schematic diagram of a gas sample collection device according to an embodiment of the present invention;

[0036] Fig.10 The marks in the figure are: 14-air bag, 15-disposable mouthpiece, 16-inlet valve, 17-outlet valve;

[0037] Fig.11 Schematic diagram of the analysis process of the traditional Chinese medicine olfaction instrument according to an embodiment of the present invention;

[0038] Fig.12 A is the classification result of exhaled breath of heart failure patients and healthy people detected by a traditional Chinese medicine olfactometer equipped with a paper-based electrospray mass spectrometry ion source; B is the classification result of exhaled breath of patients with excess and deficiency syndromes of bronchial asthma detected by a traditional Chinese medicine olfactometer equipped with the ion source of the present invention. Specific implementation plan

[0039] The present invention is further described below in conjunction with specific examples, which are merely exemplary and do not limit the scope of protection of the present invention. The reagents and chromatographic papers involved in each example can be purchased.

[0040] Unless otherwise defined, the technical terms used in the following examples have the same meanings as those generally understood by those skilled in the art to which the present invention belongs. The experimental reagents used in the following examples are all conventional biochemical reagents unless otherwise specified; the experimental methods are all conventional methods unless otherwise specified.

[0041] Example 1 Preparation of p-Mercaptobenzoylhydrazide

[0042] Using methanol as solvent and concentrated sulfuric acid as catalyst, 4-mercaptobenzoic acid was reacted at 70°C for 30 minutes under microwave heating to generate 4-mercaptobenzoic acid methyl ester through esterification reaction. Using methanol as solvent, 4-mercaptobenzoic acid methyl ester was reacted with excess hydrazine hydrate at 50°C, and the final product, p-mercaptobenzoyl hydrazide, was generated through hydrazinolysis reaction of the ester. The synthesis process is as follows:

[0043]

[0044] The structural formula of 4-mercaptobenzoyl hydrazide is:

[0045]

[0046] The LC-MS results of the product are as follows Figure 1 , chromatogram A shows that the retention time of the product is about 1.4 min, and mass spectrum B shows the molecular ion peak of the product in positive ion mode [M+H] + Appearing at m / z 169, the molecular ion peak of the product in mass spectrum C negative ion mode [MH] +The presence of m / z at 167 is consistent with the molecular weight of p-mercaptobenzoyl hydrazide (MW=168.04), proving that the product is p-mercaptobenzoyl hydrazide.

[0047] The results of the H NMR spectrum of the product are as follows Figure 2 It can be seen that the chemical shift values ​​are consistent with the characteristic signals of different protons in the structure of p-mercaptobenzoylhydrazide, which verifies the correct structure of the product. Combining the results of LC-MS and H NMR, it can be determined that the compound is p-mercaptobenzoylhydrazide.

[0048] Example 2 Preparation of Enriched Paper

[0049] The paper base of nanosilver particles encapsulated with p-mercaptobenzoyl hydrazide is used to enrich VOCs in the gas. Due to the group characteristics of the enrichment reagent, it can specifically combine with aldehydes and ketones in the gas to increase the concentration of aldehydes and ketones in the sample.

[0050] Under vigorous stirring, add 2mL of 5mM p-mercaptobenzoylhydrazide 50% methanol solution to 20mL of 0.5 mM silver nitrate solution, and then add 400μL of freshly prepared 20 mM sodium borohydride aqueous solution to the solution for reaction. Transfer the obtained colloidal solution into an ultrafiltration tube with a molecular weight cutoff of 100kDa and centrifuge at 1500×g for 3min. Remove the suspension and resuspend the p-mercaptobenzoylhydrazide-encapsulated nanosilver particles in water with a concentration factor of 10. Cut the chromatographic paper into a triangle with a height of 2cm and a bottom of 1.5cm, and drop the concentrated p-mercaptobenzoylhydrazide-encapsulated nanosilver particles solution in the center of the triangular paper, 5μL each time, for a total of two drops, and obtain the triangular enrichment paper after air drying.

[0051] Transmission electron microscopy results Figure 3 The average particle size of the prepared p-thiobenzoylhydrazide-encapsulated silver nanoparticles was 8 nm.

[0052] The X-ray photoelectron spectroscopy results are as follows Figure 4 In Figure A, the black line is silver nanoparticles, and the red line is silver nanoparticles encapsulated with p-mercaptobenzohydrazide. The binding energy of Ag 3d electrons of the two moves from 368.5eV to 368.2eV; in Figure B, the black line is p-mercaptobenzohydrazide, and the red line is silver nanoparticles encapsulated with p-mercaptobenzohydrazide. The binding energy of S2p electrons of the two moves from 163.9eV to 162.4eV, indicating that p-mercaptobenzohydrazide successfully binds to silver nanoparticles.

[0053] The scanning electron microscopy results are as follows Figure 5 , no agglomeration of particles was observed.

[0054] Example 3 A micro ion trap mass spectrometer equipped with a paper-based electrospray mass spectrometry ion source of the present invention is used to detect benzaldehyde standard gas

[0055] During the test, first take 10μL of a series of benzaldehyde methanol solutions and drop them into a 50mL centrifuge tube, place it in a 37℃ incubator for 30 minutes, and obtain benzaldehyde gas as a sample for quantitative analysis. Pre-wet the dried triangular enrichment paper with 10μL methanol, put it into a clean glass syringe, use the syringe to extract 20mL of benzaldehyde gas from the centrifuge tube, and incubate it in a 60℃ constant temperature incubator for 10 minutes. Take out the triangular enrichment paper and align its tip with the injection port of the micro ion trap mass spectrometer. Clamp it with a copper clip 5mm away from the front end of the injection port, such as Figure 6 As shown, 25 μL of 0.02M 1-dodecanethiol methanol solution was added to the tail end of the enrichment paper as an eluent. A DC voltage of +3 to 5 kV was connected to the copper clip for detection, preferably 3.5 kV.

[0056] Figure 7 The detection result of 1 ppm benzaldehyde gas under MRM mode is that the m / z of the product precursor ion after the reaction is 257.1, and the m / z of the fragment ion is 179. It can be seen that the enrichment paper of the present invention can enrich aldehyde and ketone VOCs and be detected by the mass spectrometer. Figure 8 This is the result of detecting 0.1 ppt benzaldehyde gas in MRM mode, and the characteristic fragment ion 179.0 is still visible, indicating that the detection limit of the ion trap mass spectrometer equipped with the paper-based electrospray mass spectrometry ion source of the present invention is lower than 0.1 ppt, thereby improving the sensitivity of the mass spectrometer.

[0057] Example 4 Application of the paper-based electrospray mass spectrometry ion source of the present invention in the preparation of a traditional Chinese medicine olfaction instrument

[0058] The paper-based electrospray mass spectrometry ion source of the present invention can match a variety of mass spectra for preparing a traditional Chinese medicine olfactometer.

[0059] The device diagram of the portable traditional Chinese medicine olfactometer equipped with the paper-based electrospray mass spectrometry ion source of the present invention is as follows: Fig. 9 As shown, the instrument comprises: a sample collection device, a gas enrichment device 4, an ion trap mass spectrometer 5, a data processor and a display 6; the ion trap mass spectrometer 5, the data processor and the display 6 are connected in sequence.

[0060] like Fig.10 As shown, the gas sample collection device is used to collect and store exhaled gas, and includes a disposable mouthpiece 15, an air inlet valve 16, an air bag 14, and an air outlet valve 17 connected in sequence.

[0061] Exhaled breath sampling requirements: Subjects are required to fast for more than 8 hours before sampling. The sampling time is 8:00 AM. Before sampling, sit quietly in the room for 10 to 15 minutes and rinse your mouth with water. The subject opens the air inlet valve 13 and the air outlet valve 14, takes three deep breaths, takes two calm breaths, blows into the air for 10 seconds, and then holds the disposable mouthpiece 15 in the mouth and blows into the air bag until you feel a slight resistance in the lungs, and then closes the air outlet valve and the air inlet valve. No ventilation is allowed during exhalation.

[0062] Reference Fig.11 As shown, the traditional Chinese medicine olfactometer prepared by the paper-based electrospray mass spectrometry ion source of the present invention shows the olfaction sample collection and enrichment process.

[0063] During the test, pre-wet the dried enrichment paper with 10μL methanol, put it into a clean glass syringe, use the syringe to extract 20mL of exhaled air from the air bag of the sample to be tested, and incubate it in a constant temperature incubator at 60℃ for 10min. Take out the test paper and clamp it with a copper clip 5mm from the front end of the olfactometer inlet, and add 25μL, 0.02M 1-dodecanethiol methanol solution to the tail end of the test paper as eluent. Connect a DC voltage of 3.5kV to the copper clip for testing.

[0064] The ion trap mass spectrometer is used to detect the exhaled breath sample enriched by enrichment paper to obtain mass spectrum data.

[0065] The data processor and display 6 pre-process the obtained mass spectrometry data and input them into the established OPLS-DA model for classification. Orthogonal partial least squares discriminant analysis (OPLS-DA) OPLS-DA is a multivariate statistical analysis method, which is mainly used for data classification and pattern recognition, and is widely used in chemistry, biology, medicine and environmental science. Fig.12 A in the figure shows the classification results of exhaled breath of patients with heart failure (HF) and healthy people (HC), and B shows the classification results of exhaled breath of patients with excess syndrome (S) and deficiency syndrome (X) of asthma. 2 and Q 2 The R values ​​of the two OPLS-DA models established in this invention are shown in Figure 2. 2 Y and Q 2 Both are > 0.8, indicating that the diagnostic and predictive performance of the model are good. The sample points of the two groups of samples are clustered in different quadrants, indicating that the discrimination and clustering are good, proving that there are certain differences in the breath components between the groups and they can be correctly classified.

[0066] The present invention is combined with mass spectrometry to improve the accuracy of mass spectrometry results, and has great clinical application value in disease diagnosis, disease evolution and disease prognosis assessment.

[0067] The above embodiments are only exemplary and do not constitute any limitation to the scope of the present invention. It should be understood by those skilled in the art that the details and forms of the technical solution of the present invention may be modified or replaced without departing from the spirit and scope of the present invention, but these modifications and replacements fall within the scope of protection of the present invention.

Claims

1. A paper-based electrospray mass spectrometry ion source, characterized in that: The invention comprises enrichment paper, eluent and high-voltage power supply. The enrichment paper is a triangular paper base modified by nano silver particles encapsulated by 4-thiobenzoyl hydrazide, the eluent is a methanol solution of 1-dodecanethiol, and the high-voltage power supply is a direct current voltage of +3-5 kV.

2. The paper-based electrospray mass spectrometry ion source according to claim 1, characterized in that: The high voltage power supply has a DC voltage of 3.5 kV.

3. A method for preparing a paper-based electrospray mass spectrometry ion source, characterized in that: The following steps are involved: Step 1: Preparation of p-mercaptobenzoyl hydrazide: 4-mercaptobenzoic acid is subjected to an esterification reaction to generate 4-mercaptobenzoic acid methyl ester, and the ester is subjected to a hydrazinolysis reaction to generate p-mercaptobenzoyl hydrazide; Step 2: Preparation of enrichment paper: modifying chromatographic paper by encapsulating silver nanoparticles with p-mercaptobenzoyl hydrazide; Step 3: Enrichment of sample gas: Pre-wet the dried enrichment paper with methanol, put it into a clean glass syringe, extract the sample gas from the sample container with the syringe, and culture it in a constant temperature incubator; Step 4 Sample gas elution: Take out the enrichment paper and align its tip with the injection port of the mass spectrometer. Clamp it with a copper clip 5 mm away from the front end of the injection port. Add a methanol solution of 1-dodecanethiol as an eluent to the tail end of the enrichment paper. Step 5: Apply a DC voltage of +3 to 5 kV to the copper clip for ionization.

4. The method for preparing a paper-based electrospray mass spectrometry ion source according to claim 3, characterized in that: The preparation method of the enrichment paper in step 2 is as follows: under vigorous stirring, a 50% methanol solution of p-mercaptobenzohydrazide is added to a silver nitrate solution, and a newly prepared sodium borohydride aqueous solution is then added dropwise to the solution for reaction, the obtained colloidal solution is transferred into an ultrafiltration tube for centrifugation, the suspension is removed, the p-mercaptobenzohydrazide-encapsulated nanosilver particles are resuspended in water for concentration, the chromatographic paper is cut into a triangle, and the concentrated p-mercaptobenzohydrazide-encapsulated nanosilver particles solution is dropped in the center of the triangular chromatographic paper, and the triangular enrichment paper is obtained after drying.

5. The method for preparing a paper-based electrospray mass spectrometry ion source according to claim 4, characterized in that: The concentration of the p-mercaptobenzoyl hydrazide solution is 5 mM and the volume is 2 mL, the concentration of the silver nitrate solution is 0.5 mM and the volume is 20 mL, the concentration of the sodium borohydride aqueous solution is 20 mM and the volume is 400 μL, the ultrafiltration tube molecular weight cutoff is 100 kDa, and the centrifugation parameter is centrifugation at 1500×g for 3 min.

6. The method for preparing a paper-based electrospray mass spectrometry ion source according to claim 4, characterized in that: The triangle has a height of 2 cm and a base of 1.5 cm.

7. The method for preparing a paper-based electrospray mass spectrometry ion source according to claim 4, characterized in that: The solution of the p-mercaptobenzoyl hydrazide encapsulating the nano-silver particles was dropped 5 μL each time, for a total of two drops.

8. Use of the paper-based electrospray mass spectrometry ion source according to claim 1 in the preparation of a traditional Chinese medicine olfaction instrument.

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