Droplet mass spectrometry system based on alternating current electric field and sample surface mass spectrometry method thereof

Abstract

The invention provides a droplet mass spectrometry system based on an alternating current electric field and a method for sample surface mass spectrometry, and belongs to the technical field of mass spectrometry. The droplet mass spectrometry system comprises a sampling device, an ionization device and a mass spectrometry detection device, the sampling device comprises a sampling pump and a sampling pipe connected to the sampling pump, and the pressure difference provided by the sampling pump is utilized to sample extraction droplets on the surface of a to-be-detected sample; the ionization device generates an alternating electric field around the sampling pipe, so that the extraction liquid drops in the sampling pipe form electrospray; and the mass spectrum detection device is connected with the sampling tube and is used for detecting the formed electrospray. According to the invention, the alternating current electric field is adopted to enable the liquid sampling liquid drops to directly generate electrospray, so that the sensitivity of molecule detection in the liquid drops can be improved on the premise of not damaging the sample during mass spectrometry detection.

Description

Technical Field

[0001] The present invention relates to the technical field of mass spectrometry analysis, and in particular to a droplet mass spectrometry analysis system based on an alternating current electric field and a method for performing mass spectrometry analysis on a sample surface. Background Art

[0002] Open atmospheric pressure ion source mass spectrometry can realize in situ analysis and obtain spatial molecular information, demonstrating its potential in biological research, clinical diagnosis and other aspects.

[0003] In recent years, relevant technologies have begun to explore how to avoid sample damage during mass spectrometry analysis. These methods mainly fall into two categories. One is indirect detection of samples, such as surgical aerosols, medical cotton swabs, or blotting tape. The other is direct detection of surfaces through gentle detection methods, such as low-temperature plasma technology. Despite continuous efforts, most methods still have limited sensitivity.

[0004] Therefore, a method for mass spectrometry analysis of sample surfaces that does not damage the sample surface and has high sensitivity is needed. Summary of the Invention

[0005] In view of this, in order to at least partially solve the above-mentioned technical problems, the present invention provides a droplet mass spectrometry analysis system based on an alternating current electric field and a method for performing sample surface mass spectrometry analysis thereon.

[0006] According to an embodiment of one aspect of the present invention, a droplet mass spectrometry analysis system based on an alternating current electric field is provided, comprising: a sampling device, an ionization device, and a mass spectrometry detection device, wherein the sampling device comprises a sampling pump and a sampling tube connected to the sampling pump, and utilizes the pressure difference provided by the sampling pump to sample the extracted droplets on the surface of the sample to be tested; the ionization device generates an alternating current electric field around the sampling tube, causing the extracted droplets in the sampling tube to form an electrospray; and the mass spectrometry detection device is connected to the sampling tube to detect the formed electrospray.

[0007] In some embodiments, the peak voltage of the AC electric field is 0.01-10 kV; the frequency is 0.001-100 kHz.

[0008] In some embodiments, the peak voltage of the AC electric field is 1.5-2.5 kV; the frequency is 0.5-1.5 kHz.

[0009] In some embodiments, the inner diameter of the sampling tube is 0.001-1000 μm, preferably 10-500 μm.

[0010] In some embodiments, the sampling pump includes at least one of a syringe pump, a pressure pump, and a peristaltic pump.

[0011] In some embodiments, the extraction droplets are selected from at least one of water, methanol, ethanol, and acetonitrile; preferably water.

[0012] In some embodiments, the pressure difference provided by the sampling pump is 0.0001-1000 kPa.

[0013] In some embodiments, the volume of the extraction droplet is 0.01 to 30,000 μL, preferably 4 to 6 μL.

[0014] According to an embodiment of another aspect of the present invention, a method for performing mass spectrometry analysis on a sample surface using a droplet mass spectrometry analysis system as described above is provided, comprising: applying extraction droplets to the surface of a sample to be tested for extraction; collecting the extraction droplets through a sampling tube using the pressure difference generated by a sampling pump; ionizing the extraction droplets into an electrospray using an AC electric field generated by an ionization device; and analyzing and detecting the electrospray using a mass spectrometry detection device.

[0015] In some embodiments, the extraction time is 0.1 to 3600 seconds, preferably 2 to 4 seconds.

[0016] According to the droplet mass spectrometry analysis system based on AC electric field in an embodiment of the present invention, the present invention utilizes extraction droplets to extract the surface of the sample to be tested, utilizes the pressure difference provided by the sampling pump to cause the extraction droplets to flow in the sampling tube; utilizes the AC electric field generated by the ionization device to ionize the extraction droplets, and converts the extraction droplets into electrospray, which can achieve highly sensitive surface mass spectrometry analysis of the components of the sample to be tested without damaging the sample to be tested. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The above and other objects, features and advantages of the present invention will become more apparent through the following description of the embodiments of the present invention with reference to the accompanying drawings, in which:

[0018] Figure 1 A schematic structural diagram of a droplet mass spectrometry analysis system according to an embodiment of the present invention is shown;

[0019] Figure 2 A flow chart of a method for mass spectrometry analysis of a sample surface according to an embodiment of the present invention is shown;

[0020] Figure 3 A diagram showing changes in mass spectrometry signals of representative substances when the ionization device of Example 1 of the present invention is turned on and off;

[0021] Figure 4 Graphs showing changes in mass spectrometry signals when the ionization device of Example 1 of the present invention is turned on and off are shown;

[0022] Figure 5 shows a mass spectrometry detection diagram of human body surface sampling according to Example 1 of the present invention;

[0023] Figure 6 The mass spectrometry detection diagram of bacterial colony sampling in Example 2 of the present invention is shown.

[0024] In the drawings, the meanings of the reference numerals are as follows:

[0025] 1. Sampling device;

[0026] 11. Sampling pump;

[0027] 12. Sampling tube;

[0028] 2. Ionization device;

[0029] 3. Mass spectrometry detection device;

[0030] 4. Sample to be tested;

[0031] 5. Extraction droplets. DETAILED DESCRIPTION

[0032] Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. However, it should be understood that these descriptions are exemplary only and are not intended to limit the scope of the present invention. In the following detailed description, for ease of explanation, many specific details are set forth to provide a comprehensive understanding of embodiments of the present invention. However, it is apparent that one or more embodiments may also be implemented without these specific details. In addition, in the following description, descriptions of known structures and technologies are omitted to avoid unnecessary confusion of the concept of the present invention.

[0033] The terms used herein are only for describing specific embodiments and are not intended to limit the present invention. The term "comprising" used herein indicates the existence of features, steps, operations, but does not exclude the existence or addition of one or more other features.

[0034] When expressions such as “at least one of A, B, and C, etc.” are used, they should generally be interpreted in accordance with the meaning commonly understood by those skilled in the art (for example, “a system having at least one of A, B, and C” should include but is not limited to systems having A alone, B alone, C alone, A and B, A and C, B and C, and / or A, B, and C, etc.). When expressions such as “at least one of A, B, or C, etc.” are used, they should generally be interpreted in accordance with the meaning commonly understood by those skilled in the art (for example, “a system having at least one of A, B, or C” should include but is not limited to systems having A alone, B alone, C alone, A and B, A and C, B and C, and / or A, B, and C, etc.).

[0035] Droplet microextraction is a separation and enrichment method that can improve sensitivity to a certain extent. Therefore, related technologies have begun to gradually try to use droplet microextraction technology on open atmospheric pressure ion source mass spectrometry to expand its application in tissue metabolite analysis, spatial metabolomics, and single-cell metabolomics.

[0036] In the process of realizing the concept of the present invention, it was found that in an open atmospheric pressure ion source mass spectrometer, it is difficult to directly apply a high voltage to the droplets in contact with the sample surface. If a high voltage is applied directly to the sample surface, although the sensitivity of detection can be improved, it will bring the risk of damage to the sample, especially for in vivo detection, which may cause irreversible damage.

[0037] Furthermore, in order to solve the above-mentioned problems, the present invention applies an AC electric field around the extraction droplets to form an electrospray, which can perform highly sensitive mass spectrometry analysis on the surface of the sample to be tested without damaging the sample to be tested.

[0038] Specifically, according to an embodiment of one aspect of the present invention, a droplet mass spectrometry analysis system based on an alternating current electric field is provided. Figure 1 FIG2 shows a schematic diagram of the structure of a droplet mass spectrometry analysis system according to an embodiment of the present invention. Figure 1 The droplet mass spectrometry analysis system includes: a sampling device 1, an ionization device 2 and a mass spectrometry detection device 3. The sampling device 1 includes a sampling pump 11 and a sampling tube 12 connected to the sampling pump 11. The pressure difference provided by the sampling pump 11 is used to sample the extraction droplets 5 on the surface of the sample 4 to be tested; the ionization device 2 generates an AC electric field around the sampling tube 12, so that the extraction droplets 5 in the sampling tube 12 form an electrospray; the mass spectrometry detection device 3 is connected to the sampling tube 12 to detect the formed electrospray.

[0039] According to an embodiment of the present invention, by applying extraction droplets 5 to the surface of a sample 4 to be tested, molecules on the sample surface are enriched. The extraction droplets 5 are directly drawn from the surface of the sample 3 to be tested through a pressure differential (positive or negative) generated by a sampling pump 11. This eliminates the need for complex pretreatment processes (such as liquid separation or solid-phase extraction), allowing for rapid sampling of trace substances on solid surfaces or biological tissue surfaces. This allows for real-time analysis and facilitates efficient transfer of the extraction droplets 5 through pressure differentials. The present invention applies a high-frequency AC voltage around a sampling tube 12 (which can be, for example, a capillary tube) to generate periodic charge oscillations in the extraction droplets 5 within the sampling tube 12, facilitating ionization to form a stable electrospray, thereby enabling highly sensitive mass spectrometric analysis without damaging the sample 4 to be tested.

[0040] It is understandable that the sample 4 to be tested may be solid, for example, human skin, bacterial colonies, cultured cells, etc.

[0041] It should be noted that the ion flow after electrospray ionization in the present invention directly enters the mass spectrometry detection device 3, which can realize the integration of sampling, ionization, detection and other means, and helps to reduce the loss of sample transmission in traditional devices, such as the vaporization loss in gas chromatography-mass spectrometry in related technologies, and improves detection sensitivity and shortens analysis time.

[0042] Furthermore, the droplet mass spectrometry analysis system of the present invention is relatively simple, easy to set up and disassemble, and has a certain degree of mobility, making its configuration more flexible and convenient. The sampling device 1, ionization device 2, and mass spectrometry detection device 3 can be integrated into a miniaturized device, such as a portable mass spectrometer, suitable for mobile monitoring and a wider detection range. Furthermore, the low flow resistance of the sampling tube 12 facilitates long-term stable detection.

[0043] Based on this, the sampling tube 12 can contact the surface of the sample to be tested 4 through the extraction droplet 5 to realize in-situ analysis, avoiding sample contamination or sample composition changes caused by sample transfer in traditional detection devices, and will not cause damage to the sample to be tested 4, preserving the integrity of the sample to be tested 4.

[0044] Optionally, the mass spectrometry detection device 3 of the present invention may be, for example, a desktop orbital trap mass spectrometer, a time-of-flight mass spectrometer, or a quadrupole mass spectrometer. The present invention does not particularly limit the type of the mass spectrometry detection device 3 .

[0045] In some embodiments, the AC electric field has a peak voltage of 0.01 to 10 kV and a frequency of 0.001 to 100 kHz. This configuration provides a peak voltage suitable for volume-scale ionization of the extraction droplets 5, while also creating a low electric field strength and a moderate surface charge density on the extraction droplets 5. This simplifies mass spectrometry analysis and further improves detection sensitivity and accuracy. This frequency promotes periodic oscillation and deformation of the surface charge of the extraction droplets 5 as the frequency changes, leading to regular electrospray splitting, thereby enhancing the long-term stability of the mass spectrometry signal.

[0046] Optionally, the peak voltage of the AC electric field can be, for example, 0.01 kV, 0.1 kV, 1 kV, 1.5 kV, 2 kV, 2.5 kV, 3 kV, 4 kV, 5 kV, 6 kV, 7 kV, 8 kV, 9 kV or 10 kV, or a range consisting of any two of the above values.

[0047] Optionally, the frequency may be, for example, 0.001kHz, 0.1kHz, 0.5kHz, 0.7kHz, 0.9kHz, 1kHz, 1.2kHz, 1.5kHz, 10kHz, 20kHz, 40kHz, 60kHz, 80kHz or 100kHz, or a range consisting of any two of the above values.

[0048] Preferably, the peak voltage of the AC electric field is 1.5-2.5 kV, more preferably 2 kV, and the frequency is 0.5-1.5 kHz, more preferably 1 kHz. This configuration can achieve a better electrospray effect on solid surface sampling, further improving the sensitivity of detection.

[0049] In some embodiments, the inner diameter of the sampling tube 12 is 0.001 to 1000 μm. It is understood that in sampling environments applicable to the present invention, the sampling tube 12 can be a capillary tube, thereby enabling trace detection of the sample to be tested, and under the premise of trace detection, it still has high sensitivity. If the inner diameter of the sampling tube 12 is too narrow, it is difficult to achieve continuous flow of the extraction droplets 5. If the inner diameter of the sampling tube 12 is too wide, a larger amount of extraction droplets 5 is required, resulting in slower flow of the extraction droplets 5, increasing the difficulty of forming an electrospray, and reducing sampling efficiency, which may affect the accuracy of the sampling quantification (for example, when sampling single-cell droplets, multiple cells may be mistakenly sampled).

[0050] It should be noted that the sampling tube 12 can be understood as a hollow tube that can transport the extraction droplets 5. The sampling tube 12 can be vertical or horizontal, and of course it can also be as follows. Figure 1 As shown, the sampling tube 12 has a certain bending angle in the middle, which is not particularly limited in the present invention, and can be convenient for sampling the sample 4 to be tested.

[0051] Optionally, the inner diameter of the sampling tube 12 can be, for example, 0.001 μm, 0.1 μm, 1 μm, 10 μm, 25 μm, 50 μm, 75 μm, 100 μm, 200 μm, 300 μm, 400 μm, 500 μm, 700 μm, 900 μm or 1000 μm, or a range consisting of any two of the above values.

[0052] Preferably, the inner diameter of the sampling tube 12 is 10-500 μm. This configuration can improve the detection signal intensity, shorten the sampling period, and improve the stability of the electrospray.

[0053] More preferably, the inner diameter of the sampling tube 12 is 50 μm.

[0054] In some embodiments, the sampling pump 11 is configured to generate a pressure difference between the interior of the sampling tube 12 and the extraction droplets 5, thereby promoting the continuous flow of the extraction droplets 5 within the sampling tube 12. The sampling pump 11 includes at least one of a syringe pump, a pressure pump, and a peristaltic pump. The selection of the above-mentioned different pumps is mainly based on the volume of the extraction droplets 5. For example, if the volume of the extraction droplets 5 is small, the syringe pump can achieve the collection and continuous flow of the extraction droplets 5. If the volume of the extraction droplets 5 is large, or the duration of the detection is long, it can be replaced with a pressure pump or a peristaltic pump as needed to maintain the stability of the extraction droplets 5 during the long-term collection.

[0055] In some embodiments, the extraction droplets 5 are selected from at least one of water, methanol, ethanol, and acetonitrile. The extraction droplets 5 on the surfaces of different solid test samples 4 are collected. Different extraction droplets 5 can be used according to the polarity of the test substance. For example, methanol, ethanol, etc. can be used for the extraction of medium-polarity substances such as drug residues and environmental pollutants; acetonitrile is suitable for the extraction of biological macromolecules such as proteins and polypeptides.

[0056] Preferably, the extraction droplet 5 is water. During mass spectrometry analysis of biological surfaces, water, due to its non-toxic and harmless nature, can avoid adverse effects on the biological surface and maintain the initial state of the sample 4. For example, when analyzing microbial metabolites, water helps maintain the ecological stability of the sample.

[0057] More preferably, sterile water is used as the extraction droplet 5, which can further reduce the possibility of damage to the biological sample to be tested and can maintain a high sensitivity of surface mass spectrometry analysis.

[0058] In some embodiments, the pressure difference provided by the sampling pump 11 is 0.0001-1000 kPa. This configuration can promote the continuous and stable flow of the extraction droplets 5 in the sampling tube 12 through the pressure difference.

[0059] In some embodiments, the volume of the extraction droplet 5 is 0.01 to 30,000 μL. The present invention does not impose any particular limitation on the volume of the extraction droplet 5, as long as it can form a droplet shape, and then the application of an AC electric field promotes the conversion of the extraction droplet 5 into an electrospray.

[0060] Optionally, the volume of the extraction droplet 5 can be, for example, 0.01 μL, 0.1 μL, 1 μL, 4 μL, 5 μL, 6 μL, 10 μL, 50 μL, 100 μL, 500 μL, 1000 μL, 10000 μL, 20000 μL or 30000 μL, or a range consisting of any two of the above values.

[0061] Preferably, the volume of the extraction droplet is 4 to 6 μL. This configuration helps to form a stable droplet state on the surface of the sample 4 to be tested, and then has a lower flow resistance when it subsequently flows into the sampling tube 12, which helps the mass spectrometry detection device 3 to perform continuous and stable detection.

[0062] According to another embodiment of the present invention, a method for performing mass spectrometry analysis on a sample surface using the droplet mass spectrometry system as described above is provided. Figure 2 FIG. 4 shows a flow chart of a method for mass spectrometry analysis of a sample surface according to an embodiment of the present invention. Figure 2 As shown, the method includes operations S201 to S204.

[0063] In operation S201 , an extraction droplet 5 is applied to the surface 4 of the sample to be tested for extraction.

[0064] In operation S202 , the extraction droplets 5 are collected through the sampling tube 12 using the pressure difference generated by the sampling pump 11 .

[0065] In operation S203 , the extraction droplets 5 are ionized into electrospray using the AC electric field generated by the ionization device 2 .

[0066] In operation S204 , the mass spectrometry detection device 3 is used to analyze and detect the electrospray.

[0067] According to an embodiment of the present invention, in-situ extraction is achieved by in-situ contact of the extraction droplets 5 with the surface of the sample to be tested 4, thereby avoiding traditional pre-treatment steps, such as grinding and ultrasound, which damage the structure of the sample to be tested 4. In particular, the extraction method of the present invention is suitable for the extraction of sensitive samples such as biological tissues. For example, the components of different extraction droplets 5 help to extract different samples to be tested 4, thereby improving the signal purity of subsequent mass spectrometry detection. The sampling pump 11 can, for example, generate negative pressure to suck the extracted extraction droplets 5 into the sampling tube 12, thereby avoiding the damage to the extraction droplets 5 caused by the mechanical shear force of the traditional direct use of the pump. Furthermore, the introduction of the AC electric field helps to induce the extraction droplets 5 to form a stable electrospray at the end of the sampling tube 12, which helps to form an ion flow with a high charge density. When the mass spectrometry detection is subsequently performed, it can improve the sensitivity of the detection while avoiding damage to the sample to be tested 4, and is particularly suitable for the detection of organisms.

[0068] It should be noted that in the method of sample surface mass spectrometry analysis of the present invention, the relevant parameter settings of the sample to be tested 4, the extraction droplet 5, the AC voltage and frequency of the ionization device 2, the sampling pump 11, the sampling tube 12 and the mass spectrometry detection device 3 are consistent with the above and will not be repeated here.

[0069] In some embodiments, the extraction time is 0.1 to 3600 seconds. Such a setting helps to set different extraction times for different test samples 4. For example, when the test sample 4 is a small molecule with high solubility, a rapid extraction, such as 0.1 to 10 seconds, can be used. When the test sample 4 is a medium polar molecule, such as a pharmaceutical intermediate, a medium-speed extraction, such as 10 seconds to 30 minutes, can be used by extending the contact time to ensure sufficient enrichment of the test sample 4. When the test sample 4 is a macromolecule, such as a protein, a slow extraction, such as 30 minutes to 3600 seconds, can be used by further extending the contact time to achieve sufficient extraction of the test sample 4.

[0070] Preferably, when the sample 4 to be tested is biomass (e.g., biological tissue, cells, or microorganisms), the extraction time is 2 to 4 seconds, for example, 2 seconds, 3 seconds, or 4 seconds, preferably 3 seconds. This configuration maintains the activity of the biomolecules, avoids structural damage, reduces interference from the matrix, improves detection specificity, and is suitable for rapid in situ detection.

[0071] The present invention will be further described below by way of examples, drawings, and related test experiments and results thereof. In the detailed description that follows, for ease of explanation, many specific details are set forth to provide a comprehensive understanding of the embodiments of the present invention. However, it is apparent that one or more embodiments may be implemented without these specific details. Moreover, the details in the following embodiments may be arbitrarily combined into other feasible embodiments, unless conflicting.

[0072] It should be noted that the following specific examples are for illustration only and the scope of protection of the present invention is not limited thereto. The chemicals and raw materials used in the following examples were either commercially available or prepared in-house using recognized processing methods.

[0073] Example 1:

[0074] In this embodiment 1, the Figure 1 The droplet mass spectrometry analysis system based on an alternating current electric field shown includes a sampling device, an ionization device, and a mass spectrometry detection device.

[0075] The sampling tube of the sampling device is connected to the sampling pump, and the pressure difference is used to sample the extraction droplets on the surface of the sample to be tested; the ionization device generates an AC electric field around the end of the sampling tube, causing the solution in the sampling tube to produce an electrospray, and the mass spectrometry detection device uses a mass spectrometer to detect the electrospray.

[0076] The sampling tube in Example 1 is a capillary tube with an inner diameter of 50 μm. The sampling pump is a peristaltic pump. The capillary tube is directly connected to the peristaltic pump, so that the end of the capillary tube generates self-priming force. The other end of the capillary tube is placed directly in front of the inlet of the mass spectrometer detection device.

[0077] The extraction solution used sterile water with a volume of 5 μl.

[0078] The ionization device consists of a single electrode with an applied AC voltage, creating an AC electric field between it and the inlet of the mass spectrometer. This AC voltage is generated by a homemade power supply, amplified by a waveform generator, amplified by a power amplifier and a car ignition coil, and monitored by an oscilloscope equipped with an attenuation bar. The ionization device produces a sinusoidal voltage with a peak voltage of 2 kilovolts and a frequency of 1 kilohertz. The electrode is a copper sheet attached to the outside of the capillary, 1 cm from the inlet of the mass spectrometer.

[0079] The mass spectrometry detection device is a desktop Orbitrap mass spectrometer.

[0080] Human skin was used as the research object, and the above-mentioned droplet mass spectrometry analysis system was used to perform mass spectrometry analysis on the surface of human skin. The following steps were included:

[0081] A 5-microliter drop of sterile water was added to the skin surface to extract molecules for 3 seconds; the peristaltic pump was turned on to generate self-priming force at the end of the capillary; the extracted water droplets were drawn through the capillary; an ionization device was used to generate an AC electric field around the capillary to ionize the extracted droplets and generate an electrospray, which was further detected using a mass spectrometer.

[0082] Figure 3 A diagram showing changes in mass spectrometry signals of representative substances when the ionization device of Example 1 of the present invention is turned on and off; Figure 4 FIG1 shows the detection change diagram of the mass spectrometer signal when the ionization device of Example 1 of the present invention is turned on and off. Figure 3 and Figure 4 As shown in the figure, it can be seen that when the AC voltage is turned on, the mass spectrometry signal can be significantly enhanced and several representative substances can be detected. When the AC voltage is turned off, the mass spectrometry signal is low and the above representative substances cannot be detected.

[0083] Figure 5 1 shows a mass spectrometry diagram of human body surface sampling according to Example 1 of the present invention. Figure 5 As shown, it can be seen that a variety of substances can be effectively detected on the surface of human skin, verifying the feasibility of the droplet mass spectrometry analysis system constructed by the present invention, and the detection has high sensitivity without causing damage to the human skin structure.

[0084] Example 2:

[0085] This Example 2 uses the same droplet mass spectrometry analysis system as Example 1. In this Example 2, bacterial colonies are used as the research object, and the above-mentioned droplet mass spectrometry analysis system is used to perform mass spectrometry analysis on the surface of human skin. The following steps are included:

[0086] A 5-microliter drop of sterile water was added to the surface of the colony to extract molecules for 3 seconds; the peristaltic pump was turned on to generate self-priming force at the end of the capillary; the extracted water droplets were drawn through the capillary; an ionization device was used to generate an AC electric field around the capillary to ionize the extracted droplets and generate an electrospray, which was further detected using a mass spectrometer.

[0087] Figure 6 1 shows a mass spectrometry image of bacterial colony sampling according to Example 2 of the present invention. Figure 6 As shown, it can be seen that a variety of substances can be effectively detected in bacterial colonies, verifying the feasibility of the droplet mass spectrometry analysis system constructed by the present invention, and the detection has high sensitivity without causing damage to the bacterial colony structure.

[0088] The specific embodiments described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A droplet mass spectrometry analysis system based on an alternating current electric field, comprising: Sampling device, ionization device and mass spectrometry detection device, Wherein, the sampling device includes a sampling pump and a sampling tube connected to the sampling pump, and utilizes the pressure difference provided by the sampling pump to sample the extraction droplets on the surface of the sample to be tested; The ionization device generates an AC electric field around the sampling tube, so that the extraction droplets in the sampling tube form an electrospray; The mass spectrometer detection device is connected to the sampling tube to detect the formed electrospray.

2. The droplet mass spectrometry system according to claim 1, wherein: The peak voltage of the AC electric field is 0.01-10 kV; the frequency is 0.001-100 kHz.

3. The droplet mass spectrometry system according to claim 1, wherein: The peak voltage of the AC electric field is 1.5-2.5 kV; the frequency is 0.5-1.5 kHz.

4. The droplet mass spectrometry system according to claim 1, wherein: The inner diameter of the sampling tube is 0.001-1000 μm, preferably 10-500 μm.

5. The droplet mass spectrometry system according to any one of claims 1 to 4, wherein: The sampling pump includes at least one of a syringe pump, a pressure pump, and a peristaltic pump.

6. The droplet mass spectrometry system according to any one of claims 1 to 4, wherein: The extraction droplets are selected from at least one of water, methanol, ethanol, and acetonitrile; preferably water.

7. The droplet mass spectrometry system according to any one of claims 1 to 4, wherein: The pressure difference provided by the sampling pump is 0.0001~1000kPa.

8. The droplet mass spectrometry system according to any one of claims 1 to 4, wherein: The volume of the extraction droplet is 0.01-30000 μL, preferably 5 μL.

9. A method for performing mass spectrometry analysis on a sample surface using the droplet mass spectrometry system according to any one of claims 1 to 8, comprising: Applying the extraction droplets to the surface of the sample to be tested for extraction; The pressure difference generated by the sampling pump is used to collect the extraction droplets through the sampling tube; ionizing the extraction droplets into electrospray using an alternating current electric field generated by an ionization device; The electrospray is analyzed and detected using a mass spectrometry detection device.

10. The method according to claim 9, wherein: The extraction time is 0.1 to 3600 seconds, preferably 2 to 4 seconds.

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