High-sensitivity mass spectrometry device using plasma-enhanced desorption electrospray ionization

Abstract

The present invention discloses a high-sensitivity mass spectrometry analysis device for plasma enhanced desorption electrospray ionization, comprising a T-shaped insulating tube, the inlet end of the main tube section of which is provided with a sealing cap, and the outlet end is a tapered port; a capillary spray needle is provided at the center of the inner cavity, the liquid inlet of the capillary spray needle is connected to the desorption solvent with a microinjection pump, and the needle tip sprays charged micro-droplets toward the sample through the tapered port; an inner electrode ring and an outer electrode ring are provided near the tapered port of the main tube section, the two being concentrically arranged along the central axis of the main tube section, and the inner and outer electrode rings and the capillary spray needle are all connected to a high-voltage power supply; a side tube section is provided near the inlet end of the main tube section, which is connected to the air inlet line of the discharge gas and is provided with a gas heater. The high-sensitivity mass spectrometry analysis device for plasma enhanced desorption electrospray ionization provided by the present invention is a plasma composite electrospray enhanced desorption ionization source device, which has an ingenious structure, is easy to use, and can effectively improve the detection sensitivity of DESI.

Description

Technical Field

[0001] The present invention relates to the technical field of mass spectrometry analysis, and in particular to a high-sensitivity mass spectrometry analysis device using plasma-enhanced desorption electrospray ionization. Background Art

[0002] Desorption electrospray ionization (DESI) is an atmospheric pressure ionization technique used in mass spectrometry. Combining the advantages of desorption and electrospray ionization, DESI generates ions directly from the sample surface and transmits them to the mass spectrometer for detection. While DESI offers numerous advantages in mass spectrometry, such as being non-destructive, rapid, and efficient, it still faces several limitations in practical applications. Matrix components in complex samples can interfere with the ionization of target molecules, resulting in reduced signal intensity, decreased desorption, and decreased sensitivity, making accurate detection of low-concentration and trace-level targets difficult, particularly in complex matrices such as biological tissue or environmental samples. Traditional DESI relies on the mechanical action of desorption solvent droplets to desorb and ionize sample molecules, resulting in low ionization efficiency. For some samples, particularly high molecular weight and non-polar compounds, ionization results are suboptimal, resulting in limited sensitivity. Continuous application of high-voltage direct current can induce thermal effects, compromising sample stability and integrity, potentially leading to sample degradation or damage and compromising the accuracy of analytical results. High-pressure spraying consumes significant amounts of desorption solvent and can result in sample loss. Summary of the Invention

[0003] In order to improve the detection sensitivity of DESI, the present invention provides a high-sensitivity mass spectrometry device using plasma-enhanced desorption electrospray ionization, which can specifically adopt the following technical solutions:

[0004] The high-sensitivity mass spectrometry analysis device for plasma-enhanced desorption electrospray ionization of the present invention comprises a T-shaped insulating tube, which is composed of a main tube section and a side tube section connected thereto; the inlet end of the main tube section is provided with a sealing cap, and the outlet end is a tapered opening; a capillary needle extending axially is provided at the center of the inner cavity of the main tube section, the liquid inlet of the capillary needle is connected to a micro-injection pump for a desorption solvent through an injection tube located outside the T-shaped insulating tube, and the needle tip of the capillary needle is injected into the sample tube located outside the T-shaped insulating tube through the tapered opening. The product is sprayed with charged micro-droplets; the main pipe section is provided with an inner electrode ring located in a T-shaped insulating tube and an outer electrode ring located outside the T-shaped insulating tube near the conical mouth, the inner electrode ring and the outer electrode ring are concentrically arranged along the central axis of the main pipe section, the inner electrode ring, the outer electrode ring and the capillary spray needle are respectively connected to a high-voltage power supply, and the high-voltage power supply has a DC high-voltage output port, a pulse high-voltage output port and an AC high-voltage output port; the side pipe section is provided near the inlet end of the main pipe section, the inlet of the side pipe section is connected to the inlet pipeline of the discharge gas, and a gas heater is provided in the side pipe section.

[0005] The main pipe section and the side pipe section of the T-shaped insulating pipe have the same inner diameter, a wall thickness of 0.5-1 mm, and an outer diameter of 2-6 mm.

[0006] The capillary needle is a hollow needle-shaped structure made of glass, quartz or peek material, with an inner diameter of 1-100 μm; and the flow rate of the microinjection pump is 0.001-20 μL / min.

[0007] There are one or more capillary needles, each of which is connected to one of the microinjection pumps. The distance between the tip of each capillary needle and the edge of the tapered orifice is -10 mm to +10 mm.

[0008] The inner electrode ring and the outer electrode ring are both conductive metal rings, which are concentrically arranged with a spacing of 0.5 to 5 mm, and both ends of the inner electrode ring are located inside the outer electrode ring.

[0009] The length of the outer electrode ring is 10-30 mm, and the distance between the end surface of the outer electrode ring close to the tapered opening and the edge of the tapered opening is 0-10 mm.

[0010] The DC high voltage amplitude of the DC high voltage output port is -10000~+10000V; the pulse high voltage amplitude of the pulse high voltage output port is -10000~+10000V, the frequency is 10~20KHz, and the duty cycle is 0~100%; the peak value of the AC voltage of the AC high voltage output port is -20000~+20000V, and the frequency is 10~20KHz.

[0011] The discharge gas is argon, helium, nitrogen, oxygen or neon, and the maximum heating temperature is 600°C.

[0012] A flow meter is provided on the discharge gas inlet pipeline, and the flow rate of the discharge gas is controlled at 0-5 L / min.

[0013] The sample is arranged on a sample support plate, the sample surface is gradually tilted from top to bottom along the ejection direction of the charged micro-droplets, and a mass spectrometer is arranged below the sample support plate.

[0014] The high-sensitivity mass spectrometry device for plasma-enhanced desorption electrospray ionization (DESI) provided by the present invention is a plasma-composite electrospray-enhanced desorption ionization (DESI) source device with a clever structure and ease of use, effectively improving the detection sensitivity of DESI. Its operating principle is as follows:

[0015] The charged droplets generated by the capillary needle and the discharge gas in the T-shaped insulating tube break down to generate plasma, which bombards the sample surface under the action of the airflow to produce charge exchange. The droplets achieve target molecule desorption and charge exchange on the sample surface in the plasma atmosphere, thereby achieving efficient ionization of the sample molecules, which then enter the mass spectrometer for analysis.

[0016] By introducing plasma technology into the DESI ionization process, the high energy and reactive species of the plasma are used to treat the charged microdroplets, significantly improving surface desorption performance. In the high-energy environment of the plasma, sample molecules within the charged microdroplets are further ionized and dissociated, generating a stronger ion signal. Secondly, the plasma promotes rapid evaporation of the desorption solvent, concentrating the sample and improving detection sensitivity. Thirdly, the high-energy particles and free radicals in the plasma significantly reduce matrix effects, enhancing the specificity and accuracy of the analysis.

[0017] The inner and outer electrode rings and capillary spray needle of the present invention can be connected to high-voltage power supplies independently. By selecting different output ports, different types of high voltage (DC, pulsed, AC) can be applied simultaneously, providing greater operational flexibility and enabling optimization of ionization and analytical performance based on experimental requirements. Notably, the capillary spray needle can generate spray solely by relying on the electromotive force of the ring electrode without applying high voltage, reducing system complexity and operational difficulty. However, if necessary, high voltage can still be applied to the capillary spray needle to ensure spray stability, further optimizing electrospray analysis. Independent high-voltage control allows fine-tuning of voltage types and combinations to optimize the ionization process, flexibly meeting different sample and analytical requirements, and improving the reproducibility and accuracy of experimental results.

[0018] This invention not only solves the limitations of traditional DESI technology in the analysis of complex samples, greatly improving the sensitivity and reliability of mass spectrometry analysis, but also has significant advantages in electrospray analysis efficiency, flexibility, ionization effect, background noise control, operational stability and versatility. It is suitable for the high-efficiency and high-quality analysis needs in fields such as environmental monitoring, food safety, drug testing and biomedicine. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is a structural diagram of Example 1 of the present invention.

[0020] Figure 2 It is a structural diagram of Example 2 of the present invention. DETAILED DESCRIPTION

[0021] The following describes an embodiment of the present invention in detail with reference to the accompanying drawings. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and a specific working process. However, the protection scope of the present invention is not limited to the following embodiment.

[0022] Example 1:

[0023] like Figure 1 As shown, the high-sensitivity mass spectrometry analysis device for plasma-enhanced desorption electrospray ionization described in the present invention includes a T-shaped insulating tube 1 consisting of a main tube section and a side tube section connected thereto. The main tube section and the side tube section have the same inner diameter, a wall thickness of 0.6 mm, and an outer diameter of 5 mm.

[0024] The inlet end of the main pipe section is provided with a sealing cap 2, and the outlet end is a tapered opening. An axially extending capillary needle 3 is provided at the center of the inner cavity of the main pipe section. It is a hollow needle-shaped structure with an inner diameter of 1 to 100 μm and is made of glass, quartz, or peek material. The liquid inlet of the capillary needle 3 is connected to the desorption solvent microinjection pump 5 through the injection tube 4 located outside the T-shaped insulating tube 1. The needle tip of the capillary needle 3 sprays charged microdroplets toward the sample M located outside the T-shaped insulating tube 1 through the tapered opening. In this embodiment, there is one capillary needle 3, which is arranged along the central axis of the main pipe section, has an inner diameter of 10 μm, and the needle tip extends outside the tapered opening and is 1 mm away from the edge of the tapered opening. The flow rate of the microinjection pump 5 is 1 μL / min. It should be noted that the tip of the capillary needle 3 can also be retracted inside the tapered opening. Generally, the distance between the tip of the capillary needle 3 and the edge of the tapered opening needs to be maintained at -10 mm to +10 mm.

[0025] Near the tapered opening of the main tube section, an inner electrode ring 6 located within the T-shaped insulating tube 1 and an outer electrode ring 7 located outside the T-shaped insulating tube 1 are provided. Both the inner electrode ring 6 and the outer electrode ring 7 are conductive metal rings, concentrically arranged along the central axis of the main tube section with a spacing of 0.5 to 5 mm. Both ends of the inner electrode ring 6 are located inside the outer electrode ring 7, that is, within the coverage area of ​​the outer electrode ring 7, to ensure effective breakdown of the discharge gas. Typically, the length of the outer electrode ring 7 is 10 to 30 mm, and the spacing between the end face of the outer electrode ring 7 near the tapered opening of the capillary needle 3 and the edge of the tapered opening is 0 to 10 mm. In this embodiment, the outer electrode ring 7 and the inner electrode ring 6 are both 20 mm long, and the spacing between them is 3 mm.

[0026] The high-voltage power supply 8 has independently configured DC, pulsed, and AC high-voltage output ports. The inner electrode ring 6, outer electrode ring 7, and capillary needle 3 can be connected to the appropriate output port based on actual requirements. The DC high-voltage output port has a DC high-voltage amplitude of -10,000 to +10,000 V; the pulsed high-voltage output port has a pulsed high-voltage amplitude of -10,000 to +10,000 V, a frequency of 10 to 20 kHz, and a duty cycle of 0 to 100%. The AC high-voltage output port has an AC voltage peak of -20,000 to +20,000 V, and a frequency of 10 to 20 kHz.

[0027] In this embodiment, no voltage is applied to the outer electrode ring 7. A DC high voltage with an amplitude of 2000V is applied to the capillary needle 3. A pulsed voltage with an amplitude of 0-5000V, a frequency of 15 kHz, and a duty cycle of 1% is applied to the inner electrode ring 6. The high voltage between the inner and outer electrode rings 6 and 7 breaks down the discharge gas within the T-shaped insulating tube 1, generating plasma. Furthermore, the desorption solvent stream ejected from the capillary needle 3, under the dual effects of the electric field and airflow, produces charged microdroplets.

[0028] The side section of the T-shaped insulating tube 1 is located near the inlet of the main section. Its inlet is connected to the discharge gas inlet line, which is equipped with a flow meter 9. Furthermore, a gas heater 10 is installed within the side section to improve the desorption efficiency of target substances in subsequent samples. In this embodiment, helium (argon, nitrogen, oxygen, or neon can also be used) is selected as the discharge gas, with a flow rate of 1 L / min and a heating temperature of 200°C.

[0029] A sample support 11 is mounted at the outlet of the T-shaped insulating tube 1, securing the sample M. The sample surface is gradually tilted downward in the direction of the charged droplet ejection. A mass spectrometer 12 is mounted beneath the sample support 11 for sample analysis. Charged droplets generated at the outlet of the T-shaped insulating tube 1, driven by airflow, strike the surface of the sample M, generating charge exchange. In the plasma atmosphere, the droplets desorb target molecules from the sample M surface and exchange charge, achieving efficient ionization of the sample molecules. The sample then enters the mass spectrometer 12 for analysis.

[0030] During operation, a certain amount of desorption solvent is first injected into the microinjection pump 5, and then transported into the capillary needle 3 at a set speed. Subsequently, the flow meter 9 on the side pipe section is turned on to allow the discharge gas to pass through the gas heater 10 into the main pipe section at a set flow rate. On the one hand, it serves as a medium for generating plasma, and also as a carrier gas to transport the desorption solvent ions and plasma to the sample; finally, the ground wire is connected, and the high-voltage power supply 8 is turned on to apply a high voltage to the inner electrode ring 6, the outer electrode ring 7 and the capillary needle 3. Among them, when the discharge gas passes through the inner electrode ring 6 and the outer electrode ring 7, a plasma jet is generated. At the same time, the electromotive force generated by the inner electrode ring 6 acts on the desorption solvent in the capillary needle 3, causing it to form small and uniform spray charged droplets at the outlet. After mixing with the plasma jet, the sample is desorbed by plasma and electrospray simultaneously.

[0031] Example 2:

[0032] The structure of the device described in this embodiment is basically the same as that of Example 1, with the only difference being that three capillary needles 3 are arranged in parallel at the center of the T-shaped insulating tube 1, and their inlet ends are connected to three micro-injection pumps 5 respectively after passing through the sealing cap 2, for introducing multiple desorption solvents to desorb the sample under different desorption solvent environments. This multiple desorption solvent system can more comprehensively dissolve and desorb various compounds in the sample, thereby improving the overall desorption efficiency and capacity; different desorption solvents have different desorption effects on different types of samples. The use of multiple desorption solvents can expand the scope of application of the present invention and make it applicable to a wider range of sample types; it can effectively reduce the matrix effect, and the combination of different desorption solvents can optimize the separation of the sample and the matrix, thereby reducing the interference of the matrix on the analysis results.

[0033] In this embodiment, the inner ring electrode 6 applies a low-frequency AC high voltage with an amplitude of -1500 to 1500 V and a frequency of 50 Hz. This creates a relatively gentle dynamic electric field in the sample region, facilitating pre-ionization of sample molecules and providing the foundational electric field environment for helium plasma generation. The outer ring electrode 7 applies a high-frequency pulsed high voltage with an amplitude of 0 to 3000 V, a frequency of 10 kHz, and a duty cycle of 10%. This high-frequency pulse voltage triggers discharge in the helium, generating a plasma. The plasma provides additional energy for ionization of sample molecules, significantly improving ionization efficiency and making it particularly suitable for samples that are difficult to ionize. The capillary needle 3 applies a DC high voltage with an amplitude of 0 to 1000 V, ensuring stable spray generation and maintaining continuous ion transport. This DC high voltage, combined with the auxiliary effect of the plasma, optimizes spray stability and ionization efficiency. Simultaneously, the helium is heated to 200°C as it passes through the insulating tube between the inner and outer ring electrodes 6. This further enhances the helium's activity and allows the high-frequency pulses of the outer ring electrode 7 to generate a more effective plasma. Heating the helium not only promotes plasma formation but also improves the ionization efficiency of the sample, making the detection of volatile and semi-volatile compounds more sensitive and efficient.

[0034] Conventional DESI suffers from limitations such as matrix interference, low ionization efficiency, and sample loss in complex samples, making it difficult to accurately detect low-concentration and trace amounts of target compounds. To address these issues, the present invention proposes a plasma-combined electrospray-enhanced desorption ionization source. The inner and outer electrode rings, as well as the capillary needle, can be connected to separate high-voltage power supplies. By selecting different output ports, different types of high voltage (DC, pulsed, AC) can be applied simultaneously, providing greater operational flexibility and enabling optimization of ionization and analytical performance based on experimental requirements. Notably, the capillary needle can generate the spray solely based on the electromotive force of the ring electrode, without the need for high voltage, reducing system complexity and operational difficulty. However, if necessary, high voltage can still be applied to the capillary needle to ensure spray stability, further optimizing electrospray analysis. Independent high-voltage control allows for fine-tuning of voltage types and combinations to optimize the ionization process, flexibly meeting diverse sample and analytical requirements, and improving the reproducibility and accuracy of experimental results.

[0035] This invention not only solves the limitations of traditional DESI technology in the analysis of complex samples, greatly improving the sensitivity and reliability of mass spectrometry analysis, but also has significant advantages in electrospray analysis efficiency, flexibility, ionization effect, background noise control, operational stability and versatility. It is suitable for the high-efficiency and high-quality analysis needs in fields such as environmental monitoring, food safety, drug testing and biomedicine.

[0036] It should be noted that, in the description of the present invention, terms indicating orientation or positional relationships such as “front”, “rear”, “left”, “right”, “vertical”, “horizontal”, “inside”, and “outside” are based on the orientation or positional relationships shown in the accompanying drawings and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention.

Claims

1. A high-sensitivity mass spectrometry device using plasma-enhanced desorption electrospray ionization, characterized in that: The invention comprises a T-shaped insulating tube, wherein the T-shaped insulating tube is composed of a main tube section and a side tube section connected thereto; the inlet end of the main tube section is provided with a sealing cap, and the outlet end is a tapered opening; a capillary needle extending in the axial direction is provided at the center of the inner cavity of the main tube section, the liquid inlet of the capillary needle is connected to a micro-injection pump for desorption solvent through an injection tube located outside the T-shaped insulating tube, and the needle tip of the capillary needle sprays charged micro-droplets toward the sample located outside the T-shaped insulating tube through the tapered opening; the main tube section is close to the tapered opening. An inner electrode ring located inside a T-shaped insulating tube and an outer electrode ring located outside the T-shaped insulating tube are provided at the outlet. The inner electrode ring and the outer electrode ring are concentrically arranged along the central axis of the main tube section. The inner electrode ring, the outer electrode ring and the capillary nozzle are respectively connected to a high-voltage power supply. The high-voltage power supply has a DC high-voltage output port, a pulsed high-voltage output port and an AC high-voltage output port. The side tube section is arranged near the inlet end of the main tube section. The inlet of the side tube section is connected to the inlet pipeline of the discharge gas. A gas heater is provided in the side tube section. The inner electrode ring and the outer electrode ring are both conductive metal rings, which are concentrically arranged with a spacing of 0.5 to 5 mm, and both ends of the inner electrode ring are located inside the outer electrode ring.

2. The high-sensitivity mass spectrometry device using plasma-enhanced desorption electrospray ionization according to claim 1, characterized in that: The main pipe section and the side pipe section of the T-shaped insulating pipe have the same inner diameter, a wall thickness of 0.5-1 mm, and an outer diameter of 2-6 mm.

3. The high-sensitivity mass spectrometry device using plasma-enhanced desorption / electrospray ionization according to claim 1, characterized in that: The capillary needle is a hollow needle-shaped structure made of glass, quartz or peek material, with an inner diameter of 1-100 μm; and the flow rate of the microinjection pump is 0.001-20 μL / min.

4. The high-sensitivity mass spectrometry device using plasma-enhanced desorption electrospray ionization according to claim 1, characterized in that: There are one or more capillary needles, each of which is connected to one of the microinjection pumps. The distance between the tip of each capillary needle and the edge of the tapered orifice is -10 mm to +10 mm.

5. The high-sensitivity mass spectrometry device using plasma-enhanced desorption electrospray ionization according to claim 1, characterized in that: The length of the outer electrode ring is 10-30 mm, and the distance between the end surface of the outer electrode ring close to the tapered opening and the edge of the tapered opening is 0-10 mm.

6. The high-sensitivity mass spectrometry device using plasma-enhanced desorption electrospray ionization according to claim 1, characterized in that: The DC high voltage amplitude of the DC high voltage output port is -10000~+10000V; the pulse high voltage amplitude of the pulse high voltage output port is -10000~+10000V, the frequency is 10~20KHz, and the duty cycle is 0~100%; the peak value of the AC voltage of the AC high voltage output port is -20000~+20000V, and the frequency is 10~20KHz.

7. The high-sensitivity mass spectrometry device using plasma-enhanced desorption electrospray ionization according to claim 1, characterized in that: The discharge gas is argon, helium, nitrogen, oxygen or neon, and the maximum heating temperature is 600°C.

8. The high-sensitivity mass spectrometry device using plasma-enhanced desorption electrospray ionization according to claim 1, characterized in that: A flow meter is provided on the discharge gas inlet pipeline, and the flow rate of the discharge gas is controlled at 0-5 L / min.

9. The high-sensitivity mass spectrometry device using plasma-enhanced desorption electrospray ionization according to claim 1, characterized in that: The sample is arranged on a sample support plate, the sample surface is gradually tilted from top to bottom along the ejection direction of the charged micro-droplets, and a mass spectrometer is arranged below the sample support plate.

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