Mass spectrometry ion generating device and method of manufacturing the same, mass spectrometry ion transporting device, control system and control method

Abstract

The present disclosure relates to the technical field of mass spectrometry ion, and discloses a mass spectrometry ion generation device and a preparation method thereof, a mass spectrometry ion conveying device, a control system and a control method. The mass spectrometry ion generation device comprises a main flow channel, a liquid limiting structure, an aerosol generation flow channel and a sound wave generation device. The liquid containing space of the liquid limiting structure can communicate the main flow channel and the aerosol generation flow channel, and can block the to-be-tested liquid in the liquid containing space from flowing into the aerosol generation flow channel. The sound wave generation device outputs a surface acoustic wave to the to-be-tested liquid in the liquid containing space to generate a to-be-tested aerosol in the aerosol generation flow channel. The main flow channel allows various types of to-be-tested liquid to flow quickly to flush the connection between the main flow channel and the liquid containing space, so that the to-be-tested liquid is more easily introduced into the liquid containing space, while effectively avoiding blockage, improving the tolerance of various to-be-tested liquids and ensuring the analysis sensitivity.

Description

Technical Field

[0001] This disclosure relates to the field of mass spectrometry ion technology, specifically to a mass spectrometry ion generation device, a method for preparing a mass spectrometry ion generation device, a mass spectrometry ion delivery device, a mass spectrometry ion control system, and a mass spectrometry ion control method. Background Technology

[0002] The detection sensitivity and robustness of mass spectrometry are largely limited by the efficiency of the ionization technology at the front-end liquid chromatography interface. Traditional electrospray ionization (ESI) widely relies on applying a strong electrostatic field of several thousand volts (typically 3-5 kV) to a metal capillary with an inner diameter of several hundred micrometers. In this strongly coupled system, the high-voltage electric field is not only responsible for charging the target analyte, but must also provide the mechanical kinetic energy to tear the surface tension of the fluid and cause the Taylor cone to burst.

[0003] This strong coupling of energy and fluid dynamics leads to highly destructive limitations: conventional ESI suffers from severe ion uplift when faced with the high inorganic salt content in blood, tissue fluid, or environmental monitoring samples. Simultaneously, the conventional system forcibly pushes the entire bulk liquid phase (flow rate of several mL / min) containing extremely high salt concentrations into the charged atomization region, causing a large amount of crystalline salt to precipitate at the mass spectrometer's inlet cone within a very short time, resulting in physical blockage of the metal capillary. Furthermore, the thousands of volts of high voltage and high-temperature gas flow in conventional ESI often disrupts the fragile non-covalent bonds between proteins or protein-ligands, causing protein denaturation.

[0004] Furthermore, in techniques such as atmospheric pressure photoionization (APPI) or chemical ionization (APCI) that require the introduction of dopants and gas-phase discharge, the introduction of continuous-flow reagents can cause serious problems of high background noise and high consumption pollution. On the other hand, if a DC bias is directly applied to a traditional dielectric barrier discharge (DBD) electrode, it is very easy to cause surface charge accumulation, which leads to discharge "quenching". The presence of a large number of high-mobility electrons is also very easy to recombine with nascent free radical cations, which seriously weakens the ion abundance that is finally transported to the mass spectrometer. Summary of the Invention

[0005] In view of at least some of the problems existing in the prior art, at least one object of this disclosure is to effectively avoid clogging, improve tolerance to various test liquids, and ensure analytical sensitivity.

[0006] To achieve the above objectives, in a first aspect, this disclosure provides a mass spectrometry ion generation apparatus, which includes a main channel, an aerosol generation channel, a liquid confinement structure, and an acoustic wave generator. The main channel is configured to receive a liquid to be tested; the aerosol generation channel is configured to generate a analyte aerosol; the liquid confinement structure includes a liquid containment space configured to connect the main channel and the aerosol generation channel, and to prevent the liquid to be tested entering the liquid containment space from the main channel from flowing into the aerosol generation channel; the acoustic wave generator is configured to output surface acoustic waves to the liquid to be tested entering the liquid containment space, thereby driving the liquid to be tested to generate a analyte aerosol within the aerosol generation channel.

[0007] In this mass spectrometry ion generation device, the liquid containment space of the liquid-limiting structure connects the main flow channel and the aerosol generation channel, preventing the analyte liquid entering the liquid containment space from the main flow channel from flowing into the aerosol generation channel. The acoustic wave generator outputs surface acoustic waves to the analyte liquid entering the liquid containment space, driving it to generate aerosols within the aerosol generation channel. This allows various types of analyte liquids to flow rapidly through the main flow channel, flushing the connection between the main flow channel and the liquid containment space, making it easier for the analyte liquid to enter the liquid containment space and preventing blockage. The surface acoustic waves drive the analyte liquid in the liquid containment space to generate aerosols within the aerosol generation channel, effectively preventing blockage while improving tolerance to various analyte liquids and ensuring analytical sensitivity. Furthermore, this mass spectrometry ion generation device does not disrupt the fragile non-covalent bonds between proteins or protein-ligands, making its detection particularly advantageous.

[0008] In some embodiments, the mass spectrometry ion generation device includes a bypass channel with a waste outlet, wherein the bypass channel is provided with a unidirectional structure that opens when a set condition is met to connect the waste outlet and the main channel.

[0009] In some embodiments, the mass spectrometry ion generation device includes a detachable module, wherein the detachable module includes at least the main flow channel, the aerosol generation channel, and the liquid limiting structure.

[0010] In some embodiments, the mass spectrometry ion generation device further includes electrodes and a bias power supply, wherein the bias power supply is configured to output a dynamically controllable micropotential to inject charge, enabling the electrodes to conduct charge through aerosol particles of the aerosol to be tested, thereby ionizing them.

[0011] In some embodiments, the electrode includes a conductive thin-film electrode, and the bias power supply provides a steady-state DC bias voltage or a transient pulse bias voltage controlled by a feedback loop.

[0012] In some embodiments, the liquid containment space includes a slit, wherein the surface acoustic waves generated by the acoustic wave generating device enable the laminar flow at least near the acoustic wave generating device within the slit to overcome surface tension under the high-speed shear stress of the local parallel acoustic flow and to be continuously stripped laterally towards the aerosol generation channel, so as to atomize into the aerosol to be tested within the aerosol generation channel.

[0013] In some embodiments, the liquid limiting structure includes a cover plate, a piezoelectric substrate of the acoustic wave generator, and a support disposed between the piezoelectric substrate and the cover plate, wherein the support causes the gap to be formed between the piezoelectric substrate and the cover plate.

[0014] In some embodiments, the height of the gap is 5μm-50μm.

[0015] In some embodiments, the mass spectrometry ion generation device further includes a temperature control module thermally coupled to the acoustic wave generator to absorb and remove the heat generated by the acoustic wave generator during operation.

[0016] In some embodiments, the temperature control module includes a temperature sensor and a semiconductor thermoelectric cooler, wherein the semiconductor thermoelectric cooler and the sound wave generator are thermally coupled, the temperature sensor monitors the real-time temperature of the sound wave generator and feeds back the monitored real-time temperature to an external controller, and the external controller controls the power supply to the semiconductor thermoelectric cooler so that the semiconductor thermoelectric cooler can absorb and dissipate the heat generated by the sound wave generator during operation, thereby dynamically controlling the operating temperature of the sound wave generator.

[0017] In a second aspect, this disclosure provides a mass spectrometry ion delivery device configured for use in conjunction with any of the mass spectrometry ion generation devices described in the first aspect above. The mass spectrometry ion delivery device includes a delivery channel, an annular accelerating gas channel, and an annular nozzle gas channel arranged around the same central axis. The delivery channel is configured to receive and output a test aerosol. The annular accelerating gas channel is configured to provide an annular accelerating gas curtain around the test aerosol output from the delivery channel to accelerate the test aerosol into an ion stream. The annular nozzle gas channel is configured to provide an annular nozzle gas curtain around the ion stream, serving as a gas phase tube wall transport channel for the ion stream to suspend and travel.

[0018] In this mass spectrometry ion delivery device, the delivery channel receives and outputs the aerosol to be tested generated by any of the mass spectrometry ion generation devices described in the first aspect. The annular accelerating gas channel provides an annular accelerating gas curtain surrounding the output aerosol to be tested. This annular accelerating gas curtain accelerates the aerosol to be tested into an ion stream, thereby rapidly carrying the aerosol to be tested downstream and effectively physically isolating downstream heat, preventing downstream heat from heating the transducer of the acoustic wave generator of any of the mass spectrometry ion generation devices described in the first aspect. Subsequently, the annular nozzle gas channel provides an annular nozzle gas curtain surrounding the ion stream. This annular nozzle gas curtain, as a gas phase tube wall transport channel for the ion stream to suspend and travel, can effectively wrap and capture the ion stream to counteract the lateral diffusion momentum at the vector level, stably and reliably delivering the ion stream downstream. In addition, this mass spectrometry ion delivery device does not damage the fragile non-covalent bonds between proteins or protein-ligands, thus being particularly advantageous for their detection.

[0019] In some embodiments, the annular accelerating air passage provides the annular accelerating air curtain at the outlet of the delivery channel.

[0020] In some embodiments, the outlet end of the annular acceleration airway tapers toward the central axis.

[0021] In some embodiments, the inner diameter of the first upper sidewall at the outlet end of the annular accelerating airway is the same as and larger than the inner diameter of the first lower sidewall at the outlet end of the annular accelerating airway, so as to form an inverted frustum-shaped airflow field at the outlet end of the annular accelerating airway.

[0022] In some embodiments, the outlet end of the annular nozzle passage and the outlet end of the annular acceleration passage are axially spaced in the direction of the central axis.

[0023] In some embodiments, the outlet end of the annular nozzle air passage tapers toward the central axis.

[0024] In some embodiments, the inner diameter of the second upper sidewall at the outlet end of the annular nozzle air passage is larger than the inner diameter of the second lower sidewall at the outlet end of the annular nozzle air passage, so as to form an inverted frustum-shaped airflow field at the outlet end of the annular nozzle air passage.

[0025] In some embodiments, the annular acceleration air passage provides room temperature inert gas as the annular acceleration air curtain; the annular nozzle air passage provides thermal inert gas as the annular nozzle air curtain.

[0026] In some embodiments, the annular nozzle air passage is arranged around the annular acceleration air passage, which in turn is arranged around the delivery channel.

[0027] In some embodiments, the mass spectrometry ion delivery device includes a delivery conduit having the delivery channel, a first tube and a second tube disposed inside and outside to form the annular accelerating gas passage therebetween, and a third tube and a fourth tube disposed inside and outside to form the annular nozzle gas passage therebetween, wherein the first tube is disposed on the delivery conduit and the third tube is disposed on the second tube.

[0028] Thirdly, this disclosure provides a mass spectrometry ion control system, which includes any of the mass spectrometry ion generation devices described in the first aspect above.

[0029] In some embodiments, the mass spectrometry ion control system further includes any of the mass spectrometry ion delivery devices described in the second aspect above, wherein the aerosol to be tested generated by the mass spectrometry ion generation device can enter the delivery channel, the annular accelerating gas curtain provided by the annular accelerating gas channel can accelerate the aerosol to be tested into an ion stream, and the annular nozzle gas curtain provided by the annular nozzle gas channel delivers the ion stream downstream of the mass spectrometry ion control system.

[0030] In some embodiments, the mass spectrometry ion control system further includes a piezoelectric pulse jet device configured to jet the required volume of reagent into the ion stream delivered to the annular nozzle gas curtain.

[0031] In some embodiments, the piezoelectric pulse jet device is configured to receive a scan cycle trigger signal from a downstream mass spectrometer and jet the required volume of reagent into the annular nozzle gas curtain only during the ion accumulation window of the mass spectrometer.

[0032] In some implementations, the required volume is in the range of nanoliters to picoliters.

[0033] In some embodiments, the mass spectrometry ion control system further includes a microplasma reactor, wherein a ring electrode, a gas injection port, and a grid located at the outlet end of the reaction chamber are disposed within the reaction chamber of the microplasma reactor, the ring electrode and the grid are electrically connected to a controller, wherein the controller controls the microplasma reactor to have at least the following ionization modes: Soft ionization / electrostatic lens mode: The controller cuts off the high-frequency AC drive, so that the ring electrode acts as a pure ion optical lens without discharge. The controller applies a pure DC bias voltage controlled by the mass spectrometer scanning sequence to the ring electrode, and performs dynamic lens mapping adjustment at least according to the mass-to-charge ratio and aerodynamic resistance of the target ion being scanned, so as to ensure that the weak bond non-covalent complex in the ion stream enters the mass spectrometer without damage. Atmospheric pressure chemical ionization mode: The controller outputs a continuous high-frequency high-voltage alternating current to the annular electrode to excite dielectric barrier discharge, generating high-energy electrons and metastable nitrogen molecules, inducing strong gas-phase ion-molecule collision ionization. Atmospheric pressure ultraviolet photoionization mode: A set amount of high-purity argon or helium is injected through the gas injection port, and the controller applies an ultra-short pulse high voltage to the annular electrode to generate transient excimers and release high-intensity ultraviolet photons to perform efficient single-photon ionization.

[0034] In some embodiments, in the atmospheric pressure chemical ionization mode or the atmospheric pressure ultraviolet photoionization mode, the controller synchronously applies a DC bias to the grid.

[0035] Fourthly, this disclosure provides a method for preparing a mass spectrometry ion generation device, wherein the method includes: providing a main channel for receiving a liquid to be tested; providing an aerosol generation channel for generating an aerosol to be tested; providing a liquid limiting structure including a liquid containing space, such that the liquid containing space can connect the main channel and the aerosol generation channel, and can prevent the liquid to be tested entering from the main channel into the liquid containing space from flowing into the aerosol generation channel; and providing an acoustic wave generating device, such that the acoustic wave generating device can output surface acoustic waves to the liquid to be tested entering the liquid containing space, so as to drive the liquid to be tested entering the liquid containing space to generate an aerosol to be tested in the aerosol generation channel.

[0036] The mass spectrometry ion generation device prepared by this method has the advantage that the liquid containment space of the liquid-limiting structure can connect the main channel and the aerosol generation channel, and can prevent the test liquid entering the liquid containment space from the main channel from flowing into the aerosol generation channel. The acoustic wave generator can output surface acoustic waves to the test liquid entering the liquid containment space to drive the test liquid entering the liquid containment space to generate the test aerosol in the aerosol generation channel. In this way, the main channel allows various types of test liquids to flow rapidly to flush the connection between the main channel and the liquid containment space, making it easier for the test liquid to enter the liquid containment space and avoiding blockage. The surface acoustic waves can drive the test liquid in the liquid containment space to generate the test aerosol in the aerosol generation channel, thereby effectively avoiding blockage while improving the tolerance to various test liquids and ensuring analytical sensitivity.

[0037] In some embodiments, a slit is prepared to serve as a liquid-containing space.

[0038] In some embodiments, a piezoelectric single-crystal wafer with an interdigitated transducer electrode array photolithographically patterned on its surface is provided as a piezoelectric substrate; a support material is disposed on the upper surface of the piezoelectric single-crystal wafer to construct a planar intermediate support layer; a partial material removal and curing process is performed on the intermediate support layer to form a cured retention region, the cured retention region including a channel with sidewalls; a cover plate is attached to the cured retention region and covers the channel, such that the channel forms the slit.

[0039] Fifthly, this disclosure provides a mass spectrometry ion control method, which includes: injecting a test liquid at a predetermined flow rate into the main channel of a mass spectrometry ion generation device to enter the liquid containment space of the liquid limiting structure of the mass spectrometry ion generation device, and the liquid containment space preventing the test liquid entering the liquid containment space from the main channel from flowing into the aerosol generation channel of the mass spectrometry ion generation device; activating a sound wave generator to output surface acoustic waves to the test liquid entering the liquid containment space, so as to drive the test liquid entering the liquid containment space to generate a test aerosol in the aerosol generation channel.

[0040] In this mass spectrometry ion control method, the liquid containment space of the liquid-limiting structure can connect the main flow channel and the aerosol generation channel, and can prevent the test liquid entering the liquid containment space from the main flow channel from flowing into the aerosol generation channel. The acoustic wave generator can output surface acoustic waves to the test liquid entering the liquid containment space to drive the test liquid entering the liquid containment space to generate the test aerosol in the aerosol generation channel. In this way, the main flow channel allows various types of test liquids to flow rapidly to flush the connection between the main flow channel and the liquid containment space, making it easier for the test liquid to enter the liquid containment space and avoiding blockage. The surface acoustic waves can drive the test liquid in the liquid containment space to generate the test aerosol in the aerosol generation channel, thereby effectively avoiding blockage while improving the tolerance to various test liquids and ensuring analytical sensitivity. In addition, this mass spectrometry ion control method does not destroy the fragile non-covalent bonds of protein-protein or protein-ligand, which is particularly advantageous for their detection.

[0041] In some embodiments, a micropotential with a set voltage is applied to the aerosol to be tested via electrodes to conduct charge to the aerosol particles of the aerosol to be tested, thereby ionizing them.

[0042] In some implementations, an annular accelerating gas curtain is provided around the aerosol to be tested via an annular accelerating gas channel to accelerate the aerosol to be tested into an ion stream.

[0043] In some implementations, an annular nozzle air curtain is provided around the ion stream via an annular nozzle air passage to suspend and propel the ion stream.

[0044] In some embodiments, the controller of the microplasma reactor is controlled according to the properties of the target compound, causing the microplasma reactor to operate in any of the following ionization modes: Soft ionization / electrostatic lens mode: The controller cuts off the high-frequency AC drive of the ring electrode, so that the ring electrode acts as a pure ion optical lens without discharge. The controller applies a pure DC bias voltage controlled by the mass spectrometer scanning sequence to the ring electrode, and performs dynamic lens mapping adjustment at least according to the mass-to-charge ratio and aerodynamic resistance of the target ion being scanned, so as to ensure that the weak bond non-covalent complex in the ion stream enters the mass spectrometer without damage. Atmospheric pressure chemical ionization mode: The controller outputs a continuous high-frequency high-voltage alternating current to the annular electrode to excite dielectric barrier discharge, generating high-energy electrons and metastable nitrogen molecules, inducing strong gas-phase ion-molecule collision ionization. Atmospheric pressure ultraviolet photoionization mode: A set amount of high-purity argon or helium is injected, and the controller applies an ultra-short pulse high voltage to the annular electrode to generate transient excimers and release high-intensity ultraviolet photons to perform efficient single-photon ionization.

[0045] In some embodiments, in the atmospheric pressure chemical ionization mode or the atmospheric pressure ultraviolet photoionization mode, the controller synchronously applies a DC bias to the grid at the outlet end of the reaction chamber of the microplasma reactor.

[0046] In some implementations, the scanning cycle trigger signal of the downstream mass spectrometer is obtained, and the required volume of reagent is injected into the annular nozzle gas curtain only during the ion accumulation window of the mass spectrometer via a piezoelectric pulse jet device.

[0047] Other features and aspects of this disclosure will become apparent from the following detailed description and accompanying drawings. Attached Figure Description

[0048] Figure 1 This is a schematic diagram of a mass spectrometry ion control system provided according to one embodiment of the present disclosure.

[0049] Figure 2 This is a partial structural schematic diagram of a mass spectrometry ion generation apparatus provided according to one embodiment of the present disclosure.

[0050] Figure 3 This is a schematic flowchart of a mass spectrometry ion generation device provided according to one embodiment of the present disclosure.

[0051] Figure 4 This is a schematic diagram of a mass spectrometry ion generation apparatus with a bypass channel provided according to one embodiment of the present disclosure.

[0052] Figure 5 This is a schematic diagram of an acoustic wave generator of a mass spectrometry ion generation apparatus according to an embodiment of the present disclosure, thermally coupled with a temperature control module.

[0053] Figure 6 This is a partial structural schematic diagram of a mass spectrometry ion control system provided according to an embodiment of the present disclosure, showing a mass spectrometry ion delivery device provided according to an embodiment of the present disclosure.

[0054] Explanation of reference numerals in the attached figures 1-Main flow channel, 2-Aerosol generation channel, 3-Liquid containment space, 4-Acoustic wave generator, 5-Bypass channel, 6-Unidirectional structure, 7-Electrode, 8-Bias power supply, 9-Gap, 10-Cover plate, 11-Piezoelectric substrate, 12-Support body, 13-Orifice, 14-Liquid film, 15-Temperature control module, 16-Temperature sensor, 17-Semiconductor thermoelectric cooler, 18-External controller, 19-Mass spectrometer ion delivery device, 20-Mass spectrometer ion generation device, 21-Central axis, 22-Delivery channel, 23-Annular accelerating gas channel, 24 - Annular nozzle air passage, 25-First upper sidewall, 26-First lower sidewall, 27-Axial spacing, 28-Second upper sidewall, 29-Second lower sidewall, 30-Delivery pipe, 31-First pipe, 32-Second pipe, 33-Third pipe, 34-Fourth pipe, 35-Piezoelectric pulse jet device, 36-Micro plasma reaction device, 37-Reaction chamber, 38-Annular electrode, 39-Gas injection port, 40-Grid, 41-Controller, 42-Surface acoustic wave, 111-Interdigital transducer, 121-Planar intermediate support layer, 122-Cure retention area. Detailed Implementation

[0055] Before explaining any implementation of this disclosure in detail, it should be understood that the application of this disclosure is not limited to the details of the construction and arrangement of the components described in the following description or shown in the accompanying drawings. This disclosure can have other implementations and can be practiced or implemented in various ways. Furthermore, it should be understood that the wording and terminology used herein are for descriptive purposes and should not be considered limiting.

[0056] In the following detailed description of embodiments, reference is made to the accompanying drawings, which form part of this description. The drawings illustrate specific embodiments in which this disclosure is implemented by way of example. The embodiments shown are not intended to be exhaustive of all embodiments according to this disclosure. It is understood that other embodiments may be utilized, and structural or logical changes may be made without departing from the scope of this disclosure. With respect to the drawings, directional terms such as “down,” “up,” “left,” “right,” etc., are used with reference to the orientation of the described drawings. Since components of the embodiments of this disclosure can be implemented in various orientations, these directional terms are for illustrative purposes and not for limiting purposes. Therefore, the following specific embodiments are not intended to be limiting, and the scope of this disclosure is defined by the appended claims.

[0057] It should be noted that the mass spectrometry ion generation device provided in the first aspect and the mass spectrometry ion delivery device provided in the second aspect can be manufactured, used, sold, offered for sale, imported, etc., as separate accessories.

[0058] Figure 2 An embodiment of a mass spectrometry ion generation apparatus is shown, with reference to Figure 2 The mass spectrometry ion generation apparatus 20 provided in the first aspect of this disclosure includes a main channel 1, an aerosol generation channel 2, a liquid limiting structure, and an acoustic wave generator 4. The main channel 1 is configured to receive a liquid to be tested; the aerosol generation channel 2 is configured to generate aerosols to be tested; the liquid limiting structure includes a liquid containing space 3, which is configured to connect the main channel 1 and the aerosol generation channel 2 and to prevent the liquid to be tested entering the liquid containing space 3 from the main channel 1 from flowing into the aerosol generation channel 2; the acoustic wave generator 4 is configured to output surface acoustic waves 42 (SAWs) to the liquid to be tested entering the liquid containing space 3. Figure 2 The surface acoustic wave 42 in the diagram is only schematic, which drives the test liquid entering the liquid containment space 3 to generate the test aerosol in the aerosol generation channel 2.

[0059] In this mass spectrometry ion generation device 20, the liquid containment space 3 of the liquid limiting structure can connect the main flow channel 1 and the aerosol generation channel 2, and can prevent the test liquid entering the liquid containment space 3 from the main flow channel 1 from flowing into the aerosol generation channel 2. The acoustic wave generator 4 can output surface acoustic waves to the test liquid entering the liquid containment space 3 to drive the test liquid entering the liquid containment space 3 to generate the test aerosol in the aerosol generation channel 2. For example, the orifice 13 of the liquid containment space 3 prevents the test liquid in the liquid containment space 3 from flowing directly into the aerosol generation channel 2. The surface acoustic waves output by the acoustic wave generator 4 can cause the test liquid in the liquid containment space 3 to flow out of the orifice 13. 3 flows out to form a liquid film 14, which is then atomized in the aerosol generation channel 2 to form the aerosol to be tested. In this way, the main channel 1 allows various types of test liquids to flow rapidly to flush the connection between the main channel 1 and the liquid containment space 3, making it easier for the test liquid to enter the liquid containment space 3 and thus avoiding blockage. Meanwhile, the surface acoustic wave can drive the test liquid in the liquid containment space 3 to generate the test aerosol in the aerosol generation channel 2, thereby effectively avoiding blockage while improving the tolerance to various test liquids and ensuring analytical sensitivity. In addition, this mass spectrometry ion generation device does not destroy the fragile non-covalent bonds of protein-protein or protein-ligand, which is particularly advantageous for their detection.

[0060] Additionally, in some implementations, see Figure 4 The mass spectrometry ion generation device includes a bypass channel 5 with a waste liquid outlet. The bypass channel 5 is equipped with a one-way structure 6, which opens when a set condition is met to connect the waste liquid outlet and the main channel 1. Thus, when the flow rate or pressure of the analyte entering the main channel 1 is too high and reaches the predetermined condition of the one-way structure 6 (including but not limited to opening pressure or opening flow rate), the one-way structure 6 will open to connect the waste liquid outlet and the main channel 1, thereby draining the analyte from the waste liquid outlet and limiting the establishment of destructive high pressure, thus preventing damage to the internal structure of the mass spectrometry ion generation device. Alternatively, in some embodiments, the mass spectrometry ion generation device may not have a bypass channel 5.

[0061] Furthermore, the one-way structure 6 can be of various types. Regardless of the type, it is sufficient to close the bypass channel 5 at normal flow rates and open it when predetermined conditions are met. For example, in some types, the one-way structure 6 can be a one-way valve. In other types, the one-way structure 6 can be an orifice with a set size. In this case, at a normally matched flow rate, the surface tension of the fluid closes the orifice. If a large volume of liquid exceeding the range is accidentally introduced, the increased pressure will immediately force open the orifice, diverting the destructive water flow directly to the waste port for discharge. In other types, the one-way structure 6 can be a diaphragm flap. In this case, if the operator accidentally introduces a high flow rate (e.g., including but not limited to 1.5 mL / min) of the test liquid, the increased pressure in the main flow channel will drive the diaphragm flap to open, diverting the overloaded test liquid flow to be discharged from the waste port. When the flow rate returns to normal, the diaphragm flap can close again.

[0062] In some embodiments, the mass spectrometry ion generation device includes a detachable module, which at least includes a main flow channel 1, an aerosol generation flow channel 2, and a liquid containment structure. For example, the detachable module may include the main flow channel 1, the aerosol generation flow channel 2, the liquid containment structure, and an acoustic wave generator 4. As another example, the detachable module may include the main flow channel 1, the aerosol generation flow channel 2, the liquid containment structure, the acoustic wave generator 4, and a bypass flow channel 5. In this way, the detachable module can be used as a disposable consumable, thereby improving the adaptability and safety of the detection. The detachable module can be replaced independently, is plug-and-play, and can adapt to different flow rate ranges (including but not limited to nanoflow, microflow, and analytical flow). Of course, in other embodiments, the mass spectrometry ion generation device may not include a detachable module, which requires effective disinfection and cleaning to avoid contamination.

[0063] Furthermore, in some embodiments of this mass spectrometry ion generation device, see [link to documentation]. Figure 2 The mass spectrometry ion generation device also includes an electrode 7 and a bias power supply 8, wherein the bias power supply is configured to output a dynamically controllable micropotential to inject charge, enabling the electrode 7 to conduct charge to the aerosol particles of the aerosol to be measured, thereby ionizing them. In some embodiments, the electrode 7 may be positioned at the outlet of the aerosol generation channel 2. In some embodiments, the absolute value of the micropotential is limited to an operating range of 10 V to 300 V. In some embodiments, the electrode 7 and the bias power supply 8 may form a contact charging device.

[0064] In addition, the electrode 7 can be of various types. Regardless of the type of electrode 7, as long as it can conduct charge to the aerosol particles of the aerosol to be tested to ionize them, for example, the electrode 7 includes, but is not limited to, conductive thin film electrodes, needle electrodes, etc., while the bias power supply 8 provides a steady-state DC bias voltage or a transient pulse bias voltage controlled by the feedback loop.

[0065] For example, in some embodiments, the bias power supply is configured to output a micropotential to inject charge, which is dynamically controlled to ensure that the local electric field strength at the outlet location of the aerosol generation channel 2 (e.g., the slit described below) is not only always below the threshold for Townsend avalanche gas ionization, but also below the critical recombination breakdown electric field sufficient to induce surface Fowler-Nordheim field emission, in order to achieve soft ionization physical charge conduction of aerosol particles (including but not limited to biomacromolecules) without carbonization.

[0066] Furthermore, the liquid-containing space 3 of the mass spectrometry ion generation device can be provided in various ways, as long as the above-mentioned functions are achieved. For example, in some embodiments, see... Figure 2 The liquid containment space 3 includes a slit 9, wherein the surface acoustic wave generated by the acoustic wave generator enables the laminar flow at least near the acoustic wave generator in the slit 9 to overcome the surface tension under the high-speed shear stress of the local parallel acoustic flow and continuously peel off laterally towards the aerosol generation channel 2, so as to atomize into the aerosol to be tested in the aerosol generation channel 2. In some embodiments, the vertical height h of the slit 9 is configured to simultaneously satisfy the dynamic hydrodynamic boundary: (1) greater than the viscous boundary layer thickness of the Schlichting stream excited in the working fluid at the current specific angular frequency by the acoustic wave generator; (2) less than the Yang-Laplace capillary critical breakdown height corresponding to the macroscopic hydrostatic pressure in the main channel 1; when the acoustic wave generator 4 is not excited, the continuous fluid in the main channel 1 is maintained at the dynamic fluid interface balance at the slit (e.g., a slit) by the capillary pinning resistance of the gas-liquid-solid phase contact interface; when the acoustic wave generator 4 is in the excited state, the surface acoustic wave energy it generates is injected into the fluid in the slit at the Rayleigh angle, and the bottom fluid closely attached to the piezoelectric substrate is overcome by the high-speed shear stress of the local parallel acoustic flow and continuously peeled away laterally to the outside, and is purely mechanically atomized into aerosol outside the main fluid channel (i.e., inside the aerosol generation channel 2).

[0067] Furthermore, in some embodiments, the mass spectrometry ion generation device can be configured to be suitable for kinematic viscosities between 0.8 × 10⁻⁶. -6 Up to 15.0×10 -6 m 2The working fluid is an aqueous chromatographic mobile phase or a non-polar organic solvent extract, with a speed between 1 / s. In some embodiments, the operating frequency of the acoustic wave generator is fixed in the range of 10 MHz to 50 MHz, and correspondingly matched, the fixed vertical height h of the slit is between 5 μm and 50 μm, but it should be understood that the fixed vertical height h of the slit is not limited to this. In some embodiments, the slit is a planar physical gap without vertical perforations.

[0068] Furthermore, the gap 9 can be formed in various ways; whatever method is used, as long as the gap 9 satisfies the aforementioned functions, it is acceptable. For example, in some embodiments, see... Figure 3 The liquid containment structure includes a cover plate 10, a piezoelectric substrate 11 of the acoustic wave generator, and a support 12 disposed between the piezoelectric substrate 11 and the cover plate 10, wherein the support 12 forms a gap 9 between the piezoelectric substrate 11 and the cover plate 10. In this case, the piezoelectric substrate 11 of the acoustic wave generator is fully utilized to form the gap 9, thereby making the structure of the mass spectrometry ion generation device more compact.

[0069] In addition, see Figure 5 The mass spectrometry ion generation device also includes a temperature control module 15, which is thermally coupled to the acoustic wave generator to absorb and export the heat generated by the acoustic wave generator during operation to maintain thermodynamic balance, thereby eliminating the local thermal drift phenomenon of the piezoelectric substrate of the acoustic wave generator, stabilizing the acoustic wave resonant frequency, and preventing thermal degradation of heat-sensitive biomacromolecule samples in the aerosol generation channel 2 (e.g., slit).

[0070] Furthermore, the temperature control module 15 can be of various types; whatever type is used, as long as it can achieve the above-mentioned functions, it is acceptable. For example, in some embodiments, see... Figure 5 The temperature control module includes a temperature sensor 16 and a thermoelectric cooler 17. The thermoelectric cooler 17 is thermally coupled to the acoustic wave generator 4. The temperature sensor monitors the real-time temperature of the acoustic wave generator and feeds back the monitored real-time temperature to an external controller 18. The external controller 18 controls the power supply to the power supply terminal of the thermoelectric cooler 17, enabling the thermoelectric cooler 17 to absorb and dissipate the heat generated by the acoustic wave generator 4 during operation, thereby dynamically controlling the operating temperature of the acoustic wave generator 4. In some embodiments, a layer of thermally conductive silicone grease or thermal interface material is disposed between the thermoelectric cooler 17 and the acoustic wave generator 4 to improve heat transfer efficiency. In some embodiments, the temperature sensor 16 may be disposed on the bottom surface of the piezoelectric substrate of the acoustic wave generator 4 or at the cold end of the thermoelectric cooler 17. In some embodiments, the thermoelectric cooler 17 may include multiple alternating arrays of P-type and N-type semiconductor pillars.

[0071] In a second aspect, this disclosure provides a mass spectrometry ion delivery device 19 configured for use in conjunction with any of the mass spectrometry ion generation devices 20 described in the first aspect above, wherein, see [link to relevant documentation]. Figure 6 The mass spectrometer ion delivery device includes a delivery channel 22, an annular accelerating gas channel 23, and an annular nozzle gas channel 24 arranged around the same central axis 21. The delivery channel 22 is configured to receive and output the aerosol to be tested. The annular accelerating gas channel 23 is configured to provide an annular accelerating gas curtain around the aerosol to be tested output from the delivery channel 22 to accelerate the aerosol to be tested into an ion stream. The annular nozzle gas channel 24 is configured to provide an annular nozzle gas curtain around the ion stream to serve as a gas phase tube wall transport channel for the ion stream to suspend and travel.

[0072] In this mass spectrometry ion delivery device, the delivery channel receives and outputs the aerosol to be tested generated by any of the mass spectrometry ion generation devices described in the first aspect. An annular accelerating gas channel provides an annular accelerating gas curtain surrounding the output aerosol to be tested. This annular accelerating gas curtain accelerates the aerosol to be tested into an ion stream, thereby rapidly carrying the aerosol to be tested downstream and effectively physically isolating downstream heat, preventing downstream heat from heating the transducer of the acoustic wave generator of any of the mass spectrometry ion generation devices described in the first aspect. Subsequently, an annular nozzle gas channel provides an annular nozzle gas curtain surrounding the ion stream. This annular nozzle gas curtain, as a gas phase tube wall transport channel for the ion stream to suspend and travel, can effectively encapsulate and trap the ion stream to counteract lateral diffusion momentum at the vector level, stably and reliably delivering the ion stream downstream. Furthermore, this mass spectrometry ion delivery device does not disrupt the fragile non-covalent bonds between proteins or protein-ligands, thus being particularly advantageous for their detection.

[0073] In some embodiments of this mass spectrometry ion delivery device, the annular accelerating gas channel 23 provides an annular accelerating gas curtain at the outlet of the delivery channel 22, which facilitates the acceleration of the aerosol to be measured within the delivery channel 22. Of course, in other alternative embodiments, the annular accelerating gas channel 23 and the outlet of the delivery channel 22 can maintain a set axial distance.

[0074] In some embodiments of this mass spectrometry ion delivery device, the outlet end of the annular accelerating gas channel 23 tapers towards the central axis. This allows the annular accelerating gas curtain provided by the tapered outlet end of the annular accelerating gas channel 23 to more smoothly converge with the aerosol to be measured, thereby further accelerating the aerosol. In an alternative embodiment, the outlet end of the annular accelerating gas channel 23 may be parallel to the central axis.

[0075] In some embodiments of this mass spectrometry ion delivery device, see [link to documentation]. Figure 6The inner diameter of the first upper sidewall 25 at the outlet end of the annular accelerating airway is the same as and larger than the inner diameter of the outlet end of the delivery channel, which is larger than the inner diameter of the first lower sidewall 26 at the outlet end of the annular accelerating airway, so as to form an inverted frustum-shaped airflow field at the outlet end of the annular accelerating airway. This inverted frustum-shaped airflow field can more easily draw in and accelerate the aerosol to be tested.

[0076] In some embodiments of this mass spectrometry ion delivery device, see [link to documentation]. Figure 6 The outlet ends of the annular nozzle gas passage and the annular acceleration gas passage maintain an axial distance of 27 in the direction of the central axis. This allows the accelerated ion stream to travel smoothly along the axial distance 27 for a certain distance, resulting in a more stable flow. Of course, the axial distance 27 can have any suitable value, and this disclosure does not specifically limit it. In an alternative embodiment, this axial distance is not provided between the outlet ends of the annular nozzle gas passage and the annular acceleration gas passage; for example, the second upper sidewall 28 of the outlet end of the annular nozzle gas passage may contact the first lower sidewall 26 of the outlet end of the annular acceleration gas passage.

[0077] Furthermore, in some embodiments of this mass spectrometry ion delivery device, see [link to documentation]. Figure 6 The outlet end of the annular nozzle passage 24 tapers towards the central axis. This allows the annular nozzle air curtain provided by the tapered outlet end of the annular nozzle passage 24 to more smoothly converge with the accelerated ion flow, thereby further accelerating the ion flow and correcting its trajectory, thus accelerating desolvation. In an alternative embodiment, the outlet end of the annular nozzle passage 24 may be parallel to the central axis.

[0078] In some embodiments of this mass spectrometry ion delivery device, see [link to documentation]. Figure 6 The inner diameter of the second upper sidewall 28 at the outlet end of the annular nozzle air passage is larger than the inner diameter of the second lower sidewall 29 at the outlet end of the annular nozzle air passage, so as to form an inverted frustum-shaped airflow field at the outlet end of the annular nozzle air passage. This inverted frustum-shaped airflow field can more easily draw in ion flow, accelerate ion flow, and correct the trajectory of ion flow.

[0079] Furthermore, in some embodiments of this mass spectrometry ion delivery device, see [link to documentation]. Figure 6 The annular acceleration air passage provides, but is not limited to, room temperature inert gas as an annular acceleration air curtain; the annular nozzle air passage provides, but is not limited to, hot inert gas as an annular nozzle air curtain.

[0080] Furthermore, in some embodiments of this mass spectrometry ion delivery device, see [link to documentation]. Figure 6The annular nozzle passage 24 is arranged around the annular acceleration passage 23, and the annular acceleration passage 23 is arranged around the delivery channel 22. This makes full use of the radial dimension, resulting in a more compact structure for the mass spectrometry ion delivery device. In an alternative embodiment, the delivery channel 22, the annular acceleration passage 23, and the annular nozzle passage 24 can be arranged along the axial direction.

[0081] Furthermore, in some embodiments of this mass spectrometry ion delivery device, see [link to documentation]. Figure 1 The mass spectrometry ion delivery device includes a delivery conduit 30 with a delivery channel, a first tube 31 and a second tube 32 disposed inside and outside to form an annular accelerating gas passage 23 between them, and a third tube 33 and a fourth tube 34 disposed inside and outside to form an annular nozzle gas passage 24 between them, wherein the first tube 31 is disposed on the delivery conduit 30 and the third tube 33 is disposed on the second tube 32. In alternative embodiments, the delivery channel 22, the annular accelerating gas passage 23 and the annular nozzle gas passage 24 can be provided by other structures, including but not limited to a single injection-molded component.

[0082] Thirdly, see Figure 6 This disclosure provides a mass spectrometry ion control system, which includes any of the mass spectrometry ion generation devices described in the first aspect above.

[0083] In some embodiments of the mass spectrometry ion control system, the mass spectrometry ion control system further includes any of the mass spectrometry ion transport devices described in the second aspect above, wherein the aerosol to be tested generated by the mass spectrometry ion generating device can enter the transport channel, the annular accelerating gas curtain provided by the annular accelerating gas channel can accelerate the aerosol to be tested into an ion stream, and the annular nozzle gas curtain provided by the annular nozzle gas channel transports the ion stream downstream of the mass spectrometry ion control system.

[0084] In some embodiments of the mass spectrometry ion control system, the system further includes a piezoelectric pulse jet device 35 configured to jet a required volume of reagent into the ion stream delivered to the annular nozzle gas curtain. The piezoelectric pulse jet device 35 can be positioned in any suitable location, as long as it can jet the required volume of reagent into the ion stream delivered to the annular nozzle gas curtain. For example, see... Figure 6 The annular nozzle passage 24 extends axially to form an extension tube, or the outlet end of the annular nozzle passage 24 is connected to an extension tube. The piezoelectric pulse jet device 35 can be arranged laterally on the tube wall of the extension tube to jet the required volume of reagent into the ion flow inside the extension tube.

[0085] In some embodiments of the mass spectrometry ion control system, the piezoelectric pulse jet device is configured to receive the scan cycle trigger signal from the downstream mass spectrometer and jet the required volume of reagent into the ion stream delivered to the annular nozzle gas curtain only during the ion accumulation window of the mass spectrometer. This achieves a hard decoupling of the piezoelectric pulse jet device from the electronic control system of the mass spectrometer in the time dimension. Instead of continuously pumping reagent, it monitors the scan timing of the downstream mass spectrometer (e.g., ion trap), and only when the mass spectrometer is within the millisecond-level "ion accumulation window" does the piezoelectric pulse jet device precisely jet the required volume of reagent into the ion stream, such as, but not limited to, photoionization / chemical ionization aid microdroplets. This "on-demand titration" drastically reduces chemical reagent consumption to less than 5% of that of traditional continuous addition methods, and while enhancing the signal intensity of the targeted molecule, it achieves extreme suppression of background cluster ion interference. Therefore, it completely solves the problems of high background noise and high consumption pollution caused by the introduction of traditional continuous dopants. In some embodiments, the required volume includes, but is not limited to, nanoliters to picoliters.

[0086] In addition, see Figure 6 In some embodiments, the mass spectrometry ion control system further includes a microplasma reactor 36. The microplasma reactor 36 has a reaction chamber 37 containing a ring electrode 38, a gas injection port 39, and a grid 40 located at the outlet end of the reaction chamber. The ring electrode 38 and the grid 40 are electrically connected to a controller 41. The controller controls the microplasma reactor 36 to have at least the following ionization modes: Soft ionization / electrostatic lens mode: The controller cuts off the high-frequency AC drive, so that the ring electrode acts as a pure ion optical lens without discharge. The controller applies a pure DC bias voltage to the ring electrode, which is controlled by the mass spectrometer scanning sequence, and performs dynamic lens mapping adjustment at least according to the mass-to-charge ratio of the target ion and the aerodynamic resistance to ensure that the weak bond non-covalent complex in the ion stream enters the mass spectrometer without damage. Atmospheric pressure chemical ionization mode: The controller outputs a continuous high-frequency high-voltage alternating current (including but not limited to peak-to-peak values ​​of 2kV to 8kV and frequencies of 10kHz to 100kHz) to the ring electrode to excite dielectric barrier discharge, generating high-energy electrons and metastable nitrogen molecules, inducing strong gas-phase ion-molecule collision ionization. Atmospheric pressure ultraviolet photoionization mode: A set amount of high-purity argon or helium is injected through the gas injection port, and the controller applies an ultra-short pulse high voltage (including but not limited to peak value of 3kV to 10kV, rise time and pulse width <100ns) to the ring electrode to generate transient excimers and release high-intensity ultraviolet photons to perform efficient single-photon ionization.

[0087] In addition, see Figure 3In some implementations, to address signal attenuation during plasma operation, in atmospheric pressure chemical ionization mode or atmospheric pressure ultraviolet photoionization mode, the controller synchronously applies a DC bias (e.g., including but not limited to ±200V to ±1000V) to the grid to forcibly remove high-mobility electrons as they are blown out by the gas flow. This not only fundamentally prevents discharge "choking" caused by charge accumulation on the insulating surface, but also eliminates the fatal re-neutralization recombination reaction between escaped electrons and analyte free radical cations, greatly improving the absolute abundance of the mass spectrometry signal in hard ionization mode.

[0088] Fourthly, this disclosure provides a method for preparing a mass spectrometry ion generation device, wherein the method includes: providing a main channel for receiving a liquid to be tested; providing an aerosol generation channel for generating an aerosol to be tested; providing a liquid limiting structure including a liquid containing space, such that the liquid containing space can connect the main channel and the aerosol generation channel, and can prevent the liquid to be tested entering from the main channel into the liquid containing space from flowing into the aerosol generation channel; and providing an acoustic wave generating device, such that the acoustic wave generating device can output surface acoustic waves to the liquid to be tested entering the liquid containing space, so as to drive the liquid to be tested entering the liquid containing space to generate an aerosol to be tested in the aerosol generation channel.

[0089] The mass spectrometry ion generation device prepared by this method has the advantage that the liquid containment space of the liquid-limiting structure can connect the main channel and the aerosol generation channel, and can prevent the test liquid entering the liquid containment space from the main channel from flowing into the aerosol generation channel. The acoustic wave generator can output surface acoustic waves to the test liquid entering the liquid containment space to drive the test liquid entering the liquid containment space to generate the test aerosol in the aerosol generation channel. In this way, the main channel allows various types of test liquids to flow rapidly to flush the connection between the main channel and the liquid containment space, making it easier for the test liquid to enter the liquid containment space and avoiding blockage. The surface acoustic waves can drive the test liquid in the liquid containment space to generate the test aerosol in the aerosol generation channel, thereby effectively avoiding blockage while improving the tolerance to various test liquids and ensuring analytical sensitivity.

[0090] In some embodiments of the method, a slit is prepared to serve as a liquid containment space.

[0091] In some implementations of the method, see ​A piezoelectric single-crystal wafer with an interdigitated transducer 111 electrode array photolithographically patterned on its surface is provided as a piezoelectric substrate; a support material is arranged on the upper surface of the piezoelectric single-crystal wafer to construct a planar intermediate support layer 121; a partial material removal and curing process is performed on the intermediate support layer to form a cured retention region 122, the cured retention region including a channel with sidewalls; a cover plate is attached to the cured retention region and covers the channel, so that the channel is formed as a gap.

[0092] For example, in one embodiment of the method, a piezoelectric single-crystal wafer with an interdigitated transducer (IDT) electrode array photolithographically patterned on its surface is provided as the underlying working substrate; a photosensitive photoresist polymer or a plasma-bonded thin film elastomer is spin-coated onto the surface of the piezoelectric single-crystal wafer to construct a planar intermediate support layer; by controlling the spin-coating speed or thin film casting process parameters, the physical film thickness of the intermediate support layer is made strictly equal to the vertical height h of the slit corresponding to the working fluid properties; using an optical mask with the mainstream channel geometric network pattern, an alignment exposure and solvent development process is performed on the intermediate support layer; the piezoelectric single-crystal wafer is exposed in the development removal area to define the atomization region corresponding to the slit, and a channel with sidewalls of a specified thickness is formed in the curing retention area; a flat upper dielectric microfluidic cover plate is covered and bonded to the curing retention area through oxygen plasma surface activation or thermo-press bonding process, so that the cover plate is naturally suspended above the laterally exposed piezoelectric single-crystal wafer, thereby defining a micro / nano slit with precise positioning function, such as an open slit, through the intermediate support layer.

[0093] Fifthly, this disclosure provides a mass spectrometry ion control method, which includes: injecting a test liquid into the main flow channel of a mass spectrometry ion generation device at a predetermined flow rate to enter the liquid containment space of the liquid limiting structure of the mass spectrometry ion generation device, and the liquid containment space preventing the test liquid entering the liquid containment space from the main flow channel from flowing into the aerosol generation channel of the mass spectrometry ion generation device; activating an acoustic wave generator to output surface acoustic waves to the test liquid entering the liquid containment space, so as to drive the test liquid entering the liquid containment space to generate a test aerosol in the aerosol generation channel.

[0094] In this mass spectrometry ion control method, the liquid containment space of the liquid-limiting structure connects the main flow channel and the aerosol generation channel, preventing the analyte liquid entering the liquid containment space from the main flow channel from flowing into the aerosol generation channel. The acoustic wave generator outputs surface acoustic waves to the analyte liquid entering the liquid containment space, driving it to generate aerosols within the aerosol generation channel. This allows various types of analyte liquids to flow rapidly through the main flow channel, flushing the connection between the main flow channel and the liquid containment space, making it easier for the analyte liquid to enter the liquid containment space and preventing blockage. The surface acoustic waves then drive the analyte liquid in the liquid containment space to generate aerosols within the aerosol generation channel. This effectively avoids blockage while improving tolerance to various analyte liquids and ensuring analytical sensitivity. Furthermore, this mass spectrometry ion control method does not disrupt the fragile non-covalent bonds between proteins or protein-ligands, making its detection particularly advantageous.

[0095] In some embodiments of this mass spectrometry ion control method, a micropotential with a set voltage is applied to the aerosol to be tested via electrodes to conduct charge on the aerosol particles of the aerosol to be tested, thereby ionizing them.

[0096] In some embodiments of this mass spectrometry ion control method, an annular accelerating gas curtain is provided around the aerosol to be tested through an annular accelerating gas channel to accelerate the aerosol to be tested into an ion stream, thereby rapidly carrying the aerosol to be tested downstream and effectively physically isolating downstream heat to prevent downstream heat from heating the transducer of the acoustic wave generator of the mass spectrometry ion generation device.

[0097] In some embodiments of this mass spectrometry ion control method, an annular nozzle gas curtain is provided around the ion stream via an annular nozzle gas channel to suspend and propagate the ion stream. This annular nozzle gas curtain, as a gas phase tube wall transport channel for the ion stream's suspension and propagation, can effectively encapsulate and trap the ion stream to counteract lateral diffusion momentum at the vector level, ensuring a stable and reliable delivery of the ion stream downstream.

[0098] In some embodiments of this mass spectrometry ion control method, the controller of the microplasma reactor is controlled according to the properties of the target compound, causing the microplasma reactor to operate in any of the following ionization modes: Soft ionization / electrostatic lens mode: The controller cuts off the high-frequency AC drive of the ring electrode, so that the ring electrode acts as a pure ion optical lens without discharge. The controller applies a pure DC bias voltage to the ring electrode, which is controlled by the mass spectrometer scanning sequence, and performs dynamic lens mapping adjustment at least according to the mass-to-charge ratio of the target ion and the aerodynamic resistance to ensure that the weak bond non-covalent complex in the ion stream enters the mass spectrometer without damage. Atmospheric pressure chemical ionization mode: The controller outputs a continuous high-frequency high-voltage alternating current to the ring electrode to excite dielectric barrier discharge, generating high-energy electrons and metastable nitrogen molecules, inducing strong gas-phase ion-molecule collision ionization. Atmospheric pressure ultraviolet photoionization mode: A set amount of high-purity argon or helium is injected, and the controller applies an ultra-short pulse high voltage to the ring electrode to generate transient excimers and release high-intensity ultraviolet photons to perform efficient single-photon ionization.

[0099] In some embodiments of this mass spectrometry ion control method, in atmospheric pressure chemical ionization mode or atmospheric pressure ultraviolet photoionization mode, the controller synchronously applies a DC bias to the grid at the outlet end of the reaction chamber of the microplasma reactor to forcibly sweep away high-mobility electrons the instant they are blown out by the gas flow. This not only fundamentally prevents discharge "choking" caused by charge accumulation on the insulating surface, but also eliminates the fatal re-neutralization recombination reaction between escaped electrons and analyte free radical cations, greatly improving the absolute abundance of the mass spectrometry signal in hard ionization mode.

[0100] In some embodiments of this mass spectrometry ion control method, the scan cycle trigger signal of the downstream mass spectrometer is acquired, and a piezoelectric pulse jet device injects the required volume of reagent into the ion stream delivered to the annular nozzle gas curtain only during the ion accumulation window of the mass spectrometer. This achieves a hard decoupling of the piezoelectric pulse jet device from the electronic control system of the mass spectrometer in the time dimension. Instead of continuously pumping reagent, it monitors the scan sequence of the downstream mass spectrometer (e.g., ion trap), and only injects the required volume of reagent, such as, but not limited to, photoionization / chemical ionization aid microdroplets, into the ion stream at a specific point during the millisecond-level instantaneous "ion accumulation window." This "on-demand titration" drastically reduces chemical reagent consumption to less than 5% of that of traditional continuous addition methods, and while enhancing the signal intensity of the targeted molecule, it achieves extreme suppression of background cluster ion interference. Therefore, it completely solves the problems of high background noise and high consumption pollution caused by the introduction of traditional continuous dopants. In some embodiments, the required volume includes, but is not limited to, nanoliters to picoliters.

[0101] While this disclosure has been described in detail with reference to some preferred embodiments, variations and modifications exist within the scope and spirit of one or more independent aspects of the described disclosure. Furthermore, those skilled in the art will understand that the above embodiments are exemplary and not restrictive. Different technical features appearing in different embodiments can be combined to achieve beneficial effects. Those skilled in the art, based on a study of the drawings, specification, and claims, should be able to understand and implement other variations of the disclosed embodiments. The appearance of certain technical features in different dependent claims does not mean that these technical features cannot be combined to achieve beneficial effects.

Claims

1. A mass spectrometry ion generation device, comprising: Main channel (1), the main channel (1) is configured to receive the liquid to be tested; Aerosol generation channel (2), the aerosol generation channel (2) is configured to generate the aerosol to be tested; A liquid limiting structure, the liquid limiting structure including a liquid containing space (3), the liquid containing space (3) being configured to connect the main channel (1) and the aerosol generating channel (2), and to prevent the test liquid entering the liquid containing space (3) from the main channel (1) from flowing into the aerosol generating channel (2); and A sound wave generating device (4) is configured to output surface acoustic waves to the liquid to be tested entering the liquid containment space (3) so as to drive the liquid to be tested entering the liquid containment space (3) to generate aerosol to be tested in the aerosol generation channel (2).

2. The mass spectrometry ion generation device according to claim 1, wherein, The mass spectrometer ion generation device includes a bypass channel (5) with a waste liquid outlet, wherein the bypass channel (5) is provided with a one-way structure (6), which opens when a set condition is met to connect the waste liquid outlet and the main channel (1).

3. The mass spectrometry ion generation device according to claim 1, wherein, The mass spectrometer ion generation device includes a detachable module, wherein the detachable module includes at least the main flow channel (1), the aerosol generation channel (2), and the liquid limiting structure.

4. The mass spectrometry ion generation device according to claim 1, wherein, The mass spectrometry ion generation device further includes an electrode (7) and a bias power supply (8), wherein the bias power supply is configured to output a dynamically controllable micropotential to inject charge, so that the electrode (7) can conduct charge to the aerosol particles of the aerosol to be tested to ionize them.

5. The mass spectrometry ion generation device according to claim 4, wherein, The electrode (7) includes a conductive thin film electrode, and the bias power supply (8) provides a steady-state DC bias voltage or a transient pulse bias voltage controlled by a feedback loop.

6. The mass spectrometry ion generation apparatus according to any one of claims 1-5, wherein, The liquid containment space (3) includes a gap (9), wherein the surface acoustic wave generated by the acoustic wave generating device enables the laminar flow at least near the acoustic wave generating device in the gap (9) to overcome the surface tension under the high-speed shear stress of the local parallel acoustic flow and to continuously peel off laterally towards the aerosol generating channel (2) so as to atomize into the aerosol to be tested in the aerosol generating channel (2).

7. The mass spectrometry ion generation apparatus according to claim 6, wherein, The liquid limiting structure includes a cover plate (10), a piezoelectric substrate (11) of the acoustic wave generating device, and a support (12) disposed between the piezoelectric substrate (11) and the cover plate (10), wherein the support (12) forms the gap (9) between the piezoelectric substrate (11) and the cover plate (10).

8. The mass spectrometry ion generation apparatus according to claim 6, wherein, The height of the gap (9) is 5μm-50μm.

9. The mass spectrometry ion generation device according to claim 1, wherein, The mass spectrometry ion generation device also includes a temperature control module (15), which is thermally coupled to the acoustic wave generator to absorb and remove the heat generated when the acoustic wave generator is working.

10. The mass spectrometry ion generation apparatus according to claim 9, wherein, The temperature control module includes a temperature sensor (16) and a semiconductor thermoelectric cooler (17), wherein the semiconductor thermoelectric cooler (17) and the sound wave generator (4) are thermally coupled. The temperature sensor monitors the real-time temperature of the sound wave generator and feeds back the monitored real-time temperature to an external controller (18). The external controller (18) controls the power supply of the semiconductor thermoelectric cooler (17) so that the semiconductor thermoelectric cooler (17) can absorb and dissipate the heat generated by the sound wave generator (4) during operation, so as to dynamically control the operating temperature of the sound wave generator (4).

11. A mass spectrometry ion delivery device, wherein, The mass spectrometer ion delivery device (19) is configured for use in conjunction with the mass spectrometer ion generation device (20) according to any one of claims 1-10, wherein the mass spectrometer ion delivery device includes a delivery channel (22), an annular accelerating gas channel (23), and an annular nozzle gas channel (24) arranged around the same central axis (21), wherein, The delivery channel (22) is configured to receive and output the aerosol to be tested; The annular accelerating air channel (23) is configured to provide an annular accelerating air curtain to accelerate the aerosol to be tested into an ion stream by the aerosol output from the delivery channel (22). The annular nozzle air passage (24) is configured to provide an annular nozzle air curtain around the ion stream as a gas phase tube wall transport channel for the ion stream to suspend and travel.

12. The mass spectrometry ion delivery device according to claim 11, wherein, The annular acceleration air passage (23) provides the annular acceleration air curtain at the outlet of the delivery channel (22).

13. The mass spectrometry ion delivery device according to claim 11, wherein, The outlet end of the annular acceleration airway (23) tapers toward the central axis.

14. The mass spectrometry ion delivery device according to claim 13, wherein, The inner diameter of the first upper sidewall (25) at the outlet end of the annular accelerating airway is the same as and larger than the inner diameter of the outlet end of the conveying channel, which is larger than the inner diameter of the first lower sidewall (26) at the outlet end of the annular accelerating airway, so as to form an inverted frustum-shaped airflow field at the outlet end of the annular accelerating airway.

15. The mass spectrometry ion delivery device according to claim 11, wherein, The outlet end of the annular nozzle air passage and the outlet end of the annular acceleration air passage are axially spaced (27) in the direction of the central axis.

16. The mass spectrometry ion delivery device according to claim 11, wherein, The outlet end of the annular nozzle air passage (24) gradually tapers toward the central axis.

17. The mass spectrometry ion delivery device according to claim 16, wherein, The inner diameter of the second upper sidewall (28) at the outlet end of the annular nozzle air passage is larger than the inner diameter of the second lower sidewall (29) at the outlet end of the annular nozzle air passage, so as to form an inverted frustum-shaped airflow field at the outlet end of the annular nozzle air passage.

18. The mass spectrometry ion delivery device according to claim 11, wherein, The annular acceleration air passage provides room temperature inert gas as the annular acceleration air curtain; the annular nozzle air passage provides thermal inert gas as the annular nozzle air curtain.

19. The mass spectrometry ion delivery device according to any one of claims 11-18, wherein, The annular nozzle air passage (24) is arranged around the annular acceleration air passage (23), and the annular acceleration air passage (23) is arranged around the delivery channel (22).

20. The mass spectrometry ion delivery device according to claim 19, wherein, The mass spectrometer ion delivery device includes a delivery pipe (30) having the delivery channel, a first pipe (31) and a second pipe (32) disposed inside and outside to form the annular acceleration airway (23) between them, and a third pipe (33) and a fourth pipe (34) disposed inside and outside to form the annular nozzle airway (24) between them, wherein the first pipe (31) is disposed on the delivery pipe (30) and the third pipe (33) is disposed on the second pipe (32).

21. A mass spectrometry ion control system, comprising the mass spectrometry ion generation device according to any one of claims 1-10.

22. The mass spectrometry ion control system according to claim 21, wherein, The mass spectrometry ion control system further includes a mass spectrometry ion delivery device according to any one of claims 11-20, wherein the aerosol to be tested generated by the mass spectrometry ion generation device can enter the delivery channel, the annular accelerating gas curtain provided by the annular accelerating gas channel can accelerate the aerosol to be tested into an ion stream, and the annular nozzle gas curtain provided by the annular nozzle gas channel delivers the ion stream downstream of the mass spectrometry ion control system.

23. The mass spectrometry ion control system according to claim 22, wherein, The mass spectrometry ion control system further includes a piezoelectric pulse jet device (35) configured to jet the required volume of reagent into the ion stream delivered to the annular nozzle gas curtain.

24. The mass spectrometry ion control system according to claim 23, wherein, The piezoelectric pulse jet device is configured to receive a scan cycle trigger signal from a downstream mass spectrometer and jet the required volume of reagent into the annular nozzle gas curtain only during the ion accumulation window of the mass spectrometer.

25. The mass spectrometry ion control system according to claim 24, wherein, The required volume is from nanoliter to picoliter.

26. The mass spectrometry ion control system according to claim 22, wherein, The mass spectrometry ion control system further includes a microplasma reactor (36), wherein a ring electrode (38), a gas injection port (39), and a grid (40) are disposed in the reaction chamber (37) of the microplasma reactor (36). The ring electrode (38) and the grid (40) are electrically connected to a controller (41), wherein the controller controls the microplasma reactor (36) to have at least the following ionization modes: Soft ionization / electrostatic lens mode: The controller cuts off the high-frequency AC drive, so that the ring electrode acts as a pure ion optical lens without discharge. The controller applies a pure DC bias voltage controlled by the mass spectrometer scanning sequence to the ring electrode, and performs dynamic lens mapping adjustment at least according to the mass-to-charge ratio and aerodynamic resistance of the target ion being scanned, so as to ensure that the weak bond non-covalent complex in the ion stream enters the mass spectrometer without damage. Atmospheric pressure chemical ionization mode: The controller outputs a continuous high-frequency high-voltage alternating current to the annular electrode to excite dielectric barrier discharge, generating high-energy electrons and metastable nitrogen molecules, inducing strong gas-phase ion-molecule collision ionization. Atmospheric pressure ultraviolet photoionization mode: A set amount of high-purity argon or helium is injected through the gas injection port, and the controller applies an ultra-short pulse high voltage to the annular electrode to generate transient excimers and release high-intensity ultraviolet photons to perform efficient single-photon ionization.

27. The mass spectrometry ion control system according to claim 26, wherein, In the atmospheric pressure chemical ionization mode or the atmospheric pressure ultraviolet photoionization mode, the controller synchronously applies a DC bias to the grid.

28. A method for preparing a mass spectrometry ion generation device, wherein, The method includes: Provides a main channel for receiving the liquid to be tested; Provides an aerosol generation channel for generating the aerosol to be tested; A liquid limiting structure is provided, including a liquid containing space, such that the liquid containing space can connect the main flow channel and the aerosol generating flow channel, and can prevent the test liquid entering the liquid containing space from the main flow channel from flowing into the aerosol generating flow channel; A sound wave generating device is provided, which is capable of outputting surface acoustic waves to the liquid to be tested entering the liquid containment space, so as to drive the liquid to be tested entering the liquid containment space to generate aerosol to be tested in the aerosol generation channel.

29. The method according to claim 28, wherein, A slit is prepared to serve as a space for containing the liquid.

30. The method according to claim 29, wherein, A piezoelectric single-crystal wafer with an interdigital transducer electrode array photolithographically patterned on its surface is provided as a piezoelectric substrate; A support material is arranged on the upper surface of the piezoelectric single crystal wafer to construct a planar intermediate support layer; A partial material removal and curing process is performed on the intermediate support layer to form a cured retention area, the cured retention area including channels with sidewalls; The cover plate is attached to the cured retention area and covers the channel, so that the channel forms the gap.

31. A mass spectrometry ion control method, comprising: The test liquid is injected into the main channel of the mass spectrometer ion generator at a predetermined flow rate to enter the liquid containment space of the liquid limiting structure of the mass spectrometer ion generator, and the liquid containment space prevents the test liquid entering the liquid containment space from the main channel from flowing into the aerosol generation channel of the mass spectrometer ion generator. The acoustic wave generator is activated to output surface acoustic waves to the liquid to be tested that enters the liquid containment space, thereby driving the liquid to be tested to generate aerosol in the aerosol generation channel.

32. The mass spectrometry ion control method according to claim 31, wherein, A micropotential with a set voltage is applied to the aerosol under test through electrodes to conduct charge to the aerosol particles of the aerosol under test so as to ionize them.

33. The mass spectrometry ion control method according to claim 31, wherein, An annular accelerating gas curtain is provided around the aerosol to be tested through an annular accelerating gas channel to accelerate the aerosol to be tested into an ion stream.

34. The mass spectrometry ion control method according to claim 33, wherein, An annular nozzle air curtain is provided around the ion stream through an annular nozzle air passage to suspend and propel the ion stream.

35. The mass spectrometry ion control method according to claim 34, wherein, The controller of the microplasma reactor is controlled according to the properties of the target compound, enabling the microplasma reactor to operate in any of the following ionization modes: Soft ionization / electrostatic lens mode: The controller cuts off the high-frequency AC drive of the ring electrode, so that the ring electrode acts as a pure ion optical lens without discharge. The controller applies a pure DC bias voltage controlled by the mass spectrometer scanning sequence to the ring electrode, and performs dynamic lens mapping adjustment at least according to the mass-to-charge ratio and aerodynamic resistance of the target ion being scanned, so as to ensure that the weak bond non-covalent complex in the ion stream enters the mass spectrometer without damage. Atmospheric pressure chemical ionization mode: The controller outputs a continuous high-frequency high-voltage alternating current to the annular electrode to excite dielectric barrier discharge, generating high-energy electrons and metastable nitrogen molecules, inducing strong gas-phase ion-molecule collision ionization. Atmospheric pressure ultraviolet photoionization mode: A set amount of high-purity argon or helium is injected, and the controller applies an ultra-short pulse high voltage to the annular electrode to generate transient excimers and release high-intensity ultraviolet photons to perform efficient single-photon ionization.

36. The mass spectrometry ion control method according to claim 35, wherein, In the atmospheric pressure chemical ionization mode or the atmospheric pressure ultraviolet photoionization mode, the controller synchronously applies a DC bias to the grid at the outlet end of the reaction chamber of the microplasma reactor.

37. The mass spectrometry ion control method according to claim 34, wherein, The downstream mass spectrometer's scan cycle trigger signal is obtained, and the required volume of reagent is injected into the annular nozzle gas curtain via a piezoelectric pulse jet device only during the mass spectrometer's ion accumulation window.

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