An array pulse induced electrospray ionization source

Abstract

The present invention relates to the technical field of mass spectrometers, and in particular to an array pulse induced electrospray ionization source. It includes a microinjection pump, a vacuum ionization source cavity, a spray capillary array group, a sensing electrode, a pulse power supply, a radio frequency ion transmission system and an ion outlet electrode, wherein the vacuum ionization source cavity is provided with a spray capillary array group, a radio frequency ion transmission system and an ion outlet electrode from left to right, the sensing electrode is arranged at the bottom of the spray capillary array group and connected to the pulse power supply, the spray capillary array group is connected to the microinjection pump, and the ion outlet electrode is connected to a mass spectrometer; the microinjection pump injects a sample into the spray capillary array group, the sample forms spray droplets under a pulse voltage and ionizes to generate ions, and the radio frequency ion transmission system focuses and transmits the ions, so that the ions pass through the ion outlet electrode and enter the mass spectrometer. The present invention improves the detection sample flux, and realizes the improvement of the ionization efficiency and single detection sensitivity of ESI.

Description

Technical Field

[0001] The invention relates to the technical field of mass spectrometers, and in particular to an array pulse induced electrospray ionization source. Background Art

[0002] Ionization is the primary link of mass spectrometry. The most commonly used ion source for commercial mass spectrometers is the electrospray ionization source (ESI), which has been widely used in the fields of biology, pharmaceuticals, environmental analysis, etc. However, the traditional ESI source has problems such as large droplets and poor ionization efficiency. Nanoliter electrospray ionization (nESI) technology can effectively improve the ionization efficiency of ESI, but its flow rate is too low, which affects the analysis throughput. Pulse induction / induction nanoliter electrospray ionization source (InESI) places a planar electrode outside the spray capillary and applies alternating current to the electrode, thereby generating an induced electric field inside the capillary, and finally achieving spraying and ionization. Its structure is simple and it is easy to realize the array of nESI, which is conducive to high-throughput experiments. Although these technical improvements have achieved a certain improvement in the ionization efficiency of ESI, there are still many problems: such as insufficient sample volume for single analysis, resulting in limited sensitivity. In addition, most of the ions generated by InESI under normal pressure are lost, and the utilization rate is too low, which further reduces the detection sensitivity of the entire system. Therefore, it is conceivable whether the array InESI can be combined with efficient RF transmission under vacuum to simultaneously improve the InESI ionization efficiency, single sample amount and transmission efficiency, which can theoretically greatly improve the detection sensitivity of the system.

[0003] Through the search of patents and papers, the relevant patents related to array and electrospray ionization are retrieved as follows: 1. Guangzhou Huayuexing Instrument Co., Ltd. applied for and disclosed an injection device and mass spectrometry analysis system based on inductive electrospray on July 19, 2019, including: at least two spray needles, the spray needle includes a capillary, an electrode and a distance adjustment member, and the distance adjustment member adjusts the distance between the electrode and the capillary; the spray needle is driven by the driving unit to translate; the power supply electrode is suitable for connecting to an external power supply, and is driven by the second driving unit to translate in a direction parallel to the extension direction of the spray needle, so that the power supply electrode contacts and separates from the electrode in the spray needle. The array design of this invention can improve the detection flux. 2. Zhang Xinrong of Tsinghua University applied for and disclosed a non-contact DC inductive electrospray ionization device and ionization method on May 12, 2014. It includes an electrode, a high-voltage DC power supply and an nESI nozzle. The axis of the nESI nozzle and the long straight wire electrode are in the same straight line, and the nozzle is located between the electrode and the mass spectrometry injection port. The electric field lines generated by the electrode tip under high voltage excitation converge after passing through the conical liquid dielectric, greatly amplifying the electric field strength at the tip of the nozzle, causing electrospray ionization of the liquid to be tested. This invention solves the problem that nESI cannot directly ionize several nanoliter-level samples, and can also be used for nESI array analysis. However, these two patents cannot improve the amount of samples detected in a single test and the utilization rate of ions after ionization, and the sensitivity is still limited. Summary of the invention

[0004] In view of the above problems, the object of the present invention is to provide an array pulse induced electrospray ionization source to improve the detection sensitivity of electrospray ionization mass spectrometry.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions:

[0006] The invention provides an array pulse induced electrospray ionization source, comprising a micro-injection pump, an injection pipeline, a vacuum ionization source cavity, a spray capillary array group, an induction electrode, a pulse power supply, a radio frequency ion transmission system and an ion outlet electrode, wherein the vacuum ionization source cavity is provided with the spray capillary array group, the radio frequency ion transmission system and the ion outlet electrode in sequence from left to right, the induction electrode is arranged at the bottom of the spray capillary array group and is connected to the pulse power supply through a wire, the spray capillary array group is connected to the micro-injection pump through the injection pipeline, and the ion outlet electrode is connected to a mass spectrometer; the micro-injection pump injects a sample into the spray capillary array group through the injection pipeline, the pulse power supply applies a pulse voltage to the induction electrode, the sample in the spray capillary array group forms spray droplets under the pulse voltage and is ionized to generate ions, the radio frequency ion transmission system performs focused transmission on the ions under vacuum, and the ions pass through the ion outlet electrode and enter the mass spectrometer.

[0007] The spray capillary array group is composed of two or more capillaries arranged in parallel. The left end of the spray capillary array group is sealed and fixed by a sealing sleeve. The left end of the sealing sleeve is provided with an inlet connected to the injection pipeline. The sample in the micro-injection pump is injected into the sealing sleeve through the injection pipeline and transmitted to the spray capillary array group.

[0008] The spray capillary array group is composed of quartz capillaries, and the inner diameter of the quartz capillaries is 5 to 530 um.

[0009] The radio frequency ion transmission system comprises more than three electrode sheets which are arranged in parallel and at intervals, and the electrode sheets are flat plate structures with circular through holes in the middle.

[0010] The radio frequency ion transmission system adopts an ion funnel structure. The diameter of the circular through hole of the electrode sheet in the radio frequency ion transmission system is 2 to 100 mm, and the diameter of the circular through hole decreases from left to right.

[0011] Adjacent electrode sheets in the RF ion transmission system are applied with RF voltages of opposite phases and the same amplitude, the RF voltage amplitude ranges from 10 to 1000 V, and the RF frequency ranges from 0.5 to 3 MHz; adjacent electrode sheets in the RF ion transmission system are connected via equal-value resistors, and a DC voltage is applied to the first and last electrode sheets of the RF ion transmission system, thereby forming an ion transmission electric field of 1 to 50 V / cm in the axial direction of the RF ion transmission system.

[0012] The radio frequency ion transmission system is a combined radio frequency multipole structure.

[0013] The radio frequency ion transmission system is a combined segmented radio frequency multipole structure.

[0014] The ion outlet electrode is a flat plate structure with a truncated cone-shaped through hole in the middle, and the diameter of the through hole is 0.1-2 mm.

[0015] The flow rate of the microinjection pump is 0.01-10 μL / min;

[0016] The pulse voltage frequency output by the pulse power supply is 10-2000 Hz, and the amplitude is 2000-4000 V; the vacuum ionization source cavity is connected to a vacuum pump, and the internal air pressure is controlled to be 100-10000 Pa.

[0017] The advantages and beneficial effects of the present invention are as follows: the present invention provides an array pulse induced electrospray ionization source, which improves the detection sample throughput through an array capillary group, improves the ESI desolvation efficiency under a negative pressure environment, and cleverly combines the pulse induced electrode application method and the high-efficiency radio frequency ion transmission system under vacuum, ultimately achieving the improvement of ESI ionization efficiency and single detection sensitivity. The present invention can effectively improve the detection sensitivity of the electrospray source in a mass spectrometer, and has broad application prospects in the fields of biology, pharmaceuticals, environmental analysis, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The accompanying drawings further illustrate the present invention, but the contents in the accompanying drawings do not constitute any limitation to the present invention.

[0019] Figure 1 Schematic diagram of the structure of an array pulse induced electrospray ionization source in Example 1 of the present invention;

[0020] Figure 2 It is a schematic diagram of the structure of an array pulse induced electrospray ionization source in the second embodiment of the present invention;

[0021] Figure 3 It is a schematic diagram of the structure of an array pulse induced electrospray ionization source in Embodiment 3 of the present invention;

[0022] In the figure: 1 is a microinjection pump, 2 is a sample injection pipeline, 3 is a sealing sleeve, 4 is a vacuum ionization source cavity, 5 is a pulse power supply, 6 is ions, 7 is an ion outlet electrode, 8 is a radio frequency ion transmission system, 9 is a sensing electrode, and 10 is a spray capillary array group. DETAILED DESCRIPTION

[0023] It should be noted that, in the absence of conflict, the embodiments of the present invention and the features in the embodiments can be combined with each other. The present invention will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0024] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is by no means intended to limit the present invention and its application or use. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0025] In the description of the present invention, it is necessary to understand that the directions or positional relationships indicated by directional words such as "front, back, up, down, left, right", "lateral, vertical, perpendicular, horizontal" and "top, bottom" are usually based on the directions or positional relationships shown in the drawings. They are only for the convenience of describing the present invention and simplifying the description. Unless otherwise specified, these directional words do not indicate or imply that the device or element referred to must have a specific direction or be constructed and operated in a specific direction. Therefore, they cannot be understood as limiting the scope of protection of the present invention: the directional words "inside and outside" refer to the inside and outside relative to the contours of each component itself.

[0026] like Figure 1 As shown, the first embodiment of the present invention provides an array pulse induced electrospray ionization source, including a microinjection pump 1, an injection pipeline 2, a vacuum ionization source cavity 4, a spray capillary array group 10, a sensing electrode 9, a pulse power supply 5, a radio frequency ion transmission system 8 and an ion outlet electrode 7, wherein the vacuum ionization source cavity 4 is provided with the spray capillary array group 10, the radio frequency ion transmission system 8 and the ion outlet electrode 7 from left to right, the sensing electrode 9 is arranged at the bottom of the spray capillary array group 10 and is connected to the pulse power supply 5 through a wire, and the spray capillary array group 10 is connected to the pulse power supply 5 through a wire. The array group 10 is connected to the microinjection pump 1 through the injection line 2, and the ion outlet electrode 7 is connected to the mass spectrometer; the microinjection pump 1 injects the sample into the spray capillary array group 10 through the injection line 2, the pulse power supply 5 applies a pulse voltage to the sensing electrode 9, the sample in the spray capillary array group 10 forms spray droplets under the pulse voltage, and is ionized to generate ions 6 under a vacuum environment, and the radio frequency ion transmission system 8 focuses and transmits the ions 6 under a vacuum environment, so that the ions 6 pass through the ion outlet electrode 7 and enter the mass spectrometer for mass spectrometry analysis.

[0027] In an embodiment of the present invention, the spray capillary array group 10 is composed of two or more capillaries arranged in parallel, the left end of the spray capillary array group 10 is sealed and fixed by a sealing sleeve 3, and an inlet connected to the injection pipeline 2 is provided at the left end of the sealing sleeve 3. The sample in the microinjection pump 1 is injected into the sealing sleeve 3 through the injection pipeline 2 and transmitted to the spray capillary array group 10.

[0028] Furthermore, the spray capillary array group 10 is composed of quartz capillaries, and the inner diameter of the quartz capillaries is 5 to 530 um.

[0029] like Figure 1 As shown, in the first embodiment of the present invention, the radio frequency ion transmission system 8 includes more than three parallel and spaced electrode sheets, and the electrode sheets are flat plate structures with circular through holes in the middle.

[0030] Specifically, the radio frequency ion transmission system 8 adopts an ion funnel structure, the diameter of the circular through hole of the electrode sheet in the radio frequency ion transmission system 8 is 2 to 100 mm, and the diameter of the circular through hole decreases from left to right.

[0031] During operation, adjacent electrode sheets in the RF ion transmission system 8 are applied with RF voltages of opposite phases and the same amplitude, the RF voltage amplitude ranges from 10 to 1000 V, and the RF frequency ranges from 0.5 to 3 MHz; adjacent electrode sheets in the RF ion transmission system 8 are connected by equal resistances, and a DC voltage is applied to the first and last electrode sheets of the RF ion transmission system 8, forming an ion transmission electric field of 1 to 50 V / cm in the axial direction of the RF ion transmission system 8.

[0032] In the first embodiment of the present invention, the ion outlet electrode 7 is a flat plate structure with a truncated cone-shaped through hole in the middle, and the through hole diameter is 0.1 to 2 mm. The through hole of the ion outlet electrode 7 is connected to a mass spectrometer on its right side, and the mass spectrometer is a time-of-flight mass spectrometer, a quadrupole mass spectrometer, a magnetic mass spectrometer, an ion trap mass spectrometer, an electrostatic trap mass spectrometer, or various types of tandem mass spectrometers.

[0033] like Figure 1 As shown, in this embodiment, rightward is X direction and upward is Y direction; vacuum ionization source cavity 4 is a hollow closed cavity structure, vacuum ionization source cavity 4 is connected to a vacuum pump, and the internal air pressure is controlled to be 100-10000 Pa. The flow rate of the microinjection pump 1 is 0.01-10 μL / min; the pulse voltage frequency output by the pulse power supply 5 is 10-2000 Hz, and the amplitude is 2000-4000 V.

[0034] In this embodiment, the sample in the microinjection pump 1 is injected into the sealing sleeve 3 through the injection line 2 and transmitted to the spray capillary array group 10. The right end of the spray capillary array group 10 enters the interior from the outside of the vacuum ionization source cavity 4 along the X direction and the outer wall surface is sealed and connected to the vacuum ionization source cavity 4; the induction electrode 9 is a rectangular flat plate structure, which is arranged below the spray capillary array group 10 of the vacuum ionization source cavity 4, and the induction electrode 9 is connected to the pulse power supply 5 outside the vacuum ionization source cavity 4 through a wire. Preferably, the flow rate of the microinjection pump 1 is 0.1μL / min, and the spray capillary array group 10 is composed of ten quartz capillaries, and the inner diameter of the quartz capillary is 20um. The radio frequency ion transmission system 8 adopts an ion funnel structure, with a radio frequency amplitude of 300V, a radio frequency frequency of 2MHz, a DC electric field of 10V / cm, and an inner diameter of the electrode plate decreasing from 30mm to 2mm. The pulse power supply 5 connected to the induction electrode 9 outputs a pulse voltage with a frequency of 50 Hz and an amplitude of 3000 V. The through hole diameter of the ion outlet electrode 7 is 1 mm; the mass spectrometer is a tandem mass spectrometer. The vacuum ionization source cavity 4 is connected to a vacuum pump to control the internal air pressure to 200 Pa, ensuring a certain injection volume while meeting the working air pressure required by the radio frequency transmission system.

[0035] During specific operation, first, the microinjection pump 1 injects the sample into the sealing sleeve 3 at a certain speed and transmits it to the spray capillary array group 10; then, the pulse power supply 5 applies a pulse voltage to the induction electrode 9 below the spray capillary array group 10, and the sample in the spray capillary array group 10 forms spray droplets under the pulse voltage; the spray droplets can be efficiently desolvated in the vacuum environment of the vacuum ionization source cavity 4, thereby obtaining a high ionization efficiency; the ions 6 generated after desolvation utilize the focusing ability of the radio frequency ion transmission system 8 under vacuum, gradually converge to the axis of the radio frequency ion transmission system 8, and efficiently pass through the ion outlet electrode 7 to enter the mass spectrometer for analysis.

[0036] like Figure 2 As shown, the second embodiment of the present invention provides an array pulse induced electrospray ionization source. The structure of this embodiment is basically the same as that of the first embodiment, except that the radio frequency ion transmission system 8 is a combined radio frequency multipole structure.

[0037] like Figure 3 As shown, the third embodiment of the present invention provides an array pulse induced electrospray ionization source, and the structure of this embodiment is basically the same as that of the first embodiment, except that the radio frequency ion transmission system 8 is a combined segmented radio frequency multipole structure. The radio frequency ion transmission system 8 can also use other radio frequency focusing technologies under vacuum.

[0038] The traditional atmospheric pressure electrospray ionization source (ESI) has a problem of low ionization efficiency due to poor solvation efficiency, and most of the ions produced under atmospheric pressure are lost, which greatly affects the detection sensitivity. The present invention discloses an array pulse induced electrospray ionization technology, which improves the detection sample flux through an array capillary group, utilizes a negative pressure environment to improve the desolvation efficiency of ESI, and cleverly combines the pulse induced electrode application method and the efficient radio frequency ion transmission system under vacuum, ultimately achieving the improvement of the ionization efficiency and single detection sensitivity of ESI. The present invention can effectively improve the detection sensitivity of the electrospray source in the mass spectrometer, and has broad application prospects in the fields of biology, pharmacy, environmental analysis, etc.

[0039] The technical principle of the present invention is described above in conjunction with specific embodiments. These descriptions are only for explaining the principle of the present invention and cannot be interpreted as limiting the scope of protection of the present invention in any way. Based on the explanations herein, those skilled in the art can associate other specific embodiments of the present invention without creative work, and these equivalent variations or substitutions are all included in the scope defined by the claims of this application.

Claims

1. An array pulse induced electrospray ionization source, characterized in that: The invention comprises a microinjection pump (1), a sample injection pipeline (2), a vacuum ionization source chamber (4), a spray capillary array group (10), a sensing electrode (9), a pulse power supply (5), a radio frequency ion transmission system (8) and an ion outlet electrode (7), wherein the vacuum ionization source chamber (4) is provided with the spray capillary array group (10), the radio frequency ion transmission system (8) and the ion outlet electrode (7) in sequence from left to right, the sensing electrode (9) is arranged at the bottom of the spray capillary array group (10) and is connected to the pulse power supply (5) via a wire, and the spray capillary array group (10) is connected to the pulse power supply (5) via a wire. 0) is connected to a microinjection pump (1) through an injection pipeline (2), and an ion outlet electrode (7) is connected to a mass spectrometer; the microinjection pump (1) injects a sample into a spray capillary array group (10) through the injection pipeline (2), a pulse power supply (5) applies a pulse voltage to a sensing electrode (9), the sample in the spray capillary array group (10) forms spray droplets under the pulse voltage and is ionized to generate ions (6), and a radio frequency ion transmission system (8) focuses and transmits the ions (6) under vacuum, so that the ions (6) pass through the ion outlet electrode (7) and enter the mass spectrometer.

2. The array pulse induced electrospray ionization source according to claim 1, characterized in that: The spray capillary array group (10) is composed of two or more capillaries arranged in parallel. The left end of the spray capillary array group (10) is sealed and fixed by a sealing sleeve (3). The left end of the sealing sleeve (3) is provided with an inlet connected to the injection pipeline (2). The sample in the micro-injection pump (1) is injected into the sealing sleeve (3) through the injection pipeline (2) and is transmitted to the spray capillary array group (10).

3. The array pulse induced electrospray ionization source according to claim 2, characterized in that: The spray capillary array group (10) is composed of quartz capillaries, and the inner diameter of the quartz capillaries is 5 to 530 um.

4. The array pulse induced electrospray ionization source according to claim 1, characterized in that: The radio frequency ion transmission system (8) comprises more than three parallel and spaced electrode sheets, each of which is a flat plate structure with a circular through hole in the middle.

5. The array pulse induced electrospray ionization source according to claim 4, characterized in that: The radio frequency ion transmission system (8) adopts an ion funnel structure. The diameter of the circular through hole of the electrode sheet in the radio frequency ion transmission system (8) is 2 to 100 mm, and the diameter of the circular through hole decreases from left to right.

6. The array pulse induced electrospray ionization source according to claim 5, characterized in that: Adjacent electrode sheets in the radio frequency ion transmission system (8) are applied with radio frequency voltages of opposite phases and the same amplitude, the radio frequency voltage amplitude range is 10 to 1000 V, and the radio frequency frequency is 0.5 to 3 MHz; adjacent electrode sheets in the radio frequency ion transmission system (8) are connected via equal value resistors, and a direct current voltage is applied to the first and last electrode sheets of the radio frequency ion transmission system (8), so as to form an ion transmission electric field with a magnitude of 1 to 50 V / cm in the axial direction of the radio frequency ion transmission system (8).

7. The array pulse induced electrospray ionization source according to claim 1, characterized in that: The radio frequency ion transmission system (8) is a combined radio frequency multipole structure.

8. The array pulse induced electrospray ionization source according to claim 1, characterized in that: The radio frequency ion transmission system (8) is a combined segmented radio frequency multipole structure.

9. The array pulse induced electrospray ionization source according to claim 1, characterized in that: The ion outlet electrode (7) is a flat plate structure with a truncated cone-shaped through hole in the middle, and the diameter of the through hole is 0.1 to 2 mm.

10. The array pulse induction electrospray ionization source according to claim 1, characterized in that: The flow rate of the microinjection pump (1) is 0.01 to 10 μL / min; The pulse voltage frequency output by the pulse power supply (5) is 10-2000 Hz, and the amplitude is 2000-4000 V; the vacuum ionization source cavity (4) is connected to a vacuum pump to control the internal air pressure to be 100-10000 Pa.

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