Microspray ionization device

Abstract

The invention discloses a micro-spray ionization device, comprising a sealed housing, a sample introduction mechanism, a spray needle, a high voltage connection mechanism and a reflection electron microscope; the sealed housing is sealed and connected to the inlet end of a mass spectrometer and a sealed cavity is formed inside the sealed housing, the sample introduction mechanism is sealed and installed in the sealed housing and one end is connected to a sample input pipeline; the spray needle is installed in the sample introduction mechanism and the angle between the spray needle and the center line of the inlet of the mass spectrometer is between 0 and 90 degrees, the distance between the needle tip of the spray needle and the inlet of the mass spectrometer is 2 to 30 mm, the high voltage connection mechanism is electrically connected to the spray needle and the power supply respectively; the reflection electron microscope is arranged in the sealed cavity and faces the inlet of the mass spectrometer, and the reflection electron microscope is electrically connected to an external adjustable power supply. The atomization efficiency of the micro-spray ionization device is greatly improved, and 100% ion collection can be achieved, and the measurement sensitivity is greatly improved, and it is particularly suitable for micro-sprays with a flow rate of less than 10 microliters / minute.

Description

Technical Field

[0001] The invention relates to the technical field of liquid mass spectrometry ion sources, in particular to a micro-spray ionization device. Background Art

[0002] A mass spectrometer is an instrument that generates, separates and detects charged particles. It is the most advanced instrument in the field of modern chemical analysis. During mass spectrometry, the sample is first ionized in the ion source. The generated ions and neutral molecules are then separated from each other under the cross-action of the electromagnetic field and the gravitational field. Ions of different masses enter the high vacuum chamber and are separated by mass under the action of the electromagnetic field. The separated ions are finally measured one by one by the charged particle detection device.

[0003] At present, the most commonly used ion source in liquid mass spectrometry is the electrospray ion source. The ionization reaction is carried out under normal pressure conditions, while the ion separation must be carried out in a vacuum. The ions must undergo a collection process from normal pressure to high vacuum. Therefore, ionization efficiency and collection efficiency are the two most critical indicators of the ion source and are also the most important factors determining the sensitivity of the mass spectrometer.

[0004] The ionization efficiency of the electrospray ion source is directly related to the atomization efficiency. Under given voltage conditions, the smaller the volume of liquid atomized per unit time, the higher the atomization efficiency and the higher the ionization efficiency. Therefore, from the perspective of improving the sensitivity of the mass spectrometer alone, micro or ultra-micro spraying will inevitably improve the atomization efficiency, thereby greatly improving the sensitivity of mass spectrometry. Based on this fact, many types of micro-spray ion sources have been introduced, such as nano-spray ion source, DART ion source, in-situ ionization ion source, paper spray ion source, glow discharge ion source, etc.

[0005] Among them, the nano-spray ion source uses a capillary with an inner diameter of tens of microns and a very fine tip close to and facing the entrance of the mass spectrometer, and sprays under the drive of 1-2KV DC voltage. It is often used for the analysis of biological macromolecules (such as proteins). Because the spray is very close to the entrance of the mass spectrometer, the spray voltage cannot be too high, otherwise it is easy to produce a breakdown short circuit; if the voltage is not high, it is difficult to obtain the best spray efficiency; if the distance between the spray capillary and the mass spectrometer entrance is increased, the collection efficiency is affected. There is also a nano-spray ion source on the market that directly extends the spray needle into the mass spectrometer entrance capillary for spraying. The collection efficiency of this ion source reaches the limit, that is, full collection, but the spray space is extremely small, and the atomization efficiency cannot reach the ideal state. As for other various micro-spray ion sources, no matter how the spray efficiency is, it is impossible to achieve the effect of full collection.

[0006] Therefore, it is necessary to provide a micro-spray ionization device that can ensure sufficient atomization and achieve 100% collection efficiency to solve the above problems. Summary of the invention

[0007] The object of the present invention is to provide a micro-spray ionization device which can ensure sufficient atomization and achieve 100% collection efficiency.

[0008] To achieve the above object, the technical scheme of the present invention is as follows: a micro-spray ionization device is provided, which is connected to a mass spectrometer, and comprises a sealed housing, a sample introduction mechanism, a spray needle, a high voltage connection mechanism and a reflection electron microscope; wherein the sealed housing is sealed and connected to the inlet end of the mass spectrometer, and a sealed cavity is formed inside the sealed housing, and the sealed cavity is communicated with the inlet of the mass spectrometer; the sample introduction mechanism is sealedly installed in the sealed housing and one end is connected to a sample input pipeline; the spray needle is installed in the sample introduction mechanism and is communicated with the sample pipeline, the spray needle extends into the sealed cavity and the angle between the spray needle and the center line of the inlet of the mass spectrometer is between 0 and 90°, the distance between the needle tip of the spray needle and the inlet of the mass spectrometer is 2 to 30 mm, and the inner diameter of the spray needle is between 20 and 200 mm; the high voltage connection mechanism is electrically connected to the spray needle and the power supply, respectively, for providing a spray voltage to the spray needle; the reflection electron microscope is arranged in the sealed cavity and faces the inlet of the mass spectrometer, and the reflection electron microscope is electrically connected to an external adjustable power supply.

[0009] Preferably, the reflection electron mirror is made of metal material and its surface facing the inlet of the mass spectrometer is a smooth plane or spherical structure. The size of the reflection electron mirror is larger than the size of the atomized cloud formed by the spray needle. The reflection electron mirror pushes the ions of the object to be measured in the atomized cloud into the inlet of the mass spectrometer to ensure that all the ions to be measured are collected by the mass spectrometer, thereby improving the collection efficiency.

[0010] Preferably, the sealed housing is made of metal, non-metal or a combination of the two materials that can withstand temperatures above 300 degrees Celsius for a long time, and the volume of the sealed cavity is greater than or equal to the volume of the atomized cloud formed by the spray needle.

[0011] Preferably, the volume of the sealed cavity is greater than or equal to the volume of an ellipsoidal atomized cloud formed by the spray needle with a major axis of 5 to 30 mm and a minor axis of 5 to 20 mm.

[0012] Preferably, the sample introduction mechanism is provided with a sealing slide, and the spray needle can be slidably installed in the sealing slide. When the spray needle slides, its distance relative to the inlet of the mass spectrometer can be adjusted, thereby optimizing the efficiency of ions generated by spray ionization being collected by the mass spectrometer.

[0013] Preferably, the high voltage connection mechanism comprises a high voltage wire and a connector connected thereto, wherein the connector is passed through the sealed housing and contacts the spray needle or the sample solution in the spray needle.

[0014] Preferably, the micro-spray ionization device also includes an ultrasonic vibration device, which includes a piezoelectric transducer arranged in the sealed cavity and an ultrasonic generator arranged outside the sealed cavity. The spray needle is tightly connected to the piezoelectric transducer, and the axial direction of the spray needle is perpendicular to the vibration direction of the piezoelectric transducer. The ultrasonic oscillation generated by the ultrasonic generator is transmitted to the piezoelectric transducer to drive it to generate mechanical vibration and drive the spray needle to resonate, thereby making the spray needle itself an ultrasonic resonance rod, transmitting the ultrasonic vibration to the needle tip of the spray needle, thereby greatly improving the efficiency of atomizing the sample solution on the needle tip.

[0015] Preferably, the micro-spray ionization device further comprises a heating mechanism disposed in the sealed cavity, wherein the heating mechanism is disposed around the atomized cloud formed by the spray needle to heat the atomized cloud to improve atomization and ionization efficiency.

[0016] Preferably, the heating mechanism includes an infrared coating uniformly coated on the inner wall of the sealed cavity and two electrodes respectively in contact with the infrared coating, the electrodes are electrically connected to a power supply, and the infrared coating generates infrared radiation when energized to heat the atomized cloud formed by the spray needle. As the temperature rises, the solvent of the liquid droplets in the atomized cloud evaporates faster, causing the liquid droplets to shrink rapidly, and the thinned mist droplets undergo Coulomb explosion to produce ions. Accelerating the Coulomb explosion can improve the ionization efficiency of the substance to be measured, thereby improving the measurement sensitivity.

[0017] Preferably, the heating mechanism includes an electromagnetic induction coil arranged in the sealed cavity and an electromagnetic wave generator connected to the electromagnetic induction coil, wherein the electromagnetic induction coil is arranged outside the spray needle. After the electromagnetic wave generator is started, the electromagnetic induction coil heats the atomized cloud formed by the spray needle to promote rapid refinement of liquid droplets in the atomized cloud, thereby improving ionization efficiency.

[0018] Compared with the prior art, the micro-spray ionization device of the present invention has the following advantages: firstly, its sealed housing is sealed and connected to the inlet of the mass spectrometer, and the sealed cavity formed inside the sealed housing is connected to the inlet of the mass spectrometer. Therefore, the vacuum of the mass spectrometer passes through the inlet to form a vacuum state in the sealed cavity of the ion source, which is conducive to more effective atomization of the sample solution. The atomized sample can be completely sucked into the mass spectrometer by the vacuum of the mass spectrometer without destroying the internal vacuum degree; secondly, the angle between the spray needle extending into the sealed cavity and the center line of the inlet of the mass spectrometer is between 0 and 90 degrees, the distance between the needle tip of the spray needle and the inlet of the mass spectrometer is 2 to 30 mm, the inner diameter of the spray needle is between 20 and 200 mm, the spray needle makes the sample flow rate not exceed 10 microliters per minute, and can ensure sufficient atomization, have the best spray effect, and thus improve the ionization efficiency; furthermore, through the effect of the reflection electron microscope, all the ions generated in the ion source can be driven into the interior of the mass spectrometer. In summary, the micro-spray ionization device 100 of the present invention has an atomization efficiency 10 to 1000 times higher than that of a conventional liquid chromatography-mass spectrometry (LC / MS) electrospray ionization source and can achieve 100% ion collection, thereby greatly improving the measurement sensitivity, and is particularly suitable for micro-spray with a flow rate below 10 μL / min. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is a schematic structural diagram of the first embodiment of the micro-spray ionization device of the present invention.

[0020] Figure 2 It is a schematic structural diagram of the second embodiment of the micro-spray ionization device of the present invention.

[0021] Figure 3 It is a schematic structural diagram of the third embodiment of the micro-spray ionization device of the present invention.

[0022] Figure 4 It is a schematic structural diagram of the fourth embodiment of the micro-spray ionization device of the present invention. DETAILED DESCRIPTION

[0023] The embodiments of the present invention are now described with reference to the accompanying drawings, in which like element numbers represent like elements. The micro-spray ionization device 100 provided by the present invention is mainly suitable for ionization of micro-samples, and is particularly suitable for micro-spraying with a sample flow rate of less than 10 μl / min, but is not limited thereto.

[0024] Let's combine Figure 1-Figure 4As shown, the micro-spray ionization device 100 provided by the present invention comprises a sealed housing 110, a sample introduction mechanism 120, a spray needle 130, a high voltage connection mechanism 140 and a reflection electron microscope 150. The sealed housing 110 is sealed and connected to the end where the inlet 210 of the mass spectrometer 200 is located, and a sealed cavity 111 is formed inside the sealed housing 110, which is connected to the inlet 210 of the mass spectrometer 200, and the volume of the sealed cavity 111 is greater than or equal to the volume of the atomized cloud to be formed, preferably greater than the volume of the atomized cloud to be formed. The sample introduction mechanism 120 is sealedly installed on the sealed housing 110 and one end of which is connected to the sample input pipeline; the spray needle 130 is installed on the sample introduction mechanism 120 and is connected to the sample pipeline, the spray needle 130 extends into the sealed cavity 111 and the angle between the spray needle 130 and the center line P of the inlet 210 of the mass spectrometer 200 is between 0 and 90 degrees, the distance L between the needle tip of the spray needle 130 and the inlet 210 is 2 to 30 mm, and the inner diameter of the spray needle 130 is between 20 and 200 mm; the high voltage connection mechanism 140 is electrically connected to the spray needle 130 and the power supply, respectively, and is used to provide a spray voltage. The reflection electron mirror 150 is arranged in the sealed cavity 111 and faces the entrance 210 of the mass spectrometer 200, and the reflection electron mirror 150 is electrically connected to an external adjustable power supply. The reflection electron mirror 150 is used to push the ions of the object to be measured into the entrance 210 of the mass spectrometer 200 to ensure that all the ions to be measured are collected by the mass spectrometer 200, thereby improving the collection efficiency.

[0025] See below Figure 1-Figure 4 As shown, different embodiments of the micro-spray ionization device 100 of the present invention are described in detail.

[0026] See first Figure 1 In the first embodiment of the micro-spray ionization device 100 of the present invention, it is sealed and connected to the mass spectrometer 200 with the inlet 210 on the side. Specifically, the sealed housing 110 is sealed and connected to the side end of the mass spectrometer 200 with the inlet 210, that is, the sealed housing 110 is located at the side of the mass spectrometer 200. The sample introduction mechanism 120 is installed on the top of the sealed housing 110, and the spray needle 130 is installed on the sample introduction mechanism 120 and extends along the height direction of the sealed housing 110, so that the spray needle 130 and the center line P of the inlet 210 of the mass spectrometer 200 form an angle of about 90°, and the distance L between the needle tip of the spray needle 130 and the center line P of the inlet 210 is 2 to 30 mm, and the distance L between the two can be specifically optimized and adjusted according to the ionization properties of the object to be detected; the reflection electron microscope 150 is arranged on an inner wall in the width direction of the sealed cavity 111 and faces the inlet 210 of the mass spectrometer 200.

[0027] In this embodiment, there is no special requirement for the external shape of the sealed housing 110, and it can be set to a square, round or other shape, preferably for aesthetics and convenient loading and unloading operations, and no specific limitation is made here. The shape of the sealed cavity 111 of the sealed housing 110 is also not specifically limited, and can be cylindrical, square, funnel-shaped or any other shape, as long as it is large enough to allow the spray needle 130 inserted into the sealed cavity 111 to fully spray the sample solution, that is, the formed atomized cloud does not touch the inner wall of the sealed cavity 111, and the volume of the sealed cavity 111 needs to be slightly larger than the volume of the atomized cloud. In this embodiment, the spray needle 130 forms an ellipsoidal atomized cloud, and the dimensions of the ellipsoidal atomized cloud are generally 5 to 30 mm in long axis and 5 to 20 mm in short axis. Therefore, the volume of the sealed cavity 111 needs to be slightly larger than or equal to the volume of the ellipsoidal atomized cloud with a long axis of 5 to 30 mm and a short axis of 5 to 20 mm.

[0028] In addition, the sealed shell 110 is made of a material that can withstand temperatures above 300°C for a long time, such as metal, quartz, glass, polytetrafluoroethylene, PEEK, PTFE, etc., but is not limited to this. It can also be made of other metals, non-metals or a combination of the two that can withstand temperatures above 300°C for a long time.

[0029] Continue to view Figure 1 At least one sample introduction mechanism 120 is provided, and the connection between each sample introduction mechanism 120 and the sealed housing 110 must ensure airtightness, and each sample introduction mechanism 120 includes at least one inner interface 121, the opening of the inner interface 121 faces the inside of the sealed cavity 111, and is used to connect the spray needle 130 and connect the spray needle 130 to the sample pipeline. The inner interface 121 can be a perforation directly opened on the sealed housing 110 that just allows the spray needle 130 to penetrate, or it can be a connector with a pipeline. Furthermore, the sample introduction mechanism 120 can also include at least one outer interface 122, which is used to connect with the sample pipeline and possible auxiliary fluid pipelines. At this time, the sample introduction mechanism 120 can be, but not limited to, a two-way, three-way or multi-way connector.

[0030] In this embodiment, the sample introduction mechanism 120 includes an inner interface 121 and an outer interface 122 , wherein the outer interface 122 is connected to the sample pipeline, and the spray needle 130 is installed in the inner interface 121 .

[0031] More preferably, a sealing slide can also be provided on the sample introduction mechanism 120, and the spray needle 130 can be slidably installed in the sealing slide. When the spray needle 130 slides in the sealing slide, its distance relative to the inlet 210 of the mass spectrometer 200 can be adjusted, thereby optimizing the efficiency of ions generated by spray ionization being collected by the mass spectrometer 200.

[0032] Continue to view Figure 1 As shown, in the present invention, the spray needle 130 can be a hollow needle or a solid needle, which is used to conduct high voltage to the sample solution and transmit the sample solution to the needle tip so that it is atomized under the action of high voltage. In this embodiment, the spray needle 130 is a metal capillary with an inner diameter between 20 and 200 microns, which needs to ensure smooth flow of the sample solution and spray effect at the same time.

[0033] like Figure 1 As shown, in this embodiment, the high voltage connection mechanism 140 includes a connector 141 and a high voltage wire 142 connected thereto. The connector 141 is inserted into a borehole opened on the sealed housing 110 and contacts the spray needle 130 or the sample solution in the spray needle 130. The high voltage wire 142 is electrically connected to a power source. Through the high voltage connection mechanism 140, the voltage applied to the spray needle 130 is between 1 and 8 kV, and the preferred micro-spray voltage is 2 to 6 kV. It should be noted that for a metal spray needle 130, the high voltage connection mechanism 140 may only include a high voltage wire 142, which is directly connected to any part of the metal spray needle 130 except the needle tip through the high voltage wire 142, thereby simplifying the structure of the high voltage connection mechanism 140.

[0034] See again Figure 1 As shown, the reflection electron mirror 150 is made of metal material, and its shape can be square, round or other shapes. The size of the reflection electron mirror 150 is sufficient to cover the size of the atomized cloud formed by the spray needle 130. In this embodiment, the size of the reflection electron mirror 150 is sufficient to cover an ellipse with a major axis between 5 and 30 mm. The minimum allowable size needs to be determined according to the spray volume (that is, the size of the atomized cloud). At the same time, the surface of the reflection electron mirror 150 facing the entrance 210 of the mass spectrometer 200 is a smooth spherical structure, and the reflection electron mirror 150 is concave in the direction away from the entrance 210; the reflection electron mirror 150 is connected to an adjustable voltage, the voltage is continuously adjustable, and the polarity (that is, positive and negative) is consistent with the polarity of the ions to be measured. For example, by applying a DC voltage consistent with the polarity of the ions to be measured to the reflection electron mirror 150 and adjusting the voltage, the ions to be measured in the atomized cloud can be pushed into the entrance 210 of the mass spectrometer 200 to ensure that all the ions to be measured are collected by the mass spectrometer 200.

[0035] It is understandable that the surface of the reflection electron mirror 150 facing the inlet 210 of the mass spectrometer 200 is not limited to a spherical surface, and it can also be set to a plane or other structures.

[0036] See again Figure 1As shown, in the micro-spray ionization device 100 of the present invention, since the sealed chamber 111 and the inlet 210 of the mass spectrometer 200 form a sealed connection, the vacuum of the mass spectrometer 200 passes through the inlet 210 so that the interior of the sealed chamber 111 is in a vacuum and negative pressure state; when the spray needle 130 introduces the sample solution into the sealed chamber 111 at a flow rate lower than 10 μL / min, the sample solution forms a charged atomized cloud at the needle tip of the spray needle 130 under the action of high voltage, and the substance to be tested in the sample solution is ionized as the liquid droplets in the charged atomized cloud continuously undergo Coulomb explosion, and the generated ions are completely sucked into the interior of the mass spectrometer 200 by the vacuum of the mass spectrometer 200 without destroying the vacuum degree therein, and coupled with the effect of the reflection electron mirror 150 facing the inlet 210, the ions generated in the ion source can all be driven into the interior of the mass spectrometer 200, achieving 100% ion collection, thereby greatly improving the measurement sensitivity.

[0037] See below Figure 2 As shown, in the second embodiment of the micro-spray ionization device 100 of the present invention, the difference from the first embodiment is that it also includes an ultrasonic vibration device 160, which is connected to the spray needle 130 inside the sealed chamber 111. Since the characteristics of ultrasonic waves are high frequency, short wavelength, and weak diffraction, they have good directivity and are not easy to affect the movement path of ions. When the sound propagates in the air, it drives the particles in the air to vibrate back and forth and does work on the particles. In addition, the ultrasonic wave has a high frequency and high energy, and can produce a significant thermal effect when absorbed by the medium, and also plays a role of auxiliary heat. Therefore, in this embodiment, the spray needle 130 itself becomes an ultrasonic resonance rod, and the ultrasonic vibration is transmitted to its needle tip, which can greatly improve the efficiency of atomization and ionization of the sample solution on the needle tip.

[0038] More specifically, the ultrasonic vibration device 160 includes a piezoelectric transducer 161 disposed in the sealed cavity 111 and an ultrasonic generator 162 disposed outside the sealed cavity 111. The piezoelectric transducer 161 is connected to the inner wall of the sealed cavity 111. The spray needle 130 is tightly connected to the piezoelectric transducer 161, and the axial direction of the spray needle 130 is perpendicular to the vibration direction of the piezoelectric transducer 161. A layer of hard insulating material (not numbered, such as Figure 2 As described above, the ultrasonic generator 162 is connected to the piezoelectric transducer 161. When the ultrasonic oscillation generated by the ultrasonic generator 162 is transmitted to the piezoelectric transducer 161, the piezoelectric transducer 161 can be driven to generate mechanical vibrations to drive the spray needle 130 to resonate, thereby making the spray needle 130 itself an ultrasonic resonance rod, and transmitting the ultrasonic vibration to the needle tip of the spray needle 130, thereby greatly improving the efficiency of atomization of the sample solution on the needle tip.

[0039] The piezoelectric transducer 161 may be a vibrator made of a piezoelectric ceramic sheet, a piezoelectric silicon sheet, a piezoelectric ceramic stack or other piezoelectric materials, without specific limitation. In this embodiment, one or more piezoelectric ceramic stacks are used, and the spray needle 130 is tightly connected to the piezoelectric ceramic stack. A layer of hard insulating material (see FIG. 1 ) is provided between the upper end of the spray needle 130 and the piezoelectric ceramic stack. Figure 2 ) are isolated and tightly combined, and ensure that the axial direction of the spray needle 130 is perpendicular to the vibration direction of the piezoelectric ceramic stack. At the same time, the piezoelectric ceramic stack is connected to an ultrasonic generator 162 with a frequency of more than 1.7MHz. After the ultrasonic vibration device 160 is started, the ultrasonic oscillation generated by the ultrasonic generator 162 is transmitted to the piezoelectric ceramic stack, and the piezoelectric ceramic stack generates mechanical vibrations with a vibration frequency consistent with the output frequency of the ultrasonic generator 162. The piezoelectric ceramic stack drives the spray needle 130 to resonate. The tip of the spray needle 130 has the largest amplitude due to being suspended in the air, and the sample solution flowing out of the needle tip is subjected to high-frequency ultrasonic vibrations and is atomized.

[0040] In this embodiment, through the dual effects of the piezoelectric transducer 161 and the high voltage on the spray needle 130, the sample solution forms a charged atomized cloud at the tip of the spray needle 130, and the substance to be tested in the sample solution is ionized as the liquid droplets in the charged atomized cloud continuously undergo Coulomb explosion, which prompts the sample solution flowing to the needle tip to be quickly atomized, and the atomization efficiency is significantly improved compared to pure electrospray or other forms of spray. It should be noted that in this embodiment, the situation where the high voltage is directly connected to the spray needle 130 is equivalent to a composite ion source of electrospray and APCI (Atmospheric Pressure Chemical Ionization).

[0041] In this embodiment, the structure, arrangement and working principle of other parts are the same as those in the first embodiment described above and will not be described in detail.

[0042] Combine the following Figure 3-4 As shown, the micro-spray ionization device 100 of the present invention may further be provided with a heating mechanism, wherein the heating mechanism is disposed at the periphery of the atomized cloud formed by the spray needle 130 to heat the atomized cloud to improve the atomization and ionization efficiency.

[0043] See first Figure 3 As shown, in the third embodiment of the micro-spray ionization device 100 of the present invention, a heating mechanism 170 is further provided on the basis of the second embodiment, and the heating mechanism 170 is preferably an infrared heating mechanism.

[0044] Specifically, the micro-spray ionization device 100 in this embodiment is sealed and connected to the mass spectrometer 200 with the inlet 210 at the top, that is, the sealed housing 110 is sealed and connected to the top of the mass spectrometer 200 with the inlet 210, and the sealed housing 110 is located above the mass spectrometer 200. The sample introduction mechanism 120 is installed on the top of the sealed housing 110 and faces the inlet 210 of the mass spectrometer 200. The spray needle 130 is installed on the sample introduction mechanism 120 and extends along the height direction of the sealed housing 110. The spray needle 130 faces the inlet 210 of the mass spectrometer 200. The axial direction of the spray needle 130 is on the same straight line as the center line P of the inlet 210 of the mass spectrometer 200, that is, the two form an angle of 0°. The distance L between the needle tip of the spray needle 130 and the inlet 210 of the mass spectrometer 200 is 2 to 30 mm. In this embodiment, the distance L is specifically the distance to the end face of the inlet 210, such as Figure 3 As shown, of course, the distance L between the two can be optimized and adjusted according to the ionization properties of the object to be tested; the reflection electron mirror 150 and the ultrasonic vibration device 160 are both installed on the top of the sealed cavity 111, and the ultrasonic vibration device 160 is located above the reflection electron mirror 150, so that the reflection electron mirror 150 is facing the inlet 210 of the mass spectrometer 200, and the spray needle 130 passes through the ultrasonic vibration device 160 and the reflection electron mirror 150 in turn and extends into the interior of the sealed cavity 111.

[0045] In this embodiment, the structure, arrangement and working principle of the ultrasonic vibration device 160 are the same as those in the second embodiment described above, and will not be described again here.

[0046] Continue to view Figure 3 As shown, in this embodiment, the sealed shell 110 is made of quartz and the sealed cavity 111 is cylindrical. The inner diameter of the sealed cavity 111 is about 45 mm. The bottom end of the sealed shell 110 forms an airtight and fastened connection with the inlet 210 of the mass spectrometer 200. A stainless steel disc with a diameter consistent with the inner diameter of the sealed cavity 111 is embedded in the top end. The periphery of the stainless steel disc is firmly bonded to the inner wall of the sealed cavity 111 with vacuum glue. The stainless steel is the reflection electron microscope 150.

[0047] More specifically, the heating mechanism 170 in this embodiment includes an infrared coating 171 uniformly coated on the inner wall of the sealed cavity 111 and two electrodes 172 in contact with the infrared coating 171. The infrared coating 171 is formed of infrared paint and has a thickness of about 0.1 to 0.5 mm. The electrodes 172 are externally connected to two output ends of a 0 to 100 V continuously adjustable AC or DC power supply. A voltage of 2 to 50 V is applied to the infrared coating 171 through the two electrodes 172. The AC and DC are not limited. When the infrared coating 171 is energized, infrared radiation is generated to heat the atomized cloud surrounded therein. The atomized cloud is radiated and heated to 50 to 400° C. As the temperature rises, the solvent of the liquid droplets in the atomized cloud evaporates faster, causing the liquid droplets to shrink rapidly. The thinned mist droplets undergo Coulomb explosion to produce ions. Accelerating the Coulomb explosion can improve the ionization efficiency of the substance to be measured, thereby improving the measurement sensitivity.

[0048] See again Figure 3 As shown, when the micro-spray ionization device 100 of this embodiment is working, the voltage is adjusted to 5V. At this time, the temperature in the sealed chamber 111 is about 100 degrees Celsius. The sample solution is input into the spray needle 130 from the sample pipeline above the sealed housing 110. Under the action of high voltage, the sample solution forms a charged atomized cloud at the tip of the spray needle 130. The substance to be tested in the sample solution is ionized as the liquid droplets in the charged atomized cloud continuously undergo Coulomb explosion. The generated ions are not only attracted by the high voltage and the vacuum of the mass spectrometer 200, but also by the reflection electron microscope 150, so that they are collected more completely. In addition, after the infrared coating 171 is energized, the infrared coating generates infrared radiation to heat the atomized cloud. The heating temperature can be controlled by adjusting the power supply voltage, which can reach up to 400 degrees Celsius, further improving the atomization and ionization efficiency (obtaining thorough atomization and finer mist droplets). The atomization efficiency is higher than that of conventional liquid chromatography mass spectrometry (LCMS). Spectrometer, LC / MS) electrospray ion source is 10 to 1000 times higher, so the measurement sensitivity will be greatly improved.

[0049] See below Figure 4 As shown, in the fourth embodiment of the micro-spray ionization device 100 of the present invention, the difference from the third embodiment is that the heating mechanism 170 is different, and the other parts are the same, and the same parts will not be repeated.

[0050] In this embodiment, the heating mechanism 170 adopts electromagnetic radiation heating, which includes an electromagnetic induction coil 173, two joints 174 connected to the electromagnetic induction coil 173, and an electromagnetic wave generator electrically connected to the joint 174. The electromagnetic induction coil 173 is arranged in the sealed cavity 111 and is spirally shaped. The electromagnetic induction coil 173 is wrapped outside the spray needle 130 so that the electromagnetic induction coil 173 can surround the atomized cloud. The electromagnetic wave generator can generate electromagnetic waves with a frequency higher than 100kHz. After the electromagnetic wave generator is started, the electromagnetic induction coil 173 heats the atomized cloud formed by the spray needle 130, so that the atomized cloud generates strong heat due to induction, the temperature rises rapidly, and the liquid droplets in the atomized cloud are rapidly refined to cause Coulomb explosion, thereby greatly improving the ionization efficiency of the substance to be detected and thus improving its detection sensitivity.

[0051] In combination with the above description, the micro-spray ionization device 100 of the present invention, firstly, its sealed housing 110 is sealedly connected to the end where the inlet 210 of the mass spectrometer 200 is located, and the sealed cavity 111 formed inside the sealed housing 110 is connected to the inlet 210 of the mass spectrometer 200. Therefore, the vacuum of the mass spectrometer 200 passes through its inlet 210 to form a vacuum state in the sealed cavity 111 of the ion source, which is conducive to more effective atomization of the sample solution. The atomized sample can be completely sucked into the interior of the mass spectrometer 200 by the vacuum of the mass spectrometer 200 without destroying the internal vacuum degree; secondly, its spray needle 130 extends The spray needle 130 is inserted into the sealed cavity 111 and the angle between the center line P of the spray needle 130 and the inlet 210 of the mass spectrometer 200 is between 0 and 90 degrees. The distance L between the tip of the spray needle 130 and the inlet 210 of the mass spectrometer 200 is between 2 and 30 mm. The inner diameter of the spray needle 130 is between 20 and 200 mm. The spray needle 130 makes the sample flow rate not exceed 10 microliters per minute, and can ensure sufficient atomization, have the best spray effect, and thus improve the ionization efficiency; furthermore, through the action of the reflection electron microscope 150, all the ions generated in the ion source can be driven into the interior of the mass spectrometer 200. In summary, the micro-spray ionization device 100 of the present invention has an atomization efficiency 10 to 1000 times higher than that of a conventional liquid chromatography mass spectrometer (LC / MS) electrospray ion source, and can achieve 100% ion collection, thereby greatly improving the measurement sensitivity, and is particularly suitable for micro-sprays with a flow rate of less than 10 microliters per minute.

[0052] The structure, configuration and working principle of the mass spectrometer 200 involved in the present invention are conventional configurations well known to ordinary technicians in the field and will not be described in detail here.

[0053] The above disclosure is only the preferred embodiment of the present invention, which certainly cannot be used to limit the scope of rights of the present invention. Therefore, equivalent changes made according to the scope of the patent application of the present invention are still within the scope covered by the present invention.

Claims

1. A microspray ionization device, connected to a mass spectrometer, characterized in that: include: A sealed housing, which is sealed and connected to the inlet end of the mass spectrometer, and has a sealed cavity formed inside the sealed housing, the sealed cavity being in communication with the inlet of the mass spectrometer; A sample introduction mechanism, which is sealingly mounted on the sealing housing and one end of which is connected to a sample input pipeline; A spray needle, which is installed in the sample introduction mechanism and connected to the sample pipeline, the spray needle extends into the sealed cavity and the angle between the spray needle and the center line of the inlet of the mass spectrometer is between 0 and 90 degrees, the distance between the needle tip of the spray needle and the inlet of the mass spectrometer or the center line of the inlet of the mass spectrometer is 2 to 30 mm, and the inner diameter of the spray needle is between 20 and 200 mm; A high voltage connection mechanism, which is electrically connected to the spray needle and a power source, respectively, and is used to provide a spray voltage to the spray needle; A reflection electron mirror, which is arranged in the sealed cavity and faces the entrance of the mass spectrometer, the reflection electron mirror is made of metal material, and the reflection electron mirror is electrically connected to an external adjustable power supply; Wherein, the volume of the sealed cavity is greater than or equal to the volume of the atomized cloud formed by the spray needle.

2. The microspray ionization device according to claim 1, characterized in that: The surface of the reflection electron mirror facing the inlet of the mass spectrometer is a smooth plane or spherical structure, and the size of the reflection electron mirror is larger than the size of the atomized cloud formed by the spray needle.

3. The microspray ionization device according to claim 1, characterized in that: The sealed housing is made of metal, non-metal or a combination of the two materials that can withstand temperatures above 300 degrees Celsius for a long time.

4. The microspray ionization device according to claim 3, characterized in that: The volume of the sealed cavity is greater than or equal to the volume of the ellipsoidal atomized cloud formed by the spray needle with a major axis of 5 to 30 mm and a minor axis of 5 to 20 mm.

5. The microspray ionization device according to claim 1, characterized in that: The sample introduction mechanism is provided with a sealing slideway, and the spray needle is slidably installed in the sealing slideway. When the spray needle slides, the distance between the spray needle and the inlet of the mass spectrometer can be adjusted.

6. The microspray ionization device according to claim 1, characterized in that: The high voltage connection mechanism comprises a high voltage wire and a connector connected thereto, wherein the connector is arranged through the sealed housing and contacts the spray needle or the sample solution in the spray needle.

7. The microspray ionization device according to claim 1, characterized in that: It also includes an ultrasonic vibration device, which includes a piezoelectric transducer arranged in the sealed cavity and an ultrasonic generator arranged outside the sealed cavity. The spray needle is tightly connected to the piezoelectric transducer, and the axial direction of the spray needle is perpendicular to the vibration direction of the piezoelectric transducer. The ultrasonic oscillation generated by the ultrasonic generator is transmitted to the piezoelectric transducer to drive it to generate mechanical vibration and drive the spray needle to resonate.

8. The microspray ionization device according to claim 1 or 7, characterized in that: It also includes a heating mechanism disposed in the sealed cavity, wherein the heating mechanism is disposed around the atomized cloud formed by the spray needle to heat the atomized cloud.

9. The microspray ionization device according to claim 8, characterized in that: The heating mechanism includes an infrared coating evenly coated on the inner wall of the sealed cavity and two electrodes respectively contacting the infrared coating, the electrodes are electrically connected to a power supply, and the infrared coating generates infrared radiation when energized to heat the atomized cloud formed by the spray needle.

10. The microspray ionization device according to claim 8, characterized in that: The heating mechanism includes an electromagnetic induction coil arranged in the sealed cavity and an electromagnetic wave generator connected to the electromagnetic induction coil. The electromagnetic induction coil is arranged outside the spray needle. After the electromagnetic wave generator is started, the electromagnetic induction coil heats the atomized cloud formed by the spray needle.

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