Mass spectrum nanoliter ion source and method for adjusting mass spectrum nanoliter ion source

Abstract

The invention discloses a mass spectrum nanoliter ion source and an adjusting method of the mass spectrum nanoliter ion source, and relates to the technical field of mass spectrometers.The mass spectrum nanoliter ion source comprises an ion source outer cover, a vacuum interface cavity is formed in the ion source outer cover, and a conical cover is formed at the end of the vacuum interface cavity; a quadrupole rod and a vacuum pump interface are arranged in the vacuum interface cavity; a sample injection hole is formed in the conical cover; the adjusting mechanism and the ion source outer cover are fixedly arranged relative to each other; the nano-liter spray needle is arranged on the adjusting mechanism, and the nano-liter spray needle is suitable for adjusting the distance and / or posture between the nano-liter spray needle and the sample injection hole through the adjusting mechanism; and the nanoliter spray needle is electrified so as to form an electric field between the nanoliter spray needle and the conical cover, wherein the electric field enables target ions to move towards the conical cover. The mass spectrum nanoliter ion source provided by the embodiment of the invention has the advantages of high ionization efficiency, short trapping time, good applicability and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of mass spectrometry, in particular, to a mass spectrometry nanoliter ion source and a method for adjusting the mass spectrometry nanoliter ion source. BACKGROUND

[0002] The mass spectrometry nanoliter ion source is to penetrate the sample into the charged solution through the micropore, to use the high-voltage electric field to generate the driving force, to bring the sample molecules into the charged aerosol, and to generate the ionization effect after entering the mass spectrometer, and finally to form the charged substance ions. Due to the smaller nozzle and the extremely low flow (usually several nanoliters per minute), the nozzle diameter is usually only a few microns, so that smaller droplets can be generated and the ionization efficiency can be improved. Due to the smaller nozzle and the low flow, the nanoliter ion source can obtain high sensitivity analysis results with very small sample amount, and is particularly suitable for analyzing trace samples, which can significantly improve the efficiency and sensitivity of mass spectrometry analysis. It is very suitable for trace samples, valuable samples and low concentration analysis, and can be applied to the analysis of various samples such as biological macromolecules, small molecules, metal ions and organic molecules, and is particularly suitable for the analysis of biological molecules such as proteins, peptides and metabolites.

[0003] In the related art, the mass spectrometry nanoliter ion source uses pneumatic assisted atomization or hot gas assisted volatilization to promote the separation of ions and solvent.

[0004] The pneumatic assisted atomization is to set an atomizer or a sheath gas tube, based on Bernoulli effect, to form a negative pressure to increase the kinetic energy of the liquid, thereby assisting to overcome the surface tension of the droplets to disperse the droplets. However, in fact, the kinetic energy of the droplets is too large, which can easily lead to excessive fragmentation of the droplets, thereby reducing the ionization efficiency.

[0005] The hot gas assisted volatilization is to set inert gas such as nitrogen and heating device, so that the nanoscale charged droplets are completely desolvated under the assistance of the heated nitrogen gas flow to form free gaseous ions. In this method, if the concentration of nitrogen gas is low, the heating effect is poor, and if the concentration of nitrogen gas is too high, part of the nanoscale charged droplets can be easily taken away, which requires to prolong the ion capture time, which is not conducive to improving the efficiency and sensitivity of the analysis, and this method is not suitable for the analysis of heat-sensitive samples such as biological molecules. SUMMARY

[0006] The present application aims to at least solve one of the technical problems existing in the prior art. To this end, the present application proposes a mass spectrometry nanoliter ion source, which has the advantages of high ionization efficiency, short capture time, good applicability and the like.

[0007] The present application also proposes a method for adjusting the mass spectrometry nanoliter ion source.

[0008] To achieve the above object, according to an embodiment of the first aspect of the present application, a nanoliter ion source for mass spectrometry is provided, comprising: an ion source housing, wherein a vacuum interface cavity is arranged in the ion source housing, an end of the vacuum interface cavity forms a conical cover, a quadrupole rod and a vacuum pump interface are arranged in the vacuum interface cavity, and a sample inlet hole is arranged on the conical cover; an adjusting mechanism, which is fixedly arranged in a position opposite to the ion source housing; a nanoliter spray needle, which is arranged on the adjusting mechanism, is adapted to adjust the distance and / or attitude relative to the sample inlet hole through the adjusting mechanism, and is electrically connected to form an electric field between the nanoliter spray needle and the conical cover to move target ions towards the conical cover.

[0009] The nanoliter ion source for mass spectrometry according to the embodiment of the present application has the advantages of high ionization efficiency, short trapping time, and good applicability.

[0010] In addition, the nanoliter ion source for mass spectrometry according to the above embodiment of the present application can also have the following additional technical features: According to an embodiment of the present application, the nanoliter spray needle is movable at least in the axial direction of the sample inlet hole.

[0011] According to an embodiment of the present application, the nanoliter spray needle is adapted to adjust the angle with the axial direction of the sample inlet hole through the adjusting mechanism.

[0012] According to an embodiment of the present application, the ion source housing is provided with an observation window adapted to observe the Taylor cone formed by the droplets sprayed by the nanoliter spray needle.

[0013] According to an embodiment of the present application, the nanoliter ion source for mass spectrometry further comprises a chromatographic column connected to the nanoliter spray needle, and the nanoliter spray needle and / or the chromatographic column is / are detachably mounted on the adjusting mechanism.

[0014] According to an embodiment of the present application, the conical cover is electrically grounded.

[0015] According to an embodiment of the present application, the adjusting mechanism is provided with an electrically conductive sheet for electrical connection, and the nanoliter spray needle is detachably electrically connected to the electrically conductive sheet.

[0016] According to an embodiment of the present application, the nanoliter ion source for mass spectrometry further comprises a supporting platform, the adjusting mechanism is arranged on the supporting platform, the supporting platform is pushably and pullably connected to the ion source housing between a pushed-in position and a pulled-out position, the nanoliter spray needle extends into the ion source housing when the supporting platform is in the pushed-in position, and the nanoliter spray needle is located outside the ion source housing when the supporting platform is in the pulled-out position.

[0017] According to one embodiment of the present application, the nano-liter ion source further comprises a guide rod connected to the ion source housing, and the supporting platform is slidably arranged on the guide rod.

[0018] According to one embodiment of the present application, one of the guide rod and the supporting platform is provided with a positioning groove, and the other is provided with a positioning bead, and the positioning bead is adapted to be disengagedly fitted in the positioning groove when the supporting platform is in the pushed-in position.

[0019] According to one embodiment of the second aspect of the present application, a method for adjusting a nano-liter ion source for mass spectrometry is provided, the nano-liter ion source comprising a nano-liter spray needle and an ion source housing, the ion source housing being provided with a vacuum interface cavity, an end of the vacuum interface cavity forming a conical cover, the conical cover being provided with a sample inlet hole, the method comprising the following steps: adjusting the relative spatial position relationship between the nano-liter spray needle and the sample inlet hole, and detecting the signal intensity of target ions downstream of the ion source housing until the signal intensity reaches a set threshold value; measuring the cone angle of the Taylor cone formed by the liquid droplets sprayed by the nano-liter spray needle at this time to obtain a target cone angle; adjusting the relative spatial position relationship between the nano-liter spray needle and the sample inlet hole until the cone angle of the Taylor cone formed by the liquid droplets sprayed by the nano-liter spray needle reaches the target cone angle.

[0020] The method for adjusting the nano-liter ion source for mass spectrometry according to the embodiments of the present application has the advantages of high ionization efficiency, short trapping time, good applicability, etc.

[0021] Additional aspects and advantages of the present application will be in part apparent and in part pointed out hereinafter. BRIEF DESCRIPTION OF DRAWINGS

[0022] The above and / or additional aspects and advantages of the present application will become apparent and be readily appreciated from the following description, taken in conjunction with the accompanying drawings, in which: Figure 1 is a schematic diagram of the working principle of a nano-liter ion source for mass spectrometry according to an embodiment of the present application.

[0023] Figure 2 is a schematic diagram of the structure of a nano-liter ion source for mass spectrometry according to an embodiment of the present application.

[0024] Figure 3 is a schematic diagram of the structure of a nano-liter ion source for mass spectrometry according to an embodiment of the present application.

[0025] Figure 4 is a schematic diagram of the structure of an adjusting mechanism of a nano-liter ion source for mass spectrometry according to an embodiment of the present application.

[0026] Figure 5 This is a flowchart of a method for adjusting a nanoliter mass spectrometer ion source according to an embodiment of the present invention.

[0027] Figure reference numerals: 1. Mass spectrometer nano-ion source; 10. Ion source outer cover; 11. Conical cover; 12. Sample inlet; 13. Observation window; 14. Vacuum interface cavity; 15. Quadrupole; 16. Vacuum pump interface; 20. Adjustment mechanism; 21. Differential displacement stage; 22. Spray needle mounting base; 22. Baffle; 221. Notch; 222. Differential head; 23. Triaxial displacement stage; 24. First horizontal adjustment knob; 25. Second horizontal adjustment knob; 26. Lifting adjustment knob; 27. Chromatographic column mounting base; 28. Connecting rod; 29. ​​Nano-inlet spray needle; 30. Chromatographic column; 40. Support platform; 50. Positioning bead; 51. Guide rod; 60. Positioning groove; 61. Taylor cone; 2. Target ion; 3. Neutral ion; 4. Detailed Implementation

[0028] This application is based on the findings and understanding of the following facts and issues: In related technologies, the nanoliter ion source for mass spectrometry uses pneumatic-assisted atomization or hot gas-assisted volatilization to promote the separation of ions from solvents.

[0029] Pneumatically assisted atomization works by using an atomizer or sheath tube to create negative pressure based on the Bernoulli effect, increasing the kinetic energy of the liquid and thus helping to overcome the surface tension of the droplets and disperse them. However, in reality, excessive kinetic energy of the droplets can easily lead to excessive droplet fragmentation, which can actually reduce ionization efficiency.

[0030] Hot gas-assisted evaporation involves using an inert gas such as nitrogen and a heating device to completely desolvate nanoscale charged droplets under the assistance of a heated nitrogen flow, forming free gaseous ions. However, this method suffers from poor heating effects when the nitrogen concentration is too low, while excessively high concentrations can carry away some of the nanoscale charged droplets, necessitating a longer ion collection time. This negatively impacts analytical efficiency and sensitivity, and the method is unsuitable for analyzing heat-sensitive samples such as biomolecules.

[0031] Specifically, the fundamental principle of nanoliter ion sources is based on the formation of Taylor cones by droplets through Coulomb explosions under the action of an electric field, thereby dispersing them into droplets or molecules at the nanoscale, thus separating ions from the solvent. However, if the droplets are excessively fragmented or have too much kinetic energy, it is not conducive to the sufficient accumulation of charge and the generation of Coulomb explosions. Therefore, the scale of droplet dispersion often does not reach the nanoscale, or the proportion of droplets or molecules that reach the nanoscale is low, resulting in a decrease in ionization efficiency.

[0032] Embodiments of the present application are described below in detail with reference to the accompanying drawings, in which like or similar elements or features are denoted by the same or similar reference signs, and examples of the embodiments are shown in the drawings. The embodiments described below are exemplary only, and are not intended to limit the present application.

[0033] In the description of the present application, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "upper", "lower", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential" and the like indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and therefore cannot be understood as indicating or implying that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as limiting the present application. In addition, the features defined as "first" and "second" can be explicitly or implicitly included one or more features. In the description of the present application, the meaning of "a plurality of" is two or more, unless otherwise specified. In the description of the present application, it should be noted that unless otherwise specified and limited, the terms "mounting", "connecting", "connection" should be understood broadly, for example, it can be fixedly connected, or it can be detachably connected, or integrally connected; it can be mechanically connected, or it can be electrically connected; it can be directly connected, or it can be indirectly connected through an intermediate medium; it can be the communication inside two elements. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0034] The mass spectrometry nanoliter ion source 1 according to an embodiment of the present application is described below with reference to the accompanying drawings.

[0035] As shown in Figures 1-5 The mass spectrometry nanoliter ion source 1 according to an embodiment of the present application includes an ion source housing 10, an adjusting mechanism 20, and a nanoliter spray needle 30.

[0036] The ion source housing 10 is provided with a vacuum interface cavity 14, the end of the vacuum interface cavity 14 forms a conical cover 11, the vacuum interface cavity 14 is provided with a quadrupole rod 15 and a vacuum pump interface 16, and the conical cover 11 is provided with a sample inlet hole 12. The adjusting mechanism 20 is fixedly arranged in a position opposite to the ion source housing 10. The nanoliter spray needle 30 is arranged on the adjusting mechanism 20, the nanoliter spray needle 30 is adapted to adjust the distance and / or attitude between the nanoliter spray needle 30 and the sample inlet hole 12 through the adjusting mechanism 20, and the nanoliter spray needle 30 is connected to electricity to be configured to form an electric field between the nanoliter spray needle 30 and the conical cover 11 to move the target ions 3 towards the conical cover 11.

[0037] Specifically, the nanoliter spray needle 30 is made of a conductor material and is loaded with a voltage, for example, 5-8 kV. The loaded voltage is the same in polarity as the target ions 3 to be analyzed, that is, a positive voltage is loaded when positive ions are to be analyzed, and a negative voltage is loaded when negative ions are to be analyzed. The liquid droplets output by the nanoliter spray needle 30 are powered by a peristaltic pump.

[0038] The adjusting mechanism 20 is provided with a conductive sheet, and the nanoliter spray needle 30 is connected to the conductive sheet for electricity. The nanoliter spray needle 30 is detachably connected to the conductive sheet.

[0039] The conical cover 11 is made of a conductor material, and the conical cover 11 forms an end of the vacuum interface cavity 14. The vacuum interface cavity 14 is provided with a quadrupole rod 15, and the vacuum interface cavity 14 is provided with a vacuum pump interface 16. The conical cover 11 is grounded. A high-voltage electric field is formed between the conical cover 11 and the nanoliter spray needle 30.

[0040] The liquid droplets output from the nanoliter spray needle 30 form a Taylor cone 2 under the action of the electric field force and are finally dispersed into microparticles of nanometer scale.

[0041] These microparticles include neutral liquid droplets or molecules, negatively or positively charged nanometer liquid droplets or macromolecules, among which the liquid droplets or macromolecules with the target polarity (the same as the polarity loaded by the nanoliter spray needle 30) are the most.

[0042] This is because the liquid droplets output from the nanoliter spray needle 30 are not aerodynamically accelerated, but mainly rely on the power provided by the upstream peristaltic pump to be discharged from the nanoliter spray needle 30, and the aperture of the nanoliter spray needle 30 is small, for example, less than or equal to 10 microns, so the kinetic energy of the output liquid droplets is low, mainly relying on the electric field force to overcome the surface tension to cause Coulomb explosion, and under the action of the electric field force, the ions with the same polarity as the polarity loaded by the nanoliter spray needle 30 will gather more in the far end of the Taylor cone 2, so that Coulomb explosion is more likely to occur.

[0043] After Coulomb explosion, in addition to the liquid droplets or macromolecules with the target polarity, liquid droplets or molecules with opposite polarity and neutrality will also be formed; the liquid droplets or molecules with opposite polarity to the target polarity will move away from the conical cover 11 under the repulsion of the electric field; the liquid droplets or macromolecules with the target polarity and neutrality will enter the vacuum interface cavity 14 from the sample inlet hole 12 under the negative pressure suction of the vacuum interface cavity 14, and the liquid droplets or macromolecules with the target polarity will move downstream along the quadrupole rod 15 under the electric field constraint of the quadrupole rod 15, while the neutral ions 4 will be discharged from the vacuum interface cavity 14 through the vacuum pump interface 16.

[0044] The present application is made based on the discovery and understanding of the following facts and problems: In the above process, it is crucial to control the balance between the electric field force received by the droplet and the surface tension to be overcome, and insufficient electric field force will result in low ionization efficiency, and too high electric field force will result in excessive fragmentation of the droplet, and the dispersion scale of the droplet cannot reach the nanoscale; specifically, the judgment method corresponding to the electric field force and the surface tension to be overcome can be to judge based on the cone angle of the Taylor cone, to judge the optimal cone angle based on the ionization efficiency, and to adjust the electric field distribution between the nanoliter spray needle and the conical cover to make the cone angle reach the range of the optimal cone angle, so as to ensure that the ionization efficiency reaches the optimum, without the need for pneumatic auxiliary atomization and hot gas auxiliary volatilization.

[0045] Since the voltage loaded on the nanoliter spray needle 30 is a kilovolt high voltage, the adjustment difficulty is high and the energy consumption is high, and only by adjusting the relative position relationship and orientation between the nanoliter spray needle 30 and the conical cover 11, the electric field distribution between the nanoliter spray needle 30 and the conical cover 11 can be adjusted.

[0046] By adjusting the distance between the nanoliter spray needle 30 and the sample inlet hole 12 of the conical cover 11, and detecting the signal intensity of the target ion 3, when the ionization efficiency is high, the signal intensity of the target ion 3 is high; by adjusting the distance between the nanoliter spray needle 30 and the sample inlet hole 12 of the conical cover 11, the signal intensity of the target ion 3 reaches the highest; at this time, the cone angle of the Taylor cone 2 at this time can be measured through the optical microscopic system, that is, the target cone angle, and subsequently only the observation of whether the cone angle reaches the target cone angle can know whether the ionization efficiency reaches the optimum.

[0047] According to the mass spectrometry nanoliter ion source 1 of the embodiment of the present application, by setting the adjusting mechanism 20, the distance between the nanoliter spray needle 30 and the conical cover 11 can be conveniently adjusted, so as to adjust the electric field distribution between the nanoliter spray needle 30 and the conical cover 11, and the cone angle of the Taylor cone 2 changes. In this way, by adjusting the distance between the nanoliter spray needle 30 and the sample inlet hole 12 of the conical cover 11, and detecting the signal intensity of the target ion 3, when the ionization efficiency is high, the signal intensity of the target ion 3 is high, by adjusting the adjusting mechanism 20, the signal intensity of the target ion 3 is the highest, at this time, the cone angle of the Taylor cone 2 at this time is measured, that is, the target cone angle, and subsequently only the observation of whether the cone angle reaches the target cone angle can know whether the ionization efficiency reaches the optimum. Compared with the way of improving ionization efficiency by relying on pneumatic auxiliary atomization in the related art, the problem that excessive fragmentation of droplets caused by excessive kinetic energy leads to reduced ionization efficiency can be avoided, and the ionization efficiency of the mass spectrometry nanoliter ion source 1 is improved. Compared with the way of improving ionization efficiency by relying on hot gas auxiliary volatilization in the related art, the ion trapping time can be conveniently shortened, the analysis efficiency and sensitivity are improved, and the mass spectrometry nanoliter ion source 1 can be applied to the analysis of heat-sensitive samples such as biomolecules, and the applicability of the mass spectrometry nanoliter ion source 1 is improved.

[0048] Therefore, the nanoliter ion source 1 according to the embodiments of the present application has the advantages of high ionization efficiency, short trapping time, good applicability, etc.

[0049] The nanoliter ion source 1 according to the embodiments of the present application is described below with reference to the accompanying drawings.

[0050] In some embodiments of the present application, as shown in Figures 1-5 The nanoliter ion source 1 according to the embodiments of the present application includes an ion source housing 10, an adjusting mechanism 20, and a nanoliter spray needle 30.

[0051] Specifically, as shown in Figures 1-3 The nanoliter spray needle 30 is movable at least in the axial direction of the sample inlet hole 12. This facilitates adjustment of the distance between the nanoliter spray needle 30 and the sample inlet hole 12 in the axial direction of the sample inlet hole 12, adjustment of the cone angle of the Taylor cone 2, and thus adjustment of the ionization efficiency.

[0052] More specifically, as shown in Figures 2-4 The nanoliter spray needle 30 is adapted to be adjusted by the adjusting mechanism 20 in the angle with the axial direction of the sample inlet hole 12. This facilitates adjustment of the orientation of the nanoliter spray needle 30 by adjusting the angle of the nanoliter spray needle 30, so as to make the Taylor cone 2 assume a symmetrical shape, and thus adjust the cone angle of the Taylor cone 2.

[0053] Specifically, the adjusting mechanism 20 can adjust the position of the nanoliter spray needle 30 in the up-down, left-right, and front-back directions (the up-down, left-right, and front-back directions are shown by arrows in the drawings). In the adjustment, first, the Taylor cone 2 is made to assume a symmetrical shape by adjusting the left-right, up-down, and angle, and then the distance between the nanoliter spray needle 30 and the sample inlet hole 12 is adjusted by the front-back adjustment, so as to adjust the cone angle of the Taylor cone 2 and avoid the influence of the asymmetrical shape of the Taylor cone 2 on the adjustment of the cone angle.

[0054] Advantageously, as shown in Figure 2 and Figure 3 The ion source housing 10 is provided with an observation window 13 adapted to observe the Taylor cone 2 formed by the liquid droplets sprayed by the nanoliter spray needle 30. Specifically, the observation window 13 is adapted to be connected to a microscope, so as to facilitate observation of the cone angle of the Taylor cone 2 by the microscope. This facilitates observation and measurement of the cone angle of the Taylor cone 2, and thus adjustment of the ionization efficiency.

[0055] More advantageously, the nanoliter spray needle 30 is detachably mounted on the adjusting mechanism 20. This facilitates maintenance and replacement of the nanoliter spray needle 30.

[0056] Further, as shown in Figure 1As shown, the nanoliter ion source 1 further comprises a chromatographic column 40 connected with the nanoliter spray needle 30, and the chromatographic column 40 is detachably mounted on the adjusting mechanism 20. Specifically, the chromatographic column 40 is connected with the nanoliter spray needle 30. In this way, the chromatographic column 40 can be used to separate the target solution to the nanoliter spray needle 30, so as to facilitate the nanoliter spray needle 30 to spray the droplets of the target solution, and the detachable arrangement can facilitate the maintenance and replacement of the chromatographic column 40.

[0057] Further, the adjusting mechanism 20 is provided with a conductive sheet for electrical connection, and the nanoliter spray needle 30 is detachably in conductive contact with the conductive sheet. In this way, the nanoliter spray needle 30 can be conveniently disassembled and assembled, and repeated electrical connection is not required when the nanoliter spray needle 30 is disassembled and assembled, and the replacement of the chromatographic column 40 is facilitated.

[0058] Specifically, since the nanoliter ion source in the related art needs to replace the chromatographic column directly on the mounted spray needle, the operation is relatively inconvenient, but the spray needle needs to be disassembled and then the chromatographic column is replaced, which is time-consuming. By arranging the conductive sheet, the nanoliter spray needle 30 can be disassembled and then the chromatographic column 40 is replaced, which is convenient and saves operation time.

[0059] Figures 2-4 A nanoliter ion source 1 according to some examples of the present application is shown. As Figures 2-4 shown, the nanoliter ion source 1 further comprises a supporting platform 50, and the adjusting mechanism 20 is arranged on the supporting platform 50. The supporting platform 50 is push-pullably connected with the ion source cover 10 between a pushed-in position and a pulled-out position. When the supporting platform 50 is in the pushed-in position, the nanoliter spray needle 30 extends into the ion source cover 10, and when the supporting platform 50 is in the pulled-out position, the nanoliter spray needle 30 is located outside the ion source cover 10. In this way, when the nanoliter spray needle 30 and the chromatographic column 40 need to be maintained and replaced, the supporting platform 50 can be pulled out to the pulled-out position, and after maintenance and replacement, the supporting platform 50 can be pushed in to the pushed-in position, thereby facilitating the maintenance and replacement of the nanoliter spray needle 30 and the chromatographic column 40.

[0060] Specifically, as Figures 2-4 shown, the nanoliter ion source 1 further comprises a guide rod 60, and the guide rod 60 is connected with the ion source cover 10. The supporting platform 50 is slidably arranged on the guide rod 60. In this way, the guide rod 60 can be used to guide the movement of the supporting platform 50, thereby facilitating smooth and stable movement of the supporting platform 50.

[0061] More specifically, as Figure 2 and Figure 4As shown, one of the guide rod 60 and the supporting platform 50 is provided with a positioning groove 61 and the other is provided with a positioning bead 51, and the positioning bead 51 is adapted to be disengagedly fitted in the positioning groove 61 when the supporting platform 50 is in the pushing-in position. Specifically, the positioning groove 61 can be multiple and arranged along the axial direction of the guide rod 60. In this way, the supporting platform 50 can be positioned by the cooperation of the positioning groove 61 and the positioning bead 51, so as to prevent the supporting platform 50 from moving at will and affecting the adjustment effect of the nanoliter spray needle 30.

[0062] Reference will be made to the drawings below Figures 2-4 The adjustment mechanism 20 of the mass spectrometry nanoliter ion source 1 according to the embodiments of the present application is described below.

[0063] The adjustment mechanism 20 of the mass spectrometry nanoliter ion source according to the embodiments of the present application comprises a differential displacement stage 21, a spray needle mounting seat 22 and a baffle 221.

[0064] The spray needle mounting seat 22 is adapted to mount the nanoliter spray needle 30, and the spray needle mounting seat 22 is arranged on the differential displacement stage 21. The differential head 23 is adapted to drive the differential displacement stage 21 to move so as to adjust the distance between the nanoliter spray needle 30 and the sample inlet hole 12 of the conical cover 11 of the mass spectrometry nanoliter ion source 1.

[0065] By arranging the differential head 23 to drive the differential displacement stage 21, the displacement adjustment of the differential displacement stage 21 in microns can be realized by adjusting the differential head 23, which facilitates the fine adjustment of the cone angle of the Taylor cone 2 and the accurate adjustment of the ionization efficiency of the mass spectrometry nanoliter ion source 1.

[0066] Specifically, as Figures 2-4 shown, the adjustment mechanism 20 of the mass spectrometry nanoliter ion source further comprises a three-axis displacement stage 24, and the differential displacement stage 21 is arranged on the three-axis displacement stage 24. Specifically, the three-axis displacement stage 24 can adjust the position of the differential displacement stage 21 in the up-down, left-right and front-back directions (the up-down, left-right and front-back directions are shown by arrows in the drawings). In this way, the position of the nanoliter spray needle 30 in each direction can be adjusted, and the Taylor cone 2 can be made to have a symmetrical shape, thereby facilitating the adjustment of the cone angle of the Taylor cone 2.

[0067] More specifically, as Figures 2-4 shown, the three-axis displacement stage 24 comprises a first horizontal displacement stage, a second horizontal displacement stage and a lifting displacement stage. The first horizontal displacement stage is adapted to move along a first horizontal direction. The second horizontal displacement stage is adapted to move along a second horizontal direction, and the second horizontal direction is perpendicular to the first horizontal direction. The lifting displacement stage is adapted to move along the up-down direction, and the first horizontal displacement stage, the second horizontal displacement stage and the lifting displacement stage are arranged in series, and the differential displacement stage 21 is adapted to move along the first horizontal direction. Specifically, Figures 2-4The diagram illustrates an implementation where the first horizontal direction is the front-to-back direction and the second horizontal direction is the left-to-right direction. The second horizontal displacement platform is mounted on the support platform 50, the lifting displacement platform is mounted on the second horizontal displacement platform, the first horizontal displacement platform is mounted on the lifting displacement platform, and the differential displacement platform 21 is mounted on the first horizontal displacement platform. This allows the differential displacement platform 21 to move in various directions by moving the various displacement platforms, thereby achieving adjustment of the position of the nano-volume nozzle 30 in various directions.

[0068] Furthermore, such as Figures 2-4 As shown, the adjustment mechanism 20 of the nanoliter ion source for mass spectrometry also includes a first horizontal adjustment knob 25, a second horizontal adjustment knob 26, and a lifting adjustment knob 27. The first horizontal adjustment knob 25 is drivenly connected to the first horizontal displacement stage. The second horizontal adjustment knob 26 is drivenly connected to the second horizontal displacement stage. The lifting adjustment knob 27 is drivenly connected to the lifting displacement stage. This allows for the movement of each displacement stage by rotating the knobs, facilitating the adjustment of the three-axis displacement stage 24.

[0069] Advantageously, such as Figures 1-4 As shown, the differential displacement stage 21 moves along the axial direction of the injection port 12. This facilitates adjustment of the distance between the nanoliter nozzle 30 and the injection port 12, thereby facilitating adjustment of the cone angle of the Taylor cone 2.

[0070] More advantageously, such as Figures 2-4 As shown, the nozzle mount 22 is rotatably mounted on the differential displacement stage 21, with its rotation axis perpendicular to the axial direction of the injection port 12 and parallel to the horizontal direction. This facilitates adjustment of the orientation of the nanoliter nozzle 30, makes it easier to make the Taylor cone 2 symmetrical, and thus facilitates adjustment of the cone angle of the Taylor cone 2.

[0071] Specifically, during adjustment, the nano-needle 30 is first adjusted left and right, up and down, and angle by rotating the second horizontal adjustment knob 26, the lifting adjustment knob 27, and the needle mounting base 22, so that the Taylor cone 2 presents a symmetrical shape. Then, the distance between the nano-needle 30 and the sample inlet 12 is roughly adjusted by the first horizontal adjustment knob 25 to adjust the cone angle of the Taylor cone 2. Finally, the distance between the nano-needle 30 and the sample inlet 12 is finely adjusted by the micrometer head 23, so that the ionization efficiency reaches the maximum value.

[0072] Optionally, such as Figures 1-4 As shown, the adjustment mechanism 20 of the nano-ion source for mass spectrometry also includes a column mounting base 28, which is connected to a needle mounting base 22. The column mounting base 28 is adapted to mount a chromatographic column 40. Specifically, the chromatographic column 40 is connected to a nano-needle 30. This facilitates the installation of the chromatographic column 40.

[0073] Further, as shown in Figures 1-4 The connecting rod 29 is arranged on the needle mounting seat 22, and the column mounting seat 28 is arranged on the connecting rod 29, and the connecting rod 29 is parallel to the nanoliter needle 30. In this way, the connection between the column mounting seat 28 and the needle mounting seat 22 is facilitated, the arrangement of the column mounting seat 28 is facilitated, and the installation of the column 40 is facilitated.

[0074] Further, as shown in Figures 1-4 The baffle 221 is arranged on the needle mounting seat 22, and the notch 222 is arranged on the baffle 221, and the nanoliter needle 30 is adapted to pass through the notch 222. In this way, the baffle 221 can be used to block the splashing of droplets, so as to avoid affecting the operation of the mass spectrometry nanoliter ion source 1.

[0075] The adjustment method of the mass spectrometry nanoliter ion source according to the embodiment of the present application is described below. The mass spectrometry nanoliter ion source comprises a nanoliter needle and an ion source cover, a vacuum interface cavity is arranged in the ion source cover, an end of the vacuum interface cavity forms a conical cover, a sample inlet hole is arranged on the conical cover, and the adjustment method comprises the following steps: Adjusting the relative spatial position relationship between the nanoliter needle and the sample inlet hole, and detecting the signal intensity of target ions downstream of the ion source cover until the signal intensity reaches a set threshold value; Measuring the cone angle of the Taylor cone formed by the droplets sprayed by the nanoliter needle at this time to obtain a target cone angle; Adjusting the relative spatial position relationship between the nanoliter needle and the sample inlet hole until the cone angle of the Taylor cone formed by the droplets sprayed by the nanoliter needle reaches the target cone angle.

[0076] The adjustment method of the mass spectrometry nanoliter ion source according to the embodiment of the present application has the advantages of high ionization efficiency, short trapping time, good applicability, and the like.

[0077] The other configurations and operations of the mass spectrometry nanoliter ion source 1 and the adjustment method of the mass spectrometry nanoliter ion source according to the embodiment of the present application are known to those skilled in the art, and will not be described in detail here.

[0078] In the description of the present specification, the description of the terms "one embodiment", "some embodiments", "exemplary embodiment", "example", "specific example", or "some examples" means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In the present specification, the exemplary description of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0079] While embodiments of the application have been shown and described, it is to be understood that the embodiments described are merely exemplary of the principles and application of the present application. Numerous modifications and changes can be made by those skilled in the art without departing from the spirit and scope of the application. The scope of the application is not to be limited by the embodiments shown and described, but only by the claims and their equivalents.

Claims

1. A mass spectrometry nanoliter ion source, characterized in that, The mass spectrometer nanoliter ion source comprises a nanoliter spray needle and an ion source housing, the ion source housing is internally provided with a vacuum interface cavity, an end of the vacuum interface cavity forms a conical cover, the vacuum interface cavity is internally provided with a quadrupole rod and a vacuum pump interface, the conical cover is provided with a sample injection hole, and the adjusting method comprises the following steps: An adjusting mechanism is fixedly arranged opposite to the ion source housing; The nanoliter spray needle is arranged on the adjusting mechanism, the nanoliter spray needle is adapted to adjust the distance and / or posture relative to the sample injection hole through the adjusting mechanism, the nanoliter spray needle is connected to electricity to form an electric field between the nanoliter spray needle and the conical cover to move target ions towards the conical cover. The nanoliter spray needle is movable at least in the axial direction of the sample injection hole.

2. The mass spectrometry nanoliter ion source of claim 1, wherein, The nanoliter spray needle is adapted to adjust the angle with the axial direction of the sample injection hole through the adjusting mechanism.

3. The mass spectrometry nanoliter ion source of claim 1, wherein, The ion source housing is provided with an observation window adapted to observe the Taylor cone formed by the liquid droplets sprayed by the nanoliter spray needle.

4. The mass spectrometry nanoliter ion source of claim 1, wherein, Further comprising a chromatographic column connected to the nanoliter spray needle, the nanoliter spray needle and / or the chromatographic column is detachably mounted on the adjusting mechanism.

5. The mass spectrometry nanoliter ion source of claim 1, wherein, The conical cover is electrically connected to ground.

6. The mass spectrometry nanoliter ion source of claim 1, wherein, The adjusting mechanism is provided with a conductive sheet for electricity connection, and the nanoliter spray needle is detachably and conductively connected to the conductive sheet.

7. The mass spectrometry nanoliter ion source of claim 1, wherein, Further comprising a supporting platform, the adjusting mechanism is arranged on the supporting platform, the supporting platform is push-pull connected to the ion source housing between a pushed-in position and a pulled-out position, the nanoliter spray needle extends into the ion source housing when the supporting platform is in the pushed-in position, and the nanoliter spray needle is located outside the ion source housing when the supporting platform is in the pulled-out position.

8. The mass spectrometry nanoliter ion source of claim 1, wherein, Further comprising a guide rod connected to the ion source housing, and the supporting platform is slidably arranged on the guide rod.

9. The mass spectrometry nanoliter ion source of claim 8, wherein, One of the guide rod and the supporting platform is provided with a positioning groove, and the other is provided with a positioning bead, and the positioning bead is adapted to be disengageably matched in the positioning groove when the supporting platform is in the pushed-in position.

10. The mass spectrometry nanoliter ion source of claim 9, wherein, The mass spectrometer nanoliter ion source comprises a nanoliter spray needle and an ion source housing, the ion source housing is internally provided with a vacuum interface cavity, an end of the vacuum interface cavity forms a conical cover, the conical cover is provided with a sample injection hole, and the adjusting method comprises the following steps:

11. A method of conditioning a mass spectrometry nanoliter ion source, the method comprising: Adjust the relative spatial position relationship between the nanoliter spray needle and the sample injection hole, and detect the signal intensity of target ions downstream of the ion source housing until the signal intensity reaches a set threshold value; Measure the cone angle of the Taylor cone formed by the liquid droplets sprayed by the nanoliter spray needle at this time to obtain a target cone angle; Adjust the relative spatial position relationship between the nanoliter spray needle and the sample injection hole until the cone angle of the Taylor cone formed by the liquid droplets sprayed by the nanoliter spray needle reaches the target cone angle. ​

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