Mass spectrometry nanoliter ion source and method of conditioning a mass spectrometry nanoliter ion source

Abstract

The application discloses a kind of mass spectrometry nanoliter ion source and the adjusting method of mass spectrometry nanoliter ion source, it is related to mass spectrometry technical field, the mass spectrometry nanoliter ion source includes: ion source cover, vacuum interface cavity is equipped in the ion source cover, the end of the vacuum interface cavity forms conical cover, quadrupole rod and vacuum pump interface are equipped in the vacuum interface cavity, sample inlet hole is equipped on the conical cover;Adjusting mechanism, the adjusting mechanism is fixedly arranged with the relative position of the ion source cover;Nanoliter spray needle, the nanoliter spray needle is equipped on the adjusting mechanism, the nanoliter spray needle is suitable for adjusting the distance and / or attitude between the sample inlet hole by the adjusting mechanism, the nanoliter spray needle is connected with electricity to be configured to make the nanoliter spray needle and the conical cover form the electric field that makes target ion move towards the conical cover.The mass spectrometry nanoliter ion source according to the embodiment of the application has the advantages of high ionization efficiency, short trapping time, good applicability and the like.

Description

Technical Field

[0001] This invention relates to the field of mass spectrometry, and more specifically, to a nanoliter mass spectrometry ion source and a method for adjusting the nanoliter mass spectrometry ion source. Background Technology

[0002] A nanoliter ion source for mass spectrometry (MS / MS) involves permeating the sample through a micropore into a charged solution. A high-voltage electric field generates a driving force that carries the sample molecules into a charged sol, where they undergo ionization upon entering the mass spectrometer, ultimately forming charged ions. Due to the use of smaller nozzles and extremely low flow rates (typically a few nanoliters per minute), with nozzle diameters typically only a few micrometers, smaller droplets can be generated, improving ionization efficiency. Because of its small nozzle and low flow rate, the nanoliter ion source can obtain highly sensitive analytical results with very small sample volumes, making it particularly suitable for analyzing trace samples and significantly improving the efficiency and sensitivity of mass spectrometry analysis. It is ideal for analyzing trace samples, valuable samples, and low-concentration analyses, and can be applied to the analysis of various samples, including biomolecules, small molecules, metal ions, and organic molecules, especially suitable for the analysis of biomolecules such as proteins, peptides, and metabolites.

[0003] 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.

[0004] 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.

[0005] 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. Summary of the Invention

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

[0007] This invention also proposes a method for adjusting a nanoliter mass spectrometer ion source.

[0008] To achieve the above objectives, according to an embodiment of the first aspect of the present invention, a nano-ion source for mass spectrometry is provided, the nano-ion source comprising: an ion source housing, a vacuum interface cavity provided inside the ion source housing, a conical shroud formed at the end of the vacuum interface cavity, a quadrupole and a vacuum pump interface provided inside the vacuum interface cavity, and a sample inlet on the conical shroud; an adjustment mechanism fixedly disposed relative to the ion source housing; and a nano-injector disposed on the adjustment mechanism, the nano-injector being adapted to adjust the distance and / or attitude relative to the sample inlet by the adjustment mechanism, the nano-injector being energized to form an electric field between the nano-injector and the conical shroud that causes target ions to move toward the conical shroud.

[0009] The nanoliter mass spectrometry ion source according to embodiments of the present invention has advantages such as high ionization efficiency, short collection time, and good applicability.

[0010] In addition, the mass spectrometry nano-ion source according to the above embodiments of the present invention may also have the following additional technical features:

[0011] According to one embodiment of the present invention, the nano-needle is movable at least in the axial direction of the injection port.

[0012] According to one embodiment of the present invention, the nano-needle is adapted to adjust the angle with respect to the axial direction of the injection port via the adjustment mechanism.

[0013] According to one embodiment of the present invention, the outer casing of the ion source is provided with an observation window suitable for observing the Taylor cone formed by the droplets ejected from the nanoliter nozzle.

[0014] According to one embodiment of the present invention, the mass spectrometry nano-ion source further includes a chromatographic column connected to the nano-injector, the nano-injector and / or the chromatographic column being detachably mounted on the adjustment mechanism.

[0015] According to one embodiment of the present invention, the conical shield is grounded.

[0016] According to one embodiment of the present invention, the adjusting mechanism is provided with a conductive sheet for connecting to electricity, and the nano-liter nozzle is detachably conductively contacting the conductive sheet.

[0017] According to one embodiment of the present invention, the mass spectrometer nano-ion source further includes a support platform, and the adjustment mechanism is disposed on the support platform. The support platform is slidably connected to the ion source outer cover between a push-in position and a pull-out position. When the support platform is in the push-in position, the nano-injector extends into the ion source outer cover, and when the support platform is in the pull-out position, the nano-injector is located outside the ion source outer cover.

[0018] According to one embodiment of the present invention, the mass spectrometer nano-ion source further includes a guide rod, the guide rod being connected to the ion source outer casing, and the support platform being slidably disposed on the guide rod.

[0019] According to one embodiment of the present invention, one of the guide rod and the supporting platform is provided with a positioning groove and the other is provided with a positioning bead, wherein the positioning bead is adapted to be detachably engaged in the positioning groove when the supporting platform is in the pushed-in position.

[0020] According to an embodiment of a second aspect of the present invention, a method for adjusting a nanoliter mass spectrometry ion source is provided. The nanoliter mass spectrometry ion source includes a nanoliter nozzle and an ion source cover. A vacuum interface cavity is provided inside the ion source cover, and a conical cover is formed at the end of the vacuum interface cavity. An inlet port is provided on the conical cover. The adjustment method includes the following steps:

[0021] Adjust the relative spatial position between the nano-liter nozzle and the injection port, and detect the signal intensity of the target ion downstream of the ion source cover until the signal intensity reaches a set threshold.

[0022] The target cone angle is obtained by measuring the angle of the Taylor cone formed by the droplets ejected from the nanoliter nozzle at this time;

[0023] Adjust the relative spatial position between the nano-needle and the injection port until the cone angle of the Taylor cone formed by the droplets ejected from the nano-needle reaches the target cone angle.

[0024] The adjustment method of the nanoliter ion source for mass spectrometry according to embodiments of the present invention has the advantages of high ionization efficiency, short collection time, and good applicability.

[0025] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Attached Figure Description

[0026] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which:

[0027] Figure 1 This is a schematic diagram illustrating the working principle of a nanoliter mass spectrometer ion source according to an embodiment of the present invention.

[0028] Figure 2 This is a schematic diagram of the structure of a nanoliter mass spectrometer ion source according to an embodiment of the present invention.

[0029] Figure 3 This is a schematic diagram of the structure of a nanoliter mass spectrometer ion source according to an embodiment of the present invention.

[0030] Figure 4This is a schematic diagram of the adjustment mechanism of the mass spectrometer nano-ion source according to an embodiment of the present invention.

[0031] 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.

[0032] 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

[0033] This application is based on the findings and understanding of the following facts and issues:

[0034] 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.

[0035] 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.

[0036] 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.

[0037] 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.

[0038] Embodiments of the present invention are described in detail below. Examples of these embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present invention, and should not be construed as limiting the present invention.

[0039] In the description of this invention, it should be understood that the terms "center," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," "counterclockwise," "axial," "radial," and "circumferential," etc., indicating orientation or positional relationships, are based on the orientation or positional relationships shown in the accompanying drawings and are only for the convenience of describing the invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of the invention. Furthermore, features defined with "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this invention, unless otherwise stated, "a plurality of" means two or more.

[0040] In the description of this invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances.

[0041] The mass spectrometer nano-ion source 1 according to an embodiment of the present invention is described below with reference to the accompanying drawings.

[0042] like Figures 1-5 As shown, the mass spectrometer nano-ion source 1 according to an embodiment of the present invention includes an ion source cover 10, an adjustment mechanism 20, and a nano-injection needle 30.

[0043] The ion source outer casing 10 has a vacuum interface cavity 14, the end of which forms a conical cover 11. The vacuum interface cavity 14 contains a quadrupole 15 and a vacuum pump interface 16. The conical cover 11 has a sample inlet 12. An adjustment mechanism 20 is fixedly positioned relative to the ion source outer casing 10. A nano-needle 30 is mounted on the adjustment mechanism 20. The nano-needle 30 is adapted to adjust its distance and / or orientation relative to the sample inlet 12 via the adjustment mechanism 20. The nano-needle 30 is energized to create an electric field between the nano-needle 30 and the conical cover 11, causing the target ion 3 to move towards the conical cover 11.

[0044] Specifically, the nano-needle 30 is made of a conductive material and is voltage-loaded, for example, 5-8 kV. The applied voltage has the same polarity as the target ion to be analyzed; that is, a positive voltage is applied when positive ions are to be analyzed, and a negative voltage is applied when negative ions are to be analyzed. The droplets output by the nano-needle 30 are powered by a peristaltic pump.

[0045] The adjustment mechanism 20 is equipped with a conductive sheet, and the nano-needle 30 is connected to electricity through the conductive sheet. The nano-needle 30 is detachably connected to the conductive sheet.

[0046] The conical cover 11 is made of conductive material and forms the end of the vacuum interface cavity 14. A quadrupole 15 is provided inside the vacuum interface cavity 14, and a vacuum pump interface 16 is provided on the vacuum interface cavity 14. The conical cover 11 is grounded. A high-voltage electric field is formed between the conical cover 11 and the nanoliter nozzle 30.

[0047] The droplets output from the nano-jet needle 30 form Taylor cones 2 under the action of an electric field, and are eventually dispersed into nanoscale particles.

[0048] These particles include neutral droplets or molecules such as solvents, negatively or positively charged nanodroplets or macromolecules, with droplets or macromolecules bearing the target polarity (the same polarity loaded on the nano-needle 30) being the most numerous.

[0049] This is because the droplets output by the nano-needle 30 are not pneumatically accelerated. They are mainly discharged from the nano-needle 30 by the power provided by the upstream peristaltic pump. Furthermore, the aperture of the nano-needle 30 is relatively small, for example, less than or equal to 10 micrometers. Therefore, the output droplets have low kinetic energy and mainly rely on the electric field force to overcome the surface tension and undergo Coulomb explosion. Under the action of the electric field force, ions with the same polarity as those loaded by the nano-needle 30 will accumulate more at the far end of the Taylor cone 2, making it easier for Coulomb explosion to occur.

[0050] After a Coulomb explosion, in addition to forming droplets or macromolecules with the target polarity, droplets or molecules with opposite polarity and neutral polarity will also be formed. Droplets or molecules with opposite polarity to the target polarity will move away from the conical cover 11 under the repulsive effect of the electric field. Droplets or macromolecules with the target polarity and neutral polarity will enter the vacuum interface cavity 14 from the sample inlet 12 under the negative pressure suction of the vacuum interface cavity 14. Droplets or macromolecules with the target polarity will move downstream along the quadrupole 15 under the electric field constraint of the quadrupole 15, while neutral ions 4 will be discharged from the vacuum interface cavity 14 along the vacuum pump interface 16.

[0051] This application is based on the findings and understanding of the following facts and issues:

[0052] In the above process, it is crucial to control the electric field force on the droplets to maintain a balance with the surface tension they need to overcome. Insufficient electric field force will lead to low ionization efficiency, while excessive electric field force will lead to excessive droplet fragmentation, and the droplet dispersion scale will not reach the nanoscale. Specifically, the method of determining the correspondence between electric field force and surface tension to be overcome can be based on the cone angle of the Taylor cone. The optimal cone angle is determined based on the ionization efficiency, and then the electric field distribution between the nanoliter nozzle and the conical orifice is adjusted to make the cone angle reach the range of the optimal cone angle, which can ensure that the ionization efficiency reaches the optimal level without the need for pneumatic assisted atomization and hot gas assisted volatilization.

[0053] Since the voltage applied to the nano-pressure nozzle 30 is a high voltage of kilovolts, it is difficult to adjust and consumes a lot of energy. The electric field distribution between the nano-pressure nozzle 30 and the conical cover 11 can only be adjusted by adjusting the relative position and orientation between the nano-pressure nozzle 30 and the conical cover 11.

[0054] By adjusting the distance between the nano-spray needle 30 and the sample inlet 12 of the conical shroud 11, and detecting the signal intensity of the target ion 3, the signal intensity of the target ion 3 is high when the ionization efficiency is high. By adjusting the distance between the nano-spray needle 30 and the sample inlet 12 of the conical shroud 11, the signal intensity of the target ion 3 is maximized. At this time, the cone angle of the Taylor cone 2 can be measured by an optical microscopy system, which is the target cone angle. Subsequently, it is only necessary to observe whether the cone angle reaches the target cone angle to know whether the ionization efficiency has reached the optimal level.

[0055] According to an embodiment of the present invention, the nano-ion source 1 for mass spectrometry can easily adjust the distance between the nano-needle 30 and the conical shroud 11 by setting an adjustment mechanism 20, thereby adjusting the electric field distribution between the nano-needle 30 and the conical shroud 11 and changing the cone angle of the Taylor cone 2. By adjusting the distance between the nano-needle 30 and the sample inlet 12 of the conical shroud 11 and detecting the signal intensity of the target ion 3, a high ionization efficiency results in a high signal intensity of the target ion 3. By adjusting the adjustment mechanism 20 to maximize the signal intensity of the target ion 3, the cone angle of the Taylor cone 2 at this point is measured, which is the target cone angle. Subsequent observation of whether the cone angle reaches the target cone angle is sufficient to determine whether the ionization efficiency has reached its optimal level. Compared to related technologies that rely on pneumatically assisted atomization to improve ionization efficiency, this method avoids the problem of excessive droplet fragmentation due to excessive kinetic energy, which could lead to a decrease in ionization efficiency, thus improving the ionization efficiency of the nano-ion source 1 for mass spectrometry. Compared to related technologies that rely on hot gas-assisted volatilization to improve ionization efficiency, this method can shorten ion collection time, improve analytical efficiency and sensitivity, and is applicable to the analysis of heat-sensitive samples such as biomolecules, thus improving the applicability of the mass spectrometry nano-ion source 1.

[0056] Therefore, the mass spectrometry nano-ion source 1 according to the embodiments of the present invention has advantages such as high ionization efficiency, short collection time, and good applicability.

[0057] The following description, with reference to the accompanying drawings, describes a specific embodiment of a mass spectrometry nano-ion source 1 according to the present invention.

[0058] In some specific embodiments of the present invention, such as Figures 1-5 As shown, the mass spectrometer nano-ion source 1 according to an embodiment of the present invention includes an ion source cover 10, an adjustment mechanism 20, and a nano-injection needle 30.

[0059] Specifically, such as Figures 1-3 As shown, the nano-needle 30 is movable at least in the axial direction of the inlet port 12. This facilitates adjustment of the distance between the nano-needle 30 and the inlet port 12 in the axial direction, and facilitates adjustment of the cone angle of the Taylor cone 2, thereby facilitating the adjustment of the ionization efficiency.

[0060] More specifically, such as Figures 2-4 As shown, the nano-needle 30 is adapted to have its angle with the inlet port 12 adjusted by the adjustment mechanism 20. This allows the orientation of the nano-needle 30 to be adjusted by changing its angle, making it easier to make the Taylor cone 2 have a symmetrical shape, thus facilitating the adjustment of the cone angle of the Taylor cone 2.

[0061] Specifically, the adjustment mechanism 20 can adjust the position of the nano-needle 30 in the up-down, left-right, and front-back directions (as shown by the arrows in the figure). During adjustment, firstly, the Taylor cone 2 is made symmetrical by adjusting left-right, up-down, and angle. Then, the distance between the nano-needle 30 and the injection port 12 is adjusted by adjusting the front-back direction to adjust the cone angle of the Taylor cone 2, so as to avoid the asymmetry of the Taylor cone 2 shape affecting the cone angle adjustment.

[0062] Advantageously, such as Figure 2 and Figure 3 As shown, the ion source housing 10 is provided with an observation window 13 suitable for observing the Taylor cone 2 formed by droplets ejected from the nanoliter nozzle 30. Specifically, the observation window 13 is adapted to be docked with a microscope to facilitate observation of the cone angle of the Taylor cone 2. This facilitates the observation and measurement of the cone angle of the Taylor cone 2, thereby facilitating the adjustment of the ionization efficiency.

[0063] More advantageously, the nano-needle 30 is detachably mounted on the adjustment mechanism 20. This facilitates the maintenance and replacement of the nano-needle 30.

[0064] Furthermore, such as Figure 1As shown, the mass spectrometry nano-ion source 1 also includes a chromatographic column 40 connected to a nano-spray needle 30, and the chromatographic column 40 is detachably mounted on the adjustment mechanism 20. Specifically, the chromatographic column 40 is connected to the nano-spray needle 30. This allows the target solution to be separated by the chromatographic column 40 and sent to the nano-spray needle 30, facilitating the ejection of droplets of the target solution by the nano-spray needle 30. The detachable configuration also facilitates the maintenance and replacement of the chromatographic column 40.

[0065] Furthermore, the adjustment mechanism 20 is equipped with a conductive plate for electrical connection, and the nano-needle 30 is detachably electrically connected to the conductive plate. This facilitates the installation and removal of the nano-needle 30, eliminating the need for repeated electrical connection during installation and removal, and also makes it easier to replace the chromatographic column 40.

[0066] Specifically, because the nano-ion source in the related technology requires direct replacement of the chromatographic column on the installed spray needle, this operation is inconvenient. However, removing the spray needle to replace the column is time-consuming. By incorporating a conductive plate to facilitate the installation and removal of the nano-spray needle 30, the nano-spray needle 30 can be removed before replacing the chromatographic column 40, making the operation convenient and saving time.

[0067] Figures 2-4 A nanoliter mass spectrometry ion source 1 according to some examples of the present invention is shown. For example... Figures 2-4 As shown, the mass spectrometry nano-ion source 1 also includes a support platform 50, and an adjustment mechanism 20 is disposed on the support platform 50. The support platform 50 is slidably connected to the ion source housing 10 between a pushed-in position and a pulled-out position. When the support platform 50 is in the pushed-in position, the nano-injection needle 30 extends into the ion source housing 10; when the support platform 50 is in the pulled-out position, the nano-injection needle 30 is outside the ion source housing 10. This allows the support platform 50 to be pulled out to the pulled-out position when maintenance or replacement of the nano-injection needle 30 and the chromatographic column 40 is required, and then pushed back into the pushed-in position after maintenance or replacement, thus facilitating the maintenance and replacement of the nano-injection needle 30 and the chromatographic column 40.

[0068] Specifically, such as Figures 2-4 As shown, the nano-ion source 1 for mass spectrometry also includes a guide rod 60, which is connected to the ion source casing 10. The support platform 50 is slidably mounted on the guide rod 60. This allows the guide rod 60 to guide the movement of the support platform 50, facilitating smooth and stable movement of the support platform 50.

[0069] More specifically, such as Figure 2 and Figure 4As shown, one of the guide rod 60 and the support platform 50 is provided with a positioning groove 61 and the other with a positioning bead 51. When the support platform 50 is in the pushed-in position, the positioning bead 51 is adapted to be detachably engaged within the positioning groove 61. Specifically, there can be multiple positioning grooves 61, which are spaced apart along the axial direction of the guide rod 60. This allows the support platform 50 to be positioned using the engagement of the positioning grooves 61 and the positioning beads 51, preventing the support platform 50 from moving arbitrarily and affecting the adjustment effect on the nano-lift nozzle 30.

[0070] The following is for reference. Figures 2-4 The adjustment mechanism 20 of the mass spectrometer nanoliter ion source 1 according to an embodiment of the present invention is described.

[0071] The adjustment mechanism 20 of the mass spectrometer nano-ion source according to an embodiment of the present invention includes a differential displacement stage 21, a nozzle mounting base 22, and a baffle 221.

[0072] A nano-sized nozzle 30 is mounted on a nozzle mounting base 22, which is located on a differential displacement stage 21. A differential head 23 is adapted to drive the differential displacement stage 21 to move and adjust the distance between the nano-sized nozzle 30 and the sample inlet 12 of the conical shroud 11 of the mass spectrometer nano-ion source 1.

[0073] By setting the differential head 23 to drive the differential displacement stage 21, the displacement of the differential displacement stage 21 at the micrometer level can be adjusted by adjusting the differential head 23, which facilitates fine adjustment of the cone angle of the Taylor cone 2 and accurate adjustment of the ionization efficiency of the mass spectrometer nano-ion source 1.

[0074] Specifically, such as Figures 2-4 As shown, the adjustment mechanism 20 of the nano-ion source for mass spectrometry also includes a triaxial displacement stage 24, on which a differential displacement stage 21 is mounted. Specifically, the triaxial displacement stage 24 can adjust the position of the differential displacement stage 21 in the up-down, left-right, and front-back directions (as indicated by the arrows in the figure). This facilitates the adjustment of the position of the nano-jet needle 30 in various directions, making it easier to achieve a symmetrical shape for the Taylor cone 2, thereby facilitating the adjustment of the cone angle of the Taylor cone 2.

[0075] More specifically, such as Figures 2-4 As shown, the three-axis displacement stage 24 includes 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, which is perpendicular to the first horizontal direction. The lifting displacement stage is adapted to move in a vertical direction. The first horizontal displacement stage, the second horizontal displacement stage, and the lifting displacement stage are arranged in series. 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.

[0076] 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.

[0077] 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.

[0078] 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.

[0079] 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.

[0080] 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.

[0081] Furthermore, such as Figures 1-4 As shown, a connecting rod 29 is provided on the needle mount 22, and a column mount 28 is mounted on the connecting rod 29. The connecting rod 29 is arranged parallel to the nano-sized needle 30. This facilitates the connection between the column mount 28 and the needle mount 22, the setting of the column mount 28, and the installation of the column 40.

[0082] Furthermore, such as Figures 1-4 As shown, the nozzle mounting base 22 is provided with a baffle 221, and the baffle 221 has a notch 222, through which the nano-needle 30 is adapted. In this way, the baffle 221 can be used to block droplet splashing and avoid affecting the operation of the nano-ion source 1 of the mass spectrometer.

[0083] The following describes a method for adjusting a nano-ion source for mass spectrometry according to an embodiment of the present invention. The nano-ion source includes a nano-needle and an ion source housing. A vacuum interface cavity is provided inside the ion source housing, and a conical cover is formed at the end of the vacuum interface cavity. An inlet port is provided on the conical cover. The adjustment method includes the following steps:

[0084] Adjust the relative spatial position between the nano-liter nozzle and the injection port, and detect the signal intensity of the target ion downstream of the ion source cover until the signal intensity reaches a set threshold.

[0085] The target cone angle is obtained by measuring the angle of the Taylor cone formed by the droplets ejected from the nanoliter nozzle at this time;

[0086] Adjust the relative spatial position between the nano-needle and the injection port until the cone angle of the Taylor cone formed by the droplets ejected from the nano-needle reaches the target cone angle.

[0087] The adjustment method of the nanoliter ion source for mass spectrometry according to embodiments of the present invention has the advantages of high ionization efficiency, short collection time, and good applicability.

[0088] Other configurations and operations of the mass spectrometry nano-ion source 1 and the adjustment method of the mass spectrometry nano-ion source according to embodiments of the present invention are known to those skilled in the art and will not be described in detail here.

[0089] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "illustrative embodiment," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0090] Although embodiments of the invention have been shown and described, those skilled in the art will understand that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the claims and their equivalents.

Claims

1. A method of conditioning a nano liter ion source for mass spectrometry, the method comprising: The mass spectrometry nanoliter ion source is free of pneumatic assisted atomization and thermal gas assisted evaporation, and comprises: An ion source cover, which is provided with a vacuum interface cavity, an end of the vacuum interface cavity is formed into 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 cover; A nanoliter spray needle, which is arranged on the adjusting mechanism, is adapted to adjust a distance and / or an attitude relative to the sample inlet hole through the adjusting mechanism, is connected to electricity, and is configured to form an electric field between the nanoliter spray needle and the conical cover to move target ions towards the conical cover, and the adjusting method comprises the following steps: Adjusting a relative spatial position relationship between the nanoliter spray needle and the sample inlet hole, and detecting a signal intensity of target ions downstream of the ion source cover until the signal intensity reaches a set threshold value; Measuring a cone angle of a Taylor cone formed by liquid droplets sprayed by the nanoliter spray needle at this time to obtain a target cone angle; Adjusting the relative spatial position relationship between the nanoliter spray needle and the sample inlet hole until the cone angle of the Taylor cone formed by liquid droplets sprayed by the nanoliter spray needle reaches the target cone angle.

2. The method of claim 1, wherein the method further comprises: The nanoliter spray needle is movable at least in an axial direction of the sample inlet hole.

3. The method of claim 1, wherein the method further comprises: The nanoliter spray needle is adapted to adjust an angle with the axial direction of the sample inlet hole through the adjusting mechanism.

4. The method of claim 1, wherein the method further comprises: The ion source cover is provided with an observation window adapted to observe a Taylor cone formed by liquid droplets sprayed by the nanoliter spray needle.

5. The method of claim 1, wherein the method is performed by a mass spectrometry nanoliter ion source comprising: A chromatographic column connected to the nanoliter spray needle is further included, and the nanoliter spray needle and / or the chromatographic column is detachably mounted on the adjusting mechanism.

6. The method of claim 1, wherein the method is performed by a mass spectrometry nanoliter ion source comprising: The conical cover is electrically connected to ground.

7. The method of claim 1, wherein the method is performed by a mass spectrometry nanoliter ion source comprising: 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.

8. The method of claim 1, wherein the method is performed by a mass spectrometry nanoliter ion source comprising: A supporting platform is further included, the adjusting mechanism is arranged on the supporting platform, the supporting platform is pushably and pullably connected to the ion source cover between a pushed-in position and a pulled-out position, the nanoliter spray needle extends into the ion source cover when the supporting platform is in the pushed-in position, and the nanoliter spray needle is located outside the ion source cover when the supporting platform is in the pulled-out position.

9. The method of claim 8, wherein the method further comprises: A guide rod is further included, the guide rod is connected to the ion source cover, and the supporting platform is slidably arranged on the guide rod.

10. The method of claim 9, wherein the method further comprises: 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. 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.

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