High-throughput preparation mass spectrum device and method giving consideration to high-resolution characterization

Abstract

The invention relates to the technical field of ion characterization and preparation, in particular to a high-throughput preparation mass spectrum device and method giving consideration to high-resolution characterization. The device comprises an ion source, an ion transmission cavity, a quadrupole mass screening cavity, an ion dissociation cavity, an ion deflection cavity, an ion deceleration and deposition cavity and a high-resolution mass spectrum characterization cavity which are sequentially arranged, wherein the high-resolution mass spectrum characterization cavity is formed in one side of the ion deflection cavity in the vertical direction; soft ionization is combined with a quadrupole analyzer to screen ions, the ions are dissociated through a dissociation cavity, an ion deflection cavity is used for selecting a high-resolution characterization or high-throughput preparation function, a high-resolution mass spectrum characterization cavity is used for achieving high-resolution characterization of screened and fragmented ions, and an ion deceleration and deposition cavity is used for high-throughput preparation of the ions. According to the method, perfect compatibility of high-throughput preparation and high-resolution mass spectrum characterization is realized through ion deflection design, and the method has a wide application prospect in the fields of efficient preparation of biological macromolecules, synthetic macromolecules and the like and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of ion characterization and preparation, in particular to a high-throughput preparative mass spectrometry device and method with high-resolution characterization. BACKGROUND

[0002] Numerous studies have fully demonstrated that mass spectrometry soft ionization technology can be used for characterization of synthetic macromolecules, biological macromolecules, and weakly stable radicals. However, conventional commercial analytical mass spectrometry can only provide molecular weight information, and the ions generated by mass spectrometry cannot be recovered, so it is difficult to combine other characterization methods to provide more accurate, detailed, and comprehensive structural characterization. Preparative Mass Spectrometry (pMS) is a technology that uses mass spectrometry as a separation method to accurately screen and highly purify ions of specific mass-to-charge ratios (m / z). In particular, the ion soft landing technology developed in recent decades can maintain the integrity of molecular structure and function during deposition, achieving high selectivity, high purity, and high fidelity preparation of target molecules in a high vacuum environment. However, the pMS systems reported so far do not have high-resolution mass spectrometry identification capability, and cannot accurately characterize the molecular weight of reaction intermediates. A key reason for this is that preparative mass spectrometry usually has a strong ion beam, and the spatial charge effect and wide initial ion produced by the strong ion beam can sharply reduce the resolution of the mass spectrometer. Therefore, how to combine high-resolution mass spectrometry with high-throughput preparative mass spectrometry is a key technical problem that needs to be solved.

[0003] Through patent and paper retrieval, a relevant patent was found: an ion soft deposition device was disclosed by the Dalian Institute of Chemical Physics, Chinese Academy of Sciences on March 3, 2023. The invention controls ion deposition energy by ion deceleration, visualizes ion imaging by MCP fluorescent screen, reduces beam spot to improve unit area deposition efficiency, and can assist preparative mass spectrometry to achieve more efficient sample preparation. The invention mainly focuses on deposition control and does not have a high-resolution mass spectrometry characterization scheme. A preparative mass spectrometry and a use method were disclosed by the Dalian Institute of Chemical Physics, Chinese Academy of Sciences on May 21, 2024, mainly including a soft ionization source, an ion transmission system, a quadrupole separation system, a high-resolution mass spectrometer, and a deposition system. The invention uses high-resolution mass spectrometry to characterize ions after preparative mass spectrometry separation, thereby feeding back and optimizing preparative mass spectrometry parameters to improve preparation efficiency. However, the invention only proposes the idea of using high-resolution mass spectrometry to optimize preparative mass spectrometry parameters, but lacks specific high-resolution mass spectrometry and preparative scheme coupling structure design. Therefore, there is still a lack of coupling technology and method of high-resolution mass spectrometry characterization for high-throughput preparative mass spectrometry technology. SUMMARY

[0004] In view of the problems existing in the prior art, the purpose of the present application is to provide a high-throughput preparative mass spectrometry device and method with high-resolution characterization.

[0005] To achieve the above object, the application adopts the following technical solutions:

[0006] The application provides a high-throughput preparation mass spectrometry device with high-resolution characterization, which comprises an ion source, an ion transmission cavity, a quadrupole mass screening cavity, an ion dissociation cavity, an ion deflection cavity, an ion deceleration and deposition cavity and a high-resolution mass spectrometry characterization cavity arranged along a vertical direction on one side of the ion deflection cavity; the ion source is used for ionization of a compound; the ion transmission cavity is provided with a high-efficiency ion transmission module, the high-efficiency ion transmission module is used for transmitting ions generated by the ion source to the quadrupole mass screening cavity; the quadrupole mass screening cavity is provided with a quadrupole rod separation module, the quadrupole rod separation module is used for screening ions and introducing the ions into the ion dissociation cavity; the ion dissociation cavity is provided with an ion dissociation module, the ion dissociation module is used for realizing ion fragmentation and transmitting product ions after fragmentation to the ion deflection cavity; the ion deflection cavity is provided with a sector deflection module, the sector deflection module can control the ions to be transmitted into the ion deceleration and deposition cavity along an original direction or to be deflected by 90° to enter the high-resolution mass spectrometry characterization cavity; the high-resolution mass spectrometry characterization cavity is provided with a high-resolution mass analyzer module, the high-resolution mass analyzer module is used for accurately characterizing the mass-to-charge ratio of the ion beam introduced by the ion deflection cavity; the ion deceleration and deposition cavity is provided with an ion deceleration and deposition module, the ion deceleration and deposition module is used for decelerating and depositing the ions, thereby realizing lossless preparation.

[0007] The ion source adopts a combination of one or more atmospheric pressure ion sources, and the atmospheric pressure ion source includes an electrospray ionization source, an atmospheric pressure photoionization source, a dielectric barrier discharge ionization source or a paper spray ionization source.

[0008] Or the ion source adopts a configuration of one or more low-pressure ion sources, and the low-pressure ion source includes an electron impact ionization source, a single-photon ionization source, a multi-photon ionization source or a chemical ionization source.

[0009] The high-efficiency ion transmission module adopts one or more than two combinations of a radio frequency driven ion funnel, a multipole rod, a special-shaped multipole rod and an electrostatic lens.

[0010] The quadrupole rod separation module is a cylindrical or hyperboloid quadrupole analyzer with adjustable resolution, and the resolution adjustment range is 0.5-50 amu in half peak width.

[0011] The ion dissociation module is any one of a radio frequency multipole rod, a special-shaped radio frequency multipole rod, a segmented radio frequency multipole rod and a traveling wave toroidal electrode; and the working gas pressure can be tuned between 0.1 Pa and 100 Pa.

[0012] The fan-shaped deflection module is composed of a fan-shaped cylindrical deflection lens, and a rectangular through hole is arranged on the outer ring electrode of the fan-shaped cylindrical deflection lens group in the X direction, the width of the rectangular through hole is 2-8 mm, the center of the rectangular through hole coincides with the center of the ion beam, a rectangular slit is arranged at the Y direction outlet of the fan-shaped deflection module, the width of the rectangular slit is 0.1-2 mm, the rectangular slit is used for controlling the ion width entering the high-resolution mass spectrum characterization cavity, and the high-resolution mass spectrum ion beam current requirement is ensured.

[0013] The high-resolution mass analyzer module adopts one of a time-of-flight mass analyzer, an orbitrap analyzer and a Fourier transform ion cyclotron resonance mass analyzer; and the mass resolution is greater than 10,000.

[0014] The ion deceleration and deposition module is composed of a combination of a multistage electrostatic shaping and deceleration lens, a deposition substrate and a current measurement module.

[0015] Another aspect of the present application provides a use method of the high-throughput preparation mass spectrum device with high-resolution characterization, comprising the following steps:

[0016] a. the sample to be prepared enters the ion source, the ion source ionizes the sample entering the ion source, and the ion generated after ionization is transmitted to the ion transmission cavity;

[0017] b. the ion entering the ion transmission cavity is transmitted to the quadrupole mass screening cavity under the action of the high-efficiency ion transmission module;

[0018] c. the working mode of the quadrupole rod separation module is set to ion full pass; the ion dissociation module in the ion dissociation cavity is set to full pass; the fan-shaped deflection module in the ion deflection cavity is turned on, so that the ion is deflected by 90° and enters the high-resolution mass analyzer module in the high-resolution mass spectrum characterization cavity, mass spectrum characterization is carried out, and product ion generation distribution is evaluated;

[0019] d. according to the evaluation result of the high-resolution mass analyzer module, the working voltage of the quadrupole rod separation module is regulated, and the remaining parameters remain unchanged: the target ion to be deposited or dissociated is selected, and the high-resolution mass analyzer module is used again for evaluation, and the ion purity screened by the quadrupole rod separation module is investigated;

[0020] e. the parameters of the quadrupole rod separation module are determined and fixed after evaluation by the high-resolution mass analyzer module; if the screened ion needs to be dissociated, the working voltage, gas pressure and carrier gas parameters of the ion dissociation module in the ion dissociation cavity are controlled, ion fragmentation is carried out in the ion dissociation module, and the fragmented ion is introduced into the high-resolution mass analyzer module in the mass spectrum characterization cavity for mass spectrum characterization; according to the characterization result, the parameters of the ion dissociation module in the ion dissociation cavity are regulated and determined;

[0021] f. After determining the parameters of the ion dissociation module, the fan-shaped deflection module in the ion deflection chamber is turned off. Ions enter the ion deceleration and deposition chamber through the rectangular through-hole. They are decelerated by the ion deceleration and deposition module and finally deposited on the substrate without damage.

[0022] The advantages and beneficial effects of this invention are as follows: This invention ingeniously utilizes soft ionization combined with a quadrupole analyzer to screen ions, dissociates ions through a dissociation chamber, selects high-resolution characterization or high-throughput preparation functions using an ion deflection chamber, achieves high-resolution characterization of screened and fragmented ions through a high-resolution mass spectrometry characterization chamber, and performs high-throughput ion preparation through an ion deceleration and deposition chamber. This invention achieves perfect compatibility between high-throughput preparation and high-resolution mass spectrometry characterization through ion deflection design, and has broad application prospects in the efficient preparation of biomolecules, synthetic macromolecules, and other fields.

[0023] Other features and advantages of the invention will be set forth in the following description, and will be apparent in part from the description, or may be learned by practicing the invention. The objects and other advantages of the invention may be realized and obtained by means of the structures particularly pointed out in the written description and the accompanying drawings.

[0024] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0025] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used in conjunction with embodiments of the invention to explain the invention and do not constitute a limitation thereof. In the drawings:

[0026] Figure 1 This is a schematic diagram of the structure of a high-throughput preparative mass spectrometry device that also achieves high-resolution characterization according to the present invention.

[0027] Figure 2 This is a schematic diagram illustrating an implementation of a high-throughput preparative mass spectrometry device that also achieves high-resolution characterization according to the present invention.

[0028] In the figure: 1 is the ion source, 2 is the ion transport cavity, 3 is the quadrupole mass screening cavity, 4 is the ion dissociation cavity, 5 is the high-resolution mass spectrometry characterization cavity, 6 is the high-resolution mass analyzer module, 7 is the ion deceleration and deposition cavity, 8 is the ion deceleration and deposition module, 9 is the ion deflection cavity, 10 is the rectangular through-hole, 11 is the fan-shaped deflection module, 12 is the ion dissociation module, 13 is the quadrupole separation module, 14 is the high-efficiency ion transport module, 15 is the slit, 16 is the electrospray ion source, 17 is the radio frequency ion funnel transport module, 18 is the segmented quadrupole ion dissociation module, 19 is the deceleration ring electrode and ion deposition module, and 20 is the high-resolution time-of-flight mass analyzer. Detailed Implementation

[0029] In this invention, unless otherwise explicitly specified and limited, the terms "installation," "connection," "linking," and "fixing," etc., 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.

[0030] The preferred embodiments of the present invention will be described below with reference to the accompanying drawings. It should be understood that the preferred embodiments described herein are for illustration and explanation only and are not intended to limit the present invention.

[0031] like Figure 1 As shown, an embodiment of the present invention provides a high-throughput preparative mass spectrometry device that also achieves high-resolution characterization, comprising, in sequence, an ion source 1, an ion transmission chamber 2, a quadrupole mass screening chamber 3, an ion dissociation chamber 4, an ion deflection chamber 9, an ion deceleration and deposition chamber 7, and a high-resolution mass spectrometry characterization chamber 5 disposed vertically on one side of the ion deflection chamber 9; wherein the ion source 1 is used for ionization of compounds; the ion transmission chamber 2 is provided with a high-efficiency ion transmission module 14, which is used to transmit ions generated by the ion source 1 to the quadrupole mass screening chamber 3; the quadrupole mass screening chamber 3 is provided with a quadrupole separation module 14, which is used to screen ions and introduce them into the ion dissociation chamber 4; the ion dissociation chamber 4 is provided with an ion dissociation module 12, which... The ion dissociation module 12 is used to achieve ion fragmentation and transport the fragmented product ions to the ion deflection cavity 9. The ion deflection cavity 9 is equipped with a fan-shaped deflection module 11, which can control the ions to be transported along the original direction (X direction) into the ion deceleration and deposition cavity 7, or deflected along 90° (Y direction) and enter the high-resolution mass spectrometry characterization cavity 5 after the ion beam width is limited by the rectangular slit 15. The high-resolution mass spectrometry characterization cavity 5 is equipped with a high-resolution mass analyzer module 6, which is used to accurately characterize the mass-to-charge ratio of the ion beam introduced into the ion deflection cavity 9. The ion deceleration and deposition cavity 7 is equipped with an ion deceleration and deposition module 8, which is used to decelerate and deposit the ions, thereby achieving non-destructive preparation.

[0032] Furthermore, the ion source module 1 can employ a variety of ionization technologies, including combinations of one or more atmospheric pressure ion sources such as electrospray ionization sources, atmospheric pressure photoionization sources, dielectric barrier discharge ionization sources, or paper spray ionization sources, or configurations of one or more low-pressure ionization sources such as electron impact ionization sources, single-photon ionization sources, multi-photon ionization sources, or chemical ionization sources.

[0033] Preferably, the ion source module 1 uses a combination of two ionization sources: an electrospray ionization source and an atmospheric pressure photoionization source, which can achieve a wide range of ionization from strongly polar to non-polar compounds.

[0034] Furthermore, the high-efficiency ion transport module 14 may be configured with one or more of the following: radio frequency driven ion funnel, multipole (quadrupole, hexapole, octapole, etc.), irregular multipole (rectangular bar, irregular bar), and electrostatic lens.

[0035] Preferably, the radio frequency ion-funnel scheme is selected when the air pressure is above 100 Pa, the radio frequency multipole or irregular rod scheme is selected when the air pressure is between 0.1 and 100 Pa, and the electrostatic lens focusing scheme is selected when the air pressure is below 0.1 Pa.

[0036] Furthermore, the quadrupole separation module 13 is a cylindrical or hyperboloid quadrupole analyzer with adjustable resolution, and the resolution adjustment range is 0.5~50 amu.

[0037] Preferably, the quadrupole separation module 13 is a cylindrical quadrupole analyzer with adjustable resolution, which can achieve higher processing accuracy.

[0038] Furthermore, the ion dissociation module 12 can be selected from any one of the following: radio frequency multipole, irregular radio frequency multipole, segmented radio frequency multipole, traveling wave ring electrode group; the working gas pressure can be tuned between 0.1 and 100 Pa.

[0039] Preferably, the ion dissociation module 12 is a segmented radio frequency multipole, such as a segmented quadrupole, which not only has a better focusing effect, but also can control the axial ion kinetic energy.

[0040] Furthermore, the sector-shaped deflection module 11 is composed of a sector-shaped cylindrical deflection lens (see the cylindrical deflection lens design in J. Am. Soc. Mass Spectrom. 2021, 32, 1196−1204). A rectangular through-hole 10 is provided along the X direction on the outer ring electrode of the sector-shaped cylindrical deflection lens group. The width of the rectangular through-hole 10 (Y direction) is 2~8 mm, and the center of the rectangular through-hole 10 coincides with the center of the ion beam. A rectangular slit 15 is provided at the Y direction exit of the sector-shaped deflection module 11. The width of the rectangular slit 15 (X direction) is 0.1~2 mm. The rectangular slit 15 is used to control the width of the ions entering the high-resolution mass spectrometry characterization cavity 5 to ensure that the high-resolution mass spectrometry ion beam current requirements are met.

[0041] Preferably, the width (Y direction) of the rectangular through-hole 10 is 4 mm, which ensures sufficient ion passage width while minimizing the impact on the internal electric field of the deflection lens group. The width (X direction) of the rectangular slit 15 is 0.5 mm, which is used to reduce the initial spatial width of ions entering the high-resolution mass spectrometer and improve the mass spectrometry resolution.

[0042] Furthermore, the high-resolution mass analyzer module 6 can be selected from one of the following: time-of-flight mass analyzer, orbital trap analyzer, and Fourier transform ion cyclotron resonance mass analyzer; the mass resolution is greater than 10000.

[0043] Preferably, the high-resolution quality analyzer module 6 is a high-resolution time-of-flight quality analyzer, which has a simpler structure and a wider quality range.

[0044] Furthermore, the ion deceleration and deposition module 8 is composed of a multi-stage electrostatic shaping and deceleration lens, a deposition substrate, and a current measurement module. The multi-stage electrostatic shaping and deceleration lens consists of several sets (one or more) of coaxial electrostatic lenses with central holes. Each electrostatic lens consists of two or more coaxially arranged circular metal electrode plates. Applying a suitable voltage to the electrode plates can control and shape the passing ion beam. The deposition substrate is generally a conductive metal and is placed to the right of the multi-stage electrostatic shaping and deceleration lens to deposit ions after being shaped and decelerated by the multi-stage electrostatic shaping and deceleration lens. The current measurement module is connected to the deposition substrate through wires to monitor the real-time intensity of ions deposited on the substrate and to calculate the final deposition amount.

[0045] This invention provides a high-throughput preparative mass spectrometry device that combines high-resolution characterization with high-throughput preparation. It utilizes soft ionization combined with a quadrupole analyzer to screen ions, dissociates ions through an ion dissociation chamber, selects between high-resolution characterization and high-throughput preparation using an ion deflection chamber, achieves high-resolution characterization of screened and fragmented ions through a high-resolution mass spectrometry characterization chamber, and performs high-throughput ion preparation through an ion deceleration and deposition chamber. This invention achieves perfect compatibility between high-throughput preparation and high-resolution mass spectrometry characterization through ion deflection design, and has broad application prospects in the efficient preparation of biomolecules, synthetic macromolecules, and other related fields.

[0046] Based on the above embodiments, another embodiment of the present invention provides a method for using the high-throughput preparative mass spectrometry device that also achieves high-resolution characterization as described in the above embodiments, comprising the following steps:

[0047] a. The sample to be prepared enters the ion source module 1. The ion source module 1 ionizes the sample and transmits the ion generated after ionization to the ion transmission chamber 2.

[0048] b. Ions entering the ion transmission chamber 2 are transported to the quadrupole mass screening chamber 3 under the action of the high-efficiency ion transmission module 14.

[0049] c. Set the quadrupole separation module 13 to full-pass mode; set the ion dissociation module 12 in the ion dissociation chamber 4 to full-pass mode; turn on the fan-shaped deflection module 11 in the ion deflection chamber 9 to deflect the ions by 90° and enter the high-resolution mass analyzer module 6 in the mass spectrometry characterization chamber 5 for mass spectrometry characterization and evaluate the product ion generation distribution.

[0050] d. Based on the evaluation results of the high-resolution mass analyzer module 6, adjust the working voltage of the quadrupole separation module 13 while keeping other parameters unchanged; select the target ion to be deposited or dissociated, and evaluate it again through the high-resolution mass analyzer module 6 to examine the purity of the ions screened by the quadrupole separation module 13.

[0051] e. After evaluation by the high-resolution mass analyzer module 6, the parameters of the quadrupole separation module 13 are determined and fixed. If it is necessary to dissociate the screened ions, the working voltage, gas pressure and carrier gas parameters of the ion dissociation module 12 in the ion dissociation chamber 4 are controlled. Ion fragmentation is performed in the ion dissociation module 12, and the fragmented ions are introduced into the high-resolution mass analyzer module 12 in the mass spectrometry characterization chamber 5 for mass spectrometry characterization. Based on the characterization results, the parameters of the ion dissociation module 12 in the ion dissociation chamber 4 are adjusted and determined.

[0052] f. After determining the parameters of the ion dissociation module 12, the fan-shaped deflection module 11 in the ion deflection cavity 9 is turned off. Ions enter the ion deceleration and deposition cavity 7 through the rectangular through hole 10. The ions are decelerated by the multi-stage electrostatic deceleration lens in the ion deceleration and deposition module 8 and finally deposited on the substrate without damage.

[0053] Furthermore, this method achieves perfect compatibility between high-throughput preparation and high-resolution mass spectrometry characterization through ion deflection design, and can be used in fields such as the efficient preparation of biomacromolecules and synthetic macromolecules.

[0054] Example 1

[0055] See Figure 2As shown, in this embodiment, the ion source module 1 is an electrospray ion source 16, the ion deceleration and deposition module 8 is a deceleration ring electrode and ion deposition module 19, the high-resolution quality analyzer module 6 is a high-resolution time-of-flight quality analyzer 20, the ion dissociation module 12 is a segmented quadrupole ion dissociation module 18, and the high-efficiency ion transport module 14 is a radio frequency ion funnel transport module 17. In practice: the sample to be prepared enters the electrospray ionization source 16, which ionizes the sample and transmits the resulting ions to the ion transmission chamber 2. Ions entering the ion transmission chamber 2 are efficiently transmitted to the next stage quadrupole mass screening chamber 3 under the action of the radio frequency ion funnel transmission module 17. The quadrupole separation module 13 is set to full-pass ion mode. The segmented quadrupole ion dissociation module 18 in the ion dissociation chamber 4 is set to full-pass mode. The fan-shaped deflection module 11 in the ion deflection chamber 9 is activated, causing the ions to deflect 90° and enter the high-resolution time-of-flight mass analyzer 20 in the high-resolution mass spectrometry characterization chamber 5 for mass spectrometry characterization, evaluating the product ion generation distribution. Based on the evaluation results of the high-resolution time-of-flight mass analyzer 20, the operating voltage of the quadrupole separation module 13 is adjusted, while other parameters remain unchanged. The target ions to be deposited or dissociated are selected, and the samples are again passed through the high-resolution mass spectrometry chamber 5. The time-of-flight mass analyzer 20 evaluates the purity of the ions screened by the quadrupole separation module 13. After evaluation by the high-resolution time-of-flight mass analyzer 20, the parameters of the quadrupole separation module 13 are determined and fixed. If it is necessary to dissociate the screened ions, the working voltage, gas pressure, and carrier gas parameters of the segmented quadrupole 18 in the ion dissociation chamber 4 are controlled to perform ion fragmentation in the segmented quadrupole 18. The fragmented ions are then introduced into the high-resolution time-of-flight mass analyzer 20 in the mass spectrometry characterization chamber 5 for mass spectrometry characterization. Based on the characterization results, the parameters of the segmented quadrupole ion dissociation module 18 in the ion dissociation chamber 4 are adjusted and determined. After determining the parameters of the segmented quadrupole ion dissociation module 18, the fan-shaped deflection module 11 in the ion deflection chamber 9 is turned off. The ions enter the ion deceleration and deposition chamber 7 through the rectangular through-hole 10. The ions are decelerated by the deceleration ring electrode and the multi-stage electrostatic deceleration lens in the ion deposition module 19, and finally deposited on the substrate without damage.

[0056] This invention ingeniously utilizes ion deflection design to achieve perfect compatibility between high-throughput preparation and high-resolution mass spectrometry characterization. The apparatus and method of this invention can achieve integrated high-resolution ion characterization and deposition, or a specific part can be used independently, making it applicable to the efficient preparation of biomolecules, synthetic macromolecules, and the like.

[0057] The technical principles of the present invention have been described above with reference to specific embodiments. These descriptions are merely for explaining the principles of the invention and should not be construed as limiting the scope of protection of the invention in any way. Based on this explanation, those skilled in the art can readily conceive of other specific embodiments of the invention without inventive effort, and these equivalent variations or substitutions are all included within the scope defined by the claims of this application.

Claims

1. A high-throughput preparative mass spectrometry device that also achieves high-resolution characterization, characterized in that, The system includes, in sequence, an ion source (1), an ion transport cavity (2), a quadrupole mass screening cavity (3), an ion dissociation cavity (4), an ion deflection cavity (9), an ion deceleration and deposition cavity (7), and a high-resolution mass spectrometry characterization cavity (5) arranged vertically on one side of the ion deflection cavity (9); wherein the ion source (1) is used for ionization of compounds; the ion transport cavity (2) is equipped with a high-efficiency ion transport module (14), which is used to transport ions generated by the ion source (1) to the quadrupole mass screening cavity (3); the quadrupole mass screening cavity (3) is equipped with a quadrupole separation module (13), which is used to screen ions and introduce them into the ion dissociation cavity (4); the ion dissociation cavity (4) is equipped with an ion dissociation module (12) The ion dissociation module (12) is used to realize ion fragmentation and transfer the fragmented product ions to the ion deflection cavity (9). The ion deflection cavity (9) is equipped with a fan-shaped deflection module (11), which can control the ions to be transmitted along the original direction into the ion deceleration and deposition cavity (7), or deflected at 90° into the high-resolution mass spectrometry characterization cavity (5). The high-resolution mass spectrometry characterization cavity (5) is equipped with a high-resolution mass analyzer module (6), which is used to accurately characterize the mass-to-charge ratio of the ion beam introduced by the ion deflection cavity (9). The ion deceleration and deposition cavity (7) is equipped with an ion deceleration and deposition module (8), which is used to decelerate and deposit the ions, thereby realizing non-destructive preparation.

2. The high-throughput preparative mass spectrometry apparatus that combines high-resolution characterization according to claim 1, characterized in that: The ion source (1) adopts a combination of one or more atmospheric pressure ion sources, including electrospray ionization source, atmospheric pressure photoionization source, dielectric barrier discharge ionization source or paper spray ionization source; Alternatively, the ion source (1) may be configured with one or more low-pressure ionization sources, including electron bombardment ionization sources, single-photon ionization sources, multi-photon ionization sources, or chemical ionization sources.

3. The high-throughput preparative mass spectrometry apparatus that combines high-resolution characterization according to claim 1, characterized in that: The high-efficiency ion transport module (14) adopts one or more of the following configurations: radio frequency driven ion funnel, multipole, irregular multipole and electrostatic lens.

4. The high-throughput preparative mass spectrometry apparatus that combines high-resolution characterization according to claim 1, characterized in that: The quadrupole separation module (13) is a cylindrical or hyperboloid quadrupole analyzer with adjustable resolution, and the resolution adjustment range is 0.5~50 amu for half peak width.

5. The high-throughput preparative mass spectrometry apparatus that combines high-resolution characterization according to claim 1, characterized in that: The ion dissociation module (12) is any one of the following: radio frequency multipole, irregular radio frequency multipole, segmented radio frequency multipole, and traveling wave ring electrode; the working gas pressure can be tuned between 0.1 and 100 Pa.

6. The high-throughput preparative mass spectrometry apparatus that combines high-resolution characterization according to claim 1, characterized in that: The fan-shaped deflection module (11) is composed of a fan-shaped cylindrical deflection lens, and a rectangular through hole (10) is provided on the outer ring electrode of the fan-shaped cylindrical deflection lens group along the X direction. The width of the rectangular through hole (10) is 2~8 mm, and the center of the rectangular through hole (10) coincides with the center of the ion beam. A rectangular slit (15) is provided at the Y direction outlet of the fan-shaped deflection module (11). The width of the rectangular slit (15) is 0.1~2 mm. The rectangular slit (15) is used to control the width of the ions entering the high-resolution mass spectrometry characterization cavity (5) to ensure that the requirements of the high-resolution mass spectrometry ion beam are met.

7. The high-throughput preparative mass spectrometry apparatus that combines high-resolution characterization according to claim 1, characterized in that: The high-resolution mass analyzer module (6) adopts one of the following: time-of-flight mass analyzer, orbital trap analyzer, and Fourier transform ion cyclotron resonance mass analyzer; the mass resolution is greater than 10000.

8. The high-throughput preparative mass spectrometry apparatus that combines high-resolution characterization according to claim 1, characterized in that: The ion deceleration and deposition module (8) is composed of a multi-level electrostatic shaping and deceleration lens, a deposition substrate, and a current measurement module.

9. A method of using a high-throughput preparative mass spectrometry apparatus as described in any one of claims 1-8, characterized in that: Includes the following steps: a. The sample to be prepared enters the ion source (1), the ion source (1) ionizes the sample entering it, and transmits the ion generated after ionization to the ion transmission chamber (2). b. Ions entering the ion transport chamber (2) are transported to the quadrupole mass screening chamber (3) under the action of the high-efficiency ion transport module (14). c. Set the working mode of the quadrupole separation module (13) to ion full-pass; set the ion dissociation module (12) in the ion dissociation chamber (4) to full-pass; turn on the fan-shaped deflection module (11) in the ion deflection chamber (9) so that the ions are deflected by 90° and enter the high-resolution mass analyzer module (6) in the high-resolution mass spectrometry characterization chamber (5) for mass spectrometry characterization and evaluate the product ion generation distribution; d. Based on the evaluation results of the high-resolution mass analyzer module (6), adjust the working voltage of the quadrupole separation module (13) while keeping the other parameters unchanged: select the target ion to be deposited or dissociated, and evaluate it again through the high-resolution mass analyzer module (6) to examine the purity of the ions screened by the quadrupole separation module (13); e. After evaluation by the high-resolution mass analyzer module (6), the parameters of the quadrupole separation module (13) are determined and fixed. If it is necessary to dissociate the screened ions, the working voltage, gas pressure and carrier gas parameters of the ion dissociation module (12) in the ion dissociation chamber (4) are controlled. Ion fragmentation is performed in the ion dissociation module (12), and the fragmented ions are introduced into the high-resolution mass analyzer module (12) in the mass spectrometry characterization chamber (5) for mass spectrometry characterization. The parameters of the ion dissociation module (12) in the ion dissociation chamber (4) are adjusted and determined according to the characterization results. f. After determining the parameters of the ion dissociation module (12), the fan-shaped deflection module (11) in the ion deflection cavity (9) is closed. The ions enter the ion deceleration and deposition cavity (7) through the rectangular through hole (10), and are decelerated by the ion deceleration and deposition module (8) and finally deposited on the substrate without damage.

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