Data collection method and ion mobility mass spectrometer

Abstract

The present invention relates to the field of mass spectrometry, and more particularly to a method that can effectively improve data acquisition efficiency and / or resolution in mobility mass spectrometry. The method is applicable to DDA or DIA data acquisition and is also applicable to data acquisition in conventional ion mobility-first-order mass spectrometry. It can solve problems such as limitations in dynamic range and reduced scanning speed due to the effects of space charge in conventional data acquisition methods. This data acquisition method is applied to tandem analysis of UMA and mass spectrometer and includes a preliminary acquisition step, as well as steps for accumulating target ions and holding non-target ions in parallel. Furthermore, by adding an ion dissociation step, DDA or DIA data with high speed and a wide dynamic range can be easily obtained.

Description

Technical Field

[0001] The present invention relates to the field of mass spectrometry, and more specifically, to a data collection method, an ion mobility analyzer, and an ion mobility mass spectrometer.

Background Art

[0002] Ion mobility spectrometry (IMS) is a technique for separating ions based on the mobility of ions. For conventional drift cell ion mobility, the resolution can be improved by methods such as extending the drift tube or increasing the drift voltage. In order to further improve the resolution, it is also possible to adopt a method of applying a reverse electric field in a certain uniform gas flow field to increase the equivalent distance of ion movement. Zeleny (Zeleny, J. Philos. Mag. 46, 120 (1898)) proposed a method of analyzing ions by utilizing the balance between a gas flow and an electric field in opposite directions in a parallel flow analyzer. The Zeleny device includes two parallel grids, and ions having a specific mobility reach an equilibrium state under the action of two opposing forces (gas flow and electric field).

[0003] In recent years, there have been many attempts to move ions against the flow of air under the influence of a DC electric field. US Patent US6630662B1 proposes a method in which a uniform electric field is used and the electric field is gradually increased, causing ions to be successively discharged against the flow of air under the influence of the electric field. However, because the applicable pressure is low (Pa), the resolution is also relatively low. Chinese Patent CN101738429A proposes using different DC gradients present in different regions of a mobility analyzer to simultaneously accumulate (store) ions with different mobilities. However, since ions can only be extracted from the radial direction of each accumulation region, many detection devices are required. US Patent US8288717B2 proposes using a non-uniform electric field to first separate ions with different mobilities, and then gradually decreasing the electric field to discharge the ions axially out of the analyzer under the influence of air. In the method described above, since ions of all mobilities accumulate in a single analysis area and await mobility scanning, the space charge effect is relatively severe, which can affect the mobility resolution. Therefore, U.S. Patent US9984864 further proposes using two TIMS (Trapped Ion Mobility Spectrometer, TIMS) analyzers in series, performing preliminary sorting of the accumulated ions in the first TIMS to retain only ions within a certain target mobility range, and then transporting these ions to a second mobility analyzer. In this process, ions outside the target mobility range are lost in the system because they are no longer protected by the high-frequency electric field when emitted from the first TIMS. However, since such means of releasing high-frequency protection may not adequately remove ions, U.S. Patent US10241079B2 proposes placing an ion gate between the two TIMSs to further remove ions of non-target mobility. While the TIMS method described above allows for selective accumulation and detection of ions, the second ion mobility analyzer in the instrument can only sequentially accept ions from the upstream ion accumulation section, and ions outside the range of the target analyte cannot be reused once they have been removed by sorting.

[0004] The apparatus (U-shaped ion mobility mass spectrometer) according to Chinese patent CN109003876B can analyze ions through two channels. One of its analysis modes is similar to TIMS, namely, ion storage in the first channel and mobility scanning in the second channel. In the apparatus according to CN109003876B, one challenge is to selectively analyze specific target ions while avoiding the loss of other non-target ions, a challenge similar to that faced by the structures of US patents US9984864 and US10241079B2. Therefore, reducing space charge effects and improving ion scanning resolution while simultaneously ensuring freedom of ion selection and utilization efficiency is a key point of interest in this field for such backflow mobility analyzers. This invention builds upon the structure proposed in Gillig's patent, with further improvements and innovations to the apparatus structure and operating modes.

[0005] Furthermore, in recent years, data-independent acquisition (DIA) techniques have also developed rapidly. DIA does not perform collisional dissociation and analysis on specific parent ions, but rather on ions within a specific mass-to-charge ratio (m / z) window or total mass number, and analyzes the complex spectral data obtained. Compared to DDA (Data-Dependent Acquisition), DIA can accurately identify ions with relatively low abundance and offers higher sensitivity, dynamic range, analytical throughput, and better quantitative accuracy.

[0006] To further improve sensitivity and increase the dimensionality of orthogonal separation, an increasing number of manufacturers are combining ion mobility spectrometry (IMS) with tandem mass spectrometers, improving ion identification capabilities by further separating different ions using the differences in ion mobility properties. For example, U.S. Patent US9891194 combines TIMS technology with DIA / DDA technology to create a so-called parallel collection and sequential dissociation (PASEF) method. Its main advantage lies in improving ion identification coverage in DDA / DIA by utilizing the temporal alignment between the TIMS instrument and chromatography and mass spectrometry, as well as its high ion utilization efficiency. However, one of its limitations is that the selection of parent ions is not sufficiently flexible. This lack of flexibility was demonstrated in the first TIMS instrument, and the problem, as mentioned above, is that other non-target ions are inevitably lost during the preliminary selection process in the parent ion scanning interval. On the other hand, if preliminary sorting is not performed, an excess of ions may enter the second TIMS, potentially causing severe space charge effects. The structure and operating mode according to the present invention can be applied to mobility mass spectrometers and can solve the aforementioned problems faced in the DDA / DIA acquisition process.

[0007] To address the issue of non-target ion loss, Chinese patent application CN115223844A proposes temporarily holding ions outside the target analysis interval at a portion of the edge of each channel of a U-shaped mobility analyzer and releasing them again when the next mobility scanning cycle begins. While this method does provide some degree of retention for non-target ions, the U-shaped mobility analyzer operates in filter mode and performs sequential scanning. This differs from the selective capture-scan mode in which the U-shaped mobility analyzer operates in the present invention, and the accumulation region of non-target ions is also different, thus representing a different technical direction. Furthermore, since the structure proposed in CN115223844A operates in filter mode, modifications to the current U-shaped mobility analyzer structure are necessary to realize functions such as tandem mobility analysis. [Overview of the project] [Means for solving the problem]

[0008] In view of the above problems, the present invention provides a data acquisition method that can reduce the effect of space charge, improve resolution, or shorten mobility scanning time without fundamentally impairing sensitivity.

[0009] The inventors of this application previously developed a U-shaped ion mobility analyzer (UMA, CN109003877A), whose operating principle is also based on the combined effect of airflow and electric field on ions. The difference from TIMS is that the UMA has two parallel airflow channels, which are perpendicular to the main ion path of the mass spectrometer. Based on this feature, by designing a unique control flow, when ions are accumulated in the first channel of the UMA, it is possible to effectively select ions within their ion mobility range while also effectively retaining ions outside their ion mobility range. Furthermore, these synchronously retained non-target ions do not interfere with the analysis of the current target ion. This allows the target ion to occupy a larger space, and consequently the entire first channel, reducing the effect of space charge and improving resolution without fundamentally compromising sensitivity. This ion control flow is suitable not only for DDA and DIA data acquisition but is also applicable to conventional ion mobility-primary mass spectrometry.

[0010] Specifically, the first aspect of the present invention provides a data acquisition method, which is applied to an ion mobility mass spectrometer in which an ion source, a UMA, and a mass spectrometer are sequentially connected. A preliminary collection step in which the analyte ions ionized by the ion source are separated into a mass spectrometer via UMA, An ion accumulation step is performed in which ions within the target mobility range are accumulated in the target ion accumulation section of the first channel of the UMA, and ions outside the target mobility range are introduced and accumulated (stored) in the non-target ion accumulation sections at both ends of the first channel. An ion transfer step of transferring ions within the target mobility range in the first channel of the UMA to the second channel of the UMA, The process includes an ion scanning step of scanning and releasing ions within a target mobility range in the second channel of the UMA to a mass spectrometer, The ion accumulation step, the ion transfer step, and the ion scanning step are repeated, and in each repeated step, the target mobility range is set to the target mobility range defined in the previous scan, or to the mobility range corresponding to at least some of the ions introduced into the non-target ion accumulation section in the previous scan.

[0011] According to the data acquisition method provided by the present invention, in the ion accumulation step, only ions within the target mobility range (but not the entire mobility range) are accumulated in the target ion accumulation section of the first channel, and precise mobility analysis is not performed in the first channel. As a result, ions can be more dispersed within the second channel, thereby effectively reducing the influence of space charge.

[0012] When ions within the target mobility range accumulate in the target ion accumulation section of the first channel, at least some ions outside the target mobility range are not discarded, but are retained in the non-target ion accumulation sections at both ends of the first channel. These ions are then transported to the second channel and the mass spectrometer in subsequent steps as the target mobility range is adjusted. Therefore, these ions are not lost and are incorporated into the analysis process of the next scan, ensuring that essentially no ions are wasted throughout the entire collection process.

[0013] Furthermore, when it is necessary to remove certain ions (for example, the "noise components" mentioned above), the UMA is used as an ion mobility analyzer, and the first and second channels are used in combination in a mode that synchronizes accumulation and scanning / emission. As a result, the removed ions are not transported to subsequent stages but are directly released from the UMA. This prevents the removed ions from occupying the accumulation section and reduces the loss of dynamic range due to space charge effects. This type of ion removal method is simpler and more efficient compared to methods using ion gates, etc.

[0014] In one of the selectable technical applications of the present invention, the ion mobility mass spectrometer further includes a mass filter and an ion dissociation device provided between the UMA and the mass spectrometer, In the preliminary collection step, a two-dimensional heatmap of the ion mobility-mass spectrometry of the ion to be analyzed is obtained. Ions emitted from the second channel of the UMA pass through a mass filter and an ion dissociator before being introduced into the mass spectrometer.

[0015] The above method allows the data acquisition method to be effectively adapted for DDA or DIA analysis, solving the challenges of ion removal difficulties and dynamic range limitations faced by conventional data acquisition methods. First, by performing a preliminary acquisition once to obtain a two-dimensional heatmap of the parent ion's ion mobility-mass spectrometry, the trend line, i.e., the relationship between ion mobility and mass number, can be identified. Identifying the trend line contributes to selecting a more appropriate target mobility range and mass selection range at different stages of the same period, thereby improving scanning efficiency. Furthermore, the preliminary acquisition step can also acquire parent ion intensity information and mobility information. Parent ion intensity information is required when performing DDA analysis, and parent ion mobility information can be used to calculate the collision cross-section (CCS), contributing to qualitative analysis. In the selectable technical proposals of the present invention, the target mobility range of ions accumulated in the target ion accumulation section of the first channel is changed by adjusting the DC electric field intensity distribution of the first channel in multiple different ion accumulation steps. By adjusting the DC electric field strength distribution within different periods, different target mobility ranges can be scanned or skipped quickly and easily.

[0016] In the selectable technical configuration of the present invention, ions accumulated in the non-target ion accumulation sections at both ends of the first channel are released in the next ion accumulation step by changing the DC electric field strength distribution of the first channel and return to the target ion accumulation section, after which they enter the second channel and mobility scanning is performed. In this way, ions in the non-target ion accumulation section can be released periodically and in a timely manner, further ensuring that ions within the entire mobility range are effectively utilized, and theoretically, a duty cycle close to 100% can be achieved.

[0017] In the selectable technical configuration of the present invention, during the ion scanning step, ions in the second channel are released in order of decreasing ion mobility. Smaller parent ions typically correspond to smaller daughter ions, and since smaller daughter ions have a relatively short residence time (dwell time) in the ion dissociation apparatus, releasing ions in the order described above reduces interference between the transport of smaller daughter ions in the ion dissociation apparatus and subsequent relatively larger daughter ions, thus avoiding interference with the quality of the mobility spectrum (e.g., avoiding mobility peak mismatches) and accelerating the channel scanning of DDA or DIA.

[0018] In the selectable technical configuration of the present invention, during the ion scanning step, the mass selection range of the mass filter is a fixed-width mass window, and the mass filter sequentially scans different mass windows from the low-mass side to the high-mass side within a single analysis cycle. Since the UMA can employ a scanning method from high to low ion mobility, this scanning method can be effectively combined with the scanning method of the mass filter from low to high mass number, thereby improving the scanning speed.

[0019] In the selectable technical configuration of the present invention, the mass filter is a quadrupole mass filter, and the scanning period within the target mobility range of the UMA is synchronized with the scanning period within the mass selection range of the quadrupole mass filter.

[0020] In the selectable technical configurations of the present invention, UMA mobility scanning and quadrupole mass scanning are performed along a trend line in a two-dimensional heatmap. By performing UMA mobility scanning and quadrupole mass scanning along a trend line, target ions can be analyzed more selectively based on the type of target ion (e.g., peptides, lipids, sugars, etc.) or charge number, and since only ions with specific mobility or mass numbers are analyzed, the possibility of ions with low abundance being missed can be reduced.

[0021] In an alternative technical solution of the present invention, in the ion scanning step, a plurality of sets of ions with signal intensity higher than a threshold value in the ion mobility-mass spectrometry two-dimensional heat map are selected, or a plurality of sets of ions with relatively high signal intensity in the ion mobility-mass spectrometry two-dimensional heat map are selected. This data collection method can accurately select target ions and efficiently collect data applicable to analysis by the DDA method.

[0022] In an alternative technical solution of the present invention, in the ion scanning step, the mass selection range of the mass filter includes all mass numbers within the current mobility range in the two-dimensional heat map. This data collection method can efficiently collect data applicable to the DIA analysis of the entire mass range.

[0023] In an alternative technical solution of the present invention, in the ion scanning step, the mass selection range of the mass filter includes some mass numbers corresponding to the current target mobility range in the two-dimensional heat map, and the width of the mass scanning window is kept constant or changed based on the prediction of the two-dimensional heat map.

[0024] In an alternative technical solution of the present invention, in the ion scanning step, the width of the window of the target mobility range is kept constant or changed based on the prediction of the two-dimensional heat map.

[0025] The ion mobility mass spectrometer may adopt a scanning method that keeps the window width constant to collect data for DIA analysis corresponding to the use of the above data collection method, or adopt a scanning method that changes based on the prediction of the two-dimensional heat map to collect data for DDA analysis.

[0026] In an alternative technical solution of the present invention, the first channel and the second channel are both constituted by two sets of electrode arrays arranged opposite to each other and extending perpendicularly to the axial direction. The UMA has an ion inlet, an ion outlet, and an inter-channel ion transfer port. The ion inlet is provided on the electrode array close to the front stage side of the first channel, the ion outlet is provided on the electrode array close to the rear stage side of the second channel, and the inter-channel ion transfer port is provided on the adjacent electrode arrays of the first channel and the second channel and communicates the first channel and the second channel. In the preliminary collection step, the ion accumulation step, and the ion scanning step, the operating mode of the UMA is basically unified, there is no need to perform mode switching, and it is also convenient to synchronize with the operating cycles of other components such as mass filters.

[0027] In an alternative technical solution of the present invention, in the ion transfer step, by closing the inter-channel ion transfer port during a part of the period, ions with a part of ion mobilities or ion mobility ranges are removed (filtered). By removing some unnecessary ions in the transfer process, ions as target analytes can be efficiently accumulated, and the dynamic range of methods such as DDA can be improved.

[0028] In an alternative technical solution of the present invention, by stopping the application of the DC electric field in the non-target ion accumulation section or applying a radial DC bias, the ions in the non-target ion accumulation section are removed. The ion path of the UMA呈U-shaped, and the transport direction of the ions is not limited to the axial direction, and unnecessary ions can also be removed along the radial direction. By the above method, the discharge of the temporarily held ions can be easily completed, and it is more easily achievable compared with TIMS.

[0029] The second aspect of the present invention provides an ion mobility mass spectrometer to which the data collection method of the present invention is applied.

[0030] In the selectable technical solutions of the present invention, the mass spectrometer is one or more selected from the group consisting of a quadrupole mass spectrometer, a time-of-flight mass spectrometer, a Fourier transform mass spectrometer, an ion trap mass spectrometer, and a magnetic field mass spectrometer.

[0031] In the selectable technical configurations of the present invention, the ion mobility mass spectrometer includes an ion dissociation device, and the ion dissociation device is one or more selected from the group consisting of a collision-induced dissociation device, an electron dissociation device, an infrared photodissociation device, an ultraviolet photodissociation device, and a radical dissociation device. [Brief explanation of the drawing]

[0032] [Figure 1] A schematic diagram illustrating the configuration of an ion mobility mass spectrometer according to an embodiment of the present invention. [Figure 2] This is a schematic diagram of a conventional scanning mode used in a U-shaped ion mobility analyzer in prior art. [Figure 3] This is a flowchart of a data acquisition method according to an embodiment of the present invention. [Figure 4] This is a schematic diagram illustrating the ion behavior of the first and second channels in the preliminary collection step of an embodiment of the present invention. [Figure 5] This is a schematic diagram illustrating the ion behavior of the first and second channels in the preliminary collection step of an embodiment of the present invention. [Figure 6] This is a schematic diagram of trend lines identified based on a two-dimensional heatmap of ion mobility-mass spectrometry in an embodiment of the present invention. [Figure 7] This figure shows a method for setting the target mobility range of the first channel and the second channel in each step of one embodiment of the present invention. [Figure 8] This is a schematic diagram of the DC electric field application configurations of the first channel and the second channel in the ion storage step, ion transfer step, and ion scanning step in different mobility ranges of embodiments of the present invention. [Figure 9]This is a schematic diagram of the DC electric field application configurations of the first channel and the second channel in the ion storage step, ion transfer step, and ion scanning step in different mobility ranges of embodiments of the present invention. [Figure 10] This is a schematic diagram of the DC electric field application configurations of the first channel and the second channel in the ion storage step, ion transfer step, and ion scanning step in different mobility ranges of embodiments of the present invention. [Figure 11] This is a schematic diagram of the DC electric field application configurations of the first channel and the second channel in the ion storage step, ion transfer step, and ion scanning step in different mobility ranges of embodiments of the present invention. [Figure 12] This is a schematic diagram of an embodiment of the present invention in which a two-dimensional heat map is first segmented based on the type of compound, the number of charges, etc. [Figure 13] This figure shows a method for setting the target mobility ranges of the first channel and the second channel in each step in another embodiment of the present invention. [Modes for carrying out the invention]

[0033] Hereinafter, the technical proposals in the embodiments of the present invention will be clearly and completely described with reference to the drawings of the embodiments. The embodiments described are only a part of the present invention, not all embodiments. All other embodiments that a person skilled in the art can obtain without creative effort based on the embodiments of the present invention are all within the scope of the protection of the present invention.

[0034] <Terminology and its interpretation> The term "ion mobility mass spectrometer" is not limited to the combination of an ion mobility spectrometer and a mass spectrometer; for example, a chromatograph may be combined to form a chromatograph-ion mobility mass spectrometer.

[0035] The phrase "sequentially connected" does not mean that other components cannot be added between them; the connections between components may be indirect. For example, "sequentially connected ion source, U-shaped ion mobility analyzer, and mass spectrometer" means that the UMA is installed after the ion source, and the mass spectrometer is installed after the UMA. However, other components may be added between the UMA and the ion source, and similarly, other components may be added between the UMA and the mass spectrometer.

[0036] The term "trap-release" refers to a type of operating mode for ion mobility analyzers, applicable to various ion mobility analyzers such as UMA and TIMS. Specifically, in "trap-release" mode, ions accumulate in a certain area of ​​the ion mobility analyzer, form ion packets, and are then released to the next stage. Typically, in "trap-release" mode, ions are released in pulses in ion packet units, and during the transport path, ions are not continuously released to the next stage but rather remain and are temporarily held (i.e., trapped) in a certain area.

[0037] In the ion scanning step, "scan release" refers to sequentially releasing ions of different mobilities or mobility ranges, or ions of different mass numbers or mass number ranges. The order may be from larger to smaller, or from smaller to larger, and some mobility / mass number or mobility / mass number ranges may be skipped along the way.

[0038] This embodiment provides a data acquisition method and an ion mobility mass spectrometer 100 to which the data acquisition method is applied. <Ion mobility mass spectrometer 100>

[0039] Referring to Figure 1, the ion mobility mass spectrometer 100 according to this embodiment comprises a sequentially connected ion source 1, a U-shaped ion mobility analyzer 2, a quadrupole mass filter 3 (i.e., a mass filter), an ion dissociation device 4, and a mass spectrometer 5.

[0040] In this embodiment, ion source 1 is (i) an electrospray ionization ("ESI") ion source; (ii) an atmospheric pressure photoionization ("APPI") ion source; (iii) an atmospheric pressure chemical ionization ("APCI") ion source; (iv) a matrix-assisted laser desorption ionization ("MALDI") ion source; (v) a laser desorption ionization ("LDI") ion source; (vi) an atmospheric pressure ionization ("API") ion source; (vii) a silicon desorption ionization ("DIOS") ion source. (viii) ion source; (ix) ion source; (x) ion source; (x) ion source; (x) ion source; (x) ion source; (xii) ion source; (xiii) ion source; (xiv) ion source; (xv) ion source; (xv) ion source; (xvi The source is selected from the group consisting of: (xvii) Nickel-63 radioactive ion source; (xviii) Atmospheric pressure matrix-assisted laser desorption ionization source; (xviii) Thermospray ion source; (xix) Atmospheric sampling glow discharge ionization ("ASGDI") ion source; (xx) Glow discharge ("GD") ion source; (xxi) Impactor ion source; (xxii) Real-time direct analysis ("DART") ion source; (xxiii) Laser spray ionization ("LSI") ion source; (xxiv) Sonic spray ionization ("SSI") ion source; (xxv) Matrix-assisted inlet ionization ("MAII") ion source; (xxvi) Solvent-assisted inlet ionization ("SAII") ion source; (xxvii) Penning ionization source; (xxviii) Laser ablation electrospray ionization ("LAESI") ion source; and (xxix) He plasma (HePl) ion source. More preferably, atmospheric pressure or real-time ion sources such as electrospray ionization ("ESI") ion sources, matrix-assisted laser desorption ionization ("MALDI") ion sources, real-time direct analysis ("DART") ion sources, and laser ablation electrospray ionization ("LAESI") ion sources are used.

[0041] The U-shaped ion mobility analyzer 2 includes a first channel CH1 and a second channel CH2, both of which are composed of two sets of electrode arrays positioned opposite each other and extending perpendicular to the axial direction (referring to Figure 1, the first channel CH1 is formed between the two sets of electrode arrays on the left, i.e., the first electrode array and the second electrode array, and the second channel CH2 is formed between the two sets of electrode arrays on the right).

[0042] The U-shaped ion mobility analyzer 2 has an ion inlet 201, an ion outlet 203, and an inter-channel ion transfer port 202. The ion inlet 201 is provided on the electrode array near the upstream side of the first channel CH1, the ion outlet 203 is provided on the electrode array near the downstream side of the second channel CH2, and the inter-channel ion transfer port 202 is provided on the electrode arrays adjacent to the first channel CH1 and the second channel CH2, and connects the first channel CH1 and the second channel CH2.

[0043] The U-shaped ion mobility analyzer 2 has an airflow supply section, through which airflow passes in both the first channel CH1 and the second channel CH2. The direction of airflow is the vertical direction in Figure 1, and the equilibrium between the airflow driving force and the electric field restraining force in the U-shaped ion mobility analyzer 2 is along the vertical direction in Figure 1, i.e., the radial direction perpendicular to the axial direction. Therefore, if the conditions for balancing the airflow driving force and the electric field restraining force are not met, the ions escape and disappear through the openings at both ends in the radial direction and are not transported to the next stage. Between CH1 and CH2, ions can be transported from CH1 to CH2 or transferred to CH2 by a "dipole DC" electric field or a deflected DC electric field.

[0044] The principles for realizing the basic functions of the U-shaped ion mobility analyzer 2, such as holding, accumulating, moving, and separating ions in the first channel CH1 and the second channel CH2, can be found in prior applications, patents CN109003877A, CN109003876A, and CN115223844A, and will not be described in detail here.

[0045] The ion dissociation device 4 is a collision-induced dissociation device, an electron dissociation device, an infrared photodissociation device, an ultraviolet photodissociation device, or a radical dissociation device. Preferably, the ion dissociation device 4 is a collision-induced dissociation device.

[0046] The mass spectrometer 5 may be one or more selected from the group consisting of quadrupole mass spectrometers, time-of-flight mass spectrometers, Fourier transform mass spectrometers, ion trap mass spectrometers, and magnetic field mass spectrometers. The mass spectrometer 5 may be a quadrupole mass spectrometer or a time-of-flight mass spectrometer, and may be combined with the quadrupole mass filter 3 to form a tandem mass spectrometer of the form of Q-TOF or triple quadrupole.

[0047] In this embodiment, the ion mobility mass spectrometer 100 is further provided with ion optics 6 between the ion source 1 and the U-shaped ion mobility analyzer 2, and between the U-shaped ion mobility analyzer 2 and the quadrupole mass filter 3, for functions such as ion focusing, guiding, or holding. Note that the multi-stage vacuum structure and the corresponding arrangement of the ion optics 6 in Figure 1 are merely illustrative, and in other embodiments of the present invention, the multi-stage vacuum structure and the arrangement of the ion optics 6 may be adjusted as needed, and the present invention is not limited thereto.

[0048] Although the structure of the ion mobility mass spectrometer 100 in one preferred embodiment of the present invention has been described above, the data acquisition method according to other embodiments of the present invention can also be applied to an ion mobility mass spectrometer formed by connecting a UMA and a primary mass spectrometer in series, and in the embodiments of the present invention, it is not limited whether the mass spectrometer is a tandem mass spectrometer or not.

[0049] <Data collection method> Figure 2 is a schematic diagram of a conventional scanning mode used in a U-shaped ion mobility analyzer in the prior art. In this mode, the scanning range for ions within the entire mobility range is the same in the preliminary collection step and the subsequent analytical scanning step. Each time an analytical scanning step is performed, the ion mobility spectrometer must scan for ions within the entire mobility range. This is not only time-consuming, but also results in a large space charge effect because ions with relatively concentrated mobility will be distributed in a relatively concentrated manner.

[0050] The data collection method according to the embodiment of the present invention is shown in Figure 3.

[0051] First, a preliminary collection step S1 is performed to separate the parent ions ionized by the ion source 1 into a mass spectrometer via a U-shaped ion mobility analyzer 2, and obtain a two-dimensional heat map of the parent ions by ion mobility-mass spectrometry. Specifically, in the preliminary collection step S1, the first channel CH1 is used to accumulate ions across the entire mobility range or a relatively wide mobility range, and the second channel CH2 sequentially releases the ions accumulated in the first channel CH1 to the quadrupole mass filter 3.

[0052] Figure 4 is a schematic diagram of the ion behavior of the first channel CH1 and the second channel CH2 in the pre-collection and storage step of the pre-collection step of an embodiment of the present invention, and Figure 5 is a schematic diagram of the ion behavior of the first channel CH1 and the second channel CH2 in the pre-collection and ion transfer step of the pre-collection step of an embodiment of the present invention. Referring to Figures 4 and 5, the pre-collection step S1 includes a pre-collection and storage step and a pre-collection and ion transfer step that are performed sequentially. The straight lines or piecewise lines in Figures 4 and 5 show the electric field strength distribution of the radial DC electric field in the first channel CH1 and the second channel CH2, respectively.

[0053] Referring to Figure 4, in the preliminary collection and storage step, parent ions ionized by the ion source 1 continuously enter the first channel CH1, and at the same time, the dipole DC electric field for controlling the inter-channel ion transfer port 202 is closed, i.e., the inter-channel ion transfer port 202 is closed, and ions cannot enter the second channel CH2. By balancing the airflow driving force and the electric field restraining force, parent ions are continuously stored in the first channel CH1. The second channel CH2 releases ions in the second channel CH2 in order of decreasing ion mobility.

[0054] Referring to Figure 5, after a certain period of time, ion release from the second channel CH2 is basically completed, and the preliminary ion collection and transfer step is executed. The dipole DC electric field (i.e., deflected DC electric field) corresponding to the inter-channel ion transfer port 202 is turned on, and the parent ions accumulated in the first channel CH1 during the preliminary collection and storage step are transferred to the second channel CH2 via the inter-channel ion transfer port 202.

[0055] The ion storage and scanning methods shown in Figures 4 and 5 are the same as the conventional scanning modes used in U-shaped ion mobility analyzers.

[0056] Figure 6 shows an example of a two-dimensional ion mobility-mass spectrometry heatmap obtained in the preliminary collection step S1. After the preliminary collection step S1, the two-dimensional ion mobility-mass spectrometry heatmap is analyzed to identify the trend line (i.e., the dashed line in Figure 6). By analyzing the trend line, it is possible to more selectively select parent ions for DDA analysis or to more accurately identify the target mobility range and mass selection range for DIA analysis.

[0057] Furthermore, in the preliminary collection step S1, intensity and mobility information of the parent ions can also be obtained. The intensity information of the parent ions can be used for DDA analysis, and the mobility information of the parent ions can be used to calculate the collision cross-section (CCS), thus contributing to qualitative analysis.

[0058] After completing the preliminary collection step S1 and identifying the trend line, parent ions are accumulated, selected, and tandem analyzed. Specifically, the target mobility range of the U-shaped ion mobility analyzer 2 and the mass selection range of the quadrupole mass filter 3 are first identified based on the ion mobility-mass spectrometry two-dimensional heatmap and its trend line, at different time points within a single cycle. As shown in Figure 6, the target mobility range and mass selection range can be identified based on the two-dimensional heatmap and trend line, taking into account the interest in different types of targets in this analysis. One target mobility range and one mass selection range constitute one region of interest, and the number, width, start and end positions of the region of interest can all be adjusted according to the type of target substance selected, its charge, and the analysis results of the trend line. This ensures that as many target substances as possible are included within the region of interest composed of the target mobility range and mass selection range, and that the region of interest set along the trend line more accurately covers the target substances and avoids the generation of excessive noise.

[0059] Next, the ion accumulation step S2, ion transfer step S3, and ion scanning step S4 are repeatedly performed to obtain ion mobility-mass data for daughter ions corresponding to multiple sets of parent ions.

[0060] Here, the ion accumulation step S2 selectively accumulates parent ions within the target mobility range, which have been ionized by the ion source 1, in the target ion accumulation section of the first channel CH1 of the U-shaped ion mobility analyzer 2. Here, the target mobility range is determined based on the ion mobility-mass spectrometry two-dimensional heat map, i.e., the target mobility range corresponding to each region of interest in Figure 6.

[0061] In ion transfer step S3, parent ions within the target mobility range, held in the first channel CH1 of the U-shaped ion mobility analyzer 2, are transferred to the second channel CH2 of the U-shaped ion mobility analyzer 2.

[0062] In ion scanning step S4, after a predetermined time, parent ions within the target mobility range in the second channel CH2 of the UMA are scanned in order of target ion mobility and released into the quadrupole mass filter 3.

[0063] The quadrupole mass filter 3 further releases parent ions within the mass selectivity range to the subsequent stage. The mass selectivity range is determined based on a two-dimensional heatmap of ion mobility-mass spectrometry, i.e., the mass selectivity range corresponding to each region of interest in Figure 6.

[0064] In this embodiment, the operating modes of the UMA are basically unified in the preliminary collection step S1, the ion storage step S2, and the ion scanning step S4, eliminating the need for mode switching and making it convenient for synchronization with the operating cycle of the quadrupole mass filter 3.

[0065] Figure 7 shows the method for setting the target mobility ranges of the first channel CH1 and the second channel CH2 in each step of one embodiment of the present invention. Figures 8 to 11 are schematic diagrams of the DC electric field application modes of the first channel CH1 and the second channel CH2 in the ion storage step S2, ion transfer step S3, and ion scanning step S4 of the embodiment of Figure 7. Figures 7 to 11 illustrate seven different ion mobilitys as examples, and the straight lines or piece lines in the coordinate system of Figures 8 to 11 represent the DC electric field strength distributions of the first channel CH1 and the second channel CH2, respectively.

[0066] As shown in Figure 7, first, the ion accumulation step S2 of the first cycle is performed to set the target mobility range of the first channel CH1 to match the ion mobility of ions 1 and 2, so that ions 1 and 2 are accumulated in the target ion accumulation section 204, and ions 3 to 7 are accumulated in the non-target ion accumulation section of the first channel CH1, for example, the second non-target ion accumulation section 205b. Next, the ion transfer step S3 of the first cycle is performed to transfer ions 1 and 2 accumulated in the target ion accumulation section 204 to the second channel CH2, and then the ion scanning step S4 is performed to scan ions 1 and 2 in the second channel CH2 and release them to the downstream device.

[0067] As shown in Figures 7 and 8, when the second cycle, i.e., steps S2 to S4, is repeated for the first time, a new target mobility range is set, and the target mobility range is set to match the ion mobility of ions 3 to 5. When the ion accumulation step S2 of the second cycle is executed, among the parent ions 1 to 7 ionized by the ion source 1, ions within the defined target mobility range (ions 3, 4, and 5 in Figure 8) are selected and accumulated in the target ion accumulation section of the first channel CH1.

[0068] In this embodiment, the target ion accumulation section 204 is the section from the ion inlet 201 of the first channel CH1 to the inter-channel ion transfer port 202. However, in other embodiments, the division of the target ion accumulation section 204 may be adjusted depending on the situation. The non-target ion accumulation sections are located at both ends of the first channel CH1 and include a first non-target ion accumulation section 205a from the ion inlet 201 to the opening at one end of the first channel CH1, and a second non-target ion accumulation section 205b from the inter-channel ion transfer port 202 to the opening at the other end of the first channel CH1. Referring to Figure 8, when the ion accumulation step S2 of the second period is performed, ions outside the target mobility range, i.e., ions 1, 2, 6, and 7 in Figure 8, are held within the non-target ion accumulation sections in the first channel CH1. Here, ions 1 and 2, which have relatively high ion mobility, are retained in the first non-target ion accumulation section 205a, which is closer to the ion inlet 201, while ions 6 and 7, which have relatively low ion mobility, are retained in the second non-target ion accumulation section 205b, which is closer to the ion transfer port 202.

[0069] Since the UMA has dual channels and is independently controlled, the ion scanning step S4 can be performed simultaneously with the ion storage step S2. That is, when the second channel CH2 is releasing target ions within the current target mobility range, the target ion storage section 204 of the first channel CH1 is storing target ions within the target mobility range that need to be released in the next ion scanning step S4. Furthermore, the target ion storage section 204 can store target ions within the target mobility range that are continuously acquired from the ion source 1, or it can receive and store ions from the first non-target ion storage section 205a or the second non-target ion storage section 205b at either end that were not within the target mobility range in the previous step but are now within the adjusted target mobility range in this step. This flow allows for efficient management of ion storage and release within the dual channels, achieving both ion utilization efficiency and scanning speed.

[0070] Specifically, as shown in Figure 8, when performing the ion accumulation step S2 and the ion scanning step S4, a linear DC electric field is applied to the entire radial direction of the first channel CH1 (left-right direction in Figure 8, i.e., the length direction of the UMA). In the first non-target ion accumulation section 205a, the electric field strength is relatively small, so the electric field force experienced by the ions is small, and ions 1 and 2, which have a small collision cross-section CCS (high ion mobility), can balance with the airflow and the electric field force and are retained in that region. In the intermediate target ion accumulation section 204, the electric field strength is moderate, and accordingly, the target ion accumulation section 204 of the first channel CH1 accumulates ions 3, 4, and 5, which have moderate mobility. In the second non-target ion accumulation section 205b, the electric field strength is relatively large, so the electric field force experienced by the ions is large, and ions 6 and 7, which have a large collision cross-section CCS (low ion mobility), can balance with the airflow and the electric field force and are retained in the second non-target ion accumulation section 205b. Furthermore, the second channel CH2 scans and releases high-mobility ions 1 and 2 that could not be analyzed in the previous period (first period) to the next stage. As shown in Figure 8, in this embodiment, different regions along the length of the first channel CH1 can all retain ions, and in the target ion accumulation section 204, which is the main part of the first channel CH1, the ion accumulation step S2 and the ion transfer step S3 are two different steps, so the target ions within the target mobility range are first retained in the target ion accumulation section 204 and then rapidly transferred to the second channel CH2. In the ion accumulation step S2, the gradient of the DC electric field can be set to be relatively small (for example, a DC electric field that changes linearly along the entire target ion accumulation section 204 as shown in Figure 8), thereby allowing ions within the target mobility range to be distributed more dispersedly along the length of the target ion accumulation section 204 without concentrating in a specific region. This method effectively reduces the space charge effect and improves the resolution for low-abundance ions.

[0071] As shown in Figure 9, after a certain period of time, the release of parent ions from the second channel CH2 is basically completed, and the ion transfer step S3 of the second cycle is executed, transferring the parent ions in the target ion accumulation section 204 of the first channel CH1 to the second channel CH2 via the inter-channel ion transfer port 202.

[0072] In this embodiment, the U-shaped ion mobility analyzer 2 can rapidly transfer ions between the first channel CH1 and the second channel CH2 and improve the duty cycle by adjusting the DC electric field distributed on the electrode array and the dipole DC electric field around the inter-channel transfer port 202. Specifically, as shown in Figure 9, by continuously decreasing the electric field at the inter-channel ion transfer port 202 and turning on the dipole DC electric field, ions 3 to 5 can be quickly moved to their respective positions and introduced into the second channel CH2 via the inter-channel ion transfer port 202.

[0073] The duration of the ion transfer step S3 is much shorter than that of the ion storage step S2, resulting in a shorter overall operating cycle and thus an improved duty cycle. Specifically, within the same cycle, the duration of the ion transfer step S3 is 1 / 10, or even less than 1 / 100, of the duration of the ion storage step S2.

[0074] In some embodiments, ions with certain ion mobilities or ion mobility ranges can be removed (filtered) by closing the inter-channel ion transfer port 202 during certain periods. By removing some unwanted parent ions during the ion transfer process, parent ions as the target analyte can be accumulated with high efficiency, improving the dynamic range of methods such as DDA.

[0075] In some other embodiments, ions within the non-target ion accumulation section or ions partially originating from the target ion accumulation section can also be removed by stopping the application of a DC electric field to the non-target ion accumulation section or by applying a radial DC bias. Specifically, ions in the second non-target ion accumulation section 205b can be removed by stopping the application of a DC electric field (the ions are carried out axially by the airflow), or ions in the first non-target ion accumulation section 205a or the second non-target ion accumulation section 205b can be removed by applying a radial DC bias. As a result, the removal of temporarily held ions can be completed simply and is easier to implement compared to TIMS.

[0076] Continuing to refer to Figure 10, as the second channel CH2 sequentially releases ions 3 through 5, the first channel CH1 repeatedly performs the ion accumulation step S2 of the third period. However, the target mobility range of this ion accumulation step S2 is adjusted again (by adjusting the gradient of the DC electric field or changing the distribution of the DC electric field, etc.), specifically to selectively accumulate low-mobility ions 6 and 7. As shown in Figure 10, ions 6 and 7 from the ion inlet 201 accumulate in the target ion accumulation section 204. At the same time, ions 6 and 7 that were temporarily held in the second non-target ion accumulation section 205b in the previous ion accumulation step S2 also return to the target ion accumulation section 204 due to the action of airflow or electric field force. Simultaneously, in the first channel CH1, high-mobility ions 1 and 2, and medium-mobility ions 3 through 5 are temporarily held in the first non-target ion accumulation section 205a.

[0077] Once the scanning and release of ions 3-5 in the second channel CH2 is basically complete, the ion transfer step S3 is executed again to transfer ions 6 and 7 in the first channel CH1 to the second channel CH2. Figure 11 may be used to show the specific method for setting the electric field distribution. After the ion transfer step S3, the third period's ion scanning step S4 is executed to sequentially release ions 6 and 7 in the second channel CH2 to the quadrupole mass filter 3.

[0078] After the ion scanning step S4, or synchronized with the ion scanning step S4, the daughter ion collection step is performed, and the scanned and released ions are sequentially passed through the quadrupole mass filter 3 and the ion dissociator 4, and finally introduced into the mass spectrometer 5. Specifically, the selected parent ions enter the ion dissociator 4 and dissociate to generate daughter ions, which are then entered into the mass spectrometer 5 for analysis, and ion mobility-mass data of the daughter ions is obtained. This embodiment describes the case of DDA / DIA data collection as an example, but after all parent ions are selected and the ion mobility-mass data of the corresponding parent or daughter ions is collected, the flow can be terminated, or all of the above-described preliminary collection steps S1, ion storage step S2, ion transfer step S3, and ion scanning step S4 can be repeated one or more times. In the repeated ion storage step S2, ion transfer step S3, and ion scanning step S4, some parameter settings may be changed compared to the previous storage and scanning / release. For example, by changing parameters such as the size of the target mobility range or window in parent ion selection, or the size of the mass selection range or window, or by changing the order of parent ion selection, or by changing the collision energy or residence time of the ion dissociation apparatus 4, more information can be obtained, thereby improving the coverage and depth of the analysis.

[0079] As described above, the data acquisition method according to this embodiment divides ions into multiple sets according to their mobility in the first channel CH1, and can hold ions within the target mobility range and ions outside the target mobility range in different regions. This allows for highly efficient use of each region along the length of the first channel CH1 to hold ions, and ion packets with different mobility ranges are introduced into the second channel CH2 in batches for analysis, thereby avoiding excessive concentration of ions and reducing space charge effects. Furthermore, although only ions within a specific mobility range are selected in the first channel CH1 at one time, ions with other mobilities are not lost during this selection process, but are temporarily held in the non-target ion accumulation section 205 and continue to enter the second channel CH2 for analysis in subsequent steps, so that the sensitivity of the entire process does not decrease.

[0080] <Target mobility range and mass selection range> In this embodiment, the target mobility range and mass selection range can be specified according to the analytical method used by the coupling device. For example, if the coupling device employs DDA data analysis, it can select multiple sets of parent ions with signal intensity higher than a threshold in the ion mobility-mass spectrometry two-dimensional heatmap, or select multiple sets of parent ions with relatively high signal intensity in the ion mobility-mass spectrometry two-dimensional heatmap. That is, it selects the few sets of parent ions with the strongest or relatively strongest signal intensity and performs the analysis. In the process of selecting parent ions, the trend line can provide reference information about the charge status or molecular type of the parent ions, contributing to a more accurate selection of parent ions. Of course, in some other embodiments, it is also possible to select and analyze parent ions with relatively low abundance as targets.

[0081] When employing the DIA data analysis method, as shown in Figure 6, it is possible to select fixed-width mass windows and ion mobility windows stepwise along the trend line, and the period during which the U-shaped ion mobility analyzer 2 scans the target mobility range is synchronized with the period during which the quadrupole mass filter 3 scans the mass selection range. Specifically, within one analysis cycle, the U-shaped ion mobility analyzer 2 sequentially scans different ion mobility windows from high mobility to low mobility (i.e., from large collision cross-section CCS to small collision cross-section), while within one analysis cycle, the quadrupole mass filter 3 sequentially scans different mass windows from low mass to high mass. During the daughter ion collection step, smaller parent ions typically correspond to smaller daughter ions, and since smaller daughter ions have a relatively short residence time in the ion dissociation apparatus 4, their transport within the ion dissociation apparatus 4 is less susceptible to interference from subsequent larger daughter ions. Therefore, the quality of the mobility spectrum is not affected (for example, mobility peak mismatches are avoided), and the channel scanning of DDA or DIA can be accelerated.

[0082] Referring to Figure 12, different types of compounds (sugars, peptides, proteins, etc.) are typically distributed in different regions in a two-dimensional ion mobility-mass spectrometry heatmap, and ions with different charge numbers are typically distributed along trend lines with different slopes. Based on the distribution regions and trend lines in the heatmap, substances with different charge numbers and types can be distinguished relatively clearly, thereby enabling more selective selection of target parent ions for DDA analysis, or more accurate identification of the target mobility range and mass selectivity range for DIA analysis. Therefore, in some preferred embodiments, the two-dimensional heatmap can be divided into corresponding local areas (local images shown by dashed frames in Figure 12) based on the accumulation state of dots of different types and charge numbers of compounds, a single trend line can be individually identified for each local area, and DIA / DDA data can be collected individually for each local area. This method allows for more accurate identification of the appropriate target mobility range and mass selectivity range, effectively improving the accuracy of qualitative or quantitative analysis and accelerating scanning.

[0083] In this embodiment, the U-shaped ion mobility analyzer 2 is used as an ion mobility analyzer, and a mode is adopted in which accumulation and scanning / release are performed in sync, using a combination of the first channel CH1 and the second channel CH2. As a result, ions are transported to the next stage by passing through the U-shaped ion mobility analyzer 2, or are temporarily held in the non-target ion accumulation section (first non-target ion accumulation section 205a or second non-target ion accumulation section 205b). This allows almost all ions to be utilized, achieving an ion utilization efficiency close to 100%.

[0084] In particular, the ion mobility-mass spectrometry two-dimensional heatmap obtained by the preliminary collection step S1 allows for more accurate identification of the target mobility range. This enables more selective accumulation of ions within the specific target mobility range in the ion scanning step S4, thus avoiding the occupying of the accumulation interval by non-target ions and affecting the dynamic range.

[0085] By combining the U-shaped ion mobility analyzer 2 with the data acquisition method provided in this embodiment, the coupling device can perform data acquisition suitable for different analytical methods (e.g., DIA and DDA methods in different modes), thereby solving the problems of difficulty in ion removal and limitations in dynamic range that conventional data acquisition methods face.

[0086] Referring to Figure 13, an embodiment of the present invention further provides a high dynamic range selective exclusion scanning mode. If, within the entire mobility range, some ions in a certain range are not the target ions, or if no ions exist in that range (which can be confirmed based on a two-dimensional heatmap during preliminary acquisition), the data acquisition method of this embodiment allows the second channel CH2 to skip scanning this mobility range, thereby allocating more scanning time to the target ions, or shortening the scanning time, thereby further improving the resolution or analysis speed of the target ions. As an example in Figure 13, by skipping the scanning of ions 3, 4, and 5, the scanning method ensures that all selected ions are detected in the same quantity, while saving the time required to scan ions 3, 4, and 5.

[0087] The foregoing are merely preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should all be included within the scope of protection of the present invention. [Explanation of Symbols]

[0088] 100 Ion mobility mass spectrometer 1. Ion source 2. U-shaped ion mobility analyzer 201 Aeon Entrance 202 Inter-channel ion transfer port 203 Aeon Exit 204 Target ion accumulation section 205a First non-target ion accumulation section 205b Second non-target ion accumulation section 3. Quadrupole Mass Filter 4. Ion dissociation apparatus 5 Mass spectrometer 6. Ion Optical Apparatus CH1 First Channel CH2 Second channel

Claims

1. A data acquisition method applicable to an ion mobility mass spectrometer, The ion mobility mass spectrometer comprises a sequentially connected ion source, a U-shaped ion mobility analyzer, and a mass spectrometer. The aforementioned data collection method is: A preliminary collection step in which the ion to be analyzed, ionized by the ion source, is separated into the mass spectrometer via the U-shaped ion mobility analyzer, An ion accumulation step in which ions within the target mobility range are accumulated in the target ion accumulation section of the first channel of the U-shaped ion mobility analyzer, and ions outside the target mobility range are introduced and accumulated in the non-target ion accumulation sections at both ends of the first channel, An ion transfer step of transferring ions within the target mobility range in the first channel of the U-shaped ion mobility analyzer to the second channel of the U-shaped ion mobility analyzer, The ion scanning step includes scanning and releasing ions within the target mobility range in the second channel of the U-shaped ion mobility analyzer to the mass spectrometer, A data acquisition method characterized in that, in the repeated steps of the ion accumulation step, the ion transfer step, and the ion scanning step, the target mobility range is either the target mobility range defined in the previous scan, or a mobility range corresponding to at least a portion of the ions introduced into the non-target ion accumulation section in the previous scan.

2. The ion mobility mass spectrometer further comprises a mass filter and an ion dissociation device provided between the U-shaped ion mobility analyzer and the mass spectrometer, In the preliminary collection step, a two-dimensional heat map of the ion mobility-mass spectrometry of the ion to be analyzed is obtained. The data acquisition method according to claim 1, characterized in that the ions emitted from the second channel of the U-shaped ion mobility analyzer pass through the mass filter and the ion dissociation device and are introduced into the mass spectrometer.

3. The data acquisition method according to claim 1, characterized in that the target mobility range of ions accumulated in the target ion accumulation section of the first channel is changed by adjusting the DC electric field strength distribution of the first channel in a plurality of different ion accumulation steps.

4. The data acquisition method according to claim 1, characterized in that ions accumulated in the non-target ion accumulation sections at both ends of the first channel are released in the next ion accumulation step by changing the DC electric field strength distribution of the first channel and introduced into the target ion accumulation section, and then enter the second channel where mobility scanning is performed.

5. The data acquisition method according to claim 1, characterized in that, in the ion scanning step, the ions in the second channel are released in order of decreasing ion mobility.

6. The data acquisition method according to claim 2, characterized in that, in the ion scanning step, the mass selection range of the mass filter is a mass window of fixed width, and the mass filter sequentially scans different mass windows from the low mass side to the high mass side within one analysis cycle.

7. The data acquisition method according to claim 6, characterized in that the mass filter is a quadrupole mass filter, and the scanning period of the U-shaped ion mobility analyzer within the target mobility range is synchronized with the scanning period of the quadrupole mass filter within the mass selection range.

8. The data acquisition method according to claim 7, characterized in that the mobility scanning of the U-shaped ion mobility analyzer and the mass scanning of the quadrupole mass filter are performed along the trend line in the two-dimensional heat map.

9. The data acquisition method according to claim 2, characterized in that, in the ion scanning step, multiple sets of ions whose signal intensity in the ion mobility-mass spectrometry two-dimensional heat map is higher than a threshold, or multiple sets of ions whose signal intensity in the ion mobility-mass spectrometry two-dimensional heat map is relatively high.

10. The data acquisition method according to claim 2, characterized in that, in the ion scanning step, the mass selection range of the mass filter includes all mass numbers within the current mobility range in the ion mobility-mass spectrometry two-dimensional heat map.

11. The data acquisition method according to claim 2, characterized in that, in the ion scanning step, the mass selection range of the mass filter includes a subset of mass numbers corresponding to the target mobility range in the ion mobility-mass spectrometry two-dimensional heatmap, and the width of the mass scanning window is kept constant or changed based on the prediction of the ion mobility-mass spectrometry two-dimensional heatmap.

12. The data acquisition method according to claim 2, characterized in that, in the ion scanning step, the window width of the target mobility range is kept constant or changed based on the prediction of the ion mobility-mass spectrometry two-dimensional heat map.

13. Both the first channel and the second channel are composed of two sets of electrode arrays that are arranged opposite each other and extend perpendicular to the axial direction. The U-shaped ion mobility analyzer has an ion inlet, an ion outlet, and an inter-channel ion transfer port. The data acquisition method according to claim 1, characterized in that the ion inlet is provided in an electrode array near the upstream side of the first channel, the ion outlet is provided in an electrode array near the downstream side of the second channel, and the inter-channel ion transfer port is provided in an electrode array adjacent to the first channel and the second channel, and connects the first channel and the second channel.

14. The data acquisition method according to claim 13, characterized in that, in the ion transfer step, some ions with a certain ion mobility or ion mobility range are removed by closing the inter-channel ion transfer port for a certain period of time.

15. The data acquisition method according to claim 1, further comprising the step of removing ions in the non-target ion accumulation section by stopping the application of a DC electric field to the non-target ion accumulation section or by applying a radial DC bias.

16. An ion mobility mass spectrometer characterized by applying the data acquisition method described in any one of claims 1 to 15.

17. The ion mobility mass spectrometer according to claim 16, characterized in that the mass spectrometer is one or more selected from the group consisting of a quadrupole mass spectrometer, a time-of-flight mass spectrometer, a Fourier transform mass spectrometer, an ion trap mass spectrometer, and a magnetic field mass spectrometer.

18. The ion mobility mass spectrometer according to claim 16, characterized in that the ion mobility mass spectrometer includes an ion dissociation device, and the ion dissociation device is one or more selected from the group consisting of a collision-induced dissociation device, an electron dissociation device, an infrared photodissociation device, an ultraviolet photodissociation device, and a radical dissociation device.

19. A first channel having a first electrode array and a second electrode array arranged opposite each other, wherein the first electrode array is provided with an ion inlet, and the second electrode array is provided with an inter-channel ion transfer port, and the installation positions of the inter-channel ion transfer port and the ion inlet are offset from each other, A second channel that receives ions from the first channel via the inter-channel ion transfer port, An airflow supply unit that supplies or exhausts gas to at least the first channel and forms an airflow that flows along the first channel, A power supply that applies an electric field to at least the first channel and utilizes the balance between the electric field force, which is in opposite directions, and the driving force on the ions due to the airflow to accumulate ions within the target mobility range in the target ion accumulation section between the ion inlet and the inter-channel ion transfer port, and accumulates ions outside the target mobility range in non-target ion accumulation sections at both ends of the first channel, An ion mobility analyzer characterized by having the following features.

20. The ion mobility analyzer according to claim 19, characterized in that the power supply further applies an electric field to the second channel and scans and emits ions within the target mobility range in the second channel.

Images