Data acquisition method and hybrid ion mobility spectrometer-mass spectrometer

Abstract

A method which can effectively increase the acquisition efficiency and / or resolution of ion mobility spectrometry-mass spectrometry. The method can be suitable for DDA or DIA data acquisition, and can also be suitable for common ion mobility spectrometry-primary mass spectrometry data acquisition, solving the problems in existing data acquisition methods of being affected by a space charge effect, such that the dynamic range is limited, and scanning speed being too slow. The data acquisition method is applied to serial UMA and mass spectrometry analysis, and comprises a pre-acquisition step (S1), and a step of performing target ion accumulation (S2) and parallel storage of target external ions. An ion dissociation step can further be added, so that high-speed, high-dynamic range DDA or DIA data can be conveniently obtained.

Description

Data acquisition method and ion mobility spectrometry-mass spectrometry Technical Field

[0001] The present invention relates to the field of mass spectrometry, and in particular to a data acquisition method, an ion mobility analyzer, and an ion mobility spectrometer-mass spectrometer. Background Art

[0002] Ion mobility spectrometry is a technique for separating ions based on their mobility. For conventional drift cell ion mobility spectrometry, resolution can be improved by extending the length of the drift cell, increasing the migration voltage, and other methods. To further improve resolution, a method of applying a reverse electric field in a uniform airflow field can also be adopted to increase the equivalent distance of ion migration. Zeleny (Zeleny, J. Philos. Mag. 46, 120 (1898)) proposed a method for analyzing ions in a parallel flow analyzer by balancing airflow and electric field in opposite directions. Zeleny's device contains two parallel grids, and ions with specific mobility are balanced under the action of two opposing forces (airflow and electric field).

[0003] In recent years, there have been many attempts to make ions move in the opposite direction of the airflow under the action of a DC electric field. U.S. Patent No. 6630662B1 proposes to use a uniform electric field. As the electric field slowly increases, the ions overcome the effect of the airflow under the action of the electric field and are expelled. However, due to the low applicable air pressure (Pa), the resolution of this method is also low. Chinese Patent No. CN101738429 A proposes to use the different DC gradients existing in different areas of the mobility analyzer to enrich ions of different mobilities at the same time. However, since the ions in this patent can only be extracted radially in their respective enrichment areas, more detection devices are required. U.S. Patent No. 8288717B2 proposes to use a non-uniform electric field to first separate ions with different mobilities, and then slowly reduce the electric field so that the ions are expelled from the analyzer axially under the action of the airflow. In the above methods, since ions of all mobilities are enriched in one analysis area waiting for the mobility spectrum scan, the space charge effect is more serious, and mobility resolution is therefore affected. Therefore, U.S. Patent No. 9,984,864 further proposed the use of two TIMS (Trapped Ion Mobility Spectrometer, TIMS) analyzers in series, and in the first TIMS, the enriched ions were preliminarily screened, only retaining ions within a certain target mobility range, and then these ions were sent to the second mobility analyzer. In this process, ions that are not within the target mobility range will no longer be protected by the radio frequency electric field when they are released from the first TIMS, and will therefore be lost in the system. However, this measure of removing the radio frequency protection may not be sufficient for ion removal, so U.S. Patent No. 10,241,079B2 proposed placing an ion gate between the two TIMS to further remove non-target mobility ions. The above TIMS method can selectively enrich and detect ions, but the second ion mobility analyzer in its device can only sequentially accept ions from the upstream ion storage area, and once ions that are not within the target analyte range are selected, they cannot be reused.

[0004] The device proposed by Chinese patent CN109003876B (U-type ion mobility mass spectrometer) can analyze ions separately through two channels; one of the modes of this analysis process is similar to TIMS, that is, the first channel can store ions and the second channel can perform mobility scanning. In the device provided by CN109003876B, how to further selectively analyze certain target ions without losing other non-target ions is also a challenge, which is similar to the challenges faced by the structures of U.S. patents US9984864 and US10241079B2. Therefore, how to reduce the space charge effect and improve the ion scanning resolution in the design of this type of countercurrent mobility spectrometer while also ensuring the freedom of ion selection and utilization efficiency is one of the current focuses of the industry. The present invention is a further improvement and innovation of the device structure and working mode based on the structure proposed by Gillig patent.

[0005] In addition, data-independent acquisition (DIA) technology has also seen rapid development in recent years. Rather than targeting specific precursor ions for collisional dissociation and analysis, DIA targets specific mass-to-charge ratio windows or ions across the full mass range, then analyzes the resulting complex spectral data. Compared to DDA, DIA can accurately identify relatively low-abundance ions, offering higher sensitivity, dynamic range, analytical throughput, and improved quantification.

[0006] To further enhance sensitivity and increase the dimension of orthogonal separation, an increasing number of manufacturers are coupling ion mobility spectrometers (IMS) to tandem mass spectrometry instruments. This allows for further separation of different ions by leveraging differences in their ion mobility properties, thereby improving ion identification capabilities. For example, U.S. Patent No. 9,891,194 combines TIMS technology with DIA / DDA technology to form the so-called parallel acquisition serial dissociation (PASEF) approach. Its core advantage is the utilization of the time-matched relationship between the TIMS instrument, the chromatogram, and the mass spectrometer, as well as its high ion utilization efficiency, to improve the ion identification coverage in DDA / DIA. However, a limitation of this process is the lack of flexibility in parent ion selection. This inflexibility manifests itself in the first TIMS instrument. As mentioned above, during the initial selection of the parent ion scanning interval, other non-target ions are inevitably lost. Conversely, if no initial selection is performed, an excessive number of ions will enter the second TIMS, potentially leading to severe space charge effects. The structure and operating mode proposed in this invention can be applied to mobility spectrometry-mass spectrometry instruments to address the aforementioned issues encountered during DDA / DIA acquisition.

[0007] To solve the problem of non-target ion loss, Chinese patent application CN115223844A proposes to temporarily store ions that are not in the target analysis area at the edge of each channel of the U-shaped migration spectrum analyzer, and then release them during the next migration spectrum scanning cycle. This method has played a certain role in retaining non-target ions, but at this time, the U-shaped migration spectrum analyzer operates in filter mode and sequential scanning, which is different from the selective capture-scan mode (trap scan) in which the U-shaped migration spectrum analyzer operates in the present invention. The area of ​​non-target ion enrichment is also different, so it is two different technical directions. At the same time, because the structure proposed by CN115223844A operates in filter mode, when realizing functions such as cascade migration spectrum, the current U-shaped migration spectrum analyzer structure must be modified to a certain extent.

[0008] Summary of the Invention

[0009] In response to the above problems, the present invention provides a data acquisition method that can reduce the influence of space charge, improve resolution or reduce the time of migration spectrum scanning without substantially losing sensitivity.

[0010] Previously, we developed a U-shaped ion mobility analyzer (UMA, CN109003877A), whose operating principle is also based on the combined effects of airflow and electric fields on ions. Unlike TIMS, the UMA has two parallel airflow channels that are perpendicular to the main ion path of the mass spectrometer. Based on this feature, by designing a special ion control process, we can effectively filter the ion mobility range of the enriched ions when they are enriched in the UMA's first channel, while also effectively storing ions outside the ion mobility range. At the same time, these synchronously stored non-target ions will not interfere with the analysis of the current target ions. In this way, the target ions can occupy a larger space, or even the entire first channel, reducing the impact of space charge and improving resolution without significantly compromising sensitivity. This ion control process is not only suitable for DDA and DIA data acquisition, but can also be applied to standard ion mobility spectrometry-first-stage mass spectrometry analysis.

[0011] Specifically, a first aspect of the present invention provides a data acquisition method applied to an ion mobility spectrometer-mass spectrometer, wherein the ion mobility spectrometer-mass spectrometer includes an ion source, a UMA, and a mass spectrometer connected in sequence, and the data acquisition method includes the following steps:

[0012] In the pre-collection step, the ions to be analyzed obtained by ionization in the ion source are separated by the UMA and sent to the mass spectrometer;

[0013] Ion accumulation step: ions within the target mobility range are accumulated in the target ion enrichment interval of the first channel of the UMA. At the same time, ions outside the target mobility range enter the non-target ion enrichment intervals at both ends of the first channel for enrichment.

[0014] an ion transfer step, transferring ions within the target mobility range in the first channel of the UMA to the second channel of the UMA;

[0015] an ion scanning step, scanning and releasing ions within a target mobility range in the second channel of the UMA to a mass spectrometer;

[0016] Repeat the ion accumulation step, the ion transfer step and the ion scanning step. In the repeated step, the target mobility range is the target mobility range defined in the previous scan, or the mobility range corresponding to at least a portion of the ions that entered the non-target ion enrichment interval in the previous scan.

[0017] According to the data acquisition method provided by the present invention, because in the ion accumulation step, only ions within the target mobility range (rather than the full mobility range) are accumulated in the target ion enrichment interval of the first channel, and the first channel does not perform fine mobility analysis, the ions can be distributed more dispersedly in the second channel, thereby effectively reducing the influence of space charge.

[0018] When ions within the target mobility range accumulate in the target ion enrichment zone of the first channel, at least some of the ions outside the target mobility range, except for those "noise ions" with extremely low or high mobilities (such as solvent ions or clustered ions), are not lost. Instead, they are stored in the non-target ion enrichment zones at both ends of the first channel and can continue to be 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 continue to participate in the analysis process of the next scan, so that essentially all ions are not wasted during the entire acquisition process.

[0019] Furthermore, when some ions need to be removed (such as the "noise ions" mentioned above), because the UMA is used as an ion mobility analyzer and the first and second channels are used in a synchronous accumulation and scan release mode, the filtered ions can directly leave the UMA without being transported to the subsequent stage, thus preventing the filtered ions from occupying the accumulation area and reducing the dynamic range loss that may be caused by spatial effects. This method of ion filtering is simpler and more efficient than methods such as using ion gates.

[0020] In an optional technical solution of the present invention, the ion mobility spectrometer-mass spectrometer further includes a mass filter and an ion dissociation device arranged between the UMA and the mass spectrometry device.

[0021] The pre-acquisition step obtains a two-dimensional heat map of the ion mobility spectrum-mass spectrum of the ions to be analyzed;

[0022] After the ions leave the second channel of the UMA, they pass through the mass filter and ion dissociation device and enter the mass spectrometer.

[0023] By the above means, the data acquisition method can be effectively adapted to DDA or DIA analysis, solves the problem of being difficult to filter out ions and limited dynamic range faced by existing data acquisition methods. By first carrying out a pre-collection to obtain the ion mobility spectrum-mass spectrum two-dimensional heat map of the parent ion, it is possible to determine a trend line (trend line), i.e., the relationship between ion mobility and mass number, and the determination of the trend line helps to select more suitable target mobility range and mass selection range in the different stages of the same cycle, thereby improving scanning efficiency. In addition, the pre-collection step can also obtain the intensity information and mobility information of the parent ion, and the intensity information of the parent ion is needed in implementing DDA analysis, and the mobility information of the parent ion can be used to calculate the collision cross-sectional area CCS, to help qualitative analysis. In the optional technical solution of the present invention, in multiple different ion accumulation steps, the DC electric field intensity distribution of the first channel is adjusted, so as to change the target mobility range of the ions accumulated in the target ion enrichment interval of the first channel. By adjusting the DC electric field intensity distribution in different cycles, it is possible to quickly and easily scan or jump to scan different target mobility ranges.

[0024] In an optional technical solution of the present invention, ions enriched in the non-target ion enrichment zones at both ends of the first channel are released during the next ion accumulation step by changing the DC electric field strength distribution of the first channel. They return to the target ion enrichment zone and then enter the second channel for mobility scanning. This method allows for the periodic and timely release of ions in the non-target ion enrichment zone, further ensuring that ions within the entire mobility range are effectively utilized, theoretically achieving a duty cycle close to 100%.

[0025] In an optional technical solution of the present invention, during the ion scanning step, ions in the second channel are released in descending order of ion mobility. Because smaller parent ions typically correspond to smaller daughter ions, and small daughter ions have shorter residence times within the ion dissociation device, releasing ions in this order prevents the transmission of small daughter ions within the ion dissociation device from being interfered with by subsequent larger daughter ions. This does not affect the quality of their mobility spectra (e.g., avoiding mobility spectrum peak mismatches), and can also accelerate channel scanning in DDA or DIA.

[0026] In an optional technical solution of the present invention, during the ion scanning step, the mass filter's mass selection range is a fixed-width mass window, and the mass filter sequentially scans different mass windows from small to large within a single analysis cycle. Because the UMA can scan ions from large to small in terms of ion mobility, this scanning method can effectively cooperate with the mass filter's mass number scanning method, which scans from small to large in terms of mass number, thereby improving scanning speed.

[0027] In an optional technical solution of the present invention, the mass filter is a quadrupole mass filter, and the scanning period of the UMA within the target mobility range is synchronized with the scanning period of the quadrupole mass filter within the mass selection range.

[0028] In an optional technical solution of the present invention, the UMA mobility scan and the quadrupole mass filter mass scan are performed along the trend line in the two-dimensional heat map. By performing the UMA mobility scan and the quadrupole mass filter mass scan along the trend line, the target ion analysis can be more targeted based on the type (such as peptides, lipids, carbohydrates, etc.) or charge number. Moreover, because the analysis is not limited to ions with a specific mobility or mass number, the possibility of missing less abundant ions can be reduced.

[0029] In an optional technical solution of the present invention, during the ion scanning step, multiple groups of ions whose signal intensities in the ion mobility spectrum-mass spectrometry two-dimensional heat map are above a threshold value are selected, or multiple groups of ions whose signal intensities in the ion mobility spectrum-mass spectrometry two-dimensional heat map are relatively high are selected. This data acquisition method can accurately screen target ions and efficiently acquire data suitable for analysis using the DDA method.

[0030] In an alternative embodiment of the present invention, during the ion scanning step, the mass filter's mass selection range includes all mass numbers within the current mobility range in the two-dimensional heat map. This data acquisition method can efficiently acquire data suitable for full mass range DIA analysis methods.

[0031] In an optional technical solution of the present invention, in the ion scanning step, the mass selection range of the mass filter includes part of the mass numbers corresponding to the current target mobility range in the two-dimensional thermal map, and the mass scanning window width remains unchanged or changes according to the prediction of the two-dimensional thermal map.

[0032] In an optional technical solution of the present invention, in the ion scanning step, the window width of the target mobility range remains unchanged or is changed according to the prediction of the two-dimensional thermal map.

[0033] The ion mobility spectrometer-mass spectrometer uses the aforementioned data acquisition method. It can use a scanning method with a constant window width to collect data for DIA analysis, or it can use a scanning method that changes according to the prediction of the two-dimensional thermal map to collect data for DDA analysis.

[0034] In an optional technical solution of the present invention, the first and second channels are each composed of two sets of electrode arrays arranged opposite 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 arranged in the electrode array near the front end of the first channel, the ion outlet is arranged in the electrode array near the back end of the second channel, and the inter-channel ion transfer port is arranged in the electrode array adjacent to the first and second channels, connecting the first and second channels. The UMA's operating mode during the pre-collection step, the ion accumulation step, and the ion scanning step is essentially unified, eliminating the need for mode switching and facilitating synchronization with the operating cycles of other components, such as the mass filter.

[0035] In an alternative embodiment of the present invention, during the ion transfer step, ions with a certain ion mobility or range of ion mobilities are filtered out by partially closing the inter-channel ion transfer ports. By filtering out unwanted ions during the transfer process, the target analyte ions can be efficiently enriched, thereby increasing the dynamic range of methods such as DDA.

[0036] In an optional technical solution of the present invention, ions in the non-target ion enrichment interval are removed by removing the DC electric field in the non-target ion enrichment interval or adding a radial DC bias. The ion path of the UMA is U-shaped, and the direction of ion transmission is not limited to the axial direction. Unwanted ions can also be removed in the radial direction. In this way, the removal of temporarily stored ions can be completed conveniently, which is easier to achieve than TIMS.

[0037] A second aspect of the present invention provides an ion mobility spectrometer-mass spectrometer using the data acquisition method of the present invention.

[0038] In an optional technical solution of the present invention, the mass spectrometry device is one or more of a quadrupole mass spectrometer, a time-of-flight mass spectrometer, a Fourier transform mass spectrometer, an ion trap mass spectrometer, and a magnetic mass spectrometer.

[0039] In an optional technical solution of the present invention, the ion mobility spectrometer-mass spectrometer includes an ion dissociation device, which is one or more of a collision-induced dissociation device, an electron dissociation device, an infrared photon dissociation device, an ultraviolet photon dissociation device, and a free radical dissociation device. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] FIG1 is a schematic structural diagram of a mass mobility spectrometer-mass spectrometer according to an embodiment of the present invention;

[0041] FIG2 is a schematic diagram of a conventional scanning mode used in a U-shaped ion mobility analyzer in the prior art;

[0042] FIG3 is a flow chart of a data acquisition method provided by an embodiment of the present invention;

[0043] FIG4 is a schematic diagram of ion behavior in the first channel and the second channel in the pre-collection step according to an embodiment of the present invention;

[0044] FIG5 is a schematic diagram of ion behavior in the first channel and the second channel in the pre-collection step according to an embodiment of the present invention;

[0045] FIG6 is a schematic diagram of a trend line determined based on an ion mobility spectrometry-mass spectrometry two-dimensional heat map according to an embodiment of the present invention;

[0046] FIG7 shows a method for setting target mobility ranges for the first channel and the second channel in each step according to an embodiment of the present invention;

[0047] 8 to 11 are schematic diagrams of DC electric field application methods in the first channel and the second channel during the ion accumulation step, ion transfer step, and ion scanning step within different mobility ranges according to an embodiment of the present invention;

[0048] FIG12 is a schematic diagram of a method for first partitioning a two-dimensional heat map according to the type, charge number, etc. of the compound according to an embodiment of the present invention;

[0049] FIG. 13 shows a method for setting target mobility ranges for the first channel and the second channel in each step in another embodiment of the present invention.

[0050] Figure 1: 100 - ion mobility spectrometer-mass spectrometer; 1 - ion source; 2 - U-type ion mobility analyzer; 201 - ion inlet; 202 - inter-channel ion transfer port; 203 - ion outlet; 204 - target ion enrichment interval; 205a - first non-target ion enrichment interval; 205b - second non-target ion enrichment interval; 3 - quadrupole mass filter; 4 - ion dissociation device; 5 - mass spectrometry device; 6 - ion optical device; CH1 - first channel; CH2 - second channel. DETAILED DESCRIPTION

[0051] The following will be combined with the accompanying drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0052] <Terms and their explanations>

[0053] The term "ion mobility spectrometer-mass spectrometer" is not limited to the combination of ion mobility spectrometer and mass spectrometer, and can also be combined with equipment such as chromatography to form a chromatography-ion mobility spectrometer-mass spectrometer.

[0054] The phrase "sequentially connected" does not necessarily prohibit the placement of other components between them; connections between components can be indirect. For example, "an ion source, a U-type ion mobility analyzer, and a mass spectrometer connected sequentially" implies that the UMA is placed after the ion source, and the mass analyzer is placed after the UMA. However, other components can be placed between the UMA and the ion source, and similarly, between the UMA and the mass analyzer.

[0055] The term "trap-release" refers to an operating mode of an ion mobility analyzer, used in various ion mobility analyzers, including UMA and TIMS. Specifically, in "trap-release" mode, ions are concentrated in a certain area of ​​the ion mobility analyzer, forming ion packets that are then released to the next level. Generally speaking, in "trap-release" mode, ions are released in pulses, with packets being retained and temporarily stored (i.e., trapped) in certain areas of the transmission path, rather than being continuously released to the next level.

[0056] "Scan release" in the ion scanning step refers to the sequential release of ions of different mobilities or mobility ranges, or the sequential release of ions of different mass numbers or mass number ranges. The order can be from large to small or from small to large, and some mobilities / mass numbers or mobility / mass number ranges can be skipped in the middle.

[0057] This embodiment provides a data acquisition method and an ion mobility spectrometer-mass spectrometer 100 using the data acquisition method.

[0058] <Ion Mobility Spectrometry-Mass Spectrometry 100>

[0059] 1 , the ion mobility spectrometer-mass spectrometer 100 provided in this embodiment includes an ion source 1 , a U-shaped ion mobility analyzer 2 , a quadrupole mass filter 3 (ie, a mass filter), an ion dissociation device 4 and a mass spectrometer 5 connected in sequence.

[0060] In this embodiment, the ion source 1 includes an ion source 1 selected from the group consisting of: (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) desorption ionization on silicon ("DIOS") ion source; (viii) electron impact ("EI") ion source; (ix) chemical ionization ("CI") ion source; (x) field ionization ("FI") ion source; (xi) field desorption ("FD") ion source; (xii) inductively coupled plasma ("ICP") ion source; (xiii) fast atom bombardment ("FAB") ion source; (xiv) liquid secondary ion mass spectrometry ("LSIMS") ion source ; (xv) desorption electrospray ionization ("DESI") ion source; (xvi) nickel-63 radioactive ion source; (xvii) atmospheric pressure matrix-assisted laser desorption ionization ion source; (xviii) thermal spray ion source; (xix) atmospheric sampling glow discharge ionization ("ASGDI") ion source; (xx) glow discharge ("GD") ion source; (xxi) impactor ion source; (xxii) direct analysis in real time ("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 ion source; (xxviii) laser ablation electrospray ionization ("LAESI") ion source; (xxix) He plasma (HePl) ion source. More preferably, an electrospray ionization ("ESI") ion source, a matrix-assisted laser desorption ionization ("MALDI") ion source, a direct analysis in real time ("DART") ion source, a laser ablation electrospray ionization ("LAESI") ion source, or a real-time ion source is used.

[0061] The U-shaped ion mobility analyzer 2 includes a first channel CH1 and a second channel CH2, and the first channel CH1 and the second channel CH2 are both composed of two groups of electrode arrays that are oppositely arranged and extend perpendicular to the axial direction (refer to Figure 1, the two groups of electrode arrays on the left, i.e., the first electrode array and the second electrode array, define the first channel CH1, and the two groups of electrode arrays on the right define the second channel CH2).

[0062] 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 arranged at the electrode array close to the front side of the first channel CH1, the ion outlet 203 is arranged at the electrode array close to the rear side of the second channel CH2, and the inter-channel ion transfer port 202 is arranged at the electrode array adjacent to the first channel CH1 and the second channel CH2. The inter-channel ion transfer port 202 connects the first channel CH1 and the second channel CH2.

[0063] The U-shaped ion mobility analyzer 2 has an airflow supply unit that supplies airflow to both the first channel CH1 and the second channel CH2. The direction of the airflow is along the vertical direction in Figure 1. The balance between the airflow driving force and the electric field binding force in the U-shaped ion mobility analyzer 2 is along the vertical direction in Figure 1, that is, the radial direction perpendicular to the axial direction. Therefore, when the ions do not meet the conditions for achieving a balance between the airflow driving force and the electric field binding force, they will escape from the openings at both ends of the radial direction and annihilate, rather than being transported further to the next stage. Between CH1 and CH2, a "dipole DC" electric field, or a deflected DC electric field, can be used to transport or transfer ions from CH1 to CH2.

[0064] The implementation principles of basic functions such as storage, accumulation, movement, and separation of ions in the first channel CH1 and the second channel CH2 of the U-shaped ion mobility analyzer 2 can be referred to the previously applied patents CN109003877A, CN109003876A, and CN115223844A and will not be repeated here.

[0065] The ion dissociation device 4 is a collision-induced dissociation device, an electron dissociation device, an infrared photon dissociation device, an ultraviolet photon dissociation device, or a free radical dissociation device. Preferably, the ion dissociation device 4 is a collision-induced dissociation device.

[0066] The mass spectrometer 5 can be one or more of a quadrupole mass spectrometer, a time-of-flight mass spectrometer, a Fourier transform mass spectrometer, an ion trap mass spectrometer, and a magnetic mass spectrometer. Optionally, the mass spectrometer 5 is a quadrupole mass spectrometer or a time-of-flight mass spectrometer, and together with the quadrupole mass filter 3, forms a tandem mass spectrometer in the form of a Q-TOF or triple quadrupole.

[0067] In this embodiment, the ion mobility spectrometer-mass spectrometer 100 is further provided with an ion optical device 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 performing functions such as ion convergence, guidance, or storage. It should be noted that the multi-stage vacuum structure and the corresponding configuration of the ion optical device 6 in FIG1 are merely exemplary. In other embodiments of the present invention, the configuration of the multi-stage vacuum structure and the ion optical device 6 can be adjusted according to actual needs, and the present invention is not limited thereto.

[0068] The above introduces the structure of the ion mobility spectrometer-mass spectrometer 100 in a preferred embodiment of the present invention. In other embodiments of the present invention, the data acquisition method provided therein can also be applied to an ion mobility spectrometer-mass spectrometer formed by a UMA and a primary mass spectrometer connected in series. In the embodiments of the present invention, there is no limitation on whether the mass spectrometer is a tandem mass spectrometer.

[0069] <Data Collection Method>

[0070] Figure 2 is a schematic diagram of the conventional scanning mode used in prior art U-shaped ion mobility analyzers. In this mode, the scanning range for ions within the full mobility range is the same during the pre-collection step and the subsequent analytical scan step. During the analytical scan step, each ion mobility spectrum scan is performed for ions within the full mobility range. This process is time-consuming and, for ions with relatively concentrated mobilities, the ions are also distributed more concentratedly, resulting in a significant space charge effect.

[0071] The data collection method provided by the embodiment of the present invention is shown in FIG3 .

[0072] First, pre-collection step S1 is performed, whereby parent ions ionized by ion source 1 are separated by a U-shaped ion mobility analyzer 2 and transferred to a mass spectrometer to obtain a two-dimensional ion mobility spectrum-mass spectrum heat map of the parent ions. Specifically, in pre-collection step S1, the first channel CH1 is used to accumulate ions across the full mobility range or a wide mobility range, while the second channel CH2 sequentially releases the ions accumulated in the first channel CH1 into the quadrupole mass filter 3.

[0073] Figure 4 is a schematic diagram of the ion behavior of the first channel CH1 and the second channel CH2 during the pre-collection accumulation step of the pre-collection step according to an embodiment of the present invention; Figure 5 is a schematic diagram of the ion behavior of the first channel CH1 and the second channel CH2 during the pre-collection ion transfer step of the pre-collection step according to an embodiment of the present invention. Referring to Figures 4 and 5 , pre-collection step S1 includes a pre-collection accumulation step and a pre-collection ion transfer step that occur sequentially. The straight lines or broken line segments in Figures 4 and 5 represent the radial DC electric field intensity distributions of the first channel CH1 and the second channel CH2, respectively.

[0074] Referring to Figure 4 , during the pre-collection accumulation step, parent ions ionized by ion source 1 continuously enter the first channel CH1. Simultaneously, the dipole DC control for controlling inter-channel ion transfer port 202 is closed, preventing ions from entering the second channel CH2. By balancing the airflow driving force and the electric field binding force, parent ions continuously accumulate in the first channel CH1. The second channel CH2 then releases ions in the order of ion mobility.

[0075] Referring to Figure 5, after a period of time, the ions in the second channel CH2 are basically released, and the pre-collection ion transfer step is executed. The dipole DC electric field (i.e., the deflection 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 in the pre-collection accumulation step are transferred to the second channel CH2 via the inter-channel ion transfer port 202.

[0076] It is worth noting that the ion accumulation and scanning methods shown in Figures 4 and 5 are the same as the traditional scanning mode used by the U-type ion mobility analyzer.

[0077] Figure 6 shows an example of a two-dimensional ion mobility spectrum-mass spectrum heat map obtained in pre-acquisition step S1. After pre-acquisition step S1, this two-dimensional ion mobility spectrum-mass spectrum heat map is analyzed to identify a trend line (i.e., the dotted line in Figure 6). Trend line analysis allows for more targeted selection of target precursor ions for DDA analysis, as well as more accurate determination of the target mobility range and mass selection range for DIA analysis.

[0078] In addition, in the pre-collection step S1, the intensity information and mobility information of the parent ion can also be obtained. The intensity information of the parent ion can be used for DDA analysis, while the mobility information of the parent ion can be used to calculate the collision cross-section area CCS to assist in qualitative analysis.

[0079] After completing the pre-collection step S1 and determining the trend line, the accumulation, selection and cascade analysis of the parent ions are performed. Specifically, first, based on the ion mobility spectrum-mass spectrum two-dimensional thermal map and its trend line, the target mobility range of the U-shaped ion mobility analyzer 2 and the mass selection range of the quadrupole mass filter 3 in different time periods within a cycle are determined. As shown in Figure 6, based on the two-dimensional thermal map and the trend line, the target mobility range and the mass selection range can be determined in combination with the analytical interest of this analysis for different types of targets. A target mobility range and a mass selection range constitute an interest frame. The number of interest frames, window width, first and last positions, etc. can be adjusted according to the selected target substance type, charge and trend line analysis results, so that as many target substances as possible are included in the interest frame composed of the target mobility range and the mass selection range, and the interest frame set along the trend line can cover the target substance more accurately and avoid the generation of excessive noise.

[0080] Then, the ion accumulation step S2, the ion transfer step S3 and the ion scanning step S4 are repeatedly performed to obtain ion mobility spectrum-mass spectrum data of multiple groups of daughter ions corresponding to the parent ions.

[0081] Among them, the ion accumulation step S2 is to selectively accumulate the parent ions within the target mobility range obtained by ionization of the ion source 1 in the target ion enrichment interval of the first channel CH1 of the U-shaped ion mobility analyzer 2, wherein the target mobility range is determined according to the ion mobility spectrum-mass spectrum two-dimensional thermal map, that is, the target mobility range corresponding to each interest box in Figure 6.

[0082] The ion transfer step S3 is to transfer the parent ions within the target mobility range stored in the first channel CH1 of the U-type ion mobility analyzer 2 to the second channel CH2 of the U-type ion mobility analyzer 2.

[0083] The ion scanning step S4 is to scan and release the parent ions within the target mobility range in the second channel CH2 of the UMA to the quadrupole mass filter 3 in the order of target ion mobility after a specified time.

[0084] The quadrupole mass filter 3 further releases the parent ions within the mass selection range to the subsequent stage. The mass selection range is determined according to the ion mobility spectrum-mass spectrum two-dimensional heat map, that is, the mass selection range corresponding to each interest box in Figure 6.

[0085] In this embodiment, in the pre-collection step S1 , the ion accumulation step S2 , and the ion scanning step S4 , the working mode of the UMA is basically unified, and no mode switching is required, which also facilitates synchronization with the working cycle of the quadrupole mass filter 3 .

[0086] Figure 7 illustrates the method for setting the target mobility ranges for the first channel CH1 and the second channel CH2 in various steps of one embodiment of the present invention. Figures 8-11 are schematic diagrams of the DC electric field application method for the first channel CH1 and the second channel CH2 during the ion accumulation step S2, ion transfer step S3, and ion scanning step S4 of the embodiment of Figure 7. Figures 7-11 illustrate seven ions with different ion mobilities as examples. The straight lines and broken lines in the coordinate systems of Figures 8-11 represent the DC electric field intensity distributions for the first channel CH1 and the second channel CH2, respectively.

[0087] Referring to Figure 7 , the first cycle of ion accumulation step S2 is performed. The target mobility range of first channel CH1 is set to match the ion mobilities of ions 1 and 2. Ions 1 and 2 are accumulated in target ion enrichment interval 204, while ions 3-7 are accumulated in the non-target ion enrichment interval of first channel CH1, such as second non-target ion enrichment interval 205b. Next, the first cycle of ion transfer step S3 is performed, transferring ions 1 and 2 accumulated in target ion enrichment interval 204 to second channel CH2. Subsequently, ion scanning step S4 is performed, scanning and releasing ions 1 and 2 in second channel CH2 to downstream devices.

[0088] Referring to Figures 7 and 8, in the second cycle, that is, when steps S2-S4 are 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 3-5. When the ion accumulation step S2 of the second cycle is executed, among the parent ions 1-7 ionized by the ion source 1, ions within the specified target mobility range (ions 3, 4 and 5 in Figure 8) are selected and accumulated in the target ion enrichment interval of the first channel CH1.

[0089] It should be noted that in this embodiment, the target ion enrichment interval 204 is the interval between the ion inlet 201 of the first channel CH1 and the inter-channel ion transfer port 202. In other embodiments, the division of the target ion enrichment interval 204 may be adjusted according to the circumstances. The non-target ion enrichment intervals are located at both ends of the first channel CH1, including a first non-target ion enrichment interval 205a extending from the ion inlet 201 to an opening at one end of the first channel CH1, and a second non-target ion enrichment interval 205b extending from the inter-channel ion transfer port 202 to an opening at the other end of the first channel CH1. Referring to Figure 8, when executing the ion accumulation step S2 of the second cycle, in the first channel CH1, ions that are not within the target mobility range, i.e., ions No. 1, No. 2, No. 6, and No. 7 in Figure 8, are stored in the non-target ion enrichment interval, wherein ions No. 1 and No. 2 with larger ion mobility are stored in the first non-target ion enrichment interval 205a close to the ion inlet 201 side, and ions No. 6 and No. 7 with smaller ion mobility are stored in the second non-target ion enrichment interval 205b close to the ion transfer port 202 side.

[0090] Because the UMA has dual channels and is independently controlled, the ion scanning step S4 can be performed simultaneously with the ion accumulation step S2, that is, when the second channel CH2 releases the target ions within the current target mobility range, the target ion enrichment interval 204 of the first channel CH1 is accumulating the target ions within the target mobility range required to be released in the next ion scanning step S4. In addition, the target ion enrichment interval 204 can not only accumulate the target ions within the target mobility range continuously obtained from the ion source 1, but also receive and accumulate ions that were not within the target mobility range in the previous stage but are within the adjusted target mobility range in this stage from the first non-target ion enrichment interval 205a or the second non-target ion enrichment interval 205b at both ends. Through the above process design, the accumulation and release of ions in the dual channels can be efficiently coordinated, taking into account both the utilization efficiency and scanning speed of ions.

[0091] Specifically, referring to FIG8 , 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 (the left-right direction in FIG8 , i.e., the length direction of the UMA). At the first non-target ion enrichment interval 205a, because the electric field strength is relatively low and the electric field force exerted on the ions is relatively small, ions No. 1 and No. 2, which have a relatively small collision cross-sectional area CCS (larger ion mobility), are able to achieve a balance between the airflow and the electric field force and are thus stored in this area. At the middle target ion enrichment interval 204, the electric field strength is moderate. Accordingly, target ion enrichment interval 204 of the first channel CH1 accumulates ions No. 3, No. 4, and No. 5, which have medium mobility. At the second non-target ion enrichment interval 205b, because the electric field strength is relatively high and the electric field force exerted on the ions is relatively large, ions No. 6 and No. 7, which have a relatively large collision cross-sectional area CCS (smaller ion mobility), are able to achieve a balance between the airflow and the electric field force and are thus stored in the second non-target ion enrichment interval 205b. At the same time, the second channel CH2 releases the high-mobility ions No. 1 and No. 2 that have not been analyzed in the previous cycle (first cycle) to the subsequent scanning stage. Referring to Figure 8, it can be seen that in this embodiment, different regions along the length direction of the first channel CH1 can store ions. Among them, for the main part of the first channel CH1, namely the target ion storage area 204, because the ion accumulation step S2 and the ion transfer step S3 are two different steps, the target ions within the target mobility range will first be stored in the target ion enrichment area 204 and then quickly transferred to the second channel CH2. In the ion accumulation step S2, the gradient of the DC electric field can be set to be smaller (for example, the DC electric field that changes linearly along the entire target ion enrichment area 204 as shown in Figure 8), so that the ions within the target mobility range can be distributed more dispersedly along the length direction of the target ion enrichment area 204, rather than concentrated in a specific area. This method can effectively reduce the space charge effect and improve the resolution of low-abundance ions.

[0092] 9 , after a period of time, the parent ions of the second channel CH2 are basically released, and the second cycle of ion transfer step S3 is executed to transfer the parent ions in the target ion enrichment interval 204 of the first channel CH1 to the second channel CH2 via the inter-channel ion transfer port 202 .

[0093] It should be noted that in this embodiment, the U-shaped ion mobility analyzer 2 can rapidly transfer ions between the first channel CH1 and the second channel CH2 by adjusting the DC electric field distributed across the electrode array and the dipole DC electric field surrounding the inter-channel transfer port 202, thereby increasing the duty cycle. Specifically, referring to FIG9 , the electric field at the inter-channel ion transfer port 202 can be continuously reduced and the dipole DC electric field activated, allowing ions 3-5 to rapidly migrate toward this location and enter the second channel CH2 through the inter-channel ion transfer port 202.

[0094] The duration of the ion transfer step S3 is much shorter than the duration of the ion accumulation step S2, and consumes less time in the entire operation cycle, thereby improving the duty cycle. Specifically, within the same cycle, the duration of the ion transfer step S3 is less than 1 / 10 or even 1 / 100 of the duration of the ion accumulation step S2.

[0095] In some embodiments, the inter-channel ion transfer port 202 can be partially closed to filter out ions with a certain ion mobility or ion mobility range. Filtering out some unwanted parent ions during the ion transfer process can effectively enrich the parent ions of the target analyte and improve the dynamic range of methods such as DDA.

[0096] In other embodiments, the ions in the non-target ion enrichment interval or partially from the target ion enrichment area can be removed by removing the DC electric field in the non-target ion enrichment interval or adding a radial DC bias. Specifically, the ions in the second non-target ion enrichment interval 205b can be removed by removing the DC electric field (the airflow can carry the ions away axially); or the ions in the first non-target ion enrichment interval 205a or the second non-target ion enrichment interval 205b can be removed by applying a radial DC bias. In the above manner, the removal of temporarily stored ions can be completed conveniently, which is easier to achieve than TIMS.

[0097] Continuing with reference to FIG10 , when the second channel CH2 sequentially releases ions 3-5, the first channel CH1 repeats the third cycle of ion accumulation step S2, but the target mobility range of this ion accumulation step S2 is adjusted (by adjusting the DC electric field gradient or changing the DC electric field distribution), specifically to select low-mobility ions 6 and 7 for enrichment. As shown in FIG10 , ions 6 and 7 from the ion inlet 201 are enriched in the target ion enrichment interval 204. At the same time, ions 6 and 7, which were temporarily stored in the second non-target ion enrichment interval 205b during the previous ion accumulation step S2, also return to the target ion enrichment interval 204 due to the action of airflow or electric field force. At the same time, in the first channel CH1, the high-mobility ions 1 and 2, and the medium-mobility ions 3-5, are temporarily stored in the first non-target ion enrichment interval 205a.

[0098] When the basic scan and release of ions 3-5 in the second channel CH2 is complete, ion transfer step S3 is executed again to transfer ions 6 and 7 in the first channel CH1 to the second channel CH2. The specific electric field distribution setting method can be seen in Figure 11. After ion transfer step S3, the third cycle of ion scanning step S4 is executed to sequentially release ions 6 and 7 in the second channel CH2 into quadrupole mass filter 3.

[0099] After the ion scanning step S4, or synchronously with the ion scanning step S4, the daughter ion collection step is implemented, and the scanned and released ions are sequentially passed through the quadrupole mass filter 3 and the ion dissociation device 4, and finally passed into the mass analysis device 5. Specifically, the selected parent ions enter the ion dissociation device 4 for dissociation to produce daughter ions, and the daughter ions enter the mass spectrometry device 5 for analysis to obtain the ion mobility spectrum-mass spectrum data of the daughter ions. This embodiment is described by performing DDA / DIA data collection. After all parent ions have been selected and the corresponding parent ion or daughter ion ion mobility spectrum-mass spectrum data have been collected, the process can be terminated, or all of the above-mentioned pre-collection steps S1, ion accumulation step S2, ion transfer step S3 and ion scanning step S4 can be performed again one or more times. In the repeated ion accumulation step S2, ion transfer step S3 and ion scanning step S4, certain parameter settings can be changed compared to the previous accumulation and scanning release, such as changing the target mobility range or window size for parent ion selection, or the mass selection range or window size, or changing the order of parent ion selection, or changing the collision energy or retention time of the ion dissociation device 4, etc., so that more information can be obtained by changing the parameters to improve the coverage and depth of the analysis.

[0100] In the above manner, the data acquisition method provided by this embodiment can divide ions in the first channel CH1 into multiple groups according to mobility, and store ions within the target mobility range and ions outside the target mobility range in different areas, thereby efficiently utilizing the various areas in the length direction of the first channel CH1 for ion storage, and introducing ion packets of different mobility ranges into the second channel CH2 for analysis in batches, thereby avoiding excessive concentration of ions and reducing space charge effects. Moreover, although only ions of a specific mobility range are selected at a time in the first channel CH1, ions of other mobilities are not lost during the selection process, but are temporarily stored in the non-target ion enrichment interval 205, and will continue to enter the second channel CH2 and participate in the analysis in subsequent steps, so the sensitivity of the entire process will not decrease.

[0101] <Target mobility range and quality selection range>

[0102] In the present embodiment, the target mobility range and the mass selection range can be determined according to the analytical method used by the coupling instrument. For example, when the coupling instrument adopts the DDA data analysis method, it is possible to select multiple groups of parent ions whose signal intensity is higher than threshold value in the ion mobility spectrum-mass spectrum two-dimensional heat map, or to select multiple groups of parent ions whose signal intensity is relatively high in the ion mobility spectrum-mass spectrum two-dimensional heat map. That is, several groups of parent ions with the strongest or relatively strong signal intensity are selected to analyze. In the process of selecting parent ion, trend line can provide reference information for the charge situation or molecular type of parent ion, so that parent ion can be selected more accurately. Of course, in some other embodiments, the parent ion with relatively low abundance can also be selected to analyze as target.

[0103] When adopting the DIA data analysis method, referring to Figure 6, the mass window and ion mobility window of fixed width can be selected stepwise following the trend line, and the cycle of the U-shaped ion mobility analyzer 2 scanning the target mobility range is synchronized with the cycle of the quadrupole mass filter 3 scanning the mass selection range. Specifically, the U-shaped ion mobility analyzer 2 scans different ion mobility windows in sequence from high to low (i.e., collision cross-sectional area CCS from large to small) in one analysis cycle, and the quadrupole mass filter 3 scans different mass windows in sequence from small to large in one analysis cycle. When performing the daughter ion acquisition step, since smaller parent ions usually correspond to smaller daughter ions, and the retention time of small daughter ions in the ion dissociation device 4 is also shorter, its transmission in the ion dissociation device 4 is not easily interfered with by subsequent larger daughter ions, and therefore will not affect the quality of its migration spectrum (such as avoiding migration spectrum peak mismatch, etc.), and can speed up the channel scanning speed of DDA or DIA.

[0104] With reference to Figure 12, because different types of compounds (sugars, peptides, proteins, etc.) are usually distributed in different regions in ion mobility spectrum-mass spectrometry two-dimensional heat map, and ions of different charge numbers are usually distributed along the trend line of different slopes. Based on the distribution area and trend line in the heat map, it is possible to more obviously distinguish between different charge numbers and types of materials, thereby more specifically selecting target parent ions to carry out DDA analysis, or more accurately determining target mobility range and mass selection range to carry out DIA analysis. Therefore, in some better embodiments, the two-dimensional heat map can first be divided into multiple different local (partial images as shown in the dotted box in Figure 12) according to the aggregation state of the points of the compound of different types and charge numbers, and a trend line is determined separately for each local, then DIA / DDA data acquisition is implemented separately for each local. This mode can more accurately determine suitable target mobility range and mass selection range, effectively improves qualitative or quantitative accuracy, and speeds up scanning speed.

[0105] In this embodiment, because a U-shaped ion mobility analyzer 2 is used as the ion mobility analyzer, and a mode of simultaneous accumulation and scanning release is adopted in combination with the first channel CH1 and the second channel CH2, ions can pass through the U-shaped ion mobility analyzer 2 and be transported to the lower level, or be temporarily stored in the non-target ion enrichment interval (the first non-target ion enrichment interval 205a or the second non-target ion enrichment interval 205b), and almost all ions can be utilized, obtaining an ion utilization efficiency close to 100%.

[0106] In particular, the ion mobility spectrum-mass spectrum two-dimensional thermal map obtained according to the pre-acquisition step S1 can more accurately determine the target mobility range, thereby more specifically enriching ions within the specific target mobility range in the ion scanning step S4, avoiding non-target ions occupying the cumulative area and affecting the dynamic range.

[0107] Through the above method, the U-shaped ion mobility analyzer 2 cooperates with the data acquisition method provided in this embodiment, so that the combined instrument can implement data acquisition that matches different analysis methods (such as DIA and DDA methods of different modes), solving the problems faced by existing data acquisition methods such as difficulty in filtering out ions and limited dynamic range.

[0108] Referring to Figure 13, an embodiment of the present invention also provides a high dynamic range selective exclusion scanning mode. If there is a partial range of ions in the full mobility range that are not target ions, or there are no ions in this range (which can be determined based on the two-dimensional thermal map during pre-collection), in the data acquisition method of this embodiment, the second channel CH2 can skip the scan of this mobility range, allocate more scanning time to the target ions, or shorten the scanning time, further improving the resolution or analysis speed of the target ions. Taking Figure 13 as an example, because the scanning of ions No. 3, No. 4 and No. 5 is skipped, this scanning method, on the one hand, allows the selected ions to be detected in the same quantity, and on the other hand, saves the time required for scanning ions No. 3, No. 4 and No. 5.

[0109] The above are only 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 be included in the scope of protection of the present invention.

Claims

1. A data acquisition method, applied to an ion mobility spectrometer-mass spectrometer, characterized in that: The ion mobility spectrometer-mass spectrometer comprises an ion source, a U-shaped ion mobility analyzer and a mass spectrometer connected in sequence, and the data acquisition method comprises the following steps: A pre-collection step, wherein the ions to be analyzed obtained by ionization of the ion source are separated into the mass spectrometer through the U-shaped ion mobility analyzer; an ion accumulation step, accumulating the ions within the target mobility range among the ions to be analyzed in the target ion enrichment interval of the first channel of the U-shaped ion mobility analyzer, and at the same time, the ions outside the target mobility range enter the non-target ion enrichment intervals at both ends of the first channel for enrichment; an ion transfer step, 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; an ion scanning step, scanning and releasing ions within the target mobility range in the second channel of the U-shaped ion mobility analyzer to the mass spectrometer; Repeat the ion accumulation step, the ion transfer step and the ion scanning step. In the repeating step, the target mobility range is the target mobility range defined in the last scan, or the mobility range corresponding to at least a part of the ions entering the non-target ion enrichment interval in the last scan.

2. The data collection method according to claim 1, characterized in that: The ion mobility spectrometer-mass spectrometer also includes a mass filter and an ion dissociation device arranged between the U-shaped ion mobility analyzer and the mass spectrometer. The pre-collection step obtains a two-dimensional heat map of the ion mobility spectrum-mass spectrum of the ions to be analyzed; After the ions leave the second channel of the U-shaped ion mobility analyzer, they pass through the mass filter and the ion dissociation device and enter the mass spectrometry device.

3. The data collection method according to claim 1, characterized in that: In a plurality of different ion accumulation steps, the DC electric field intensity distribution of the first channel is adjusted to change the target mobility range of the ions accumulated in the target ion enrichment interval of the first channel.

4. The data collection method according to claim 1, characterized in that: The ions enriched in the non-target ion enrichment intervals at both ends of the first channel are released and enter the target ion enrichment interval by changing the DC electric field strength distribution of the first channel in the next ion accumulation step, and then enter the second channel for mobility scanning.

5. The data collection method according to claim 1, characterized in that: In the ion scanning step, the ions in the second channel are released in the order of ion mobility from large to small.

6. The data collection 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 with a fixed width, and the mass filter scans different mass windows in sequence from small to large within one analysis cycle.

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

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

9. The data collection method according to claim 2, characterized in that: In the ion scanning step, multiple groups of ions whose signal intensities are higher than a threshold value in the ion mobility spectrum-mass spectrometry two-dimensional heat map are selected, or multiple groups of ions whose signal intensities are relatively high in the ion mobility spectrum-mass spectrometry two-dimensional heat map are selected.

10. The data collection 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 in the current mobility range of the two-dimensional thermal map.

11. The data collection method according to claim 2, characterized in that: In the ion scanning step, the mass selection range of the mass filter includes part of the mass numbers corresponding to the target mobility range in the two-dimensional thermal map, and the mass scanning window width remains unchanged or changes according to the prediction of the two-dimensional thermal map.

12. The data collection method according to claim 2, characterized in that: In the ion scanning step, the window width of the target mobility range remains unchanged or is changed according to the prediction of the two-dimensional heat map.

13. The data collection method according to claim 1, characterized in that: The first channel and the second channel are each composed of two groups of electrode arrays that are arranged opposite to 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 ion inlet is arranged at the electrode array close to the front stage side of the first channel, the ion outlet is arranged at the electrode array close to the rear stage side of the second channel, and the inter-channel ion transfer port is arranged at the electrode array adjacent to the first channel and the second channel, and the inter-channel ion transfer port connects the first channel and the second channel.

14. The data collection method according to claim 13, characterized in that: In the ion transfer step, the ions with a certain ion mobility or a certain range of ion mobility are filtered out by closing the inter-channel ion transfer port at a certain time.

15. The data collection method according to claim 1, characterized in that: The following steps are also included: The ions in the non-target ion enrichment interval are cleared by removing the DC electric field in the non-target ion enrichment interval or adding a radial DC bias.

16. An ion mobility spectrometer-mass spectrometer, characterized in that: Apply the data collection method as described in any one of claims 1 to 15.

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

18. The ion mobility spectrometer-mass spectrometer according to claim 16, characterized in that: The ion mobility spectrometer-mass spectrometer comprises an ion dissociation device, and the ion dissociation device is one or more of a collision induced dissociation device, an electron dissociation device, an infrared photon dissociation device, an ultraviolet photon dissociation device, and a free radical dissociation device.

19. An ion mobility analyzer, characterized in that: include: The first channel has a first electrode array and a second electrode array arranged opposite to each other, the first electrode array is provided with an ion inlet, the second electrode array is provided with an inter-channel ion transfer port, and the inter-channel ion transfer port and the ion inlet are arranged at positions staggered with each other; a second channel, receiving ions from the first channel via the inter-channel ion transfer port; an air flow supply unit, for supplying or extracting gas to at least the first channel to form an air flow flowing along the first channel; A power supply applies an electric field to at least the first channel, and utilizes the balance between the electric field force in opposite directions and the driving force of the gas flow on the ions to accumulate ions within the target mobility range in a target ion enrichment interval between the ion inlet and the ion transfer port between the channels, and at the same time, enriches ions outside the target mobility range in non-target ion enrichment intervals at both ends of the first channel.

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

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