Tandem U-type ion mobility spectrometry instrument and ion mobility analysis method

Abstract

To provide an ion mobility spectrometry instrument, in particular, a tandem U-shaped one and an ion mobility analysis method that are related to the field of ion mobility analysis.SOLUTION: A tandem U-type ion mobility spectrometry instrument includes two tandemly coupled U-shaped ion mobility analyzers, where a first U-shaped ion mobility analyzer operates in a filter mode, a second ion inlet of a second U-shaped ion mobility analyzer is arranged corresponding to a first ion outlet, and an ion dissociative device is arranged to receive and dissociate ions from the first U-shaped ion mobility analyzer and release fragment ions generated by the dissociation into the second U-shaped ion mobility analyzer.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001] The present invention relates to the field of ion mobility spectrometry, and more particularly to a tandem U-type ion mobility spectrometry device and method. [Background technology]

[0002] Ion mobility spectrometry is a technique that separates ions according to their mobility, and is widely used in bioanalysis because it can distinguish isomers that are normally indistinguishable by mass spectrometry.

[0003] In recent years, tandem configurations of ion mobility spectrometry instruments with other instruments have been widely adopted to increase the number of parameters on which analysis depends. Generally, an ion mobility spectrometry instrument and a mass spectrometer are combined into a single tandem mass spectrometry instrument to further separate different ions based on their ion mobility characteristics, thereby improving ion identification capabilities. For example, in Patent Document 1, TIMS technology and DIA / DDA technology were combined to discover the Parallel Accumulation Serial Fragmentation (PASEF) technology.

[0004] Furthermore, some studies have proposed tandem coupling of two ion mobility spectrometry devices to improve the separation efficiency (resolution) of ions with respect to the ion mobility of ions in ion mobility spectrometry. Based on the different physical mechanisms of IMS and FAIMS, Patent Document 2 proposes coupling FAIMS and IMS instruments to achieve greater separation efficiency (resolution).

[0005] Patent Document 3 proposes a method and apparatus for accurately identifying gas-phase ions using multiple tandem filter devices, and proposes improving the specificity and sensitivity of IMS detection by combining two tandem DMAs. One of the DMAs operates at a high electric field at least within the nonlinear mobility range. However, due to limitations in the DMA's filter mode, only ions within the target mobility range can be selected during a single scan, while the remaining ions are lost. This results in relatively low ion utilization efficiency and a relatively low duty cycle for the entire system. Furthermore, the fact that DMAs select ions based on differential ion mobility is disadvantageous for molecular structural characterization, and there is a lack of a reference theoretical database for complex tasks such as bioomics research.

[0006] Regarding the ion mobility analysis of trace substances in complex mixtures, Patent Document 4 further proposes an ion analysis method and a tandem ion mobility spectrometry device suitable for the ion analysis method. The tandem ion mobility spectrometry device includes two tandem TIMS (Trapped Ion Mobility Spectrometer) analyzers and an ion gate and fragmentation means disposed between the two tandem TIMS analyzers. This tandem TIMS ion mobility spectrometry device performs preliminary ion mobility separation on ions, then intentionally fragments ions within a target mobility range, and then performs ion mobility analysis on the resulting fragment ions. The resolution of the TIMS is relatively high, and ions can be accumulated in the first TIMS, thereby improving the duty cycle of tandem ion mobility spectrometry.

[0007] However, the following problems still exist in the tandem ion mobility spectrometry devices of the prior art.

[0008] First, for omics research of complex samples, the content differences between different components are extremely large, and an extremely high dynamic range is required to obtain relatively good qualitative and quantitative results. However, to achieve 100% ion utilization efficiency in parallel accumulation technology, ions must be accumulated in the first TIMS. However, because TIMS is developed based on the principle of ion trapping, some low-abundance ions are pushed out due to the space charge effect, and the dynamic range of the tandem instrument is limited by the ion capacity of the first TIMS.

[0009] In the second embodiment, the operations of the two TIMSs must be synchronized with each other, which increases the complexity of electric field application and places strict demands on control precision. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] US Patent US9891194 [Patent Document 2] US Patent US7148474B2 [Patent Document 3] US Patent US7855360B2 [Patent Document 4] US Patent US10794861B2 [Patent Document 5] China patent CN113495112A Summary of the Invention [Problem to be solved by the invention]

[0011] In response to the above problems, the present invention provides a tandem U-type ion mobility spectrometry device and ion mobility analysis method that reduces the complexity and precision requirements of electric field application, has relatively high resolution and dynamic range, and is applicable to research on complex topics such as bioomics.

[0012] Previously, the inventors of the present invention developed a U-shaped ion mobility analyzer (UMA, Patent Document 5), which operates in filter mode using a similar operating principle based on the cooperative action of airflow and electric field on ions. During a given time period, ions within a target mobility range are selected and continuously released into a downstream device, while ions outside the target mobility range are blocked or filtered out solely by the balance between the airflow driving force and the electric field force. Unlike pulsed release selection methods such as TIMS, the UMA operating in filter mode enables continuous selection and continuous release of ions, allowing ions within the target mobility range to constantly move along a predetermined path without being confined or stored.

[0013] Specifically, according to a first aspect of the present invention, there is provided a tandem U-shaped ion mobility spectrometry apparatus, which includes two tandemly coupled U-shaped ion mobility analyzers. Specifically, the tandem U-shaped ion mobility spectrometry apparatus in the present application includes a first U-shaped ion mobility analyzer, a second U-shaped ion mobility analyzer, an airflow supply unit, a power supply, and an ion dissociator.

[0014] The first U-shaped ion mobility analyzer operates in a filter mode and has a first passage and a second passage, the first passage having a first ion inlet and the second passage having a first ion outlet; the second U-shaped ion mobility analyzer has a third passage and a fourth passage, the third passage having a second ion inlet and the fourth passage having a second ion outlet, the second ion inlet being located corresponding to the first ion outlet.

[0015] The airflow supply unit supplies airflow to the first and second passages of the first U-shaped ion mobility analyzer and the third and fourth passages of the second U-shaped ion mobility analyzer.

[0016] The power supply is electrically connected to the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer and is positioned to apply an electric field force to the ions in the first passage, the second passage, the third passage, and the fourth passage in a direction opposite to the force acting on the ions by the airflow.

[0017] The ion dissociator is positioned to receive and dissociate ions from the first U-shaped ion mobility analyzer, and to emit fragment ions produced by the dissociation to the second U-shaped ion mobility analyzer.

[0018] In the tandem U-shaped ion mobility spectrometry device provided by the present invention, the first U-shaped ion mobility analyzer operates in filter mode and does not have a specific operating cycle, so there is no need to strictly synchronize the second U-shaped ion mobility analyzer with the operating cycle of the first U-shaped ion mobility analyzer. This allows for relatively free configuration of the electric field application method or control flow, and effectively utilizes the characteristics of the second U-shaped ion mobility analyzer, which has flexible control and a high achievable duty cycle, to achieve a wide range of functions similar to those of the MRM mode in tandem mass spectrometry.

[0019] Furthermore, ions within the first target mobility range can travel along a predetermined path from the first ion inlet to the first ion outlet of the first U-shaped ion mobility analyzer without any stagnation or slowdown, making it easier to maintain the concentration of high-abundance ions below the detector saturation limit while stably transporting low-abundance ions to downstream devices. This effectively improves the quantitative accuracy of high-abundance ions and the detection sensitivity of low-abundance ions, thereby expanding the detection dynamic range. Furthermore, the UMA operating in filter mode can arbitrarily select the path to be filtered, and can perform not only sequential scanning but also skip scanning, thereby improving the scan rate and avoiding interference from unwanted ions.

[0020] In the technical solution applied to the present invention, the first passage, the second passage, the third passage and the fourth passage are arranged parallel to each other, and the air flow path formed by the air flow supply part includes four air flow sub-paths along the first passage, the second passage, the third passage and the fourth passage, respectively.

[0021] In the tandem U-type ion mobility spectrometry apparatus applied to the present invention, a single UMA typically includes four electrode arrays arranged in parallel, and a passage defined by a pair of two electrode arrays becomes an ion passage, with an ion inlet and an ion outlet opening in the electrode array.

[0022] Therefore, the first, second, third and fourth passages are arranged in parallel with each other, i.e., the total of eight electrode arrays of the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer are all arranged in parallel to define four parallel ion passages, and by providing four airflow sub-paths, airflow can be supplied to the four passages individually.

[0023] In the technical solution applied to the present invention, the airflow path formed by the airflow supply unit includes an airflow path passing through both the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer.

[0024] According to the tandem U-shaped ion mobility spectrometry device applied to the present invention, a single airflow path supplied by the airflow supply unit passes through both the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer simultaneously, thereby eliminating at least one airflow path, reducing the amount of airflow supplied by the airflow supply unit, and reducing the cost and volume of the pump.

[0025] In the technical solution applied to the present invention, the first U-shaped ion mobility analyzer includes a first ion direct path from the first ion inlet to the first ion outlet, and the second U-shaped ion mobility analyzer includes a second ion direct path from the second ion inlet to the second ion outlet, the first ion direct path and the second ion direct path are installed corresponding to each other to form an ion direct path, and the second and third paths are installed respectively on both sides of the ion direct path and are connected collinearly end to end along the length direction.

[0026] According to the tandem U-shaped ion mobility spectrometry device applied to the present invention, the first ion direct path of the first U-shaped ion mobility analyzer and the second ion direct path of the second U-shaped ion mobility analyzer are installed corresponding to each other, so that when ion mobility analysis is not required, ions can pass through the tandem U-shaped ion mobility spectrometry device along the direct ion path and be ejected from the second ion outlet.

[0027] By providing the second and third passages at both ends of the ion direct path and connecting them collinearly end-to-end along the length, the second and third passages can be connected to form a long ion passage perpendicular to the ion direct path, allowing ions within the target mobility range to be released directly from the end of the second passage away from the first ion transfer port, and after being dissociated by the ion dissociator, the fragment ions enter the second U-shaped ion mobility analyzer from the end corresponding to the third passage. The airflow supply unit only needs to supply one airflow path along the long passage consisting of the second and third passages, which eliminates one airflow path compared to providing four independent airflow paths and allows the structure of the tandem U-shaped ion mobility spectrometry device to be more compact.

[0028] In a technical solution applied to the present invention, the tandem U-shaped ion mobility spectrometry device further includes a housing, which includes a first chamber, a second chamber, and an airflow guide, wherein the first chamber covers the outer surface of the first U-shaped ion mobility analyzer, has an airflow inlet at one end, communicates with the airflow guide at the other end, and has a first through-hole opened at a position corresponding to the first ion outlet of the first chamber, and the second chamber covers the outer surface of the second U-shaped ion mobility analyzer, has an airflow outlet at one end, communicates with the airflow guide at the other end, and has a second through-hole opened at a position corresponding to the second ion inlet of the second chamber.

[0029] In the tandem U-shaped ion mobility spectrometry device applied to the present invention, the housing covering and guides allow the two airflow paths supplied from the airflow supply unit to the first and second passages to be connected to the third and fourth passages, respectively.This reduces the number of parallel airflow paths to two, reduces the required airflow flow rate, and reduces the volume of the pump, making it easier to miniaturize the device, provided that the independence of ion control by the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer is ensured.

[0030] In the technical solution applied in the present invention, the second U-shaped ion mobility analyzer operates in a filter mode.

[0031] According to the tandem U-shaped ion mobility spectrometry device applied to the present invention, fragment ions within the second target mobility range continuously move to the second ion outlet in the second U-shaped ion mobility analyzer and are continuously released to the lower stage through the second ion outlet.

[0032] In the technical solution applied to the present invention, the power supply is arranged as follows: A first DC electric field is applied to the first passage, a second DC electric field is applied to the second passage, and the first DC electric field and the second DC electric field do not change in one detection period; a third DC electric field is applied to the third passage, and a fourth DC electric field is applied to the fourth passage; in one detection period, the field intensities of the third DC electric field and the fourth DC electric field increase synchronously, and the field intensity difference between the third DC electric field and the fourth DC electric field does not change.

[0033] In the tandem U-shaped ion mobility spectrometry apparatus applied to the present invention, the first U-shaped ion mobility analyzer is set to a filter-selective ion monitoring (filter-SIM) mode, which allows only ions within a fixed first target mobility range to pass over a long period of time, and the second U-shaped ion mobility analyzer is set to a filter-scan mode, which allows ions within different mobility ranges to pass simultaneously at different times, and enables selective scanning or full scanning of the allowable mobility range for fragment ions.

[0034] In this way, the first U-shaped ion mobility analyzer can continuously release ions within a fixed first target mobility range downstream, and the second U-shaped ion mobility analyzer can receive fragment ions obtained by dissociating ions released by the first U-shaped ion mobility analyzer through the first ion outlet at any time during the detection cycle. This eliminates the need to synchronize the first and second U-shaped ion mobility analyzers. Furthermore, by analyzing fragment ions in filter-scan mode, ions filtered out at one point during a detection cycle can be stored in the ion storage area of ​​the second U-shaped ion mobility analyzer without being lost during the scan, and can be released at other times during the scan. This improves ion utilization efficiency and increases the duty ratio of tandem U-shaped ion mobility spectrometry, theoretically reaching 100%.

[0035] In the technical solution applied to the present invention, the power source is A first DC electric field is applied to the first passage, a second DC electric field is applied to the second passage, and the first and second DC electric fields do not change during one detection period. Also, a third DC electric field is applied to the third passage, and a fourth DC electric field is applied to the fourth passage, and the third and fourth DC electric fields do not change during one detection period.

[0036] In the tandem U-shaped ion mobility spectrometry apparatus applied to the present invention, both the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer operate in filter-selected ion monitoring (filter-SIM) mode, thereby continuously acquiring fragment ions within a second target mobility range that are generated when ions within a first target mobility range are dissociated. This enables the entire tandem U-shaped ion mobility spectrometry apparatus to perform static ion mobility analysis, facilitating repeated analysis using a subsequent device, and eliminating the need to install the subsequent device and the tandem U-shaped ion mobility spectrometry apparatus in a synchronized manner, making it easy to use in combination with a subsequent device.

[0037] In the technical solution applied to the present invention, an ion dissociation device dissociates ions in a target region, and the target region is disposed between a first ion outlet and a second ion inlet.

[0038] In the tandem U-type ion mobility spectrometry apparatus applied to the present invention, an ion dissociator is installed between the first ion outlet and the second ion inlet, thereby making it possible to avoid any obstruction to the movement of ions and fragment ions within a target mobility range along a predetermined path.

[0039] In the technical solution applied to the present invention, the ion dissociation device is one or more of a collision induced dissociation device, an electron dissociation device, a radical dissociation device, and an electron transfer dissociation device.

[0040] In a second aspect of the present invention, a U-shaped ion mobility analyzer is disclosed, comprising a first passage, a second passage, an airflow supply unit, a power source, and an ion dissociator, wherein the first passage comprises a first electrode array and a second electrode array arranged in parallel and facing each other, and the second passage comprises a third electrode array and a fourth electrode array arranged in parallel and facing each other, the first electrode array has an ion inlet, the fourth electrode array has an ion outlet, and the second electrode array and the third electrode array each have an ion direct-through port and an ion transfer port, the ion direct-through port, the ion inlet, and the ion outlet are arranged corresponding to each other, and the ion transfer port and the ion direct-through port are offset from each other, the airflow supply unit supplies airflow to the first passage and the second passage, and the power source is electrically connected to the first electrode array, the second electrode array, the third electrode array, and the fourth electrode array, respectively, and is arranged to apply an electric field force to ions in the first passage and the second passage in a direction opposite to the force acting on the ions by the airflow, and the ion dissociator is arranged between the two ion direct-through ports.

[0041] In one detection cycle, the electric field application method by the power supply is configured as follows: During a first time period, the U-shaped ion mobility analyzer is placed in filter mode, and target ions obtained by filtering are stored in the second passage. During a second time period after the first time period, the target ions stored in the second passage are dissociated by an ion dissociator to obtain fragment ions, which are then transferred to the first passage. During a third time period after the second time period, ion mobility analysis is performed on the fragment ions using a predetermined path that passes through the first passage, ion transfer port, second passage, and ion outlet in that order.

[0042] By using the above method, two-stage or multi-stage IMS / IMS tandem analysis can be realized using a single U-shaped ion mobility analyzer, further reducing the requirements for the volume and airflow rate of the instrument.

[0043] In a third aspect of the present invention, an ion filtering step of filtering target ions having ion mobilities within a target mobility range from the ion beam by a first U-shaped ion mobility analyzer configured in a filter mode; an ion dissociation step of receiving and dissociating the target ions filtered by the first U-shaped ion mobility analyzer to obtain fragment ions corresponding to the target ions; and a fragment ion analyzing step of performing ion mobility analysis on the fragment ions.

[0044] In the technical solution applied in the present invention, the fragment ion analysis step is carried out by a second U-type ion mobility analyzer.

[0045] In the technical solution applied in the present invention, the first U-shaped ion mobility analyzer is set in a filter-selected ion monitoring mode, and the second U-shaped ion mobility analyzer is set in a filter-scanning mode.

[0046] In the technical solution applied in the present invention, the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer are both configured in a filter-selected ion monitoring mode.

[0047] In the technical solution applied to the present invention, the fragment ion analysis step is performed by a first U-shaped ion mobility analyzer, and the ion dissociation device performing the ion dissociation step is installed between the two ion direct ports of the first U-shaped ion mobility analyzer. In the ion filter step, the target ions are stored in the second channel of the first U-shaped ion mobility analyzer. In the ion dissociation step, the target ions stored in the second channel are dissociated as they pass through the ion direct port to obtain fragment ions, which are then transferred back to the first channel of the first U-shaped ion mobility analyzer. In the fragment ion analysis step, ion mobility analysis is performed on the fragment ions using a predetermined path that passes through the first channel and the second channel in sequence. [Brief explanation of the drawings]

[0048] [Figure 1] FIG. 1 is a perspective view of a schematic structure of a single U-shaped ion mobility analyzer. [Figure 2] FIG. 1 is a side view of a schematic diagram of the structure of a single U-shaped ion mobility analyzer. [Figure 3] 1 is a structural schematic diagram of a tandem U-type ion mobility spectrometry device according to Example 1 of the present invention. [Figure 4] FIG. 1 is a structural schematic diagram of a tandem U-type ion mobility spectrometry device according to Example 2 of the present invention. [Figure 5] FIG. 10 is a structural schematic diagram of a tandem U-type ion mobility spectrometry device according to Example 3 of the present invention. [Figure 6] FIG. 10 is a structural schematic diagram of a tandem U-type ion mobility spectrometry device according to Example 4 of the present invention. [Figure 7] FIG. 10 is a structural schematic diagram of a tandem U-type ion mobility spectrometry device according to Example 5 of the present invention. [Figure 8] 1 is a flow chart of an ion mobility spectrometry method according to an embodiment of the present invention. [Figure 9] FIG. 1 is a schematic diagram illustrating the process of implementing an ion mobility analysis method according to an embodiment of the present invention by using a U-shaped ion mobility analyzer with a conventional hardware structure, in combination with an additional ion dissociator and a specific electric field application method. DETAILED DESCRIPTION OF THE INVENTION

[0049] Hereinafter, the technical solutions in the embodiments of the present invention will be clearly and completely described with reference to the drawings in the embodiments of the present invention, and it is clear that the described embodiments are only some embodiments of the present invention, and are not all embodiments. Based on the embodiments of the present invention, all other embodiments that can be obtained by a person skilled in the art without creative efforts fall within the protection scope of the present invention.

[0050] <Terms and their interpretation> "Filter mode" is an operating mode applicable to ion mobility analyzers that is similar to the filter mode of a typical quadrupole mass filter. This operating mode is characterized in that only ions within a specific mobility range are allowed to pass through the ion mobility analyzer during a certain time period, while ions outside that mobility range are prevented from passing through the ion mobility analyzer.

[0051] In filter mode, ions pass continuously through the ion mobility analyzer, and while ions pass through the ion mobility analyzer, target ions are not accumulated or stored inside the ion mobility analyzer, but always move continuously along a predetermined path.

[0052] In an embodiment of the present invention, the physical quantity analyzed or measured by an ion mobility analyzer is limited to ion mobility in low electric fields, which is directly related to the collision cross section (CCS) of the ion, i.e., the ion mobility analyzer can be used to obtain CCS information. An ion mobility analyzer operating in "filter mode" continuously filters ions in a specific mobility range, while the ion inlet is always continuously receiving sample.

[0053] The "filter mode" of a U-type ion mobility analyzer includes at least two types: a static mode, which allows only ions within a certain target mobility range to pass over a long period of time, and is generally called a filter-selected ion monitoring (filter-SIM) mode; and a dynamic scan mode, which allows target ions within different mobility ranges to pass sequentially by synchronously adjusting the upper and lower limits (second and first thresholds) of the target mobility range corresponding to the target ions at different times, and is called a filter-scan mode.

[0054] Note that the term "dissociation" also includes activation and unfolding in protein analysis. Activation includes changing the protein ion energy or removing salt clusters, water clusters, etc. on the protein surface (referred to as desolvation or declustering). Unfolding means changing the form of the protein molecule to obtain more structural information. The means to achieve these two functions is similar to collision-induced dissociation. Usually, a strong direct current field is applied to cause the protein molecule to collide with the background gas.

[0055] <U-shaped ion mobility analyzer> Figures 1 and 2 show the hardware structure of a single U-shaped ion mobility analyzer 100. As shown in Figure 1, a single U-shaped ion mobility analyzer 100 includes four sets of electrode arrays (the first electrode array 11, the second electrode array 12, the third electrode array 13, and the fourth electrode array 14). The electrodes in each set of electrode arrays are arranged in the same plane. The planes where the four sets of electrode arrays are located are parallel to each other. The airflows G1 and G2 are blown between the first electrode array 11 and the second electrode array 12, and between the third electrode array 13 and the fourth electrode array 14 along the direction parallel to the electrode arrays. DC electric fields E1 and E2, whose directions of the acting forces on the ions are opposite to the airflows G1 and G2, are applied to the first electrode array 11 and the second electrode array 12, and the third electrode array 13 and the fourth electrode array 14, respectively. For the convenience of illustration, in the drawings after Figure 1, the structure of the U-shaped ion mobility analyzer 100 and the movement trajectories of the ions inside it are often shown in a side view.

[0056] FIG. 2 is a side view of the structure of a single U-shaped ion mobility analyzer 100. As shown in FIG. 2, two parallel rows of a first electrode array 11 and a second electrode array 12 form a first passage CH1, and two parallel rows of a third electrode array 13 and a fourth electrode array 14 form a second passage CH2, each of which includes a plurality of linearly arranged electrodes. The first passage CH1 has a first ion inlet 41, which is opened in the first electrode array 11 near the front end of the first passage CH1. A first ion transfer port 42 is opened correspondingly in the second electrode array 12 near the rear end of the first passage CH1 and in the third electrode array 13 near the front end of the second passage CH2. A first ion outlet 43 is opened in the fourth electrode array 14 near the rear end of the second passage CH2. The first ion inlet 41 corresponds to the first ion outlet 43 and is offset from the first ion transfer port 42. Specifically, the first ion inlet 41 is located near the left end of the first electrode array 11, the first ion transfer port 42 is located near the right ends of the second electrode array 12 and the third electrode array 13, and the first ion outlet 43 is located near the left end of the fourth electrode array 14.

[0057] An airflow supply unit 2 causes airflows G1 and G2 to pass through the first passage CH1 and the second passage CH2, respectively, and the airflows pass along the length directions of the first passage CH1 and the second passage CH2 in the figure. A power supply 3 is electrically connected to each electrode of each electrode array and is positioned so as to apply an electric field force to the ions in the first passage CH1 and the second passage CH2 in a direction opposite to the force of the airflow acting on the ions. By controlling the power supply 3, it is possible to adjust the electric field strength distribution in the first passage CH1 and the second passage CH2, and thereby control the balance between the airflow propulsion force and the electric field force in the first passage CH1 and the second passage CH2.

[0058] Between the first passage CH1 and the second passage CH2, a "dipole DC" electric field or a deflected DC electric field is used to transport or transfer ions in the first passage CH1 from the first ion transfer port 42 to the second passage CH2, thereby forming a U-shaped ion migration path that passes through the first ion entrance 41, the first ion transfer port 42, and the first ion exit 43 in sequence, i.e., a predetermined path 8 along which ions travel in the U-shaped ion mobility analyzer 100.

[0059] Specifically, in the first passage CH1, a linear or nonlinear first DC electric field E1 can be applied to the electrode arrays 11 and 12, and the arrow at E1 in the figure indicates the direction of action of the first DC electric field on the ions. There is also an airflow G1 flowing through the first passage CH1, and the direction of the force it exerts on the ions is opposite to the direction of the electric field force exerted on the ions by the first DC electric field E1.

[0060] In the second passage CH2, a linear or nonlinear second DC electric field E2 is applied to the electrode arrays 13 and 14, and an airflow G2 flows through the second passage CH2, and the direction of the force that the airflow G2 exerts on the ions is opposite to the direction of the electric field force that the second DC electric field E2 exerts on the ions. At the same time, the airflow G2 flows in the same direction as the airflow G1 in the first passage CH1, so that the airflow G1 and the airflow G2 are supplied by a single airflow supply unit 2.

[0061] The filter modes of the U-shaped ion mobility analyzer 100 include the following two types.

[0062] (1) filter-SIM mode The power supply 3 is arranged to keep the first DC electric field E1 in the first passage CH1 and the second DC electric field E2 in the second passage CH2 constant, while maintaining a fixed difference ΔE between E1 and E2, and to continuously filter ions of a fixed mobility range or a fixed mobility (ΔE=0) by the balance between the airflow driving force and the electric field force in the first passage CH1 and the second passage CH2.

[0063] By setting E1 and E2 fixed, the difference between E1 and E2 is maintained at a fixed difference ΔE, thereby achieving either (a) or (b) below.

[0064] a. Ions with ion mobility greater than a first threshold can be ejected through the first passage CH1 to the second passage CH2, and ions with ion mobility less than a second threshold (greater than the first threshold) can be ejected through the second passage CH2 to the downstream device. Ions with ion mobility less than the first threshold are eliminated from the right end of the first passage CH1, and ions with ion mobility greater than the second threshold are eliminated from the left end of the second passage CH2.

[0065] b. The first channel CH1 allows ions with ion mobility less than the second threshold to be ejected into the second channel CH2, and the second channel CH2 allows ions with ion mobility greater than the first threshold (less than the second threshold) to be ejected into the downstream device. Ions with ion mobility greater than the second threshold are eliminated by leaving the left end of the first channel CH1, and ions with ion mobility less than the first threshold are eliminated by leaving the right end of the second channel CH2 (the situation shown in Figure 2).

[0066] Ions within a target mobility range between the first and second thresholds are designated as target ions.

[0067] (2) filter-scan mode The power supply 3 is configured to keep the difference ΔE between the first DC electric field E1 in the first passage CH1 and the second DC electric field E2 in the second passage CH2 constant, and to synchronously vary E1 and E2, for example, from low to high intensity, to scan different mobility ranges or mobility values ​​(ΔE=0) within a fixed mobility window, for example, to pass ions in order from highest to lowest mobility. In other words, the difference from the filter-SIM mode is that in the filter-scan mode, E1 and E2 change over time, and the first and second thresholds corresponding to E1 and E2 also change over time, thereby changing the target mobility range for the target ions.

[0068] The U-shaped ion mobility analyzer 100 operating in filter mode uses only the balance between the airflow driving force (the magnitude of which depends on the CCS, airflow velocity, etc.) and the electric field force to select ions that fit within a target mobility range and continuously move them along a predetermined path 8, while ions outside the target mobility range are removed from the predetermined path 8 and filtered out or lost from both ends of the first passage CH1 or the second passage CH2, or transported to and stored at the end of the first passage CH1 or the second passage CH2, and the selected ions within the target mobility range are continuously released from the first ion outlet 43. Specific details of the ion movement, storage, and filter-out processes can be found in Patent Document 5, and a detailed description thereof will be omitted here.

[0069] <Tandem U-type ion mobility spectrometry device> <Example 1> 3 is a schematic diagram of the structure of a tandem U-shaped ion mobility spectrometer according to this embodiment. As shown in FIG. 3, the tandem U-shaped ion mobility spectrometer according to this embodiment is configured with two U-shaped ion mobility analyzers 100 connected in tandem (i.e., ions flowing out of a first U-shaped ion mobility analyzer 4 flow into a second U-shaped ion mobility analyzer 5). The first U-shaped ion mobility analyzer 4 and the second U-shaped ion mobility analyzer 5 can both adopt basically the same hardware structure as the U-shaped ion mobility analyzer 100, and therefore, a description thereof will be omitted here.

[0070] In the tandem U-shaped ion mobility spectrometry device of this technical solution, the first ion outlet 43 of the first U-shaped ion mobility analyzer 4 is arranged corresponding to the second ion inlet 51 of the second U-shaped ion mobility analyzer 5, and ions emitted from the first ion outlet 43 of the first U-shaped ion mobility analyzer 4 can enter the second U-shaped ion mobility analyzer 5 through the second ion inlet 51.

[0071] The first U-shaped ion mobility analyzer 4 further has a first ion direct path 91 that runs directly from the first ion inlet 41 to the first ion outlet 43, and the second U-shaped ion mobility analyzer 5 has a second ion direct path 92 that runs directly from the second ion inlet 51 to the second ion outlet 53, and the first ion direct path 91 and the second ion direct path 92 are provided corresponding to each other to form an ion direct path 9. The ion direct path 9 can be a preliminary path other than the predetermined path 8, and when ion mobility analysis is not required, ions pass through the ion direct path 9, pass through the first ion inlet 41, pass through the tandem U-shaped ion mobility spectrometry device, and exit from the second ion outlet 53.

[0072] An ion source may be provided upstream of the first passage CH1, and ions generated in the ion source enter the first passage CH1 through the first ion inlet 41. Another detection device may be provided downstream of the fourth passage CH4, and fragment ions emitted from the second ion outlet 53 may enter the downstream detection device for further detection. The downstream detection device may be, for example, a mass spectrometer, particularly an MS / MS tandem mass spectrometer, especially a high-resolution tandem mass spectrometer such as a Q-TOF, which is suitable for omics analysis of proteins, polypeptides, etc.

[0073] In some applicable embodiments, the ion source is at least one of: (i) electrospray ionization ("ESI") ion source, (ii) atmospheric pressure photoionization ("APPI") ion source, (iii) atmospheric pressure chemical ionization ("APCI") ion source, (iv) matrix-assisted laser desorption ionization ("MALDI") ion source, (v) laser desorption ionization ("LDI") ion source, (vi) atmospheric pressure ionization ("API") ion source, (vii) silicon-on-silicon desorption ionization ("SIL") ion source, (viii) ion source, (viv) laser desorption ionization ("LDI") ion source, (viii) silicon-on-silicon desorption ionization ("SIL ... (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 (xxiv) sonic spray ionization ("SSI") ion source, (xxv) matrix-assisted entrance ionization ("MAII") ion source, (xxvi) solvent-assisted entrance ionization ("SAII") ion source, (xxvii) Penning ionization source, (xxviii) laser ablation electrospray ionization ("LAESI") ion source, (xxix) He plasma (HeP1) ion source. It is preferred to employ a room pressure or real-time ion source such as an electrospray ionization ("ESI") ion source, a matrix-assisted laser desorption ionization ("MALDI") ion source, a direct analysis in real time ("DART") ion source, or a laser ablation electrospray ionization ("LAESI") ion source.

[0074] The mass analyzer may be one or a combination of a quadrupole mass analyzer, a time-of-flight mass analyzer, a Fourier transform mass analyzer, an ion trap mass analyzer, and a magnetic mass analyzer.

[0075] The tandem U-shaped ion mobility spectrometry device according to this embodiment further includes an ion dissociator 6 that is arranged to receive and dissociate ions emitted from the first ion outlet 43, and to emit fragment ions generated by the dissociation to the second ion entrance 51. In Figures 3-7 and 9, the indicated position of the ion dissociator 6 is the position of the target region targeted by the ion dissociator 6.

[0076] The ion dissociator 6 may be an additional ion dissociator 6 based on the tandem structure of the first U-shaped ion mobility analyzer 4 and the second U-shaped ion mobility analyzer 5, such as an additional collision-induced dissociator, electron dissociator, radical dissociator, or mobile dissociator. In some applicable embodiments, a target region is further formed in the UMA analyzer 2, and the ion dissociator 6 dissociates ions in the target region. The target region may be located at multiple reasonable positions downstream of the first ion outlet 43, for example, the target region may be located between the first ion outlet 43 and the second ion entrance 51. Referring to FIG. 3 , in some applicable embodiments, the ion dissociator 6 may be an acceleration electrode 19 located between the first ion outlet 43 and the second ion entrance 51. The acceleration electrode 19 rapidly accelerates ions in this region and causes them to collide with gas molecules, thereby dissociating ions.

[0077] In other applicable embodiments, the ion dissociation device 6 may further include one or more ion dissociation devices selected from the group consisting of a collision-induced dissociation (CID) device, a surface-induced dissociation (SID) device, an electron transfer dissociation (ETD) device, an electron capture dissociation (ECD) device, an electron collision or impact dissociation device, a photoinduced dissociation (PID) device, a laser-induced dissociation device, an infrared radiation-induced dissociation device, an ultraviolet radiation-induced dissociation device, a nozzle-separator interface dissociation device, an in-source dissociation device, an in-source collision-induced dissociation device, a thermal or temperature source dissociation device, an electric field-induced dissociation device, a magnetic field-induced dissociation device, an enzymatic digestion or enzymatic degradation dissociation device, an ion-ion reactive dissociation device, an ion-molecular reactive dissociation device, an ion-atom reactive dissociation device, an ion-metastable ion reactive dissociation device, an ion-metastable molecule reactive dissociation device, and an electron ionization dissociation (EID) device.

[0078] In the tandem U-shaped ion mobility spectrometry device of this embodiment, the first U-shaped ion mobility analyzer 4 operates in a filter mode (filter-SIM or filter-scan), but the operation mode of the second U-shaped ion mobility analyzer 5 is not limited and may operate in the filter mode or another mode. For example, the second U-shaped ion mobility analyzer 5 can operate in a "trap-release" mode to achieve a higher duty ratio.

[0079] Preferably, the first U-shaped ion mobility analyzer 4 operates in filter-SIM mode. The filter-SIM mode is a static filter mode that can continuously release ions within a fixed ion mobility window range from the first ion outlet 43. Therefore, the lower ion dissociator 6 and the second U-shaped ion mobility analyzer 5 do not need to be installed in synchronization with the first U-shaped ion mobility analyzer 4, and can receive ions within the first target mobility window range released from the first ion outlet 43 at any time.

[0080] Furthermore, the second U-shaped ion mobility analyzer 5 can operate in filter-SIM or filter-scan mode. When the second U-shaped ion mobility analyzer 5 operates in filter-SIM mode, fragment ions within the second target mobility range generated after ion dissociation within the first target mobility range can be continuously obtained from the first ion outlet 43.

[0081] When the second U-shaped ion mobility analyzer 5 operates in filter-scan mode, it can allow ions in different mobility ranges to pass through sequentially at different times, thereby enabling selective scanning or full scanning analysis of ion fragments. Furthermore, ions filtered out during a certain period can be stored in the ion storage area of ​​the second U-shaped ion mobility analyzer 5 and released during a scanning period, improving the ion utilization efficiency and the duty cycle of tandem U-shaped ion mobility spectrometry.

[0082] In this manner, two U-shaped ion mobility analyzers 100 can be connected in tandem. Ions enter the first U-shaped ion mobility analyzer 4 through the first ion inlet 41. The first U-shaped ion mobility analyzer 4, operating in filter mode, filters the ions based on their mobility using only the reverse airflow propulsion and electric field force. Specifically, ions that are not within the first target mobility range are filtered out and exit the predetermined path 8. Ions that are within the first target mobility range continue to travel along the predetermined path 8 to the first ion outlet 43 and are continuously released before entering the ion dissociator 6 for dissociation. The resulting fragment ions enter the second U-shaped ion mobility analyzer 5 through the second ion inlet 51. The fragment ions are then subjected to ion mobility analysis in the second U-shaped ion mobility analyzer 5 and are then released through the second ion outlet 53 to the downstream device.

[0083] In the tandem U-shaped ion mobility spectrometry device of this embodiment, the first U-shaped ion mobility analyzer 4 and the second U-shaped ion mobility analyzer 5 must be connected in tandem, and therefore the airflow supply unit 2 must supply airflow to the first U-shaped ion mobility analyzer 4 and the second U-shaped ion mobility analyzer 5 simultaneously.

[0084] Generally, as shown in Figure 3, a single U-shaped ion mobility analyzer has two ion passages and requires two gas flow paths. The first ion outlet 43 of the first U-shaped ion mobility analyzer 4 is opened to the electrode array 14, and the second ion inlet 51 of the second U-shaped ion mobility analyzer 5 is opened to the electrode array 15. The first ion outlet 43 is aligned with the second ion inlet 51. That is, when the first U-shaped ion mobility analyzer 4 and the second U-shaped ion mobility analyzer 5 are arranged parallel to each other, the first passage CH1, the second passage CH2, the third passage CH3, and the fourth passage CH4 are arranged parallel to each other.

[0085] Since the first passage CH1, the second passage CH2, the third passage CH3, and the fourth passage CH4 are arranged in parallel and independently, the airflow supply unit 2 needs to supply airflow to each of the first passage CH1, the second passage CH2, the third passage CH3, and the fourth passage CH4, and the formed airflow path includes four airflow sub-paths G1, G2, G3, and G4 that run along the first passage CH1, the second passage CH2, the third passage CH3, and the fourth passage CH4, respectively.

[0086] In some other application embodiments, considering that each passage supplies approximately the same airflow rate, adding one airflow sub-path will correspondingly increase the airflow supply amount, which requires a vacuum pump with a higher pumping speed in the airflow supply unit 2, thereby increasing the volume of the vacuum system. In order to reduce the airflow supply amount of the airflow supply unit 2, some airflow paths are integrated in some embodiments of the present invention.

[0087] Figures 4 and 5 show two more specific structural schematic diagrams of a tandem U-shaped ion mobility spectrometry instrument that shares an airflow path.

[0088] <Example 2> FIG. 4 shows a tandem U-shaped ion mobility spectrometer with three rows of channels. As shown in FIG. 4, the second channel CH2 of the first U-shaped ion mobility analyzer 4 and the third channel CH3 of the second U-shaped ion mobility analyzer 5 are connected to each other. Specifically, the second channel CH2 and the third channel CH3 are located on either side of the ion direct channel 9 and are connected end-to-end along a collinear line along their length. The second channel CH2 and the third channel CH3 communicate with each other to form a long ion channel perpendicular to the ion direct channel 9. The ion dissociator 6 is located between the opposing ends of the second channel CH2 and the third channel CH3. As a result, ions are released directly from the end of the second channel CH2 away from the first ion transfer port 42, dissociated by the ion dissociator 6, and then enter the second U-shaped ion mobility analyzer 5 from the end corresponding to the third channel CH3. Since only one airflow path G2 is formed in the long ion passage consisting of the second passage CH2 and the third passage CH3, the airflow supply unit 2 only needs to supply three airflow paths G1, G2, and G3, which eliminates one airflow path and makes the structure of the tandem U-type ion mobility spectrometry device more compact.

[0089] As shown in FIG. 4 , the ends of the second passage CH2 and the third passage CH3 are directly connected to form a predetermined path 8 for target ions and their fragment ions within the target mobility range to travel. Therefore, to prevent ions outside the target mobility range from entering the second passage CH2 in the reverse direction when filtered out in the third passage CH3 and to improve the duty ratio of the system, a first ion storage region 55 may be provided at the end of the third passage CH3 corresponding to the second passage CH2. An RF field is applied to the electrode corresponding to the first ion storage region 55 when ions are stored to restrain the ions. When mobility analysis is required, the stored ions can be quickly transferred to the second U-shaped ion mobility analyzer 5 for mobility analysis.

[0090] By using the above method, the tandem U-type ion mobility spectrometry device of this embodiment can reduce the number of paths to three. Furthermore, since it has nine direct ion paths, sample ions can pass through quickly when mobility analysis is not required, thereby expanding the range of usage scenarios for the product.

[0091] Example 3 5 shows a tandem U-shaped ion mobility spectrometer with two rows of passages. As shown in FIG. 5, in another applicable tandem U-shaped ion mobility spectrometer with a shared airflow path, the first U-shaped ion mobility analyzer 4 and the second U-shaped ion mobility analyzer 5 are arranged parallel to each other, and the first ion outlet 43 is provided corresponding to the second ion inlet 51.

[0092] 5 differs from the tandem U-shaped ion mobility spectrometry device of FIG. 3 in that the exteriors of the first U-shaped ion mobility analyzer 4 and the second U-shaped ion mobility analyzer 5 are further covered with a housing 7, and the housing 7 includes a first chamber 71, a second chamber 72, and an airflow guide unit 73. The first chamber 71 covers the exterior of the first U-shaped ion mobility analyzer 4, has an airflow inlet at its left end, is connected to the airflow guide unit 73 at its right end, and has a first through-hole opened in the first chamber 71 at a position corresponding to the first ion outlet 43. The second chamber 72 covers the exterior of the second U-shaped ion mobility analyzer 5, has an airflow outlet at its left end, is connected to the airflow guide unit 73 at its right end, and has a second through-hole opened in the second chamber 72 at a position corresponding to the second ion inlet 51.

[0093] The airflow supply unit 2 can supply two airflows G1 and G2 to the first passage CH1 and the second passage CH2 from the airflow inlet of the first chamber 71. The airflow path of one airflow G1 flows along the first passage CH1 to the airflow guide unit 73, and the airflow path of the other airflow G2 flows along the second passage CH2 to the airflow guide unit 73. After joining together, the two airflows G1 and G2 are bent at the airflow guide unit 73 and then pass through the third passage CH3 and the fourth passage CH4 in opposite directions, respectively, before finally flowing out through the airflow outlet.

[0094] The airflow guiding effect of the airflow guide unit 73 allows the number of parallel airflow passages to be reduced to two, while still ensuring the independence of ion control between the first U-shaped ion mobility analyzer 4 and the second U-shaped ion mobility analyzer 5. This reduces the required airflow rate and the volume of the vacuum pump, making it easier to miniaturize the instrument. Furthermore, in this embodiment, ions can pass directly through the tandem U-shaped ion mobility spectrometry device via the direct ion path 9 and exit through the second ion outlet 53, thereby effectively improving the versatility of the tandem U-shaped ion mobility spectrometry device in different usage scenarios.

[0095] Example 4 6 shows another tandem U-shaped ion mobility spectrometer having two rows of passages. Referring to FIG. 6, the tandem U-shaped ion mobility spectrometer includes a first U-shaped ion mobility analyzer 4 and a second U-shaped ion mobility analyzer 5, which are collinear and face each other, and a reflux transition section 20 disposed between the first U-shaped ion mobility analyzer 4 and the second U-shaped ion mobility analyzer 5. The reflux transition section 20 includes a fifth passage CH5 and a sixth passage CH6, where the first passage CH1, the fifth passage CH5, and the third passage CH3 are connected end-to-end in sequence, and the second passage CH2, the sixth passage CH6, and the fourth passage CH4 are connected end-to-end in sequence.

[0096] The reflux transition section 20 further includes a reflux port 21 connecting the fifth passage CH5 and the sixth passage CH6, and an ion dissociator 6 is provided within the reflux port 21. Target ions flowing out of the second passage CH2 enter the sixth passage CH6 and are dissociated into fragment ions through the reflux port 21. The fragment ions are transported to the fifth passage CH5. After entering the fifth passage CH5, the fragment ions flow into the third passage CH3 of the second U-shaped ion mobility analyzer 5 and undergo mobility analysis along a U-shaped predetermined path 8 of the second U-shaped ion mobility analyzer 5, sequentially passing through the third passage CH3, the second ion transfer port 52, the fourth passage CH4, and the second ion outlet 53.

[0097] The second U-shaped ion mobility analyzer 5 may operate in a filter mode or any other reasonable mode, such as a trap-release mode, and the present application is not limited thereto. In some embodiments, the fifth passage CH5 of the reflux transition section 20 may have a first ion storage region 55 and the end of the fourth passage CH4 may be provided with a second ion storage region 56 to temporarily store fragment ions outside of some target mobility ranges and improve the duty cycle of the instrument.

[0098] In some embodiments, the fifth passage CH5 may further include an ion removal device (not shown) that removes ions that are not within the target mobility range and that were filtered out in the first passage CH1 and / or the third passage CH3, thereby preventing them from affecting the analysis in the third passage CH3. There are various methods for removing ions, such as removing the RF restraint voltage in the region or applying a negative DC potential to attract positive ions to the electrode and cause them to disappear.

[0099] As a result, the tandem U-shaped ion mobility spectrometry device of this embodiment can reduce the number of parallel airflow paths to two, resulting in more uniform airflow. Furthermore, by configuring the second U-shaped ion mobility analyzer 5 in filter mode, ions can still be continuously transported to the lower stage through the tandem U-shaped ion mobility spectrometry device, avoiding the impact of space charge effects on the detection of low-abundance ions due to ion storage. This effectively meets the detection requirements for low-abundance ions in omics research on proteins, polypeptides, etc.

[0100] <Example 5> 7 shows a three-dimensional tandem U-shaped ion mobility spectrometry device formed by stacking a first U-shaped ion mobility analyzer 4 and a second U-shaped ion mobility analyzer 5. Referring to FIG. 7, the four channels are distributed in a 2x2 arrangement, i.e., the third channel CH3 and the fourth channel CH4 are installed on the same side of the first channel CH1 and the second channel CH2, respectively, and the electrode array of the third channel CH3 is arranged corresponding to the electrode array of the first channel CH1, and the electrode array of the fourth channel CH4 is arranged corresponding to the electrode array of the second channel CH2.

[0101] For convenience of illustration, FIG. 7 shows the third passage CH3 and the fourth passage CH4, which are actually located in the lower layer, and the first passage CH1 and the second passage CH2, which are actually located in the upper layer, in the same drawing.

[0102] Referring to Figure 7, ions enter the first passage CH1 from the first ion inlet 41 along a direction perpendicular to the paper, then reach the ion transition port 22 via a U-shaped predetermined path 8, where their direction of movement changes from along the paper to a direction perpendicular to the paper. After reaching the fourth passage CH4 in the lower layer, they are first dissociated in the ion dissociator 6, and then undergo mobility analysis of the fragment ions via the U-shaped predetermined path 8. Fragment ions that meet the conditions are transported to the lower device via the second ion outlet 53.

[0103] The tandem U-shaped ion mobility spectrometry device of this embodiment has a compact and regular structure, a short axial length, and a uniform airflow field. Furthermore, the first ion inlet 41 and the second ion outlet 53 are positioned in correspondence with each other, so that ions can pass through the tandem U-shaped ion mobility spectrometry device without mobility analysis.

[0104] Hereinafter, based on a tandem U-type ion mobility spectrometry apparatus according to an embodiment of the present invention, an ion mobility analysis method applied to the tandem U-type ion mobility spectrometry apparatus will be described in detail with reference to the drawings.

[0105] <Ion mobility spectrometry> In some embodiments of the present invention, there is further provided an ion mobility spectrometry method. Figure 8 is a flow chart of an ion mobility spectrometry method. The ion mobility spectrometry method includes: an ion filtering step S1 of filtering target ions having ion mobilities within a target mobility range from the ion beam by a first U-shaped ion mobility analyzer 4 placed in a filter mode; an ion dissociation step S2 in which target ions filtered by the first U-shaped ion mobility analyzer 4 are received and dissociated to obtain fragment ions corresponding to the target ions; and a fragment ion analysis step S3 of performing ion mobility analysis on the fragment ions.

[0106] This ion mobility analysis method can be applied not only to the tandem U-type ion mobility spectrometry devices according to Examples 1-5, but also to a U-type ion mobility analyzer 100 with a conventional hardware structure, by changing the application method of the control electric field.

[0107] FIG. 9 is a schematic diagram of the flow for implementing the ion mobility analysis method of an embodiment of the present invention by using a U-shaped ion mobility analyzer 100 with a conventional hardware structure, in combination with an additional ion dissociator 6 and a specific electric field application method.

[0108] In this embodiment, ions are periodically generated or transported to the first ion entrance 41 and enter the first passage CH1 of the U-shaped ion mobility analyzer 100 from the first ion entrance 41. Referring to Figure 9, unlike the conventional filter mode in which filtered target ions are directly transported to a downstream device, in this embodiment, in one detection cycle, in the ion filtering step S1 corresponding to the first time period, the filtered target ions are gradually accumulated or stored at a position close to the first ion exit 43 of the second passage CH2.

[0109] When the pulsed ion pack enters the U-shaped ion mobility analyzer 100 and filtering is completed, ion generation or transport is stopped, and ions stored in the second passage CH2 near the first ion outlet 43 can be dissociated and analyzed. Specifically, the ion dissociator 6 is disposed between the two ion direct ports 93 of the ion direct path 9.

[0110] During a second time period after the first time period, the ions stored in a position near the first ion outlet 43 of the second passage CH2 pass through the ion direct port 93 and return in the reverse direction from the second passage CH2 to the first passage CH1, during which time they are ionized by the ion dissociator 6 to obtain fragment ions.

[0111] In the third time period following the second time period, the fragment ions are again subjected to ion mobility analysis via the U-shaped predetermined path 8, and the ions obtained from the analysis can be transported to the lower stage.

[0112] As described above, the ion mobility spectrometry method according to this embodiment can realize two-stage or multi-stage IMS / IMS tandem analysis using a single U-shaped ion mobility analyzer 100, further reducing the requirements for the device volume and airflow rate.

[0113] The ion mobility analysis method according to this embodiment can also be applied to a tandem U-shaped ion mobility spectrometry device having a first U-shaped ion mobility analyzer 4 and a second U-shaped ion mobility analyzer 5, for example, the tandem U-shaped ion mobility spectrometry device according to Examples 1 to 5 of the present invention.

[0114] In some embodiments, both the first U-shaped ion mobility analyzer 4 and the second U-shaped ion mobility analyzer 5 can operate in filter-selected ion monitoring (filter-SIM) mode.

[0115] 3, the tandem U-shaped ion mobility spectrometry device first executes an ion filtering step S1. In the ion filtering step S1, the power supply 3 applies a first DC electric field E1 to the first passage CH1 of the first U-shaped ion mobility analyzer 4 and a second DC electric field E2 to the second passage CH2 of the first U-shaped ion mobility analyzer 4, and the first DC electric field E1 and the second DC electric field E2 are kept constant during one detection cycle. Ions generated in the upper ion source of the tandem U-shaped ion mobility spectrometry instrument continuously enter the first U-shaped ion mobility analyzer 4 through the first ion inlet 41. Due to the combined action of the first DC electric field E1 and the air flow G1 in the first passage CH1, ions whose ion mobility is greater than the first target mobility range are filtered out by escaping from the end of the first passage CH1. The remaining ions are deflected by the action of the deflecting electric field in the first ion transfer port 42 and enter the second passage CH2 through the first ion transfer port 42. Due to the combined action of the second DC electric field E2 and the air flow G2 in the second passage CH2, ions whose ion mobility is less than the first target mobility range are filtered out by escaping from the end of the second passage CH2. Thus, ions within the fixed first target mobility range can continuously travel along a predetermined path 8 from the first ion inlet 41 to the first ion outlet 43, and are continuously released from the first ion outlet 43 into the second U-shaped ion mobility analyzer 5.

[0116] Next, an ion dissociation step S2 is performed. In the ion dissociation step S2, the ion dissociator 6 receives the ions emitted from the first ion outlet 43, dissociates the ions to generate fragment ions, and introduces the resulting fragment ions into the second ion inlet 51 of the second U-shaped ion mobility analyzer 5. In Fig. 3, an electrode array 19 is provided as the ion dissociator 6 between the first ion outlet 43 and the second ion inlet 51. The ions emitted from the first ion outlet 43 are accelerated by the electrode array 19 and collide with gas molecules, causing them to dissociate. The dissociated fragment ions then enter the second ion inlet 51.

[0117] Finally, fragment ion analysis step S3 is performed. In fragment ion analysis step S3, the power supply 3 applies a third DC electric field E3 to the third passage CH3 of the second U-shaped ion mobility analyzer 5, and a fourth DC electric field E4 to the fourth passage CH4 of the second U-shaped ion mobility analyzer 5, and the third DC electric field E3 and the fourth DC electric field E4 are kept constant within one detection period. The fragment ions dissociated by the ion dissociator 6 continuously enter the second U-shaped ion mobility analyzer 5 through the second ion inlet 51. Due to the action of the third DC electric field E3 and the airflow G3 in the third passage CH3, fragment ions whose ion mobility is greater than the second target mobility range are filtered out by escaping from the end of the third passage CH3. The remaining fragment ions are deflected by the action of the deflecting electric field in the second ion transfer port 52 and enter the fourth passage CH4 through the second ion transfer port 52. Due to the action of the fourth DC electric field E4 and the airflow G4 in the fourth passage CH4, fragment ions whose ion mobility is less than the target mobility range are filtered out by escaping from the end of the fourth passage CH4. As a result, the fragment ions within the fixed second target mobility range can continuously travel along a predetermined path 8 from the second ion inlet 51 to the second ion outlet 53, and are continuously released from the second ion outlet 53 to the lower-stage device.

[0118] As a result, ions are passed through two filtering processes without a storage process, so that target ions are always transported continuously to the downstream device, further solving the problem of reduced resolution of low-abundance ions due to the space charge effect, and enabling tandem mobility analysis of specific parent-daughter ion pairs.

[0119] In another embodiment, the first U-shaped ion mobility analyzer 4 may be placed in filter-selected ion monitoring (filter-SIM) mode and the second U-shaped ion mobility analyzer 5 may be placed in filter-scan mode.

[0120] 4 and 7, an ion filter step S1 is first performed. In the ion filter step S1, target ions within a fixed first target mobility range can continuously travel a predetermined path 8 from the first ion inlet 41 to the first ion outlet 43 (the end of the second passage away from the first ion transfer port 42) and are continuously released from the end of the second passage CH2 away from the first ion transfer port 42.

[0121] Next, an ion dissociation step S2 is performed. In the ion dissociation step S2, the ion dissociator 6 receives the ions released from the first ion outlet 43, dissociates the ions to generate fragment ions, and introduces the resulting fragment ions back into the second ion inlet 51 of the second U-shaped ion mobility analyzer 5 (the end of the third passage CH3 away from the second ion transition port 52).

[0122] Finally, the fragment ion analysis step S3 is performed. In the fragment ion analysis step S3, the power supply 3 applies a third DC electric field E3 to the third channel CH3 of the second U-shaped ion mobility analyzer 5 and a fourth DC electric field E4 to the fourth channel CH4 of the second U-shaped ion mobility analyzer 5. During one detection cycle, the field strengths of the third DC electric field E3 and the fourth DC electric field E4 are increased synchronously, while the field strength difference ΔE between the third DC electric field E3 and the fourth DC electric field E4 is kept constant. During the synchronous increase of E3 and E4, the field strength difference between the main portions of the third channel CH3 and the fourth channel CH4 is always maintained at ΔE, thereby scanning the entire mobility range within a specific mobility window. The increase of E3 and E4 may be synchronous, either gradually or stepwise. As the electric field strength in the main body increases, the electric field strength on the right side of the first ion storage region 55 remains stable at its highest value, while the electric field strength on the left side of the second ion storage region 56 remains stable at its lowest value. Therefore, as the third DC electric field E3 increases, the electric field strength gradient in the first ion storage region 55 decreases, and the mobility range covered by the first ion storage region 55 is correspondingly reduced. As the mobility of the ions in the first ion storage region 55 is scanned, they gradually enter the target mobility range, move leftward along their length, and are transported to the fourth passage CH4 through the second ion transfer port 52.

[0123] The second U-shaped ion mobility analyzer 5 operates in filter-scan mode, and ions outside the target mobility range are still stored in the first ion storage area 55 or the second ion storage area 56. The stored ions can be released and used at the appropriate time, allowing most of the fragment ions to be used efficiently and a high dynamic range to be obtained. Furthermore, since the first U-shaped ion mobility analyzer 4 operates in filter-SIM mode, the second U-shaped ion mobility analyzer 5 can receive and analyze fragment ions dissociated from the target ion even if it is not installed in sync with the first U-shaped ion mobility analyzer 4.

[0124] The above are only preferred embodiments of the present invention, and are not intended to limit the present invention. Any modifications, equivalent replacements, and improvements made within the spirit and principle of the present invention should be included in the protection scope of the present invention. [Explanation of symbols]

[0125] 100 U-type ion mobility analyzer 11 First electrode array 12 Second electrode array 13 Third electrode array 14. Fourth electrode array 15 Electrode Array 19 Accelerating electrode 20 Reflux Transition Section 21 Reflux port 22 Ion Transfer Port 2 Air flow supply section 3 Power supply 4. First U-type ion mobility analyzer 41 First ion inlet 42 First ion transfer port 43 First ion outlet 5. Second U-type ion mobility analyzer 51 Second ion inlet 52 Second Ion Transfer Port 53 Second ion outlet 55 First Ion Conservation Area 56 Second Ion Conservation Area 6 Ion dissociator 7. Housing 71 First Chamber 72 Second Chamber 73 Air flow guide section 8 Predetermined Route 9 Ion Direct Route 91 First Ion Direct Route 92 Second Ion Direct Path 93 AEON direct entrance CH1 First aisle CH2 2nd aisle CH3 3rd aisle CH4 4th aisle CH5 Fifth aisle CH6 Sixth Pathway

Claims

1. A tandem U-type ion mobility spectrometry apparatus, comprising: a first U-shaped ion mobility analyzer operating in a filter mode, having a first passage and a second passage, the first passage having a first ion inlet opening and the second passage having a first ion outlet opening; a second U-shaped ion mobility analyzer having a third passage and a fourth passage, a second ion inlet opening in the third passage and a second ion outlet opening in the fourth passage, the second ion inlet being provided corresponding to the first ion outlet; an airflow supply unit that supplies airflow to the first passage, the second passage, the third passage, and the fourth passage; a power supply electrically connected to the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer, and configured to apply an electric field force to ions in the first passage, the second passage, the third passage, and the fourth passage in a direction opposite to the force acting on the ions by the gas flow; an ion dissociator arranged to receive and dissociate ions from the first U-shaped ion mobility analyzer and release fragment ions produced by the dissociation into the second U-shaped ion mobility analyzer.

2. the first passage, the second passage, the third passage, and the fourth passage are arranged in parallel to one another, 2. The tandem U-type ion mobility spectrometry device according to claim 1, wherein the airflow path formed by the airflow supply unit includes four airflow sub-paths along the first passage, the second passage, the third passage, and the fourth passage, respectively.

3. 2. The tandem U-shaped ion mobility spectrometry device according to claim 1, wherein the airflow path formed by the airflow supply unit includes an airflow path passing through both the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer.

4. the first U-shaped ion mobility analyzer includes a first ion direct path from the first ion inlet to the first ion outlet, and the second U-shaped ion mobility analyzer includes a second ion direct path from the second ion inlet to the second ion outlet; the first ion direct path and the second ion direct path are disposed correspondingly to form an ion direct path; 4. The tandem U-shaped ion mobility spectrometry device according to claim 3, wherein the second passage and the third passage are provided on either side of the ion direct path, respectively, and are connected end-to-end along the length direction in a collinear manner.

5. The airflow guide further includes a housing including a first chamber, a second chamber, and an airflow guide portion; the first chamber covers an outer surface of the first U-shaped ion mobility analyzer, has an airflow inlet at one end and the other end communicates with the airflow guide unit, and has a first through-hole opened at a position of the first chamber corresponding to the first ion outlet; 4. The tandem U-shaped ion mobility spectrometry device according to claim 3, wherein the second chamber covers an outer surface of the second U-shaped ion mobility analyzer, has an airflow outlet at one end, and the other end communicates with the airflow guide section, and has a second through-hole opened at a position of the second chamber corresponding to the second ion inlet.

6. 2. The tandem U-shaped ion mobility spectrometry apparatus according to claim 1, wherein the second U-shaped ion mobility analyzer operates in a filter mode.

7. 7. The tandem U-shaped ion mobility spectrometry apparatus of claim 6, wherein the first U-shaped ion mobility analyzer is configured in a filter-selected ion monitoring mode, and the second U-shaped ion mobility analyzer is configured in a filter-scanning mode.

8. The tandem U-shaped ion mobility spectrometry apparatus according to claim 6, wherein the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer are both configured in a filter-selected ion monitoring mode.

9. 2. The tandem U-type ion mobility spectrometry device of claim 1, wherein the ion dissociator performs dissociation of ions within a target region, and the target region is located between the first ion outlet and the second ion inlet.

10. 2. The tandem U-type ion mobility spectrometry apparatus according to claim 1, wherein the ion dissociation device is one or more of a collision-induced dissociation device, an electron dissociation device, a radical dissociation device, and a mobile dissociation device.

11. A U-type ion mobility analyzer, a first passageway including first and second parallel opposing electrode arrays; a second passage including a third electrode array and a fourth electrode array facing each other in parallel, wherein the first electrode array, the second electrode array, the third electrode array, and the fourth electrode array are arranged in parallel in order, the first electrode array has an ion inlet, the fourth electrode array has an ion outlet, the second electrode array and the third electrode array both have an ion direct port and an ion transfer port, the ion direct port, the ion inlet, and the ion outlet are provided corresponding to each other, and the ion transfer port and the ion direct port are provided offset from each other; an airflow supply unit that supplies airflow to the first passage and the second passage; a power supply electrically connected to the first electrode array, the second electrode array, the third electrode array, and the fourth electrode array, respectively, and configured to apply an electric field force to ions in the first passage and the second passage in a direction opposite to a force acting on the ions by the airflow; an ion dissociator provided between the two ion direct ports; Equipped with In one detection period, During a first time period, the U-shaped ion mobility analyzer is placed in a filter mode, and target ions obtained by the filter are stored in the second passage; During a second time period after the first time period, the target ions stored in the second passage are dissociated by the ion dissociator to obtain fragment ions, and the fragment ions are transferred to the first passage; In a third time period after the second time period, ion mobility analysis is performed on the fragment ions using a predetermined path that sequentially passes through the first passage, the ion transfer port, the second passage, and the ion outlet. A U-shaped ion mobility analyzer, characterized in that an electric field application method using the power supply is installed.

12. an ion filtering step of filtering target ions having ion mobilities within a target mobility range from the ion beam using a first U-shaped ion mobility analyzer configured in a filter mode; an ion dissociation step of receiving and dissociating the target ions filtered by the first U-shaped ion mobility analyzer to obtain fragment ions corresponding to the target ions; a fragment ion analysis step of performing ion mobility analysis on the fragment ions.

13. 13. The method of claim 12, wherein the fragment ion analyzing step is performed by a second U-shaped ion mobility analyzer.

14. 14. The ion mobility spectrometry method of claim 13, wherein the first U-shaped ion mobility analyzer is configured in a filter-selected ion monitoring mode and the second U-shaped ion mobility analyzer is configured in a filter-scanning mode.

15. The ion mobility spectrometry method of claim 13, wherein the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer are both configured in a filter-selected ion monitoring mode.

16. the fragment ion analysis step is performed by the first U-shaped ion mobility analyzer, and an ion dissociation device performing the ion dissociation step is installed between two ion direct ports of the first U-shaped ion mobility analyzer; In the ion filtering step, the target ions are stored in a second passage of the first U-shaped ion mobility analyzer; In the ion dissociation step, the target ions stored in the second passage are dissociated when passing through the ion direct passage to obtain fragment ions, and the fragment ions are transferred to the first passage of the first U-shaped ion mobility analyzer; 13. The ion mobility analysis method according to claim 12, wherein in the fragment ion analysis step, ion mobility analysis is performed on the fragment ions using a predetermined path that passes through the first path and the second path in this order.

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