Tandem u-shaped 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 analysis, and more specifically, to a tandem U-type ion mobility spectrometry apparatus and an ion mobility analysis method.

Background Art

[0002] Ion mobility spectrometry is a technique for separating ions according to their ion mobilities. Generally, since it can distinguish isomers that cannot be distinguished by mass spectrometry, ion mobility spectrometry is widely used in the field of biological analysis.

[0003] In recent years, in order to increase the dimensionality of parameters on which analysis depends, many tandem forms of ion mobility spectrometry apparatuses and other apparatuses have been adopted. Generally, an ion mobility spectrometry apparatus and a mass spectrometer are combined into a single tandem mass spectrometry instrument, and different ions are further separated according to the differences in the properties of ion mobilities, thereby improving the ion discrimination ability. For example, in Patent Document 1, the TIMS technology and the DIA / DDA technology were combined to discover the Parallel Accumulation SErial Fragmentation (PASEF) technology.

[0004] Furthermore, in some studies, in order to improve the separation efficiency (resolution) of ions in ion mobility spectrometry with respect to ion mobility, it has been proposed to tandemly couple two ion mobility spectrometry apparatuses. In Patent Document 2, it has been proposed to combine FAIMS and IMS devices based on different physical mechanisms of IMS and FAIMS to achieve a larger separation efficiency (resolution).

[0005] In Patent Document 3, a method and apparatus for accurately identifying gas-phase ions using a plurality of tandem filter devices have been proposed, and it has been proposed to improve the specificity and sensitivity of IMS detection based on two DMA tandem combinations. One of the DMAs is operated at a high electric field within at least a non-linear mobility range. However, due to the limitations of the filter mode of the DMA itself, only ions within the target mobility range can be selected during one scanning period, and all the remaining ions are lost, resulting in a relatively low utilization efficiency of the DMA ions and a relatively low duty cycle of the entire system. In addition, the selection of the DMA based on differential ion mobility is disadvantageous for molecular structure characterization, and there is a lack of a reference theoretical database for complex issues such as bio-omics research.

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

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

[0008] First, for the omics research of complex samples, the difference in the content of different components is extremely large, and a very high dynamic range is required to obtain relatively good qualitative and quantitative results. However, in order to achieve 100% ion utilization efficiency in the parallel accumulation technology, it is necessary to accumulate ions in the first TIMS. Since TIMS is developed based on the principle of ion trap, some ions with low abundance are pushed out due to the space charge effect, and the dynamic range of the tandem device is limited by the ion capacity of the first TIMS.

[0009] In the second aspect, the operations of the two TIMSs need to be synchronized with each other, and the complexity of the electric field application is high and the requirements for control accuracy are strict.

Prior Art Documents

Patent Documents

[0010]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Summary of the Invention

Problems to be Solved by the Invention

[0011] In view of the above problems, the present invention provides a tandem U-type ion mobility spectrometry device and an ion mobility analysis method that reduce the complexity and accuracy requirements of electric field application, have relatively high resolution and dynamic range, and are applicable to the research of complex problems such as biological omics.

[0012] Previously, the inventor of the present invention developed a U-shaped ion mobility analyzer (UMA, Patent Document 5) that operates in filter mode based on the operating principle of the combined action of air flow and electric field on ions. In a predetermined time period, ions within the target mobility range are selected and continuously released to the lower-stage device, and ions outside the target mobility range are blocked or filtered out only by the balance between the air flow propulsion force and the electric field force. Different from the selection method of pulse emission such as TIMS, according to the UMA operating in filter mode, continuous selection and continuous emission of ions can be realized, and ions within the target mobility range are not constrained or stored and can always move along a predetermined path.

[0013] Specifically, according to the first aspect of the present invention, a tandem U-shaped ion mobility spectrometry device is provided, and the tandem U-shaped ion mobility spectrometry device includes two tandem-connected U-shaped ion mobility analyzers. Specifically, the tandem U-shaped ion mobility spectrometry device in the present application includes a first U-shaped ion mobility analyzer, a second U-shaped ion mobility analyzer, an air flow supply unit, a power source, and an ion dissociation device.

[0014] Among them, the first U-shaped ion mobility analyzer operates in filter mode and has a first passage and a second passage. A first ion inlet is opened in the first passage, and a first ion outlet is opened in the second passage. The second U-shaped ion mobility analyzer has a third passage and a fourth passage. A second ion inlet is opened in the third passage, and a second ion outlet is opened in the fourth passage. The second ion inlet is provided corresponding to the first ion outlet.

[0015] The air flow supply unit supplies air flow to the first passage and the second passage of the first U-shaped ion mobility analyzer, and the third passage and the fourth passage 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 arranged to apply an electric field force in a direction opposite to the acting force on the ions due to the air flow to the ions in the first passage, the second passage, the third passage, and the fourth passage.

[0017] The ion dissociation device is arranged to receive ions from the first U-shaped ion mobility analyzer, dissociate them, and release the fragment ions generated by the dissociation to the second U-shaped ion mobility analyzer.

[0018] According to the tandem U-shaped ion mobility spectrometry device provided by the present invention, since the first U-shaped ion mobility analyzer operates in a filter mode and does not have a specific operation cycle, it is not necessary to strictly synchronize the second U-shaped ion mobility analyzer with the operation cycle of the first U-shaped ion mobility analyzer. The electric field application method or the control flow can be set relatively freely, and the control of the second U-shaped ion mobility analyzer is flexible. The feature of a high achievable duty ratio is effectively utilized to realize rich functions similar to the MRM mode in tandem mass spectrometry.

[0019] In addition, the ions within the first target mobility range can always move along a predetermined path from the first ion inlet to the first ion outlet of the first U-shaped ion mobility analyzer with almost no stagnation or slowdown. It is easy to maintain the concentration of high-abundance ions below the saturation limit of the detector, and low-abundance ions can be stably transported to the lower-stage device. Thereby, the quantitative accuracy of high-abundance ions and the detection sensitivity of low-abundance ions are effectively improved, and the dynamic range of detection is improved. Also, the UMA operating in the filter mode can arbitrarily select the filter target passage, and can not only sequentially scan but also skip scan, improving the scan rate and avoiding interference from unnecessary 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 in parallel with each other, and the airflow path formed by the airflow supply unit includes four airflow sub-paths respectively along the first passage, the second passage, the third passage, and the fourth passage.

[0021] According to the tandem U-shaped ion mobility spectrometry apparatus applied to the present invention, usually, a single UMA includes four electrode arrays installed in parallel, and the passages defined by taking two electrode arrays as a set become ion passages, and the ion inlet and the ion outlet are opened to the electrode arrays.

[0022] Therefore, the fact that the first passage, the second passage, the third passage, and the fourth passage are arranged in parallel with each other means that a total of eight electrode arrays of the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer are all provided in parallel to define four parallel ion passages. 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 apparatus applied to the present invention, by having a single airflow path supplied by the airflow supply unit pass through both the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer simultaneously, at least one airflow path can be saved, the airflow supply amount by the airflow supply unit can be reduced, and the cost and volume of the pump can be reduced.

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

[0026] According to the tandem U-shaped ion mobility spectrometry apparatus applicable to the present invention, by installing 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 corresponding to each other, when ion mobility analysis is not required, ions can be directly discharged from the second ion outlet through the tandem U-shaped ion mobility spectrometry apparatus along the ion direct path.

[0027] By providing the second passage and the third passage at both ends of the ion direct path respectively and connecting them end-to-end and collinearly along the length direction, the second passage and the third passage can be communicated to form a long ion passage perpendicular to the ion direct path. Ions within the target mobility range can be directly released from the end of the second passage away from the first ion transfer port, and after being dissociated by the ion dissociation device, the fragment ions enter the second U-shaped ion mobility analyzer from the corresponding end of the third passage. The air flow supply unit only needs to supply one air flow path in the long passage composed of the second passage and the third passage. Thus, compared with independently supplying four air flow paths, one air flow path can be saved, and the structure of the tandem U-shaped ion mobility spectrometry apparatus can be made more compact.

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

[0029] According to the tandem U-shaped ion mobility spectrometry device applied to the present invention, through the covering and guiding of the housing, the two air flow paths supplied from the air flow supply part to the first path and the second path can be respectively communicated with the third path and the fourth path. On the premise of ensuring the independence of ion control by the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer, the number of parallel air flow paths can be reduced to two, the required air flow rate can be reduced, the volume of the pump can be reduced, and the device can be easily miniaturized.

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

[0031] According to the tandem U-shaped ion mobility spectrometry device applied to the present invention, the 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 discharged downward through the second ion outlet.

[0032] In the technical solution applied to the present invention, the power supply is arranged as follows. Apply a first DC electric field to the first channel, apply a second DC electric field to the second channel, the first DC electric field and the second DC electric field do not change within one detection period, apply a third DC electric field to the third channel, apply a fourth DC electric field to the fourth channel, within one detection period, the electric field strengths of the third DC electric field and the fourth DC electric field rise synchronously, and the electric field strength difference between the third DC electric field and the fourth DC electric field does not change.

[0033] According to the tandem U-type ion mobility spectrometry apparatus applicable to the present invention, set the first U-type ion mobility analyzer to a filter-selection ion monitoring (filter-SIM) mode in which only ions within a certain fixed first target mobility range can pass through over a long period of time, and set the second U-type ion mobility analyzer to a filter-scan mode, so that ions within different mobility ranges at different times can be allowed to pass through in a batch, and selective scanning or global scanning of the mobility allowable range for fragment ions can be performed.

[0034] In the above manner, the first U-type ion mobility analyzer can continuously release ions within the fixed first target mobility range downstream, and the second U-type ion mobility analyzer can, at any timing within the detection period, receive fragment ions obtained by dissociating the ions released through the first ion outlet by the first U-type ion mobility analyzer, and there is no need to set the first U-type ion mobility analyzer and the second U-type ion mobility analyzer in synchronization. Also, by analyzing fragment ions in the filter-scan mode, ions filtered out at a certain point within one detection period can be stored in the ion storage region of the second U-type ion mobility analyzer without loss during scanning and can be released during scanning at other points, thereby improving the utilization efficiency of ions, increasing the duty ratio of tandem U-type ion mobility spectrometry, and theoretically being able to reach 100%.

[0035] In the technical solution applicable to the present invention, the power supply is A first DC electric field is applied to a first passage, and a second DC electric field is applied to a second passage. The first DC electric field and the second DC electric field do not change within one detection period. Also, a third DC electric field is applied to a third passage, and a fourth DC electric field is applied to a fourth passage, and the third DC electric field and the fourth DC electric field are arranged so as not to change within one detection period.

[0036] According to 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 a filter-selected ion monitoring (filter-SIM) mode, so that ions within a first target mobility range are dissociated to continuously obtain fragment ions within a second target mobility range generated thereby. The entire tandem U-shaped ion mobility spectrometry apparatus is used for static ion mobility analysis, facilitating repeated analysis by a subsequent device, and there is no need to install it so as to synchronize the subsequent device with the tandem U-shaped ion mobility spectrometry apparatus, making it easy to use in combination with the subsequent device.

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

[0038] According to the tandem U-shaped ion mobility spectrometry apparatus applied to the present invention, by installing the ion dissociation device between the first ion outlet and the second ion inlet, it is possible to avoid inhibiting the movement of ions and fragment ions within the target mobility range in 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 including a first passage, a second passage, an air flow supply unit, a power source, and an ion dissociation device is disclosed. Among them, the first passage includes a first electrode array and a second electrode array that face each other in parallel, the second passage includes a third electrode array and a fourth electrode array that face each other in parallel, the first electrode array, the second electrode array, the third electrode array, and the fourth electrode array are arranged in parallel in sequence, the first electrode array has an ion inlet, the fourth electrode array has an ion outlet, and both the second electrode array and the third electrode array have an ion straight-through port and an ion transfer port. The ion straight-through port, the ion inlet, and the ion outlet are provided corresponding to each other, and the ion transfer port and the ion straight-through port are provided offset. The air flow supply unit supplies air flow to the first passage and the second passage, 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 in a direction opposite to the acting force of the air flow on the ions in the first passage and the second passage. The ion dissociation device is provided between the two ion straight-through ports.

[0041] In one detection cycle, the electric field application method by the power source is arranged as follows. In the first time period, the U-shaped ion mobility analyzer is arranged in the filter mode, and the target ions obtained by filtering are stored in the second passage. In the second time period after the first time period, the target ions stored in the second passage are dissociated by the ion dissociation device to obtain fragment ions, and the fragment ions are transferred to the first passage. In the 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.

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

[0043] In a third aspect of the present invention, An ion filter step of filtering target ions having an ion mobility within a target mobility range from an ion beam by a first U-shaped ion mobility analyzer arranged 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 analysis step of performing ion mobility analysis on the fragment ions are disclosed.

[0044] In the technical solution applied to the present invention, the fragment ion analysis step is performed by a second U-shaped ion mobility analyzer.

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

[0046] In the technical solution applied to the present invention, both the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer are arranged 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 the first U-shaped ion mobility analyzer, and an ion dissociation device for performing the ion dissociation step is installed between two ion direct-through ports of the first U-shaped ion mobility analyzer. In the ion filter step, the target ions are stored in the 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-through port to obtain fragment ions. The fragment ions are transferred back to the first passage 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 passing through the first passage and the second passage in sequence.

Brief Description of the Drawings

[0048]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Modes for Carrying Out the Invention

[0049] Hereinafter, with reference to the drawings in the embodiments of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described. It is obvious that the described embodiments are only a 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 those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0050] <Terms and Their Interpretations> "Filter mode" is an operating mode applicable to an ion mobility analyzer similar to the filter mode of a general quadrupole mass filter. In such an operating mode, only ions within a specific mobility range can pass through the ion mobility analyzer during a certain time period in the ion mobility analyzer, and ions outside the mobility range cannot pass through the ion mobility analyzer.

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

[0052] In an embodiment of the present invention, the physical quantity analyzed or measured by the ion mobility analyzer is limited to the ion mobility in a low electric field, and the ion mobility is directly related to the collision cross section (CCS) of the ions. That is, it is possible to obtain CCS information using the ion mobility analyzer. The ion mobility analyzer operating in the "filter mode" continuously filters ions within a specific mobility range, and the ion inlet is always continuously injected with samples.

[0053] The "filter mode" of the U-shaped ion mobility analyzer includes at least the following two types. One is the static mode, that is, a mode in which only ions within a certain target mobility range can pass through over a long period of time, and it is generally called the filter-selected ion monitoring (filter-SIM) mode. The other is the dynamic scan mode, that is, a mode in which the upper limit value (second threshold value) and the lower limit value (first threshold value) of the target mobility range corresponding to the target ions are adjusted synchronously and highly or lowly at different times, and the target ions within different mobility ranges are sequentially passed through, and it is called the 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 DC electric field is applied to collide the protein molecule 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 rows of parallel first electrode arrays 11 and second electrode arrays 12 form a first passage CH1, and two rows of parallel third electrode arrays 13 and fourth electrode arrays 14 form a second passage CH2. Each electrode array includes electrodes arranged in a plurality of straight lines. The first passage CH1 has a first ion inlet 41, and the first ion inlet 41 is opened in the first electrode array 11 near the front side of the first passage CH1. A first ion transfer port 42 is correspondingly opened in the second electrode array 12 near the rear side of the first passage CH1 and the third electrode array 13 near the front side of the second passage CH2. A first ion outlet 43 is opened in the fourth electrode array 14 near the rear side of the second passage CH2. The first ion inlet 41 corresponds to the first ion outlet 43 and is provided offset from the first ion transfer port 42. Specifically, the first ion inlet 41 is located at a position near the left end of the first electrode array 11, the first ion transfer port 42 is located at a position near the right ends of the second electrode array 12 and the third electrode array 13, and the first ion outlet 43 is located at a position near the left end of the fourth electrode array 14.

[0057] By the airflow supply unit 2, airflows G1 and G2 are respectively passed through the first passage CH1 and the second passage CH2, and the passing directions of the airflows are along the length directions of the first passage CH1 and the second passage CH2 in the figure. The power supply 3 is electrically connected to each electrode of each electrode array and is arranged to apply an electric field force in a direction opposite to the acting force of the airflow on the ions in the first passage CH1 and the second passage CH2. By controlling the power supply 3, the electric field strength distribution in the first passage CH1 and the second passage CH2 can be adjusted, and thus the balance between the airflow propulsion force and the electric field force in the first passage CH1 and the second passage CH2 can be controlled.

[0058] Between the first channel CH1 and the second channel CH2, by means of a single "dipole DC" electric field or a deflecting DC electric field, ions in the first channel CH1 are transported or transferred from the first ion transfer port 42 to the second channel CH2, thereby forming a U-shaped ion movement path that sequentially passes through the first ion inlet 41, the first ion transfer port 42, and the first ion outlet 43, that is, a predetermined path 8 through which ions move in the U-shaped ion mobility analyzer 100.

[0059] Specifically, in the first channel CH1, a linear or non-linear first DC electric field E1 can be applied to the electrode arrays 11 and 12. The arrow in E1 in the figure indicates the acting direction of the first DC electric field on the ions. There is also an air flow G1 flowing through the first channel CH1, and the direction of the force it exerts on the ions is opposite to the direction of the electric field force exerted by the first DC electric field E1 on the ions.

[0060] In the second channel CH2, a linear or non-linear second DC electric field E2 is applied to the electrode arrays 13 and 14. There is an air flow G2 flowing through the second channel CH2, and the direction of the force it exerts on the ions is opposite to the direction of the electric field force exerted by the second DC electric field E2 on the ions. At the same time, for the air flow G2, the air flow G1 in the first channel CH1 is in the same direction as the air flow G2 so that the single air flow supply unit 2 supplies the air flow G1 and the air flow G2.

[0061] The filter mode of the U-shaped ion mobility analyzer 100 includes 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 channel CH1 and the second DC electric field E2 in the second channel CH2 unchanged, set the difference between E1 and E2 as a fixed difference ΔE, and continuously filter ions with a fixed mobility range or a fixed mobility (ΔE = 0) by the balance of the air flow propulsion force and the electric field force in the first channel CH1 and the second channel CH2.

[0063] By setting the fixed E1 and E2 and maintaining the difference between E1 and E2 as the fixed difference ΔE, the following (a) or (b) is realized.

[0064] a. Through the first channel CH1, ions with an ion mobility greater than the first threshold can be released into the second channel CH2, and through the second channel CH2, ions with an ion mobility smaller than the second threshold (greater than the first threshold) can be released to the lower-stage device. Ions with an ion mobility smaller than the first threshold are dissipated away from the right end of the first channel CH1, and ions with an ion mobility greater than the second threshold are dissipated away from the left end of the second channel CH2.

[0065] b. Through the first channel CH1, ions with an ion mobility smaller than the second threshold can be released into the second channel CH2, and through the second channel CH2, ions with an ion mobility greater than the first threshold (smaller than the second threshold) can be released to the lower-stage device. Ions with an ion mobility greater than the second threshold are dissipated away from the left end of the first channel CH1, and ions with an ion mobility smaller than the first threshold are dissipated away from the right end of the second channel CH2. (The situation shown in FIG. 2)

[0066] Ions within the target mobility range between the first threshold and the second threshold are defined as target ions.

[0067] (2) filter-scan mode The power supply 3 keeps the difference ΔE between the first DC electric field E1 of the first channel CH1 and the second DC electric field E2 of the second channel CH2 constant, and synchronously changes E1 and E2 so as to scan, for example, from low intensity to high intensity, thereby scanning different mobility ranges or mobility values (ΔE = 0) within a fixed mobility window, and is arranged to pass ions, for example, in the order from those with a higher mobility to those with a lower mobility. In other words, the difference from the filter-SIM mode is that in the filter-scan mode, E1 and E2 change with time, and accordingly, the first threshold and the second threshold corresponding to E1 and E2 also change with time, and ultimately, the target mobility range corresponding to the target ions is changed.

[0068] The U-shaped ion mobility analyzer 100 operating in the filter mode utilizes only the balance between the airflow propulsion force (the magnitude depends on CCS, airflow velocity, etc.) and the electric field force to select ions that match the target mobility range and continuously move them along a predetermined path 8. At the same time, ions outside the target mobility range are made to depart from the predetermined path 8, filtered out and lost from both ends of the first passage CH1 or the second passage CH2, or transported to and stored at the ends of the first passage CH1 or the second passage CH2. The ions within the selected target mobility range can be continuously emitted from the first ion outlet 43. For the specific ion movement, storage, and filter-out process, reference can be made to Patent Document 5, and the description is omitted here.

[0069] <Tandem U-shaped ion mobility spectrometry device><Example 1> Figure 3 is a structural schematic diagram of the tandem U-shaped ion mobility spectrometry device according to this embodiment. As shown in Figure 3, the tandem U-shaped ion mobility spectrometry device in this embodiment is composed of a tandem connection of two U-shaped ion mobility analyzers 100 (that is, the ions flowing out from the first U-shaped ion mobility analyzer 4 flow into the second U-shaped ion mobility analyzer 5). Among them, both the first U-shaped ion mobility analyzer 4 and the second U-shaped ion mobility analyzer 5 can adopt basically the same hardware structure as the above-mentioned U-shaped ion mobility analyzer 100, and the description is 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 provided corresponding to the second ion inlet 51 of the second U-shaped ion mobility analyzer 5, and the 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 from the second ion inlet 51.

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

[0072] Among them, an ion source may be provided in the front stage of the first passage CH1, and the ions generated by the ion source enter from the first ion inlet 41 of the first passage CH1. Other detection devices may be provided in the rear stage of the fourth passage CH4. The fragment ions released from the second ion outlet 53 can enter the rear stage detection device and be further detected. The rear stage detection device may be, for example, a mass spectrometer, especially an MS / MS tandem mass spectrometer, and among them, a high-resolution tandem mass spectrometer such as Q-TOF suitable for omics analysis of proteins, polypeptides, etc. may also be used.

[0073] In some applicable embodiments, the ion source includes at least one ion source 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) a desorption ionization on silicon (DIOS) ion source, (viii) an electron impact (EI) ion source, (ix) a chemical ionization (CI) ion source, (x) a field ionization (FI) ion source, (xi) a field desorption (FD) ion source, (xii) an inductively coupled plasma (ICP) ion source, (xiii) a fast atom bombardment (FAB) ion source, (xiv) a liquid secondary ion mass spectrometry (LSIMS) ion source, (xv) a desorption electrospray ionization (DESI) ion source, (xvi) a nickel-63 radioactive ion source, (xvii) an atmospheric pressure matrix-assisted laser desorption ionization source, (xviii) a sputtering ion source, (xix) an atmospheric sampling glow discharge ionization (ASGDI) ion source, (xx) a glow discharge (GD) ion source, (xxi) an impactor ion source, (xxii) a direct analysis in real time (DART) ion source, (xxiii) a laser spray ionization (LSI) ion source, (xxiv) a sonic spray ionization (SSI) ion source, (xxv) a matrix-assisted inlet ionization (MAII) ion source, (xxvi) a solvent-assisted inlet ionization (SAII) ion source, (xxvii) a Penning ionization ion source, (xxviii) a laser ablation electrospray ionization (LAESI) ion source, (xxix) a He plasma (HePl) ion source. It is preferable to employ a room pressure or real-time ion source such as an electrospray ionization (ESI) ion source, a matrix-assisted laser desorption ionization ion source (MALDI), a direct analysis in real time ion source (DART), or a laser ablation electrospray ionization (LAESI) ion source.

[0074] The mass spectrometer may be one or a combination 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.

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

[0076] The ion dissociation device 6 may be an additionally installed ion dissociation device based on the tandem structure of the first U-type ion mobility analyzer 4 and the second U-type ion mobility analyzer 5. For example, it may be an additionally installed collision-induced dissociation device, electron dissociation device, radical dissociation device, or movable dissociation device. In some applicable embodiments, a target region is further formed in the UMA analyzer 2, and the ions in the target region are dissociated by the ion dissociation device 6. The target region may be provided at a plurality of reasonable positions on the downstream side of the first ion outlet 43. For example, the target region may be provided between the first ion outlet 43 and the second ion inlet 51. Referring to FIG. 3, in some applicable embodiments, the ion dissociation device 6 may be an acceleration electrode 19 provided between the first ion outlet 43 and the second ion inlet 51. When the acceleration electrode 19 is used, the ions are rapidly accelerated in this region and collide with gas molecules, thereby dissociating the 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 impact or shock dissociation device, a photo-induced 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 reaction dissociation device, an ion-molecule reaction dissociation device, an ion-atom reaction dissociation device, an ion metastable ion reaction dissociation device, an ion metastable molecule reaction dissociation device, and an electron ionization dissociation (EID) device.

[0078] In the tandem U-type ion mobility spectrometry device in this embodiment, the first U-type ion mobility analyzer 4 operates in the filter mode (filter-SIM or filter-scan), but there is no restriction on the operation mode of the second U-type ion mobility analyzer 5, and it may operate in the filter mode or other modes. For example, the second U-type ion mobility analyzer 5 can operate in the "trap-release" mode to achieve a higher duty ratio.

[0079] Preferably, the first U-type ion mobility analyzer 4 operates in the filter-SIM mode. The filter-SIM mode, as a static filter mode, can continuously release ions within the fixed ion mobility window range from the first ion outlet 43. Therefore, the lower-stage ion dissociation device 6 and the second U-type ion mobility analyzer 5 do not need to be installed synchronously with the first U-type ion mobility analyzer 4, and can receive the 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 the filter-SIM or filter-scan mode. When the second U-shaped ion mobility analyzer 5 operates in the filter-SIM mode, fragment ions within a second target mobility range generated after dissociation of ions within a 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 the filter-scan mode, it can allow ions within different mobility ranges to pass sequentially at different timings, thereby enabling selective scanning analysis or global scanning analysis of ion fragments. Furthermore, ions filtered out during a certain time period can be stored in the ion storage region of the second U-shaped ion mobility analyzer 5 and released during scanning in another time period, improving the utilization efficiency of ions and the duty cycle of tandem U-shaped ion mobility spectrometry.

[0082] In the above manner, two U-shaped ion mobility analyzers 100 can be tandem-coupled. Ions enter the first U-shaped ion mobility analyzer 4 from the first ion inlet 41, and the first U-shaped ion mobility analyzer 4 operating in the filter mode utilizes only the reverse airflow propulsion force and the electric field force to perform filter selection on the ion mobility of the ions. Specifically, ions not within the first target mobility range are filtered out outside the predetermined path 8, and ions within the first target mobility range continuously move along the predetermined path 8 to the first ion outlet 43 and are continuously released, then enter the ion dissociation device 6 and are dissociated. The fragment ions obtained after dissociation enter the second U-shaped ion mobility analyzer 5 from the second ion inlet 51. After performing ion mobility analysis on the fragment ions in the second U-shaped ion mobility analyzer 5, they are released from the second ion outlet 53 to the lower-stage device.

[0083] In the tandem U-shaped ion mobility spectrometry apparatus according to this embodiment, since it is necessary to tandemly couple the first U-shaped ion mobility analyzer 4 and the second U-shaped ion mobility analyzer 5, the air flow supply unit 2 needs to supply air flows to the first U-shaped ion mobility analyzer 4 and the second U-shaped ion mobility analyzer 5 simultaneously.

[0084] Generally, as shown in FIG. 3, a single U-shaped ion mobility analyzer has two ion passages and requires two gas flow paths. At the same time, the first ion outlet 43 of the first U-shaped ion mobility analyzer 4 is opened to the electrode array 14, the second ion inlet 51 of the second U-shaped ion mobility analyzer 5 is opened to the electrode array 15, and 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 provided in parallel and independently, the air flow supply unit 2 needs to supply air flows to the first passage CH1, the second passage CH2, the third passage CH3, and the fourth passage CH4 respectively, and the formed air flow path includes four air flow sub-paths G1, G2, G3, and G4 along the first passage CH1, the second passage CH2, the third passage CH3, and the fourth passage CH4 respectively.

[0086] In some other applicable embodiments, considering that the air flow rates supplied by each passage are approximately the same, with the increase of one air flow sub-path, the air flow supply amount also increases correspondingly. Accordingly, a vacuum pump with a larger pump speed is required for the air flow supply unit 2, which will increase the volume of the vacuum system. In order to reduce the air flow supply amount by the air flow supply unit 2, in some embodiments of the present invention, some air flow paths are integrated.

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

[0088] <Example 2> Figure 4 is a tandem U-shaped ion mobility spectrometry apparatus having three rows of passages. As shown in Figure 4, the second passage CH2 of the first U-shaped ion mobility analyzer 4 and the third passage CH3 of the second U-shaped ion mobility analyzer 5 are connected to each other. Specifically, the second passage CH2 and the third passage CH3 are provided on both sides of the ion direct passage 9 along the length direction and are connected end-to-end collinearly. The second passage CH2 and the third passage CH3 communicate with each other to form a long ion passage perpendicular to the ion direct passage 9. The ion dissociation device 6 is provided between the opposing ends of the second passage CH2 and the third passage CH3. Thus, ions are directly emitted from the end of the second passage CH2 away from the first ion transfer port 42, dissociated by the ion dissociation device 6, and then enter the second U-shaped ion mobility analyzer 5 from the corresponding end of the third passage CH3. Since only one air flow path G2 is formed in the long ion passage composed of the second passage CH2 and the third passage CH3, only the three air flow paths G1, G2, and G3 need to be supplied by the air flow supply unit 2, and one air flow path can be saved, making the structure of the tandem U-shaped ion mobility spectrometry apparatus more compact.

[0089] As shown in FIG. 4, since the ends of the second passage CH2 and the third passage CH3 are directly connected to form a predetermined path 8 through which target ions within a target mobility range and their fragment ions move, when ions within a non-target mobility range in the third passage CH3 are filtered out, it is possible to prevent them from entering the second passage CH2 in the reverse direction and also to improve the duty ratio of the system. Thus, 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 electric field is applied to the electrode corresponding to the first ion storage region 55 to confine the ions when they are stored. During the time period 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 the above method, the tandem U-shaped ion mobility spectrometry apparatus according to this embodiment can reduce the number of passages to three. Furthermore, since it has an ion direct path 9, when mobility analysis is not required, sample ions can pass through quickly, enriching the usage scenarios of the product.

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

[0092] In the embodiment of FIG. 5, the outside of the first U-shaped ion mobility analyzer 4 and the second U-shaped ion mobility analyzer 5 is further covered by a housing 7. The housing 7 is different from the tandem U-shaped ion mobility spectrometry device of FIG. 3 in that it includes a first chamber 71, a second chamber 72, and an air flow guide portion 73. Among them, the first chamber 71 covers the outer surface of the first U-shaped ion mobility analyzer 4, an air flow inlet is provided at the left end, the right end communicates with the air flow guide portion 73, and a first through hole is opened at a position where the first chamber 71 corresponds to the first ion outlet 43. The second chamber 72 covers the outer surface of the second U-shaped ion mobility analyzer 5, an air flow outlet is provided at the left end, the right end communicates with the air flow guide portion 73, and a second through hole is opened at a position where the second chamber 72 corresponds to the second ion inlet 51.

[0093] The air flow supply unit 2 can supply two air flows G1 and G2 from the air flow inlet of the first chamber 71 to the first passage CH1 and the second passage CH2. The air flow path of one air flow G1 flows along the first passage CH1 to the air flow guide portion 73, and the air flow path of the other air flow G2 flows along the second passage CH2 to the air flow guide portion 73. After the two air flows G1 and G2 merge, they are bent through the air flow guide portion 73 and then pass through the third passage CH3 and the fourth passage CH4 in the reverse direction, and finally flow out through the air flow outlet.

[0094] Due to the guiding action of the air flow guide portion 73 on the air flow, on the premise of ensuring the independence of ion control of the first U-shaped ion mobility analyzer 4 and the second U-shaped ion mobility analyzer 5, the number of parallel air flow paths can be reduced to two, the required air flow rate can be decreased, the volume of the vacuum pump can be reduced, and it is easier to miniaturize the device. Also, in this embodiment, ions can pass directly through the tandem U-shaped ion mobility spectrometry device through the ion direct passage 9 and flow out from 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> FIG. 6 provides another tandem U-shaped ion mobility spectrometry apparatus having two columns of channels. Referring to FIG. 6, the tandem U-shaped ion mobility spectrometry apparatus includes a first U-shaped ion mobility analyzer 4 and a second U-shaped ion mobility analyzer 5 that are collinear and face each other, and a reflux transition section 20 provided 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 channel CH5 and a sixth channel CH6. The first channel CH1, the fifth channel CH5, and the third channel CH3 are sequentially communicated end-to-end. The second channel CH2, the sixth channel CH6, and the fourth channel CH4 are sequentially communicated end-to-end.

[0096] The reflux transition section 20 further includes a reflux port 21 that communicates the fifth channel CH5 and the sixth channel CH6, and an ion dissociation device 6 is provided in the reflux port 21. The target ions flowing out of the second channel CH2 enter the sixth channel CH6 and then are dissociated through the reflux port 21 to become fragment ions, and the fragment ions are transported to the fifth channel CH5. After entering the fifth channel CH5, the fragment ions flow into the third channel CH3 of the second U-shaped ion mobility analyzer 5, and mobility analysis is performed using the U-shaped predetermined path 8 of the second U-shaped ion mobility analyzer 5 that sequentially passes through the third channel CH3, the second ion transfer port 52, the fourth channel CH4, and the second ion exit 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 does not limit this. In some embodiments, a first ion storage region 55 is provided in the fifth channel CH5 of the reflux transition section 20 and a second ion storage region 56 is provided at the end of the fourth channel CH4 to temporarily store some fragment ions outside a certain target mobility range and improve the duty cycle of the device.

[0098] In some embodiments, an ion removal device (not shown) may be further provided in the fifth channel CH5 to remove ions that are not within the target mobility range and have been filtered out by the first channel CH1 and / or the third channel CH3, thereby avoiding the influence on the analysis of the third channel CH3. There are various methods for removing ions. For example, the RF confinement voltage in the region can be removed, or a negative DC potential can be applied to attract positive ions to the electrode and eliminate them.

[0099] As described above, the tandem U-shaped ion mobility spectrometry device according to this embodiment can reduce the number of parallel air flow channels to two, making the air flow more uniform. Also, in such a tandem U-shaped ion mobility spectrometry device, by arranging the second U-shaped ion mobility analyzer 5 in the filter mode, ions can still be continuously transported downward through the tandem U-shaped ion mobility spectrometry device, avoiding the influence on the detection of low-abundance ions due to the space charge effect caused by ion storage, and effectively meeting the detection requirements for low-abundance ions in omics research such as proteins and polypeptides.

[0100] <Example 5> FIG. 7 provides 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 sets of channels are distributed in a 2×2 arrangement pattern, that is, the third channel CH3 and the fourth channel CH4 are respectively installed on the same side of the first channel CH1 and the second channel CH2, the electrode array of the third channel CH3 and the electrode array of the first channel CH1 are arranged corresponding to each other, and the electrode array of the fourth channel CH4 and the electrode array of the second channel CH2 are arranged corresponding to each other.

[0101] In FIG. 7, for the convenience of illustration, the third channel CH3 and the fourth channel CH4 that are actually located in the lower layer and the first channel CH1 and the second channel CH2 that are actually located in the upper layer are shown in the same figure.

[0102] Referring to FIG. 7, after ions enter the first passage CH1 from the first ion inlet 41 along the direction perpendicular to the paper surface, they reach the ion transfer port 22 via the U-shaped predetermined path 8. The movement direction changes from the direction along the paper surface at the ion transfer port 22 to the direction perpendicular to the paper surface. After reaching the fourth passage CH4 in the lower layer, the ions are first dissociated by the ion dissociation device 6, and further, mobility analysis of the fragment ions is performed by the U-shaped predetermined path 8. The fragment ions that meet the conditions are transported to the lower-stage device through the second ion outlet 53.

[0103] The tandem U-type ion mobility spectrometry apparatus according to this embodiment has a compact and regular structure, a small axial length, and a uniform gas flow field. In addition, the positions of the first ion inlet 41 and the second ion outlet 53 correspond to each other. When mobility analysis is not required, ions may pass through the tandem U-type spectrometry apparatus directly.

[0104] Hereinafter, based on the tandem U-type ion mobility spectrometry apparatus in the embodiments of the present invention, the 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 Analysis Method> In some embodiments of the present invention, an ion mobility analysis method is further provided. FIG. 8 is a flowchart of the ion mobility analysis method. The ion mobility analysis method includes an ion filtering step S1 of filtering target ions with ion mobility within a target mobility range from an ion beam by a first U-type ion mobility analyzer 4 arranged in a filter mode, and an ion dissociation step S2 of receiving and dissociating the target ions filtered by the first U-type ion mobility analyzer 4 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] The ion mobility analysis method can be applied not only to the tandem U-type ion mobility spectrometry apparatus according to Examples 1-5, but also to the U-type ion mobility analyzer 100 with a conventional hardware structure. In that case, it is realized by changing the application method of the control electric field.

[0107] FIG. 9 is a schematic diagram of a flow for realizing the ion mobility analysis method of the embodiment of the present invention by combining the additional ion dissociation device 6 and a specific electric field application method using the U-type ion mobility analyzer 100 with a conventional hardware structure.

[0108] In this embodiment, ions are periodically generated or transported to the first ion inlet 41 and enter the first passage CH1 of the U-type ion mobility analyzer 100 from the first ion inlet 41. Referring to FIG. 9, different from the method in which the filtered target ions are directly transported to the lower device like the conventional filter mode, in this embodiment, in one detection cycle, in the ion filter step S1 corresponding to the first time zone, the filtered target ions are gradually accumulated or stored at a position close to the first ion outlet 43 of the second passage CH2.

[0109] When the pulsed ion packet enters the U-type ion mobility analyzer 100 and the filtering is completed, the generation or transportation of ions is stopped, and dissociation and analysis can be performed on the ions stored at a position close to the first ion outlet 43 of the second passage CH2. Specifically, the ion dissociation device 6 is provided between the two ion direct-through ports 93 of the ion direct-through path 9.

[0110] In the second time zone after the first time zone, the ions stored at a position close to the first ion outlet 43 of the second passage CH2 pass through the ion direct-through port 93 and return from the second passage CH2 to the first passage CH1 in the reverse direction, and are ionized by the ion dissociation device 6 during this process to obtain fragment ions.

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

[0112] As described above, the ion mobility analysis 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, and further reduce the requirements for the device volume and air flow rate.

[0113] The ion mobility analysis method according to this embodiment is also applicable 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 Embodiments 1-5 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 the filter-selected ion monitoring (filter-SIM) mode.

[0115] Taking the tandem U-shaped ion mobility spectrometry apparatus shown in FIG. 3 as an example, first, an ion filtering step S1 is executed. In the ion filtering step S1, a first DC electric field E1 is applied to the first passage CH1 of the first U-shaped ion mobility analyzer 4 by the power supply 3, and a second DC electric field E2 is applied to the second passage CH2 of the first U-shaped ion mobility analyzer 4. In one detection cycle, the first DC electric field E1 and the second DC electric field E2 are kept unchanged. The ions generated by the upper ion source of the tandem U-shaped ion mobility spectrometry apparatus continuously enter the first U-shaped ion mobility analyzer 4 from the first ion inlet 41. Due to the combined action of the first DC electric field E1 and the gas flow G1 in the first passage CH1, the ions with an ion mobility greater than the first target mobility range flow out from the end of the first passage CH1 and are filtered out. The remaining ions are deflected by the deflecting electric field at the first ion transfer port 42 and enter the second passage CH2 through the first ion transfer port 42. Due to the action of the second DC electric field E2 and the gas flow G2 in the second passage CH2, the ions with an ion mobility smaller than the first target mobility range flow out from the end of the second passage CH2 and are filtered out. Thus, the ions within the fixed first target mobility range can continuously move along the predetermined path 8 from the first ion inlet 41 to the first ion outlet 43, and are continuously discharged from the first ion outlet 43 to the second U-shaped ion mobility analyzer 5.

[0116] Next, an ion dissociation step S2 is executed. In the ion dissociation step S2, the ion dissociation device 6 receives the ions discharged from the first ion outlet 43, dissociates the ions to generate fragment ions, and introduces the obtained 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 dissociation device 6 between the first ion outlet 43 and the second ion inlet 51. The ions discharged from the first ion outlet 43 collide with gas molecules and dissociate due to the acceleration by the electrode array 19, and the dissociated fragment ions enter the second ion inlet 51.

[0117] Finally, the fragment ion analysis step S3 is executed. In the fragment ion analysis step S3, a third DC electric field E3 is applied to the third passage CH3 of the second U-shaped ion mobility analyzer 5 by the power supply 3, and a fourth DC electric field E4 is applied to the fourth passage CH4 of the second U-shaped ion mobility analyzer 5. Within one detection cycle, the third DC electric field E3 and the fourth DC electric field E4 are kept unchanged. The fragment ions dissociated by the ion dissociation device 6 continuously enter the second U-shaped ion mobility analyzer 5 from the second ion inlet 51. Due to the action of the third DC electric field E3 and the air flow G3 in the third passage CH3, the fragment ions with an ion mobility greater than the second target mobility range flow out from the end of the third passage CH3 and are filtered out. The remaining fragment ions are deflected by the action of the deflection electric field at 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 air flow G4 in the fourth passage CH4, the fragment ions with an ion mobility smaller than the target mobility range flow out from the end of the fourth passage CH4 and are filtered out. Thus, the fragment ions within the fixed second target mobility range can continuously move along the predetermined path 8 from the second ion inlet 51 to the second ion outlet 53, and are continuously discharged from the second ion outlet 53 to the downstream device.

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

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

[0120] Specifically, referring to FIGS. 4 and 7, first, an ion filter step S1 is executed. In the ion filter step S1, the target ions can continuously move along a predetermined path 8 from the first ion inlet 41 to the first ion outlet 43 (the end portion away from the first ion transfer port 42 of the second passage), which is within a fixed first target mobility range, and are continuously emitted from the end portion away from the first ion transfer port 42 of the second passage CH2.

[0121] Next, an ion dissociation step S2 is executed. In the ion dissociation step S2, the ion dissociation device 6 receives the ions emitted from the first ion outlet 43, dissociates the ions to generate fragment ions, and introduces the obtained fragment ions again into the second ion inlet 51 (the end portion away from the second ion transfer port 52 of the third passage CH3) of the second U-shaped ion mobility analyzer 5.

[0122] Finally, the fragment ion analysis step S3 is executed. In the fragment ion analysis step S3, a third DC electric field E3 is applied to the third passage CH3 of the second U-shaped ion mobility analyzer 5 by the power supply 3, and a fourth DC electric field E4 is applied to the fourth passage CH4 of the second U-shaped ion mobility analyzer 5. In one detection period, the electric field strengths of the third DC electric field E3 and the fourth DC electric field E4 are increased synchronously, and the electric field strength difference ΔE between the third DC electric field E3 and the fourth DC electric field E4 is kept unchanged. In the process of synchronously increasing E3 and E4, by always maintaining the electric field strength difference between the main body parts of the third passage CH3 and the fourth passage CH4 at ΔE, the entire mobility range is scanned within a specific mobility window. The increase of E3 and E4 may gradually increase synchronously or increase step by step synchronously. At the same time as the electric field strength of the main body part increases, the electric field strength on the right side of the first ion storage region 55 is stably maintained at the maximum value, and the electric field strength on the left side of the second ion storage region 56 is stably maintained at the minimum value. Therefore, with the increase of the third DC electric field E3, the electric field strength gradient within the first ion storage region 55 decreases, and the corresponding covered mobility range is reduced. The ions in the first ion storage region 55 sequentially enter the target mobility range along with the scanning of the mobility, move left along the length direction, 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 the filter-scan mode. Ions outside the target mobility range are still stored in the first ion storage region 55 or the second ion storage region 56, and the stored ions can be released and utilized at an appropriate timing. Therefore, most of the fragment ions can be efficiently utilized, and a high dynamic range can be obtained. Also, based on the fact that the first U-shaped ion mobility analyzer 4 operates in the filter-SIM mode, even if the second U-shaped ion mobility analyzer 5 is not installed synchronously with the first U-shaped ion mobility analyzer 4, it can receive and analyze the fragment ions dissociated from the target ions.

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

Explanation of Signs

[0125] 100 U-shaped ion mobility analyzer 11 First electrode array 12 Second electrode array 13 Third electrode array 14 Fourth electrode array 15 Electrode array 19 Acceleration electrode 20 Reflux transition section 21 Reflux port 22 Ion transfer port 2 Airflow supply unit 3 Power supply 4 First U-shaped ion mobility analyzer 41 First ion inlet 42 First ion transfer port 43 First ion outlet 5 Second U-shaped ion mobility analyzer 51 Second ion inlet 52 Second ion transfer port 53 Second ion outlet 55 First ion storage area 56 Second ion storage area 6 Ion dissociation device 7 Housing 71 First chamber 72 Second chamber 73 Airflow guide part 8 Predetermined path 9 Ion direct path 91 First ion direct path 92 Second ion direct path 93 Ion direct port CH1 First passage CH2 Second passage CH3 Third passage CH4 Fourth passage CH5 Fifth passage CH6 Sixth Pathway

Claims

1. A tandem U-shaped ion mobility spectrometry device, operating in filter mode, having a first passage and a second passage, with a first ion inlet opening into the first passage and a first ion outlet opening into the second passage, a first U-shaped ion mobility analyzer; having a third passage and a fourth passage, with a second ion inlet opening into the third passage and a second ion outlet opening into the fourth passage, the second ion inlet being provided corresponding to the first ion outlet, a second U-shaped ion mobility analyzer; an air flow supply unit for supplying air flow to the first passage, the second passage, the third passage and the fourth passage; electrically connected to the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer, and arranged to apply an electric field force in a direction opposite to the acting force of the air flow on the ions in the first passage, the second passage, the third passage and the fourth passage; an ion dissociation device arranged to receive ions from the first U-shaped ion mobility analyzer, dissociate them, and release the fragment ions generated by the dissociation to the second U-shaped ion mobility analyzer. The U-shaped ion mobility spectrometry device is characterized by including the above.

2. The first passage, the second passage, the third passage and the fourth passage are arranged in parallel with each other; The air flow path formed by the air flow supply unit includes four air flow sub-paths respectively along the first passage, the second passage, the third passage and the fourth passage. The tandem U-shaped ion mobility spectrometry device according to claim 1 is characterized by this.

3. The air flow path formed by the air flow supply unit includes an air flow path passing through both the first U-shaped ion mobility analyzer and the second U-shaped ion mobility analyzer. The tandem U-shaped ion mobility spectrometry device according to claim 1 is characterized by this.

4. The first U-shaped ion mobility analyzer includes a first ion direct passage from the first ion inlet to the first ion outlet, and the second U-shaped ion mobility analyzer includes a second ion direct passage from the second ion inlet to the second ion outlet; The first ion direct passage and the second ion direct passage are installed corresponding to each other to form an ion direct passage. The second passage and the third passage are provided on both sides of the ion direct passage, respectively, and are connected end-to-end and collinearly along the length direction. The tandem U-type ion mobility spectrometry device according to claim 3, characterized in that.

5. Further comprising a housing including a first chamber, a second chamber, and an air flow guide portion. The first chamber covers the outer surface of the first U-type ion mobility analyzer, has an air flow inlet provided at one end, communicates with the air flow guide portion at the other end, and a first through hole is opened at a position corresponding to the first ion outlet of the first chamber. The second chamber covers the outer surface of the second U-type ion mobility analyzer, has an air flow outlet provided at one end, communicates with the air flow guide portion at the other end, and a second through hole is opened at a position corresponding to the second ion inlet of the second chamber. The tandem U-type ion mobility spectrometry device according to claim 3, characterized in that.

6. The second U-type ion mobility analyzer operates in a filter mode. The tandem U-type ion mobility spectrometry device according to claim 1, characterized in that.

7. The first U-type ion mobility analyzer is arranged in a filter-selected ion monitoring mode, and the second U-type ion mobility analyzer is arranged in a filter-scanning mode. The tandem U-type ion mobility spectrometry device according to claim 6, characterized in that.

8. Both the first U-type ion mobility analyzer and the second U-type ion mobility analyzer are arranged in a filter-selected ion monitoring mode. The tandem U-type ion mobility spectrometry device according to claim 6, characterized in that.

9. The ion dissociation device dissociates ions in a target region, and the target region is provided between the first ion outlet and the second ion inlet. The tandem U-type ion mobility spectrometry device according to claim 1, characterized in that.

10. The ion dissociation device is one or more of a collision-induced dissociation device, an electron dissociation device, a radical dissociation device, and a movable dissociation device. The tandem U-type ion mobility spectrometry device according to claim 1, characterized in that.

11. A U-type ion mobility analyzer, A first passage including a first electrode array and a second electrode array facing each other in parallel; 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 side by side in parallel in order. The first electrode array has an ion inlet, the fourth electrode array has an ion outlet, and both the second electrode array and the third electrode array have an ion direct passage and an ion transfer passage. The ion direct passage, the ion inlet, and the ion outlet are provided correspondingly, and the ion transfer passage and the ion direct passage are provided offset from each other. The second passage; An air flow supply unit for supplying an air flow 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 arranged to apply an electric field force in a direction opposite to the direction of the acting force of the air flow on the ions in the first passage and the second passage; An ion dissociation device provided between the two ion direct passages; Comprising; In one detection cycle, In a first time period, the U-shaped ion mobility analyzer is arranged in a filter mode, and the target ions obtained by the filter are stored in the second passage; In a second time period after the first time period, the target ions stored in the second passage are dissociated by the ion dissociation device 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 by using a predetermined path that sequentially experiences the first passage, the ion transfer passage, the second passage, and the ion outlet; The electric field application method by the power supply is installed. A U-shaped ion mobility analyzer characterized by this.

12. An ion filter step of filtering target ions having an ion mobility within a target mobility range from an ion beam by a first U-shaped ion mobility analyzer arranged 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, characterized in that it comprises an ion mobility analysis method.

13. The fragment ion analysis step is carried out by a second U-type ion mobility analyzer, characterized in that it is the ion mobility analysis method according to claim 12.

14. The first U-type ion mobility analyzer is arranged in the filter-selection ion monitoring mode, and the second U-type ion mobility analyzer is arranged in the filter-scanning mode, characterized in that it is the ion mobility analysis method according to claim 13.

15. Both the first U-type ion mobility analyzer and the second U-type ion mobility analyzer are arranged in the filter-selection ion monitoring mode, characterized in that it is the ion mobility analysis method according to claim 13.

16. The fragment ion analysis step is carried out by the first U-type ion mobility analyzer, and the ion dissociation device for carrying out the ion dissociation step is installed between two ion through ports of the first U-type ion mobility analyzer. In the ion filter step, the target ions are stored in the second passage of the first U-type ion mobility analyzer. In the ion dissociation step, the target ions stored in the second passage are dissociated when passing through the ion through port to obtain fragment ions, and the fragment ions are transferred to the first passage of the first U-type ion mobility analyzer. In the fragment ion analysis step, ion mobility analysis is performed on the fragment ions by using a predetermined path passing through the first passage and the second passage in sequence, characterized in that it is the ion mobility analysis method according to claim 12.

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