Tandem ion mobility spectrometry device and ion mobility analysis method

Abstract

To provide a tandem ion mobility spectrometer and an ion mobility analysis method related to the field of ion mobility analysis.SOLUTION: A tandem ion mobility spectrometer incorporates an ion dissociation device into a basic structure of a UMA (U-shaped ion Mobility Analyzer), enabling ion mobility spectrometric analysis of ions within a target mobility range as well as fragment ions resulting from dissociation of the ions, achieving higher resolution. Additionally, by configuring an electric field in a first channel to allow ions to accumulate therein, when the ions within the target ion mobility range are selected and released, ions outside the target ion mobility range which need to be analyzed can remain stored in the first channel and be released for analysis later, making ion utilization more efficient.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] The present invention relates to the field of ion mobility spectrometry, and in particular to tandem ion mobility spectrometry devices and methods. [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, in order to increase the number of parameters on which analysis depends, many ion mobility spectrometry devices have been used in tandem with other devices.

[0004] Generally, an ion mobility spectrometry device and a mass spectrometer are combined into a tandem mass spectrometry instrument to further separate different ions based on their ion mobility characteristics, thereby improving the ability to identify ions. For example, in Patent Document 1, TIMS technology and DIA / DDA technology are combined to discover the Parallel Accumulation Serial Fragmentation (PASEF) technology.

[0005] 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).

[0006] 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 based on the tandem combination of two DMAs. One of the DMAs is operated at a high electric field at least within the nonlinear mobility range. However, due to limitations in the DMA's filter mode itself, only ions within the target ion mobility range can be selected in one scan cycle, while all remaining ions are lost. This results in low ion utilization efficiency for the DMA and a low duty cycle for the entire system.

[0007] Regarding 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 installed between the two tandem TIMS analyzers. This tandem TIMS ion mobility spectrometry device can perform preliminary ion mobility separation on ions, then intentionally fragment ions within a target ion mobility range, and then perform ion mobility analysis on the generated fragment ions. The high resolution of the TIMS and the ability to accumulate ions in the first TIMS improve the duty cycle of the tandem ion mobility spectrometry device.

[0008] However, one of the limitations of a tandem TIMS analyzer is that ions outside the target mobility range are lost during the initial selection process of ions within the ion mobility range by the first TIMS, making it difficult to further improve the duty ratio. Furthermore, because the TIMS transports ions only in the axial direction, eliminating ions outside the target mobility range requires the installation of a device such as an ion gate at the ion exit of the first TIMS, which further removes ions with non-target mobilities, making the system configuration complicated. [Prior art documents] [Patent documents]

[0009] [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 CN109003877A [Patent Document 6] China patent CN109003876A [Patent Document 7] China patent CN115223844A Summary of the Invention [Problem to be solved by the invention]

[0010] In response to the above problems, the present invention provides a tandem ion mobility spectrometry apparatus and an ion mobility analysis method that can solve at least some of the problems of the prior art.

[0011] The inventors of the present invention have previously developed a U-shaped ion mobility analyzer (UMA, Patent Document 5), whose operating principle is also based on the joint action of airflow and electric field on ions. Unlike a TIMS, a UMA has two parallel airflow paths arranged perpendicular to the main ion path of the mass spectrometer. Based on this feature, an ion control process designed based on this feature can effectively select the ion mobility range of the concentrated ions when concentrating them in the first path of the UMA, while also effectively storing ions within and outside the ion mobility range. Furthermore, non-target ions synchronously stored in this way do not interfere with the analysis of the current target ion. Therefore, the target ions can occupy a larger space in the first path, or even the entire space, reducing the effect of space charge and improving resolution without significantly sacrificing sensitivity. This ion control process can also be applied to the analysis of tandem ion mobility spectra in this application.

[0012] Specifically, a first aspect of the present invention is a tandem ion mobility spectrometry device in the present application improved based on UMA, which specifically includes a hardware structure of UMA, which includes a first passage, a second passage, an airflow supply, and a power supply. The first passage has a first electrode array and a second electrode array facing each other, the first electrode array has an ion inlet, the second electrode array has a first ion transfer port, the ion inlet and the first ion transfer port are offset in the extending direction of the first passage, the second passage has a third electrode array and a fourth electrode array facing each other, the third electrode array has a second ion transfer port, and the fourth electrode array has an ion outlet, the first ion transfer port and the second ion transfer port are connected and aligned in the extending direction of the second passage, and the ion outlet is offset from the ion inlet on the side of the second ion transfer port. The airflow supply unit supplies an 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 the ions in the first passage and the second passage in a direction opposite to the force acting on the ions by the airflow. In particular, the tandem ion mobility spectrometry apparatus of the present application includes an ion dissociator configured to receive and dissociate ions from a first passageway and to emit fragment ions produced by the dissociation into a second passageway. [Effects of the Invention]

[0013] In the tandem ion mobility spectrometry device according to the present invention, ions to be analyzed enter the first passage through the ion inlet. Due to the balance between the opposing electric field restraining force and the airflow driving force within the first passage, ions that meet the conditions first move along the first passage to the first ion transfer port and are sorted within the first passage in order of ion mobility. Then, ions within the target ion mobility range are deflected and ejected from the first ion transfer port. The ion dissociator receives the ions ejected from the first ion transfer port and dissociates them to generate fragment ions. The generated fragment ions enter the second passage, where the balance between the opposing electric field restraining force and the airflow driving force within the second passage performs ion mobility analysis on the fragment ions. This allows those skilled in the art to freely select and adjust the electric field strength distributions applied to the first and second passages as needed, enabling ion mobility analysis of ions and their dissociated fragment ions to be completed within the two passages of a single UMA device, thereby achieving higher ion resolution.

[0014] In addition, when ions within the target ion mobility range are released from the first passage, the remaining ions awaiting analysis that are outside the target ion mobility range remain stored in the first passage and can be released later for analysis, thereby improving ion utilization efficiency. For ions that do not need to be analyzed, the electric field strength and airflow magnitude within the first passage are adjusted so that ions that do not meet the conditions flow out from both ends of the first passage and are filtered out, eliminating the need to install a separate ion gate in the ion migration path and not affecting the migration of ions within the first passage.

[0015] In the technical solution applied to the present invention, the power supply is: applying a first electric field to the first passageway during a first time period such that ions within the target mobility range accumulate in a target ion enriched area of ​​the first passageway and at least some ions outside the target mobility range enter and are concentrated in a non-target ion enriched area located at an end of the first passageway; During the second time period, a second electric field is applied to the first passage so that at least some of the ions concentrated in the non-target ion high concentration area during the first time period move to the first ion transfer port and pass through the first ion transfer port.

[0016] In the tandem ion mobility spectrometry apparatus according to the present application, when ions within a target mobility range are captured in the first passage and transported to the first ion transfer port, at least some ions outside the target mobility range are not lost and are stored in a target ion high concentration area of ​​the first passage, which may be located at either end of the first passage or at both ends of the first passage.

[0017] During the second time period, the target ion mobility range of the target ion high concentration area is adjusted to select ions originally concentrated in the non-target ion high concentration area, and then the ions are transported through the first ion transfer port to the ion dissociator and the second passage. This process is repeated until all ions in the first passage are analyzed. Therefore, ions in the non-target ion high concentration area are not lost during one analysis process, but are directly involved in the analysis process of the next scan, and the ion utilization efficiency during the ion selection process of the first passage can reach 100%.

[0018] In addition, ions in the non-target ion high concentration area in the first passage can be quickly reselected simultaneously with the ejection of ions within the target mobility range, thereby improving the analytical efficiency of the tandem ion mobility spectrometry device.

[0019] In the technical solution applied in the present invention, the non-target ion high concentration areas are located at both ends of the first passage.

[0020] According to the tandem ion mobility spectrometry device of the present application, by providing non-target ion high concentration areas at both ends of the first passage, ions with relatively high ion mobility and ions with relatively low ion mobility can be stored in the two non-target ion high concentration areas at both ends, respectively, and ions within the target ion mobility range can be concentrated in the target ion high concentration area in the center of the first passage, making it easier to deflect ions within the target ion mobility range and release them from the first ion transfer port.

[0021] In the technical solution applied to the present invention, an ion dissociation device dissociates ions in a target region, and the target region is located at an end of the second passage close to the second ion transfer port and farther from the ion exit than the second ion transfer port.

[0022] According to the tandem ion mobility spectrometry device of the present application, ions ejected from the first passage enter the second passage through the second ion transfer port, and can then be controlled by an electric field applied to the second passage to move the ions in a direction away from the ion outlet. Fragment ions dissociated by an ion dissociator at the end of the ions away from the ion outlet are scanned and ejected in order of ion mobility, move to the ion outlet, and are then ejected to a subsequent device.

[0023] The tandem ion mobility spectrometry device of the present application can be used as a conventional UMA ion mobility spectrometry device by placing a target region outside the ion migration path, and by adjusting the electric field strength distribution, it is possible to analyze the ion mobility of the dissociated fragment ions after the ions enter the target region and dissociate.

[0024] In the technical solution applied in the present invention, the power source is arranged to apply a third electric field to the second passage corresponding to the target region, so as to confine ions within the target region.

[0025] According to the tandem ion mobility spectrometry device of the present application, ions within a target mobility range are confined within a target region at the end, and dissociation of ions within the target region can be performed using an ion dissociation device (e.g., infrared multiphoton dissociation, ultraviolet photon dissociation) that dissociates ions confined within a fixed region. By providing a target region, the tandem ion mobility spectrometry of the present application can be applied to a wider variety of ion dissociation devices, and can achieve photodissociation of ions without interfering with the migration paths of other ions.

[0026] In the technical solution applied in the present invention, an ion dissociation device dissociates ions in a target region, and the target region is located between the first ion transfer port and the second ion transfer port.

[0027] According to the tandem ion mobility spectrometry device of the present application, the target position is set outside the first and second passages, eliminating the need to occupy space within the passages. By controlling the electric field applied to the first and second ion transfer ports, the ion transfer speed can be increased, causing the ions to collide with gas molecules and achieving dynamic ion dissociation.

[0028] In the technical solution applied to the present invention, an ion dissociation device dissociates ions in a target region, the target region being located in the second passage and forming a portion extending from the second ion transfer port toward the ion outlet.

[0029] According to the tandem ion mobility spectrometry device of the present application, by disposing an ion dissociator at a location corresponding to the second ion transition port in the second passage, rapid dissociation of ions in the ion migration path can be achieved, and the fragment ions after dissociation can be directly subjected to ion mobility spectrum analysis in the second passage.

[0030] In the technical solution applied in the present invention, the second passage is arranged to arrange the fragment ions at different positions in the second passage in order of ion mobility, and sequentially release them through the ion outlet.

[0031] According to the tandem ion mobility spectrometry device of the present application, by performing scan-ejection on the fragment ions in the second passage, the fragment ions are sequentially ejected in order of the magnitude of their ion mobility to a downstream device, such as a mass spectrometer, where the fragment ions can be further detected.

[0032] 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 transfer dissociation device, an infrared multiphoton dissociation device, an ultraviolet photon dissociation device, a radical-induced dissociation device, and a surface-induced dissociation device.

[0033] In a second aspect of the present invention, there is provided an ion mobility analysis method for application to a tandem ion mobility spectrometry device in any of the above technical solutions, the ion mobility analysis method comprising: an ion selection step of applying a first electric field to the first passageway during a first time period such that ions within the target mobility range accumulate in a target ion enriched area of ​​the first passageway and at least some ions outside the target mobility range enter and concentrate in a non-target ion enriched area at an end of the first passageway; a concentrated ion releasing step of applying a second electric field to the first passage during a second time period so that at least some of the ions concentrated in the non-target ion high concentration area during the first time period move to the first ion transfer port and pass through the first ion transfer port; and a dissociation step of receiving and dissociating the ions released from the first passage in the ion selection step and / or the concentrated ion release step, and releasing the fragment ions generated by the dissociation into the second passage.

[0034] In the technical solution applied to the present invention, the ion mobility spectrometry method comprises: The method further includes a fragment ion analyzing step of applying a fourth electric field to the second passage so that the fragment ions are arranged at different positions in the second passage in order of ion mobility and sequentially released through an ion outlet of the second passage. [Brief explanation of the drawings]

[0035] [Figure 1] 1 is a schematic diagram of the basic structure of a UMA in a tandem ion mobility spectrometry apparatus according to an embodiment of the present application. [Figure 2] 1 is a schematic diagram of the overall structure of a tandem ion mobility spectrometry device when an ion dissociator according to an embodiment of the present application is in a first position. [Figure 3] 2 is a schematic diagram of the overall structure of a tandem ion mobility spectrometry device when the ion dissociator according to the present application is in a second position. FIG. [Figure 4]2 is a schematic diagram of the overall structure of a tandem ion mobility spectrometry device when the ion dissociator according to the present application is in a third position. FIG. [Figure 5] 1 is a flow chart of the ion mobility spectrometry method of the present application. [Figure 6] 1 is a schematic diagram of an ion selection method according to an ion selection step and a concentrated ion release step in an ion mobility spectrometry method of the present application. [Figure 7] 1 is a schematic diagram of a DC electric field application method for a first passage in an ion selection step and a concentrated ion release step in the ion mobility spectrometry method of the present application. [Figure 8] 1 is a schematic diagram of a DC electric field application method for a first passage in an ion selection step and a concentrated ion release step in the ion mobility spectrometry method of the present application. DETAILED DESCRIPTION OF THE INVENTION

[0036] 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.

[0037] <Terms and their interpretation> The term "scan release" in the ion scanning step refers to the sequential release of ions of different mobilities or mobility ranges, or of different mass numbers or mass ranges, either in increasing or decreasing order, and with some mobilities / mass numbers or mobility / mass ranges skipped along the way.

[0038] The present embodiment provides a tandem ion mobility spectrometry device and an ion mobility analysis method applied to the tandem ion mobility spectrometry device.

[0039] <Tandem ion mobility spectrometry equipment> Figure 1 shows the hardware structure of the UMA analyzer 2 in the tandem ion mobility spectrometry system according to this embodiment. In addition to the UMA analyzer 2 shown in Figure 1, the tandem ion mobility spectrometry system according to this embodiment is equipped with an ion dissociator (not shown in Figure 1) installed within the UMA analyzer 2. The ion dissociator receives and dissociates ions emitted from the first channel CH1 of the UMA analyzer 2, and emits fragment ions generated by the dissociation into the second channel CH2.

[0040] 1, the UMA analyzer 2 of the tandem ion mobility spectrometry apparatus of this embodiment includes four sets of electrode arrays (first electrode array 12, second electrode array 13, third electrode array 14, and fourth electrode array 15, from top to bottom in FIG. 1) arranged in parallel, where the first electrode array 12 and the second electrode array 13 face each other, and the ion path defined by the first electrode array 12 and the second electrode array 13 is the first path CH1. The third electrode array 14 and the fourth electrode array 15 face each other, and the ion path defined by the third electrode array 14 and the fourth electrode array 15 is the second path CH2.

[0041] The first passage CH1 has an ion inlet 201 and a first ion transfer port 202a. The ion inlet 201 is located on the first electrode array 12 near the upstream side of the first passage CH1, and the first ion transfer port 202a is located on the second electrode array 13 adjacent to the first passage CH1 and the second passage CH2. The second passage CH2 has an ion outlet 203 and a second ion transfer port 202b. The second ion transfer port 202b is located on the third electrode array 14 adjacent to the second passage CH2 and the first passage CH1, and the ion outlet 203 is located on the fourth electrode array 15 near the downstream side of the second passage CH2. The first ion transfer port 202a and the second ion transfer port 202b are located correspondingly to communicate the first passage CH1 and the second passage CH2. The ion entrance 201 and the ion exit 203 are arranged correspondingly and are offset from the first ion transfer port 202a and the second ion transfer port 202b, thereby forming a U-shaped passage that passes through the ion entrance 201, the first ion transfer port 202a, the second ion transfer port 202b and the ion exit 203 in sequence, i.e., a U-shaped ion mobility analyzer.

[0042] An airflow supply unit 3 supplies airflow to each of the first passage CH1 and the second passage CH2, and the airflow supply direction is along the horizontal direction shown in Fig. 1. A power supply 4 is electrically connected to each of the first electrode array 12, the second electrode array 13, the third electrode array 14, and the fourth electrode array 15, and can apply an electric field force to the ions in the first passage CH1 and the second passage CH2 in the opposite direction to the force acting on the ions by the airflow. By controlling the power supply 4 to adjust the electric field strength in the first passage CH1 and the second passage CH2, it is possible to control the balance between the airflow propulsion force and the electric field restraint force in the first passage CH1 and the second passage CH2.

[0043] In the tandem ion mobility spectrometry device of this embodiment, the balance between the airflow propulsion force and the electric field restraint force is perpendicular to the upstream-to-rearward direction from the ion entrance 201 to the ion exit 203, along the horizontal direction in FIG. 1 . Therefore, if ions do not satisfy the condition that the balance between the airflow propulsion force and the electric field restraint force can be achieved, they will escape from the openings at both ends in the horizontal direction, be removed or disappear, and will not be transported to the rear. Between the first passage CH1 and the second passage CH2, a "dipole DC" electric field or a deflected DC electric field can be used to transport or transfer ions in the first passage CH1 from the first ion transfer opening 202a and the second ion transfer opening 202b to the second passage CH2.

[0044] For the principles of realizing basic functions such as storing, accumulating, moving, and separating ions in the first passage CH1 and second passage CH2 of the UMA analyzer 2, please refer to Patent Documents 5, 6, 7, and PCT / CN2023 / 116312, and a detailed explanation will be omitted here.

[0045] Referring to FIG. 1, the typical ion migration path in the UMA analyzer 2 can be described as follows: ions generated by a pre-stage device enter the ion entrance 201 in a direction perpendicular to the electrode array. Because the ion entrance 201 and the first ion transfer entrance 202a are offset, ions within a first mobility range first migrate along the first passage CH1 to the first ion transfer entrance 202a due to the balance between the propulsive force of the airflow and the restraining force of the electric field. By changing the electric field distribution applied to the first passage CH1, ions can be aligned at different positions along the length of the first passage CH1 according to their ion mobility. Next, by applying a dipole DC electric field to the first ion transfer entrance 202a and the second ion transfer entrance 202b, some ions that meet certain conditions are deflected at the first ion transfer entrance 202a, enter the second ion transfer entrance 202b, and then travel through the second passage CH2 in a direction opposite to the direction of the first passage CH1 to the ion exit 203, where they are released to the downstream device in a direction perpendicular to the electrode array.

[0046] The ion source can be installed before the first passage CH1 so that ions generated by the ion source enter the first passage CH1 through the first ion inlet 201. Another detection device, such as a mass spectrometer, can be installed after the second passage CH2.

[0047] In some alternative embodiments, the ion source is at least one 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 silicon-on-silicon desorption ionization ("SIL") ion source; (viii) electron impact ("EI") ion source, (ix) chemical ionization ("CI") ion source, (x) field ionization ("FI") ion source, (xi) field desorption ("FD") ion source, (xii) inductively coupled plasma ("ICP") ion source, (xiii) fast atom bombardment ("FAB") ion source, (xiv) liquid secondary ion mass spectrometry ("LSIMS") ion source, (xv) desorption electrospray ionization ("DESI") ion source (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 more preferred to employ room pressure or real-time ion sources such as electrospray ionization ("ESI") ion sources, matrix-assisted laser desorption ionization ("MALDI") ion sources, direct analysis in real time ("DART") ion sources, and laser ablation electrospray ionization ("LAESI") ion sources.

[0048] The mass spectrometer may be one or more of a quadrupole mass spectrometer, a time-of-flight mass spectrometer, a Fourier transform mass spectrometer, an ion trap mass spectrometer, and a magnetic mass spectrometer.

[0049] In addition to the hardware structure of the UMA analyzer 2 described above, the tandem ion mobility spectrometry apparatus of this embodiment further includes an ion dissociator (not shown in FIG. 1, and will be described below by way of example with reference to FIGS. 2-4), which is arranged to receive and dissociate ions from the first passage CH1, and release the fragment ions generated by the dissociation into the second passage CH2.

[0050] The ion dissociator may be a separately added ion dissociator based on the hardware structure of the UMA analyzer 2, such as a separately added collision-induced dissociator, electron transfer dissociator, infrared multiphoton dissociator, ultraviolet photon dissociator, radical-induced dissociator, or surface-induced dissociator. Alternatively, a conventional hardware structure of the UMA analyzer 2 may be used to rapidly accelerate ions in a certain region by controlling the electric field, causing them to collide with gas molecules and dissociate the ions. In some embodiments, the UMA analyzer 2 further includes a target region (not shown in FIG. 1 , which will be described below with reference to FIGS. 2-4 ) and the ion dissociator may be installed within or near the target region to dissociate ions in the target region. The target region may be located at any position downstream of the first ion transfer port 202a of the first passage CH1.

[0051] In other alternative embodiments, the ion dissociation device may further comprise 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 collision 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.

[0052] 2-4 show schematic diagrams of the overall structure of a tandem ion mobility spectrometry device 1 in which the ion dissociator 11 or the target region is installed at different positions, as an example. Hereinafter, the migration path of ions in the tandem ion mobility spectrometry device 1 when the ion dissociator 11 is installed at a different position in the UMA analyzer 2 will be described with reference to the drawings.

[0053] 2 shows an embodiment in which the target region 206 is installed at an end of the second passage CH2 close to the second ion transfer port 202b and is farther away from the ion outlet 203 than the second ion transfer port 202b. After ions released from the first passage CH1 enter the second passage CH2 through the second ion transfer port 202b, the ions can be controlled to move in a direction away from the ion outlet 203 by an electric field applied to the second passage CH2. After being dissociated by the ion dissociator 11 at the end far from the ion outlet 203, the dissociated fragment ions are scanned and released into the ion outlet 203 in order of ion mobility and then released to a downstream device.

[0054] As an alternative embodiment, the power supply 4 is configured to apply a third electric field to the second passage CH2 corresponding to the target region 206, thereby confining ions within the target mobility range within the target region 206. This allows ions within the target region 206 to be dissociated using an ion dissociator 11 (e.g., infrared multiphoton dissociation, ultraviolet photon dissociation) that dissociates ions confined within a fixed region. For example, a laser irradiation device can be installed within the electrode array of the second passage CH2 of the target region 206, or a laser irradiation device can be installed outside the electrode array and irradiate a laser into the passage directly or through a gap between the electrode array, thereby achieving photodissociation of the confined ions within the target region 206.

[0055] According to the tandem ion mobility spectrometry apparatus of this embodiment, by placing the target region 206 outside the ion migration path, the tandem ion mobility spectrometry apparatus can be used as a conventional UMA ion mobility spectrometry apparatus, and by adjusting the electric field strength distribution, after ions enter the target region 206 and dissociate, ion mobility analysis can be performed on the dissociated fragment ions, thereby achieving ion dissociation without interfering with the migration paths of other ions. Furthermore, because ions are confined and stationary in the target region 206, an ion dissociator 11 whose frequency differs from the operating frequency of the UMA can be used, and therefore the tandem ion mobility spectrometry apparatus of the present application can be applied to a wider variety of ion dissociator 11.

[0056] 3 shows an embodiment in which the target region 206 is located between the first ion transfer port 202a and the second ion transfer port 202b. By locating the target region 206 outside the first passage CH1 and the second passage CH2, it is not necessary to occupy space within the passages. In this embodiment, by controlling the electric field applied to the first ion transfer port 202a and the second ion transfer port 202b to improve the ion transfer speed, ions can be caused to collide with gas molecules, thereby achieving dynamic ion dissociation.

[0057] 4 shows an embodiment in which the target region 206 is installed in the second passage CH2 and is configured in a portion extending from the second ion transfer port 202b toward the ion outlet 203. By installing the ion dissociator 11 at a position corresponding to the second ion transfer port 202b in the second passage CH2, rapid dissociation of ions can be achieved in the ion transfer path, and the dissociated fragment ions can be directly subjected to ion mobility spectrum analysis in the second passage CH2.

[0058] Hereinafter, based on the tandem ion mobility spectrometry apparatus 1 of this embodiment, the ion mobility analysis method applied to the tandem ion mobility spectrometry apparatus 1 and the electric field arrangement in the first channel CH1 and the second channel CH2 of the power supply 4 in the tandem ion mobility spectrometry apparatus 1 when performing the ion mobility analysis method will be described in detail with reference to the drawings.

[0059] <Ion mobility spectrometry> In the analytical scan step of the conventional scan mode used in U-type ion mobility analyzers, ions must be scanned over the entire mobility range in each ion mobility spectrum, which is time-consuming and results in a relatively concentrated distribution of ions with relatively concentrated mobilities, leading to a relatively large space charge effect.

[0060] An ion mobility spectrometry method according to an embodiment of the present invention is shown in FIG. The ion mobility spectrometry method includes: an ion selection step S1 of applying a first electric field to the first passage CH1 during a first time period so that ions within the target mobility range are accumulated in a target ion-rich area 204 of the first passage CH1 and at least some ions outside the target mobility range enter and are concentrated in a non-target ion-rich area 205 located at the end of the first passage CH1; an ion transfer step S2 in which ions within the target mobility range in the target ion high concentration area 204 are transferred to the second passage CH2; a dissociation step S3 of receiving and dissociating the ions released from the first passage CH1 in the ion selection step S1, and releasing fragment ions generated by the dissociation into the second passage CH2; and a fragment ion scanning step S4 of applying a fourth electric field to the second passage CH2 to arrange the fragment ions at different positions in the second passage CH2 in order of ion mobility, and sequentially releasing them through the ion outlet 203 of the second passage CH2.

[0061] Next, the target mobility range is changed, and the above steps S1-S4 are repeated. In the process of repeating the above steps, the target mobility range may be changed to a target mobility range corresponding to the ions originally concentrated in the non-target ion high concentration area 205, that is, a concentrated ion releasing step S5 is performed in which a second electric field is applied to the first passage CH1 during a second time period so that at least some of the ions concentrated in the non-target ion high concentration area 205 during the first time period move to the first ion transfer port 202a and pass through the first ion transfer port 202a; a dissociation step S6 of receiving and dissociating the ions released from the first channel CH1 in the concentrated ion release step S5, and releasing fragment ions generated by the dissociation into the second channel CH2; and a fragment ion scanning step S7 of applying a fourth electric field to the second passage CH2 to arrange the fragment ions at different positions in the second passage CH2 in order of ion mobility, and sequentially releasing them through the ion outlet 203 of the second passage CH2.

[0062] In other embodiments, the dissociation step S3 and fragment ion scanning step S4 are performed for ions in only some mobility ranges and are not repeated in every cycle.

[0063] In the ion selection step S1, all ions within the entire mobility range can be concentrated in the first passage CH1, among which ions within the target mobility range are accumulated in the target ion high concentration area 204 of the first passage CH1, i.e., the main body of the first passage CH1 from the ion entrance 201 to the first ion transfer opening 202a.

[0064] Ions outside the target mobility range are concentrated in the non-target ion high concentration area 205. In this embodiment, the non-target ion high concentration area 205 is located at both ends of the first passage CH1. Specifically, the non-target ion high concentration area 205 includes a first non-target ion high concentration area 205a located at one end of the first passage CH1 closer to the ion inlet 201, and a second non-target ion high concentration area 205b located at one end of the first passage CH1 closer to the first ion transfer port 202a.

[0065] The target mobility ranges set for different time periods may be determined by a prior ion mobility spectrum-mass analysis two-dimensional heat map, or may be freely selected according to actual analysis requirements, and are not limited thereto. In an optional embodiment, some ions that enter the first passage CH1 and do not belong to the target mobility range may also be filtered out by being ejected from both ends of the first passage CH1.

[0066] In the concentrated ion release step S5, after the ions within the first mobility range in the ion selection step S1 have been released, the power supply 4 adjusts the electric field applied to the first passage CH1 to a second electric field, causing the ions concentrated in the non-target ion high concentration area 205 to move again through the first passage CH1 to the target ion high concentration area 204. Next, a second ion selection and release can be performed by configuring the second electric field so that the ions within the second mobility range within the target mobility range exactly correspond to the electric field strength range in the region near the first ion transfer port 202a.

[0067] Figure 6 is a schematic diagram of an ion selection method in multiple cycles in the ion mobility spectrometry method of the present application. Figures 7 and 8 are schematic diagrams of a DC electric field application method for the first passage CH1 in the concentrated ion release step S5 in the ion mobility spectrometry method of the present application. Figures 6-8 use ions with seven different ion mobilities as examples, and the straight line segments or broken line segments in the coordinate systems of Figures 6-8 respectively represent the DC electric field strength distribution in the first passage CH1.

[0068] Referring to FIG. 6 , the ion selection step S1 of the first cycle is first performed. The target mobility range of the first channel CH1 is set to match the ion mobilities of the first and second ions. The first and second ions are accumulated in the target ion high concentration area 204, while the third to seventh ions are accumulated in the non-target ion high concentration area 205 of the first channel CH1. Next, the first and second ions concentrated in the target ion high concentration area 204 are released through the first ion transfer port 202a. The first and second ions may be simultaneously released to the ion dissociator 11 for dissociation, or they may be scanned and released. In the embodiment in which the first and second ions are scanned and released, the dissociation of the first ion is completed, fragment ions are scanned and released through the second channel CH2, and then the second ion is released to the ion dissociator 11 for dissociation through the first channel CH1.

[0069] For example, a linear electric field having a relatively small electric field strength on the left side and a relatively large electric field strength on the right side is applied to the second passage CH2, and one scanning emission process can be completed by increasing the electric field strength on the left side while keeping the electric field strength on the right side fixed.

[0070] 6 and 7, when the second cycle, i.e., concentrated ion release step S5, is performed, a new target mobility range is set to match the ion mobility of ions 3 to 5. Ions 3 to 5 originally concentrated in non-target ion high concentration area 205 are first transferred to target ion high concentration area 204 and accumulated in target ion high concentration area 204 together with ions 3 to 5 that entered ion inlet 201 during the second cycle.

[0071] In this embodiment, the target ion high concentration area 204 is the region from the ion entrance 201 of the first passage CH1 to the first ion transfer port 202a, and the non-target ion high concentration areas 205 are located at both ends of the first passage CH1 and include a first non-target ion high concentration area 205a from the ion entrance 201 to the opening at one end of the first passage CH1, and a second non-target ion high concentration area 205b from the first ion transfer port 202a to the opening at the other end of the first passage CH1. Referring to Figure 7, when the concentrated ion ejection step S5 of the second cycle is performed, in the first passage CH1, ions outside the target mobility range, i.e., ions 1, 2, 6, and 7 in Figure 7, are stored in the non-target ion high concentration area 205, of which ions 1 and 2 with high ion mobility are stored in the first non-target ion high concentration area 205a closer to the ion entrance 201, and ions 6 and 7 with low ion mobility are stored in the second non-target ion high concentration area 205b closer to the first ion transfer port 202a.

[0072] When the concentrated ion ejection step S5 of the second cycle is performed, a linear DC electric field is applied across the entire horizontal direction of the first passage CH1 (i.e., the length direction of the UMA analyzer 2) shown in each drawing. Because the electric field strength is relatively small in the first non-target ion high concentration area 205a, the electric field force experienced by the ions is also small. As a result, ions No. 1 and No. 2, which have small collision cross-sections CCS (large ion mobilities), can be stored in this region by balancing the airflow and the electric field force. Meanwhile, the electric field strength in the target ion high concentration area 204 located between the first non-target ion high concentration area 205a and the second non-target ion high concentration area 205b is moderate. Accordingly, ions No. 3, No. 4, and No. 5, which have medium mobilities, are accumulated in the target ion high concentration area 204 of the first passage CH1. Because the electric field strength in the second non-target ion-rich area 205b is relatively strong, the electric field force experienced by the ions is also strong. Ions Nos. 6 and 7, which have relatively large collision cross sections CCS (relatively small ion mobilities), can be stored in the second non-target ion-rich area 205b by balancing the airflow and the electric field force. As shown in FIG. 7 , in this embodiment, the first passage CH1 can store ions in different regions along its length. During the ion concentration process of the ion selection step S1, the DC electric field gradient can be set to be relatively small (e.g., a DC electric field that varies linearly along the entire target ion-rich area 204, as shown in FIG. 7 ). This allows ions within the target mobility range to be dispersed and distributed along the length of the target ion-rich area 204 rather than concentrated in a specific region. This method effectively reduces the space charge effect and improves resolution for low abundance ions.

[0073] 8, after the fragment ions released from the first passage CH1 after ion dissociation are completely released from the second passage CH2, the ion transfer step S2 of the second cycle is executed, and the ions in the target ion high concentration area 204 of the first passage CH1 are re-released through the first ion transfer port 202a.

[0074] In this embodiment, the UMA analyzer 2 adjusts the DC electric field distributed in the electrode array and the dipole DC electric field around the first ion transfer port 202a to quickly complete the transfer of ions between the first passage CH1 and the second passage CH2 and improve the duty ratio. Specifically, referring to Figure 8, by continuously lowering the electric field at the first ion transfer port 202a and turning on the dipole DC electric field, ions 3-5 can be quickly transferred to the corresponding positions and released through the first ion transfer port 202a.

[0075] In other embodiments, the first ion transfer port 202a may be closed at a specific timing to filter out ions with a certain ion mobility or ion mobility range, thereby efficiently concentrating the target analyte ions by filtering out some unwanted ions during the ion transfer process.

[0076] In some other embodiments, ions in the non-target ion-rich area 205 or some ions from the target ion-rich area may be removed by removing the DC electric field in the non-target ion-rich area 205 or by adding a radial DC bias. Specifically, ions in the second non-target ion-rich area 205b can be removed (the ions are carried away by the airflow) by removing the DC electric field, or ions in the first non-target ion-rich area 205a or the second non-target ion-rich area 205b can be removed by applying a radial DC bias. These methods allow for convenient removal of temporarily stored ions and are easier to achieve than conventional TIMS methods.

[0077] After the ions are selected and released by the first passage CH1, a dissociation step S6 is performed. In the dissociation step S6, the dissociation position may be any position below the first ion transfer port 202a in the UMA analyzer 2. Alternatively, the dissociation position may be selected to be a position where the target region 206 is located, and may be set to any of the following positions: an end of the second passage CH2 away from the ion exit 203, a portion between the first ion transfer port 202a and the second ion transfer port 202b of the first passage CH1 and the second passage CH2, or a portion within the second passage CH2 extending from the second ion transfer port 202b toward the ion exit 203.

[0078] In another alternative embodiment, when the target region 206 is located at the end of the second passage CH2 away from the ion outlet 203, the dissociation step S6 further includes applying a third electric field to the second passage CH2 corresponding to the target region 206 to confine ions within the target region 206. The third electric field may be, for example, an RF electric field that forms an ion trap in the target region 206 to confine ions therein, or may be a DC electric field with a relatively large gradient. In this case, ions can be dissociated by irradiating the ions trapped therein with dissociating light using an infrared multiphoton dissociation device or an ultraviolet photon dissociation device.

[0079] The dissociated fragment ions continue to be confined to the target position, and after a certain time has passed, when the ions in the target region 206 have completely dissociated, a fragment ion scanning step S7 is executed, a fourth electric field is applied to the second passage CH2, and the fragment ions are arranged at different positions in the second passage CH2 in order of ion mobility, and are sequentially released through the ion outlet 203 of the second passage CH2.

[0080] Specifically, in the fragment ion scanning step S7, the electric field in the second passage CH2 is in a scanning mode, and the fragment ions in the second passage CH2 can be scanned and ejected to the ion outlet 203 in the order of fragment ion mobility.

[0081] Because the UMA analyzer 2 has two independently controllable channels, the dissociation step S3 and fragment ion scanning step S4 can be performed in parallel with the ion concentration process in the concentrated ion release step S5. That is, while fragment ions are being analyzed and released through the second channel CH2, the target ion high-concentration area 204 of the first channel CH1 accumulates target ions within the target mobility range required for the next dissociation step S3. Furthermore, the target ion high-concentration area 204 not only accumulates target ions within the target mobility range continuously obtained through the ion inlet 201, but can also receive and store ions from the non-target ion high-concentration areas 205 at both ends that were outside the target mobility range in the previous stage but are now within the adjusted target mobility range. This flow design efficiently integrates the accumulation and release of ions in the two channels, achieving both ion utilization efficiency and scan speed.

[0082] As described above, the ion mobility analysis method according to this embodiment can separate ions into multiple groups based on their mobilities in the first channel CH1, storing ions within the target mobility range and ions outside the target mobility range in separate regions. This effectively utilizes each region along the length of the first channel CH1 for ion storage, and dissociates ions of different target mobility ranges in a stepwise manner in the dissociation step S3. The dissociated fragment ions are then introduced into the second channel CH2 for analysis, avoiding excessive ion concentration and reducing the space charge effect. Furthermore, while only ions of a specific mobility range are selected in the first channel CH1 at a time, ions of other mobilities are not lost during the selection process. Instead, they are temporarily stored in the non-target ion high concentration area 205 and subsequently enter the ion dissociator 11 for dissociation in subsequent steps. After dissociation, they enter the second channel CH2 for analysis, thereby further improving the duty cycle of the tandem ion mobility spectrometry device 1.

[0083] In the tandem ion mobility spectrometry system 1 according to this embodiment, a dissociation device can be added to the basic structure of the UMA to form a tandem ion mobility analyzer, thereby enabling ion mobility spectrum analysis of ions within the target mobility range and fragment ions generated after dissociation of the ions, thereby improving ion identification capabilities. Furthermore, by linking the first channel CH1 and the second channel CH2 in a mode in which accumulation and scanning discharge are performed synchronously, ions outside the target mobility range can be temporarily stored in the non-target ion high concentration area 205, and almost all ions can be utilized, achieving an ion utilization efficiency of nearly 100%.

[0084] 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]

[0085] 1. Tandem ion mobility spectrometry instrument 11 Ion dissociator 12 First electrode array 13 Second electrode array 14 Third electrode array 15. Fourth electrode array 2. UMA Analyzer 201 AEON Entrance 202a First ion transfer port 202b Second ion transfer port 203 Ion outlet 204 Target ion high concentration area 205 Non-target ion high concentration area 205a First non-target ion high concentration area 205b Second non-target ion high concentration area 206 Target area 3 Airflow supply section 4 Power supply CH1 First aisle CH2 2nd aisle

Claims

1. 1. A tandem ion mobility spectrometry apparatus comprising: a first passage having a first electrode array and a second electrode array facing each other, an ion inlet provided in the first electrode array, a first ion transfer port provided in the second electrode array, and the ion inlet and the first ion transfer port being offset from each other in the extending direction of the first passage; a second passage having a third electrode array and a fourth electrode array facing each other, a second ion transfer port provided in the third electrode array, an ion outlet provided in the fourth electrode array, the first ion transfer port and the second ion transfer port connected and extending in the direction of the second passage, and the ion outlet provided shifted to the side of the second ion transfer port closer to the ion inlet; 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 the ions in the first passage and the second passage in a direction opposite to the force acting on the ions by the airflow; an ion dissociator positioned to receive and dissociate ions from the first passageway and to release fragment ions produced by the dissociation into the second passageway.

2. The power supply a first electric field is applied to the first passageway during a first time period such that ions within a target mobility range accumulate in a target ion enriched area of ​​the first passageway and at least some ions outside the target mobility range enter and are concentrated in a non-target ion enriched area located at an end of the first passageway; 2. The tandem ion mobility spectrometry device of claim 1, wherein a second electric field is applied to the first passage during a second time period so that at least some of the ions concentrated in the non-target ion high concentration area during the first time period move to the first ion transfer port and pass through the first ion transfer port.

3. 3. The tandem ion mobility spectrometry device of claim 2, wherein the non-target ion high concentration areas are located at both ends of the first passage.

4. 2. The tandem ion mobility spectrometry device of claim 1, wherein the ion dissociator performs dissociation on ions within a target region, the target region being located at an end of the second passage close to the second ion transfer port and farther from the ion outlet than the second ion transfer port.

5. The power supply 5. The tandem ion mobility spectrometry apparatus of claim 4, configured to apply a third electric field to the second passageway corresponding to the target region to confine ions within the target region.

6. 2. The tandem ion mobility spectrometry apparatus according to claim 1, wherein the ion dissociation device dissociates ions within a target region located between the first ion transfer port and the second ion transfer port.

7. 2. The tandem ion mobility spectrometry apparatus according to claim 1, wherein the ion dissociator is installed in the second passage and dissociates ions within a target region that forms a portion extending from the second ion transfer port toward the ion outlet.

8. 2. The tandem ion mobility spectrometry device according to claim 1, wherein the second passage is arranged to arrange the fragment ions at different positions in the second passage in order of ion mobility and sequentially release them through the ion outlet.

9. 2. The tandem 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 transfer dissociation device, an infrared multiphoton dissociation device, an ultraviolet photon dissociation device, a radical-induced dissociation device, and a surface-induced dissociation device.

10. A method for ion mobility analysis using a tandem ion mobility spectrometry device according to any one of claims 1 to 9, an ion selection step of applying a first electric field to the first passageway during a first time period such that ions within a target mobility range accumulate in a target ion enriched area of ​​the first passageway and at least some ions outside the target mobility range enter and concentrate in a non-target ion enriched area at an end of the first passageway; a concentrated ion releasing step of applying a second electric field to the first passage during a second time period so that at least some of the ions concentrated in the non-target ion high concentration area during the first time period move to the first ion transfer opening and pass through the first ion transfer opening; a dissociation step of receiving and dissociating ions released from the first passage in the ion selection step and / or the concentrated ion release step, and releasing fragment ions generated by the dissociation into the second passage.

11. a fragment ion scanning step of applying a fourth electric field to the second passage so that the fragment ions are arranged at different positions in the second passage in order of ion mobility and sequentially emitted through the ion outlet of the second passage; 11. The ion mobility spectrometry method of claim 10, comprising:

Images