Tandem ion mobility spectrometer 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 analysis, and more particularly to a tandem 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. Since it can usually 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.

[0004] 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 identification 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.

[0005] 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 greater separation efficiency (resolution).

[0006] 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 a tandem combination of two DMAs. 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 DMAs itself, within one scanning cycle, only ions within the target ion mobility range can be selected, and all the remaining ions will be lost. Therefore, the utilization efficiency of ions in the DMAs is reduced, and the duty cycle of the entire system is also low.

[0007] 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) analyzers, and an ion gate and fragmentation means installed 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 ions within the target ion mobility range, ion mobility analysis can be performed on the generated fragment ions. The resolution of TIMS is high, and ions can be accumulated in the first TIMS, thereby improving the duty cycle of the tandem ion mobility spectrometry apparatus.

[0008] However, one of the limitations of the tandem TIMS analyzer is that in the process of the first TIMS initially selecting ions within the ion mobility interval, ions not included in the target mobility range are lost, and the duty cycle cannot be further improved. In addition, since TIMS transports ions only in the axial direction, in order to exclude (kill) ions outside the target mobility range, it is necessary to install a device such as an ion gate at the ion outlet of the first TIMS to further remove ions with non-target mobility, which complicates the system configuration.

Prior Art Documents

Patent Documents

[0009]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Patent Document 6

Patent Document 7

Summary of the Invention

Problems to be Solved by the Invention

[0010] In view of 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 above prior art.

[0011] Previously, the inventor of the present invention developed a U-shaped ion Mobility Analyzer (UMA, Patent Document 5), and its operating principle is also based on the combined action of air flow and electric field on ions. Different from TIMS, UMA has two parallel air flow channels arranged perpendicular to the main ion passage of the mass spectrometer. Based on this feature, in the ion control process designed, when concentrating ions in the UMA first channel, it is possible to effectively select the ion mobility range of the concentrated ions, and it is also possible to effectively preserve the ions inside and outside the ion mobility range. Moreover, the non-target ions thus synchronously preserved do not interfere with the analysis of the current target ions. Therefore, the target ions can occupy a wider space in the first channel and even the entire space, reducing the influence of space charge with almost no loss of sensitivity and improving the resolution. The said ion control process is also applicable to the analysis of tandem ion mobility spectra in the present application.

[0012] Specifically, the first aspect of the present invention is a tandem ion mobility spectrometry device in the present application improved based on UMA. Specifically, the tandem ion mobility spectrometry device in the present application includes the hardware structure of UMA composed of a first channel, a second channel, an air flow supply unit, and a power source. Among them, the first channel has a first electrode array and a second electrode array facing each other. An ion inlet is installed in the first electrode array, and a first ion transfer port is installed in the second electrode array. The ion inlet and the first ion transfer port are installed offset in the extending direction of the first channel. The second channel has a third electrode array and a fourth electrode array facing each other. A second ion transfer port is installed in the third electrode array, and an ion outlet is installed in the fourth electrode array. The first ion transfer port and the second ion transfer port are connected and along the extending direction of the second channel. The ion outlet is installed offset to the side closer to the ion inlet of the second ion transfer port. The airflow supply unit supplies airflow to the first passage and the second passage, and the power supply 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 on the ions in the airflow to the ions in the first passage and the second passage. In particular, the tandem ion mobility spectrometry device of the present application includes an ion dissociation device, and is arranged to receive and dissociate the ions from the first passage, and release the fragment ions generated by the dissociation into the second passage.

Advantages of the Invention

[0013] According to the tandem ion mobility spectrometry device of the present invention, the ions to be analyzed enter the first passage from the ion inlet, and due to the balanced action of the opposing electric field restraint force and the airflow propulsion force in the first passage, the ions that meet the conditions first move along the first passage to the first ion transfer port and are arranged in the first passage in the order of the magnitude of the ion mobility. Next, the ions within the target ion mobility range are deflected and released from the first ion transfer port. The ion dissociation device receives the ions released from the first ion transfer port, dissociates the ions to generate fragment ions, and the generated fragment ions enter the second passage. Due to the balanced action of the opposing electric field restraint force and the airflow propulsion force in the second passage, ion mobility analysis is performed on the fragment ions. As a result, those skilled in the art can freely select and adjust the electric field strength distribution applied to the first passage and the second passage as needed, and it becomes possible to complete the ion mobility analysis of ions and the fragment ions obtained by dissociating the ions in the two passages of one UMA device, and the resolution of the ions becomes higher.

[0014] Also, when ions within the target ion mobility range are emitted from the first passage, the remaining ions waiting for analysis outside the target ion mobility range are continuously stored in the first passage and can be emitted later for analysis, thus improving the utilization efficiency of ions. For ions that do not require analysis, by adjusting the electric field strength and the magnitude of the air flow within the first passage, ions that do not meet the conditions flow out from both ends of the first passage and are filtered out, eliminating the need to separately install an ion gate in the ion migration path and having no impact on the migration of ions within the first passage.

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

[0016] According to the tandem ion mobility spectrometry apparatus according to the present application, when ions within the 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 stored in the target ion high-concentration area of the first passage without being lost. The target ion high-concentration area may be installed at either one end of the first passage or simultaneously at both ends of the first passage.

[0017] In the second time period, by adjusting the target ion mobility range in the target ion high-concentration area, after ions originally concentrated in the non-target ion high-concentration area are selected, they continue to be transported through the first ion transfer port to the ion dissociation device and the second passage. This process is repeated until all the analysis of the ions in the first passage is completed. Therefore, in one analysis process, the ions in the non-target ion high-concentration area are not lost and are directly involved in the analysis process of the next scan, and the ion utilization efficiency in the ion selection process of the first passage can reach 100%.

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

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

[0020] According to the tandem ion mobility spectrometry device of the present application, by installing the non-target ion high-concentration area at both ends of the first passage, ions with relatively large ion mobility and ions with relatively small ion mobility can be stored in the two non-target ion high-concentration areas at both ends respectively, and the ions within the target ion mobility range can be concentrated in the target ion high-concentration area in the central part of the first passage, facilitating the deflection of the ions within the target ion mobility range and releasing them from the first ion transfer port.

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

[0022] According to the tandem ion mobility spectrometry apparatus of the present application, the ions emitted from the first passage enter the second passage through the second ion transfer port, and then can be controlled by the electric field applied to the second passage to move the ions in a direction away from the ion exit. The fragment ions dissociated by the ion dissociation device at the end where the ions leave the ion exit are scanned and emitted in the order of ion mobility, move to the ion exit, and are emitted to the subsequent device.

[0023] The tandem ion mobility spectrometry apparatus according to the present application can be used as a conventional UMA ion mobility spectrometry apparatus by installing a target region outside the ion movement path. By adjusting the electric field strength distribution, after the ions enter the target region and dissociate, ion mobility analysis can also be performed on the dissociated fragment ions.

[0024] In the technical solution applied to the present invention, the power supply applies a third electric field to the second passage corresponding to the target region and is arranged to confine the ions within the target region.

[0025] According to the tandem ion mobility spectrometry apparatus of the present application, ions within the target mobility range are confined within the target region at the end, and an ion dissociation device (for example, infrared multiphoton dissociation, ultraviolet photon dissociation) that dissociates the ions confined within the fixed region can be used to dissociate the ions within the target region. By installing the target region, the tandem ion mobility spectrum of the present application is applicable to a more diverse range of ion dissociation devices and can achieve photo-dissociation of ions without interfering with the movement paths of other ions.

[0026] In the technical solution applied to the present invention, the ions within the target region are dissociated by the ion dissociation device, and the target region is installed between the first ion transfer port and the second ion transfer port.

[0027] According to the tandem ion mobility spectrometry apparatus of the present application, by setting the target position outside the first passage and the second passage, it is no longer necessary to occupy the space inside the passage. By controlling the electric fields applied to the first ion transfer orifice and the second ion transfer orifice, the movement speed of the ions can be improved, and thereby the ions can be collided with gas molecules to realize the dynamic dissociation of the ions.

[0028] In the technical solution applied to the present invention, dissociation is performed on the ions in the target region by an ion dissociation device, and the target region is installed in the second passage and constitutes a portion extending from the second ion transfer orifice toward the ion exit.

[0029] According to the tandem ion mobility spectrometry apparatus of the present application, by arranging the ion dissociation device at a position corresponding to the second ion transfer orifice in the second passage, rapid dissociation of the ions in the ion movement path can be realized, and the fragmented ions after dissociation can be directly analyzed by ion mobility spectrometry in the second passage.

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

[0031] According to the tandem ion mobility spectrometry apparatus of the present application, by performing scan-emission on the fragmented ions in the second passage, the fragmented ions can be sequentially discharged to a lower device, for example, a mass spectrometer, in the order of the magnitude of the ion mobility, and further detection of the fragmented ions can be performed.

[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 the tandem ion mobility spectrometry apparatus in any of the above technical solutions. The ion mobility analysis method includes: In a first time period, an ion selection step of applying a first electric field to the first passage so that ions within a target mobility range are accumulated in a target ion high-concentration area of the first passage, and at least some ions outside the target mobility range enter and are concentrated in a non-target ion high-concentration area at an end of the first passage; In a second time period, a concentrated ion release step of applying a second electric field to the first passage so that at least some ions concentrated in the non-target ion high-concentration area in the first time period are moved to the first ion transfer port and pass through the first ion transfer port; A dissociation step of receiving and dissociating the ions released from the first passage in the ion selection step and / or in 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 analysis method further includes: A fragment ion analysis 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 the order of ion mobility and sequentially released through the ion outlet of the second passage.

Brief Description of the Drawings

[0035]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Embodiments for Carrying out the Invention

[0036] 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 belong to the protection scope of the present invention.

[0037] <Terms and Their Explanations> "Scan release" in the ion scanning step means sequentially releasing ions with different mobilities or mobility ranges, or sequentially releasing ions with different mass numbers or mass number ranges. The order can be in descending order or ascending order, and it is also possible to partially skip the mobility / mass number or mobility / mass number range in the middle.

[0038] This embodiment provides a tandem ion mobility spectrometry device and an ion mobility analysis method applicable to the tandem ion mobility spectrometry device.

[0039] <Tandem Ion Mobility Spectrometry Device> FIG. 1 shows the hardware structure of the UMA analyzer 2 in the tandem ion mobility spectrometry device according to this embodiment. The tandem ion mobility spectrometry device according to this embodiment, in addition to the UMA analyzer 2 in FIG. 1, further includes an ion dissociation device installed in the UMA analyzer 2 (not shown in FIG. 1). The ion dissociation device receives and dissociates the ions emitted from the first passage CH1 of the UMA analyzer 2, and emits the fragment ions generated by the dissociation to the second passage CH2.

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

[0041] The first channel CH1 has an ion inlet 201 and a first ion transfer port 202a. The ion inlet 201 is installed on the first electrode array 12 near the front stage side of the first channel CH1, and the first ion transfer port 202a is installed on the second electrode array 13 adjacent to the first channel CH1 and the second channel CH2. The second channel CH2 has an ion outlet 203 and a second ion transfer port 202b. The second ion transfer port 202b is installed on the third electrode array 14 adjacent to the second channel CH2 and the first channel CH1, and the ion outlet 203 is installed on the fourth electrode array 15 near the rear stage side of the second channel CH2. The first ion transfer port 202a and the second ion transfer port 202b are correspondingly installed so as to communicate the first channel CH1 and the second channel CH2. The ion inlet 201 and the ion outlet 203 are correspondingly installed and are both offset from the first ion transfer port 202a and the second ion transfer port 202b. Thereby, a U-shaped channel, that is, a U-shaped ion mobility analyzer, which sequentially passes through the ion inlet 201, the first ion transfer port 202a, the second ion transfer port 202b, and the ion outlet 203, is formed.

[0042] By the airflow supply unit 3, airflow is supplied to the first channel CH1 and the second channel CH2 respectively, and the supply direction of the airflow is along the horizontal direction shown in FIG. 1. The power supply 4 is electrically connected to the first electrode array 12, the second electrode array 13, the third electrode array 14, and the fourth electrode array 15 respectively, and an electric field force in the direction opposite to the acting force on the ions by the airflow can be applied to the ions in the first channel CH1 and the second channel CH2. By controlling the power supply 4 and adjusting the electric field strength in the first channel CH1 and the second channel CH2, the balance between the airflow propulsion force and the electric field restraint force in the first channel CH1 and the second channel CH2 can be controlled.

[0043] In the tandem ion mobility spectrometry apparatus of the present embodiment, the balance between the airflow propulsion force and the electric field confinement force is perpendicular to the front-rear direction from the ion inlet 201 to the ion outlet 203 along the horizontal direction in FIG. 1. Therefore, when the ions do not satisfy the condition of realizing the balance between the airflow propulsion force and the electric field confinement force, they escape from the openings at both ends in the horizontal direction and are removed or disappear, and are not transported to the subsequent stage. Between the first passage CH1 and the second passage CH2, the ions in the first passage CH1 can be transported or transferred to the second passage CH2 from the first ion transfer port 202a and the second ion transfer port 202b by one "dipole DC" electric field or a deflection DC electric field.

[0044] For the realization principle of the basic functions such as ion storage, accumulation, movement, and separation in the first passage CH1 and the second passage CH2 of the UMA analyzer 2, reference may be made to Patent Document 5, Patent Document 6, Patent Document 7, and PCT / CN2023 / 116312, and the description is omitted here.

[0045] Referring to FIG. 1, the normal movement path of ions in the UMA analyzer 2 can be such that the ions generated by the previous stage device enter the ion inlet 201 along the direction perpendicular to the electrode array. Since the ion inlet 201 and the first ion transfer port 202a are offset, the ions within the first mobility range first move to the first ion transfer port 202a along the first passage CH1 under the balance action of the airflow propulsion force and the electric field confinement force. By changing the electric field distribution applied to the first passage CH1, the ions can be arranged at different positions in the length direction of the first passage CH1 according to the magnitude of the ion mobility. Next, by applying a dipole DC electric field to the first ion transfer port 202a and the second ion transfer port 202b, some ions that meet the conditions are deflected at the first ion transfer port 202a, enter from the first ion transfer port 202a to the second ion transfer port 202b, and move along the reverse direction of the direction in the first passage CH1 to the ion outlet 203 in the second passage CH2, and can be released to the subsequent stage device along the direction perpendicular to the electrode array.

[0046] Among them, the ion source can be installed in the front stage of the first passage CH1 so that ions generated by the ion source enter from the first ion inlet 201 of the first passage CH1. Other detection devices, such as a mass spectrometer, can be installed in the rear stage of the second passage CH2.

[0047] In some alternative embodiments, the ion source comprises 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 sputter 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 relatively preferred to employ a room pressure or real-time ion source such as an electrospray ionization ("ESI") ion source, a matrix-assisted laser desorption ionization ion source ("MALDI"), a direct analysis in real time ion source ("DART"), or a laser ablation electrospray ionization ("LAESI") ion source.

[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 above UMA analyzer 2, the tandem ion mobility spectrometry device according to the present embodiment further includes an ion dissociation device (not shown in FIG. 1, and will be described below with reference to FIGS. 2-4 for example), which receives ions from the first passage CH1, dissociates them, and is arranged to emit the fragment ions generated by the dissociation to the second passage CH2.

[0050] Based on the hardware structure of the UMA analyzer 2, the ion dissociation device may be a separately added ion dissociation device, for example, a separately added collision-induced dissociation device, an electron transfer dissociation device, an infrared multiphoton dissociation device, an ultraviolet photon dissociation device, a radical-induced dissociation device, or a surface-induced dissociation device, etc. Using the hardware structure of the conventional UMA analyzer 2, by electric field control, the ions may be rapidly accelerated in some regions and collide with gas molecules, thereby dissociating the ions. In some embodiments, a target region (not shown in FIG. 1, and will be described below with reference to FIGS. 2-4 for example) is further formed in the UMA analyzer 2, and the ion dissociation device may be installed in the target region, near the target region, or at any position on the downstream side of the first ion transfer port 202a of the first passage CH1 so as to dissociate the ions in the target region.

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

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

[0053] FIG. 2 shows an embodiment in which the target region 206 is installed at an end portion close to the second ion transfer port 202b of the second passage CH2 and is farther from the ion exit 203 than the second ion transfer port 202b. After the 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 exit 203 by the electric field applied to the second passage CH2. After being dissociated by the ion dissociation device 11 at the end portion away from the ion exit 203, the dissociated fragment ions are scanned and released to the ion exit 203 in the order of ion mobility and then released to the subsequent device.

[0054] As a selective embodiment, the power supply 4 is arranged to apply a third electric field to the second passage CH2 corresponding to the target region 206 to confine ions within the target mobility range within the target region 206. Thereby, the ions within the target region 206 can be dissociated by using an ion dissociation device 11 (for example, infrared multiphoton dissociation, ultraviolet photon dissociation) that dissociates the ions confined within a fixed region. For example, a laser irradiation device is installed within the electrode array of the second passage CH2 of the target region 206, or a laser irradiation device is installed outside the electrode array, and the laser is irradiated into the passage directly or through the gap between the electrode arrays to realize photodissociation of the ions confined within the target region 206.

[0055] According to the tandem ion mobility spectrometry device in this embodiment, by installing the target region 206 outside the ion movement path, the tandem ion mobility spectrometry device can be used as a conventional UMA ion mobility spectrometry device. At the same time, by adjusting the electric field strength distribution, after the ions enter the target region 206 and dissociate, ion mobility analysis can also be performed on the fragment ions after dissociation, and ion dissociation can be realized without disturbing the movement paths of other ions. Also, since the ions are confined and stationary in the target region 206, an ion dissociation device 11 with a frequency different from the operating frequency of UMA can be applied. Thereby, the tandem ion mobility spectrometry device of this application is applicable to a more diverse range of ion dissociation devices 11.

[0056] FIG. 3 shows an embodiment in which the target region 206 is installed between the first ion transfer port 202a and the second ion transfer port 202b. By installing the target region 206 outside the first passage CH1 and the second passage CH2, it is no longer necessary to occupy the space within the passage. 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 movement speed of the ions, the ions can be made to collide with gas molecules, and dynamic dissociation of the ions can be realized.

[0057] FIG. 4 shows an embodiment in which the target region 206 is arranged 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 dissociation device 11 at a location corresponding to the second ion transfer port 202b in the second passage CH2, rapid dissociation of ions in the ion movement path can be realized, and the dissociated fragment ions can directly perform analysis of the ion mobility spectrum within the second passage CH2.

[0058] Hereinafter, based on the tandem ion mobility spectrometry device 1 in this embodiment, while referring to the drawings, the ion mobility analysis method applied to the tandem ion mobility spectrometry device 1 and the electric field arrangements in the first passage CH1 and the second passage CH2 of the power supply 4 in the tandem ion mobility spectrometry device 1 when executing the ion mobility analysis method will be described in detail.

[0059] <Ion Mobility Analysis Method> In the analysis scanning step of the conventional scanning mode used in the U-shaped ion mobility analyzer, it is necessary to scan ions over the entire mobility range in each ion mobility spectrum. This process takes time, and ions with relatively concentrated mobilities are also distributed relatively concentratedly, resulting in a relatively large space charge effect.

[0060] The ion mobility analysis method according to the embodiment of the present invention is shown in FIG. 5. The ion mobility analysis method includes an ion selection step S1 of applying a first electric field to the first passage CH1 so that ions within the target mobility range are accumulated in the target ion high-concentration area 204 of the first passage CH1 and at least some ions outside the target mobility range enter and are concentrated in the non-target ion high-concentration area 205 located at the end of the first passage CH1 in the first time period, and an ion transfer step S2 of transferring ions within the target mobility range in the target ion high-concentration area 204 to the second passage CH2, and In the ion selection step S1, receive the ions released from the first passage CH1 and dissociate them, and in the dissociation step S3, release the fragment ions generated by the dissociation into the second passage CH2. Apply a fourth electric field to the second passage CH2, arrange the fragment ions in different positions of the second passage CH2 in the order of ion mobility, and include a fragment ion scanning step S4 of sequentially releasing them through the ion outlet 203 of the second passage CH2.

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

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

[0063] In the ion selection step S1, all ions within the entire mobility range can be concentrated in the first passage CH1, and among them, the ions within the target mobility range are accumulated in the target ion high-concentration area 204 of the first passage CH1, that is, the main body part of the first passage CH1 from the ion inlet 201 to the first ion transfer port 202a.

[0064] Ions that do not belong to the target mobility range are concentrated in the non-target ion high-concentration area 205. In this embodiment, an example will be described in which 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 near the ion inlet 201 of the first passage CH1, and a second non-target ion high-concentration area 205b located at one end near the first ion transfer port 202a of the first passage CH1.

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

[0066] In the concentrated ion release step S5, after the ions within the first mobility range in the ion selection step S1 are released, by adjusting the electric field applied by the power supply 4 to the first passage CH1 to a second electric field, the ions concentrated in the non-target ion high-concentration area 205 move to the target ion high-concentration area 204 in the first passage CH1 again. Next, by arranging 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 vicinity of the first ion transfer port 202a, the second ion selection and release can be performed.

[0067] FIG. 6 is a schematic diagram of an ion selection method in a plurality of cycles in the ion mobility analysis method of the present application. FIGS. 7 and 8 are schematic diagrams of a DC electric field application method of the first passage CH1 in the concentrated ion release step S5 in the ion mobility analysis method of the present application. In FIGS. 6-8, ions with 7 different ion mobilities are taken as examples for explanation, and the straight line sections or broken line sections in the coordinate systems of FIGS. 6-8 respectively show the DC electric field strength distributions of the first passage CH1.

[0068] Referring to FIG. 6, first, the ion selection step S1 of the first cycle is executed, and by setting the target mobility range of the first channel CH1 to match the ion mobilities of ions No. 1 and No. 2, ions No. 1 and No. 2 are accumulated in the target ion high-concentration area 204, and ions No. 3-7 are accumulated in the non-target ion high-concentration area 205 of the first channel CH1. Next, ions No. 1 and No. 2 concentrated in the target ion high-concentration area 204 are released from the first ion transfer port 202a. Ions No. 1 and No. 2 may be all released into the ion dissociation device 11 at once for dissociation, or they may be scanned and released. In the embodiment where ions No. 1 and No. 2 are scanned and released, after the dissociation of ion No. 1 is completed and the fragment ions are scanned and released by the second channel CH2, ion No. 2 is released into the ion dissociation device 11 by the first channel CH1 for dissociation.

[0069] Exemplarily, in the second channel CH2, a linear electric field with a relatively small left-side electric field strength and a relatively large right-side electric field strength is applied, and by increasing the left-side electric field strength while keeping the right-side electric field strength fixed, a single scanning and release process can be completed.

[0070] Referring to FIGS. 6 and 7, when the second cycle, i.e., the concentrated ion release step S5, is executed, a new target mobility range is set and set to match the ion mobilities of ions No. 3-5. Originally, ions No. 3-5 concentrated in the non-target ion high-concentration area 205 are first transferred to the target ion high-concentration area 204 and accumulated in the target ion high-concentration area 204 together with ions No. 3-5 that entered the ion inlet 201 within the second cycle.

[0071] In addition, in the present embodiment, the target ion high-concentration area 204 is the area from the ion inlet 201 of the first passage CH1 to the first ion transfer port 202a, and the non-target ion high-concentration area 205 is located at both ends of the first passage CH1, including a first non-target ion high-concentration area 205a from the ion inlet 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 FIG. 7, when the concentrated ion release step S5 of the second cycle is executed, in the first passage CH1, ions outside the target mobility range, that is, ions No. 1, No. 2, No. 6, and No. 7 in FIG. 7, are stored in the non-target ion high-concentration area 205. Among them, ions No. 1 and No. 2 with a large ion mobility are stored in the first non-target ion high-concentration area 205a near the ion inlet 201, and ions No. 6 and No. 7 with a small ion mobility are stored in the second non-target ion high-concentration area 205b near the first ion transfer port 202a.

[0072] When executing the second cycle of concentrated ion emission step S5, 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. In the first non-target ion high-concentration area 205a, since the electric field strength is relatively small, the electric field force received by the ions is also small, and the collision cross-sectional area CCS is small (the ion mobility is large), so the first and second ions can be stored in this area by balancing the air flow and the electric field force. On the other hand, 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, the electric field strength is medium. Accordingly, in the target ion high-concentration area 204 of the first passage CH1, the third, fourth, and fifth ions with medium mobility are accumulated. Since the electric field strength in the second non-target ion high-concentration area 205b is relatively large, the electric field force received by the ions is also large, and the collision cross-sectional area CCS is relatively large (the ion mobility is relatively small), so the sixth and seventh ions can be stored in the second non-target ion high-concentration area 205b by balancing the air flow and the electric field force. As shown in FIG. 7, in this embodiment, ions can be stored in different regions along the length direction of the first passage CH1. In the ion concentration process of the ion selection step S1, the gradient of the DC electric field can be set relatively small (for example, a DC electric field that linearly changes along the entire target ion high-concentration area 204 as shown in FIG. 7). Thereby, the ions within the target mobility range are not concentrated in a specific region but are dispersed and distributed along the length direction of the target ion high-concentration area 204. In such a manner, the space charge effect can be effectively reduced, and the resolution for low-abundance ions can be improved.

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

[0074] In this embodiment, the UMA analyzer 2 can quickly complete the ion transfer between the first channel CH1 and the second channel CH2 and improve the duty ratio by adjusting the DC electric field distributed in the electrode array and the dipole DC electric field around the first ion transfer port 202a. Specifically, referring to FIG. 8, by continuously reducing the electric field at the first ion transfer port 202a and turning on the dipole DC electric field, ions numbered 3-5 can be quickly moved to this position 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 some ion mobilities or within an ion mobility range. By filtering out some unnecessary ions during the ion transfer process, the ions that are the target analytes can be efficiently concentrated.

[0076] In some other embodiments, by removing the DC electric field in the non-target ion high-concentration area 205 or adding a radial DC bias, the ions in the non-target ion high-concentration area 205 can be removed, or some ions from the target ion high-concentration area can be removed. Specifically, by removing the DC electric field, the ions in the second non-target ion high-concentration area 205b can be removed (carried away by the air flow), or by applying a radial DC bias, the ions in the first non-target ion high-concentration area 205a or the second non-target ion high-concentration area 205b can be removed. By the above methods, the removal of the temporarily stored ions can be conveniently implemented, and its realization is easier compared with the conventional TIMS method.

[0077] After the ions are selected and released through the first passage CH1, the dissociation step S6 is executed. In the dissociation step S6, the dissociation position may be any position below the first ion transfer port 202a in the UMA analyzer 2. In other alternative forms, as the dissociation position, the location where the target region 206 is located can be selected, and for example, it can be set at any of the following positions: the end away from the ion outlet 203 of the second passage CH2, or 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 the portion within the second passage CH2 and extending from the second ion transfer port 202b towards the ion outlet 203.

[0078] In other alternative embodiments, when the target region 206 is installed at the end away from the ion outlet 203 of the second passage CH2, the dissociation step S6 further includes applying a third electric field to the second passage CH2 corresponding to the target region 206 to confine the 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 the internal ions, or a DC electric field with a relatively large gradient. At this time, by using an infrared multiphoton dissociation device or an ultraviolet photon dissociation device to irradiate the confined ions with dissociation light, the dissociation of the ions can be realized.

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

[0081] Since the UMA analyzer 2 has two independently controllable channels, the dissociation step S3 and the fragment ion scanning step S4 can be executed in parallel with the ion concentration process in the concentrated ion emission step S5. That is, while the fragment ions are being analyzed and emitted by the second channel CH2, in the target ion high-concentration area 204 of the first channel CH1, the target ions within the target mobility range required for the next dissociation step S3 are being accumulated. Also, in the target ion high-concentration area 204, not only are the target ions within the target mobility range continuously obtained from the ion inlet 201 accumulated, but it is also possible to receive and accumulate 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 within the adjusted target mobility range in this stage. With the above flow design, the accumulation and emission of ions in the two channels can be efficiently integrated, achieving both high ion utilization efficiency and high scanning speed.

[0082] As described above, by the ion mobility analysis method according to this embodiment, ions are divided into multiple groups based on mobility in the first channel CH1, and the ions within the target mobility range and the ions outside the target mobility range can be stored in separate regions. Thereby, the ions can be stored by effectively using each region in the length direction of the first channel CH1, the ions in different target mobility ranges are dissociated in the dissociation step S3 step by step, the dissociated fragment ions are introduced into the second channel CH2 for analysis, excessive ion concentration is avoided, and the space charge effect is reduced. Also, only the ions within a specific mobility range are selected at one time in the first channel CH1, but the ions with other mobilities are not lost during the selection process and are temporarily stored in the non-target ion high-concentration area 205, and then continue to enter the ion dissociation device 11 for dissociation in subsequent steps and enter the second channel CH2 for analysis after dissociation, so that the duty ratio of the tandem ion mobility spectrometry device 1 can be further improved.

[0083] According to the tandem ion mobility spectrometry apparatus 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 after dissociation of the ions, improving the ion discrimination ability. Further, by coordinating the first passage CH1 and the second passage CH2 in a mode of synchronously performing accumulation and scanning emission, ions outside the target mobility range can be temporarily stored in the non-target ion high-concentration area 205, and almost all ions are utilized, so the ion utilization efficiency reaches almost 100%.

[0084] The above is only a preferred embodiment of the present invention and does not limit the present invention. Any modifications, equivalent substitutions, 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 Reference Numerals

[0085] 1 Tandem ion mobility spectrometry apparatus 11 Ion dissociation device 12 First electrode array 13 Second electrode array 14 Third electrode array 15 Fourth electrode array 2 UMA analyzer 201 Ion inlet 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 unit 4 Power supply CH1 First passage CH2 Second passage

Claims

1. A tandem ion mobility spectrometry apparatus, comprising: a first electrode array and a second electrode array facing each other, an ion inlet being provided in the first electrode array, a first ion transfer port being provided in the second electrode array, and the ion inlet and the first ion transfer port being offset in the extending direction of a first passage; the first passage; a third electrode array and a fourth electrode array facing each other, a second ion transfer port being provided in the third electrode array, an ion outlet being provided in the fourth electrode array, the first ion transfer port and the second ion transfer port being connected and along the extending direction of a second passage, and the ion outlet being offset toward the ion inlet side of the second ion transfer port; 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 acting force on the ions by the air flow to the ions in the first passage and the second passage; an ion dissociation device arranged to receive and dissociate ions from the first passage and release the fragment ions generated by the dissociation into the second passage. The tandem ion mobility spectrometry apparatus is characterized by the above.

2. The power supply is arranged such that: in a first time period, a first electric field is applied to the first passage so that ions within a target mobility range are accumulated in a target ion high-concentration area of the first passage, and at least some ions outside the target mobility range enter and are concentrated in a non-target ion high-concentration area located at an end of the first passage; in a 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 in the first time period move to and pass through the first ion transfer port. The tandem ion mobility spectrometry apparatus according to Claim 1 is characterized by the above.

3. The tandem ion mobility spectrometry apparatus according to Claim 2, wherein the non-target ion high-concentration area is located at both ends of the first passage.

4. The ion dissociation device dissociates ions within a target region, the target region being installed at an end portion of the second passage that is close to the second ion transfer port and being farther from the ion exit than the second ion transfer port. The tandem ion mobility spectrometry device according to claim 1, characterized in that.

5. The power supply is A third electric field is applied to the second passage corresponding to the target region, and is arranged to confine ions within the target region. The tandem ion mobility spectrometry device according to claim 4, characterized in that.

6. The ion dissociation device dissociates ions within a target region installed between the first ion transfer port and the second ion transfer port. The tandem ion mobility spectrometry device according to claim 1, characterized in that.

7. The ion dissociation device is installed in the second passage and dissociates ions within a target region that constitutes a portion extending from the second ion transfer port toward the ion exit. The tandem ion mobility spectrometry device according to claim 1, characterized in that.

8. The second passage arranges the fragment ions at different positions in the second passage in order of ion mobility and is arranged to sequentially discharge them through the ion exit. The tandem ion mobility spectrometry device according to claim 1, characterized in that.

9. 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. The tandem ion mobility spectrometry device according to claim 1, characterized in that.

10. Ion mobility analysis method, using the tandem ion mobility spectrometry device according to any one of claims 1-9, In the first time period, an ion selection step of applying a first electric field to the first passage so that ions within a target mobility range are accumulated in the target ion high-concentration area of the first passage, and at least some ions outside the target mobility range enter and are concentrated in the non-target ion high-concentration area at the end of the first passage. A concentrated ion release step of applying a second electric field to the first passage so as to move at least a part of the ions concentrated in the non-target ion high-concentration area in the first time zone to the first ion transfer port and pass through the first ion transfer port in the second time zone; 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, characterized in that the ion mobility analysis method includes the above steps.

11. A fragment ion scanning step of applying a fourth electric field to the second passage so as to arrange the fragment ions in order of ion mobility at different positions in the second passage and sequentially release them through the ion outlet of the second passage, characterized in that the ion mobility analysis method according to claim 10 includes the above steps.

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