Captured ion mobility separator with moving electric field barrier

Abstract

The present invention relates to a method of separating ions, and a trapped ion mobility separator. The trapping ion mobility separator has an ion guide extending in a closed loop containing a substantially stationary gas through which ions pass. According to the invention, an axial force acting on the ions is set, which axial force is caused by an electric field barrier having an electric field gradient moving around the ion guide and having an effect on the movement of the ions depending on the mobility of the ions. At least one operating parameter of the trapping ion mobility separator that affects mobility separation varies over time such that ions are controllably urged along a moving electric field barrier toward a high electric field end of the electric field barrier, where the ions eject laterally from the ion guide before sliding through the electric field barrier.

Description

Technical Field

[0001] The present invention relates to an apparatus and a method for separating ions according to the principle of ion mobility spectrometry (IMS). In particular, the present invention relates to a trapped ion mobility separator and a method for analyzing ions according to ion mobility. The apparatus and method are suitable for use in combination with mass spectrometry (MS), for example, in a hybrid IMS / MS instrument. Background Art

[0002] Ion mobility spectrometry (IMS) is an analytical technique that is used to study the mobility of ions in a gas and to separate ions according to their mobility.

[0003] An inherent feature of ion mobility spectrometry is that the mobility of ions in a gas depends on the molecular geometry of the ions, such that isomers or conformers that cannot be resolved by mass spectrometry can generally be resolved and thus separated. Many applications also utilize the ability to determine the cross-section of an analyte ion based on the measured mobility of the analyte ion. Knowledge of the mobility or cross-section has proven to be of great significance in many fields, including: identification of analytes (e.g., in proteomics and metabolomics), separation of compound classes, and determination of molecular structure (e.g., in structural biology).

[0004] In trapped ion mobility spectrometry, ions are typically trapped by a spatially non-uniform direct current (DC) electric field and a counterflow gas stream, or by a spatially uniform DC electric field and a counterflow gas stream having a spatially non-uniform axial velocity profile along the axis. The trapped ions are separated in space according to their ion mobility and are subsequently eluted over time according to their mobility by adjusting the gas velocity or the axial DC electric field strength (see, for example, U.S. Patent No. 6,630,662 B1 to Loboda and U.S. Patent No. 7,838,826 B1 to Park). The theoretical basis of trapped ion mobility spectrometry is also described, for example, in the article “Fundamentals of Trapped Ion Mobility Spectrometry” by Michelmann et al. (J. Am. Soc. Mass Spectrom., 2015, 26, 14-24).

[0005] There is a general interest in continuously improving the performance of trapped ion mobility separators, such as resolution and charge capacity. In the context of the present invention, a trapped ion mobility separator is hereinafter referred to as a “TIMS”.

[0006] Patent US 9 429 543 B2 discloses an ion mobility analyzer having an electrode system surrounding an analysis space and a power supply device for attaching an ion mobility potential field moving along a space axis to the electrode system. During the process of analyzing the mobility of ions to be measured, by always placing the ions to be measured in the moving ion mobility potential field and keeping the moving direction of the ion mobility potential field consistent with the direction of the electric field acting on the ions to be measured within the ion mobility potential field, an infinitely long migration path can theoretically be formed, thereby enabling the differentiation of ions with very small differences in mobility or ion cross-section.

[0007] The following publications do not claim to provide additional insights into the technical background of the present invention in a complete manner:

[0008] Patent application publications WO 2013093513 A1 and WO 2013093515 A1 each relate to an ion mobility separator having a radio frequency ion guide with a plurality of electrodes arranged to form an ion guide path extending in a closed loop. A DC voltage gradient is maintained along at least a portion of the longitudinal axis of the ion guide, where the voltage gradient drives the ions to undergo one or more cycles around the ion guide and thus causes the ions to be separated according to their ion mobility as they pass through the ion guide. The ion guide described in WO 2013093513 A1 has an ion exit region at a fixed position on the ion guide, while the ion guide described in WO 2013093515 A1 has an ion exit region that moves around the ion guide such that the ions leave the ion guide at different positions at different time points.

[0009] For example, in patent application publications WO 2007066114 A2, WO 2013124207 A1, and WO 2015136266 A1, other devices for separating ions according to their ion mobility and having a closed-loop ion guide path are disclosed.

[0010] In view of the above, the task of the present invention is to improve and enrich the prior art. In particular, the object of the present invention is to provide a trapped ion mobility separator with improved mobility resolution. Those of ordinary skill in the art can easily know other objects to be achieved after reading the following disclosure. Finally, there is still a need to expand and improve the analytical capabilities of hybrid mass spectrometry systems. Summary of the Invention

[0011] The present invention is based on the method for separating ions according to their ion mobility as claimed in claim 1, the trapped ion mobility separator as claimed in claim 19, and the mass spectrometry system as claimed in claim 32 to solve the above tasks. Advantageous embodiments of the present invention are the subject matter of the dependent claims and are explained in more detail below.

[0012] In a first aspect, the present invention provides a method for separating ions according to their ion mobility, comprising the steps of:

[0013] - providing an ion guide extending in a closed loop having at least one ion inlet region where ions are injected into the ion guide, the ion guide containing a gas that is substantially at rest, and the ions passing through the gas along the drift length of the ion guide, and the ion guide having a plurality of electrodes shaped and arranged to guide ions along the drift length of the ion guide, wherein at least some of the electrodes are supplied with a confinement potential at least temporarily to prevent ions from laterally escaping from the ion guide;

[0014] - generating an axial force applied to the ions along the drift length of the ion guide by applying a potential to the electrodes to form at least one electric field barrier within the ion guide, the electric field barrier having a low electric field end and a high electric field end, and moving around the closed-loop ion guide, for example, repeatedly, cyclically or periodically, wherein the moving electric field barrier has at least one first part represented by an electric field gradient, and wherein the moving electric field barrier pushes the ions along the drift length of the ion guide, whereby the ions are separated along the electric field barrier according to their ion mobility;

[0015] - while moving the electric field barrier around the closed-loop ion guide, changing at least one operating parameter that affects mobility separation over time to controllably push at least one ion species along the first part of the moving electric field barrier towards the high electric field end of the electric field barrier; and

[0016] - providing at least one ion outlet region in the ion guide and ejecting at least one ion species laterally from the ion guide in the at least one ion outlet region before the ion species slides past the moving electric field barrier.

[0017] Therefore, the trapped ion mobility separator according to the present invention is referred to as a moving barrier trapped ion mobility separator (mbTIMS).

[0018] The present invention is based on the recognition that the resolution of a trapped ion mobility separator can be improved by providing an electric field barrier that moves around a closed-loop ion guide, for example, repeatedly, cyclically, or periodically, and while moving the electric field barrier around the closed-loop ion guide, changing at least one operating parameter over time in order to controllably push at least one ion species along the first portion of the moving electric field barrier towards the high electric field end of the electric field barrier. In the context of the present invention, the expression "moving cyclically or periodically around a closed-loop ion guide" can mean a single cycle and multiple cycles, where, in the case of multiple cycles, the period durations of the respective cycles can be different. In the context of the present invention, an operating parameter should be understood as a variable physical quantity that can be modified during the operation of the device, in this case the device being a device for separating ions, in particular a trapped ion mobility separator. In particular, the operating parameter can control the rate of movement or the electric field strength of the moving electric field barrier, or can control the pressure or temperature of the gas through which the ions pass within the ion guide. Thus, changing at least one operating parameter over time while moving the electric field barrier around the closed-loop ion guide can include: changing the rate of movement and / or the electric field strength of the moving electric field barrier over time while moving the electric field barrier around the closed-loop ion guide, and / or changing the pressure and / or temperature of the gas through which the ions pass within the ion guide.

[0019] In a preferred embodiment, the step of changing at least one operating parameter that affects mobility separation can include changing at least one of the following characteristics: (i) increasing the rate of movement of the electric field barrier, (ii) decreasing the electric field strength of the moving electric field barrier, (iii) increasing the pressure of the gas through which the ions pass, and (iv) decreasing the temperature of the gas through which the ions pass. Preferably, the step of changing at least one operating parameter includes specifically changing one of the above characteristics in the manner described for each characteristic above. In another embodiment, it is conceivable to change more than one or all of the above characteristics simultaneously in the manner described for each characteristic above in order to controllably push at least one ion species along the first portion of the moving electric field barrier towards the high electric field end of the electric field barrier. In particular, when changing more than one or all of the above characteristics simultaneously in the manner described for each characteristic above, the respective characteristics can be adjusted in a coordinated manner.

[0020] In a TIMS analyzer of the prior art, where a moving gas is typically used to generate one of two axial forces applied to ions along the drift length of an ion guide, an important factor affecting the mobility resolution of the device is the gas velocity, by which ions move against a reaction DC field barrier. This moving gas is generated due to a pressure difference of the gas pumped out at one end of the TIMS analyzer. Thus, the gas velocity, which is typically in the range of 100 m / s to 200 m / s, may be limited by the pumping speed of a commercial pump, especially in the case of a laterally extended TIMS analyzer (see, e.g., US 2022 / 0299473A1, which is incorporated herein by reference in its entirety). However, the electric field barrier generated according to the present invention can move around a closed-loop ion guide at a significantly higher moving rate, and thus the ions moving along the drift length of the ion guide correspondingly have a higher speed. The mobility resolution is substantially proportional to the moving rate at which the electric field barrier moves around the ion guide. Therefore, by using a moving electric field barrier instead of a moving gas to provide the axial force, the resolution can be significantly improved.

[0021] By using a closed-loop geometry, an electric field barrier that moves around a closed-loop ion guide, for example, repeatedly, cyclically, or periodically, can drive ions through multiple loops of a cycle. To keep an ion species within the electric field barrier, or in other words, to prevent a single ion species from slipping past the electric field barrier when the electric field barrier moves at a given moving rate, a certain electric field strength is required, which increases as the moving rate of the electric field barrier increases.

[0022] By moving the electric field barrier, ions with different ion mobilities will accumulate at the respective equilibrium positions (equilibrium points) of the moving electric field barrier. In other words, ions with different ion mobilities reach dynamic equilibrium in an electric field of appropriate intensity on the moving electric field barrier. Thereby, the ions are separated according to their ion mobilities. Since the mobility of an ion is proportional to the pressure of the gas through which the ion passes and inversely proportional to the temperature of the gas, these respective equilibrium points depend on these properties of the gas. As long as the moving rate and electric field intensity of the moving electric field barrier, as well as the pressure and temperature of the gas through which the ions pass, remain constant, the ions are trapped at these respective relative positions. By changing the operating parameters that affect mobility separation, in particular by increasing the moving rate of the electric field barrier and / or decreasing the electric field intensity of the moving electric field barrier and / or increasing the pressure of the gas through which the ions pass and / or decreasing the temperature of the gas through which the ions pass while moving the electric field barrier around a closed-loop ion guide over time, the separated ion species can be controllably pushed along the moving electric field barrier and subsequently ejected. By combining the high speed at which ions pass through the ion guide with the controllably varying moving rate and / or electric field intensity of the moving electric field barrier, and / or the pressure and / or temperature of the gas through which the ions pass, it is allowed to improve the mobility resolution by means of factors.

[0023] Compared with the TIMS devices and methods of the prior art, the mbTIMS method and device according to the present invention can operate with a substantially stationary gas, while in prior art TIMS analyzers, the axial force applied to the ions is typically generated using a moving gas. Operating with a stationary gas has many advantages compared to prior art TIMS. For example, as in prior art TIMS, a parabolic flow curve is generated when the gas laminarly flows through the analyzer. Therefore, the gas flow near the lateral boundary of the analyzer, and thus the force acting on the ions, will be lower than the gas flow and the resulting force acting on the ions near the axis of the device. Since ions always have a certain degree of spatial expansion due to diffusion and space charge repulsion, some of these ions do not experience the highest gas velocity at the center, which results in a reduction in resolution. Operating with a stationary gas will result in a reduced dependence on the equilibrium position of the ions in the radial direction and thus an increase in resolution. Another advantage of using a stationary gas is that there are no axial pressure, velocity, and temperature differences within the ion guide, making it easier to generate a moving electric field (or a potential curve along the drift length of the ion guide) within the ion guide as needed. In addition, the transverse cross-section and length of TIMS necessarily determine its gas conductivity. Therefore, the lateral dimensions and length of prior art TIMS analyzers using an axial gas flow as the axial force will be limited by the pumping speed of commercial pumps. The advantage of mbTIMS operating with a stationary gas is that the lateral extension of the device does not affect or limit its resolution. Finally, the effect of operating with a stationary gas is that substantially no gas flows out of the mbTIMS. This provides the advantage that more expensive gases, such as helium, can also be used, which is beneficial for separating small ion species and reducing ion heating.

[0024] In the context of the present invention, the drift length of the ion guide corresponds to the length along the longitudinal axis of the ion guide.

[0025] The electric field barrier has a low electric field end and a high electric field end. In the context of the present invention, the low electric field end can represent the starting point of the electric field barrier, and the high electric field end can represent the end point of the electric field barrier, towards which the ions are pushed before being ejected from the ion guide. The electric field barrier moves along the ion guide such that the electric potential at a particular electrode rises from a low electric potential to a high electric potential for most of the cycle and then drops back to a low electric potential. One of the operating parameters can change over time, particularly by increasing the rate of movement of the electric field barrier and / or reducing the electric field strength of the moving electric field barrier and / or increasing the pressure of the gas through which the ions pass and / or reducing the temperature of the gas through which the ions pass, and can be stepwise, continuous, or approximately continuous. In particular, the electric field strength between the low electric field end and the high electric field end of the electric field barrier does not have to rise monotonically.

[0026] In the context of the present invention, "slipping past a moving electric field barrier" should be understood to mean that the ions do not re-enter the moving electric field barrier. Due to the closed loop, the end point of the moving electric field barrier (represented as the high electric field end) is spatially followed by the starting point of the electric field gradient of the moving electric field barrier (represented as the low electric field end). Thus, ions that have not yet been ejected from the ion guide before slipping past the moving electric field barrier will re-enter the moving electric field barrier again, which will lead to an undesired mixing of ion species.

[0027] In a preferred embodiment, the moving electric field barrier comprises a second part represented by a plateau having a substantially constant electric field. The second part is spatially adjacent to the high electric field end of the electric field gradient. By providing a plateau with a substantially constant electric field that is spatially adjacent to the high electric field end of the electric field gradient, it is possible to further improve the mobility resolution of mbTIMS. In particular, this can be achieved by the fact that as the rate of movement of the electric field barrier increases over time, and / or the electric field strength of the moving electric field barrier decreases, and / or the pressure of the gas through which the ions pass increases, and / or the temperature of the gas through which the ions pass decreases over time, the ion species reaching the second part increases its moving speed, resulting in better spatial separation of the ion species from the ion species following spatially when the ion species crosses over to the second part.

[0028] In another preferred embodiment, the moving electric field barrier is formed along substantially the entire drift length of the ion guide. In this way, the volume of the ion guide can be utilized to the greatest possible extent, which reduces the influence of space charge to achieve better mobility separation.

[0029] In another preferred embodiment, the moving electric field barrier is formed within a portion of the drift length of the ion guide. This provides the possibility that multiple electric field barriers can be formed within the ion guide, which together occupy the entire length of the ion guide.

[0030] In another preferred embodiment, one or more additional moving electric field barriers are formed within the ion guide. The moving electric field barriers are formed sequentially along the drift length of the ion guide. Preferably, each of the additional moving electric field barriers has a first portion represented by an electric field gradient and a second portion represented by a plateau having a substantially constant electric field. The second portion is spatially adjacent to the high electric field end of the electric field gradient. For the following reasons, using multiple electric field barriers can further improve the mobility resolution of mbTIMS: In order to keep an ion species on the plateau, or in other words, to prevent a particular single ion species from slipping past the electric field barrier when the electric field barrier moves at a given speed, a certain electric field strength is required, which increases with the increase in the moving rate of the electric field barrier. The electric field strength is caused by the electric potential applied to the electrodes, but also depends on the distance between the electrodes. With the applied electric potential remaining unchanged, if the distance between the electrodes becomes smaller, the resulting electric field strength becomes higher. Since there is a risk of dangerous discharge in the surrounding area, the value of the voltage that can be applied is limited. However, setting more than one electric field barrier within the drift length of the ion guide beneficially results in the fact that, because the individual spatial extension within the multiple electric field barriers in the ion guide is smaller, a lower voltage is required for each individual electric field barrier to obtain the same field strength as a single electric field barrier formed over the entire drift length of the ion guide. Due to the possible higher electric field strength, the multiple electric field barriers can be moved at a higher speed, which can further improve the mobility resolution because the mobility resolution is substantially proportional to the moving rate at which the electric field barrier moves around the ion guide. Therefore, using multiple electric field barriers for each individual loop enables high field strength to be achieved at a medium voltage, higher speed to be achieved at a medium voltage, and thus higher resolution to be achieved at a medium voltage. Another advantage is that by using two moving electric field barriers, tandem IMS can be provided in a single device.

[0031] In another preferred embodiment, one or more additional ion exit regions are provided in the ion guide at least temporarily. Preferably, the number of ion exit regions corresponds to the number of the moving electric field barriers, and one of the ion exit regions is assigned to each of the moving electric field barriers. By providing an ion exit region for each of the moving electric field barriers, ions that have reached the end point of the corresponding electric field barrier are allowed to be ejected before slipping past the corresponding moving electric field barrier.

[0032] In another preferred embodiment, to induce the axial force, a transient direct current (DC) electric potential is applied to the electrodes to generate a transient axial direct current field (DC field). By applying a DC electric potential to the electrodes to form an electric field barrier, ions can be separated along the electric field barrier according to their ion mobilities.

[0033] In another preferred embodiment, the transient direct current (DC) potential applied to the electrodes is provided by a plurality of DC voltage generators, each DC voltage generator generating a time-dependent voltage, wherein each of the electrodes is connected to a separate one of the DC voltage generators. In this way, different potentials can be supplied to the individual electrodes to form an electric field barrier. The time-dependent time potential curve applied to the electrodes along the drift length of the ion guide can be equal for each electrode, wherein the time potential curve is applied to subsequent central electrodes along the drift length of the ion guide with a gradual time offset (gradual time delay), thus causing the movement of the electric field barrier along the drift length of the ion guide. For an embodiment having one barrier for each loop, the time delay between adjacent electrodes is equal to the time period (the time period is the length of the closed loop divided by the velocity of the moving field barrier) divided by the number of electrodes. However, those skilled in the art will understand that in the context of the present invention, the above-mentioned plurality of (DC voltage) generators can also be understood as a common electrical component having different electrical units.

[0034] It is also conceivable that, in order to induce the axial force, an alternating current (AC) potential is applied to the electrodes to generate an axial alternating current field (AC field), wherein the average value of the applied AC voltage varies in space and time to form a transient effective potential. By applying an AC potential to the electrodes to form an electric field barrier, ions can be separated along the electric field barrier according to the combination of ion mobility and mass.

[0035] In another preferred embodiment, ions are injected into the ion guide at an ion inlet region that extends along substantially the entire length of the ion guide with the electrodes. Alternatively, ions are injected into the ion guide at an ion inlet region at a fixed specific electrode provided in one or more parts of the ion guide.

[0036] In another preferred embodiment, ions are ejected from the ion guide at an ion exit region which is arranged adjacent to the high electric field end of the moving electric field barrier and moves with the moving electric field barrier, such that the ions are continuously ejected in a timely manner when reaching the high electric field end of the moving electric field barrier. In the case where the electric field barrier only has a first part represented by an electric field gradient, the high electric field end of the moving electric field barrier corresponds to the high electric field end of the electric field gradient. In the case where the electric field barrier has a first part represented by an electric field gradient and a second part represented by a plateau with a substantially constant electric field, the high electric field end of the moving electric field barrier corresponds to the end of the plateau of the moving electric field barrier. By arranging the ion exit region which moves with the moving electric field barrier, it is allowed to more precisely determine the time when ions are ejected from the ion guide. Alternatively, ions are ejected from the ion guide at an ion exit region which is at least temporarily arranged at one or more fixed specific electrodes in the ion guide, such that the ions are ejected at the specific electrode. In particular, when the high electric field end of the moving electric field barrier passes by the fixed specific electrode, the ions can be ejected from the ion guide at the fixed specific electrode. Thus, the ion exit region can be arranged in a time-limited manner. In particular, this means that the ion exit region can be arranged at the ejection electrode only when the end point of the electric field barrier passes by the ejection electrode. In this way, uncontrolled ejection can be prevented, because ions that have not reached the high electric field end of the electric field barrier will also be ejected when passing through a non-time-limited ion exit region. The high electric field end of the moving electric field barrier can be defined as described above. In the case of multiple ion exit regions, each ion exit region is assigned one of multiple electric field barriers, and the above alternative is also a possible embodiment.

[0037] In another preferred embodiment, a barrier is arranged adjacent to the high electric field end of the moving electric field barrier to prevent ions from slipping past the moving electric field barrier before ejection. In particular, if the ion exit region is temporarily arranged at a fixed specific electrode, it is reasonable to arrange a barrier adjacent to the high electric field end of the moving electric field barrier. In this way, the ions can be beneficially held at the high electric field end of the electric field barrier until these ions reach the ion exit region.

[0038] In another preferred embodiment, ions pass through one side of the ion guide and are injected into the ion guide or ejected from the ion guide along a radial direction.

[0039] In another preferred embodiment, ions pass through the top or bottom of the ion guide and are injected into the ion guide or ejected from the ion guide along an axial direction.

[0040] In another preferred embodiment, an ion channel is provided, wherein the ion channel guides ions to be injected into the ion guide towards the ion guide or propels forward ions ejected from the ion guide. In particular, the ions to be injected are guided by the ion channel into the ion guide, or the ions ejected from the ion guide are propelled forward by the ion channel.

[0041] To prevent ions from laterally escaping from the ion guide, at least some of the electrodes are at least temporarily supplied with a confinement voltage. In this way, ion losses due to lateral diffusion are reduced and ion transfer efficiency is increased. The confinement voltage can be provided by the above-mentioned generator or by one or more separate generators. However, those skilled in the art will understand that in the context of the present invention, such multiple generators can also be understood as a common electrical component having different electrical units. The confinement field generated in this way can be superimposed on the moving electric field barrier. Ions can be confined by a direct current potential (DC confinement), a radio frequency pseudopotential (RF confinement), or a combination of both; depending on the pressure conditions within the ion guide, atmospheric pressure ion confinement (APIC) can be used instead of RF confinement (see US2022 / 0057363 A1, which is incorporated herein by reference in its entirety). In a preferred embodiment, in the lateral direction where the size of the ion guide is limited by the central electrode, ions can be confined by a radio frequency pseudopotential. In another preferred embodiment, in the lateral direction where the size of the ion guide is limited by the side electrodes, ions can be confined by a direct current potential. In particular, in this preferred embodiment, a direct current (DC) potential is applied to the electrodes of the ion guide before the ions are ejected, such that a lateral electric field is generated, which keeps the ions within the ion guide, and during the ejection of the ions, the direct current (DC) potential applied to the electrodes is adjusted in the part of the ion guide where the ion exit region is provided, so as to laterally eject the ions.

[0042] In another preferred embodiment, the electric field barrier moves at a speed of less than 1000 m / s, preferably less than 750 m / s, and most preferably less than 500 m / s. The speed (or rate of movement) at which the electric field barrier moves around the ion guide is substantially proportional to the resolution of the ion mobility. This means that increasing the rate of movement advantageously results in an improvement in the mobility resolution. However, increasing the rate of movement leads to an increase in the effective ion temperature. Therefore, there is a trade-off between resolution and ion heating.

[0043] In another preferred embodiment, one of the following gases is used as the gas through which the ions pass: nitrogen (N), helium (He), neon (Ne), argon (Ar), sulfur hexafluoride (SF6), hydrogen (H), or air. For example, helium, which has a small molecular weight, is thus beneficial for separating ion species of lower mass (especially below 200 Da) according to mobility. In addition, helium is beneficial for reducing ion heating. Alternatively, a mixture of these gases may be used. It is conceivable that, in addition to the above gases, other gases, or any mixture of other gases, or a mixture of the above gases and any other gases are used. Optionally, a modifier may be introduced into the gas. The modifier may include acetonitrile, methanol, small molecule hydrocarbons, or any other vapor.

[0044] The method may be carried out in a trapped ion mobility separator, in particular in a moving barrier trapped ion mobility separator (mbTIMS). Preferably, the method may be carried out in a mass spectrometry system.

[0045] In a second aspect, the present invention provides a trapped ion mobility separator having:

[0046] - an ion guide extending in a closed loop, having at least one ion inlet region where ions are injected into the ion guide and at least one ion outlet region where ions are ejected from the ion guide, the ion guide containing a gas that is substantially stationary, and the ions passing through the gas along the drift length of the ion guide, and the ion guide including a plurality of electrodes shaped and arranged to guide ions along the drift length of the ion guide, wherein at least some of the electrodes are at least temporarily supplied with a confinement potential to prevent ions from laterally escaping from the ion guide,

[0047] - at least one generator that forms at least one electric field barrier in the ion guide by applying a potential to the electrodes, thereby causing an axial force applied to the ions along the drift length of the ion guide, the electric field barrier having a low electric field end and a high electric field end, and moving around the closed-loop ion guide, for example, repeatedly, cyclically, or periodically, wherein the moving electric field barrier has at least one first part represented by an electric field gradient, and wherein the moving electric field barrier pushes the ions to move along the drift length of the ion guide, whereby the ions are separated along the electric field barrier according to their ion mobility,

[0048] - An electrical controller that communicates with the generator to change, over time, at least one operating parameter of the trapped ion mobility separator that affects mobility separation while the electric field barrier moves around the closed-loop ion guide, so as to controllably push at least one ion species along the first part of the moving electric field barrier towards the high potential end, wherein the at least one ion species is laterally ejected from the ion guide in the ion exit region before slipping past the electric field barrier.

[0049] The above-described trapped ion mobility separator according to the present invention is referred to as a moving barrier trapped ion mobility separator (mbTIMS). A moving barrier trapped ion mobility separator can be part of a mass spectrometry system. In particular, the above method for separating ions can be performed in a moving barrier ion mobility separator.

[0050] In a preferred embodiment, changing at least one operating parameter that affects mobility separation includes at least one of the following characteristics: (i) increasing the moving rate of the electric field barrier, (ii) decreasing the electric field strength of the moving electric field barrier, (iii) increasing the pressure of the gas through which the ions pass, and (iv) decreasing the temperature of the gas through which the ions pass. Preferably, changing at least one operating parameter includes specifically changing one of the above characteristics in the manner described for each characteristic. In another embodiment, it is conceivable to change more than one or all of the above characteristics simultaneously in the manner described for each characteristic, so as to controllably push at least one ion species along the first part of the moving electric field barrier towards the high electric field end of the electric field barrier. In particular, when changing more than one or all of the above characteristics simultaneously in the manner described for each characteristic, the corresponding characteristics can be adjusted in a coordinated manner.

[0051] In a preferred embodiment, the generator is arranged to apply an electric potential to the electrodes such that a platform with a substantially constant electric field is formed near the high electric field end of the electric field gradient, i.e., the second part of the moving electric field barrier. By forming a platform with a substantially constant electric field spatially adjacent to the high electric field end of the electric field gradient, it is allowed to further improve the mobility resolution. In particular, this is achieved by the fact that while the moving rate of the electric field barrier increases over time, and / or the electric field strength of the moving electric field barrier decreases, and / or the pressure of the gas through which the ions pass increases, and / or the temperature of the gas through which the ions pass decreases over time, the ion species reaching the second part increase their moving rate, which results in the ion species crossing over to the second part being better spatially separated.

[0052] In another preferred embodiment, the generator is arranged to apply an electric potential to the electrodes such that one or more additional electric field barriers are formed within the ion guide. Preferably, the additional electric field barriers are structurally corresponding to the first electric field barrier and are arranged in sequence along the drift length of the ion guide. In particular, a plurality of formed electric field barriers may together extend over the entire drift length of the ion guide. Using a plurality of electric field barriers can further improve the mobility resolution, as in the embodiment of forming one or more additional moving electric field barriers within the ion guide as described in the context of the method according to the invention. In particular, using two moving electric field barriers allows for providing tandem IMS in a single device.

[0053] In another preferred embodiment, the trapped ion mobility separator has a plurality of generators, each of which is a DC voltage generator. The number of DC voltage generators corresponds to the number of electrodes forming the closed-loop ion guide. Each of the electrodes is assigned one of the DC voltage generators. In particular, each pair of electrodes may be assigned one of the DC voltage generators. In this way, different voltages can be supplied to the individual electrodes to form an electric field barrier. An electric field barrier is formed by applying a DC electric potential to the electrodes such that ions can be separated along the electric field barrier according to their ion mobility. The time-dependent electric potential curve applied to the electrodes along the drift length of the ion guide may be equal for each electrode, where the time-dependent electric potential curve is applied to subsequent central electrodes along the drift length of the ion guide with a gradual time offset (gradual time delay), thereby causing the electric field barrier to move along the drift length of the ion guide. For an embodiment having one barrier per loop, the time delay between adjacent electrodes is equal to the time period (the time period is the length of the closed loop divided by the velocity of the moving field barrier) divided by the number of electrodes. However, those skilled in the art will understand that in the context of the present invention, the above-mentioned plurality of generators may also be understood as a common electrical component having different electrical units.

[0054] It is also conceivable that the generator is an AC voltage generator that applies a voltage to the electrodes to generate an axial alternating current (AC) field, thereby forming the electric field barrier, wherein the average value of the applied alternating (AC) voltage varies in space and time to form a transient effective electric potential. An electric field barrier is formed by applying an AC electric potential to the electrodes such that ions can be separated along the electric field barrier according to a combination of their ion mobility and mass.

[0055] In another preferred embodiment, the electrodes are arranged such that the ion guide has a substantially circular shape or an oval shape. Alternatively, the electrodes are arranged such that the ion guide has a figure-of-eight shape. Preferably, in the case of the figure-of-eight shape, the trajectories along which the ions move along the ion guide do not cross, but extend at least partially in different planes. Any other closed-loop geometry is conceivable, such as a stadium shape.

[0056] An ion guide having a plurality of electrodes may have from 50 to 200 electrodes, preferably from 80 to 120 electrodes, more preferably about 100 electrodes. In a preferred embodiment, the plurality of electrodes have apertured electrodes. The apertures may be slot-shaped apertures through which ions can be guided. Alternatively or concurrently, the plurality of electrodes have electrode modules, each electrode module consisting of electrode units. The apertured electrodes and / or the electrode units are preferably shaped and / or arranged such that the ion guide has a substantially convex cross-section. The ion guide may have a substantially circular cross-section. In this embodiment, the apertured electrodes and / or the electrode units may be shaped to be curved. Alternatively, preferably the ion guide has a rectangular cross-section. In this embodiment, the apertured electrodes and / or the electrode units may be shaped to be straight respectively. The apertured electrodes and / or the electrode units may be discrete electrode sheets. Alternatively, the electrode units may be embedded in the surface of a printed circuit board (PCB). The electrode units may have a plurality of central electrode pairs and / or side electrode pairs. In particular, the side electrode pairs may have a plurality of inner electrode pairs and outer electrode pairs. The central electrodes may be segmented in the radial direction, wherein different electric potentials are supplied to the radial segments such that the axial field strength of the outer segment is higher than that of the inner segment so as to have an independent angular velocity along the radial direction.

[0057] In another preferred embodiment, the trapped ion mobility separator further has an ion channel. The ion channel has an electrode array. The electrodes are arranged to direct ions to be injected into the ion guide towards the ion guide. Alternatively or additionally, the electrodes are arranged to propel ions ejected from the ion guide forward. The trapped ion mobility separator may have more than one ion channel, each ion channel having an electrode array. In particular, the first ion channel may have an electrode array for directing ions to be injected into the ion guide towards the ion guide, and the second ion channel may have an electrode array for propelling ions ejected from the ion guide forward. The electrode array may be shaped and arranged as described in the following three paragraphs.

[0058] In a first preferred embodiment, the rotational axis of the ion channel is substantially coaxial with the rotational axis of the ion guide. The ion channel may extend through the center of the ion guide, where the ion channel may be elongated in the z-dimension on the top side, the bottom side, or both the top side and the bottom side of the ion guide, excluding the region where the ion guide is located. One end of the ion channel that is elongated in the z-dimension on the top side of the ion guide may be coupled to the inner edge of the top side of the ion guide. One end of the ion channel that is elongated in the z-dimension on the bottom side of the ion guide may be coupled to the inner edge of the bottom side of the ion guide. It is also conceivable that the ion channel has an inner boundary, which is represented as an inner radius coupled to the inner edge of the ion guide, and an outer boundary, which is represented as an outer radius coupled to the outer edge of the ion guide, with a gap provided between the outer radius and the inner radius. This gap may be an annulus, i.e., the spacing (annular space) between the outer radius and the inner radius through which ions can pass. This shaping can increase the charge capacity. The electrode array may have stacked annular electrodes arranged at uniform intervals from each other. All the electrodes may have the same diameter, or may have diameters that decrease along the extension direction of the ion guide. Thus, the ion channel may be shaped to have a circular cross-section or shaped as an ion funnel.

[0059] In a second preferred embodiment, the longitudinal axis of the ion channel is substantially perpendicular to the rotational axis of the ion guide. One end of the ion channel may be coupled to a portion of the outer edge of the ion guide. The electrode array may have segmented electrodes arranged at uniform intervals from each other. These electrodes may be shaped and arranged such that the ion channel has a substantially rectangular cross-section.

[0060] In particular, in a conceivable embodiment, the trapped ion mobility separator has first and second ion channels, where the rotational axis of the first ion channel is substantially coaxial with the rotational axis of the ion guide, and the longitudinal axis of the second ion channel is substantially perpendicular to the rotational axis of the ion guide.

[0061] In another preferred embodiment, the trapped ion mobility separator further has an ion trap for storing ions. The ion trap is located within the ion channel upstream of the ion guide. The ion trap advantageously allows the mbTIMS to operate in a parallel accumulation mode. This means that ions can be accumulated in the ion trap in a favorable manner while being separated in the downstream ion guide. In particular, the ion trap allows a parallel accumulation mode with a duty cycle close to one hundred percent. Preferably, the ion trap may have substantially the same dimensions as the ion channel.

[0062] In another preferred embodiment, the trapped ion mobility separator further has at least one second ion guide. Preferably, the trapped ion mobility separator further has a plurality of additional ion guides. Each of the additional ion guides may have the same structure as the aforementioned ion guide. Each of the additional ion guides may operate in the same mode as the aforementioned ion guide. These ion guides may be arranged sequentially. In addition, the ion guides may have a common ion channel that links the individual ion guides to each other. By combining a plurality of ion guides, a significantly higher storage capacity can be achieved, which increases the number of ions that can be analyzed. Preferably, the electrical controller causes one ion species to be ejected laterally from these additional ion guides synchronously.

[0063] In another preferred embodiment, the trapped ion mobility separator is coupled to a vacuum system that is designed and configured to operate the trapped ion mobility separator at a gas pressure in the range of 0.1 mbar to 20 mbar. Preferably, the vacuum system is designed and configured to operate the trapped ion mobility separator at a gas pressure in the range of 2 mbar to 10 mbar. For this purpose, the vacuum system may have a pump. A pressure range of 0.1 mbar to 50 mbar allows the ions to be laterally confined by using a radio frequency electric field. It is also conceivable that the vacuum system is designed and configured to operate the trapped ion mobility separator at a gas pressure in a range greater than 50 mbar. However, in a pressure range greater than 50 mbar, only the lateral confinement of ions is allowed by using atmospheric pressure ion confinement (APIC).

[0064] The trapped ion mobility separator according to the present invention can be operated as a separate device (or stand-alone device) for measuring ion mobility. Alternatively, it is conceivable that the mbTIMS is coupled to other devices, such as a mass spectrometer (mass analyzer). When the mbTIMS is coupled to a mass spectrometer, the mobility and mass of the ions can be determined from the measured data.

[0065] The preferred embodiments of the method for separating ions described above are also the preferred embodiments of the trapped ion mobility separator according to the present invention. The preferred embodiments of the trapped ion mobility separator are also the preferred embodiments of the method for separating ions described above.

[0066] In a third aspect, the present invention provides a mass spectrometry system. The mass spectrometry system has an ion source and a mass analyzer with an ion detector. In addition, the mass spectrometry system has at least one first trapped ion mobility separator located downstream of the ion source. Simultaneously, or in an alternative embodiment, the first trapped ion mobility separator is located upstream of the mass analyzer. The first trapped ion mobility separator has:

[0067] - An ion guide extending in a closed loop, having at least one ion inlet region where ions are injected into the ion guide, and at least one ion outlet region where ions are ejected from the ion guide. The ion guide contains a gas that is substantially stationary, and ions traverse the gas along the drift length of the ion guide. The ion guide has a plurality of electrodes shaped and arranged to guide the ions along the drift length of the ion guide, where at least some of the electrodes are supplied with a confinement potential at least temporarily to prevent the ions from laterally escaping from the ion guide.

[0068] - At least one generator that forms at least one electric field barrier within the ion guide by applying a potential to the electrodes, thereby causing an axial force applied to the ions along the drift length of the ion guide. The electric field barrier has a low - electric - field end and a high - electric - field end and moves around the closed - loop ion guide, for example, repetitively, cyclically, or periodically. The moving electric field barrier has at least a first part represented by an electric - field gradient, and the moving electric field barrier pushes the ions along the drift length of the ion guide, whereby the ions are separated according to their ion mobilities along the electric field barrier.

[0069] - An electrical controller that communicates with the generator to change, over time, at least one operating parameter of the mobility separator that affects mobility separation while the electric field barrier moves around the closed - loop ion guide, so as to controllably push at least one ion species along the first part of the moving electric field barrier towards the high - potential end, where the at least one ion species is ejected laterally from the ion guide in the ion outlet region before sliding past the electric field barrier.

[0070] Thus, the above - mentioned mobility separator can be part of a hybrid mass spectrometry system that additionally has at least one ion source located upstream of the mobility separator and a mass analyzer with an ion detector located downstream of the mobility separator. The above - mentioned mobility separator according to the present invention is called a moving - barrier trapped ion mobility separator (mbTIMS).

[0071] The ion source of the mass spectrometry system is configured to generate ions. For example, the ion source of the mass spectrometry system can generate ions using spray ionization (such as electrospray ionization (ESI) or thermal spraying). Alternatively, the ion source of the mass spectrometry system can generate ions using desorption ionization (such as matrix-assisted laser / desorption ionization (MALDI) or secondary ion mass spectrometry (SIMS)). In another alternative, the ion source of the mass spectrometry system can generate ions using chemical ionization (CI). In another alternative, the ion source of the mass spectrometry system can generate ions using photoionization (PI). In another alternative, the ion source of the mass spectrometry system can generate ions using electron impact ionization (EI). In another alternative, the ion source of the mass spectrometry system can generate ions using gas discharge ionization.

[0072] The mass analyzer of the mass spectrometry system is configured to analyze ions based on the mass of the ions, or more precisely based on the mass-to-charge ratio. For example, the mass analyzer can be a time-of-flight analyzer. Preferably, the mass analyzer can be a time-of-flight analyzer with orthogonal injection of ions. Alternatively, the mass analyzer can be a Kingdon-type electrostatic ion trap, such as from Thermo Fisher Scientific In another alternative, the mass analyzer can be a radiofrequency ion trap. In another alternative, the mass analyzer can be an ion cyclotron resonance (ICR) ion trap or a quadrupole mass filter.

[0073] In a preferred embodiment, changing at least one operating parameter includes at least one of the following characteristics: (i) increasing the movement rate of the electric field barrier, (ii) decreasing the electric field strength of the moving electric field barrier, (iii) increasing the pressure of the gas through which the ions pass, and (iv) decreasing the temperature of the gas through which the ions pass. Preferably, changing at least one operating parameter includes specifically changing one of the above characteristics in the manner described for each characteristic above. In another embodiment, it is conceivable to change more than one or all of the above characteristics simultaneously in the manner described for each characteristic above in order to controllably push at least one ion species along the first part of the moving electric field barrier towards the high electric field end of the electric field barrier. In particular, when changing more than one or all of the above characteristics simultaneously in the manner described for each characteristic above, the corresponding characteristics can be adjusted in a coordinated manner.

[0074] In a preferred embodiment, the mass spectrometry system further has a second ion mobility separator, preferably a trapped ion mobility separator. Preferably, the second ion mobility separator is located downstream of the first trapped ion mobility separator. The second ion mobility separator may be another ion mobility separator according to the present invention. Alternatively, the second ion mobility separator may be a trapped ion mobility separator that is configured and operable to disperse ions according to ion mobility, preferably at low field limits. Alternatively, the second ion mobility separator may be a differential trapped ion mobility separator (dTIMS) that separates ions according to the differential mobility of the ions (see U.S. Provisional Application No. 63 / 510,706, which is incorporated herein by reference in its entirety). The first trapped ion mobility separator and the second ion mobility separator may be nested and coupled, i.e., the first trapped ion mobility separator operates on a much larger time scale than the second ion mobility separator, such that the second ion mobility separator can analyze individual ion species separated by the first trapped ion mobility separator, or each fragment provided by the first trapped ion mobility separator.

[0075] It is contemplated that in another preferred embodiment, the mass spectrometry system may further have a first housing assigned to the first trapped ion mobility separator. In particular, the first housing may enclose the first trapped ion mobility separator. Alternatively, the mass spectrometry system may have a second housing assigned to the second ion mobility separator. In particular, the second housing may enclose the second ion mobility separator. The first housing and the second housing may each be a vacuum chamber. The first housing and the second housing may each maintain the gas environment within the trapped ion mobility separator. The gas assigned to the first ion mobility separator may be different from the gas assigned to the second ion mobility separator. Using different gases within the first and second trapped ion mobility separators enables, in an advantageous manner, ions that may not have been fully separated within the first ion mobility separator to be separated within the second ion mobility separator, since the type of gas affects the drift velocity of the ions.

[0076] In a preferred embodiment, the mass spectrometry system further has a fragmentation cell. The fragmentation cell is configured to dissociate ions into ion fragments. Preferably, the fragmentation cell is located between the first trapped ion mobility separator and the mass analyzer. It is also conceivable that the fragmentation cell is located between the first trapped ion mobility separator and the second trapped ion mobility separator. For example, ions can be dissociated in the fragmentation cell by collision-induced dissociation (CID). Alternatively, ions can be dissociated in the fragmentation cell by surface-induced dissociation (SID). In another alternative, ions can be dissociated in the fragmentation cell by photodissociation (PD). In another alternative, ions can be dissociated in the fragmentation cell by electron-induced dissociation, such as electron capture dissociation (ECD), electron transfer dissociation (ETD), post-collision activation of electron transfer dissociation (ETcD), or simultaneous activation of electron transfer dissociation (AI-ETD). In another alternative, ions can be dissociated in the fragmentation cell by reaction with highly excited or radical-neutral particles.

[0077] In another preferred embodiment, the mass spectrometry system further has a mass filter, such as a radio frequency rod quadrupole mass filter. Preferably, the mass filter is located between the first trapped ion mobility separator and the fragmentation cell.

[0078] In another preferred embodiment, the mass spectrometry system further has at least one ion trap. The ion trap is configured to store ions. Preferably, the first ion trap is located upstream of the first trapped ion mobility separator. Additionally, or alternatively, a second ion trap may be located between the first trapped ion mobility separator and the second ion mobility separator.

[0079] Furthermore, the mass spectrometry system may have a separation device. The separation device may be a gas chromatography device. Alternatively, the separation device may be a liquid chromatography device. It is also conceivable that the mass spectrometry system further has an electrophoresis device. Alternatively, the electrophoresis device can be coupled to a hybrid mass spectrometry system.

[0080] The above-described method for separating ions and the preferred embodiments of the above-described trapped ion mobility separator are also preferred embodiments of the mass spectrometry system. The preferred embodiments of the mass spectrometry system involving the trapped ion mobility separator are also the preferred embodiments of the above-described trapped ion mobility separator. BRIEF DESCRIPTION OF THE DRAWINGS

[0081] The present invention can be better understood by referring to the following drawings. The elements in the drawings are not necessarily drawn to scale, but rather the emphasis is placed on (usually schematically) illustrating the principle of the present invention.

[0082] Principle:

[0083] Figure 1aShows a schematic three-dimensional view of a first embodiment of a trapped ion mobility separator according to the present invention,

[0084] Figure 1b Shows a schematic cross-sectional view of a first embodiment of a trapped ion mobility separator,

[0085] Figure 2 Shows the spatial curve of the electric potential applied to the central electrode along the drift length of the ion guide,

[0086] Figure 3 Shows the spatial curve of the electric potential applied to the side electrode along the drift length of the ion guide,

[0087] Figure 4 Shows the time curve of the electric potential applied to a single pair of central electrodes changing with time,

[0088] Figure 5 Shows the spatial curve of the electric potential applied to the central electrode along the drift length of the ion guide in the second alternative mode of operating the trapped ion mobility separator according to FIG. 1,

[0089] FIG. 6 shows a third alternative mode of operating the trapped ion mobility separator according to FIG. 1, wherein, Figure 6a Shows a trapped ion mobility separator,

[0090] Figure 6b Represents the time curve of the electric potential applied to the drive / collection electrode changing with time within a single moving cycle of the electric field barrier,

[0091] Figure 6c Represents the time curve of the electric potential applied to the ejection electrode changing with time within a single moving cycle of the electric field barrier,

[0092] Figure 7 Shows a schematic three-dimensional view of a second embodiment of a trapped ion mobility separator according to the present invention,

[0093] Figure 8 Shows a schematic three-dimensional view of a third embodiment of a trapped ion mobility separator according to the present invention,

[0094] Figure 9 Shows a schematic three-dimensional view of a fourth embodiment of a trapped ion mobility separator according to the present invention,

[0095] Figure 10 Shows a schematic three-dimensional view of a fifth embodiment of a trapped ion mobility separator according to the present invention,

[0096] Figure 11Shows a schematic three-dimensional view of a sixth embodiment of a trapped ion mobility separator according to the present invention,

[0097] Figure 12 Shows a schematic diagram of a mass spectrometry system according to the present invention. Detailed Description

[0098] Although the present invention has been shown and described with reference to several different embodiments, those skilled in the art will recognize that various changes in form and detail may be made herein without departing from the scope of the present invention as defined by the appended claims.

[0099] Figure 1a Shows a schematic three-dimensional view of a first embodiment of a trapped ion mobility separator 10 according to the present invention, and Figure 1b Shows a schematic cross-sectional view of a first embodiment of the trapped ion mobility separator 10 in the z-direction. Thus, the trapped ion mobility separator 10 is a moving barrier type trapped ion mobility separator (mbTIMS). The trapped ion mobility separator 10 is used to trap and separate ions according to the mobility of the ions. In particular, the trapped ion mobility separator 10 can be part of a mass spectrometry system. For better illustration, a coordinate system is included in FIG. 1, and in particular, the central angle φ is shown.

[0100] The trapped ion mobility separator 10 has an ion guide 12. The ion guide 12 contains a gas that is substantially stationary, and the ions pass through the gas along the drift length 14 of the ion guide 12 in the direction of the dashed arrow ( Figure 1b ). In this embodiment, the gas contained in the ion guide 12 is helium.

[0101] The ion guide 12 has a plurality of electrodes that are configured and arranged to guide ions along the drift length 14 of the ion guide 12. In this embodiment, the ion guide 12 has one hundred electrodes, where each electrode is respectively composed of electrode units, namely a first electrode unit and a second electrode unit. The first electrode unit has a pair of central electrodes, that is, a first central electrode 16a arranged on the top side 18 of the ion guide 12, and a second central electrode 16b arranged on the bottom side 20 of the ion guide 12. For better illustration, only one of the central electrodes 16a, 16b is provided with a reference numeral. The second electrode unit has a pair of side electrodes, namely an inner electrode and an outer electrode 26, where the inner electrode is segmented into two sections, and only one section 22a of which is shown in the figure, and it is arranged facing the center of the ion guide 12 (at Figure 1b1 and 12. In the embodiment of the present invention, the inner electrode 22a and the outer electrode 26 are arranged on a first side 24 of the ion guide 12 (marked with an "X" in the figure), and the outer electrode 26 is arranged on a second side 28 of the ion guide 12 away from the center of the ion guide 12. Again, for better illustration, only one of the inner electrode 22a and the outer electrode 26 is provided with a reference numeral. Each electrode unit is a discrete electrode sheet. In the present embodiment, the electrode units are arranged so that the ion guide 12 has a continuous circular shape and has a substantially rectangular cross-section along the drift length 14 of the ion guide 12.

[0102] Furthermore, the ion guide 12 is provided with an ion inlet region on the inner side 24 . The ion inlet region is provided to allow ions to be injected from the ion channel 42 into the ion guide 12 .

[0103] Furthermore, the ion guide is provided with an ion exit region 32, which is provided to allow ions to be ejected from the ion guide 12. In the exemplary embodiment, the ion exit region 32 is exemplarily indicated by a shaded electrode, which is periodically moved around the closed-loop ion guide 12.

[0104] The trapped ion mobility separator 10 has an electrical component 34 ( Figure 12 ). In the present embodiment, the electrical component 34 has a plurality of electrical units, each of which is a DC voltage generator 36. The generator 36 induces an axial force exerted on the ions along the drift length 14 of the ion guide 12. In order to induce the axial force, in the present embodiment, the generator 36 applies an electric potential to the electrode to form an electric field barrier having a low electric field end and a high electric field end inside the ion guide 12, and the electric field barrier periodically moves around the closed-loop ion guide 12. In the present embodiment, the moving electric field barrier includes a first portion (A) represented by an electric field gradient, and a second portion (B) represented by a platform having a substantially constant electric field, which second portion is spatially adjacent to the high electric field end of the electric field gradient (see Figure 2 ). The axial force affects the motion of the ions, which depends on the mobility through the interaction of the ions with the gas.

[0105] In particular, the generator 36 is configured to generate a time-dependent voltage to be applied to a pair of central electrodes, wherein the voltage varies at each new time interval, as shown in FIG. Figure 4 The number of generators 36 corresponds to the number of pairs of central electrodes, wherein a separate generator 36 is assigned to each pair of central electrodes.

[0106] The trapped ion mobility separator 10 has an electrical controller 40 ( Figure 12)。The electrical controller 40 communicates with the generator 36. The electrical controller 40 is arranged to increase the rate of movement of the electric field barrier over time while the electric field barrier moves around the closed-loop ion guide 12, and to decrease the electric field strength of the moving electric field barrier.

[0107] In addition, the trapped ion mobility separator 10 has an ion channel 42. The ion channel 42 has an electrode array for guiding ions to be injected into the ion guide towards the ion guide 12 and for propelling the ions ejected from the ion guide 12 forward. In the present embodiment, the electrode array consists of stacked annular electrodes 44, all of the annular electrodes having the same diameter and being arranged at uniform intervals from each other. For better illustration, only one of the annular electrodes 44 is provided with a reference numeral. The ion channel 42 extends through the center X of the ion guide 12, wherein the ion channel 42 extends in the up and down directions in the z-dimension relative to the ion guide 12, except in the region where the ion guide 12 is located. In the present embodiment, the rotational axis of the ion channel 42 is coaxial with the rotational axis (R; shown in dashed lines) of the ion guide 12.

[0108] Hereinafter, a mode of operating the first embodiment of the trapped ion mobility separator 10 according to the present invention will be described:

[0109] Ions are injected into the ion guide 12. Specifically, the ions are guided from the ion channel 42 towards the ion guide 12 for injection into the ion guide 12. In the present embodiment, the ions pass through the first inner side 24 of the ion guide 12 along substantially the entire drift length 14 of the ion guide 12 and are injected into the ion guide 12 in the radial direction. To allow this, a DC potential is applied between the inner and outer electrodes of the ion guide 12 such that a transverse electric field is generated, which pulls the ions away from the center X and into the ion guide 12. Subsequently, a DC potential for radial confinement is applied to the side electrodes to prevent the ions from escaping laterally from the ion guide 12.

[0110] Subsequently, a potential is applied to the central electrode pair to form an electric field barrier inside the ion guide 12, thereby generating an axial force applied to the ions along the drift length 14 of the ion guide 12 by the generator 36. In the present embodiment, a direct current (DC) potential is applied to the central electrode pair to generate an axial DC field (DC field). The potential is applied such that an electric field barrier is formed along substantially the entire drift length 14 of the ion guide 12. In addition, the potential is applied such that the electric field barrier has the first part (A) and the second part (B) as described above.

[0111] In an embodiment, the generated electric field barrier moves periodically around the closed-loop ion guide 12. In particular, the generated electric field barrier moves in a direction in which the electric field of the electric field barrier at a particular position of the ion guide 12 gradually increases from a low electric field to a high electric field and then drops back to the low electric field for most of a period. By moving the electric field barrier, ions with different ion mobilities will accumulate at their respective equilibrium positions (equilibrium points) on the electric field barrier, whereas without the movement, these ions would typically move to the low electric field end of the electric field gradient. Or, in other words, ions with different mobilities reach a dynamic equilibrium in an electric field of an appropriate intensity on the electric potential curve. Thus, the ions are separated according to their ion mobilities. At the same time, the ions are pushed by the moving electric field barrier to move along the drift length of the ion guide 12, whereby the ions will be trapped at these respective relative positions as long as the moving rate of the moving electric field barrier, the electric field strength, and the pressure and temperature of the gas through which the ions pass remain constant.

[0112] At the same time, a confinement potential is applied to the electrodes to prevent the ions from laterally escaping from the ion guide. In the lateral direction in which the dimensions of the ion guide 12 are limited by the side electrode pair, the ions are confined by a DC potential as described above and as can be seen with reference to Figure 3 the foregoing. In the lateral direction in which the dimensions of the ion guide 12 are limited by the center electrode pair, the ions are confined by an RF pseudopotential.

[0113] The electrical controller 40 changes the axial force over time. In this embodiment, the axial force is changed such that when the electric field barrier moves around the closed-loop ion guide 12, the moving rate of the electric field barrier increases over time and the electric field strength of the moving electric field barrier decreases over time. In another conceivable embodiment, alternatively or additionally, when the electric field barrier moves around the closed-loop ion guide 12, the pressure of the gas through which the ions pass in the ion guide 12 can increase over time, and / or the temperature of the gas through which the ions pass in the ion guide 12 can decrease over time. In this way, ion species are pushed towards the high electric field end of the electric field barrier along the first part (A) of the moving electric field barrier, where ion species with different ion mobilities subsequently reach the second part (B) of the electric field end. While the moving rate of the electric field barrier increases over time and / or the electric field strength of the moving electric field barrier decreases over time, the ion species that reach the second part increase their moving rate. In this way, the ion species that cross over to the second part can be better spatially separated.

[0114] Ion species that have crossed over to the second part are ejected from the ion guide 12, respectively, before slipping past the electric field barrier. The ions are ejected from the ion guide 12 at the exit region that moves with the electric field barrier. In the present embodiment, the ions pass through the first side 24 of the ion guide 12 and are ejected from the ion guide 12 in the radial direction. To allow this, the DC potential applied between the outer electrode and the inner electrode of the ion guide 12 is changed such that a transverse electric field is generated that pushes the ions towards the center X of the ion guide 12. In particular, in the present embodiment, the ion exit region is arranged adjacent to the high electric field end of the moving electric field barrier and moves periodically with the moving electric field barrier such that the ion exit region remains at the high electric field end of the moving electric field barrier and the ions are ejected continuously in a timely manner when they reach the high electric field end of the moving electric field barrier. Subsequently, the ions ejected from the ion guide 12 are advanced forward by the ion channel 42 for further analysis.

[0115] In the present embodiment, the trapped ion mobility separator 10 operates at a gas pressure of 5 mbar.

[0116] Figure 2 The spatial curve (solid line) of the potential applied to the center electrode pair along the drift length 14 of the ion guide 12 is shown. This potential is related to the DC voltage and gives rise to an axial force as described with reference to FIG. 1. In addition, Figure 2 The spatial curve (dashed line) of the generated electric field along the drift length 14 of the ion guide 12 is shown. In principle, the electric field is the spatial derivative of the potential. The curve shown corresponds to the state at the time point "zero", i.e., the time point when the potential is started to be applied to the electrodes, just before the start of the movement of the electric field barrier around the closed-loop ion guide.

[0117] The potential (V) applied to the center electrode pair is shown on the ordinate, and the central angle φ (rad), which represents the extension of the ion guide 12 in its longitudinal direction, is shown on the abscissa. As can be seen in the drawing, the electric field barrier is formed along substantially the entire drift length of the ion guide. In addition, it can be seen from the drawing that the potential applied to the center electrode increases quadratically in the first part (A) and linearly in the second part (B). Accordingly, an electric field as claimed in the present invention is generated, which has an electric field gradient (the first part of the electric field barrier) and a plateau with a substantially constant electric field (the second part of the electric field barrier), which plateau is adjacent to the high electric field end of the first part. In the angular range adjacent to the second part, in the third part (C), a constant potential is applied to the center electrode, resulting in the axial electric field being cancelled in this region, and thus it represents the ion exit region (ejection region).

[0118] Figure 3Shows the spatial curve (solid line) of the potential applied to the side electrode pair along the drift length 14 of the ion guide 12. This potential is related to the DC voltage and causes a radial DC confinement as described with reference to FIG. 1. In addition, for comparison, Figure 3 Shows as Figure 2 The curve (dashed line) of the potential applied to the central electrode along the drift length 14 of the ion guide 12 as shown in. The curves shown correspond to the state at the time point "zero", i.e., the time point when the potential is first applied to the electrodes, just before the movement of the electric field barrier around the closed-loop ion guide begins.

[0119] The potential (V) applied to the side electrode pair is shown on the ordinate, and the central angle φ (rad) representing the extension of the ion guide 12 in its longitudinal direction is shown on the abscissa. As can be seen in the drawing, within the angular ranges related to the first and second parts of the electric field barrier, the potentials applied to the inner and outer electrodes are comparable to each other. In addition, as can be seen in the drawing, within the angular ranges related to the first and second parts of the electric field barrier, the potential applied to the side electrodes is comparable to the potential applied to the central electrode, but the former is slightly offset to a higher potential in order to laterally confine the ions. However, within the angular range related to the ejection region, the potentials applied to the inner electrode, outer electrode, and central electrode are different from each other. In particular, a potential gradient is created between the inner and outer electrodes, where a relatively low potential is applied to the inner electrode and a relatively high potential is applied to the outer electrode, thereby causing the ions to radially eject towards the center of the ion guide in the ion exit region (ejection region).

[0120] Figure 4Shows a time curve of the potential applied to a single pair of central electrodes varying with time. As explained with reference to FIG. 1, the electric field barrier moves periodically around the closed-loop ion guide in the direction of the dashed arrow. In this embodiment, a case where the electric field barrier moves around the ion guide 12 three times (cycle n, cycle n + 1, cycle n + 2) is exemplarily shown, wherein the time curve depicts the variation of the potential applied to a single pair of central electrodes with time within three movement cycles. In this embodiment, the potential applied to a single pair of central electrodes is provided by a DC voltage generator 36, which generates a voltage varying with time, and the voltage value thereof varies according to the shown curve. As described with reference to FIG. 1, in this embodiment, there are a plurality of additional DC voltage generators 36 (not shown in the figure), wherein each pair of central electrodes is assigned a separate one of the generators, which respectively generate time-related voltages. The time-varying potentials provided by the generator 36 and applied to each pair of the central electrode pairs respectively correspond to the shown curve, wherein, as shown in the drawings, the time-varying potential curves are applied to subsequent central electrode pairs along the drift length 14 of the ion guide 12 with a gradual time offset (gradual time delay), thus causing the electric field barrier to move along the drift length 14 of the ion guide 12, as described with reference to FIG. 1 and Figure 2 as described. The time delay between adjacent electrodes is equal to the period divided by the number of electrodes.

[0121] Figure 5 Shows a spatial curve of the potential applied to the central electrode pairs along the drift length 14 of the ion guide 12. This potential is related to the DC voltage and causes an axial force. The shown spatial curve corresponds to the state at the time point "zero", i.e., the time point when the potential starts to be applied to the electrodes.

[0122] The potential (V) applied to the central electrode pairs is shown on the vertical axis, and the central angle φ (rad), which represents the extension of the ion guide 12 in its longitudinal direction, is shown on the horizontal axis. As can be seen in the drawings, a plurality of electric field barriers are formed inside the drift length 14 of the ion guide 12. In particular, three electric field barriers are formed inside the drift length 14 of the ion guide 12, and these three electric field barriers are arranged in sequence. In this embodiment, each of these electric field barriers corresponds to a single electric field barrier as described with reference to Figure 2 as described. However, since a plurality of electric field barriers are formed inside the drift length 14 of the ion guide 12, these electric field barriers respectively have a greater gradient in the first part (A).

[0123] Figures 6a to 6c Represents the third alternative mode of operating the trapped ion mobility separator 10, wherein, Figure 6a shows a cross-sectional view of the trapped ion mobility separator 10 in the z direction,Figure 6b represents the spatial curve of the electric potential applied to the drive / collection electrodes, and Figure 6c the curve of the electric potential applied to the ejection electrode. The curves shown correspond to the state at the time point "zero", i.e., the time point when the electric potential starts to be applied to the electrodes, just before the movement of the electric field barrier around the closed-loop ion guide begins.

[0124] Figure 6a The trapped ion mobility separator 10 is shown in a cross-sectional view in the z direction. The trapped ion mobility separator is operated in a mode in which the ion exit region 32 (marked by the shaded electrode) is provided at a fixed specific electrode in a part of the ion guide 12 (fixed ejection region) such that ions are periodically ejected at this specific electrode. In the present embodiment, in the drawings, the fixed specific electrode where the ion exit region 32 is provided is marked with shading and is hereinafter referred to as the ejection electrode. As described with reference to FIG. 1, ions pass through the first side 24 of the ion guide 12 and are ejected from the ion guide 12 in the radial direction. In the following description of the present embodiment, all the remaining central electrode pairs around the ejection electrode are referred to as drive / collection electrodes.

[0125] Figure 6b represents the time curves of the electric potential applied to the drive / collection electrodes respectively over a single movement cycle of the electric field barrier. The solid line represents the electric potential applied to the central drive / collection electrode pair, and the dashed line represents the electric potential applied to the side drive / collection electrode pair. The electric potential (V) applied to the drive / collection electrode pair is shown on the vertical axis, and the time (1 / cycle period) is shown on the horizontal axis. As can be seen in the drawings, the electric potential applied to the drive / collection electrode pair over time generally corresponds to the electric potential applied to a single pair of central electrodes as described with reference to Figure 4 wherein, instead of the linear continuation at the end of the second part (B), a potential barrier is provided at the second part (B) adjacent to the moving electric field barrier to prevent ions from slipping past the moving electric field barrier before ejection.

[0126] Figure 6cA time curve showing the potential applied to the ejection electrodes as a function of time during a single movement cycle of the electric field barrier. Again, the solid line represents the potential applied to the central electrode pair, while the dashed line represents the potential applied to the side electrode pair. In an embodiment, the ejection electrodes have three pairs of central ejection electrodes and a corresponding number of side ejection electrode pairs. The potential (V) applied to the ejection electrode pairs is shown on the ordinate, and the time (1 / cycle period) is shown on the abscissa. As can be seen in the drawing, within the time ranges associated with the first and second portions (A, B) of the electric field barrier, the potentials applied to the inner and outer ejection electrodes are comparable to each other. Additionally, as can be seen in the drawing, within the time ranges associated with the first and second portions (A, B) of the electric field barrier, the potential applied to the side ejection electrode pairs is comparable to the potential applied to the central ejection electrode pairs, but the former is slightly shifted to a higher potential to confine ions in the direction of the side electrodes. However, within the time range associated with the ejection region (C), the potentials applied to the inner ejection electrode, outer ejection electrode, and central electrode are different from each other. In particular, as referred to Figure 3 as described, a potential gradient is created between the inner and outer ejection electrodes, where a relatively lower potential is applied to the inner ejection electrode and a relatively higher potential is applied to the outer ejection electrode, thereby causing ions to radially eject towards the center of the ion guide in the ion exit region 32 (ejection region). Thus, as can be seen in the drawing, the ion exit region 32 is set at a timing. In particular, this means that the ion exit region 32 is set at the ejection electrodes only when the end of the plateau (second portion B) with a substantially constant electric field passes the ejection electrodes.

[0127] Figure 7 A schematic three-dimensional view showing a second embodiment of the trapped ion mobility separator 46 according to the present invention. Thus, the trapped ion mobility separator 46 is a moving barrier type trapped ion mobility separator (mbTIMS). The trapped ion mobility separator 46 substantially corresponds to the trapped ion mobility separator 10 according to FIG. 1 in terms of its structure and its (first) operating mode. The same elements are provided with the same reference numerals. In this regard, reference is also made to the foregoing description.

[0128] The trapped ion mobility separator 46 differs from the trapped ion mobility separator 10 in FIG. 1 in that the former has a plurality of ion guides 12. In the present embodiment, the trapped ion mobility separator 46 has five ion guides 12a - 12e, each ion guide having the same structure and operating in the same mode (e.g., as described with reference to FIG. 1). The ion guides 12a - 12e are arranged in sequence. In addition, the ion channel 48 of the trapped ion mobility separator 46 differs from the ion channel 42 of the trapped ion mobility separator 10 in its elongated structure, which links the respective ion guides 12a - 12e of the trapped ion mobility separator 46. Thus, the ion channel 48 is arranged to direct ions to be injected into one of the ion guides 12 along these sequentially arranged ion guides 12a - 12e. Each of the sequentially arranged ion guides 12a - 12e is provided with an ion inlet region for a certain period of time, while during this period, the corresponding other ion guides are not provided with an ion inlet region, such that ions can enter their respective predetermined ion guides 12 within a given period of time. Ions ejected from any one of the ion guides 12a - 12e are advanced forward by the ion channel 48 for further analysis. As referred to Figure 4 as described above, the electric potential applied to the central electrode pair is provided by a plurality of generators, each generator being arranged to generate a time - dependent voltage. In particular, in the present embodiment, the ion guides 12a - 12e are operated in a time - offset manner to allow ion species to be ejected synchronously from the sequentially arranged ion guides 12a - 12e, such that the ion species ejected from the first ion guide 12 and the last ion guide 12e reach the end of the ion channel simultaneously (synchronously).

[0129] It is also conceivable that, as described with reference to Figure 5 there are formed several electric field barriers within each of the plurality of ion guides 12a - 12e.

[0130] Figure 8 FIG. shows a schematic three - dimensional view of a third embodiment of a trapped ion mobility separator 50 according to the present invention. Thus, the trapped ion mobility separator 50 is a moving - barrier trapped ion mobility separator (mbTIMS). The trapped ion mobility separator 50 substantially corresponds to the trapped ion mobility separator 10 according to FIG. 1 in terms of its structure and its (first) operating mode. The same elements are provided with the same reference numerals. In this regard, reference is also made to the foregoing description.

[0131] The trapped ion mobility separator 50 differs from the trapped ion mobility separator 10 according to FIG. 1 in the structure of the ion channel 52. The ion channel 52 has an inner boundary, which is represented as an inner radius 54. In addition, the ion channel 52 has an outer boundary, which is represented as an outer radius 56. A gap is provided between the outer radius and the inner radius. The gap is an annulus, that is, the spacing between the outer radius and the inner radius through which ions pass.

[0132] In addition, due to the structure of the ion channel 52, the trapped ion mobility separator 50 differs from the trapped ion mobility separator 10 according to FIG. 1 in that ions are injected into the ion guide 12 along the axial direction through the bottom side 20 of the ion guide 12 and ejected from the ion guide 12 along the axial direction through the top side 18 of the ion guide 12.

[0133] In addition, due to the structure of the ion channel 52, the trapped ion mobility separator 50 differs from the trapped ion mobility separator 10 according to FIG. 1 in that the central electrodes are arranged and designed differently. Instead of arranging the pair of central electrodes such that the first central electrode is arranged on the top side 18 of the ion guide 12 and the second central electrode is arranged on the bottom side 20 of the ion guide 12, for each pair of central electrodes, the first and second central electrodes are each segmented into two sections. In an embodiment, the first section 16aa of the first central electrode is arranged above the outer electrode 26, and the second section 16ab of the first central electrode is arranged above the inner electrode (not shown in the figure). A similar arrangement is made for the first and second sections of the second central electrode. The first section 16ba of the second central electrode is arranged below the outer electrode 26, and the second section (not shown in the figure) of the second central electrode is arranged below the inner electrode (not shown in the figure).

[0134] Figure 9 A schematic three-dimensional view of a fourth embodiment of a trapped ion mobility separator 58 according to the present invention is shown. Thus, the trapped ion mobility separator 58 is a moving barrier trapped ion mobility separator (mbTIMS). The trapped ion mobility separator 58 corresponds substantially to the trapped ion mobility separator 10 according to FIG. 1 in terms of its structure and its (first) operating mode. The same elements are provided with the same reference numerals. In this regard, reference is also made to the foregoing description.

[0135] The trapped ion mobility separator 58 differs from the trapped ion mobility separator 10 according to FIG. 1 in the structure of the ion guide 60, which is caused by the different implementation of the electrodes. Instead of (as described with reference to FIG. 1) having the ion guide with electrodes each consisting of electrode units formed as separate discrete electrode sheets, the ion guide 60 has first and second printed circuit boards (PCBs) 62, 64, which are arranged opposite to each other to form a closed-loop ion guide 12 therebetween, wherein the first printed circuit board 62 is arranged on the top side 18 of the ion guide 60, and the second printed circuit board 64 is arranged on the bottom side 20 of the ion guide 60. The first printed circuit board 62 has a plurality of central electrodes (not shown in the figure), which are evenly spaced and embedded in the surface 68 of the first printed circuit board 62, and the surface 68 faces the surface 70 of the second printed circuit board 64. A plurality of inner electrodes and outer electrodes (not shown in the figure), the number of which respectively corresponds to the number of central electrodes, are also embedded in the surface of the first printed circuit board 62, wherein the inner electrodes are respectively arranged on one side of the central electrodes facing the first (inner) side 24 of the ion guide 60, and the outer electrodes are respectively arranged on the other side of the central electrodes facing the second (outer) side 28 of the ion guide 60. Correspondingly, the second printed circuit board 64 has a plurality of central electrodes 66b, which are evenly spaced and embedded in the surface 70 of the second printed circuit board 64, and the surface 70 faces the surface 68 of the first printed circuit board 62; it also has a plurality of inner electrodes 72b and outer electrodes 74b, the number of which respectively corresponds to the number of central electrodes 66b, wherein the inner electrodes 72b are arranged on one side of the central electrodes 66b facing the first (inner) side 24 of the ion guide 60, and the outer electrodes 74b are arranged on the other side of the central electrodes 66b facing the second (outer) side 28 of the ion guide 60.

[0136] Figure 10 FIG. shows a schematic three-dimensional view of a fifth embodiment of a trapped ion mobility separator 76 according to the present invention. Thus, the trapped ion mobility separator 76 is a moving barrier type trapped ion mobility separator (mbTIMS). The trapped ion mobility separator 76 is substantially corresponding to the trapped ion mobility separator 58 in terms of its structure and operation mode according to Figure 9 The same elements are provided with the same reference numerals. In this regard, reference is also made to the foregoing description. For better illustration, only the electrodes on the printed circuit board structure are shown in the figure, and the printed circuit board itself is not shown. It is conceivable to use discrete electrodes instead of the electrodes embedded in the printed circuit board.

[0137] The trapped ion mobility separator 76 differs from the trapped ion mobility separator 58 according to Figure 9 in that the radius of the ion guide 60 is significantly larger thanFigure 9 The radius of the ion guide. This enables high storage capacity. In addition, the trapped ion mobility separator 76 and according to Figure 9 The trapped ion mobility separator 58 is different in its ion channel. The trapped ion mobility separator 76 has a first ion channel 78a for guiding ions to be injected into the ion guide towards the ion guide 60, and also has a second ion channel 78b for propelling the ions ejected from the ion guide 60 forward.

[0138] The first ion channel 78a is arranged such that the longitudinal axis (L; shown as a dashed line) of the ion channel 78a is substantially perpendicular to the rotational axis (R; shown as a dashed line) of the ion guide 60 and is spatially offset from this rotational axis. The first end 80 of the ion channel 78a is coupled to a part of the outer edge 86a of the ion guide 60. The ion channel 78a has an electrode array composed of segmented electrodes 82, and these segmented electrodes are shaped and arranged such that the ion channel 78a has a substantially rectangular cross-section. For better illustration, only one of the segmented electrodes 82 is provided with a reference numeral.

[0139] The second ion channel 78b is arranged such that the rotational axis of the ion channel 78b is coaxial with the rotational axis of the ion guide 60. The first end 84 of the ion channel 78b is coupled to the inner edge 86b of the ion guide 60. The ion channel 78b has an electrode array composed of stacked annular electrodes 88 arranged at uniform intervals from each other, and among these electrodes 88, the diameters decrease along the extending direction of the ion guide 78b. Therefore, the ion guide 78b is shaped as an ion funnel. For better illustration, only one of the annular electrodes 88 is provided with a reference numeral.

[0140] Figure 11 A schematic three-dimensional view of a sixth embodiment of a trapped ion mobility separator 90 according to the present invention is shown. Therefore, the trapped ion mobility separator 90 is a moving-barrier trapped ion mobility separator (mbTIMS). The trapped ion mobility separator 90 is substantially corresponding to the trapped ion mobility separator 58 according to Figure 9 in terms of its structure and operation mode. The same elements are provided with the same reference numerals. In this regard, reference is also made to the previous description.

[0141] The trapped ion mobility separator 90 is different from the trapped ion mobility separator 58 according to Figure 9 in the shape of its ion guide 92. The electrodes embedded in the surface of the printed circuit board as described with reference to Figure 9 are arranged such that the ion guide 92 has a substantially elliptical shape, and in particular, the ion guide 92 is shaped as a stadium shape.

[0142] In addition, the captured ion mobility separator 90 differs from the captured ion mobility separator 58 according to Figure 9 in the mode in which ions are ejected from the ion guide 92. As described with reference to FIG. 6, the ion exit region 32 is provided at a fixed specific electrode in the portion P (marked with a double-headed arrow) of the ion guide 92, such that ions are periodically ejected at these specific electrodes. In particular, in the present embodiment, in the ion exit region 32 provided in a portion P of the ion guide 92, the printed circuit board has eight pairs of central electrodes and a plurality of associated inner and outer electrodes.

[0143] In addition, the captured ion mobility separator 90 differs from the captured ion mobility separator 58 according to Figure 9 in its ion channel 94. The ion channel 94 is arranged such that the longitudinal axis (L; shown as a dashed line) of the ion channel 94 is substantially perpendicular to the rotational axis (R; shown as a dashed line) of the ion guide 92 and is spatially offset from this rotational axis. In particular, the ion channel 94 is arranged parallel to the portion P of the ion guide 92 which is substantially shaped like an ellipse. Accordingly, in the present embodiment, ions pass through the second side 28 of the ion guide 92, are injected into the ion guide 92 in a radial direction, and are ejected therefrom. The ion channel 94 has an electrode array which consists of segmented electrodes embedded in the surfaces of the printed circuit boards 96, 98 (corresponding to the electrode arrangement within the printed circuit board which produces the ion guide 92), and these segmented electrodes are shaped and arranged such that the ion channel 94 has a substantially rectangular cross-section. For better illustration, the segmented electrodes in the printed circuit board are not provided with reference numerals.

[0144] Figure 12 FIG. shows a schematic diagram of a mass spectrometry system 100 according to the present invention. The mass spectrometry system 100 is used for analyzing ions. The mass spectrometry system 100 has a plurality of analysis devices, which will be described below.

[0145] The mass spectrometry system 100 has a separation device (not shown in the figure) for separating a mixture of substances. In an embodiment, the separation device is a liquid chromatography device. Other separation devices (not shown in the figure), such as electrophoresis devices, may be provided and may be coupled to the mass spectrometry system 100.

[0146] In addition, the mass spectrometry system 100 has an ion generator 110. The ion generator 110 has an ion source 112. In this embodiment, the ion source 112 is an electrospray ionization (ESI) source. The ion source 112 operates at atmospheric pressure. Other ion source types that can be used include, for example: thermal spraying, desorption ionization (e.g., matrix-assisted laser / desorption ionization (MALDI) or secondary ionization), chemical ionization (CI), photoionization (PI), electron impact ionization (EI), and gas discharge ionization. In addition, the ion generator 110 has an ion source chamber 114. The ion source chamber 114 is maintained at atmospheric pressure. In particular, the ion source chamber 114 incorporates the ion source 112. The ion generator 110 is located downstream of the liquid chromatography device. In addition, a transfer capillary 116 is provided. The transfer capillary 116 has a first end 118. The first end 118 of the transfer capillary 116 is connected to the ion source chamber 114. In addition, the transfer capillary 116 has a second end 120. The second end 120 of the transfer capillary 116 is connected to the vacuum chamber 124 of the trapped ion mobility separator 122. In particular, the transfer capillary 116 is arranged to introduce ions generated by the (electrospray) ion source 112 into the vacuum chamber 124. In this embodiment, the transfer capillary 116 is a short and wide bore capillary having an inner diameter greater than or equal to 1 mm and a length less than or equal to 180 mm. Optionally, a single capillary, multiple capillaries, or single / multi-orifice inlets with different lengths and diameters can be used to transfer ions from the ion source chamber 114 to the vacuum chamber 124.

[0147] In addition, the mass spectrometry system 100 has a trapped ion mobility separator 122. In the present embodiment, the trapped ion mobility separator is a moving barrier trapped ion mobility separator (mbTIMS) 122 according to the present invention. In particular, in the present embodiment, the first trapped ion mobility separator 122 corresponds to the trapped ion mobility separator 10 according to FIG. 1. In this regard, reference is also made to the foregoing description. The trapped ion mobility separator 122 is located downstream of the ion generator 110. The trapped ion mobility separator 122 has a vacuum chamber 124. In the present embodiment, the vacuum chamber 124 is maintained at a high pressure between 300 Pa and 3000 Pa. It is contemplated that in another preferred embodiment, the vacuum chamber has an additional sub-atmospheric electrospray ion source. In addition, the trapped ion mobility separator 122 has a deflection electrode 126. It is contemplated that in another preferred embodiment, an additional MALDI source (not shown in the figure) may be placed at the location of the deflection electrode. In addition, the trapped ion mobility separator 122 has an inlet funnel 128 that guides ions into an ion channel 130. In particular, the inlet funnel 128 is a radio frequency inlet funnel. In addition, the trapped ion mobility separator 122 has an ion channel 130. The ion channel 130 is arranged to direct ions to be injected into the ion guide 132 or to advance ions ejected from the ion guide 132. It is contemplated that in another preferred embodiment, the trapped ion mobility separator 122 has an ion trap located within the ion channel 130 of the trapped ion mobility separator. In addition, the trapped ion mobility separator 122 has an ion guide 132. The ion guide 132 is arranged for trapping and separating ions. In the present embodiment, the trapped ion mobility separator 122 operates at a pressure of 5 mbar.

[0148] In addition, the mass spectrometry system 100 has an ion guiding device 134. The ion guiding device 134 is arranged to guide ions. The ion guiding device 134 is located downstream of the mbTIMS 122. The ion guiding device 134 has a radio frequency ion guide 136. In addition, the ion guiding device 134 has an ion guiding chamber 138. The ion guiding chamber 138 incorporates the radio frequency ion guide 136.

[0149] In addition, the mass spectrometry system 100 includes a mass filter device 140. The mass filter device 140 is arranged to direct or filter ions according to their mass. The mass filter device 140 is located downstream of the ion guiding device 134. The mass filter device 140 has a mass filter 142. In the present embodiment, the mass filter 142 is a quadrupole mass filter. In addition, the mass filter device 140 has a mass filter chamber 144. The mass filter chamber 144 houses the quadrupole mass filter 142.

[0150] In addition, the mass spectrometry system 100 has a fragmentation cell 146. The fragmentation cell 146 is arranged to fragment larger ions to allow mass spectrometry measurements of the ion fragments. The fragmentation cell 146 is located downstream of the mass filter device 140. In this embodiment, fragmentation is achieved by collision-induced dissociation (CID). However, any other known type of fragmentation method can also be used, including but not limited to: infrared multiphoton dissociation (IRMPD) or ultraviolet photodissociation (UVPD), surface-induced dissociation (SID), photodissociation (PD), electron capture dissociation (ECD), electron transfer dissociation (ETD), post-collision activation of electron transfer dissociation (ETcD), simultaneous activation of electron transfer dissociation (AI-ETD), and fragmentation occurring by reaction with highly excited or radical-neutral particles. The fragmentation cell 146 has electrodes 148. In addition, the fragmentation cell 146 has a fragmentation cell chamber 150. The fragmentation cell chamber 150 contains the electrodes 148. Fragmentation by collision-induced dissociation can be switched on and off, controlled by controlling instrument parameters such as the axial acceleration voltage. Precursor ions can be trapped in the fragmentation cell 146 without being fragmented, and when fragmented, the ion fragments can also be trapped in the fragmentation cell.

[0151] In addition, the mass spectrometry system 100 has a mass analyzer 152. In this embodiment, the mass analyzer 152 is a time-of-flight analyzer with orthogonal injection of ions (OTOF-MS). Other possible mass analyzers include electrostatic ion traps, radiofrequency ion traps, ion cyclotron frequency ion traps, and quadrupole mass filters. The mass analyzer 152 is arranged to analyze ions according to their mass. The mass analyzer 152 is located downstream of the fragmentation cell 146. The mass analyzer 152 has an accelerator 154 (or pulse generator). In addition, the mass analyzer 152 has a flight tube 156. In this embodiment, the flight tube 156 is field-free. In addition, the mass analyzer 152 has a reflector 158. In addition, the mass analyzer 152 has an ion detector 160. An additional reflector can be located between the accelerator 154 and the ion detector 160 such that the ions are reflected twice in the reflector 158 and move in a W-shaped trajectory rather than a V-shaped trajectory.

[0152] Hereinafter, the basic mode of operating the mass spectrometry system 100 according to the present invention is described:

[0153] Sample material is eluted from a liquid chromatography apparatus (not shown in the figure). Ions are generated by an (electrospray) ion source 112 using the sample material eluted from the liquid chromatography apparatus. The generated ions are introduced into a first vacuum chamber 124 of a first capture ion mobility separator, i.e., mbTIMS 122, through a transfer capillary 116. Subsequently, by applying a repulsive DC potential to a deflection electrode 126 of the mbTIMS 122, the ions are deflected into a radio frequency inlet funnel 128 of the mbTIMS 122. The radio frequency inlet funnel 128 collects the ions and guides the ions into an ion channel 130 of the mbTIMS 122. The ions are directed by the ion channel 130 towards an ion guide 132 and are injected into the ion guide 132 at an ion inlet region. An electric field barrier is generated in the ion guide 132. By moving the electric field barrier, ions with different ion mobilities accumulate at their respective equilibrium positions (equilibrium points) along the electric field barrier and are thus separated according to their ion mobilities. At the same time, the ions are pushed by the moving electric field barrier to move along the drift length of the ion guide 12, so that as long as the moving rate or electric field strength of the moving electric field barrier remains constant, the ions are captured at these respective positions. By continuously increasing the moving rate of the electric field barrier and decreasing the electric field strength of the moving electric field barrier over time while moving the electric field barrier around a closed-loop ion guide, the fragments of the captured ions are gradually driven to the high electric field end of the electric field barrier according to their ion mobilities, and when the ions reach the high electric field end of the moving electric field barrier where an ion exit region is provided, they are ejected in a timely and continuous manner.

[0154] Subsequently, the ions released from the mbTIMS 122 enter an ion guide chamber 138 of an ion guiding device 134 located downstream. A radio frequency ion guide 136 guides the ions into a mass filter chamber 144 of a mass filter device 140 located further downstream, where a mass filter 142 is located. In the mass filter 142, ions are guided or screened according to their mass. Subsequently, the ions passing through the mass filter 140 are directed to a fragmentation cell 146, which is located in a fragmentation cell chamber 150 downstream of the mass filter device 140. In the fragmentation cell 146, larger ions are fragmented into ion fragments to allow mass spectrometry measurement of the ion fragments. A DC voltage is applied to an electrode 148 of the fragmentation cell 146 to generate an axial DC field for ejecting the ion fragments into a mass analyzer 152 located downstream, where these ions are analyzed according to their mass.

[0155] In the foregoing, the present invention has been shown and described with reference to a number of different embodiments. However, those skilled in the art will understand that various aspects or details of the present invention can be changed or, if feasible, various aspects or details of different embodiments can be combined arbitrarily without departing from the scope of the present invention. Generally, the foregoing description is for illustration only and not for limiting the present invention, which is defined only by the appended claims and includes any equivalent embodiments according to the specific circumstances.

[0156] Description of Reference Numerals

[0157] 10 Trapping ion mobility separator

[0158] 12 Ion guide

[0159] 14 Drift length

[0160] 16a First central electrode

[0161] 16aa First section of the first central electrode

[0162] 16ab Second section of the first central electrode

[0163] 16b Second central electrode

[0164] 16ba First section of the second central electrode

[0165] 18 Top side of the ion guide

[0166] 20 Bottom side of the ion guide

[0167] 22a Inner electrode

[0168] 24 First side of the ion guide

[0169] 26 Outer electrode

[0170] 28 Second side of the ion guide

[0171] 32 Ion exit region

[0172] 34 Electrical component

[0173] 36 DC voltage generator

[0174] 40 Electric controller

[0175] 42 Ion channel

[0176] 44 Ring electrode

[0177] 46 Trapping ion mobility separator

[0178] 48 Ion channel

[0179] 50 Trapped Ion Mobility Separator

[0180] 52 Ion Channel

[0181] 54 Inner Radius of Ion Channel

[0182] 56 Outer Radius of Ion Channel

[0183] 58 Trapped Ion Mobility Separator

[0184] 60 Ion Guide

[0185] 62 First Printed Circuit Board (PCB)

[0186] 64 Second Printed Circuit Board (PCB)

[0187] 66b Second Central Electrode

[0188] 68 Surface of the First Printed Circuit Board

[0189] 70 Surface of the Second Printed Circuit Board

[0190] 72b Inner Electrode

[0191] 74b Outer Electrode

[0192] 76 Trapped Ion Mobility Separator

[0193] 78a First Ion Channel

[0194] 78b Second Ion Channel

[0195] 80 First End of Ion Channel 78a

[0196] 82 Segmented Electrode

[0197] 84 First End of Ion Channel 78b

[0198] 86a Outer Edge

[0199] 86b Inner Edge

[0200] 88 Ring Electrode

[0201] 90 Trapped Ion Mobility Separator

[0202] 92 Ion Guide

[0203] 94 Ion Channel

[0204] 96 Printed Circuit Board

[0205] 98 Printed Circuit Board

[0206] 100 Mass Spectrometry System

[0207] 110 Ion Generator

[0208] 112 ion source

[0209] 114 ion source chamber

[0210] 116 transfer capillary

[0211] 118 The first end of the transfer capillary

[0212] 120 The second end of the transfer capillary

[0213] 122 Captured Ion Mobility Separator

[0214] 124 Vacuum Chamber

[0215] 126 Deflection electrode

[0216] 128 entrance funnel

[0217] 130 Ion channels

[0218] 132 Ion Guide

[0219] 134 Ion guide equipment

[0220] 136 RF ion guide

[0221] 138 Ion Guide Chamber

[0222] 140 quality filter equipment

[0223] 142 Quality Filters

[0224] 144 Mass Filter Chamber

[0225] 146 cracking pool

[0226] 148 electrodes

[0227] 150 lysis pool room

[0228] 152 Mass Analyzer

[0229] 154 Accelerator

[0230] 156 Flight Tube

[0231] 158 reflector

[0232] 160 ion detector

[0233] The first part of the electric field barrier

[0234] B The second part of the electric field barrier

[0235] Part 3

[0236] L longitudinal axis

[0237] Axis of rotation R

[0238] Part of the ion guide P

[0239] Central angle φ

Claims

1. A method for separating ions according to ion mobility, comprising the following steps: - providing an ion guide extending in a closed loop, having at least one ion inlet region, at which ions are injected into the ion guide, the ion guide containing a gas, the gas being substantially stationary, and the ions passing through the gas along a drift length of the ion guide, and the ion guide having a plurality of electrodes, the plurality of electrodes being constructed and arranged to guide the ions along the drift length of the ion guide, wherein at least some of the electrodes are at least temporarily supplied with a confining potential to prevent ions from escaping laterally from the ion guide, - generating an axial force applied to the ions along the drift length of the ion guide by applying an electric potential to the electrodes to form at least one electric field barrier within the ion guide, the electric field barrier having a low electric field end and a high electric field end and moving around the closed loop ion guide, wherein the moving electric field barrier has at least one first portion represented by an electric field gradient, and wherein the moving electric field barrier pushes the ions along the drift length of the ion guide, whereby the ions are separated along the electric field barrier according to their ion mobility, - varying over time at least one operating parameter having an effect on mobility separation while moving the electric field barrier around a closed loop ion guide to controllably push at least one ion species along the first portion of the moving electric field barrier toward the high electric field end of the electric field barrier; and - at least one ion exit region is arranged in the ion guide and at least one ion species is ejected laterally from the ion guide in the at least one ion exit region before sliding over the moving electric field barrier.

2. The method according to claim 1, wherein: Changing at least one operating parameter includes at least one of (i) increasing the rate of movement of the electric field barrier, (ii) decreasing the electric field strength of the moving electric field barrier, (iii) increasing the pressure of the gas through which ions pass, and (iv) decreasing the temperature of the gas through which ions pass.

3. The method according to claim 1, wherein: The mobile electric field barrier includes a second portion represented by a plateau having a substantially constant electric field, wherein the second portion is spatially adjacent to the high electric field end of the electric field gradient.

4. The method according to claim 1, wherein: The moving electric field barrier is formed along substantially the entire drift length of the ion guide.

5. The method according to claim 1, wherein: The moving electric field barrier is formed within a portion of a drift length of the ion guide.

6. The method according to claim 5, wherein: One or more additional mobile electric field barriers are formed in the ion guide, and the mobile electric field barriers are formed sequentially along the drift length of the ion guide. Preferably, each of the additional mobile electric field barriers has a first part represented by an electric field gradient, and a second part represented by a platform with a substantially constant electric field, and the second parts are spatially adjacent to the high electric field ends of the electric field gradient, respectively.

7. A method according to claim 6, comprising at least temporarily setting one or more additional ion exit regions in the ion guide, wherein preferably, the number of ion exit regions corresponds to the number of the mobile electric field barriers, and each of the mobile electric field barriers is assigned one of the ion exit regions.

8. The method according to claim 1, wherein: To induce the axial force, a transient direct current (DC) potential is applied to the electrodes to generate a transient axial direct current field (DC field).

9. The method according to claim 8, wherein: The transient direct current (DC) potential applied to the electrodes is provided by a plurality of DC voltage generators, each of which generates a time-dependent voltage, wherein each of the electrodes is connected to a separate one of the DC voltage generators.

10. The method according to claim 1, wherein: Ions are injected into the ion guide at an ion entrance region extending along substantially the entire length of the ion guide with an electrode, or provided at a fixed specific electrode in one or more parts of the ion guide.

11. The method according to claim 1, wherein: At an ion exit region which is arranged adjacent to the high electric field end of the mobile electric field potential barrier and moves together with the mobile electric field potential barrier, ions are ejected from the ion guide so that the ions are ejected promptly and continuously when they reach the high electric field end of the mobile electric field potential barrier, or at an ion exit region which is at least temporarily arranged at a fixed specific electrode in one or more parts of the ion guide, ions are ejected from the ion guide so that the ions are ejected at the specific electrode.

12. The method of claim 1, comprising providing a barrier adjacent to the high electric field end of the moving electric field barrier to prevent ions from sliding over the moving electric field barrier prior to ejection.

13. The method according to claim 1, wherein: Ions pass through one side of the ion guide, are injected into the ion guide in a radial direction, or are ejected from the ion guide.

14. The method according to claim 1, wherein: Ions pass through the top or bottom of the ion guide, are injected into the ion guide in the axial direction, or are ejected from the ion guide.

15. The method of claim 1, comprising providing an ion channel that directs ions to be injected into the ion guide toward the ion guide and / or advances ions ejected from the ion guide.

16. The method according to claim 1, wherein: Prior to ejection, a direct current (DC) potential is applied to the electrodes of the ion guide so as to generate a transverse electric field that holds the ions inside the ion guide, and / or during ejection, in the portion of the ion guide where the ion exit region is located, the direct current (DC) potential applied to the electrodes is adjusted to eject the ions laterally.

17. The method according to claim 1, wherein: The electric field barrier moves at a speed of less than 1000 m / s, preferably less than 750 m / s, most preferably less than 500 m / s.

18. The method according to claim 1, wherein: The gas through which the ions pass is one of nitrogen (N), helium (He), neon (Ne), argon (Ar), sulfur hexafluoride (SF6), hydrogen (H), air, or a mixture of any combination of the aforementioned gases.

19. A captured ion mobility separator, comprising: - an ion guide extending in a closed loop, the ion guide having at least one ion entrance region at which ions are injected into the ion guide, and having at least one ion exit region at which ions are ejected from the ion guide, the ion guide containing a gas, the gas being substantially stationary and through which ions pass along a drift length of the ion guide, and the ion guide comprising a plurality of electrodes constructed and arranged to guide ions along the drift length of the ion guide, wherein at least some of the electrodes are at least temporarily supplied with a confining potential to prevent ions from escaping laterally from the ion guide, at least one generator for causing an axial force on the ions along the drift length of the ion guide by applying an electric potential to the electrodes to form at least one electric field barrier within the ion guide, the electric field barrier having a low electric field end and a high electric field end and moving around the closed loop ion guide, wherein the moving electric field barrier has at least one first portion represented by an electric field gradient, and wherein the moving electric field barrier urges the ions along the drift length of the ion guide, whereby the ions are separated along the electric field barrier according to their ion mobility, - an electrical controller that communicates with the generator to change over time at least one operating parameter of the trapped ion mobility separator that affects the mobility separation while moving the electric field barrier around the closed-loop ion guide so as to controllably push at least one ion species along the first portion of the moving electric field barrier toward the high potential end, wherein the at least one ion species is ejected laterally from the ion guide in the ion exit region before sliding over the electric field barrier.

20. The trapped ion mobility separator according to claim 19, wherein: Changing at least one operating parameter includes at least one of (i) increasing the rate of movement of the electric field barrier, (ii) reducing the electric field strength of the moving electric field barrier, (iii) increasing the pressure of the gas through which ions pass, and (iv) reducing the temperature of the gas through which ions pass.

21. The trapped ion mobility separator according to claim 19, wherein: The generator is arranged to apply an electric potential to the electrodes such that a plateau having a substantially constant electric field is formed adjacent the high field end of the electric field gradient, the plateau representing a second portion of the mobile electric field barrier.

22. The trapped ion mobility separator according to claim 19, wherein: The generator is configured to apply an electric potential to the electrode so as to form one or more additional electric field barriers within the ion guide, the additional electric field barriers preferably corresponding in structure to the first electric field barriers and arranged sequentially along the drift length of the ion guide.

23. The trapped ion mobility separator according to claim 19, comprising a plurality of DC voltage generators, wherein: The number of DC voltage generators corresponds to the number of the electrodes forming the closed-loop ion guide, and wherein each of the electrodes is assigned one of the DC voltage generators.

24. The trapped ion mobility separator according to claim 19, wherein: The electrodes are arranged so that the ion guide has a substantially circular or elliptical shape, or so that the ion guide has an "8" shape, wherein preferably, in the case of the "8" shape, the trajectories of ions moving along the ion guide do not cross, but extend at least partially in different planes.

25. The trapped ion mobility separator of claim 19, wherein: The plurality of electrodes comprises perforated electrodes and / or electrode modules each consisting of electrode units, wherein the perforated electrodes and / or the electrode units are designed and / or arranged such that the ion guide has a substantially convex cross section.

26. The trapped ion mobility separator of claim 19, further comprising an ion channel having an electrode array to direct ions to be injected into the ion guide toward the ion guide and / or to propel forward ions ejected from the ion guide.

27. The trapped ion mobility separator according to claim 26, wherein: The rotational axis of the ion channel is substantially coaxial with the rotational axis of the ion guide.

28. The trapped ion mobility separator of claim 26, wherein: The longitudinal axis of the ion channel is substantially perpendicular to the rotational axis of the ion guide.

29. The trapped ion mobility separator of claim 26, further comprising an ion trap for storing ions, the ion trap being located in the ion channel upstream of the ion guide.

30. The trapped ion mobility separator of claim 26, further comprising at least one second ion guide, the second ion guide preferably having the same structure and operating in the same mode as the first ion guide, wherein The first ion guide and the second ion guide are linked to each other through the ion channel.

31. The trapped ion mobility separator of claim 19, coupled to a vacuum system designed and configured to operate the trapped ion mobility separator at a gas pressure in the range of 0.1 mbar to 20 mbar, preferably 2 mbar to 10 mbar.

32. A mass spectrometry system having an ion source, a mass analyzer with an ion detector, and at least one first trapped ion mobility separator located downstream of the ion source and / or upstream of the mass analyzer, wherein: The first trapped ion mobility separator has: an ion guide extending in a closed loop, having at least one ion inlet region, at which ions are injected into the ion guide, and having at least one ion outlet region, at which ions are ejected from the ion guide, the ion guide containing a gas, the gas being substantially stationary, and through which ions pass along a drift length of the ion guide, and the ion guide comprising a plurality of electrodes, the plurality of electrodes being constructed and arranged to guide ions along the drift length of the ion guide, wherein at least some of the electrodes are at least temporarily supplied with a confining potential to prevent the ions from escaping laterally from the ion guide, at least one generator for causing an axial force on the ions along the drift length of the ion guide by applying an electric potential to the electrodes to form at least one electric field barrier within the ion guide, the electric field barrier having a low electric field end and a high electric field end and moving around the closed loop ion guide, wherein the moving electric field barrier has at least one first portion represented by an electric field gradient, and wherein the moving electric field barrier urges the ions along the drift length of the ion guide, whereby the ions are separated along the electric field barrier according to their ion mobility, - an electrical controller that communicates with the generator to change over time at least one operating parameter of the trapped ion mobility separator that affects the mobility separation while moving the electric field barrier around the closed-loop ion guide so as to controllably push at least one ion species along the first portion of the moving electric field barrier toward the high potential end, wherein the at least one ion species is ejected laterally from the ion guide in the ion exit region before sliding over the electric field barrier.

33. The mass spectrometry system of claim 32, wherein: Changing at least one operating parameter includes at least one of (i) increasing the rate of movement of the electric field barrier, (ii) reducing the electric field strength of the moving electric field barrier, (iii) increasing the pressure of the gas through which ions pass, and (iv) reducing the temperature of the gas through which ions pass.

34. A mass spectrometry system according to claim 32, further comprising at least one second ion mobility separator, which is located downstream of the first ion mobility separator, preferably, the second ion mobility separator corresponds to the first ion mobility separator in its structure and its operating mode.

35. The mass spectrometry system of claim 32, further comprising a fragmentation cell located between the first trapped ion mobility separator and the mass analyzer.

36. The mass spectrometry system of claim 35, further comprising a mass filter located between the first trapped ion mobility separator and the fragmentation cell.

37. The mass spectrometry system of claim 32, further comprising a first ion trap for storing ions, the first ion trap being located upstream of the first trapped ion mobility separator.

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