Laterally extended trapped ion mobility spectrometer

Abstract

The invention relates to a trapped ion mobility spectrometer (TIMS) and methods of operating the same, in which ions pass through an ion region of the TIMS along an axis from an inlet to an outlet, with an elongated cross-sectional profile perpendicular to the axis having a long dimension and a short dimension. First and second forces are provided that act on the ions along the axis, with at least one of the first and second forces having an ion mobility dependent influence on the ions, and with at least one of the first and second forces varying spatially along the axis, causing the ions to be trapped and separated by ion mobility. Different embodiments use different combinations of gas flow and electric field potentials to provide the first and second forces, and employ a variety of electrode structures that provide different advantageous characteristics for the system.

Description

Technical Field

[0001] This invention relates to methods and apparatus for ion mobility spectrometry, particularly for capturing ion mobility spectrometers, and to a hybrid system using ion mobility spectrometry and mass spectrometry. Background Technology

[0002] Ion mobility spectrometry (IMS) is an analytical technique used to study the mobility of ions in a gas and to separate them based on their mobility. An inherent characteristic of IMS is that the mobility of ions in a gas depends on the molecular geometry of the ions, and therefore can often be resolved, thus separating isomers or conformational isomers that cannot be resolved by mass spectrometry. Many applications also utilize the ability to determine the cross-section of analyte ions by measuring their mobility. Knowledge of mobility or cross-section has proven important in many fields, including identifying analytes (e.g., proteomics and metabolomics), separating compound classes, and determining molecular structures (e.g., in structural biology).

[0003] In Trapped Ion Mobility Spectroscopy (TIMS), ions are trapped by a reaction gas stream along a non-uniform DC electric field, typically an electric field gradient, or by a reaction gas stream with a non-uniform axial velocity distribution along a uniform DC electric field. The trapped ions are spatially separated according to their ion mobility and subsequently eluted over time by adjusting the gas velocity or the strength of the axial DC electric field according to their mobility (see, for example, U.S. Patent 6,630,662 B1 to Loboda and U.S. Patent 7,838,826 B1 to Park). The theoretical basis of TIMS is also explained, for example, in the article "Basics of Trapped Ion Mobility Spectroscopy" by Michelmann et al. (J. Am. Soc. Mass Spectrom., 2015, 26, 14-24).

[0004] U.S. Patent 9,683,964 (Park et al.) teaches a TIMS analyzer comprising a trapping region and a separation region for parallel accumulation. The TIMS analyzer accumulates ions in the trapping region and then separates the pre-accumulated ions in parallel over time in the separation region. An airflow drives the ions toward a ramp of a reaction DC electric field barrier in the trapping region, causing the ions to be axially trapped and separated according to their mobility at their position along the ramp. During the accumulation of ions in the trapping region, the airflow also drives ions that have already accumulated in the previous accumulation and transferred to the separation region toward a ramp of a reaction DC electric field barrier in the separation region, causing the ions to be axially trapped and spatially separated according to their mobility. After the accumulated ions to be analyzed are loaded into the separation region, the height of the reaction DC electric field barrier gradually decreases, thereby releasing the ion species from the separation region in order of their mobility.

[0005] U.S. Patent 10,458,944 (Park et al.) teaches the use of a high-order (order N > 2) linear multipole RF system to accumulate and analyze ions at a DC electric field barrier in a TIMS analyzer, or a purely high-order RF multipole system or such a multipole RF system in which there is a transition from high order to low order before the apex of the DC electric field barrier.

[0006] Although ions accumulate at spatially separated locations based on their mobility and the use of higher-order fields, there is still a need to further increase the storage capacity of TIMS analyzers without incurring significant ion loss due to space charge effects. Enhanced storage capacity improves sensitivity and enables the analysis and identification of more low-abundance analytes, particularly in areas involving complex samples, such as bottom-up proteomics or metabolomics. Summary of the Invention

[0007] In a first aspect, the present invention provides a Trapped Ion Mobility Separator (TIMS) comprising an ion region through which ions travel along an axis from an inlet to an outlet; a series of electrode structures; a first force generator that applies a first axial force acting on the ions along the axis and a second force generator that applies a second axial force acting on the ions along the axis, wherein the second axial force acts in opposition to the first axial force, wherein at least one of the first and second axial forces has an effect on the ions dependent on ion mobility, and wherein at least one of the first and second axial forces is spatially varied along the axis such that ions are trapped along the axis and separated by ion mobility during an accumulation phase, and wherein the first and / or second force generator is configured to change the magnitude of the first force relative to the second force over time during an elution phase such that ions are gradually driven to the outlet as a function of ion mobility.

[0008] The ion region contains the gas through which ions pass and has an elongated cross-sectional profile perpendicular to the axis, having a long dimension and a short dimension. The TIMS according to the invention is called Laterally Extended TIMS (LXTIMS). A series of electrode structures are arranged along the axis and at least along the long dimension surround the elongated cross-sectional profile, wherein each electrode structure includes an electrode or a group of electrodes to which one or more varying voltage potentials are applied to generate a first confining electric field, which exerts a confining force on the ions in the ion region relative to the short dimension. Laterally extended TIMS include means for generating the varying voltage potential, such as an RF generator.

[0009] The ratio W / H of the width W of the ion region along its long dimension to its height H along its short dimension is preferably greater than 2, more preferably greater than 5, and even greater than 10. The width W of the ion region along its long dimension is preferably greater than 20 mm, more preferably greater than 50 mm, and even greater than 100 mm. The length L of the ion region along its axis is preferably greater than 50 mm, more preferably greater than 100 mm, and even greater than 200 mm. The ratio L / W of the ion region along its axis to its width W along its long dimension is preferably less than 5, more preferably less than 2, and even less than 1. The ratio L / W is most preferably between 1.5 and 3.

[0010] Compared to conventional TIMS devices, a major advantage of laterally extended TIMS is that ions are not trapped along a line, but rather in an extended volume that is significantly elongated in a lateral direction, resulting in a significant increase in charge capacity without sacrificing mobility resolution.

[0011] The elongated cross-sectional profile is preferably convex, meaning that for any two given points within the cross-sectional profile, all points along the line segment between the two points also lie within the cross-sectional profile. Furthermore, the elongated cross-sectional profile preferably has reflective symmetry through a plane containing the axis and the long dimension. However, the cross-sectional profile can also be non-convex, such as horseshoe-shaped, serpentine, or shaped like the space between a closed outer surface and a closed inner surface, such as a ring. For example, the closed outer surface can be a circle coaxially aligned with a smaller inner circle. In the case where the closed outer surface encloses the closed inner surface, the long dimension is the closed path between the surfaces, while the short dimension is the shortest path between the surfaces. The elongated cross-sectional profile can be constant or vary along the axis.

[0012] The electrode structure can partially, for example, only along the long dimension, or completely surround the elongated cross-sectional profile of the ion region. A varying voltage potential applied to the electrode or electrode assembly can generate a second electric field that exerts a confining force on the ions in the ion region relative to the long dimension. Laterally extended TIMS may also include additional electrodes on one or both sides of the ion region along the long dimension, to which an RF or DC potential is applied to generate a second confining electric field that exerts a confining force on the ions in the ion region relative to the long dimension. The first and second confining electric fields can create a continuously extending trapping region along the long dimension or multiple separate trapping regions along the long dimension.

[0013] In a first embodiment of the electrode structure, each electrode structure includes an elongated electrode extending parallel to the long dimension, wherein the elongated electrodes are arranged alternately along the axis on a first side and a second side of the ion region relative to the short dimension, respectively, an opposite phase of a first RF voltage is applied to an adjacent elongated electrode on the first side, and an opposite phase of a second RF voltage is applied to an adjacent elongated electrode on the second side.

[0014] The first RF voltage and the second RF voltage preferably have different frequencies. The difference between the two frequencies is preferably greater than 10%, more preferably greater than 20%, and most preferably greater than 50%. The ratio between the two frequencies f1 and f2 is preferably not an integer, for example, f1 / f2 = 1.2 / 0.86 or 1.8 / 1.2, to minimize possible resonant excitation of ion movement. The average frequency is preferably between 0.5 and 10 MHz, more preferably around 1 MHz. The operating pressure is preferably less than 5000 Pa, more preferably less than 1000 Pa, and typically between 200 and 700 Pa.

[0015] The relative spacing of the elongated electrodes on the first side is preferably equal to the relative spacing of the elongated electrodes on the second side, wherein the positioning of the elongated electrodes on the second side is offset along the axis by half the relative spacing relative to the elongated electrodes on the first side. The ratio H / S between the height H of the ion region along the short dimension direction and the spacing S of the elongated electrodes is preferably less than 10, more preferably less than 5, and most preferably less than 3, at least for one subgroup of electrodes.

[0016] The elongated electrode preferably has an extension in its short dimension at each end relative to the long dimension, such that an RF potential applied to the elongated electrode generates a second confinement electric field that exerts a confinement force on ions in the ion region relative to the long dimension. More preferably, each elongated electrode includes a cylindrical portion in the long dimension direction and the extension at each end has a flat shape with a curved edge facing the ion region. However, the electrode structure of the first embodiment may alternatively include a DC electrode adjacent to the end of the elongated electrode relative to the long dimension, to which a DC potential is applied to generate a second confinement electric field that exerts a confinement force on ions in the ion region relative to the long dimension.

[0017] In a second embodiment of the electrode structure, each electrode structure includes an electrode surrounding an ion region at a location along the axis different from other electrode structures. The electrode structure may, for example, include a closed-loop electrode. A common RF voltage is applied to each electrode, with the opposite phase of the common RF voltage applied to the electrodes of adjacent electrode structures. The operating pressure is preferably less than 5000 Pa, more preferably less than 1000 Pa, and typically between 200 and 700 Pa.

[0018] In a third embodiment of the electrode structure, each electrode structure includes a plurality of electrode components spaced apart along the longitudinal dimension on opposite sides of the ion region. A transient DC potential is applied to the electrode components, such that a series of low and high DC potentials occur along the longitudinal dimension on either side of the electrode structure. The operating pressure is preferably higher than 5000 Pa, more preferably higher than 20000 Pa, and can even be higher than atmospheric pressure.

[0019] In a fourth embodiment of the electrode structure, each electrode structure includes a set of electrode assemblies extending along the longitudinal dimension on opposite sides of the ion region, and an RF voltage is applied to the electrodes of this set such that opposite phases of the RF voltage are applied to adjacent electrode assemblies and electrode assemblies aligned with each other along the longitudinal dimension on opposite sides of the ion region to create a plurality of ion channels separated along the longitudinal dimension. The operating pressure is preferably less than 5000 Pa, more preferably less than 1000 Pa, and typically between 200 and 700 Pa.

[0020] The first and second axial forces of the laterally extended TIMS can be of different corresponding types. Each of these can be generated by one of axial airflow, axial DC electric field, and axial transient DC electric field. A DC potential or transient DC potential is preferably applied to the electrode structure to generate the axial electric field or axial transient DC electric field, respectively. If the opposing forces are airflow and axial DC electric field, and the airflow velocity and field strength vary along the axis, the spatial variation of the field strength along the axis can be adjusted so that when ion species with different ion mobilities are trapped in the laterally extended TIMS, they occupy the same space along the axis.

[0021] At least one of the first and second axial forces that vary spatially along the axis preferably includes a gradient along the first portion that flattens out to a plateau of substantially constant force. The trapped ions in the ion region preferably extend parallel to the plateau near it.

[0022] The first or second axial force of the laterally extended TIMS can be a gas flow, and the system preferably includes a housing surrounding the electrode structure for guiding the gas flow. The gas flow preferably has a substantially constant velocity near the plateau of the first and / or second axial force along the long dimension in the ion region. Substantially constant means that the gas velocity preferably varies by less than 50% along the long dimension, more preferably less than 20% compared to the maximum gas velocity. The housing may have approximately the same dimensions as the ion region along the short dimension, but may extend further along the long dimension than the ion region. The ratio L / W of the axial length L of the ion region to the width W along the long dimension of the ion region can be less than 2, less than 1, or even less than 1 / 2. The gas flow can be generated by pumping gas away from the inlet or outlet of the ion region and by laterally introducing gas into the ion region, or both.

[0023] Laterally extended TIMS may also include one or more additional components, such as an ion trap located upstream of the ion region, an ion funnel located upstream of the ion region for focusing ions to the ion region inlet, and / or an ion funnel located downstream of the ion region for spatial focusing of ions released at the ion region outlet. The ion trap may be, for example, a linear multipole RF ion trap, an axially segmented linear multipole ion trap, or a stacked ring ion trap, and may include means for generating and controlling an axial DC electric field along its axis. The ion trap may also be a second laterally extended TIMS for storing ions at mobility-related locations along the axis of the ion trap.

[0024] In another embodiment, the ion trap is arranged adjacent to the ion region and coaxial with the axis of the laterally extended TIMS. The ion trap adjacent to the ion region preferably has substantially the same width and height as the ion region. In another preferred embodiment, the ion funnel is located between the ion trap and the ion region of the laterally extended TIMS, and the ion trap is arranged non-coaxially, preferably orthogonally, to the axis of the laterally extended TIMS.

[0025] The laterally extended TIMS can be part of a hybrid system comprising an ion source upstream of the laterally extended TIMS and a mass analyzer with an ion detector downstream of the laterally extended TIMS. The ion source of the hybrid system can generate ions, for example, using spray ionization (e.g., electrospray (ESI) or thermal spray), desorption ionization (e.g., matrix-assisted laser / desorption ionization (MALDI) or secondary ionization), chemical ionization (CI), photoionization (PI), electron collision ionization (EI), or gas discharge ionization. The mass analyzer of the hybrid system can be, for example, one of a time-of-flight analyzer (preferably with orthogonal ion implantation), an electrostatic ion trap, an RF ion trap, an ion cyclotron frequency ion trap, and a quadrupole mass filter.

[0026] The hybrid system may further include a fragmentation unit located between the laterally extended TIMS and the mass analyzer. For example, in the fragmentation unit, ions can be fragmented via collision-induced dissociation (CID), surface-induced dissociation (SID), photodissociation (PD), electron trapping dissociation (ECD), electron transfer dissociation (ETD), collisional activation following electron transfer dissociation (ETcD), activation concurrent with electron transfer dissociation (AI-ETD), or by reaction with highly excited or radical neutral particles. The hybrid system may also include a mass filter located between the laterally extended TIMS and the fragmentation unit.

[0027] The hybrid system may include an upstream mass filter and / or an upstream fragmentation unit, as well as additional ion mobility separators, preferably TIMS and more preferably laterally extended TIMS. The hybrid system may include two laterally extended TIMS, with an activation unit and / or fragmentation unit located therebetween. The two laterally extended TIMS can operate as tandem ion mobility spectrometers within the hybrid system. Preferably, an ion gate is located between the upstream laterally extended TIMS and the activation or fragmentation unit. The two laterally extended TIMS are preferably arranged non-coaxially, more preferably orthogonally, and each includes an upstream ion trap. Furthermore, separation devices, such as gas or liquid chromatography devices or electrophoresis devices, may be part of or coupled to the hybrid system.

[0028] In a second aspect, the present invention provides a method for analyzing ions based on mobility using a trapping ion mobility separator. The method includes the following steps:

[0029] - Provides an ion region through which ions pass along an axis from the inlet to the outlet. The ion region contains the gas through which the ions pass and has an elongated cross-sectional profile perpendicular to the axis, which has a long dimension and a short dimension.

[0030] - Provides a series of electrode structures arranged along an axis and enclosing an elongated cross-sectional profile at least along the length dimension, each electrode structure comprising one electrode or a group of electrodes;

[0031] - A first confinement electric field is generated by applying a varying voltage potential to the electrode or electrode group, which exerts a confinement force on the short-sized ions in the ion region.

[0032] - Generates the first axial force applied to the ions along the axis;

[0033] - A second axial force is generated, which is applied to the ions along the axis and resists the first force, wherein at least one of the first and second axial forces varies spatially along the first axis, such that ions are captured and separated along the axis by ion mobility; and

[0034] - Change at least one of the first and second axial forces to increase the magnitude of the first axial force relative to the second force over time, so that ions are gradually driven to the outlet of the ion region and separated as a function of ion mobility.

[0035] The method further includes generating a second confinement field by applying a varying voltage potential to an electrode or electrode assembly and / or by applying an RF potential or DC potential to an additional electrode, the second confinement field exerting a confinement force on ions in the ion region relative to the elongated dimension.

[0036] The first axial force and the second axial force can be of different types, generated by one of the following: axial airflow, axial DC electric field, and axial transient DC electric field. A DC potential or a transient DC potential can be applied to the electrode structure to generate an axial DC electric field or an axial transient DC electric field, respectively.

[0037] Ions can be generated from the molecular components of the sample in the ion source using one of the following methods: spray ionization (e.g., electrospray (ESI) or thermal spray), desorption ionization (e.g., matrix-assisted laser / desorption ionization (MALDI) or secondary ionization), chemical ionization (CI), photoionization (PI), electron collision ionization (EI), or gas discharge ionization. Furthermore, analytes can be separated by a separation device coupled to the ion source, such as a gas or liquid chromatograph or an electrophoresis apparatus.

[0038] The method also includes accumulating ions from an ion source in an ion trap located upstream of a laterally extended trap ion mobility separator, while simultaneously analyzing the ions in the laterally extended trap ion mobility separator.

[0039] The method may further include detecting the separated ions with an ion detector, or analyzing the separated ions as a function of mass in a mass analyzer located downstream of the trapped ion mobility separator. The separated ions can be broken down into fragment ions, which can be analyzed in a mass analyzer located downstream of the trapped ion mobility separator. The separated ions can be selected and / or filtered based on mass before breaking down the fragments.

[0040] The method may further include selecting ions with specific ion mobility and activating or breaking the selected ions in a downstream activation / breakdown unit, wherein the activated / breakdown ions are analyzed based on their ion mobility. Attached Figure Description

[0041] Figure 1A A schematic diagram of a general form of a laterally extended TIMS according to the present invention is shown.

[0042] Figure 1B It shows Figure 1A Laterally extended TIMS, in which ions are captured and separated.

[0043] Figure 1C It shows Figure 1A Laterally extended TIMS, in which the trapped ions are being eluted.

[0044] Figure 2A A laterally extended TIMS according to the invention is shown, which uses RF potentials of different frequencies to confine ions within the ion region and generate airflow and DC electric field gradients as first and second axial forces.

[0045] Figure 2B It shows Figure 2A A set of electrode structures for laterally extended TIMS, wherein each electrode structure comprises a single electrode.

[0046] Figure 2C It shows Figure 2B Two adjacent electrode structures are located on one side of the ion region along the shorter dimension.

[0047] Figure 2D It schematically shows how to... Figure 2B The electrode structure provides the RF potential.

[0048] Figure 2E It schematically shows how to... Figure 2B The electrode structure provides a DC potential.

[0049] Figure 2F It shows the Figure 2A A diagram illustrating the gas flow rate of the laterally extended TIMS and the DC electric field gradient generated by the applied DC potential.

[0050] Figure 2G It shows something similar to Figure 2F The diagram shows the effective velocity component of the DC electric field gradient for each of several ion species with different ion mobilities.

[0051] Figure 2H It shows something similar to Figure 2G The illustration shows elution of different ion species with different ion mobilities.

[0052] Figure 3A A laterally extended TIMS according to the invention is shown, which uses RF potentials and DC potentials of different frequencies to confine ions within the ion region and generate airflow and DC electric field gradients as first and second axial forces.

[0053] Figure 3B It shows Figure 3A A schematic perspective view of the electrode structure of a laterally extended TIMS, wherein each electrode structure includes three electrodes.

[0054] Figure 3C It shows Figure 3B A schematic cross-sectional view of the electrode structure.

[0055] Figure 3D Showing Figures 3A-3C The electrode structure is an electrode to which an RF potential is applied.

[0056] Figure 3E Showing Figures 3A-3CThe electrodes of the electrode structure are applied with a DC potential that generates a DC electric field gradient along the TIMS axis.

[0057] Figure 4A A laterally extended TIMS according to the invention is shown, which uses an RF potential of one frequency to confine ions within an ion region and generates an axial transient DC electric field and a DC electric field gradient as first and second axial forces.

[0058] Figure 4B It shows Figure 4A A set of electrode structures for laterally extended TIMS, wherein each electrode structure comprises a single electrode.

[0059] Figure 4C It shows how to Figure 4B The electrodes of the electrode structure provide RF potential.

[0060] Figure 4D It shows how to Figure 4B The electrodes of the electrode structure provide DC potential and transient DC potential, wherein the DC electric field gradient is generated by the DC potential and the axial transient DC electric field is generated by the transient DC potential.

[0061] Figure 4E It shows Figure 4D How do the DC potential and transient DC potential shown in the figure represent? Figure 4A The laterally extended TIMS provides a diagram of the opposite traveling wave and DC force.

[0062] Figure 4F It shows something similar to Figure 4E The diagram shows the effective velocity components of the axial transient DC electric field and DC electric field gradient for each of several ion species with different ion mobilities.

[0063] Figure 4G It is similar to Figure 4F The illustration shows elution of different ion species with different ion mobilities.

[0064] Figure 5A A laterally extended TIMS according to the invention is shown, which uses transient DC potential and static DC potential to confine ions within the ion region and generate airflow and electric field gradient as first and second axial forces.

[0065] Figure 5B It shows Figure 5A A set of electrode structures for laterally extended TIMS, wherein each electrode structure comprises a set of electrodes.

[0066] Figure 5C It shows Figure 5BA single electrode structure comprising a set of electrode assemblies, including small electrode assemblies above and below an ion region to which a transient DC potential is applied, and a terminal electrode assembly to which a static DC potential is applied.

[0067] Figure 5D The gas flow rate and the gas flow rate applied to the gas flow rate are shown. Figure 5A A diagram illustrating the DC electric field gradient generated by the DC potential of the laterally extended TIMS electrode structure.

[0068] Figure 5E It shows something similar to Figure 5D The diagram shows the effective velocity component of the DC electric field gradient for each of several ion species with different ion mobilities.

[0069] Figure 5F It shows something similar to Figure 5E The illustration shows elution of different ion species with different ion mobilities.

[0070] Figure 6A A laterally extended TIMS according to the invention is shown, which uses a single-frequency RF potential to confine ions within multiple ion channels and generates gas flow and electric field gradients as first and second axial forces.

[0071] Figure 6B It shows Figure 6A A schematic perspective view of a set of electrode structures for a laterally extended TIMS, wherein each electrode structure includes a set of electrode segments.

[0072] Figure 6C It shows Figure 6B A single electrode structure comprising a set of electrode segments to which an RF potential of opposite phase is applied to generate multiple ion channels.

[0073] Figure 6D The gas flow rate and the gas flow rate applied to the gas flow rate are shown. Figures 6A-6C A diagram illustrating the DC electric field gradient generated by the DC potential of the laterally extended TIMS electrode structure.

[0074] Figure 6E It shows something similar to Figure 6D The diagram shows the effective velocity component of the DC electric field gradient for each of several ion species with different ion mobilities.

[0075] Figure 6F It shows something similar to Figure 6E The illustration shows elution of different ion species with different ion mobilities.

[0076] Figure 7A laterally extended TIMS is schematically shown, having an ion region with a convex cross-sectional profile and including an inlet funnel and an outlet funnel.

[0077] Figure 8 A laterally extended TIMS is schematically shown, having an ion region with a convex cross-sectional profile and including an inlet funnel, an outlet funnel, and an ion trap.

[0078] Figure 9 A laterally extended TIMS is schematically shown, comprising an inlet funnel and an outlet funnel, and having an ion region with a convex cross-sectional profile that varies along the axis.

[0079] Figure 10 A laterally extended TIMS is schematically shown, which includes an inlet funnel and an ion region with a convex cross-sectional profile that varies along the axis but remains constant in the plateau region.

[0080] Figure 11 The diagram schematically illustrates a laterally extended TIMS, which includes an inlet funnel and an ion region with a convex cross-sectional profile that is elliptical and varies along the axis.

[0081] Figure 12 A laterally extended TIMS is schematically shown, having an ion region with a non-convex cross-sectional profile between a coaxial outer and inner circular surface.

[0082] Figure 13 The diagram schematically illustrates a laterally extended TIMS with an ion region having an arc-shaped, non-convex cross-sectional profile.

[0083] Figure 14 The diagram schematically illustrates a laterally extended TIMS with an ion region having a meandering, non-convex cross-sectional profile. Detailed Implementation

[0084] Figure 1A-1C The diagram schematically illustrates three operating phases of a general form of a laterally extended TIMS 100 according to the invention. The laterally extended TIMS 100 includes an ion region 101, which typically includes electrode structures (not shown) that at least partially surround the ion region, particularly in a plane perpendicular to the drawing plane. Each electrode structure includes one electrode or a set of electrodes for generating an electric field within the ion region 101. Figure 1AAs shown, ion 102 enters from one side of ion region 101 and eventually travels to the other side of the channel, temporarily trapped along the way at positions related to mobility. Ion 102 is a molecular component of the sample material of interest that has been ionized and introduced into the ion channel, typically from a known type of ionization source, such as an electrospray or MALDI (matrix-assisted laser desorption / ionization) type ion source or a CI (chemical ionization) ion source. Ion 102 enters ion region 101 at any position and velocity, but is separated by ion mobility before leaving the channel. From here, it can be directed to an ion detector (e.g., as part of an ion mobility spectrometer) or to another analytical system that uses the separated ions (e.g., a mass analyzer).

[0085] The direction of travel of ion 102 along ion region 101 is defined as the axis (z-direction) of the laterally extended TIMS 100, and... Figure 1A-1C The arrow indicates the direction. The separation of ions 102 by ion mobility is achieved by using opposing forces F in the axial direction relative to ion region 101. A (First Force) and F B This is accomplished by a (second force), which produces opposing velocity components, at least one of which depends on ion mobility, thus affecting mobility-related separation. One type of opposing force can be generated by an airflow along the z-axis, either in the same direction as or opposite to the ion's travel. The opposing force can also be generated by a DC electric field, acting on the ions in the presence of residual gas.

[0086] Opposite force F A and F B At least one of them also varies spatially along at least a portion of the z-axis. Opposite forces F A and F B Preferably, the equilibrium is achieved such that for each ion of interest in ion group 102, there exists an equilibrium point with zero velocity within ion region 101. Since the forces dependent on mobility have different effects on ion species with different mobilities, the spatial location along the z-axis where the net velocity of a particular ion species is zero will depend on the ion's mobility K. Therefore, as... Figure 1B As illustrated in the diagram, under opposite axial forces F A and F B Under the influence of the z-axis, each ion species is trapped at a position related to its mobility. In the figure, ion species are shown as circles, with larger diameter circles representing ions with larger cross-sections and therefore lower mobility K. However, those skilled in the art will understand that ion 102 can also separate along the z-axis from higher to lower mobility, depending on the relative arrangement of opposing axial forces.

[0087] The captured ions 102 are ultimately obtained by changing the force F.A and F B One or both of them are eluted from ion region 101, causing a change in the velocity component and the equilibrium point of the ion species to be eluted is not within ion region 101. Conversely, this relative change in axial force can be gradual, causing ion species with increased or decreased mobilities K to continuously leave the laterally extended TIMS 100 in the z-direction. For example, in Figure 1C In the process, ion 102 is eluted from the laterally extended TIMS 100 from a lower mobility K to a higher mobility K.

[0088] In addition to the opposite axial force F A and F B In addition, the present invention also utilizes a lateral restraining force F CONF This confines the ions within ion region 101. This force... Figure 1B and 1C The middle is marked as F CONF The radial arrow indicates this.

[0089] The first embodiment of the present invention is in Figures 2A-2E As shown in the image. Figure 2A A schematic perspective view shows the laterally extended housing 201 of the TIMS 200, which operates at pressures between 10 and 5000 Pa, for example, approximately 300 Pa. (As shown in...) Figure 1A-1C In a more general description, ions enter the laterally extended TIMS 200 on the first side and travel along the z-axis. Within the ion region 202 of the laterally extended TIMS 200, the ions are subjected to opposing axial forces, generated by the gas flow in the positive z-axis direction and the DC electric field gradient in the negative z-axis direction. Specifically, the gas has a substantially constant velocity along the z-direction within the ion region, while the DC electric field gradient, having the opposite polarity to the ions, increases in magnitude along the z-direction from zero to its maximum value at plateau 203. As described below, the electrode structure group 204 provides the DC electric field gradient and the constraint force on the ions within the ion region.

[0090] Figure 2B Is with Figure 2AA schematic diagram of electrode structures 211 and 212 used together in a configuration. Each electrode structure is significantly longer in its long dimension y than in its short dimension x, and includes an elongated electrode extending in the long dimension, with the elongated electrode connected to an extension located at each end of the elongated electrode. Electrode structure 211 has a spatial offset relative to electrode structure 212 in the z-direction. In this embodiment, the elongated electrode has a cylindrical profile, but other electrode shapes may also be used. Electrode structure 211 is oriented with the elongated electrode above the ion region, while electrode structure 212 is oriented with the elongated electrode below the ion region. The extension located at the end of each elongated electrode extends toward the interior of the housing in the x-direction and has a generally flat shape with a curved edge facing the ion region. Each of electrode structures 211 and 212 is spatially offset relative to electrode structure 212 in the z-direction. Figure 2C The figure is shown separately, and as shown with respect to the upper electrode structure 211, the elongated electrode is identified by reference numeral 211a, while the extension is identified by reference numeral 211b. Those skilled in the art will understand that the electrode structure 212 can be identified using the corresponding reference numerals 212a (for the elongated electrode) and 212b (for the extension).

[0091] The electrode structures are adjacent to each other and alternately arranged along the z-direction of electrode structure 211 and electrode structure 212, such as... Figure 2B As shown. For reference purposes, Figure 2B The upper electrode structure 211 is designated as electrode structures 211-1 to 211-N, and those skilled in the art will understand that similar nomenclature can be applied to the lower electrode structure 212. As described below, a DC potential is applied to the electrode structures to control the movement and positioning of ions in the ion region. Since the ion region formed by the electrode structures is elliptical, the ions in the ion region will be distributed along the y-direction, although the control of ion movement is in the axial direction (z-direction) of the TIMS.

[0092] Figure 2D yes Figure 2BA schematic diagram of electrode structures 211 and 212 in the y-direction illustrates how different RF potentials are applied to them. In this embodiment, two different RF potentials with different frequencies are used; RF1 is applied to electrode structure 211, and RF2 is applied to electrode structure 212. As shown, electrode structures 211 and 212 alternate along the z-direction, and for each RF potential, two opposite phases of the signal are used. For example, the first phase of RF1 (RF1+) is applied to every other electrode structure 211, while the opposite phase RF1- (180° out of phase with RF1+) is applied to the other electrode structures 211. Similarly, the first phase of RF2 (RF2+) is applied to every other electrode structure 212, while the opposite phase RF2- is applied to the remaining electrode structures 212. A significant advantage of applying two different frequency RF potentials to the electrode structures on both sides and offsetting the electrode structures on both sides is that virtually no pseudopotential wells are generated along the axis in the ion region.

[0093] like Figure 2E As shown, a DC potential is also applied to the electrode structure. As illustrated, a first DC potential DC211-1 is applied to the first elongated electrode 211-1 above the ion region, while a DC potential DC211-N is applied to the Nth elongated electrode 211-N above the ion region. Similarly, a DC potential DC212-1 is applied to the first elongated electrode 212-1 below the ion region, and a DC potential DC212-N is applied to the Nth elongated electrode 212-N below the ion region. Additional DC potentials are applied to each of the other electrodes in groups 211 and 212. These DC potentials remain constant over time during the accumulation phase and vary during the elution phase, and are used to generate a DC electric field along the z-direction to control the ions in the ion region, as discussed in more detail below.

[0094] One example of this embodiment has the following parameters, but those skilled in the art will understand that this is merely an example and these parameters can vary depending on the application. While the operating pressure of the TIMS may be between 10-5000 Pa (0.1-50 mbar), in this specific example it is approximately 300 Pa (3 mbar). The ion region has a length of 50 mm in the z-direction, a width of 75 mm in the y-direction, and a height of 4 mm in the x-direction. In this configuration, there are 40 electrode structures 211 and 40 electrode structures 212. RF potentials laterally confine ions to the ion region in both the x and y directions, with RF1 having a frequency of 0.86 MHz and RF2 having a frequency of 1.2 MHz. The elongated electrodes are circular rod-shaped electrodes with a diameter of approximately 1.5 mm and a spacing of 2.5 mm from adjacent electrode structures (above and below the ion region). The elongated electrodes are preferably integrated into a printed circuit board (PCB) and provided with DC and RF potentials via leads on the PCB. Finally, the gas flow rate is approximately 100 m / s.

[0095] In the laterally extended TIMS 200, the effect of opposing axial forces on ions is... Figure 2F-2H As shown, each graph is a plot of velocity (or effective velocity component) versus position along the z-axis. Figure 2F As shown, there is a constant gas velocity v gas The ions are propelled along the z-axis through the ion region. Opposite to this motion is a DC electric field -E. DC (t), which has a spatial gradient along the z-axis, produces the effective velocity component -v shown in the figure. DC (t), and the vertical direction increases from zero to z at platform 203. p The maximum value at the location, as described below, can be the elution point of the ions, at which the ions are no longer trapped in the laterally extended TIMS 200. The negative value of the DC electric field is due to its opposite direction to the longitudinal force of the gas, and it is expressed as a function of time because, in this embodiment, the strength of the DC electric field decreases during the elution of different ion species.

[0096] Figure 2G and Figure 2F Similar, but showing K for several different ion species n-1 K n and K n+1 Each of these, the "effective" velocity component -v generated by the reaction DC electric field. DC The "effective" velocity component is related to mobility in the presence of gas, and is therefore represented by a dashed line in the figure to indicate ion species K. n-1 K n and K n+1 The -v corresponding to each of the types in DCGradients. These gradients represent the gradients in the absence of airflow v. gas In the case of DC electric field E DC (t) assigns velocity components to different ion species. That is, -v DC This represents the velocity component of ions in a stationary gas at a given pressure and temperature, attributable to a DC electric field. This value is proportional to the intensity of the DC electric field and varies with different mobilities K (where vo = vo). DC =K·E DC The difference varies for each type of ion. For all ion types K n-1 K n and K n+1 In the absence of a DC electric field, the "effective" velocity provided by the airflow is v. gas .

[0097] like Figure 2G As shown, the DC electric field gradient along the z-axis results in different -v values ​​for ion species with different mobilities. DC Gradient. In the initial accumulation phase of ions, the magnitude of the DC electric field makes -v0 at different positions along the z-axis for each ion species of interest. DC With the velocity component v imparted by the airflow gas Equal and opposite. Due to the different types of ions -v DC Gradient, different types of ions will separate from each other and be trapped at different positions along the z-axis. Different ion types K n-1 K n and K n+1 exist Figure 2G The ions are represented by circles of different sizes. Larger circles correspond to ion species with larger cross-sections and therefore have lower mobilities K.

[0098] After separation of different ion species, ions can be sequentially eluted from the laterally extended TIMS 200 and guided to downstream components or ion detectors of the hybrid IMS-MS system. Elution is accomplished by gradually decreasing the magnitude of the DC electric field gradient, which correspondingly reduces v DC The magnitude of the velocity component gradient, such as Figure 2H As shown, as these gradients decrease, the velocity component v of the reaction... gas and -v DC The canceling points for each different ion species move in the +z direction toward the laterally expanding TIMS 200 outlet. The electric field structure causes the gradient to increase in the +z direction until it reaches the elution point z along the z-axis. p A plateau is reached. Since the ion trapping sites differ for each ion species, shifting these trapping sites by reducing the DC electric field gradient will cause each ion species to reach the elution point z at different times.p Upon reaching the elution point, the ionic substances are no longer captured by the reaction velocity component and leave the laterally expanding TIMS 200 along the +z direction, as shown below. Figure 2H For the K ion species n-1 As shown. In this way, the separated ion species are eluted from the laterally expanded TIMS 200 in order of increasing mobility.

[0099] Figures 3A-3E The illustration shows an alternative embodiment of the invention, wherein the electrode structure 304 includes elongated electrodes above and below the ion region, but does not have the features shown in the original text. Figures 2A-2E The extended portion of the structure. Conversely, lateral electrodes are provided on each side of each elongated electrode to provide ion confinement in the y-axis. This embodiment also uses a housing with an extended width in the y-direction to allow a more consistent airflow through the ion region.

[0100] Figure 3A The laterally extended TIMS 300 of this embodiment is shown, having an ion region 302 with an elongated cross-sectional profile and a platform region 303. As shown, the housing 301 has portions extending further than the electrode structure and ion region 302 on each side in the y-direction. These side regions of the housing accommodate airflow through the housing but not ion travel. One advantage of this configuration is that the airflow through the ion region is relatively uniform in the y-direction because any interruption in the airflow tends to be located within the side portions of the housing, near the edge of the housing in the y-direction. Therefore, in this embodiment, the width of the housing 301 is greater than the width of the ion region 302.

[0101] A separate view of electrode structure 304 Figure 3BAs shown in the diagram, the electrode structure above the ion region includes an elongated electrode 311 (comprising individual electrodes 311-1 to 311-N) and lateral electrodes 313 and 315 (comprising individual lateral electrodes 313-1 to 313-N and 315-1 to 315-N, respectively). Below the ion region are an elongated electrode 312 and lateral electrodes 314 and 316. Those skilled in the art will understand that these electrodes are parallel to electrodes 311, 313, and 315 along the x-direction, respectively, and thus follow the same pattern. Preferably, the electrodes (311, 313, 315) above the ion region are spatially offset along the z-direction relative to the electrodes (312, 314, 316) below the ion region. The electrodes above and below the ion region have a regular relative spacing along the z-direction. However, the z-direction positioning of the electrodes (312, 314, 316) below the ion region is preferably offset from the z-direction positioning of the electrodes (311, 313, 315) above the ion region by a distance equal to half of this relative spacing. In a modified configuration, the electrodes (311, 313, 315) above the ion region have no spatial offset along the z-direction relative to the electrodes (312, 314, 316) below the ion region.

[0102] like Figure 3C As shown, ions are confined in ion region 302 by the potentials on elongated electrodes 311, 312 and lateral electrodes 313, 315, 314 and 316. In a preferred version of this embodiment, two different RF potentials RF1 and RF2 are used, where RF1 is applied to elongated electrode 311 and RF2 is applied to elongated electrode 312. Figure 2D In this embodiment, two opposite phases of the RF signal are used. Figure 3D In the example shown, the first phase of RF1 (RF1+) is applied to every other electrode structure 311, while the opposite phase RF1- (which is 180° out of phase with RF1+) is applied to the other electrode structures 311. Similarly, the first phase of RF2 (RF2+) is applied to every other electrode structure 312, while the opposite phase RF2- is applied to the remaining electrode structures 312.

[0103] like Figure 3EAs shown, a DC potential is also applied to the elongated electrodes of the electrode structure. As illustrated, a DC potential DC311-1 is applied to the first elongated electrode 311 above the ion region, while a DC potential DC311-N is applied to the Nth elongated electrode 311 above the ion region. Similarly, a DC potential DC312-1 is applied to the first elongated electrode 312 below the ion region, and a DC potential DC312-N is applied to the Nth elongated electrode 312 below the ion region. Additional DC potentials are applied to each of the other electrodes in groups 311 and 312. These DC potentials can be used to generate a DC electric field along the z-direction to control ions in the ion region, as will be discussed in more detail below.

[0104] In addition to the DC potentials applied to the elongated electrodes 311 and 312, DC confinement potentials are also applied to the lateral electrodes 313, 315, 314, and 316. Unlike the DC potentials applied to the elongated electrodes, the DC potentials applied to the lateral electrodes are used to confine ions to the ion region in the y-direction. Therefore, although the values ​​of these DC potentials may vary along the z-direction, they are generally arranged in the same z-direction at each electrode location. The DC potential applied to one of the lateral electrodes 313, 315, 314, and 316 preferably has a DC offset compared to the DC potential of its adjacent elongated electrode. The DC offset between the lateral electrode and its corresponding adjacent elongated electrode can be constant or vary along the z-direction.

[0105] One example of this embodiment has the following parameters, but those skilled in the art will understand that this is merely an example and these parameters can vary depending on the application. Figures 2A-2E Similar to the embodiments described above, the operating pressure range of the TIMS can be 10-5000 Pa (0.1-50 mbar), while in this specific example it is approximately 300 Pa (3 mbar). The ion region has a length of 105 mm in the z-direction, a width of 75 mm in the y-direction, and a height of 4 mm in the x-direction. In this configuration, the total number of electrode structures 311, 312 is 70. RF potentials laterally confine the ions in the ion region in the x-direction, where the frequency of RF1 is 1.2 MHz and the frequency of RF2 is 1.8 MHz. However, the confinement in the y-direction is provided by DC potentials applied to the lateral electrodes 313, 315, 314, and 316, for example by constant DC offsets of 1-5 V relative to the corresponding DC potentials DC311 and DC312, respectively. The elongated electrodes are circular rod-shaped electrodes with a diameter of approximately 1.0 mm and a spacing of 1.5 mm from adjacent electrode structures (above and below the ion region). The elongated electrodes are preferably integrated into a printed circuit board (PCB) and provided with DC and RF potentials via leads on the PCB. Finally, the gas flow rate is approximately 100 m / s.

[0106] Figure 4A-4GAlternative embodiments of the invention are shown. The laterally extended TIMS 400 includes a series of electrode structures 404, each electrode structure 404 having a single electrode surrounding the ion region 402 in the x and y directions. (As shown) Figure 4A As shown, the housing 401 extends from the laterally expanding TIMS 400 to the platform region 403 near the outlet, surrounding the electrode structure 404. Each individual electrode 411 is a closed-loop electrode completely surrounding the ion region 402. The electrodes are parallel and equidistant along the z-direction, as shown... Figure 4B As shown, the range extends from the first electrode 411-1 to the Nth electrode 411-N.

[0107] Figure 4C This illustrates how an RF potential is applied to electrode 411. The first phase of the RF potential is applied to every other electrode, while the opposite phase (180° out of phase with the first phase) is applied to the remaining electrodes. This application of alternating phases along electrode series 411 helps confine ions within the ion-producing region. Different DC potentials are also applied to electrode 411, such as... Figure 4D As shown, each DC potential includes a first component, which is constant in time during the accumulation phase and varies during the elution phase, and a second transient component. Therefore, as shown, a potential of DC4111+tDC4111 is applied to electrode 411-1, where DC4111 is the first component and tDC4111 is the transient component. Similarly, DC411... N +tDC411 N A potential is applied to electrode 411-N, where DC411 N It is the first component, tDC411 N This is the transient component. Those skilled in the art will understand that similar combinations of the first DC potential component and the transient DC potential component also apply to other electrodes. The first component is constant in time during the accumulation phase but varies during the elution phase. It is used to generate a DC electric field gradient along the z-axis to control ions in the ion region, as will be discussed in more detail below. The transient DC potential generates a traveling wave (TW) that moves downstream along the z-axis.

[0108] In the laterally extended TIMS 400, the effect of opposing axial forces on ions is as follows: Figure 4E-4G As shown, each figure is a graphical representation of the velocity (or effective velocity component) relative to the position along the z-axis. Figure 4A-4G The difference between this embodiment and the previous embodiment is that there is no gas flow used as an axial force acting on the ions. Instead, a DC potential applied to electrode 411 provides a DC gradient along the z-direction and a traveling wave (TW) field opposite to it. Figure 4E In the example shown, the traveling wave field provides the ions with a substantially constant velocity component (shown as v). TWThis component is opposite to the velocity component generated by the DC gradient field. Because there is residual gas in the housing 401 of the TIMS, the mobility K of each ion will determine its relative position along the z-direction.

[0109] Since the effect of the DC electric field gradient on ions depends on their mobility, therefore, for different ion species K n-1 K n and K n+1 In contrast, the gradients of the velocity components are different, such as Figure 4F As shown. Furthermore, the axial velocity component v is generated by the axial transient DC potential applied to electrode structures 411-1 to 411-N. TW This also depends on the mobility, thus showing different magnitudes of these components for different ion species. During the ion accumulation phase, opposing forces are balanced, resulting in ion trapping, where ion species with different ion mobilities K are trapped at different axial positions within the laterally extended TIMS 400. Because ion species with higher mobilities are less affected by the stagnant gas present in the laterally extended TIMS 400, the equilibrium point between the opposing forces of these ion species is closer to the elution point z. p Meanwhile, ions with lower mobility are captured closer to the laterally extended TIMS 400 inlet.

[0110] The laterally extended TIMS 400 operates at approximately 100 Pa (1 mbar) pressure, with a length of 150 mm, a width of 50 mm, and a height of 4 mm. In this embodiment, ion elution is accomplished by gradually decreasing the amplitude of the DC electric field. This results in ion species being eluted in order of decreasing mobility. Figure 4G As shown, the types with relatively high ion mobility K n+1 Ions exit the laterally extended TIMS 400, while those with lower mobility remain trapped. Ultimately, all ions are eluted and transferred to downstream components of the hybrid IMS-MS system or to the ion detector.

[0111] One example of this embodiment has the following parameters, but those skilled in the art will understand that this is merely an example and these parameters can vary depending on the application. The operating pressure range of the TIMS may be 10-5000 Pa (0.1-50 mbar), while in this specific example it is approximately 100 Pa (1 mbar). The ion region has a length of 150 mm in the z-direction, a width of 50 mm in the y-direction, and a height of 4 mm in the x-direction. In this configuration, 125 electrodes 411 are used in the electrode structure. An RF potential laterally confines the ions within the ion region in both the x and y directions, and the RF frequency is 1.0 MHz. Each electrode 411 is spaced approximately 1.2 mm from adjacent electrodes. The elongated electrodes are preferably integrated into a printed circuit board (PCB) and supplied with DC and RF potentials via leads on the PCB.

[0112] Figures 5A-5F Alternative embodiments of the invention are shown. Figure 5A The laterally extended TIMS 500 shown includes a housing 501 and a series of electrode structures 504. The electrode structures 504 extend from the inlet of the laterally extended TIMS 500 to a platform area 503 near the outlet. Figure 5B As shown, each electrode structure 504 includes a set of electrodes 511. The electrodes of the electrode set 511 together surround the ion region 502 in the x and y directions.

[0113] like Figure 5C As shown, electrode assembly 511 includes small uniform electrodes (511-1 to 511-18) above ion region 502 and small uniform electrodes (511-19 to 511-36) below, wherein the larger electrode 511-37 is located at either end of ion region 502 in the y-direction. Each electrode structure 504 has the same electrode configuration, but different DC potentials can be applied to each of the individual electrodes, i.e., DC potentials can be applied to each small electrode of a single electrode structure. These DC potentials applied to the small electrodes of the electrode structure remain constant over time during the accumulation phase and vary during the elution phase. They are used to generate a DC electric field gradient along the z-direction to control the ions in ion region 502, as will be discussed in more detail below.

[0114] Figure 5CAn example is shown of how additional DC potentials are provided to electrodes (511-1 to 511-37) to laterally confine ions within ion region 502. The electrodes of electrode group 511 are labeled, with smaller electrodes designated as electrodes 511-1 to 511-36 and larger electrodes at the ends designated as electrode 511-37. Thus, in this example, there are eighteen smaller electrodes above and eighteen smaller electrodes below the ion region. Each smaller electrode (511-1 to 511-36) is marked with a "+" or "-", indicating that additional DC potentials are applied to the smaller electrode that are highly repulsive (+) or less repulsive (-) to ions in the ion region. These additional DC potentials on the smaller electrodes 511-1 to 511-36 change dynamically according to a predetermined sequence, while the DC potential applied to the larger electrode 511-37 remains repulsive. The variation of the additional DC potential on the small electrodes simulates the rotation of these potentials around the electrode assembly 511 in the direction indicated by the dashed arrow. That is, in each progressive time interval, the small electrodes are given the additional DC potential applied to the adjacent small electrodes in the previous time interval in the direction opposite to the arrow. Thus, the high and low additional potentials rotate around the electrode structure over time. The rotation of the additional DC potentials on the electrode structure provides a lateral confinement force in the x-direction to the interior of the electrode assembly 511 for ions within the ion region 502 portion, while the additional DC potential applied to the large electrodes provides a lateral confinement force in the y-direction.

[0115] In the laterally extended TIMS 500, the effect of opposing axial forces on ions is as follows: Figure 5D-5F As shown, each graph is a diagram of the velocity (or effective velocity component) relative to its position along the z-axis. Figure 5D As shown, the DC electric field gradient generated by the DC potential individually applied along the z-direction to each electrode structure 504 is opposite to the constant gas flow, thereby establishing the desired accumulation and separation of ions along the z-direction by mobility. These individual DC potentials can then be altered to reduce the DC electric field gradient, allowing ionic material to be eluted from the laterally extended TIMS 500 by mobility, as... Figure 5E and 5F As shown, it is equivalent to the explanation above. Figures 2F to 2H Ultimately, all ion species are eluted and transferred to downstream components or ion detectors of the hybrid IMS-MS system. During the accumulation and elution phases, an additional DC potential applied to the small electrode and a repulsive DC potential applied to the large electrode are kept rotating, providing the necessary lateral confinement.

[0116] The example of the laterally extended TIMS 500 operates at a pressure of approximately 20,000 Pa (200 mbar) and has a length of 50 mm, a width of 50 mm, and a height of 5 mm. However, those skilled in the art will understand that this is merely an example, and the parameters can vary depending on the application. In this form, fifty electrode structures 504 are used, each consisting of thirty-six small electrodes and two end electrodes. An additional DC potential on the small electrode assembly varies between a repulsive potential value (+V) and zero volts (-V), laterally confining ions to the ion region in the x-direction. The repulsive potential value is less than 500 V. The DC potential on the large electrode has a DC offset relative to the DC potential applied to the small electrodes to generate a DC electric field gradient, and laterally confining ions to the ion region in the y-direction. The “rotational” speed of the DC voltage potential around each electrode can be as high as 2000 m / s, depending on the operating pressure. The electrodes are preferably integrated into one or more printed circuit boards (PCBs) and DC potentials are applied via leads on the PCB. Finally, the airflow velocity is between 5 and 20 m / s.

[0117] Figure 6A -F illustrates an alternative embodiment of the invention. Figure 6A The laterally extended TIMS 600 shown includes a housing 601 and a series of electrode structures 604. The electrode structures 604 extend from the inlet of the laterally extended TIMS 600 to a platform region 603 near the outlet. Figure 6B As shown, each electrode structure 604 includes a set of electrodes 611. The electrodes of the electrode set 611 collectively surround the ion region in the x and y directions.

[0118] Figures 6A to 6F The embodiment shown differs from the previous embodiment in that, within the ion region, ions are organized along the y-direction into a series of separate ion channels 602-i. For example... Figure 6CAs shown, electrode assembly 611 provides electrodes 611-1 to 611-7 above ion channel 602-i and electrodes 611-8 to 611-14 below ion channel 602-i, wherein opposite phases of the RF potential are applied to electrodes 611-1 to 611-14 in an alternating manner. Thus, the first electrode assembly (611-1) is applied with a potential -RF, while adjacent electrodes 611-2 and 611-14 are provided with an antiphase +RF (which is 180° out of phase with -RF). This alternating application of the RF potential continues around the circumference of electrode assembly 611, confining ions in the ion region to different ion channels 602-i. Each electrode structure is applied with the same RF potential such that ion channel 602-i continues along the z-direction. In this way, the laterally extended TIMS 600 serves as an aggregation of multiple parallel TIMS, each represented by a different ion channel. Different DC potentials are applied to different corresponding electrode structures 604, although all electrodes of a single electrode structure are subjected to a common DC potential. These DC potentials applied to electrode structures 604 are constant over time during the accumulation phase and vary during the elution phase. They are used to generate a DC electric field gradient along the z-direction to control ions in the ion region, as will be discussed in more detail below.

[0119] In the laterally extended TIMS 600, the effect of opposing axial forces on ions is as follows: Figure 6D-6F As shown, each graph is a diagram of the velocity (or effective velocity component) relative to the position along the z-axis. In this embodiment, the axial force is provided by opposing airflow and a DC electric field gradient. Figure 6D As shown, in this embodiment, the gas flow is directed along the z-axis in the z-direction, opposite to the ion travel direction, and has a constant gas velocity along the z-axis. A DC electric field gradient is generated by a DC potential applied to the electrode structure 604. The intensity of the DC electric field gradient decreases along the z-axis until it reaches the plateau region 603 (at z = zp). This causes ions in each channel to separate in the z-direction by mobility from low to high. Figure 6E and 6F As shown, a DC electric field gradient is then added at the platform region 603, which causes the ions to gradually overcome the opposing force of the airflow and elute from the laterally expanding TIMS 600 in order of decreasing mobility.

[0120] In this example embodiment, a single RF frequency is applied synchronously to all electrodes of electrode structure 604 in the same manner to establish separate ion channels and trapping regions along the x and y directions. The operating pressure can range from 10 to 5000 Pa (0.1 to 50 mbar), typically around 300 Pa (3 mbar). The ion region is 50 mm long, 50 mm wide, and 4 mm high. In this configuration, there are fifty different electrode structures spaced 1 mm apart. The RF frequency is 1 MHz, and the gas flow rate is approximately 100 m / s.

[0121] Figure 7 A laterally extended TIMS 700 is illustrated, such as those discussed above with an upstream ion funnel 710 and a downstream ion funnel 720. In this arrangement, ions (e.g., from an ion source) are guided into the ion funnel 710, which, as shown in the adjacent cross-sectional illustration, maintains the width of the ion region in the y-direction while gradually decreasing in the x-dimensional. The ion region 702 is the separating portion of the laterally extended TIMS 700 and has a laterally extended shape, allowing for the simultaneous processing of ions that expand in the long dimension. As described above, ions are separated in the ion region 702 and eluted sequentially by ion mobility, exiting the plateau region 703 into a second ion funnel 720 with a decreasing profile in the y-direction. This concentrates the separated, eluted ion species into a smaller profile at the outlet of the ion funnel 720.

[0122] Figure 8 A laterally extended TIMS 800 is illustrated, comprising an upstream ion funnel 810, an ion trap 830, and a downstream ion funnel 820. The ion region 802 is a separation portion of the laterally extended TIMS 800. As in the embodiments described above, ions (e.g., from an ion source) are guided into the ion funnel 810, which, as shown in the adjacent cross-sectional illustration, maintains the width of the ion region in the y-direction while gradually decreasing the x-dimensional dimension. The ion funnel 810 guides ions into the ion trap 830, which has a laterally extended profile, to allow ion accumulation, while the pre-accumulated ions are separated in parallel by mobility within the ion region 802 of the laterally extended TIMS 800, which may utilize one of the embodiments discussed above. Following the accumulation stage, ions from the ion trap 830 are introduced into the ion region 802, separated by mobility within the ion region 802, and then sequentially eluted onto the platform region 803 into the exit funnel 820, which tapers gradually in the y-direction to concentrate the departing ions into an exit channel with a smaller profile. Preferably, the volume of the ion trap 830 is at least as large as the volume of the ion region 802; more preferably, the width and height of the ion trap 830 are equal to the width and height of the ion region 802.

[0123] Figure 9 A laterally extended TIMS 900 is shown, comprising an upstream ion funnel 910 and a downstream ion funnel 920, wherein the upstream ion funnel 910 gradually narrows in the y-direction toward the inlet of ion region 902. Ion region 902 is the separation portion of the laterally extended TIMS 900. However, in this configuration, ion region 902 itself also gradually narrows in the y-direction, such that as ions are separated by ion mobility, they also concentrate in the y-direction into a plateau region 903 with a decreasing profile in its long dimension. This narrowing profile continues in the downstream ion funnel 920 after the plateau region 903, causing ions to exit into an outlet channel with a smaller profile.

[0124] Figure 10 A laterally extended TIMS 1000 with an upstream ion funnel 1010 is shown. The ion region 1002 is a separate portion of the laterally extended TIMS 1000. In this configuration, both the ion funnel 1010 and the ion region 1002 gradually narrow in the y-direction. However, compared to… Figure 9 The configuration scheme differs; before the ions reach the platform region 1003, the cone shape of the ion region 1002 reaches a final reduced cross-section in the x and y directions. From here, the ions are eluted sequentially according to ion type to any downstream location.

[0125] Figure 11 A laterally extended TIMS 1100 with an upstream ion funnel 1110 is shown. The ion region 1102 is a separate portion of the laterally extended TIMS 1100. In this configuration, the upstream funnel 1110 gradually narrows in the x-direction from a circular cross-section to an elliptical outlet into the ion region. The ion region 1102 and the plateau region 1103 also have decreasing profiles, from an elongated elliptical shape at the inlet of the ion region 1102 to a more concentrated output profile in the plateau region 1103.

[0126] Figure 12 A laterally extended TIMS 1200 is shown, with its ion region 1202 having a non-convex cross-sectional profile. The ion region 1202 of the laterally extended TIMS has an annular cross-sectional profile created by the electrode structure and housing of the laterally extended TIMS 1200. The long dimension 1240 is along a closed path within the annular space, and the short dimension 1250 is along the radial direction between the outer and inner radii of the annular space. As described above, ions are separated by ion mobility and eluted from the platform region 120, and can be redirected as needed at the outlet of the laterally extended TIMS 1200. The advantage of the non-convex cross-sectional profile is that the influence of one charge on another is reduced, thus enhancing the charge capacity of the TIMS.

[0127] Figure 13 Another example of a laterally extended TIMS 1300 is shown, where the ion region 1302 has a non-convex cross-sectional profile. In this form, the ion region 1302 has a generally arcuate cross-sectional profile. Therefore, the extended ion region is not linear, or parallel to the y-axis, but extends laterally along the arc, thus similarly allowing the separation of a larger volume of ions by ion mobility. The longer dimension 1340 is along an azimuthal path within the arcuate space, and the shorter dimension 1350 is along a radial direction between the outer and inner arcs. In a modified embodiment, the azimuthal range of the cross-sectional profile (the length of the arcuate space) can be reduced along the axis of the laterally extended TIMS, which reduces conductivity and therefore the pumping capacity required to generate the gas flow.

[0128] Similar to Figure 13 The arrangement Figure 14 Another example of a laterally extended TIMS 1400 is shown, where the ion region 1402 has a non-convex cross-sectional profile. Here, the cross-sectional profile is meandering, so ions are distributed along several arcuate portions of the ion region 1402. The long dimension 1440 runs along the meandering shape inside the ion region 1402, while the short dimension 1450 runs radially between the outer and inner arcs. After separation and elution from the platform region 1403, ions can be collected and transported as needed.

Claims

1. A trapping ion mobility separator, comprising: an ion region through which ions travel along an axis from an inlet to an outlet, the ion region containing a gas through which the ions pass and having an elongated cross-sectional profile perpendicular to the axis, the cross-sectional profile having a long dimension and a short dimension; a series of electrode structures arranged along the axis and enclosing the elongated cross-sectional profile at least along the long dimension, each electrode structure comprising one electrode or one set of electrodes to which one or more varying voltage potentials are applied to generate a first confining electric field that exerts a confining force on the ions in the ion region with respect to the short dimension; a first force generator applying a first axial force along the axis on the ions and a second force generator applying a second axial force along the axis on the ions, wherein the second axial force acts opposite to the first axial force; wherein at least one of the first and second axial forces has an ion mobility dependent influence on the ions, and wherein at least one of the first and second axial forces spatially varies along the axis such that ions are trapped and separated along the axis by ion mobility during an accumulation phase, and wherein the first and / or second force generator is configured to change the magnitude of the first force relative to the second force over time during an elution phase such that ions are progressively driven to the outlet as a function of ion mobility, wherein each electrode structure comprises elongated electrodes extending parallel to the long dimension, wherein the elongated electrodes are positioned on a first side and a second side of the ion region, respectively, in an alternating arrangement along the axis with respect to the short dimension, opposite phases of a first RF voltage being applied to adjacent elongated electrodes on the first side and opposite phases of a second RF voltage being applied to adjacent elongated electrodes on the second side to generate the first confining electric field, and wherein the first RF voltage and the second RF voltage have different frequencies, and wherein the relative spacing of the elongated electrodes of the first side is equal to the relative spacing of the elongated electrodes of the second side, wherein the positioning of the elongated electrodes of the second side is offset by half the relative spacing along the axis with respect to the elongated electrodes of the first side.

2. The trapping ion mobility separator of claim 1, wherein the first axial force and the second axial force are different respective types generated by one of an axial gas flow, an axial direct current electric field and an axial transient direct current electric field, respectively.

3. The trapping ion mobility separator of claim 2, wherein a direct current potential or a transient direct current potential is applied to the electrode structures to generate the axial direct current electric field or the axial transient direct current electric field, respectively.

4. The trapping ion mobility separator of claim 1, wherein the spatially varying at least one of the first and second axial forces along the axis comprises a gradient along a first portion that flattens to a plateau of substantially constant force.

5. The trapping ion mobility separator of claim 4, wherein the ions in the ion region extend substantially parallel to the plateau near the plateau.

6. The trapped ion mobility separator of claim 4, wherein the first or second axial force is a gas flow having a substantially constant velocity in the ion region near the plate along the long dimension.

7. The trapped ion mobility separator of claim 1, wherein a varying voltage potential applied to an electrode or set of electrodes produces a second confining electric field that exerts a confining force on ions in the ion region with respect to the long dimension.

8. The trapped ion mobility separator of claim 1, wherein additional electrodes are included at one or both sides of the ion region in the long dimension, with RF or DC potentials applied to the additional electrodes to produce a second confining electric field that exerts a confining force on ions in the ion region with respect to the long dimension.

9. The trapped ion mobility separator of claim 1, wherein the elongated electrodes have extensions in the short dimension at each end with respect to the long dimension, such that an RF potential applied to the elongated electrodes produces a second confining electric field that exerts a confining force on ions in the ion region with respect to the long dimension.

10. The trapped ion mobility separator of claim 1, wherein a ratio H / S between a height H of the ion region in the short dimension direction and a spacing S of the elongated electrodes is less than ten.

11. The trapped ion mobility separator of claim 1, further having an ion trap located upstream of the ion region.

12. A method of analyzing ions by mobility using a trapped ion mobility separator, the method comprising the steps of: - providing an ion region through which ions pass along an axis from an inlet to an outlet, the ion region containing a gas through which the ions pass, and having an elongated cross-sectional profile perpendicular to the axis, the profile having a long dimension and a short dimension; - providing a series of electrode structures arranged along the axis and enclosing the elongated cross-sectional profile at least along the long dimension, each electrode structure comprising an electrode or a set of electrodes, wherein each electrode structure comprises an elongated electrode extending parallel to the long dimension, wherein the elongated electrodes on a first side and a second side of the ion region are respectively positioned in an alternating arrangement along the axis with respect to the short dimension, and wherein the relative spacing of the elongated electrodes on the first side is equal to the relative spacing of the elongated electrodes on the second side, wherein the positioning of the elongated electrodes on the second side is offset along the axis by a distance of half the relative spacing with respect to the elongated electrodes on the first side; - producing a first confining electric field by applying a varying voltage potential to the electrodes or sets of electrodes, the first confining electric field exerting a confining force on ions in the ion region with respect to the short dimension; - producing a first axial force applied to the ions along the axis; - producing a second axial force applied to the ions along the axis and opposing the first force, wherein at least one of the first and second axial forces varies spatially along the first axis such that the ions are trapped and separated by ion mobility along the axis; and - detecting the ions. - changing at least one of the first and second axial forces to increase the magnitude of the first axial force relative to the second force over time, such that ions are progressively driven to the exit of the ion region and separated as a function of ion mobility, - opposite phases of a first RF voltage are applied to adjacent elongated electrodes on a first side, and opposite phases of a second RF voltage are applied to adjacent elongated electrodes on a second side, wherein the first and second RF voltages have different frequencies.

13. The method of claim 12, further comprising generating a second confinement electric field by applying a varying voltage potential to an electrode or group of electrodes and / or by applying an RF potential or a direct current potential to an additional electrode, the second confinement electric field exerting a confinement force on ions in the ion region with respect to the long dimension.

14. The method of claim 12, wherein the first and second axial forces are different respective types, generated by one of an axial gas flow, an axial direct current electric field, and an axial transient direct current electric field.

15. The method of claim 12, wherein a direct current potential or a transient direct current potential is applied to an electrode structure to generate an axial direct current electric field or an axial transient direct current electric field, respectively.

16. The method of claim 12, further comprising analyzing the separated ions as a function of mass in a mass analyzer located downstream of the trapped ion mobility separator.

17. The method of claim 12, further comprising fragmenting the separated ions into fragment ions, and analyzing the fragment ions in a mass analyzer located downstream of the trapped ion mobility separator.

18. The method of claim 17, wherein the separated ions are selected and / or filtered according to mass prior to fragmentation.

19. The method of claim 12, further comprising accumulating ions from an ion source in an ion trap located upstream of the trapped ion mobility separator while analyzing ions in the trapped ion mobility separator.

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