LATERALLY EXTENDED STORAGE ION MOBILITY SPECTROMETER

Abstract

A storage ion mobility separator (100; 200; 300; 700; 800; 900; 1000; 1100; 1200; 1300; 1400) comprising the following: an ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) through which ions (102) move along an axis (z) from an input to an output, wherein the ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) contains a gas through which the ions (102) move, and has an elongated cross-sectional profile perpendicular to the axis (z) with a long dimension (1240; 1340; 1440) and a short dimension (1250; 1350; 1450); a series of electrode structures (211, 212; 304) arranged along the axis (z) and enclosing the elongated cross-sectional profile at least along the long dimension (1240; 1340; 1440), each electrode structure (211, 212; 304) comprising an electrode (211a, 212a, 311-316) or an electrode set (204) to which one or more varying voltage potentials (RF1, RF2) are applied to generate a first electric confinement field that exerts a confinement force on the ions (102) in the ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) relative to the short dimension (1250; 1350; 1450) exercises; a first force generator that exerts a first axial force on the ions (102) along the axis (z); and a second force generator that exerts a second axial force on the ions (102) along the axis (z), which counteracts the first axial force; wherein at least one of the axial forces has an effect on the ions (102) which depends on the ion mobility, and wherein at least one of the axial forces varies spatially along the axis (z) such that ions (102) are stored and separated during an accumulation phase depending on their ion mobility along the axis (z), and wherein the first and / or the second force generator is configured to vary the magnitude of the first force relative to the second force over time during an elution phase such that the ions (102) are progressively driven towards the outlet depending on their ion mobility, wherein each electrode assembly (211, 212; 304) comprises an elongated electrode (211a, 212a; 311, 312) extending parallel to the long dimension (1240; 1340; 1440), and wherein the elongated electrodes (211a, 212a; 311, 312) are arranged on a first and second side of the ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) relative to the short dimension (1250; 1350; 1450) in an alternating arrangement along the axis (z), wherein opposite phases (RF1+, RF1-) of a first RF voltage (RF1) are applied to adjacent elongated electrodes (211a, 212a; 311, 312) are applied to the first side and opposite phases (RF1+, RF1-) of a second RF voltage (RF2) are applied to adjacent elongated electrodes (211a, 212a; 311, 312) of the second side, and wherein the elongated electrodes (211a, 212a; 311, 312) of the first side have a distance equal to the distance between the elongated electrodes (211a, 212a; 311, 312) of the second side, characterized by that the first RF voltage (RF1) and the second RF voltage (RF2) have different frequencies, and that the elongated electrodes (211a, 212a; 311, 312) of the second side are offset relative to the elongated electrodes (211a, 212a; 311, 312) of the first side along the axis (z) by half the distance.

Description

Field of invention

[0001] The invention relates to methods and equipment for ion mobility spectrometry, in particular storage ion mobility spectrometry, as well as hybrid systems that use ion mobility spectrometry and mass spectrometry. State of the art

[0002] Ion mobility spectrometry (IMS) is an analytical technique used to investigate the mobility of ions in a gas and to separate these ions according to their mobility. A key feature of IMS is that ion mobility in a gas depends on the molecular geometry of the ions. This often allows for the differentiation and separation of isomers or conformational isomers that cannot be distinguished by mass spectrometry. Many applications also utilize the ability to determine the cross section of an analyte from its measured mobility. Knowledge of mobilities or cross sections has proven important in many fields, including analyte identification (e.g., in proteomics and metabolomics), the separation of substance classes, and the determination of molecular structures (e.g., in structural biology).

[0003] In trapped ion mobility spectrometry (TIMS), ions are trapped along an inhomogeneous DC electric field, typically an electric field gradient, by an opposing gas flow, or along a homogeneous DC electric field by an opposing gas flow exhibiting a non-uniform axial velocity profile. The trapped ions are spatially separated according to their mobility. Subsequently, they are eluted over time according to their mobility, either by adjusting the gas velocity or the strength of the axially oriented DC electric field (see, e.g., US Patents 6,630,662 B1 (Loboda) and 7,838,826 B1 (Park)). The theoretical basis of TIMS can also be found in the article "Fundamentals of Trapped Ion Mobility Spectrometry" by Michelmann et al. (J. Am. Soc. Mass Spectrom.)., 2015, 26, 14-24).

[0004] US patent US 9,683,964 B2 (Park et al.) describes a TIMS analyzer with a storage and a separation area for parallel accumulation. The TIMS analyzer accumulates ions in the storage area while, simultaneously, previously accumulated ions are analyzed in the separation area. A gas flow drives the ions against a ramp of an opposing DC electric field barrier in the storage area, causing the ions to be stored axially and separated at points along the ramp according to their mobility. During the accumulation of ions in the storage area, the gas flow also drives ions that were accumulated in a previous accumulation and transferred to the separation area against a ramp of an opposing DC electric field barrier in the separation area, causing the ions to be stored axially and separated spatially according to their mobility.After the separation area is loaded with ions to be analyzed, the height of the opposing DC electric field barrier is continuously reduced, so that ion species are released from the separation area in order of their mobility.

[0005] US patent US 10 458 944 B2 (Park et al.) teaches the use of higher-order linear multipole RF systems (order N > 2) for the accumulation and analysis of ions at a DC electric field barrier of a TIMS analyzer, either pure higher-order RF multipole systems or multipole RF systems with higher-order to lower-order transitions before the vertex of the DC electric field barrier.

[0006] Despite the fact that ions accumulate at spatially separated positions according to their mobility and using higher-order fields, there remains a need for higher storage capacity in TIMS analyzers without significant ion losses due to space charge effects. Higher storage capacity increases sensitivity and enables the analysis and identification of more low-abundance analytes, particularly in complex samples such as those encountered in bottom-up proteomics or metabolomics.

[0007] US Patent 2019 / 0164737 A1 describes an apparatus for analyzing ion mobility. One design proposes creating a drift zone between two electrode arrays. This drift zone is larger in a lateral direction (z) than in a vertical direction (y) and extends along a longitudinal direction (x) corresponding to the direction of gas flow. Each electrode array comprises strip electrodes arranged in an xz-plane and aligned along the lateral direction (z). The strip electrodes of the arrays are aligned. The electrode arrays are designed to apply RF voltages with different phases to adjacent electrodes.

[0008] US Patent 2019 / 0237319 A1 describes an ion separator for ion mobility spectroscopy. Electrodes with an aperture are proposed such that the ions are radially enclosed by the electrodes. Adjacent electrodes can be subjected to opposite phases of an RF voltage. The aperture can be elongated in a transverse direction, e.g., rectangular or oval. Brief description of the invention

[0009] In a first aspect, the present invention provides a storage ion mobility separator (TIMS) comprising an ion region through which ions move along an axis from an input to an output, a series of electrode structures, a first force generator exerting a first axial force on the ions along the axis, and a second force generator exerting a second axial force on the ions along the axis, which opposes the first axial force, wherein at least one of the axial forces has an effect on the ions that depends on the ion mobility, and wherein at least one of the axial forces varies spatially along the axis so that ions are stored and separated during an accumulation phase according to their ion mobility along the axis, and wherein the first and / or the second force generator is configured such thatthat it varies the magnitude of the first force relative to the second force over time during an elution phase, such that the ions are progressively driven towards the output depending on their ion mobility, wherein each electrode assembly comprises an elongated electrode extending parallel to the long dimension, and wherein the elongated electrodes on a first and second side of the ion region are arranged in an alternating arrangement along the axis relative to the short dimension, wherein opposite phases of a first RF voltage are applied to adjacent elongated electrodes on the first side and opposite phases of a second RF voltage are applied to adjacent elongated electrodes of the second side, wherein the elongated electrodes of the first side are spaced at a distance equal to the distance between the elongated electrodes of the second side, and wherein the first RF voltage and the second RF voltage have different frequencies.and wherein the elongated electrodes of the second side are offset relative to the elongated electrodes of the first side along the axis by half the distance.

[0010] The ion region contains a gas through which the ions move and has an elongated cross-sectional profile perpendicular to the axis, with a long and a short dimension. The TIMS according to the present invention is referred to as a laterally extended TIMS (LXTIMS, laterally extended TIMS). The series of electrode structures is arranged along the axis and encloses the elongated cross-sectional profile at least along the aforementioned long dimension, each electrode structure comprising an electrode or a set of electrodes to which one or more varying voltage potentials are applied to generate a first electric confinement field that exerts a confinement force on the ions in the ion region relative to the aforementioned short dimension. The laterally extended TIMS includes means for generating the varying voltage potentials, e.g., RF generators.

[0011] The ratio W:H between the width W of the ionic region along the long dimension and the height H of the ionic region along the short dimension is preferably greater than 2, more preferably greater than 5, and can even be greater than 10. The width W of the ionic region along the long dimension is preferably greater than 20 mm, more preferably greater than 50 mm, and can even be greater than 100 mm. The length L of the ionic region along the axis is preferably greater than 50 mm, more preferably greater than 100 mm, and can even be greater than 200 mm. The ratio L:W between the length L of the ionic region along the axis and the width W of the ionic region along the long dimension is preferably less than 5, more preferably less than 2, and can even be less than 1. The ratio L:W is most preferably between 1.5 and 3.

[0012] A major advantage of laterally extended TIMS compared to conventional TIMS devices is that the ions are not stored along a line, but in an extended volume that is significantly elongated in a lateral direction, thus significantly increasing the charge capacity without affecting the mobility resolution.

[0013] The elongated cross-sectional profile is preferably convex, meaning that for any two points within the cross-sectional profile, all points along a line segment between the two points also lie within the cross-sectional profile. Furthermore, the elongated cross-sectional profile is preferably mirror-symmetric about a plane containing the axis and the long dimension. However, the cross-sectional profile can also be non-convex, e.g., horseshoe-shaped, serpentine, or like the space between a closed outer surface and a closed inner surface, such as a ring. The closed outer surface can, for example, be a circle oriented coaxially with an inner circle. In the case of a closed outer surface enclosing a closed inner surface, the long dimension is a closed path between the surfaces, and the short dimension is the shortest path between the surfaces.The elongated cross-sectional profile can be constant or vary along the axis.

[0014] The electrode array can partially enclose the elongated cross-sectional profile of the ion region, e.g., only along the aforementioned long dimension, or completely. The varying voltage potential applied to the electrode or electrode array can generate a second electrical confinement field that exerts a confinement force on the ions within the ion region relative to the aforementioned long dimension. The laterally extended TIMS can also include additional electrodes on one or both sides of the ion region along the long dimension, to which RF or DC voltage potentials are applied to generate a second electrical confinement field that exerts a confinement force on the ions within the ion region relative to the aforementioned long dimension.The first and second electrical confinement fields can generate a continuously expanding storage area along said long dimension or several separate storage areas along said long dimension.

[0015] According to the invention, each electrode assembly comprises an elongated electrode extending parallel to the long dimension, wherein the elongated electrodes are located on a first and a second side of the ion region relative to the short dimension in an alternating arrangement along the axis, wherein opposite phases of a first RF voltage are applied to adjacent elongated electrodes on the first side and opposite phases of a second RF voltage are applied to adjacent elongated electrodes of the second side.

[0016] According to the invention, the first and second RF voltages have different frequencies. The two frequencies preferably vary by more than 10%, more preferably by more than 20%, and most preferably by more than 50%. The ratio between the two frequencies f1 and f2 is preferably not an integer, e.g., f1:f2 = 1.2:0.86 or 1.8:1.2, in order to minimize possible resonance excitation of the ion motion. The average frequency is preferably between 0.5 and 10 MHz, and more preferably at 1 MHz. The operating pressure is preferably less than 5,000 Pa, more preferably less than 1,000 Pa, and typically lies between 200 and 700 Pa.

[0017] According to the invention, the elongated electrodes of the first side are spaced apart at a distance equal to the distance between the elongated electrodes of the second side, wherein the elongated electrodes of the second side are offset along the axis relative to the elongated electrodes of the first side by half this distance. The ratio H:S between the height H of the ion region along the short dimension and the distance S between the elongated electrodes is preferably less than 10, more preferably less than 5, and most preferably less than 3, at least for a subset of the electrodes.

[0018] The elongated electrodes preferably have at each end, relative to said long dimension, an extended section in the short dimension, such that RF potentials applied to the elongated electrodes generate a second electric confinement field that exerts a confinement force on ions in the ionic region relative to the long dimension. In a particularly preferred manner, the elongated electrodes each comprise a cylindrical section in the long dimension, wherein the extended section at each end has a flat shape with a curved edge facing the ionic region.The electrode structures of the first embodiment can, instead of the extended sections of the elongated electrodes, include DC voltage electrodes that adjoin the ends of the elongated electrodes relative to the said long dimension and to which DC voltage potentials are applied, generating a second electric confinement field that exerts a confinement force on ions in the ion region relative to the said long dimension.

[0019] The first and second axial forces of a laterally extended TIMS are of different types, with each potentially being generated by an axial gas flow, an axial DC electric field, or an axial transient DC electric field. DC electric potentials or transient DC electric potentials are preferably applied to the electrode structures to generate the axial DC electric field or the axial transient DC electric field, respectively.If the opposing forces are a gas flow and an axial DC electric field, and the velocity of the gas flow and the field strength vary along the axis, the spatial variation of the field strength along the axis can be adjusted so that the volume occupied by ion species with different ion mobilities along the axis is the same when stored in the laterally extended TIMS.

[0020] At least one of the first and second axial forces, which varies spatially along the axis, preferably includes a gradient along a first section that flattens to a plateau with substantially constant force.

[0021] The first or second axial force of a laterally extended TIMS can be a gas flow, and the system preferably includes a housing that surrounds the electrode structures and directs the gas flow. Near the plateau of the first or second axial force, the gas flow preferably has a substantially constant velocity in the ion region along said long dimension. Substantially constant means that the gas velocity along the long dimension preferably varies by less than 50%, and more preferably by less than 20%, compared to the maximum gas velocity. The housing can be approximately the same size as the ion region along said short dimension, but can extend significantly further than the ion region along said long dimension.The ratio L:W between the length L of the ion chamber along the axis and the width W of the ion chamber along the long dimension can be less than 2, less than 1, and even less than 1 / 2. The gas flow can be generated either by pumping gas out of an inlet or outlet of the ion chamber, by introducing gas laterally into the ion chamber, or by both.

[0022] The laterally extended TIMS can 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 to focus ions into the ion region's input, and / or an ion funnel located downstream of the ion region to spatially focus ions released at the ion region's output. The ion trap can be, for example, a linear multipole RF ion trap, an axially segmented linear multipole ion trap, or a ring electrode ion trap, and it can include means for generating and controlling an axial DC electric field along its axis. The ion trap can also be a second, laterally extended TIMS used to store ions at mobility-dependent positions along the ion trap's axis.

[0023] In another embodiment, the ion trap is arranged adjacent to the ion region, coaxially to the axis of the laterally extended TIMS. An ion trap adjacent to the ion region preferably has substantially the same width and height as the ion region itself. In another preferred embodiment, an 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.

[0024] 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, by spray ionization (e.g., electro-ionization (ESI) or thermal spraying), desorption ionization (e.g., matrix-assisted laser desorption (MALDI) or secondary ionization), chemical ionization (CI), photoionization (PI), electron impact ionization (EI), or gas discharge ionization. The mass analyzer of the hybrid system can be, for example, a time-of-flight mass analyzer (preferably with orthogonal ion injection), an electrostatic ion trap, a radiofrequency (RF) ion trap, an ion cyclotron frequency (ICF) ion trap, or a quadrupole mass filter.

[0025] The hybrid system can further include a fragmentation cell located between the laterally extended TIMS and the mass analyzer. Within the fragmentation cell, ions can be fragmented, for example, by collision-induced dissociation (CID), surface-induced dissociation (SID), photo-dissociation (PD), electron capture dissociation (ECD), electron transfer dissociation (ETD), collision activation after electron transfer dissociation (ETcD), activation concurrent with electron transfer dissociation (AI-ETD), or fragmentation by reactions with highly excited or radical-neutral particles. The hybrid system can also include a mass filter located between the laterally extended TIMS and the fragmentation cell.

[0026] The hybrid system can comprise an upstream mass filter and / or a upstream fragmentation cell, and further ion mobility separators, preferably a TIMS and, in a particularly preferred manner, a laterally extended TIMS. The hybrid system can comprise two laterally extended TIMS, between which an activation cell and / or a fragmentation cell is located. The two laterally extended TIMS can be operated as a tandem ion mobility spectrometer within the hybrid system. Preferably, an ion gate is located between the upstream laterally extended TIMS and the activation or fragmentation cell. The two laterally extended TIMS are preferably arranged non-coaxially, preferably orthogonally, and each comprises an upstream ion trap.Furthermore, a separation device, such as a gas or liquid chromatography apparatus or an electrophoretic device, can be part of the hybrid system or coupled to it.

[0027] In a second aspect, the present invention provides a method for analyzing ions according to their mobility using a storage ion mobility separator. The method comprises the following steps: - Providing an ionic region through which ions move along an axis from an inlet to an outlet, wherein the ionic region contains a gas through which the ions move and has an elongated cross-sectional profile perpendicular to the axis with 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 said long dimension, each electrode structure comprising an electrode or a set of electrodes; - Generating a first electric confinement field that exerts a confinement force on the ions in the ion region relative to said short dimension by applying a varying voltage potential to the electrodes or electrode set; - Generating an initial axial force that is transferred to the ions along the axis; - Generating a second axial force that is transferred to the ions along the axis and that opposes the first force, wherein at least one of the axial forces varies spatially along the axis so that ions are stored and separated depending on their ion mobility along the axis; - Vary at least one of the axial forces to increase the magnitude of the first axial force relative to the second force over time, so that the ions are progressively driven towards the exit of the ion region and separated depending on the ion mobility, wherein each electrode assembly comprises an elongated electrode extending parallel to the long dimension, and wherein the elongated electrodes on a first and second side of the ion region are arranged in an alternating arrangement along the axis relative to the short dimension, wherein opposite phases of a first RF voltage are applied to adjacent elongated electrodes on the first side and opposite phases of a second RF voltage are applied to adjacent elongated electrodes of the second side, wherein the elongated electrodes of the first side have a distance equal to the distance between the elongated electrodes of the second side, where the first RF voltage and the second RF voltage have different frequencies, and wherein the elongated electrodes of the second side are offset relative to the elongated electrodes of the first side along the axis by half the distance.

[0028] The method further includes the generation of a second electric confinement field, which exerts a confinement force on the ions in the ion region relative to the said long dimension, by applying the varying voltage potential to the electrodes or electrode set and / or by applying RF potentials or DC voltage potentials to additional electrodes.

[0029] The first axial force and the second axial force are of different types, each of which can be generated by an axial gas flow, an axial DC electric field, or an axial transient DC electric field. DC electric potentials or transient DC electric potentials can be applied to the electrode structures to generate the axial DC electric field or the axial transient DC electric field, respectively.

[0030] The ions can be generated in an ion source from the molecular components of a sample by spray ionization (e.g., electrochemical ionization (ESI) or thermal spraying), desorption ionization (e.g., matrix-assisted laser desorption / desorption ionization (MALDI) or secondary ionization), chemical ionization (CI), photoionization (PI), electron impact ionization (EI), or gas discharge ionization. Furthermore, the analytes can be separated by a separation device, such as a gas or liquid chromatography apparatus or an electrophoretic apparatus, coupled to the ion source.

[0031] The method further includes the accumulation of ions from an ion source in an ion trap located upstream of the laterally extended storage ion mobility separator, while the ions in the laterally extended storage ion mobility separator are analyzed.

[0032] The method can further include the detection of separated ions with an ion detector or the analysis of separated ions as a function of mass in a mass analyzer located downstream of the storage ion mobility separator. Separated ions can be fragmented into fragment ions, and the fragment ions can be analyzed in a mass analyzer located downstream of the storage ion mobility separator. The separated ions can be selected and / or filtered according to their mass prior to fragmentation.

[0033] The method can further include the selection of ions with specific ion mobility and the activation or fragmentation of the selected ions in a downstream activation / fragmentation cell, wherein the activated / fragmented ions are analyzed according to their ion mobility. Brief description of the drawings Fig. Figure 1 shows a schematic representation of a general version of a laterally extended TIMS according to the present invention. Fig. shows the laterally extended TIMS from Fig. with the ions stored and separated within it. Fig. shows the laterally extended TIMS from Fig. , while the stored ions are eluted. Fig. shows a laterally extended TIMS according to the present invention, in which RF potentials of different frequencies are used to confine ions in an ion region, and a gas flow and a DC electric field gradient are generated, which act as first and second axial forces. Fig. shows a set of electrode arrays of the laterally extended TIMS Fig. , wherein each electrode assembly comprises a single electrode. Fig. shows two of the adjacent electrode structures from Fig. , which are located on both sides of the ion region along the short dimension. Fig. shows schematically how the electrode structures are made of Fig. be supplied with RF potentials. Fig. shows schematically how the electrode structures are made of Fig. be supplied with DC voltage potentials. Fig. is a graphical representation of a gas flow velocity and the DC electric field gradient generated by the applied DC voltage potentials for the laterally extended TIMS from Fig. . Fig. is a graphical representation similar to Fig. , which, however, shows the effective velocity components of the DC electric field gradient for each of the different ion species with different ion mobilities. Fig. is a graphical representation similar to Fig. , which, however, shows the elution of the different types of ions with different ion mobility. Fig. shows a laterally extended TIMS according to the present invention, in which RF potentials of different frequencies and DC electrical potentials are used to confine ions in an ion region, and a gas flow and a DC electrical field gradient are generated as the first and second axial forces. Fig. is a schematic, perspective view of the electrode structures of the laterally extended TIMS from Fig. , where each electrode assembly comprises three electrodes. Fig. is a schematic cross-sectional view of the electrode structures made of Fig. . Fig. shows the electrodes of the electrode structures of the Fig. , which are supplied with RF potentials. Fig. shows the electrodes of the electrode structures from the Fig. , which are supplied with DC voltage potentials that generate an electric DC field gradient along the axis of the TIMS. Fig. Figure 1 shows, for general explanation, a laterally extended TIMS in which RF potentials of a frequency are used to confine ions in an ion region, and an axial transient DC electric field and a DC electric field gradient are generated as the first and second axial forces. Fig. shows a set of electrode arrays of the laterally extended TIMS Fig. , wherein each electrode assembly comprises a single electrode. Fig. shows how the electrodes of the electrode structures are made of Fig. be supplied with RF potentials. Fig. shows how the electrodes of the electrode structures are made of Fig. supplied with DC potentials and transient DC potentials, whereby the DC potentials generate an electric DC field gradient and the transient DC potentials generate an axial transient electric DC field. Fig. is a graphical representation of how the in Fig. The DC potentials and transient DC potentials shown are opposing forces of the traveling wave field and the DC field for the laterally extended TIMS. Fig. generate. Fig. is a graphical representation similar to Fig. , which, however, shows the effective velocity components of the axial transient DC electric field and the DC electric field gradient for each of the different ion species with different ion mobilities. Fig. is a graphical representation similar to Fig. , which, however, shows the elution of the different types of ions with different ion mobility. Fig. Figure 1 shows, for general illustration, a laterally extended TIMS in which transient DC electrical potentials and static DC electrical potentials are used to confine ions in an ionic region, and a gas flow and a DC electrical field gradient are generated as the first and second axial forces. Fig. shows a set of electrode arrays of the laterally extended TIMS Fig. , where each electrode assembly comprises a set of electrodes. Fig. shows a single electrode structure made of Fig. , which comprises a series of electrode components, including small electrode components above and below the ion region to which transient DC electrical potentials are applied, and end electrode components to which a static DC potential is applied. Fig. is a graphical representation of a gas flow velocity and the DC electric field gradient generated by DC voltage potentials applied to the electrode structures of the laterally extended TIMS. Fig. be created. Fig. is a graphical representation similar to Fig. , which, however, shows the effective velocity components of the DC electric field gradient for each of the different ion species with different ion mobilities. Fig. is a graphical representation similar to Fig. , which, however, shows the elution of the different types of ions with different ion mobility. Fig. Figure 1 shows, for general illustration, a laterally extended TIMS in which RF potentials of a single frequency are used to confine ions in multiple ion channels, and a gas flow and a DC electric field gradient are generated as the first and second axial forces. Fig. is a schematic, perspective view of a set of electrode arrays of the laterally extended TIMS from Fig. , wherein each electrode assembly comprises a set of electrode segments. Fig. shows a single electrode structure made of Fig. , which comprises a series of electrode segments to which opposite phases of RF potentials are applied to generate multiple ion channels. Fig. is a graphical representation of a gas flow velocity and the DC electric field gradient induced by the electrode structures of the laterally extended TIMS. Fig. is generated by applied DC voltage potentials. Fig. is a graphical representation similar to Fig. , which, however, shows the effective velocity components of the DC electric field gradient for each of the different ion species with different ion mobilities. Fig. is a graphical representation similar to Fig. , which, however, shows the elution of the different types of ions with different ion mobility. Fig. schematically shows a laterally extended TIMS with an ion region having a convex cross-sectional profile, comprising an inlet ion funnel and an outlet ion funnel. Fig. Figure 1 schematically shows a laterally extended TIMS with an ion region having a convex cross-sectional profile, comprising an inlet ion funnel, an outlet ion funnel and an ion trap. Fig. schematically shows a laterally extended TIMS comprising an inlet ion funnel and an outlet ion funnel, and exhibiting an ion region with a convex cross-sectional profile that varies along the axis. Fig. Figure 1 schematically shows a laterally extended TIMS that includes an inlet ion funnel and has an ion region with a convex cross-sectional profile that varies along the axis but remains constant in the plateau region. Fig. schematically shows a laterally extended TIMS that includes an inlet ion funnel and has an ion region with a convex cross-sectional profile that is elliptically shaped and varies along the axis. Fig. schematically shows a laterally extended TIMS with an ion region having a non-convex cross-sectional profile between coaxial outer and inner circular surfaces. Fig. schematically shows a laterally extended TIMS with an ion region having a non-convex, horseshoe-shaped cross-sectional profile. Fig. schematically shows a laterally extended TIMS that includes an ion region with a non-convex, serpentine cross-sectional profile. Detailed description of the invention

[0034] The Fig. Figure 1 schematically shows three operating stages for a general version of a laterally extended TIMS 100 according to the invention. The laterally extended TIMS 100 comprises 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 plane of the drawing. Each electrode structure comprises an electrode or an electrode set for generating electric fields within the ion region 101. As shown in Figure 1, the electrodes are arranged in a single unit. Fig. As depicted, the ions 102 enter the ion channel 101 from one side and eventually migrate to the opposite side of the channel, being temporarily stored at mobility-dependent positions along the way. The ions 102 are the molecular components of a sample material to be analyzed, which have been ionized and introduced into the ion channel, typically by a known type of ion source, such as an electrospray ionization, MALDI (matrix-assisted laser desorption), or CI (chemical ionization) ion source. The ions 102 enter the ion channel 101 at any position and velocity but are separated according to their ion mobility before exiting the channel. From there, they 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).

[0035] The direction of movement of the ions 102 along the ion region 101 is defined as the axis of the laterally extended TIMS 100 (z-direction) and is shown in the Fig. Indicated by the arrows. The separation of the ions 102 according to their ion mobility is carried out using opposing forces F. A (first force) and F B (Second force) in an axial direction relative to the ion region 101, generating opposing velocity components, at least one of which depends on the ion mobility, and thus causing a mobility-dependent separation. One of the opposing forces can be generated by a gas flow along the z-axis, either in the same direction as the ion motion or in the opposite direction. It is also possible for the opposing force to be generated by a DC electric field acting on the ions in the presence of residual gas.

[0036] At least one of the opposing forces F A and F B It also varies spatially along at least one segment of the z-axis. The opposing forces F A and F B are preferably balanced such that for each relevant ion species of ion group 102 within ion range 101, an equilibrium point with zero velocity exists. Since a mobility-dependent force has a different influence on ion species with different mobilities, the spatial position along the z-axis for which the velocity of an ion species is zero depends on the mobility K of that ion. As in Fig. schematically represented, the ion species are thus under the influence of the opposing axial forces F. A and F BThe ions are stored at mobility-dependent positions along the axis. In the figure, the ion types are represented as circles, with circles of larger diameter representing ions with a larger cross-section and thus lower mobility K. However, a person skilled in the art will understand that the ions 102 could also be separated along the z-axis from higher to lower mobility, depending on the relative arrangement of the opposing axial forces.

[0037] The stored ions 102 are eventually eluted from the ion region 101 by one or both of the forces F A and F Bso that the velocity components change and the equilibrium point for a species of ion to be elutated does not lie within the ion region 101. This relative change in the opposing axial forces can occur progressively, so that ion species with increasing or decreasing mobility K successively leave the laterally extended TIMS 100 in the z-direction. Fig. For example, the ions 102 from the laterally extended TIMS 100 are eluted from a lower to a higher mobility K.

[0038] In addition to the opposing axial forces F A and F B The invention also incorporates a lateral confinement force F CONF used, which includes the ions in ion range 101. This force is used in the Fig. by the radially pointing arrow labeled F CONF depicted.

[0039] A first embodiment of the invention is described in the Fig. shown. The schematic, perspective view of Fig. Figure 201 shows an outer casing 201 of the laterally extended TIMS 200, which operates at a pressure between 10 and 5,000 Pa, e.g., approximately 300 Pa. As in the more general representation of the Fig. Ions enter the laterally extended TIMS 200 at a first side and move in the direction of the z-axis. Within the ion region 202 of the laterally extended TIMS 200, the ions are subjected to opposing axial forces generated by a gas flow in the positive direction of the z-axis and a DC electric field gradient in the negative direction of the z-axis. Specifically, the gas has a substantially constant velocity within the ion region in the z-direction, while the DC electric field gradient, whose polarity is opposite to that of the ions, increases along the z-direction from zero to a maximum value at a plateau 203. As explained below, set 204 of the electrode structures provides the DC electric field gradient as well as a confinement force on the ions in the ion region.

[0040] Fig. is a schematic view of the electrode structures 211 and 212, which are configured as follows Fig. Each electrode assembly is significantly longer in its long dimension y than in its short dimension x and comprises an elongated electrode extending along its long dimension and connected to extended sections located at each end of the elongated electrode. The electrode assemblies 211 are spatially offset relative to the electrode assemblies 212 along the z-direction. In the present embodiment, the elongated electrodes have a cylindrical profile, although other electrode shapes can also be used. The electrode assemblies 211 are arranged such that the elongated electrode is located above the ion region, while the electrode assemblies 212 are arranged such that the elongated electrode is located below the ion region.The extended sections at the ends of each elongated electrode extend in the x-direction towards the interior of the housing and are typically flat with a curved edge facing the ion region. One of the electrode structures 211 and one of the electrode structures 212 are located in . Fig. Shown in isolation. Referring to the upper electrode assembly 211, the elongated electrode is identified by reference numeral 211a, while the extended sections are identified by reference numeral 211b. A person skilled in the art will understand that the electrode assembly 212 can be identified by the corresponding reference numerals 212a (for the elongated electrode) and 212b (for the extended sections).

[0041] The electrode structures lie next to each other, in an alternating arrangement along the z-direction of electrode structures 211 and electrode structures 212, as shown in Fig. shown. For reference purposes, the upper electrode structures 211 are shown in Fig. These are designated as electrode structures 211-1 to 211-N, and a person skilled in the art will understand that a similar nomenclature can also be applied to the lower electrode structures 212. As explained below, DC electrical potentials are applied to the electrode structures to control the movement and positioning of the ions in the ion region. Due to the elongated shape of the ion region 202 formed by the electrode structures, the ions in the ion region are distributed along the y-direction, although the control of the ion movement is performed in the axial direction (z-direction) of the TIMS.

[0042] Fig. is a schematic view in the y-direction of the electrode structures 211 and 212 from Fig. The figure shows how different RF potentials are applied to them. In this embodiment, two different RF potentials with different frequencies are used, with RF1 being applied to electrode structures 211 and RF2 to electrode structures 212. As shown in the figure, the electrode structures 211 and 212 alternate along the z-direction, and two opposite phases of the signal are used for each RF potential. For example, a first phase of RF1 (RF1+) is applied to every second electrode structure 211, while an opposite phase, RF1- (which is 180° out of phase with RF1+), is applied to the remaining electrode structures 211. Similarly, a first phase of RF2 (RF2+) is applied to every second electrode structure 212, while an opposite phase, RF2-, is applied to the remaining electrode structures 212.An important advantage of applying RF potentials with two different frequencies to the electrode structures on both sides and offsetting the electrode structures on both sides is that essentially no pseudo potential wells are created within the ion region along the axis.

[0043] As in Fig. As shown, DC potentials are also applied to the electrode structures. In the figure, 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 a 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 of sets 211 and 212. These DC potentials are constant over time during the accumulation phase and vary during the elution phase.They are used to generate a DC electric field along the z-direction to control the ions in the ion region, as explained below.

[0044] An example of this embodiment has the following parameters, whereby the person skilled in the art understands that this is only an example and the parameters can be varied depending on the application. Although the operating pressure of the TIMS can range between 10 and 5,000 Pa (0.1 to 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. The number of electrode structures 211 in this version is 40, and the number of electrode structures 212 is also 40. The RF potentials ensure lateral confinement of the ions in the ion region in both the x- and y-directions, with RF1 having a frequency of 0.86 MHz and RF2 a frequency of 1.2 MHz.The elongated electrodes are rounded rod electrodes with a diameter of approximately 1.5 mm and a distance of 2.5 mm to adjacent electrode structures (both above and below the ion region). The elongated electrodes are preferably integrated into a printed circuit board (PCB) and are supplied with DC voltage and radio frequency potentials via conductors on the PCB. The gas flow velocity is approximately 100 m / s.

[0045] The effect of the opposing axial forces on the ions in the laterally extended TIMS 200 is described in the Fig. The graphs shown depict a graph of velocity (or an effective velocity component) compared to position along the z-axis. As shown from... Fig. As can be seen, there is a constant gas velocity v. gas , which drives the ions through the ionic region in the direction of the z-axis. This movement is opposed by a direct current electric field -E DC(t) opposite, which has a spatial gradient along the z-axis, which is the effective velocity component -v shown in the figures DC (t) is generated and the range from zero to a maximum at the longitudinal position z p at plateau 203, which, as discussed below, can be an elution point for ions where the ions are no longer stored 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 is shown as a function of time, since in this embodiment the strength of the DC electric field decreases during the elution of the different ion species.

[0046] Fig. similar Fig. , but shows the "effective" velocity component -v DC due to the opposing direct current electric field for each of the different ion types Kn-1 , K n and K n+1 . This “effective” velocity component is mobility-dependent in the presence of a gas, and the corresponding gradient -v DC Therefore, in the figure, K represents each of the ion types. n-1 , K n and K n+1 The gradients are shown in dashed lines. These gradients represent the velocity components that affect the different ion species due to the DC electric field E. DC (t) in the absence of gas flow v gas would be transferred. That is, -v DC is the velocity component attributable to the DC electric field for an ion in a stationary gas at a specific pressure and temperature. This value is proportional to the strength of the DC electric field and differs for each ion species with a different mobility K (where v DC = K · E DC ). For the three types of ions K n-1 , Kn and K n+1 is the “effective” velocity v caused by the gas flow in the absence of the DC electric field. gas .

[0047] The DC electric field gradient along the z-axis leads to a corresponding gradient for -v DC , which differs for ion types with different mobilities, as in Fig. depicted. During an initial accumulation phase of the ions, the magnitude of the DC electric field is such that the position at which -v DC equal to the opposite velocity component v caused by the gas flow gas is different for each type of ion. Due to the different gradients -v for the different types of ions. DCThe ions of the different ion types are separated from each other and stored at different positions along the z-axis. The different ion types, K n-1 , K n and K n+1 , are in Fig. represented by circles of different sizes, with the larger circles corresponding to ion types with a larger cross-section and thus lower mobility K.

[0048] After the separation of the different ion species, the ions can be eluted sequentially from the laterally extended TIMS 200 and directed to a downstream component of a hybrid IMS-MS system or to an ion detector. Elution is achieved by gradually reducing the magnitude of the DC electric field gradient, thereby decreasing the magnitudes of the velocity component gradients. DC reduce accordingly, as in Fig. The point at which the opposing velocity components v meet is shown. As these gradients decrease, the point at which they meet is determined. gas and -v DC The electric field is shifted in the direction of +z for each of the different ion species, specifically towards the output of the laterally extended TIMS 200. The electric field is configured such that the gradient increases in the direction of +z until it reaches the elution point z. p A plateau is reached along the z-axis. Since the ion storage position differs for each of the different ion species, shifting these storage positions by lowering the DC electric field gradient results in the individual ion species reaching the elution point z at different times. parrive. After arriving at the elution point, an ion species is no longer held by the opposing velocity components and leaves the laterally extended TIMS 200 in the direction of +z, as in Fig. for the ion type K n-1 shown. In this way, the separated ion species are eluted successively from the laterally extended TIMS 200, from low to high mobility.

[0049] In the Fig. An alternative embodiment of the invention is shown, in which the electrode structures 304 are elongated electrodes above and below the ion region, but without extended sections as in the Fig. This embodiment does not include lateral electrodes. Rather, lateral electrodes are provided on both sides of each elongated electrode to ensure ion confinement in the y-dimension. In this embodiment, a housing with a greater width in the y-direction is also used to allow for a more uniform gas flow through the ion region.

[0050] Fig. Figure 1 shows the laterally extended TIMS 300 of this embodiment, which has an ion region 302 with an elongated cross-sectional profile and a plateau region 303. As shown, the housing 301 has sections on both sides in the y-direction that extend significantly further than the electrode structures 304 and the ion region 302. These side regions of the housing allow gas flow through the housing, but not ion flow. An advantage of this configuration is that the gas flow through the ion region is relatively uniform along the y-direction, since any interruptions in this flow tend to be located within the side regions of the housing, near the edges 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.

[0051] An isolated view of the electrode structures 304 is shown in Fig. The electrode structures comprise elongated electrodes 311 (including individual electrodes 311-1 to 311-N) and lateral electrodes 313 and 315 (including individual lateral electrodes 313-1 to 313-N and 315-1 to 315-N, respectively) above the ion region. Elongated electrodes 312 and lateral electrodes 314 and 316 are located below the ion region. A person skilled in the art will understand that these electrodes are parallel to electrodes 311, 313, and 315 in the x-direction and therefore follow the same pattern. Preferably, the electrodes above the ion region (311, 313, 315) are spatially offset relative to the electrodes below the ion region (312, 314, 316) along the z-direction.The electrodes above and below the ion region have a regular relative distance along the z-direction, but the positioning of the electrodes below the ion region (312, 314, 316) in the z-direction is preferably offset from the positioning of the electrodes above the ion region (311, 313, 315) in the z-direction by a distance equal to half this relative distance. In a modified configuration, the electrodes above the ion region (311, 313, 315) have no spatial offset relative to the electrodes below the ion region (312, 314, 316) along the z-direction.

[0052] As in Fig. As shown, the ions are confined within the ion region 302 by electrical potentials at the elongated electrodes 311 and 312 and at the lateral electrodes 313, 315, 314, and 316. In a preferred version of this embodiment, two different RF potentials, RF1 and RF2, are used, with RF1 being applied to the elongated electrodes 311 and RF2 to the elongated electrodes 312. As in the embodiment shown Fig. Two opposite phases of the RF signals are used. In the Fig. In the example shown, a first phase of RF1 (RF1+) is applied to every second electrode assembly 311, while an opposite phase, RF1- (which is phase-shifted by 180° to RF1+), is applied to the other electrode assembly 311. Similarly, a first phase of RF2 (RF2+) is applied to every second electrode assembly 312, while an opposite phase, RF2-, is applied to the remaining electrode assembly 312.

[0053] As in Fig. As shown, DC potentials are also applied to the elongated electrodes of the electrode structures. As depicted in the figure, 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 a 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 of sets 311 and 312. These DC potentials can be used to generate a DC electric field in the z-direction to control the ions in the ion region, as explained below.

[0054] In addition to the DC potentials applied to the elongated electrodes 311 and 312, confinement DC potentials are also applied to the lateral electrodes 313, 315, 314, and 316. Unlike the DC potentials applied to the elongated electrodes, the confinement DC potentials applied to the lateral electrodes serve to confine the ions in the ion region in the y-direction. The DC potential applied to each of the lateral electrodes 313, 315, 314, and 316 preferably has a DC offset relative to the DC potential of the adjacent elongated electrode. The DC offset between the lateral electrodes and their corresponding adjacent elongated electrodes can be constant or vary along the z-direction.

[0055] An example of this embodiment has the following parameters, whereby the person skilled in the art understands that this is only an example and the parameters can be varied depending on the application. As with the embodiment of the Fig. The operating pressure of the TIMS can range between 10 and 5,000 Pa (0.1 and 50 mbar), while in this particular 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. The total number of electrode structures 311 and 312 in this version is 70. The RF potentials ensure lateral confinement of the ions in the ion region in the x-direction, with RF1 having a frequency of 1.2 MHz and RF2 a frequency of 1.8 MHz. However, confinement in the y-direction is achieved by the DC potentials applied to the lateral electrodes 313, 315, 314, and 316, e.g.,... B. by a constant DC voltage offset of 1-5 V relative to the corresponding DC voltage potentials DC311 or DC312.The elongated electrodes are rounded rod electrodes with a diameter of approximately 1.0 mm and a distance of 1.5 mm to adjacent electrode structures (both above and below the ion region). The elongated electrodes are preferably integrated into a printed circuit board (PCB) and are supplied with DC voltage and radio frequency potentials via conductors on the PCB. The gas flow velocity is approximately 100 m / s.

[0056] The Fig. Figure 400 shows a TIMS 400 for general explanation. The laterally extended TIMS 400 comprises a series of electrode structures 404, each electrode structure 404 having a single electrode that surrounds the ion region 402 in the x and y directions. As shown in Fig. As shown, a housing 401 surrounds the electrode structures 404 from an inlet of the laterally extended TIMS 400 to a plateau region 403 near an outlet. The individual electrodes 411 are closed electrodes that completely enclose the ion region 402. The electrodes are arranged in parallel and have the same spacing along the z-direction as shown in Fig. shown. They range from a first electrode 411-1 to an Nth electrode 411-N.

[0057] Fig. Figure 4 shows how RF potentials are applied to the electrodes 411, with a first phase of the RF potential being applied to every second electrode and an opposite phase (phase-shifted by 180° to the first phase) being applied to the remaining electrodes. This application of alternating phases along the series of electrodes 411 helps to keep the ions confined within the ionic region. Different DC voltage potentials are also applied to the electrodes 411, as shown in Figure 4. Fig. The DC potentials are represented as follows: each comprises a first component, which is constant during the accumulation phase and varies during the elution phase, and a second, transient component. Thus, as in the Fig. 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, a potential of DC411 N + tDC411 N applied to electrode 411-N, where DC411 N the first component and tDC411 NThe transient component is present. A person skilled in the art will understand that similar combinations of a first DC potential component and a transient DC potential component are also present at the other electrodes. The first components 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 the ions in the ion region, as explained below. The transient DC potentials generate a traveling wave (TW) that propagates downstream along the z-axis.

[0058] The effect of the opposing axial forces on the ions in the laterally extended TIMS 400 is described in the Fig. The diagrams shown depict the velocity (or an effective velocity component) as a function of position along the z-axis. The design of the Fig. This differs from previous embodiments in that no gas flow is used as an axial force on the ions. Instead, the DC voltage potentials applied to the electrodes 411 generate both a DC field gradient along the z-direction and a traveling wave (TW) that opposes this gradient. In the Fig. In the example shown, the traveling wave field provides the ions with an essentially constant velocity component (represented as v). TW ), which is opposite to the velocity component generated by the DC field gradient. Since there is residual gas in the housing 401 of the TIMS, the mobility K of each ion determines its relative positioning along the z-direction.

[0059] Since the effect of the DC electric field gradient on the ions is mobility-dependent, the gradients of the velocity components for the different ion species K n-1 , K n and K n+1 different, as in Fig. shown. Since the axial velocity component v TWSince the axial transient DC potentials applied to the electrode structures 411-1 to 411-N are also mobility-dependent, the different velocity components for the various ion species are also shown. During an ion accumulation phase, the opposing forces balance each other, so that ions of different ion species with different ion mobilities K are stored at different axial positions within the laterally extended TIMS 400. Because ion species with higher mobility are less affected by the presence of the ambient gas in the laterally extended TIMS 400, the equilibrium point between the opposing forces for these ion species lies closer to the elution point z. p , while the ion species with lower mobility are stored closer to the entrance of the laterally extended TIMS 400.

[0060] The laterally extended TIMS 400 operates at a pressure of approximately 100 Pa (1 mbar) and has a length of 150 mm, a width of 50 mm, and a height of 4 mm. In this design, ion elution occurs through a gradual reduction of the strength of the DC electric field. This results in a sequential elution of ion species from higher to lower mobility. As in Fig. As shown, the ion species with relatively high mobility leaves the area. Kn+1 The laterally extended TIMS 400, while the ions with lower mobility remain stored. Finally, all ions are eluted and passed on to a downstream component of a hybrid IMS-MS system or to an ion detector.

[0061] An example of this design has the following parameters, whereby those skilled in the art understand that this is only an example and the parameters can be varied depending on the application. The operating pressure of the TIMS can be in the range of 10–5,000 Pa (0.1–50 mbar), while in this specific example it is approximately 100 Pa (1 mbar). The ion chamber 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 version, 125 electrodes 411 are used in the electrode array. The RF potentials ensure lateral confinement of the ions in the ion chamber in both the x- and y-directions, at an RF frequency of 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 are supplied with DC voltage and high-frequency potentials via lines on the circuit board.

[0062] The Fig. A TIMS 500 is shown for general explanation. The one in Fig. The laterally extended TIMS 500 shown comprises a housing 501 and a series of electrode structures 504. The electrode structures 504 extend from an inlet of the laterally extended TIMS 500 to a plateau region 503 near an outlet. As shown in Fig. As shown, each of the electrode structures 504 comprises an electrode set 511. The electrodes of the electrode set 511 together enclose the ion region 502 in the x and y directions.

[0063] As in Fig. As shown, the electrode assembly 511 comprises small, uniform electrodes above (511-1 to 511-18) and below (511-19 to 511-36) the ion region 502, with larger electrodes 511-37 arranged at both ends of the ion region 502 in the y-direction. Each of the electrode assembly 504 has the same electrode configuration, but different DC potentials can be applied to each of the individual electrodes; that is, a DC potential is applied to each of the small electrodes of a single electrode assembly. These DC potentials applied to the small electrodes of the electrode assembly 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 the ions in the ion region 502, as explained below.

[0064] An example of how the electrodes (511-1 to 511-37) can be provided with additional DC electrical potentials to laterally confine the ions in the ion region 502 is shown in Fig. The electrodes of electrode set 511 are labeled, with small electrodes designated as electrodes 511-1 to 511-36 and the larger electrodes at the ends as electrodes 511-37. In this example, there are 18 small electrodes above the ion region and 18 small electrodes below it. Each small electrode (511-1 to 511-36) is marked with either "+" or "-", indicating that additional DC potentials are applied to the small electrodes, which are either strongly (+) or less strongly (-) repulsive to ions in the ion region. These additional DC potentials at the small electrodes 511-1 to 511-36 are dynamically changed according to a predetermined sequence, while the DC potentials applied to the large electrodes 511-37 are constantly repulsive.Changing the additional DC potentials at the small electrodes simulates the rotation of these potentials around the electrode assembly 511 in the direction indicated by the dashed arrows. That is, in each subsequent time interval, a small electrode receives the additional DC potential that, in the previous time interval, was applied to the small electrode adjacent to it in the opposite direction to the arrow. In this way, the high and low additional DC potentials rotate around the electrode assembly 504 over time. The rotation of the additional DC potentials at the electrode assembly causes a lateral confinement force in the x-direction on the ions within the ion region 502 inside the electrode assembly 511, while the additional DC potentials applied to the large electrode cause a lateral confinement force in the y-direction.

[0065] The effect of the opposing axial forces on the ions in the laterally extended TIMS 500 is described in the Fig. shown are graphs, each depicting a graph of the velocity (or an effective velocity component) as a function of position along the z-axis. As shown in Fig. As shown, the DC electric field gradient generated by the DC potentials individually applied to each of the electrode structures 504 along the z-direction opposes a constant gas flow, thereby achieving the desired accumulation and separation of ions depending on their mobility along the z-direction. These individual DC potentials can subsequently be changed to decrease the DC electric field gradient, so that the ion species elute from the laterally extended TIMS 500 depending on their mobility, as shown in the Fig. shown, which are shown above Fig. The process is carried out accordingly. Finally, all ion species are eluted and passed on to a downstream component of a hybrid IMS-MS system or to an ion detector. During the accumulation and elution phases, the rotation of the additional DC potentials applied to the small electrodes and the repulsive DC potentials applied to the large electrodes is maintained, resulting in the desired lateral confinement.

[0066] An 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. Those skilled in the art understand that this is only an example and that the parameters can be modified depending on the application. In this version, fifty electrode assemblies 504 are used, each consisting of thirty-six small electrodes and two end electrodes. The additional DC voltage potentials at the small electrodes alternate between a repulsive potential value (+V) and zero volts (-V), causing lateral confinement of the ions in the ion region in the x-direction. The repulsive potential value is less than 500 V.The DC potentials at the large electrodes are offset from those applied to the small electrodes to generate the DC electric field gradient, resulting in the lateral confinement of ions in the ion region in the y-direction. The rotation of the DC potentials around each electrode can reach speeds of up to 2,000 m / s, depending on the operating pressure. The electrodes are preferably integrated into one or more printed circuit boards (PCBs) and supplied with DC potentials via conductors on the PCB. The gas flow velocity is between five and twenty m / s.

[0067] The Fig. A TIMS 600 is shown for general explanation. The one in Fig. The laterally extended TIMS 600 shown comprises a housing 601 and a series of electrode structures 604. The electrode structures 604 extend from an inlet of the laterally extended TIMS 600 to a plateau region 603 near an outlet. As shown in Fig. As shown, each electrode assembly 604 comprises a set of electrodes 611. The electrodes of the electrode set 611 together enclose an ion region in the x and y directions.

[0068] The in the Fig. The illustrated design differs from previous embodiments in that the ions within the ion region are arranged along the y-direction in a series of separate ion channels 602-i. As shown in Fig. As shown, the electrode set 611 comprises electrodes 611-1 to 611-7 above and electrodes 611-8 to 611-14 below the ion channels 602-i, with alternating opposite phases of an RF potential being applied to electrodes 611-1 to 611-14. Thus, a first electrode component (611-1) is supplied with the potential -RF, while the adjacent electrodes 611-2 and 611-14 are supplied with the opposite phase +RF (which is phase-shifted by 180° to -RF). This alternating application of the RF potential continues over the entire circumference of the electrode set 611 and encloses ions in the ion region within the various ion channels 602-i. The RF potentials are applied to each electrode array in the same manner, so that the ion channels 602-i extend along the z-direction. In this way, the laterally extended TIMS 600 functions like an array of several parallel TIMSs, each represented by a different ion channel.Different DC potentials are applied to the different electrode structures 604, but a common DC potential is applied to all electrodes of a single electrode structure. These DC potentials applied to the 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 the ions in the ion region, as explained below.

[0069] The effect of the opposing axial forces on the ions in the laterally extended TIMS 600 is described in the Fig. The diagrams shown depict the velocity (or an effective velocity component) as a function of position along the z-axis. The axial forces in this design are generated by an opposing gas flow and a DC electric field gradient. As shown in Fig. As depicted, in this configuration the gas flow is directed in the -z direction along the z-axis, opposite to the direction of ion movement, and has a constant gas velocity along the z-axis. The DC electric field gradient is generated by the DC potentials applied to the electrode structures 604. The strength of the DC electric field gradient decreases along the z-axis until the plateau region 603 (at z = zp) is reached. This leads to a separation of the ions of each channel in the z-direction from low mobility to high mobility. As shown in the Fig. As shown, the electric DC field gradient is subsequently increased in the plateau region 603, so that the ions progressively overcome the opposing force of the gas flow and are eluted from the laterally extended TIMS 600 with decreasing mobility.

[0070] In one example of this design, a single RF frequency is used and applied synchronously and in the same way to all electrodes of the electrode arrays 604 to form the separate ion channels and storage regions along the x and y directions. The operating pressure can range from 10 to 5,000 Pa (0.1 to 50 mbar) and is typically 300 Pa (3 mbar). The ion region is 50 mm long, 50 mm wide, and 4 mm high. In this version, there are fifty different electrode arrays spaced 1 mm apart. The RF frequency is 1 MHz, and the gas flow velocity is approximately 100 m / s.

[0071] Fig. Figure 1 shows a laterally extended TIMS 700, as described above, with an upstream ion funnel 710 and a downstream ion funnel 720. In this arrangement, the ions (e.g., from an ion source) are directed into the ion funnel 710, which, as shown in the adjacent cross-sectional figures, maintains the width of the ion region in the y-direction while the dimension in the x-direction is progressively reduced. The ion region 702 is the separating part of the laterally extended TIMS 700 and has a laterally extended cross-section that allows for the simultaneous processing of ions distributed along the long dimension. The ions are separated in the ion region 702 and eluted one after the other depending on their ion mobility as described above, and leave the plateau region 703 in the direction of the second ion funnel 720, which has a cross-section that decreases in the y-direction.This concentrates the separated, eluted ion types into a smaller cross-section at the outlet of the ion funnel 720.

[0072] Fig. Figure 8 shows a laterally extended TIMS 800 with an upstream ion funnel 810, an ion trap 830, and a downstream ion funnel 820. The ion region 802 is the separating part of the laterally extended TIMS 800. As in the embodiment described above, ions (e.g., from an ion source) are directed into the ion funnel 810, which, as shown in the adjacent cross-sectional figures, maintains the width of the ion region in the y-direction while the dimension in the x-direction is gradually reduced. The ion funnel 810 directs the ions into the ion trap 830, which has a laterally extended cross-section to allow the accumulation of ions. Previously accumulated ions are separated in parallel in the ion region 802 of the laterally extended TIMS 800, depending on their mobility. The ion region 802 can employ one of the embodiments described above.After an accumulation phase, ions from the ion trap 830 are directed into the ion region 802, separated there according to their mobility, and then sequentially eluted via the plateau region 803 into the output ion funnel 820, which tapers in the y-direction to concentrate the exiting ions in an output channel with a smaller cross-section. Preferably, the volume of the ion trap 830 is at least as large as the volume of the ion region 802; in a particularly preferred manner, the width and height of the ion trap 830 correspond to those of the ion region 802.

[0073] Fig. Figure 900 shows a laterally extended TIMS 900 with an upstream ion funnel 910 and a downstream ion funnel 920. The upstream ion funnel 910 tapers in the y-direction towards the inlet of the ion region 902. The ion region 902 is the separating part of the laterally extended TIMS 900. In this configuration, however, the ion region 902 itself is also tapered in the y-direction, so that during separation, the ions are concentrated in a plateau region 903, depending on their ion mobility. This plateau region has a tapered cross-section in its long dimension. This tapered cross-section continues into the downstream ion funnel 920, which follows the plateau region 903, so that the ions exit into an outlet channel with a smaller cross-section.

[0074] Fig. Figure 1 shows a laterally extended TIMS 1000 with an upstream ion funnel 1010. The ion region 1002 is the separating part of the laterally extended TIMS 1000. In this configuration, the ion funnel 1010 tapers in the y-direction, as does the ion region 1002. Unlike the configuration in Figure 1, the ion region 1002 is... Fig. However, the narrowing of the ion region 1002 reaches a final narrowed cross-section in the x and y directions before the ions reach the plateau region 1003. From there, the ions are eluted sequentially according to ion species to any downstream location.

[0075] Fig. Figure 1 shows a laterally extended TIMS 1100 with an upstream ion funnel 1110. The ion region 1102 is the separating part of the laterally extended TIMS 1100. In this configuration, the upstream ion funnel 1110 tapers in the x-direction from a circular cross-section to an elliptical outlet into the ion region 1102. Both the ion region 1102 and the plateau region 1103 also have a tapered cross-section, from the elongated elliptical shape at the inlet of the ion region 1102 to a more concentrated outlet profile at the plateau region 1103.

[0076] Fig. Figure 1 shows a laterally extended TIMS 1200 with an ion region 1202 having a non-convex cross-sectional profile. The ion region 1202 of the laterally extended TIMS has an annular cross-section, which is generated by the electrode array and the housing of the laterally extended TIMS 1200. The long dimension 1240 runs along the closed path within the annular region, and the short dimension 1250 runs along the radial direction between the outer and inner radii of the annular region. The ions are separated according to their ion mobility, as described above, and eluted from the plateau region 1203. They can then be deflected as desired at the output of the laterally extended TIMS 1200. The advantage of a non-convex cross-sectional profile is that the influence of one charge on another is reduced, thus increasing the charge capacity of the TIMS.

[0077] Fig. Figure 1 shows another example of a laterally extended TIMS 1300 with an ion region 1302 that has a non-convex cross-sectional profile. In this version, the ion region 1302 has a generally arc-shaped cross-section. The extended ion region is therefore not linear or parallel to the y-axis, but extends laterally along the arc shape, thus also enabling the simultaneous separation of a larger number of ions depending on their ion mobility. The long dimension 1340 runs along an azimuthal path within the arc-shaped region, and the short dimension 1350 runs along the radial direction between the outer and inner arcs.In a modified embodiment, the azimuthal extent of the cross-sectional profile (length of the arc-shaped area) can decrease along the axis of the laterally extended TIMS, which reduces the conductance and thus the required pumping power to generate a gas flow.

[0078] In a similar arrangement to that in Fig. shows Fig. Another example of a laterally extended TIMS 1400 with an ion region 1402 having a non-convex cross-section. Here, the cross-sectional profile is serpentine, and the ions are therefore distributed along several arc-shaped sections of the ion region 1402. The long dimension 1440 runs along the serpentine line within the ion region 1402, and the short dimension 1450 runs in the direction between the outer and inner arcs. After separation and elution from the plateau region 1403, the ions can be collected and transported as needed.

Claims

[1] A storage ion mobility separator (100; 200; 300; 700; 800; 900; 1000; 1100; 1200; 1300; 1400) comprising the following: an ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) through which ions (102) move along an axis (z) from an input to an output, wherein the ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) contains a gas through which the ions (102) move, and has an elongated cross-sectional profile perpendicular to the axis (z) with a long dimension (1240; 1340; 1440) and a short dimension (1250; 1350; 1450); a series of electrode structures (211, 212; 304) arranged along the axis (z) and enclosing the elongated cross-sectional profile at least along the long dimension (1240; 1340; 1440), each electrode structure (211, 212; 304) comprising an electrode (211a, 212a, 311-316) or an electrode set (204) to which one or more varying voltage potentials (RF1, RF2) are applied to generate a first electric confinement field that exerts a confinement force on the ions (102) in the ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) relative to the short dimension (1250; 1350; 1450) exercises; a first force generator that exerts a first axial force on the ions (102) along the axis (z); and a second force generator that exerts a second axial force on the ions (102) along the axis (z), which counteracts the first axial force; wherein at least one of the axial forces has an effect on the ions (102) which depends on the ion mobility, and wherein at least one of the axial forces varies spatially along the axis (z) such that ions (102) are stored and separated during an accumulation phase depending on their ion mobility along the axis (z), and wherein the first and / or the second force generator is configured to vary the magnitude of the first force relative to the second force over time during an elution phase such that the ions (102) are progressively driven towards the outlet depending on their ion mobility, wherein each electrode assembly (211, 212; 304) comprises an elongated electrode (211a, 212a; 311, 312) extending parallel to the long dimension (1240; 1340; 1440), and wherein the elongated electrodes (211a, 212a; 311, 312) are arranged on a first and second side of the ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) relative to the short dimension (1250; 1350; 1450) in an alternating arrangement along the axis (z), wherein opposite phases (RF1+, RF1-) of a first RF voltage (RF1) are applied to adjacent elongated electrodes (211a, 212a; 311, 312) are applied to the first side and opposite phases (RF1+, RF1-) of a second RF voltage (RF2) are applied to adjacent elongated electrodes (211a, 212a; 311, 312) of the second side, and wherein the elongated electrodes (211a, 212a; 311, 312) of the first side have a distance equal to the distance between the elongated electrodes (211a, 212a; 311, 312) of the second side, characterized by , that the first RF voltage (RF1) and the second RF voltage (RF2) have different frequencies, and that the elongated electrodes (211a, 212a; 311, 312) of the second side are offset relative to the elongated electrodes (211a, 212a; 311, 312) of the first side along the axis (z) by half the distance. [2] The storage ion mobility separator (100; 200; 300; 700; 800; 900; 1000; 1100; 1200; 1300; 1400) according to claim 1, wherein the first axial force and the second axial force are each of different types and are each generated by an axial gas flow, an axial DC electric field or an axial transient DC electric field. [3] The storage ion mobility separator (100; 200; 300; 700; 800; 900; 1000; 1100; 1200; 1300; 1400) according to claim 2, wherein DC electrical potentials (DC211, DC212, DC311, DC312) or transient DC electrical potentials are applied to the electrode structures (211, 212; 304) to generate the axial DC electrical field or the axial transient DC electrical field. [4] The storage ion mobility separator (100; 200; 300; 700; 800; 900; 1000; 1100; 1200; 1300; 1400) according to any one of claims 1 to 3, wherein the at least one axial force, which varies spatially along the axis (z), comprises a gradient along a first section which flattens to a plateau (203; 303; 703; 803; 903; 1003; 1103; 1203; 1303; 1403) with substantially constant force. [5] The storage ion mobility separator (100; 200; 300; 700; 800; 900; 1000; 1100; 1200; 1300; 1400) according to claim 4, wherein the first or the second axial force is a gas flow whose velocity along the long dimension (1240; 1340; 1440) in the ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) near the plateau (203; 303; 703; 803; 903; 1003; 1103; 1203; 1303; 1403) is substantially constant. [6] The storage ion mobility separator (100; 200; 300; 700; 800; 900; 1000; 1100; 1200; 1300; 1400) according to any one of claims 1 to 5, wherein the varying voltage potential (RF1, RF2) applied to the electrode (211a, 212a, 311-316) or the electrode set (204) generates a second electric confinement field which exerts a confinement force on the ions (102) in the ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) relative to the long dimension (1240; 1340; 1440). [7] The storage ion mobility separator (100; 200; 300; 700; 800; 900; 1000; 1100; 1200; 1300; 1400) according to any one of claims 1 to 5, further comprising additional electrodes (313-316) on one or both sides of the ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) in the long dimension (1240; 1340; 1440) to which electrical RF (RF1, RF2) or DC potentials (DC211, DC212, DC311, DC312) are applied to generate a second electrical confinement field which The confinement force exerted on the ions (102) in the ionic region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) relative to the long dimension (1240; 1340; 1440). [8] The storage ion mobility separator (100; 200; 300; 700; 800; 900; 1000; 1100; 1200; 1300; 1400) according to any of the preceding claims, wherein the elongated electrodes (211a, 212a; 311, 312) have at each end, relative to the long dimension (1240; 1340; 1440), an extended section in the short dimension (1250; 1350; 1450), such that RF potentials (RF1, RF2) applied to the elongated electrodes (211a, 212a; 311, 312) generate a second electric confinement field, which exerts a confinement force on ions (102) in the ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) relative to the long dimension (1240; 1340; 1440). [9] A storage ion mobility separator (100; 200; 300; 700; 800; 900; 1000; 1100; 1200; 1300; 1400) according to any of the preceding claims, wherein a ratio H:S between a height H of the ion area (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) along the short dimension (1250; 1350; 1450) and the distance S of the elongated electrodes (211a, 212a; 311, 312) is less than ten. [10] The storage ion mobility separator (100; 200; 300; 700; 800; 900; 1000; 1100; 1200; 1300; 1400) according to any one of claims 1 to 9, which further comprises an ion trap (830) arranged upstream of the ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402). [11] A method for analyzing ions (102) as a function of their mobility using a storage ion mobility separator (100; 200; 300; 700; 800; 900; 1000; 1100; 1200; 1300; 1400), comprising the following: - Providing an ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) through which ions (102) move along an axis (z) from an inlet to an outlet, wherein the ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) contains a gas through which the ions (102) move and has an elongated cross-sectional profile perpendicular to the axis (z) with a long dimension (1240; 1340; 1440) and a short dimension (1250; 1350; 1450); - Providing a series of electrode structures (211, 212; 304) arranged along the axis (z) and enclosing the elongated cross-sectional profile at least along the long dimension (1240; 1340; 1440), each electrode structure (211, 212; 304) comprising an electrode (211a, 212a, 311-316) or an electrode set (204); - Generating a first electric confinement field that exerts a confinement force on the ions (102) in the ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) relative to the short dimension (1250; 1350; 1450) by applying a varying voltage potential (RF1, RF2) to the electrodes or electrode set (204); - Generating a first axial force that is transferred to the ions (102) along the axis (z); - Generating a second axial force that is transferred to the ions (102) along the axis (z) and that opposes the first force, wherein at least one of the axial forces varies spatially along the axis (z) so that ions (102) are stored and separated along the axis (z) depending on their ion mobility; - Vary at least one of the axial forces to increase the magnitude of the first axial force relative to the second force over time, such that the ions (102) are progressively driven towards the exit of the ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) and separated depending on the ion mobility, wherein each electrode assembly (211, 212; 304) comprises an elongated electrode (211a, 212a; 311, 312) extending parallel to the long dimension (1240; 1340; 1440), and wherein the elongated electrodes (211a, 212a; 311, 312) are located on a first and second side of the ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) relative to the short dimension (1250; 1350; 1450) are arranged in an alternating arrangement along the axis (z), wherein opposite phases (RF+, RF-) of a first RF voltage (RF1) are applied to adjacent elongated electrodes (211a, 212a;311, 312) on the first side and opposite phases (RF2+, RF2-) of a second RF voltage (RF2) are applied to adjacent elongated electrodes (211a, 212a; 311, 312) of the second side; and wherein the elongated electrodes (211a, 212a; 311, 312) of the first side have a distance equal to the distance between the elongated electrodes (211a, 212a; 311, 312) of the second side, characterized by , that the first RF voltage (RF1) and the second RF voltage (RF2) have different frequencies, and that the elongated electrodes (211a, 212a; 311, 312) of the second side are offset relative to the elongated electrodes (211a, 212a; 311, 312) of the first side along the axis (z) by half the distance. [12] The method according to claim 11, further comprising generating a second electric confinement field which exerts a confinement force on the ions (102) in the ion region (202; 302; 702; 802; 902; 1002; 1102; 1202; 1302; 1402) relative to the long dimension (1240; 1340; 1440) by applying the varying voltage potential (RF1, RF2) to the electrodes or the electrode set (204) and / or by applying RF potentials (RF1, RF2) or DC voltage potentials (DC211, DC212, DC311, DC312) to further electrodes (311-316). [13] The method according to claim 11 or 12, wherein the first axial force and the second axial force are each of a different nature and are each generated by an axial gas flow, an axial DC electric field or an axial transient DC electric field. [14] The method according to claim 13, wherein DC electrical potentials (DC211, DC212, DC311, DC312) or transient DC electrical potentials are applied to the electrode structures (211, 212; 304) to generate the axial DC electrical field or the axial transient DC electrical field. [15] The method according to any one of claims 11 to 14, further comprising the analysis of the separated ions (102) as a function of mass in a mass analyzer arranged downstream of the storage ion mobility separator (100; 200; 300; 700; 800; 900; 1000; 1100; 1200; 1300; 1400). [16] The method according to any one of claims 11 to 14, further comprising fragmenting the separated ions (102) into fragment ions and analyzing the fragment ions in a mass analyzer arranged downstream of the storage ion mobility separator (100; 200; 300; 700; 800; 900; 1000; 1100; 1200; 1300; 1400). [17] The method according to claim 16, wherein the separated ions (102) are selected and / or filtered according to their mass before fragmentation. [18] The method according to any one of claims 11 to 17, further comprising the accumulation of ions (102) from an ion source in an ion trap (830) located upstream of the storage ion mobility separator (100; 200; 300; 700; 800; 900; 1000; 1100; 1200; 1300; 1400), while ions (102) are analyzed in the storage ion mobility separator (100; 200; 300; 700; 800; 900; 1000; 1100; 1200; 1300; 1400).

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