Dual-frequency RF ion confinement device

Abstract

A mass spectrometry system includes an RF device for laterally confining ions in an ion region, which uses: (a) a first set of electrodes arranged parallel to each other in the ion traveling direction to define a first lateral boundary of the ion region, and to which a first RF voltage is applied such that opposite phases of the first RF voltage are applied to adjacent electrodes of the first set; (b) a second set of electrodes arranged parallel to each other in the ion traveling direction to define a second lateral boundary of the ion region, and to which a second RF voltage is applied such that opposite phases of the second RF voltage are applied to adjacent electrodes of the second set, the first and second lateral boundaries being opposite to each other in the lateral direction of the ion region, and the first and second RF voltages having different frequencies.

Description

Technical Field

[0001] The present invention relates to radio frequency (RF) devices having stacked electrodes for laterally confining ions, such as RF ion guides and RF ion traps, and to systems comprising such RF devices, such as mass spectrometry systems. Background Art

[0002] RF devices comprising a stack of perforated electrodes are well known in the fields of mass spectrometry and ion mobility. Opposite electric potentials of an RF voltage (typically at frequencies in the range of a few hundred kilohertz to a few megahertz, and voltages in the range of a few hundred volts) are alternately applied to the perforated electrodes arranged along the longitudinal axis of the RF device. The forces generated by the RF electric potential repel ions passing through the electrode holes. For example, the influence of the so-called pseudopotential generated by the RF electric potential and different operating methods is illustrated in the article by Gerlich (1992; Advances in Chemical Physics Series, Vol. LXXXII; title: “INHOMOGENEOUS RFFIELDS: A VERSATILE TOOL FOR THE STUDYOF PROCESSES WITH SLOW IONS”) and U.S. Patent No. 5,572,035. Ions are prevented from escaping through the intermediate space between the electrodes and are thus laterally confined within the RF device. A DC electric potential or a transient DC electric potential can be additionally applied to the perforated electrodes to actively drive the ions forward along the axis of the RF device or to trap the ions within the RF device along the axis.

[0003] RF devices with stacked electrodes include RF ion funnels, which are typically used to capture dispersed ions at a wide inlet and direct them to a narrow opening at the outlet (U.S. Patent No. 6,107,628), and RF ion channels comprising electrodes with a constant aperture area, which can be used to generate ion packets and actively drive the ion packets through the RF ion channel by applying a multiphase low-frequency or transient DC voltage to the electrodes or as a collision cell with active forward drive (U.S. Patent US 6,693,276).

[0004] Another example is disclosed in U.S. Patent US 7,391,021. Here, each RF device comprises a stack of perforated electrodes that allow the ion beam to be shaped in a cross-sectional profile so as to correspond to the acceptance profile of a downstream section of the device. For this purpose, at least some of the perforated electrodes do not have circular openings, but have openings that shape the cross-sectional profile of the exiting ion beam in a desired manner. An elliptical beam cross-section, separate ion beams, or an ion beam focused into a thin line shape can be obtained at the output of the stack of perforated electrodes.

[0005] The pseudopotentials generated by an RF device applied to a stacked electrode include potential well ripples between the stacked electrodes. These pseudopotential wells tend to collect ions, especially in the presence of a damping gas, and can only be overcome by an additional axial force acting on the ions. However, these devices are unable to laterally confine ions within the RF device with the stacked electrode and drive them along the axis of the RF device without or with minimal interference from the axial pseudopotential wells. SUMMARY OF THE INVENTION

[0006] The present invention provides an RF device for laterally confining ions in an ion region. The RF device includes a first set of electrodes arranged parallel to each other in the ion traveling direction (longitudinally) to define a first lateral boundary of the ion region, and a first RF voltage is applied thereto such that opposite phases of the first RF voltage are applied to adjacent electrodes of the first set. The RF device further includes a second set of electrodes arranged parallel to each other in the ion traveling direction to define a second lateral boundary of the ion region, and a second RF voltage is applied thereto such that opposite phases of the second RF voltage are applied to adjacent electrodes of the second set. The first and second lateral boundaries are opposite to each other in the lateral direction of the ion region, and the first and second RF voltages have different frequencies. The RF device includes first and second generators configured to generate the first and second voltages with different frequencies.

[0007] In an exemplary embodiment, the frequencies applied to the two electrode sets differ by more than 10%, and can differ by more than 20%, or more preferably by more than 50%. The ratio between the two frequencies is preferably not an integer to minimize the resonant excitation of ion motion, for example, f1 / f2 = 1.2 / 0.86 or 1.8 / 1.2. The average value of the two frequencies can be between 0.3 and 10 MHz, preferably around 1 MHz. The operating pressure can be less than 5000 Pa, more preferably less than 1000 Pa, and is typically between 200 and 700 Pa.

[0008] Each of the electrodes in the first and second sets has a relative spacing S along the direction of ion travel, and the first and second lateral boundaries have a relative distance D between them in the lateral direction, where the ratio D / S is preferably less than 10 in at least a portion of the RF device along the direction of ion travel, more preferably less than 5, and most preferably between 1.5 and 3. The small ratio D / S has the advantage that ions are not only confined to the ion region between the first and second boundaries, but are also laterally focused to an intermediate surface between the first and second boundaries. The spacing and the ratio D / S can be constant or can vary locally along the entire direction of ion travel. The RF device can, for example, have a large spacing or ratio D / S at the entrance, while the spacing or ratio D / S is relatively small towards or at the exit. This variation allows for a larger storage volume at the entrance and a stronger focusing on the intermediate surface at the exit, for example, the ions are focused through a hole into a subsequent pumping stage or analyzed according to mass or mobility. In one form of the invention, the effective pseudopotentials generated by the first and second electrodes are symmetric, and the Taylor expansion of the effective pseudopotential includes only even terms. In an asymmetric form, the Taylor expansion of the combined pseudopotential includes even and odd terms, where the first-order term (linear term) is associated with a constant force towards one of the electrode sets. The amplitudes of the first and second RF voltages can be different, especially to adjust the effective pseudopotential to a symmetric form.

[0009] In an exemplary embodiment of the invention, the relative spacing of the first set of electrodes is equal to the relative spacing of the second set of electrodes, and, relative to the first set of electrodes, the offset distance of the positioning of the second set of electrodes along the axis is preferably equal to half of the relative spacing.

[0010] Applying two different frequencies to two opposing electrode sets, especially in combination with a spatial offset between the sets, has the advantage that two pseudopotential distributions are generated independently of each other, such that the pseudopotential well along the axis between the electrodes is minimized. The RF device according to the invention is capable of focusing ions to an intermediate surface between the first and second boundaries without inhibiting their movement in the intermediate surface, especially along the longitudinal axis, while the prior art teaches focusing ions to a line without inhibiting their movement along the line.

[0011] In a first embodiment, the electrodes of the first and second sets together enclose the cross-sectional profile of the ion region. The electrodes of the first set can at least partially cross each other with the electrodes of the second set in an overlapping region. The overlapping area is preferably less than 20% of the inner boundary of the ion region.

[0012] In a second embodiment, the electrodes of the first and second sets do not completely surround the ion region. Additional electrodes or electrode segments of the first and second electrodes are applied and provided with a repulsive DC potential to laterally confine ions in the ion region to a portion of the ion region not defined by the electrodes of the first or second set. The repulsive DC potential applied to the additional electrodes or electrode segments preferably has a DC offset relative to the DC potential applied to the adjacent electrodes of the first and second sets. The DC offset can be constant or vary along the axis.

[0013] The plurality of electrodes of the first and second sets may have rod-shaped portions with a circular cross-section. The ratio of the diameter of the circular cross-section to the spacing of the rod-shaped portions is preferably about 2 to 3 (2 / 3).

[0014] The cross-sectional profile of the ion region can be convex, i.e., for any given two points within the cross-sectional profile, all points along the line segment between the two points also lie within the cross-sectional profile. The convex cross-sectional profile can be, for example, circular, elliptical, elongated rectangular, or elongated rectangular with rounded sides. However, the cross-sectional profile can also be non-convex, such as horseshoe-shaped, serpentine, or shaped like the space between a closed outer boundary and a closed inner boundary, such as annular. One advantage of a non-convex cross-sectional profile is that the influence of one type of charged ion on another type of charged ion will be reduced, and the number of ions that can be trapped will increase.

[0015] The ion region can have an elongated cross-sectional profile perpendicular to the axis, having a long dimension and a short dimension. Additionally, the elongated cross-sectional profile can have reflection symmetry about a plane containing the longitudinal axis and the long dimension of the ion region. The cross-sectional profile of the ion region can be constant or vary along the longitudinal axis of the ion region. The cross-sectional profile at the RF device inlet can be larger than the cross-sectional profile at the outlet, for example, to form a funnel for collecting ions and spatially focusing them at the outlet of the ion region.

[0016] The RF device can further include a DC voltage generator configured to apply an additional DC potential to the electrodes of the first and second sets and / or the additional electrodes. The additional DC potential is not used to laterally trap ions in the ion region.

[0017] These additional DC potentials can be repulsive and applied to a first set and / or a second set of electrodes near the inlet and outlet of the ion region such that ions are temporarily trapped along the longitudinal axis within the ion region. For example, by applying an additional DC potential, ions can be axially accelerated into or within the gas-filled RF device, thereby inducing fragmentation by collision with gas molecules. The ions or fragment ions can be trapped by the axial field generated by the additional DC potential or actively driven through the RF device. The additional DC potential can be time-dependent, for example, first trapping and then releasing ions from the RF device, or timely changing the fragmentation energy of ion collision-induced dissociation (CID). The additional DC potential can be a transient DC potential for generating a traveling wave within the RF device. The DC potential applied to the electrodes of the RF device can be generated by a resistor chain or a plurality of DC power supplies.

[0018] The RF device can be used for different purposes, for example, as an ion guide, an ion trap, a fragmentation unit, an ion mobility separator, especially a trapped ion mobility separator, or an ion accelerator / reflector, for example, in a time-of-flight mass analyzer.

[0019] The present invention also provides a mass spectrometry system comprising an ion source, an RF device according to the present invention, and a mass analyzer.

[0020] The ion source can generate ions, for example, using spray ionization (e.g., electrospray (ESI) or thermospray), desorption ionization (e.g., matrix-assisted laser desorption / ionization (MALDI) or secondary ionization), chemical ionization (CI), photoionization (PI), electron impact ionization (EI), or gas discharge ionization.

[0021] The mass spectrometry system can also include an ion guide and / or an ion trap between functional components, wherein the RF device is part of the ion guide and / or the ion trap. As described above, a DC potential can be applied to the first set and / or the second set of electrodes of the RF device to temporarily trap ions along the longitudinal axis of the ion region and / or to urge ions to pass through the ion region.

[0022] The mass analyzer can be, for example, a time-of-flight mass analyzer (preferably with orthogonal injection of ions), an electrostatic ion trap, an RF ion trap, an ion cyclotron frequency ion trap, and a quadrupole mass filter. The mass analyzer is preferably a time-of-flight mass analyzer and includes at least one of an accelerator, a flight path, and a reflector for orthogonal injection of ions, wherein the RF device can be incorporated into at least one of these components of the time-of-flight mass analyzer.

[0023] The mass spectrometry system may further include an ion mobility separator between the ion source and the mass analyzer, wherein the ion mobility separator includes an RF device according to the present invention. The ion mobility separator may be, for example, a TIMS (Trapped Ion Mobility Separator), which preferably includes an air flow along the longitudinal axis of the ion region and a DC voltage generator. The DC voltage generator is configured to provide a DC electric potential to the first and second sets of electrodes of the RF device for generating an axial DC electric field gradient that counteracts the force of the air flow, such that ions are trapped during the accumulation phase and separated by ion mobility. The DC voltage generator is also configured to change the DC electric potential applied to the first and second sets of electrodes such that ions are released from the ion mobility separator over time as a function of ion mobility during the elution phase. The ion region of the DC device incorporated in the TIMS preferably has an elongated cross-sectional profile perpendicular to the longitudinal axis, which has a long dimension and a short transverse dimension.

[0024] The mass spectrometry system may also include a fragmentation unit located between the ion source and the mass analyzer, wherein the fragmentation unit includes an RF device according to the present invention. The fragmentation unit is preferably located between the ion mobility separator and the mass analyzer. Ions can be fragmented, for example, by collision-induced dissociation (CID), surface-induced dissociation (SID), photodissociation (PD), electron capture dissociation (ECD), electron transfer dissociation (ETD), collision activation after electron transfer dissociation (ETcD), activation simultaneous with electron transfer dissociation (AI-ETD), and reaction with highly excited or radical neutral particles. The fragmentation unit may include, for example, a DC voltage generator configured to apply a DC electric potential along the axis to the first and / or second sets of electrodes such that ions are accelerated inside and / or into the gas-filled RF device, and the fragment ions generated by collision-induced dissociation are pushed through the ion region.

[0025] The mass spectrometry system may also include a mass filter, which may be located upstream of the fragmentation unit, especially between the ion mobility separator and the fragmentation unit. An additional mass filter may be located upstream of the ion mobility separator. In addition, separation devices, such as liquid chromatography devices or electrophoresis devices, may be part of or coupled to the mass spectrometry system. Description of the Drawings

[0026] Figure 1A Shows a first embodiment of an RF device according to the present invention, which is part of a trapped ion mobility separator (TIMS).

[0027] Figure 1B Shows Figure 1A the first upper and lower electrodes of the RF device.

[0028] Figure 1C Shows Figure 1ASchematic side views of the upper and lower electrodes of an RF device and the application of an RF potential thereto.

[0029] Figure 1D Shows Figure 1A Schematic side views of the upper and lower electrodes of an RF device and the application of a DC potential thereto.

[0030] Figure 1E Shows Figure 1A Illustration of opposing axial forces on ions in an RF device of

[0031] Figure 1F Shows Figure 1A Illustration of the effective velocity components of different ion species in an RF device of

[0032] Figure 1G Shows a diagram similar to Figure 1F showing the elution of ions from an RF device of Figure 1A

[0033] Figure 2A Shows a second embodiment of the RF device according to the present invention, having simplified electrodes compared to the first embodiment.

[0034] Figure 2B Shows Figure 2A the first upper and lower electrodes of an RF device of

[0035] Figure 2C Shows in the x-y plane Figure 2A the first upper and lower electrodes of an RF device of

[0036] Figure 2D Shows Figure 2A an alternative structure to the structure shown in, where the electrodes have long parallel portions near the center of the ion region and curved edges at the lateral extremes.

[0037] Figure 2E Shows Figure 2A a schematic diagram of one form of an RF device of , where the cross-sectional profile of the ion region varies along the z direction.

[0038] Figure 3A Shows a third embodiment of the RF device according to the present invention, having only DC electrodes for confining ions in one of the lateral directions.

[0039] Figure 3B Shows Figure 3A a schematic side view of the electrodes of an RF device of , showing the application of an RF potential thereto.

[0040] Figure 3C Shows Figure 3ASchematic side view of the electrode of the RF device, showing the application of a DC potential thereto.

[0041] Figure 3D Shows Figure 3A Schematic diagram of one form of an embodiment of, in which the cross-sectional profile of the ion region changes along the z-direction.

[0042] Figure 4A Shows a fourth embodiment of the RF device according to the present invention, in which the ion region is not completely surrounded by the electrodes of the RF device.

[0043] Figure 4B Shows Figure 4A Schematic diagram of one form of an embodiment of, in which the cross-sectional profile of the ion region changes along the z-direction.

[0044] Figure 5A Shows a fifth embodiment of the RF device according to the present invention, in which the ion region is non-convex and has an annular shape defined by the space between the coaxially aligned inner and outer electrodes.

[0045] Figure 5B Shows Figure 5A Schematic diagram of one form of an embodiment of, in which the cross-sectional profile of the ion region varies along the z-direction.

[0046] Figure 6A Shows a sixth embodiment of the RF device according to the present invention, in which the ion region is non-convex and has a generally bow-shaped configuration.

[0047] Figure 6B Shows Figure 6A Schematic diagram of one form of an embodiment of, in which the cross-sectional profile of the ion region varies along the z-direction.

[0048] Figure 6C Shows an embodiment of the RF device, in which the ion region is non-convex and has a generally meandering shape.

[0049] Figure 7 Shows a mass spectrometry system including at least one RF device according to the present invention. Detailed Description

[0050] The first embodiment of the RF device according to the present invention is shown in Figures 1A - 1G in.

[0051] Figure 1AAn RF device 100 is shown, which is part of a trapped ion mobility separator (TIMS). The RF device 100 includes an upper set of electrodes 101 and a lower set of electrodes 102, which have electrodes 101-1 to 101-N and 102-1 to 102-N, respectively. The upper electrode 101 intersects with the lower electrode 102 along the z direction, that is, a portion of the lower set of electrodes 102 is located between portions of the upper set of electrodes 101. The RF device 100 has an ion region 110, which has an elongated cross-sectional profile perpendicular to the z direction, with a long dimension along the y direction and a short dimension along the x direction. The first and second sets of electrodes (101, 102) together surround the convex cross-sectional profile of the ion region 110.

[0052] Ions enter from one side of the ion region 110 and will eventually travel to the opposite side. The direction of travel along the ion region 110 is defined as the longitudinal axis (z direction) of the RF device 100. Ions are molecular components of a sample of interest that have been ionized and introduced into the ion region 110, typically from an ionization source of known type, such as an electrospray or MALDI (matrix-assisted laser desorption ionization) type ion source or a CI (chemical ionization) ion source.

[0053] In a trapped ion mobility separator (TIMS), ions are temporarily trapped in an ion region 110 at mobility-dependent positions along the longitudinal axis of the RF device. Separation of ions by ion mobility is accomplished by using opposing forces (first / second forces) that produce oppositely acting velocity components along the longitudinal axis of the RF device. At least one of the first and second axial forces has an effect on the ions that is dependent on ion mobility, and at least one of the first and second axial forces varies spatially along the longitudinal axis of the RF device.

[0054] During the accumulation phase, the opposing forces are preferably balanced so that for each ion species of interest, there is an equilibrium point of zero velocity within the ion region 110. Since the mobility-dependent forces have different effects on ion species with different mobilities, the spatial position along the longitudinal axis of the RF device where the net velocity of a certain ion species is zero will depend on the mobility K of the ion species. In the subsequent elution phase, by changing one or both of the forces so that the velocity components change, the trapped ion species are eventually released from the ion region 110, and the ion species sequentially no longer have an equilibrium point in the ion region 110 and elute from the ion region depending on their mobility K. This relative change in the opposing axial forces may be gradual, so that ion species with gradually increasing or decreasing mobility K successively leave the TIMS. In addition to the opposing axial forces, the ions are laterally confined in the ion region 110 of the RF device.

[0055] As discussed in more detail below, the first force can be generated by an air flow with a constant velocity, while the second force can be generated by a DC electric field gradient that increases from zero to a maximum value at the platform along the z direction. The RF device provides the DC electric field gradient, as well as the lateral confinement of ions in the ion region 110. The trapped ion mobility separator (TIMS) operates at a pressure between 10 and 5000 Pa, typically between 200 and 700 Pa.

[0056] Figure 1B The first upper electrode 101-1 and the first lower electrode 102-1 are shown, both of which are significantly longer in the long dimension (y direction) than in the short dimension (x direction). Each electrode includes an elongated portion (101a-1, 102a-1) and two extension portions (101b-1 and 102b-1) that are located at the ends of each electrode, extend in the x direction, and have a generally flat shape with a curved edge facing the ion region 110. The extension portions of the upper electrode 101-1 partially overlap the extension portions of the lower electrode 102-1 in the x-y plane. In this embodiment, the elongated portion is a rod-shaped with a circular cross-section. Nevertheless, other electrode shapes can also be used, for example, having a circular cross-section only towards the ion region. The elongated portions of the upper and lower groups define the first and second lateral boundaries of the ion region 110. The extension portions define the left and right boundaries of the ion region 110.

[0057] Figure 1CA schematic side view (x-z plane) of the upper electrode 101 and the lower electrode 102 is shown. In this embodiment, two different RF potentials (RF1, RF2) having different frequencies are used, RF1 is applied to the electrode 101 and RF2 is applied to the electrode 102. As shown, the electrodes 101 and 102 alternate in the z direction, and for each RF potential, two opposite phases are used. For example, the first phase (RF1+) of RF1 is applied to each odd-numbered upper electrode (101-1, 101-3,...), while the opposite phase RF1- (180° out of phase with RF1+) is applied to the even-numbered upper electrodes (101-2, 101-4,...). Similarly, the first phase (RF2+) of RF2 is applied to each odd-numbered lower electrode (102-1, 102-3,...), while the opposite phase RF2- is applied to the even-numbered lower electrodes (102-2, 102-4,...). An important advantage of applying two RF potentials of different frequencies to the electrode structures on both sides and offsetting the electrode structures on both sides is that there is substantially no pseudopotential well generated in the ion region, especially along the longitudinal axis. The ions are focused to the intermediate surface between the upper and lower slender parts by the pseudopotential (generated by applying the RF potential to the slender part) without inhibiting their movement in the intermediate surface, especially the movement along the longitudinal axis. Focusing to this intermediate surface is important because the mobility resolution of the TIMS separator increases with the increase of the gas velocity, and the gas flow rate at the intermediate surface is the highest. The pseudopotential generated by applying the RF potential to the extended part further confines the ions to the left and right sides.

[0058] Figure 1D A schematic side view (x-z plane) of the upper electrode 101 and the lower electrode 102 and the DC potential applied to the two sets of electrodes (101, 102) is shown. As shown, the first DC potential DC 101-1 is applied to the first upper electrode 101-1, and the DC potential DC 101-N is applied to the Nth upper electrode 101-N. Similarly, the DC potential DC 102-1 is applied to the first lower electrode 102-1, and the DC potential DC 102-N is applied to the Nth lower electrode 102-N. Additional DC potentials are applied to each of the other upper and lower electrodes. These DC potentials are kept constant over time during the accumulation phase and vary during the elution phase to generate a DC electric field gradient in the z direction to control the ions in the ion region, as discussed in more detail below.

[0059] An example of this embodiment has the following parameters, but those skilled in the art will understand that these are just examples and these parameters can vary according to the application. Nevertheless, the operating pressure of the TIMS can be in the range of 10–5000 Pa (0.1–50 mbar), about 300 Pa (3 mbar) in this specific example. The length of the ion region in the z direction is 100 mm, the width in the y direction is 40 mm, and the height in the x direction is 4 mm. In this form, the number of upper electrodes 101 is 40, and the number of lower electrodes 102 is 40. The RF potential laterally confines the ions to the ion region in both the x and y directions, where the frequency of RF1 is 0.86 MHz and the frequency of RF2 is 1.2 MHz, or the frequency of RF1 is 1.2 MHz and the frequency of RF2 is 1.7 MHz. The slender part is a round rod-shaped electrode with a diameter of about 2 mm and a spacing of 3 mm from the adjacent electrode structures (above and below the ion region). The slender electrode is preferably integrated in a printed circuit board (PCB) and the DC and RF potentials are provided through leads on the PCB. Finally, the gas flow rate is between about 50 and 100 m / s.

[0060] Figures 1E to 1G Shows the effect of the opposing axial force on the ions in a laterally extended TIMS, and each figure is a plot of the velocity gradient (or effective velocity component) versus the position along the Z axis. As Figure 1E shown, there is a substantially constant gas velocity v gas pushing the ions through the ion region in the z-axis direction. Opposing this motion is a DC electric field -E DC (t), which has a spatial gradient along the z axis and which produces the effective velocity component -v DC (t) shown in the figure, and which increases from zero to a maximum value at the longitudinal position z p at the plateau, which, as described below, can be the elution point of the ions, at which the ions are no longer trapped in the laterally extended TIMS. The negative value of the DC electric field is due to its being in the opposite direction to the longitudinal force of the gas, and it is represented as a function of time because in this embodiment, during the elution of different ion species, the intensity of the DC electric field decreases.

[0061] Figure 1F Similar to Figure 1E but shows, for each of several different ion species K n-1 , K n and K n+1 the "effective" velocity component -v DC produced by the opposing DC electric field. And this "effective" velocity component is related to the mobility in the presence of gas, so the ion species K n-1 , K n and K n+1corresponding to each of those in -v DC gradients. These gradients represent the velocity components imparted to different ion species by the DC electric field E gas in the absence of the gas flow v DC (t). That is, -v DC represents the velocity component of the ions in a stationary gas that can be attributed to the DC electric field at a given pressure and temperature. This value is proportional to the strength of the DC electric field and is different for each ion species having a different mobility K (where v DC = K·E DC ). For all ion species K n-1 、K n and K n+1 , in the absence of the DC electric field, the "effective" velocity provided by the gas flow is v gas .

[0062] As Figure 1F shown, the DC electric field gradient along the z-axis results in different corresponding -v DC gradients for ion species with different mobilities. During the initial accumulation phase of the ions, the magnitude of the DC electric field is such that for each ion species of interest, -v DC is equal and opposite to the velocity component v gas imparted by the gas flow at different positions along the z-axis. Due to the different -v DC gradients of different ion species, different species of ions will be separated from each other and trapped at different positions along the z-axis. Different ion species K n-1 、K n and K n+1 are represented by circles of different sizes in Figure 1F , with the larger circles corresponding to ion species with larger cross-sections and thus lower mobilities K.

[0063] After the separation of different ion species, the ions can be eluted sequentially from the laterally extended TIMS and directed to the downstream components of the hybrid IMS-MS system or the ion detector. The elution is accomplished by gradually reducing the magnitude of the DC electric field gradient, which correspondingly reduces the magnitude of the v DC velocity component gradient, as Figure 1G shown. As these gradients are reduced, the point at which the reactive velocity components v gas and -v DC cancel each other out moves in the +z direction for each different ion species, towards the exit of the laterally extended TIMS. The electric field structure is such that the gradient increases in the +z direction until it reaches the elution point z p along the z-axis.reaches a plateau. Since the ion trapping positions for each different ion species are different, moving these trapping positions by reducing the DC electric field gradient will cause each ion species to reach the elution point z at different times p . After reaching the elution point, the ionic species are no longer trapped by the velocity component of the reaction force and leave the laterally extended TIMS in the +z direction, as Figure 1G shown for the ionic species K n-1 . In this way, the separated ionic species are eluted from the laterally extended TIMS in order of increasing mobility, from low mobility to high mobility.

[0064] A second embodiment of the RF device according to the present invention is shown in Figures 2A - 2E .

[0065] Figure 2A Fig. shows an RF device 200, which can also be part of a (laterally extended) trapped ion mobility separator (TIMS). Similar to the RF device 100, the RF device 200 includes an upper set of electrodes 201 and a lower set of electrodes 202, which have electrodes 201-1 to 201-N and 202-1 to 202-N, respectively. The upper electrodes 201 cross the lower electrodes 202 in the z direction and form an ion region 210. Similar to the above embodiment, the cross-sectional profile of the ion region 210 is convex and does not change along the longitudinal axis of the RF device.

[0066] Two different RF potentials (RF1, RF2) with different frequencies are used. RF1 is applied to the electrodes 201 and RF2 is applied to the electrodes 202. The electrodes 201 and the electrodes 202 alternate in the z direction, and for each RF potential, two opposite phases are used. The first phase (RF1+) of RF1 is applied to each odd-numbered upper electrode (201-1, 201-3,...), while the opposite phase RF1- (180° out of phase with RF1+) is applied to the even-numbered upper electrodes (201-2, 201-4,...). Similarly, the first phase (RF2+) of RF2 is applied to each odd-numbered lower electrode (202-1, 202-3,...), while the opposite phase RF2- is applied to the even-numbered lower electrodes (202-2, 202-4,...). The RF potentials laterally confine the ions in the ion region in the x and y directions. The ion region 210 has an elongated cross-sectional profile perpendicular to the z direction, which has a long dimension in the y direction and a short dimension in the x direction.

[0067] Similar to the above embodiment, a DC potential is also applied to the upper and lower electrodes (201, 202) to generate a DC electric field gradient that provides one of the reaction forces for the laterally extended TIMS. The other reaction force can again be generated by an air flow with a constant velocity.

[0068] Figure 2B The first upper electrode 201-1 and the first lower electrode 202-1 are shown, both of which are significantly longer in the long dimension (y-direction) than in the short dimension (x-direction). The upper and lower electrodes partially overlap at regions 220 at both ends of the long dimension.

[0069] Compared with the upper and lower electrodes (101, 102) of the above embodiment, the upper and lower electrodes (201, 202) are simplified. The upper and lower electrodes (201, 202) have a uniform thickness, which makes them easier and cheaper to produce. The upper and lower electrodes (201, 202) can be directly produced as metallized components of a printed circuit board (PCB) or by laser cutting of a metal plate, where multiple PCB boards with electrodes or metal plates are stacked along the axis. The thickness can be, for example, between 0.3 and 1 mm. The thickness is preferably about 0.5 mm, and the spacing between the upper (and lower) electrodes is about 2.5 mm.

[0070] Figure 2C The first upper electrode 201-1 and the first lower electrode 202-1 are shown in the x-y plane. The two electrodes have a common profile at two (left and right) overlapping regions 220. As shown, the cross-sectional profile is elliptical and symmetric about the y-z plane. However, the cross-sectional profile can also be elliptical only near the overlapping regions 220 and can further include a long parallel part in the middle. The cross-sectional profile can also include notches such that it is non-convex. The curvature of each set of electrodes 201 and 202 is preferably equal, but the curvature of the upper set 201 can be different from that of the lower set 202 (except for the overlapping regions 220). The curvature of the upper and lower electrodes can even be irregular, i.e., the curvature can include locally irregular notches.

[0071] Figure 2D Another configuration is shown, where the two electrodes (201-1', 202-1') of the upper set 201' and the lower set 202' respectively have a long parallel part near the center of the ion region and a curved edge at the lateral extreme. The two sets (201', 202') overlap at regions 220' at both ends of the long dimension. Compared with Figure 2C the upper and lower electrodes (201, 202), and compared with Figure 1B the upper and lower electrodes (101, 102) shown in Figure 2D the electrodes of the sets 201' and 202' are simplified. Figure 2C The upper and lower electrodes (201', 202') of the embodiment have a uniform thickness, which makes them easier and cheaper to produce. The cross-sectional profile is circular at two (left and right) overlapping regions 220' and includes a long parallel part in the middle. Compared with Figure 2DThe upper and lower electrode groups (201', 202') include additional electrodes 201-1” and 202-1”. The additional electrode 201-1” bridges the gap between the upper electrodes 201-1' in the overlapping region 220'. The additional electrode 202-1” bridges the gap between the lower electrodes 202-1' in the overlapping region 220'. Two different RF potentials with different frequencies are applied to the upper electrode group 201' and the lower electrode group 202', as described above for Figure 2C the upper and lower electrodes (201, 202). As in that embodiment, a DC potential can be applied to the upper electrode 201' and the lower electrode 202' to generate a DC electric field gradient, which provides one of the opposing forces for the laterally extended TIMS that can use this electrode. No RF potential is applied to the additional electrodes 201-1” and 202-1”, but the same DC potential as that of the electrodes (201-1', 202-1') of the upper and lower groups is applied, which are located in the same x-y plane and the additional electrodes bridge the gap between the overlapping regions 220' for this potential. The additional electrodes 201-1” and 202-1” improve the uniformity of the DC electric field gradient.

[0072] Figure 2E A schematic diagram of the ion region of the RF device 200” in the y-z plane and in the x-y plane at the inlet and outlet of the RF device 200” is shown. The RF device 200” is similar to Figure 2A the RF device 200, but the cross-sectional profile is not constant along the z direction, but changes from an elliptical cross-sectional profile at the inlet to a circular cross-sectional profile at the outlet. The extension of the ion region along the x direction remains constant, while the extension along the y direction decreases, which results in spatial focusing of the ions along the y direction. However, the cross-sectional profile can also vary in both lateral directions.

[0073] A third embodiment of the RF device according to the present invention is shown in Figures 3A - 3D it.

[0074] Figure 3A An RF device 300 is shown, which includes an upper electrode group 301, a lower electrode group 302, a left electrode group 303, and a right electrode group 304 that are stacked and arranged along the axis (z direction) of the RF device 300. The RF device 300 has an ion region 310, which has a rectangular cross-sectional profile perpendicular to the z direction, whose extension in the y direction is slightly larger than that in the x direction, and which does not change along the longitudinal axis of the RF device 300.

[0075] The upper electrode group 301 does not cross the lower electrode group 302 along the z direction, but the left and right electrode groups (303, 304) cross the upper and lower electrode groups (301, 302).

[0076] The four sets of electrodes are rod-shaped. The upper and lower sets of rod-shaped electrodes (301, 302) extend parallel to the y-direction. The left and right sets of rod-shaped electrodes (303, 304) extend parallel to the x-direction along the left and right edges of the ion region 310. For example, the electrodes can be fabricated as metallized components of a PCB board, which are supplied with appropriate RF and DC potentials, and multiple such PCB boards with electrodes can be arranged in a stack along an axis.

[0077] Figure 3B A schematic side view (x-z plane) of the upper electrode 301, the lower electrode 302, and the right electrode 304 is shown. RF potentials (RF301, RF302) are applied to the upper and lower sets of electrodes (301, 302) respectively, but not to the right set of electrodes 304, nor is it connected to the left set of electrodes 303 (not shown). As described above, the upper set of electrodes 301 does not cross the lower set of electrodes 302 in the z-direction, but the left and right sets of electrodes (303, 304) are placed between the upper and lower sets of electrodes (301, 302). Compared with the above embodiments, the electrode groups 301, 302 to which the RF potential is applied do not completely surround the ion region 310, but only surround the upper and lower boundaries of the ion region 310.

[0078] The first RF potential (RF1) is applied to the upper electrode 301, and the second RF potential (RF2) is applied to the lower electrode 302. As Figure 3B shown, for each RF potential, two opposite phases are used. For example, the first phase (RF1-) of RF1 is applied to each odd-numbered upper electrode (301-1, 301-3,...), while the opposite phase RF1+ (180° out of phase with RF1-) is applied to the even-numbered upper electrodes (301-2, 301-4,...). Similarly, the first phase (RF2-) of RF2 is applied to each odd-numbered lower electrode (302-1, 302-3,...), while the opposite phase RF2+ is applied to the even-numbered lower electrodes (302 2, 302-4,...). Therefore, the ions are confined within the ion region 310 by a pseudopotential that only acts along the x-direction, and not along (or only in a very limited way along) the y-direction. An important advantage of applying two different frequencies of RF potentials to the electrode structures at the two boundaries is that there is basically no generation of pseudopotential wells along the longitudinal axis within the ion region.

[0079] Figure 3C A schematic side view (x-z plane) of the upper electrode 301, the lower electrode 302, and the right electrode 304 of the Figure 3A embodiment is shown. DC potentials (DC304-1,...DC304-N) are applied to the right set of electrodes 304 and DC potentials (DC303-1,...DC303-N) are applied to the left set of electrodes 303 (not shown).

[0080] DC potentials (DC301-1 to DC301-N) and (DC302-1 to DC302-N) can also be applied to the upper and lower electrodes (301, 302) to actively guide ions through the RF device 300, for accelerating ions into the RF device 300 or accelerating them inside it or for trapping ions axially inside the RF device 300.

[0081] The DC potentials (DC303, DC304) applied to the left and right electrodes (303, 304) are repulsive and are used to laterally confine the ions in the ion region 310 in the y direction. Preferably, the DC potentials applied to the left and right electrodes (303, 304) are offset with respect to those applied to the directly adjacent upper and lower electrodes such that the ions are laterally confined in the y direction, while the DC potentials on the upper and lower electrodes (301, 302) vary axially, for example to drive or trap ions. The offset can be constant or can vary axially. The DC potential applied to the nth electrode 304 of the right group is preferably equal to the DC potential applied to the nth electrode 303 of the left group.

[0082] The RF device 300 can be filled with gas and used as a unit for fragmenting ions by collision-induced dissociation (CID). By applying a DC voltage between an upstream component (not shown) and the electrodes at the entrance of the RF device 300, ions can be axially accelerated into the RF device 300 and fragmented by collisions with gas molecules inside the RF device 300. Ions can also be accelerated inside the RF device 300 by applying an appropriate DC potential axially to the electrodes of the RF device 300.

[0083] The RF device 300 can also be used as an RF ion guide or an RF ion trap. A DC potential can be applied to the electrodes (301 to 304) to drive ions that are introduced into the RF device 300 or generated inside the RF device 300, through the RF device 300 to the exit, especially when it is filled with a damping gas or used as a CID fragmentation unit. By applying an appropriate DC potential at the electrodes of the RF device 300, ions introduced into the RF device 300 or generated inside the RF device 300 can be trapped inside the RF device 300. The RF device 300 can also be used as an ion mobility separator, especially as a trapping ion mobility separator.

[0084] The DC potential applied to the electrodes of the RF device 300 can be time-dependent to change the fragmentation energy of CID or to change the velocity of the ions inside the RF device 300 in a timely manner. For example, the DC potential can be a transient DC potential for generating a traveling wave inside the RF device 300. The DC potentials applied to the electrodes 301, 302, 303, and 304 can be generated by a resistor chain or by individual DC power supplies.

[0085] Figure 3D Shows a schematic view of the ion region of the RF device 300' in the y-z plane and in the x-y plane at the inlet and outlet of the RF device 300'. The RF device 300' is similar to Figure 3A the RF device 300, but the cross-sectional profile is not constant along the z direction, but changes from a square cross-sectional profile at the inlet to a rectangular cross-sectional profile at the outlet. The extension of the ion region in the y direction remains unchanged, while the extension in the x direction decreases, which results in spatial focusing of the ions in the x direction. The RF device 300' can be used as a DC / RF ion funnel. The cross-sectional profile can also vary in both transverse directions.

[0086] A fourth embodiment of the RF device according to the present invention is shown in Figure 4A and 4B is shown.

[0087] Figure 4A Shows an RF device 400, which includes an upper set of electrodes 401 (401a, 401b, 401c) and a lower set of electrodes 402 (402a, 402b, 402c) arranged in a stacked manner along the axis (z direction) of the RF device 400. The RF device 400 has an ion region 410, which has a rectangular cross-sectional profile perpendicular to the z direction, whose extension in the y direction exceeds its extension in the x direction, and which does not change along the longitudinal axis of the RF device 400.

[0088] The upper and lower sets (401, 402) each include an elongated electrode set (401b, 402b) between a left electrode set (401a, 402a) and a right electrode set (401c, 402c). Each electrode in the two sets (401, 402) is segmented and includes an elongated electrode located between two short extensions, which are arranged in a straight line along the y direction respectively. Contrary to the above embodiments, the ion region 400 is not completely surrounded by the upper and lower sets (401, 402). The ion region 400 is limited by the upper and lower electrode sets (401, 402) in the x direction and extends to the elongated electrode sets (401b, 402b) in the y direction. The upper set of electrodes (401a, 401b, 401c) is preferably offset from the lower set of electrodes (402a, 402b, 402c) in the z direction.

[0089] In this embodiment, the upper and lower sets of electrodes (401, 402) are rod-shaped with a circular cross-section. In other embodiments, the cross-sectional shape of the two sets of electrodes does not need to be circular. For example, the rod-shaped electrodes can have a circular surface only on the side facing the ion region 410. The segments of the electrodes can be simplified to three thin conductive plates or can be made as metallized parts of a PCB board. Then the thin conductive plates and the PCB board are arranged in a stack along the axis.

[0090] Two different RF potentials having different frequencies are applied to the upper and lower elongated electrodes (401b, 402b). A first RF potential RF1 is applied to the upper elongated electrode 401b and a second RF potential RF2 is applied to the lower elongated electrode 402b. The first phase of RF1 is applied to each odd-numbered upper elongated electrode, while the opposite phase is applied to the even-numbered upper elongated electrodes. Similarly, the first phase of RF2 is applied to each odd-numbered lower elongated electrode, while the opposite phase is applied to the even-numbered lower elongated electrodes. Thus, ions are confined within the ion region 410 by the pseudopotential only in the x direction and not in the y direction. Preferably, the RF potential applied to the elongated segments of the electrodes is also applied to the short extension segments.

[0091] An important advantage of applying two different frequency RF potentials to the elongated upper and lower electrodes (401b, 402b) is that substantially no pseudopotential wells are generated along the axis within the ion region.

[0092] A DC potential is applied to the left electrode group (upper 401a, lower 402a) and the right electrode group (upper 401c, lower 402c). The DC potential can also be applied to the elongated electrode group (upper 401b, lower 402b) for actively guiding ions through the RF device 400, for accelerating ions into the RF device 400 or accelerating them inside the RF device 400 or trapping ions along the axis inside the RF device 400.

[0093] The DC potential applied to the left and right electrode groups (401a, 402a, 401c, 402c) is repulsive and is used to laterally confine the ions in the ion region 410 in the y direction. Preferably, the DC potential applied to the left and right electrode groups (401a, 402a, 401c, 402c) has an offset relative to the DC potential applied to the directly adjacent elongated electrodes such that the ions are laterally confined in the y direction even if the DC potential on the elongated electrode group (401b, 402b) changes along the axis, for example to drive or trap ions along the axis. The offset can be constant or can vary along the axis. The DC potential applied to the nth electrode in the stack of the left and right groups (401a, 402a, 401c, 402c) is preferably the same.

[0094] The DC potential applied to the electrodes of the RF device 400 can be time-dependent, for example to change the fragmentation energy of CID or to change the ion velocity inside the RF device 400 in a timely manner. The DC potential can be, for example, a transient DC potential for generating a traveling wave inside the RF device 400. The DC potential applied to the electrodes 401a, 402a, 401b, 402b, 401c and 402c can be generated by a resistor chain or by separate DC power supplies.

[0095] The RF device 400 can be used as an RF ion guide, an RF ion trap, a fragmentation unit, an ion mobility separator, in particular as a trapping ion mobility separator, or in an ion accelerator / reflector of a time-of-flight mass analyzer.

[0096] Figure 4B A schematic view shows the ion region of the RF device 400' in the y-z plane and in the x-y plane at the inlet and outlet of the RF device 400'. The RF device 400' is similar to Figure 4A the RF device 400, but the cross-sectional profile is not constant along the z direction, but varies from a more elongated cross-sectional profile at the inlet to a less elongated cross-sectional profile at the outlet. The extension of the ion region in the x direction remains constant, while the extension in the y direction decreases, which results in spatial focusing of the ions in the y direction. Thus, the RF device 400' can be used as a DC / RF ion funnel. The cross-sectional profile can also vary in both transverse directions.

[0097] A fifth embodiment of the RF device according to the present invention is shown in Figure 5A and Figure 5B therein.

[0098] Figure 5A An RF device 500 is shown, which includes an outer set of annular electrodes 501 and an inner set of annular electrodes 502, which are arranged in a stack along the axis (z direction) of the RF device 500. The ion region is defined as the space between the coaxially aligned inner and outer electrodes (501, 502). The cross-sectional profile does not vary along the longitudinal axis of the RF device 500. The outer electrode 501 is preferably offset from the inner electrode 502 in the z direction.

[0099] In this embodiment, the cross-sectional profile of each ring of the inner and outer electrode sets (501, 502) is circular. In other embodiments, the cross-sectional profile of the electrodes does not need to be circular. For example, the shape of the electrodes can be circular only on the side facing the ion region. The outer set of electrodes can also be in the form of a conductive plate with a circular hole, while the inner set of electrodes can be in the form of a circular conductive plate. The inner and outer sets of electrodes can also be metallized parts of a PCB board. Then, the conductive plates and the PCB boards can be arranged in a stack along the axis.

[0100] Two different RF potentials with different frequencies are applied to the inner and outer electrodes (501, 502). A first RF potential RF1 is applied to the outer electrode 501, and a second RF potential RF2 is applied to the inner electrode 502. The first phase of RF1 is applied to each odd-numbered outer electrode, while the opposite phase is applied to the even-numbered outer electrodes. Similarly, the first phase of RF2 is applied to each odd-numbered inner electrode, while the opposite phase is applied to the even-numbered inner electrodes. Thus, the ions are confined within the ion region by the pseudopotential between the inner and outer electrodes. As described in the above embodiments, a DC potential can be applied to the electrodes of the inner and outer electrodes (501, 502).

[0101] Contrary to the above embodiments, Figure 5A The cross-sectional profile of the ion region of the illustrated embodiment is non-convex, that is, for any given two points within the cross-sectional profile, not all points along the line segment between the two points lie within the cross-sectional profile. The advantage of the non-convex cross-sectional profile is that it reduces the influence of one charged ion on another charged ion and increases the number of ions that can be trapped.

[0102] The RF device 500 can be used, for example, as an RF ion guide, an RF ion trap, a fragmentation unit, an ion mobility separator, especially as a trapping ion mobility separator.

[0103] Figure 5B A schematic view of the ion region of the RF device 500' in the y-z plane and in the x-y plane at the inlet and outlet of the RF device 500' is shown. The RF device 500' is similar to Figure 5A the RF device 500, but the cross-sectional profile is not constant along the z direction but varies such that the annular space decreases in two transverse directions, which results in spatial focusing of the ions.

[0104] A sixth embodiment of the RF device according to the present invention is shown in Figures 6A to 6C .

[0105] Figure 6A The RF device 600 is shown, which includes an arcuate outer electrode group 601 and an arcuate inner electrode group 602 arranged in a stacked manner along the axis (z direction) of the RF device 600. The inner arcuate electrode 601 is preferably offset along the z direction relative to the outer arcuate electrode 602. An electrode 603 extending parallel to the longitudinal axis of the RF device 600 is located at one end of the two arcuate electrode groups (601, 602), and an electrode 604 is located at the other end of the two arcuate electrode groups (601, 602). The ion region is defined as the space between the coaxially aligned arcuate electrodes (601, 602) bounded by the axially extending electrodes 603 and 604. The cross-sectional profile of the ion region does not vary along the longitudinal axis of the RF device 600.

[0106] In this embodiment, the inner and outer sets of electrodes (601, 602) are bent and have a circular cross-section. Nevertheless, in alternative embodiments, the cross-section of the electrodes may be circular only on the side facing the ion region (e.g., having a semi-circular cross-section). The inner and outer sets of electrodes (601, 602) may be replaced by conductive plates or may be metallized portions of a PCB board. The conductive plates and the PCB board may then be arranged in a stack along the axis. The extension electrodes (603, 604) may be segmented and may also be metallized portions of the same PCB board as the inner and outer arcuate electrodes.

[0107] Two different RF potentials having different frequencies are applied to the inner and outer arcuate electrodes (601, 602). A first RF potential RF1 is applied to the outer electrode 601 and a second RF potential RF2 is applied to the inner electrode 602. The first phase of RF1 is applied to each odd-numbered outer arcuate electrode, while the opposite phase is applied to the even-numbered outer arcuate electrodes. Similarly, the first phase of RF2 is applied to each odd-numbered inner arcuate electrode, while the opposite phase is applied to the even-numbered inner arcuate electrodes. A repulsive DC potential is applied to the extension electrodes (603, 604). The pseudopotential generated by the arcuate RF electrodes (601, 602) and the DC potential applied to the extension electrodes (603, 604) confine the ions within the ion region. As described in the above embodiment, a DC potential may also be applied to the arcuate electrodes (601, 602).

[0108] As Figure 5A and Figure 5B shown in the embodiment, the cross-sectional profile of the ion region is non-convex. The advantage of the non-convex cross-sectional profile is that it reduces the influence of one charged ion on another charged ion and increases the number of ions that can be trapped.

[0109] Figure 6B Shows a schematic view of the ion region of the RF device 600' in the y-z plane and in the x-y plane at the inlet and outlet of the RF device 600'. The RF device 600' is similar to Figure 6A the RF device 600, but the cross-sectional profile is not constant along the z direction. Alternatively, the device has a bow-shaped spatial azimuth that decreases along the longitudinal axis of the RF device.

[0110] Figure 6C Shows a schematic view of the ion region of another RF device 600'' in the y-z plane and in the x-y plane at the inlet and outlet of the RF device 600''. Here, the cross-sectional profile does not change along the longitudinal axis of the RF device 600'' and includes three arcuate portions having the same curvature, which form a meandering shape. The electrodes defining the upper and lower boundaries may be similar to Figure 6AThose shown in the embodiments of. By applying RF potentials of two different frequencies to the upper and lower electrodes, ions are confined between the upper and lower boundaries. As Figure 6A As shown in the embodiments of, additional electrodes are located at each of the two ends of the meander, and a repulsive DC potential can be applied to these electrodes.

[0111] Figure 7 A schematic diagram of a mass spectrometry system 700 is shown, in which the RF device according to the present invention can be used in different components of the mass spectrometry system 700.

[0112] The mass spectrometry system 700 may include two ion sources (711, 721), an ion mobility separator 734, a transfer ion guide 741, a mass filter 751, a fragmentation unit 761, and a mass analyzer 770. The ion mobility separator 734 is preferably a trapped ion mobility separator (TIMS), more preferably a laterally extended TIMS, as Figures 1A to 1G described in and FIGS. 2A to 2E. The TIMS separator 734 preferably operates in a parallel accumulation mode, i.e., such that ions accumulate in the upstream ion trap 731, while the pre-accumulated ions are analyzed in parallel in the TIMS separator 734 in a timely manner. The mass filter 751 is preferably a quadrupole mass filter. The mass analyzer 770 is preferably a time-of-flight analyzer with orthogonal ion injection (OTOF-MS). A separation device (not shown), such as a liquid chromatography device or an electrophoresis device, can be coupled to the mass spectrometry system 700.

[0113] The chamber 710 is maintained at atmospheric pressure and incorporates, for example, an electrospray ionization source (ESI) 711. Other possible ion source types include thermospray, desorption ionization (such as matrix-assisted laser desorption / ionization (MALDI) or secondary ionization), chemical ionization (CI), photoionization (PI), electron impact ionization (EI), and gas discharge ionization. The ions generated by the (ESI) ion source 711 are introduced into the first vacuum chamber 720 through a transfer capillary 712 and then deflected into the RF funnel 723 by a repulsive DC potential applied to the deflection electrode 722. The transfer capillary is preferably a large-bore short capillary with an inner diameter of more than 1 mm and a length of less than 180 mm.

[0114] The vacuum chamber 720 is preferably maintained at an elevated pressure between 1000 Pa and 3000 Pa and preferably includes a sub-atmospheric ESI ion source 721. The ions generated by the sub-atmospheric ESI source 721 are deflected into the RF funnel 723 by a repulsive DC potential applied to the deflection electrode 722. An additional MALDI source may be located at the position of the deflection electrode 722. The ESI ion sources 711 and 721 and the additional MALDI source can be operated simultaneously or separately from each other. The RF funnel 723 can be, for example, an RF device according to the present invention, such as Figure 2E 、3D as shown in one of 4B, 5B, or 6B. For example, ions can be driven through the RF funnel 723 by an axial DC field generated inside the RF funnel 723 or by an air flow towards the outlet of the RF funnel 723.

[0115] The vacuum chamber 730 is preferably maintained at a pressure lower than that of the upstream chamber 710, for example, at a pressure between 100 Pa and 1000 Pa. An air flow towards the outlet of the RF funnel 723 can be generated by pumping gas away from the chamber 720 through a hole between the two chambers (720, 730). Ions are transmitted from the chamber 720 through the inter-chamber hole into the ion trap 731. The ion trap 731 is preferably an RF device according to the present invention, for example, as Figure 3A described in or 4A. The cross-sectional profile and length of the ion trap 731 are preferably adapted to the cross-sectional profile and length of the downstream ion mobility separator 734, especially when the ion mobility separator 734 is a laterally extended TIMS. As described above, ions can be trapped in the ion trap 731 and then actively expelled from the ion trap by an axial DC field. The repulsive DC potential applied to the deflection electrode 732 deflects the ions released from or transmitted through the ion trap 731 into the RF funnel 733. An additional MALDI source can be located at the position of the deflection electrode 732.

[0116] The RF funnel 733 collects the ions released from the ion trap 731 or generated by an additional MALDI source in the chamber 730 and guides them to the ion mobility separator 734. The ion mobility separator is preferably a laterally extended TIMS, as in Figures 1A to 1G and 2A to 2E. Preferably, the two opposing forces of the laterally extended TIMS 734 are an air flow and a DC field gradient that are guided to the outlet of the laterally extended TIMS 734.

[0117] The air flow in the laterally extended TIMS 734 is generated by pumping gas away from the outlet of the laterally extended TIMS 734 through a pumping port (not shown) and a hole between the two chambers (730, 740).

[0118] During the accumulation phase, the two opposing forces are balanced such that for each ion species of interest, there is a balance point of zero velocity inside the laterally extended TIMS 734. During the subsequent elution phase, the trapped ion species are finally released from the laterally extended TIMS 734 by changing the DC field gradient such that the ion species in the laterally extended TIMS 734 are eluted sequentially according to their mobility K. This relative change in the opposing axial forces can be gradual such that the ion species with continuously increasing mobility K continuously exit the laterally extended TIMS 734.

[0119] Ions released from the laterally extended TIMS 734 enter the downstream chamber 740 and are guided by the RF ion guide 741 into the even more downstream chamber 750 where the mass filter 751 is located. The RF ion guide 741 can be, for example, an RF device according to the present invention, such as, as Figure 4A and 4B described therein. Chamber 740 serves as a pressure stage between the medium vacuum of the laterally extended TIMS 734 and the high vacuum for operating the mass filter 751. Ions are guided or selected in the mass filter 751 according to their mass.

[0120] Then, the ions passing through the mass filter 751 are guided to the fragmentation unit 761 in chamber 760, where larger ions can be fragmented to allow mass spectrometry measurement of the ion fragments. In an exemplary embodiment, collision-induced dissociation (CID) is used to accomplish the fragmentation. However, any other known type of fragmentation can also be used, including but not limited to infrared multiphoton dissociation (IRMPD) or ultraviolet photodissociation (UVPD), surface-induced dissociation (SID), photodissociation (PD), electron capture dissociation (ECD), electron transfer dissociation (ETD), collision activation after electron transfer dissociation (ETcD), activation simultaneous with electron transfer dissociation (AI-ETD), and fragmentation by reaction with highly excited or radical neutral particles.

[0121] For example, the fragmentation unit 761 can include an RF device according to the present invention, such as, as Figure 4A and 4B described therein. Fragmentation by CID can be controlled to be turned on and off by instrument parameters, such as the axial acceleration voltage. The precursor ions as well as the fragmenting ions during fragmentation can be trapped in the fragmentation unit 761 without being fragmented. A DC potential can be applied to the electrodes of the fragmentation unit 761 to generate an axial DC field for ejecting the trapped ions into the downstream mass analyzer 770, which can be any one of many different types of mass analyzers.

[0122] In an exemplary embodiment, the mass analyzer 770 is a time-of-flight mass analyzer with orthogonal ion injection, as known in the art. Other possible mass analyzers include an electrostatic ion trap, an RF ion trap, an ion cyclotron frequency ion trap, and a quadrupole mass filter. The time-of-flight mass analyzer 770 includes an accelerator 771, a flight path 772, a reflector 773, and an ion detector 774. The flight path 772 is preferably field-free. Additional reflectors can be located between the accelerator 771 and the ion detector 774 such that the ions are reflected twice in the reflector 773 and move in a w-shaped trajectory rather than a v-shaped trajectory. An RF device according to the present invention can be incorporated in the accelerator 771, the flight path 772, and / or the reflector 773.

Claims

1. An RF device for laterally confining ions in an ion region, which comprises: a first set of electrodes arranged parallel to each other along the ion traveling direction to define a first lateral boundary of the ion region, and a first RF voltage is applied thereto such that opposite phases of the first RF voltage are applied to adjacent electrodes of the first set; a second set of electrodes arranged parallel to each other along the ion traveling direction to define a second lateral boundary of the ion region, and a second RF voltage is applied thereto such that opposite phases of the second RF voltage are applied to adjacent electrodes of the second set, wherein the first and second lateral boundaries are opposite to each other in the lateral direction of the ion region, and the first and second RF voltages have different frequencies.

2. The RF device according to claim 1, wherein, the frequencies of the first and second RF voltages differ by more than 10%.

3. The RF device according to claim 1, wherein, each set of electrodes in the first and second sets has a relative spacing S along the ion traveling direction, and the first and second lateral boundaries have a relative distance D between each other in the lateral direction, wherein the ratio D / S is less than ten in at least a part of the RF device along the ion traveling direction.

4. The RF device according to claim 1, wherein, the relative spacing of the first set of electrodes is equal to the relative spacing of the second set of electrodes, and relative to the first set of electrodes, the second set of electrodes is positioned offset by a predetermined distance along the ion traveling direction.

5. The RF device according to claim 1, wherein, the electrodes of the first and second sets together enclose the cross-sectional profile of the ion region.

6. The RF device according to claim 5, wherein, the electrodes of the first set and the electrodes of the second set at least partially cross each other in the overlapping region.

7. The RF device according to claim 1, wherein, the electrodes of the first and second sets do not completely enclose the cross-sectional profile of the ion region, and wherein additional electrodes or electrode segments are applied and provided with a repulsive DC potential to laterally confine the ions in a part of the ion region not defined by the electrodes of the first or second set.

8. The RF device according to claim 7, wherein, a DC potential is applied to the first or second set of electrodes, and the repulsive DC potential applied to the additional electrodes or electrode segments has a DC offset with respect to the DC potential applied to the adjacent electrodes of the first and second sets.

9. The RF device according to claim 1, wherein, a plurality of electrodes in the first and / or second sets have rod-shaped portions with a circular cross-section.

10. The RF device according to claim 9, wherein, the ratio of the diameter of the circular cross-section to the spacing between adjacent rod-shaped portions is 2 to 3.

11. The RF device according to claim 1, wherein, the cross-sectional profile of the ion region is convex.

12. The RF device according to claim 1, wherein, the cross-sectional profile of the ion region is non-convex.

13. The RF device according to claim 1, wherein, the ion region has an elongated cross-sectional profile perpendicular to the ion traveling direction, and the elongated cross-sectional profile has a long dimension and a short dimension.

14. The RF device according to claim 1, wherein, The cross-sectional profile of the ion region varies along the ion travel direction.

15. The RF device according to claim 14, wherein, the cross-sectional profile at the entrance of the RF device is larger than the cross-sectional profile at the exit.

16. The RF device according to claim 1, wherein, the RF device further includes a DC voltage generator configured to apply a repulsive DC electric potential to a first set and / or a second set of electrodes near the entrance and the exit of the ion region, such that ions are temporarily trapped within the ion region along the ion travel direction.

17. The RF device according to claim 1, wherein, the RF device further includes a DC voltage generator configured to apply a DC electric potential along the ion travel direction to the first set and / or the second set of electrodes to urge ions to pass through the ion region, to be accelerated within the ion region or to be accelerated into or released from the ion region.

18. A mass spectrometry system, the mass spectrometry system comprising: an ion source; a mass analyzer; and an RF device for laterally confining ions within an ion region, which includes: a first set of electrodes arranged parallel to each other along the ion travel direction to define a first lateral boundary of the ion region, and to which a first RF voltage is applied such that opposite phases of the first RF voltage are applied to adjacent electrodes of the first set; and a second set of electrodes arranged parallel to each other along the ion travel direction to define a second lateral boundary of the ion region, and to which a second RF voltage is applied such that opposite phases of the second RF voltage are applied to adjacent electrodes of the second set, wherein the first and second lateral boundaries are opposite to each other laterally, and the first and second RF voltages have different frequencies.

19. The mass spectrometry system according to claim 18, wherein, each set of electrodes in the first and second sets has a relative spacing S along the ion travel direction, and the first and second lateral boundaries have a relative distance D between each other laterally, where the ratio D / S is less than ten in at least a part of the RF device along the ion travel direction.

20. The mass spectrometry system according to claim 18, wherein, the relative spacing of the first set of electrodes is equal to the relative spacing of the second set of electrodes, and the second set of electrodes is positioned offset by a predetermined distance along the ion travel direction with respect to the first set of electrodes.

21. The mass spectrometry system according to claim 18, wherein, the mass spectrometry system further includes an ion mobility separator between the ion source and the mass analyzer, wherein the ion mobility separator includes the RF device.

22. The mass spectrometry system according to claim 21, wherein, the mass spectrometry system further includes an air flow and a DC voltage generator along the ion travel direction, wherein the DC voltage generator is configured to supply a DC electric potential to the electrodes of the first and second sets for generating a DC electric field gradient along the ion travel direction that counteracts the force of the air flow, such that ions are trapped during an accumulation phase and separated by ion mobility, and The DC voltage generator is configured to vary the DC potential applied to the first and second sets of electrodes such that ions are released from the ion mobility separator as a function of ion mobility over time during the elution phase.

23. The mass spectrometry system according to claim 22, wherein, the ion region has an elongated cross-sectional profile perpendicular to the ion travel direction, having a long dimension and a short transverse dimension.

24. The mass spectrometry system according to claim 18, wherein, the mass spectrometry system further includes a fragmentation unit located between the ion source and the mass analyzer, wherein the fragmentation unit includes the RF device.

25. The mass spectrometry system according to claim 24, wherein, the fragmentation unit is filled with a collision gas and further includes a DC voltage generator configured to apply a DC potential to the first and / or second sets of electrodes such that ions are accelerated into the collision gas and to cause fragment ions resulting from collision-induced dissociation to pass through the ion region.

26. The mass spectrometry system according to claim 18, wherein, the mass analyzer is a time-of-flight mass analyzer and includes an RF device, the RF device being part of at least one of an accelerator for orthogonal injection of ions, a field-free flight path, and a reflector.

Images