WO2025158354A1 - Steering / focusing lens for time-of-flight mass spectrometry - Google Patents

Abstract

Disclosed are assemblies, systems, methods, and other implementations, including an ion lens assembly that includes one or more focusing apertures for receiving ions and directing the received ions along an ion path into a time-of-flight mass analyzer. The lens assembly includes a last one of said one or more focusing apertures positioned at an end of the ion path to receive the ions propagating through the ion path and to generate a focused ion beam, and at least a first steering element positioned to receive the focused ion beam and configured to steer the focused ion beam relative to a downstream pusher electrode of the time-of-flight mass analyzer.

Description

STEERING / FOCUSING LENS FOR TIME-OF-FLIGHT MASS SPECTROMETRY

Related

[0001] This application claims priority to U.S. Provisional Application No. 63/625,446 filed on January 26, 2024, the contents of which are incorporated herein by reference in their entirety.

Technical Field

[0002] The present disclosure relates generally to systems and methods for performing mass spectrometry, and more particularly to such systems and methods that utilize time-of-flight (ToF) mass analyzers, including TOF mass analyzers that use ion focusing and steering mechanisms.

Background

[0003] The present disclosure provides systems and methods for performing mass spectrometry using a time-of-flight (TOF) mass analyzer, and particularly mass spectrometry systems with improved focusing and steering functionality based on an improved focusing lens assembly in which at least one steering element is positioned downstream of the last focusing aperture in the ion path leading into a mass analyzer (typically, a TOF mass analyzer).

[0004] Mass spectrometry (MS) is an analytical technique for determining the structure of test chemical substances with both qualitative and quantitative applications. MS can be useful for identifying unknown compounds, determining the composition of atomic elements in a molecule, determining the structure of a compound by observing its fragmentation, and quantifying the amount of a particular chemical compound in a mixed sample. Mass spectrometers detect chemical entities as ions such that a conversion of the analytes to charged ions must occur.

[0005] Time-of-flight mass spectrometry relies on different arrival times for separate ions having different m/z ratios. In such systems, the mass analyzer can include a pusher electrode to which voltage pulses can be applied to direct ions arriving at the pusher electrode into an acceleration region in which the ions are accelerated via an electric field. The accelerated ions enter a field- free ion drift region in which they travel to reach an ion detector that detects the ions. The time required for the ions to pass through the drift region to reach the ion detector depends on their m/z ratios, thereby allowing the ions to be separated based on their m/z ratios.

[0006] Typically, mass spectrometers include ion lens assemblies to perform ion focusing and steering operation. Such ion lens assemblies are positioned upstream of the TOF mass analyzer, within low or medium vacuum regions, where collisions between the ions and background gas occur. Ions travel from a mass spectrometer’s collision cell, to a focusing orifice lens, and from there to the TOF analyzer. As the gas escapes from the collision cell, it will increase the pressure in the lens.

Summary

[0007] The present disclosure is directed to a proposed framework that uses a lens assembly implementation, coupling (directly or via another vacuum chamber) a downstream end section of an ion path structure to an entrance region of a TOF mass analyzer. The proposed lens assembly places two steering elements (e.g., vertical steering and a horizontal steering elements; the two steering elements may be implemented as cylindrical steering elements) on either side of a medium vacuum / high vacuum barrier (e.g., an exit lens of a pressurized collision cell section of a mass spectrometer). By placing one steering on either side of the barrier between the high and medium vacuum zones, an enhanced steering capability is achieved (due to the use of two steering elements), while avoiding focusing issues that arise when the two steering elements are arranged sequentially (adjacent to each other in a back-to-back configuration.

[0008] It is beneficial to have the capability to steer and focus ions at several locations along the beam pathway between the source of the ions (e.g., IQ2 or IQ3) and the destination (TOF accelerator). Placing one of steering elements (e.g., the horizontal steering / focusing component) in the highest vacuum section, close to the TOF accelerator, has the advantage of keeping the IQ3 as close as possible to the accelerator, and increases the separation of the vertical and horizontal focusing components. This changes the nature of the relative focusing capabilities. In such a configuration, the strength of the focusing is enhanced. In addition, the action of focusing and steering is less affected by collisions with gas exiting the collision cell. [0009] The proposed lens assembly is effective in preparing a diverging ion beam for subsequent time-of-flight mass analysis. The capability that the three elements of the lens assembly have in controlling the way the ions are diverging facilitates attainment of desired mass resolution. Manipulating an ion beam, as described herein, is performed where ion location and velocity in the time-of-flight mass spectrometer accelerator is correlated within the range that a mass analyzer can effective separate. The ability to steer the ions up/down and left/right allows for corrections of any problems with the mechanical assembly, or to allow optimization of the ion beam trajectory, to make sure that the ions are placed into the accelerator at optimal locations. Small adjustments of the ion beam’s steering and focusing can achieve useful performance improvements.

[0010] Accordingly, in one aspect, an ion lens assembly is provided that includes one or more focusing apertures for receiving ions and directing the received ions along an ion path into a time-of-flight mass analyzer. The lens assembly includes a last one of said one or more focusing apertures positioned at an end of the ion path to receive the ions propagating through the ion path and to generate a focused ion beam, and at least a first steering element positioned to receive the focused ion beam and configured to steer the focused ion beam relative to a downstream pusher electrode of the time-of-flight mass analyzer.

[0011] In various embodiments, the at least the first steering element can be configured to steer the focused ion beam across a width of said pusher electrode.

[0012] In various embodiments, the at least the first steering element and the pusher electrode can be disposed within a same vacuum chamber.

[0013] In various embodiments, the last one of said one or more focusing apertures can be positioned to receive, from a first vacuum chamber, the ions propagating along said ion path and to direct the focused ion beam to a second vacuum chamber, with the second vacuum chamber being maintained at a pressure less than a pressure of the first vacuum chamber.

[0014] In various embodiments, the pressure of the second vacuum chamber can be at least 10 times less than the pressure of the first vacuum chamber.

[0015] In various embodiments, the last one of said one or more focusing apertures and the at least the first steering element can be positioned in the second vacuum chamber. [0016] In various embodiments, the ions lens assembly can further include a second steering element positioned upstream of the last one of said one or more focusing apertures.

[0017] In various embodiments, the lens assembly can further include a collision cell positioned upstream of the second steering element.

[0018] In various embodiments, the first and the second steering elements can be configured to provide ion steering along two non-parallel directions. In various embodiments, the two non-parallel directions can be orthogonal to one another.

[0019] In various embodiments, any of the first and the second steering elements can further be configured to be switched into a focusing element.

[0020] In various embodiments, each of the first and the second steering elements can include two electrodes separated by a gap.

[0021] In various embodiments, each of the two electrodes of each of the first and the second steering elements can include a semi-circular profile.

[0022] In various embodiments, the ion lens assembly can further include at least a voltage source for applying voltages to said two electrodes of each of the first and the second steering elements.

[0023] In various embodiments, the ion lens assembly can further include a controller in communication with said at least the voltage source for controlling application of said voltages to the two electrodes via said at least the voltage source.

[0024] In various embodiments, the controller can be configured to apply different voltages to said two electrodes of each of the first and the second steering elements to provide ion steering.

[0025] In various embodiments, the controller can be further configured to cause said at least the voltage source to apply common voltages to said electrodes of at least one of the first and the second steering elements to switch that steering element into a focusing element.

[0026] In various embodiments, at least one of the first steering element and the second steering element is configured to simultaneously steer and focus ions passing therethrough. [0027] In another aspect, an ion lens assembly for directing ions into a time-of-flight (TOF) mass analyzer is provided that includes a first steering element for receiving a focused ion beam and directing the focused ion beam to a pusher electrode of the TOF mass analyzer, a focusing element positioned upstream of the first steering element to receive a plurality of ions and to generate the focused ion beam, and a second steering element positioned upstream of the first focusing element to receive ions propagating along an ion path and to direct said plurality of ions to the focusing element.

[0028] In various embodiments, the first steering element can be configured to steer the ion beam along a first direction and the second steering element is configured to steer the received ions along a second direction.

[0029] In various embodiments, the first direction can be orthogonal to a plane of the pusher electrode and the second direction can be parallel to the plane of the pusher electrode.

[0030] In a further aspect, a mass spectrometer is provided that includes a time-of-flight (TOF) mass analyzer, an ion lens assembly including one or more focusing apertures for receiving ions and directing the received ions along an ion path into a time-of-flight mass analyzer, said ion lens assembly including a last one of said one or more focusing apertures positioned at an end of the ion path to receive the ions propagating through the ion path and to generate a focused ion beam, and at least a first steering element positioned to receive the focused ion beam and configured to steer the focused ion beam relative to a downstream pusher electrode of the time-of- flight mass analyzer.

[0031] In various embodiments, the at least the first steering element can be configured to steer the focused ion beam across a width of said pusher electrode.

[0032] In various embodiments, the mass spectrometer can further include a second steering element positioned upstream of the last one of said one or more focusing apertures.

[0033] In various embodiments, the first and the second steering elements can be configured to provide ion beam steering along two non-parallel directions.

[0034] In various embodiments, the two non-parallel directions can be orthogonal directions. [0035] In various embodiments, at least one of the first steering element and the second steering element is configured to simultaneously steer and focus ions passing therethrough.

[0036] In an additional aspect, a method for operating a mass spectrometer is disclosed. The method includes steering an ion beam to a last one of one or more focusing apertures positioned at an ion path of the mass spectrometer, generating, by the last one of the one or more focusing apertures, a focused ion beam, and steering the focused ion beam, using at least a first steering element, relative to a downstream pusher electrode of a time-of-flight mass analyzer.

[0037] In various embodiments, steering the ion beam can include steering the ion beam to the last one of the one or more focusing apertures using at least a second steering element.

[0038] In various embodiments, steering the focused ion beam relative to the downstream pusher electrode can include steering the focused beam in a first direction, and steering the ion beam to the last one of the one or more focusing apertures can include steering the ion beam in a second direction that is orthogonal to the first direction.

[0039] In various embodiments, steering the focused beam in a first direction can include controllably modulating a first voltage applied to electrodes of the at least the first steering element to steer the focused ion beam in the first direction. Steering the ion beam in the second direction can include controllably modulating a second voltage applied to electrodes of the at least the second steering element.

[0040] In various embodiments, the electrodes of the at least the first steering element can include two semi-cylindrical electrodes aligned to define a cylindrical passage through which the focused ion beam passes through. The aligned semi-cylindrical electrodes dan be separated by a gap.

[0041] In various embodiments, the at least the first steering element and the pusher electrode can be disposed within a same vacuum chamber. The last of the one or more focusing apertures can be at a barrier separating the same vacuum chamber in which the at least the first steering element and the pusher electrode are disposed, and another vacuum chamber located upstream of the barrier. [0042] In various embodiments, the method can further includes applying a common voltage to electrodes of the at least the first steering element to configure the at least the first steering element to perform at least focusing operations.

[0043] In various embodiments, at least one of the first steering element and the second steering element is configured to simultaneously steer and focus ions passing therethrough.

[0044] Further understanding of various aspects of the present teachings can be obtained by reference to the following detailed description in conjunction with the associated drawings, which are described briefly below.

Brief Description of the Drawings

[0045] The skilled person in the art will understand that the drawings, described below, are for illustration purposes only. The drawings are not intended to limit the scope of the applicant’s teachings in any way.

[0046] FIG. 1A is a diagram illustrating a simulation of ion behavior in a collision cell.

[0047] FIG. IB is a cross sectional diagram illustrating a simulation of ion trajectories from a collision cell to an accelerator.

[0048] FIG. 1C is a graph showing velocity as a function of ion vertical position for the ions shown in FIG. IB.

[0049] FIG. ID is a heat map of the velocities and positions of the simulated ion trajectories of FIG. IB.

[0050] FIG. IE is a histogram of the Y positions of the simulated ions along the Y axis.

[0051] FIG. IF is a histogram of the Y velocities of the simulated ions along the Y axis.

[0052] FIG. 2 is a schematic representation of an example mass spectrometry system that includes an improved steering lens assembly.

[0053] FIG. 3 includes a diagram with frontal perspective views of steering elements of the lens assembly. [0054] FIG. 4 includes further frontal perspective view diagrams of the steering elements of the lens assembly, and a cross-sectional view of a flow restrictor/focusing orifice (FOR) located between the steering sections.

[0055] FIG. 5 is a schematic diagram of an example implementation of a linear ToF mass analyzer that may be used in conjunction with the mass spectrometry system of FIG. 2.

[0056] FIG. 6 is a flowchart of an example procedure for operating a time-of-flight (TOF) mass analyzer with the improved lens assembly described herein.

Detailed Description

[0057] It will be appreciated that for clarity, the following discussion will explicate various aspects of embodiments of the applicant’s teachings, while omitting certain specific details wherever convenient or appropriate to do so. For example, discussion of like or analogous features in alternative embodiments may be somewhat abbreviated. Well-known ideas or concepts may also, for brevity, not be discussed in any great detail. The skilled person will recognize that some embodiments of the applicant’s teachings may not require certain of the specifically described details in every implementation, which are set forth herein only to provide a thorough understanding of the embodiments. Similarly, it will be apparent that the described embodiments may be susceptible to alteration or variation according to common general knowledge without departing from the scope of the disclosure. The following detailed description of embodiments is not to be regarded as limiting the scope of the applicant’s teachings in any manner.

[0058] As used herein, the terms "about" and "substantially equal" refer to variations in a numerical quantity that can occur, for example, through measuring or handling procedures in the real world; through inadvertent error in these procedures; through differences in the manufacture, source, or purity of compositions or reagents; and the like. Typically, the terms "about" and "substantially" as used herein means 10% greater or less than the value or range of values stated or the complete condition or state. For instance, a concentration value of about 30% or substantially equal to 30% can mean a concentration between 27% and 33%. The terms also refer to variations that would be recognized by one skilled in the art as being equivalent so long as such variations do not encompass known values practiced by the prior art.

[0059] As used herein the term "and/or" includes any and all combinations of one or more of the associated listed items and may be abbreviated as

[0060] The present disclosure is directed to an improved lens assembly that couples (directly, or via another module) a TOF mass analyzer to upstream sections of a mass spectrometer section (e.g., ion guides, a mass filter, a collision cell, etc.). In various embodiments, the coupling includes a steering / focusing element that is positioned downstream of a focusing aperture that separates the TOF analyzer from the preceding (upstream) sections of the mass spectrometer. More specifically, implementations of the proposed structures and assemblies include an ion lens assembly with one or more focusing apertures for receiving ions and directing the received ions along an ion path into a time-of-flight mass analyzer. The lens assembly includes a last one of the one or more focusing apertures of the ion path to receive the ions propagating through the ion path and to generate a focused ion beam, and at least a first steering element positioned to receive the focused ion beam and configured to steer the focused ion beam relative to a downstream pusher electrode of the time-of-flight mass analyzer. For example, the last of the one or more focusing apertures may be positioned at an end of the ion path (i.e., at an interface between the ion path and the mass analyzer), in which case the at least the first steering element and the pusher electrode are disposed within a same vacuum chamber (e.g., the TOF mass analyzer’s vacuum chamber). In example embodiments, the at least the first element can be a vertical or horizontal steering element. Such a steering element may be configured to steer the focused ion beam across a width of the TOF mass analyzer’s pusher electrode.

[0061] Generally, mating an ion path, such as quadrupole ion path, to a TOF analyzer requires isolation of the separate vacuum chambers. This is often accomplished with an aperture, which separated two chambers and also functions as a lens. In various Sciex TOF analyzers (such as Sciex’ s model 5600, and also the 6600, X500, ZenoTOF 7600), this downstream end section lens assembly is referred to as the FOR lens (focusing orifice). The FOR lens can include electrodes that serve both as the gas flow conduction limiter for separating the vacuum chambers, and as a lens. The FOR orifice can be a thin lens or a thicker, “tube,” lens. These electrodes can be controlled, for example, using a user-controllable DC voltage. [0062] In some embodiments, TOF mass analyzers (such as Sciex’s mass analyzers) rely on organizing the ions in the accelerator such that the ion velocity, along the TOF accelerator force vector direction, are correlated to ion position. Such correlation can be achieved using a phenomenon called “collisional focusing.” By way of example, this can be performed using a quadrupole ion optic that is held at a pressure in the range of 3 to 15 millitorrs. A confining radio frequency (RF) voltage source repeatedly directs the ions toward the centerline of the ion path, and collisions reduce the kinetic energy. Eventually, the ions will be confined to a very small position distribution. For example, FIG. 1A includes a diagram 100 illustrating a simulation (emulating the collision cell in the X500/ZenoTOF 7600/Chiron analyzer) of behavior of ions in such an assembly. The simulation depicts in cross section the simulated ion trajectories in an RF ion path assembly where a background gas is present. The RF potential is applied orthogonally to the horizontal axis. Axial motion is caused by a DC potential along the horizontal axis. The axial DC field is created using auxiliary electrodes 101. More particularly, ions enter at entrance 106 with a large distribution of radial positions. These ions are urged along axially with electrodes that create a small axial field. During this transit, the action of the electrical fields established through application of RF voltage to the electrodes (such as electrodes 102, 103, 104, and 105; FIG. 1 A also include a cross-sectional side view diagram showing the arrangement of electrodes 101, 102, 103, 104, and 105 relative to each other), combined with the collisions, result in a very narrow radial position distribution at the exit 108. The simulation depicted in FIG. 1 A and other simulations, can be used to estimate the size of the diameter of the cross-section of the ion beam at the exit of the collision cell is about 0.15mm.

[0063] FIG. IB is a cross sectional diagram 110 illustrating a simulation of ion trajectories from a collision cell 112, via a lens assembly 113, to an accelerator 114. FIG. 1C is a graph 120 showing ion velocity as a function of ion vertical position for ions located in the accelerator, immediately prior to acceleration. The graph 120 shows the correlation of the ions in the TOF. Ion velocity in the primary TOF axis (Y axis) is plotted as a function of ion Y position. Y=0 is the centerline in the first acceleration stage of the TOF accelerator. The Y axis is the primary axis of the TOF analyzer, parallel to the force vector that accelerates the ions into the remaining sections of the TOF analyzer. The ions trajectories are shown in FIG. IB. The point of recording the ion Y positions and ion Y velocities are the locations in the accelerator where those ions within will be detected on the detector after acceleration. [0064] FIG. ID is a heat map 130 (computed using the data of FIG. 1C) of the velocities and positions of the simulated ion trajectories. The plot of FIG. ID shows the heat map of the correlation of the ions in the TOF. Ion velocity in the primary TOF axis (Y axis) is plotted as a function of ion Y position. Y=0 is the centerline in the first acceleration stage of the TOF accelerator. The Y axis is the primary axis of the TOF analyzer, parallel to the force vector that accelerates the ions into the remaining sections of the TOF analyzer. As can be seen from the graph 120 and the heat map 130, the velocities and positions of ions in the accelerator are highly correlated.

[0065] FIG. IE is a histogram 140 of the ion Y positions, while FIG. IF is a histogram 150 of the ion Y velocities. In the histogram 140 of FIG. IE, the plot shows the distribution pf the y position of the ions along the Y-axis in the first acceleration stage of the TOF accelerator. Y=0 is the centerline of the first stage of the TOF accelerator. The Y axis is the primary axis of the TOF analyzer, parallel to the force vector that accelerates the ions into the remaining sections of the TOF analyzer. For the histogram 150 of FIG. IF, the plot shows the distribution of the y velocity of the ions along the Y-axis in the first acceleration stage of the TOF accelerator. Y=0 is the centerline of the first stage of the TOF accelerator. The Y axis is the primary axis of the TOF analyzer, parallel to the force vector that accelerates the ions into the remaining sections of the TOF analyzer.

[0066] A TOF analyzer can correct for a distribution of ion positions, or ion velocities quite well. But when both are present, correcting for both becomes difficult (this is sometimes referred to as the turn-around issue for ions that share location, but have opposite, or different, velocities). By carefully adjusting the trajectory angle distribution (and therefore ion velocity distribution) of the ions exiting the lens, and making sure to preserve the ion position/velocity correlation, the focusing task of the TOF is simplified. There will be no turn-around issue. Additionally, the TOF can focus for a position distribution or a velocity distribution, for ion position in the accelerator, prior to acceleration, can be expressed as a linear function of ion velocity; or ion velocity can be expressed as a linear function of ion position.

[0067] An ion lens located between the ion focusing quad and the TOF can perform several functions. First, it provides a chamber separation, which may be important because the vacuum requirement for TOF is much higher than the pressure required to cause collisional focusing. Second, it controls the slope of the ion velocity/position correlation. There is a range of focusing available for the TOF analyzer by adjustment of the analyzer voltages, but the slope of this correlation must fall within this range. Third, the lens allows for steering of the ions both up and down. Various mass spectrometer implementations are configured to first steer the ions up and down (vertical steering), and then to steer the ions left and right (horizontal steering). The steering elements in such designs are then followed by the flow conduction limiting lens (the FOR lens).

[0068] Some previous mass spectrometry implementations did not use the horizontal steering element due to three main reasons. First, when the ions have that extra distance to expand, many ions impinge on the FOR lens and contaminate it. Elimination of one of the steering elements (e.g., the horizontal steering element) can bring the point source much closer to the FOR lens and so fewer ions impinge on the FOR lens. Second, elimination of the horizontal steering element can result in a significant boost to the system’s sensitivity because those ions previously lost on the lens could now be detected. Third, elimination of a steering section in the FOR lens assembly results in a slope of the correlation that is a better match for the analyzer.

[0069] In contrast, the proposed implementations described herein use both a vertical and a horizontal steering element, but instead of placing both steering elements upstream of the focusing orifice lens (e.g., have two steering elements arranged sequentially just ahead of the focusing orifice lens), one steering element (e.g., the horizontal element) is placed downstream of the focusing element (typically, but not necessarily, in close proximity to the focusing orifice lens) so that the downstream steering element in effect is placed past the exit boundary (formed by the structure of the focusing orifice lens) of the vacuum chamber (e.g., the collision cell vacuum chamber) in which the other steering element is placed. In other words, the focusing orifice lens has a steering element on either of its sides. In some embodiments, the steering element now moved to the downstream side of the focusing orifice is located within a vacuum chamber (e.g., the TOF vacuum chamber) with a higher vacuum, i.e., a lower pressure, than that in which the upstream steering element is located. It is noted that, in some embodiments, either of the steering elements of the proposed ion lens assembly may be configured (through controlled application of the RF or DC voltage sources) to simultaneously steer and focus ions passing therethrough.

[0070] The steering assemblies allow for application of an electric field induced force vector in a desired steering direction, thus causing ion trajectories to be altered as needed. This can be accomplished by application of a voltage difference between the two electrodes, through which the ions are passing. It should be noted that the proposed assembly (comprising of a sequence of a steering element, followed by the focusing orifice lens, followed by another steering element) can be converted from an ion steering assembly into an additional lens if a common voltage is applied to the electrodes comprising each of the steering elements of embodiments of the proposed assembly. In some examples, both a potential difference between the pair of steering electrodes and a common potential can be applied simultaneously (applying the common voltage to the electrodes of one of the steering elements, and applying the voltage difference to the electrodes of the other steering element) to cause a focusing and steering effect combination.

[0071] With reference next to FIG. 2, a schematic diagram of an example mass spectrometer 200 is shown. The example mass spectrometer 200 is implemented with a lens assembly 280 (depicted schematically as the dashed box comprising the FOR lens 282, and steering elements 284 and 286 on opposite sides of the FOR lens 282), which is an example embodiment of the proposed improved assembly.

[0072] The example mass spectrometer 200 is a liquid chromatography (LC)/mass spectrometry (MS) system that uses a TOF mass analyzer 250 to analyze the ions in an ion stream. However, in some embodiments, other types of the mass analyzers may be used. The LC-MS spectrometric system 200 includes a liquid chromatography (LC) column (not shown) that can receive a sample and deliver the eluate exiting the LC column to an ion source (not shown) that is in communication with the LC column. The ion source can ionize one or more analytes within the received eluate to generate a plurality of ions that can be received by an ion guide 210 (a QJet® ion guide in the example of FIG. 2) via an orifice 202 of the mass spectrometer 200. The QJet® ion guide 210 includes a set of rods 212 arranged in a quadrupole configuration, two of which 212a/212b are depicted in FIG. 2. The QJet® ion guide 210 employs a combination of gas dynamics and radio frequency fields to cause focusing of the ions.

[0073] As further shown in FIG. 2 the ions exiting the QJet® ion guide 210 are focused by an ion lens IQ0218 into an ion guide Q0220, which includes a set of quadrupole rods 222, two of which 222a/222b are visible in FIG. 2, to which RF voltages can be applied for causing radial confinement of the ions of an ion beam. The ion beam is, in turn, received by an ion mass filter QI 230. The ion guides QJet®, Q0, and the mass filter QI are disposed in differentially-pumped chambers that are maintained at progressively lower pressures. For example, QJet® ion guide can operate at a pressure of, for example, about 1-10 Torr, a Q0 focusing ion guide can operate at a pressure of, for example, about 1-100 mTorr, and a mass filter QI can operate at a pressure of, for example, less than 1x1 O'⁴ Torr.

[0074] An ion lens IQ1 228 focuses the ions exiting the Q0 ion guide 220 into the mass filter QI 230. The mass filter QI 230 includes a stubby lens 234 formed by a set of quadrupole rods (two of which 234a/234b are depicted in FIG. 2) to which RF voltages can be applied to cause focusing of the ions. The mass filter QI 230 further includes a set of quadrupole rods 232, two of which 232a/232b are visible in the figure, to which a combination of RF and DC voltages can be applied to allow the selection of one or more precursor ions, e.g., all precursor ions of interest when the mass spectrometer is operating in a DIA mode, having m/z ratios within a target m/z range for transmission to a downstream ion dissociation device Q2240, e.g., a collision cell in this example via an ion lens IQ2238. A stubby lens 236 that includes a set of quadrupole rods (two of which 236a/236b are visible in the figure) positioned downstream of the quadrupole rod set 232 helps focus the selected precursor ion into the downstream electron ion dissociation device Q2 240.

[0075] The mass filter QI 230 is thus configured to select an ion of interest and/or a range of ions of interest. By way of example, the quadrupole rod set for QI can be provided with RF/DC voltages suitable for operation in a mass-resolving mode, e.g., in accordance with a controller 270, or some other dedicated controller, to select an m/z ratio range that is to pass through the mass filter. Taking the physical and electrical properties of QI into account, parameters for an applied RF and DC voltage can be selected so that QI establishes a transmission window of chosen m/z ratios, such that these ions can traverse QI largely unperturbed. However, ions having m/z ratios falling outside the window, however, do not attain stable trajectories within the quadrupole and can be prevented / inhibited from traversing the quadrupole rod set QI. In some embodiments, users may interact and provide controlling commands and instructions through a user interface (which may be rendered, for example, on a display device coupled to the data processing module 260). For example, a user may specify a mass range that it wishes to examine. Based on the specified mass range, the data processing module 260 and/or the controller 170 (or some other controller not specifically depicted in FIG. 2) may determine the RF and DC voltages that need to be applied to the quadrupole rods of the mass filter QI 230 to cause ions within that range to pass through towards the downstream mass analyzer 250.

[0076] As further shown in FIG. 2, a DC voltage source 272 and an RF voltage source 274 operating under control of the controller 270 (which may be implemented, for example, as a processor-based device), are configured to controllably apply RF and DC voltages to the one or more of the sections of the mass spectrometer 200, including to controllably apply DC and RF voltages to the QJet® section, the Q0 section, the mass filter QI 230, and/or any of the other sections / modules of the mass spectrometer 200. The voltage sources 272 and 274 are generally independently electrically coupled to any of the mass spectrometer’s sections so as to independently control those sections’ operations (using the controller 270). For example, the controller 270 may be configured to control the RF voltage source 274 so that the RF voltage applied to the rods of the QI mass filter can have a frequency in a range of about 200 kHz to about 1.2 MHz and a peak-to-peak amplitude (V_pp) in a range of about 100 volts to about 10 kilovolts (kV).

[0077] With continued reference to FIG. 2, in various embodiments, the collision cell Q2 (240) includes a set of rods 242, two of which 242a/242b are visible in the figure, which are arranged in a quadrupole configuration. The collision cell is pressurized via introduction of, for example, nitrogen gas to allow collisional fragmentation of the ions received by the collision cell Q2. The RF frequency applied to the rods of the Q2 collision cell (controllable, for example, by the controller 270) can be, for example, in a range of about 1 MHz to about 5 MHz. In various embodiments, the Q2 cell can be employed for collisional focusing, where higher RF frequencies, e.g., 5 MHz or higher, can be employed.

[0078] The ions exiting the Q2 cell (240) are focused by an ion focusing assembly 280, implemented in accordance with the improved configuration described herein (and further discussed below), into a time-of-flight (TOF) mass analyzer 250 (an example embodiment of a suitable mass analyzer is the TOF mass analyzer 500, discussed in greater detail below with respect to FIG. 5). The mass analyzer 250 includes an ion detector 252, which generates ion detection data in response to the detection of ions incident thereon (e.g., generating electrical pulses representative of ion intensity, and producing a sequence of detection signals as a function of time). The ion detection signals generated by the ion detector can be processed using a data processing module 260 to generate the mass spectrum of the received ions.

[0079] As noted, and as depicted in FIG. 2, the ion focusing assembly 280 includes two steering elements 284 and 286 flanking the structure constituting the focusing orifice lens 282, which defines the orifice through which dissociated ions (formed as a result of dissociation of precursor ions via interaction with the collision gas introduced into the collision cell 240) pass onto the TOF mass analyzer 250. Thus, in some embodiments, the mass spectrometer 200 includes an ion lens assembly including one or more focusing apertures for receiving ions and directing the received ions along an ion path into a time-of-flight mass analyzer (e.g., TOF mass analyzer 250). The ion lens assembly comprises a last one of said one or more focusing apertures (e.g., the focusing aperture structure 282) positioned on the ion path (typically, but not necessarily, close to the end of the ion path) to receive the ions propagating through the ion path and to generate a focused ion beam. The ion lens assembly further comprises at least a first steering element (e.g., the steering element 286) positioned to receive the focused ion beam (i.e., the beam as focused by the last of the one or more focusing apertures) and configured to steer the focused ion beam relative to a downstream pusher electrode 254 of the time-of-flight mass analyzer. In various embodiments, the first steering element and the pusher electrode 254 (of the TOF mass analyzer 250) may be disposed within a same vacuum chamber (for example, when the steering element is positioned past the barrier between the TOF vacuum chamber and the preceding chamber, e.g., the collision cell vacuum chamber). The steering element 286 (possibly in combination with the steering element 284) may be configured to direct the ions exiting the collision cell to specific positions on or across the pusher electrode / deflector 254.

[0080] The first steering element (positioned downstream of the last focusing aperture lens, and receiving the ions focused by the last one of the one or more focusing apertures) may be configured to steer the focused ion beam across a width of the pusher electrode (e.g., when the first steering elements is the horizontal steering element). In some embodiments, the ion lens assembly may further include a second steering element (e.g., a steering element positioned upstream of the last focusing aperture). When the second steering element is a vertical steering element, it may be configured to steer an ion beam in the z-direction (e.g., above the pusher electrode). A collision cell (such as the collision cell 242) may include the second steering element (e.g., the steering element 284 in FIG. 2), or may be upstream to the second steering element. In some embodiments, the first and the second steering elements are configured to provide ion steering along two non-parallel directions. In example embodiments, the two non-parallel directions may be orthogonal to one another. For example, one steering element, such as the first steering element positioned downstream of the orifice aperture may steer the ion beam horizontally, while the second steering element, positioned upstream of the focusing aperture, may steer the ion beam vertically. However, it is to be noted that the adjacent vacuum chamber following the last focusing aperture may not be the TOF analyzer’s vacuum chamber, but rather may be a further ion guide located between the vacuum chamber with the last focusing orifice and the TOF analyzer’s vacuum chamber. Thus, in such embodiments, the last focusing aperture is positioned to receive, from a first vacuum chamber, the ions propagating along the ion path and to direct the focused ion beam to a second vacuum chamber, with the second vacuum chamber being maintained at a pressure less than that of the first vacuum chamber. An example of the pressure differential between the first and second vacuum chambers is that the pressure of the second vacuum chamber may be at least 10 times less (in in some embodiments, at least 100 times less) than a pressure of the first vacuum chamber.

[0081] FIG. 3 includes a diagram of an example embodiment of a lens assembly 300. The lens assembly 300 includes horizontal steering electrodes 312 and 314 (which may correspond to the first steering element 286 depicted schematically in FIG. 2), a focusing orifice lens 416 (not visible in FIG. 3, but shown in FIG. 4), and vertical steering electrodes 332 and 334 (which may correspond to the second steering element 284 schematically depicted in FIG. 2).

[0082] FIG. 4 includes a diagram 400 of a horizontal steering element / electrodes 412 and 414, which may be the same as the electrodes 312 and 314 shown in FIG. 3 , and a vertical steering element / electrodes 432 and 434, which may be the same as the electrodes 332 and 334 e shown in FIG. 3. The diagram 400 provides a frontal perspective view of the horizontal steering electrodes 410, i.e., showing the front, protruding semi-cylindrical projections 412 and 414 of the horizontal steering electrodes that are farther away from the FOR lens 416 (the FOR lens 416 is shown in the cross-section on FIG. 4), and that would protrude into a downstream vacuum chamber (e.g., the vacuum chamber of the TOF mass analyzer). As can be seen in FIGS. 3 and 4, the semi- cylindrical portions of the electrodes 310 and 410 extend from planar base portions. The planar base portions of the semi-cylindrical projections 412 and 414 each have an inner edge that includes a semi-circular edge portion. When the two planar portions are brought together such that the two semi-circular edge portions are aligned opposite each other (but without touching each other, so as to not short the electrical arrangement of the electrodes), the semi-circular edge portions, from which the respective semi-cylindrical electrode portions 412 and 414 extend, define a passage (or orifice) through which ions traveling through the FOR lens 416 pass en route to the downstream TOF mass analyzer. An adjustable electrical field established through application of DC and/or RF voltage (e.g., via the DC and RF sources 272 and 274 depicted in FIG. 2) can controllably steer the ion beam (e.g., steer horizontally so that, for example, the ions are steered across the width of a pusher plate of the TOF mass analyzer, or steer vertically, so that the beam is steered in the z- direction above the pusher electrode). Steering is accomplished by application of a potential difference between the electrode pair. The potential difference crates an electrical field with a force vector orthogonal to the ion beam trajectory. When ions pass through this field, they experience the orthogonal force that causes their trajectory to assume an additional velocity vector component parallel to the electric field vector. In this way, the ion trajectories are altered. Voltage adjustments to cause the desired steering pattern can be controlled according to pre-determined voltage modulation patterns / profiles of the voltages applied to the horizontal and/or vertical steering elements, which result in the desired steering patterns. It is to be noted that in FIG. 4 both the horizontal steering electrodes and the vertical steering electrodes are mounted on plates (flange) 440. The plate / flange 440 attach to the FOR lens to form the lens assembly 400.

[0083] With continued reference to FIGS. 3 and 4, the second steering element, namely, the vertical steering electrodes 420, include two semi-cylindrical-shaped electrodes 432 and 434 (in a top-bottom arrangement) that extend from semi-circular edge portions of respective planar base portions. When brought together and aligned, while leaving a small gap between the aligned portions (to avoid shorting the electrodes), the electrode portions form a circular hollow cylindrical structure frame (also referred to as a basket) defining an inner circular cylindrical passage through which ions pass (in some embodiments, this happens following the dissociation action performed by a collision cell) en route to the FOR lens 416. The vertical steering electrodes 420 are attached to the FOR lens 416. In order to prevent shorting, an insulator 413 is held used. The FOR lens 416 is attached to the mounting flange 440 and is likewise kept from shorting by holding an insulator between 415. Similarly, the horizontal steering/focusing electrodes 410 which is mounted to the flange 440, but kept form shorting by insulator 411. All fasteners are not shown for visual clarity. All fastener materials are chosen to prevent any shorting. Some fasteners are used for conducting the voltage to the electrodes, and are conductors. Some fasteners are insulators. As noted, in some variations, the horizontal steering electrodes 410 (or 310) may be located upstream of the FOR lens 416, while the vertical steering electrodes 420 (or 320 as depicted in FIG. 3) may be located downstream of the FOR lens. As ions pass through the vertical steering electrodes, adjustable voltage (DC and/or RF) is controllably applied to steer the ion stream passing through the inner space of the cylindrical frame to steer the ions in a vertical direction (upwards or downwards). It is to be noted that while the vertical steering electrodes are shown to form a cylindrical frame, in some embodiments the electrodes may comprise additional exterior surfaces covering a more substantial portions of the exterior boundaries of the cylinder formed by the vertical steering electrodes (as more particularly shown in FIG. 4, where the electrodes 432 and 434 include exterior surfaces filling the exterior boundaries of the cylindrical passage defined by the vertical electrodes).

[0084] Thus, in some embodiments, the first and second steering elements each includes two electrodes that are separated by a gap. Each of the two electrodes of each of the first and the second steering elements may include a semi-circular profile (defining a hollow cylindrical structure through which ions pass en route to the downstream TOF mass analyzer). The ion lens assembly may include, in such embodiments, at least a voltage source for applying voltages to the two electrodes of each of the first and the second steering elements. The ion lens assembly may further include a controller (such as the controller 270 or the data processing module 260 illustrated in FIG. 2) in communication with the voltage source for controlling application of voltages to the two electrodes (of each of the steering elements) via the voltage source. Such a controller (typically a processor-based device) may be configured to apply different voltages to the two electrodes of each of the first and the second steering elements to provide ion steering (vertical and/or horizontal). In some examples, the controller may be configured to cause the at least the voltage source to apply common voltages to the electrodes of at least one of the first and the second steering elements to switch that steering element into a focusing element.

[0085] With reference next to FIG. 5, a diagram of an example implementation of a linear ToF mass analyzer 500 that may be used in conjunction with the mass spectrometry system of FIG. 2 is shown. It is noted that the ion assembly lens described herein is not limited to time-of- flight analyzers with a linear configuration. Rather, the lens assembly may be used in conjunction with other types of TOF analyzer configurations, including, for example, a single ion reflector type, multiple ion reflector type, etc. The lens assembly described herein may also be used in conjunction with other types of mass spectrometers.

[0086] As shown in FIG. 5, the mass analyzer 500 includes an inlet 501 for receiving a plurality of ions propagating along a transverse axis (TA) and a deflector electrode 502 (also referred to as a pusher electrode) to which voltage pulses can be applied. A steering element 580, which may be similar to the first steering element 286 located downstream of a FOR lens (at the barrier between a collision cell and the TOF mass analyzer) is located within the vacuum chamber of the mass analyzer 500, and thus is operating at the high vacuum environment of the TOF mass analyzer. As noted, the steering element may be a horizontal or vertical steering element (electrodes), and may be configured to control the direction of the ion beam exiting the FOR lens along a first direction (e.g., along a horizontal or vertical axis of the steering element). The second steering element (positioned upstream of the FOR lens) is configured to controllably direct the ion beam (prior to its arrival at the FOR lens) in another direction (e.g., orthogonal to the first direction). Consequently, in various embodiments, the first direction may be orthogonal to a plane of the pusher electrode and the second direction may be parallel to the plane of the pusher electrode. In some examples, the steering element 580 may be configured to direct the ions exiting the collision cell to specific positions on or across the pusher electrode / deflector 502. In some situations, when there is at least another vacuum chamber separating the collision cell and the mass analyzer 500, the steering element 580 may not be included with the mass analyzer 500.

[0087] In the embodiments of FIG. 5, each voltage pulse can cause the deflection of at least a portion of ions arriving at the TOF mass analyzer (and optionally steered by the steering element 580) into an orthogonal direction along a longitudinal axis (LA) into a first ion acceleration region 504 established between the deflector (pusher) electrode 502 and a downstream grid electrode 506. More specifically, a voltage differential (VI) applied via a controllable pulser voltage source 505 operating under control of a controller 507 (which may be implemented as part of the controller 270 of FIG. 2, or the data processing module 260, or some other dedicated control module) between the deflector electrode 502 and the downstream grid electrode 506 can generate an electric field El in the region between the deflector electrode 502 and the grid electrode 506, thereby establishing the first ion acceleration region 504 in which ions can be accelerated under the influence of the electric field El to a first kinetic energy (KE1). [0088] The TOF mass analyzer 500 further includes another grid electrode 510 that is positioned downstream from the grid electrode 506 and is held at the same electrical potential as the grid electrode 506 (in this embodiment, both grid electrodes 506 and 510 are maintained at the ground electric potential) so as to establish a first field-free ion drift region 508 between the two grid electrodes 506 and 510. As no electric field is applied to the ions as they travel across the field-free ion drift region 508, ions having the same electric charge, but different masses, will undergo some degree of spatial separation before exiting the first field-free ion drift region. In other words, because the ions entering the first field-free ion drift region have the same kinetic energy (KE1), ions with different masses will have different velocities that determine the time required for the ions to traverse the field- free ion drift region.

[0089] In some embodiments, a second ion acceleration region 512 is positioned downstream of and adjacent to the first field-free ion drift region 508. The second ion acceleration region 512 is established via application of a voltage differential between the grid electrode 510 and a downstream grid electrode 514. More specifically, a DC power supply 515, which may also operate under the control of the controller 307, applies a voltage differential (V2) across the grid electrodes 510 and 514, which results in the generation of an electric field E3 in the region between the two grid electrodes 510 and 514. The ions exiting the field-free drift region 508 enter the second ion acceleration region 512 established between the grid electrodes 510 and 514 and are accelerated under the influence of the electric field in this region to achieve a kinetic energy KE2, which is greater than the kinetic energy KE1.

[0090] The linear TOF mass analyzer further includes a second field-free ion drift region 516 that is positioned downstream of the second ion acceleration region 512 and is enclosed within a shell 517 (herein also referred to as a liner) that is maintained at the same electric potential as the grid electrode 514. More specifically, the second field-free ion drift region 516 extends from the grid electrode 514 to an ion detector 518 that can detect ions passing through the second field- free ion drift region 516 and generate ion detection data. The ion detection data can, in turn, be received by a digital data processing module (herein also referred to as the computer data system 520), which may be similar to the data processing module 260 of FIG. 2, that can operate on the ion detection data to generate a mass spectrum associated with the ions detected by the mass analyzer. [0091] In the configuration of the mass analyzer depicted in FIG. 5, the flight time (FT) of an ion having a mass-to-charge ratio denoted by m/z through the mass analyzer can be obtained using the following relation:

Eq- (1)

Where:

• y denotes the ion location in the first acceleration region with y = 0 being the location adjacent to the first electrode (i.e., the deflector electrode), and y=dl being coincident with the exit grid of the first acceleration region.

• dl denotes the length of the first ion acceleration region,

• d2 denotes the length of the first field- free ion drift region,

• d3 denotes the length of the second ion acceleration region,

• d4 denotes the length of the second field- free ion drift region,

• VI denotes the voltage applied across the first ion acceleration region, and

• V3 denotes the voltage applied across the second ion acceleration region.

[0092] In various embodiments, by setting the values of the ion path length associated with the first ion acceleration region, namely, (dl and the ion path length associated with the second ion acceleration region, namely, (t/3), as well as the voltages VI and V3 to be applied across the first and the second ion acceleration regions, the values of the lengths associated with the first and the second field- free ion drift regions can be obtained according to the following relationships:

[0093] Thus, the dimensions of various regions of the mass analyzer (e.g., the mass analyzer 500) can be determined by selecting the dimensions of two regions of the mass analyzer and the voltages applied across the two ion acceleration regions. The ion path length through the mass analyzer (i.e., the path length of an ion from the deflector electrode 502 to the ion detector 518) and the voltages applied across the two ion acceleration regions can be chosen to obtain a desired resolution.

[0094] With reference now to FIG. 6, a flowchart of a procedure 600 for operating a mass spectrometer is shown. The procedure 600 includes steering 610 an ion beam to a last one of one or more focusing apertures positioned at an ion path of the mass spectrometer, generating 620, by the last one of the one or more focusing apertures, a focused ion beam, and steering 630 the focused ion beam, using at least a first steering element (e.g., the steering element 286 of FIG. 2), relative to a downstream pusher electrode (e.g., pusher electrode 254) of a time-of-flight mass analyzer.

[0095] In some embodiments, steering the ion beam may include steering the ion beam to the last one of the one or more focusing apertures (such as the focusing aperture lens 282) using at least a second steering element (e.g., the steering element 284 of FIG. 2). In some examples, steering the focused ion beam relative to the downstream pusher electrode may include steering the focused beam in a first direction, and steering the ion beam to the last one of the one or more focusing apertures may include steering the ion beam in a second direction that is orthogonal to the first direction. For example, the first steering element may steer the focused ion beam horizontally, whereas the second steering element may steer an incoming ion beam vertically.

[0096] In some embodiments, steering the focused beam in the first direction may include controllably modulating a first voltage applied to electrodes of the at least the first steering element to steer the focused ion beam in the first direction, and steering the ion beam in the second direction may include controllably modulating a second voltage applied to electrodes of the at least the second steering element. [0097] The electrodes of the at least the first steering element may include two semi- cylindrical electrodes aligned to define a cylindrical passage through which the focused ion beam passes through, with the aligned semi-cylindrical electrodes being separated by a gap. In some embodiments, the at least the first steering element and the pusher electrode may be disposed within a same vacuum chamber, and the last of the one or more focusing apertures may be at a barrier separating the same vacuum chamber in which the at least the first steering element and the pusher electrode are disposed, and another vacuum chamber located upstream of the barrier. In various embodiments, the procedure 600 may further include applying a common voltage to electrodes of the at least the first steering element to configure the at least the first steering element to perform at least focusing operations (in some situations, the at least the first steering element can be configured to perform steering and focusing operations, e.g., by focusing the ion beam in a particular desired direction).

[0098] The descriptions herein of various implementations of the present teachings have been presented for purposes of illustration and description. It is not exhaustive and does not limit the present teachings to the precise form disclosed. Modifications and variations are possible in light of the above teachings or may be acquired from practicing of the present teachings. Additionally, the described implementation includes software, though the present teachings may be implemented as a combination of hardware and software or in hardware alone. The present teachings may be implemented with both object-oriented and non-object-oriented programming systems.

[0099] The section headings used herein are for organizational purposes only and are not to be construed as limiting. While the applicant’s teachings are described in conjunction with various embodiments, it is not intended that the applicant’s teachings be limited to such embodiments. On the contrary, the applicant’s teachings encompass various alternatives, modifications, and equivalents, as will be appreciated by those of skill in the art.

Claims

What is claimed is:

1. An ion lens assembly including one or more focusing apertures for receiving ions and directing the received ions along an ion path into a time-of-flight mass analyzer, comprising: a last one of said one or more focusing apertures positioned at an end of the ion path to receive the ions propagating through the ion path and to generate a focused ion beam; and at least a first steering element positioned to receive the focused ion beam and configured to steer the focused ion beam relative to a downstream pusher electrode of the time-of-flight mass analyzer.

2. The ion lens assembly of Claim 1, wherein the at least the first steering element is configured to steer the focused ion beam across a width of said pusher electrode.

3. The ion lens assembly of Claim 1, wherein the at least the first steering element and the pusher electrode are disposed within a same vacuum chamber.

4. The ion lens assembly of Claim 1, wherein the last one of said one or more focusing apertures is positioned to receive, from a first vacuum chamber, the ions propagating along said ion path and to direct the focused ion beam to a second vacuum chamber, wherein the second vacuum chamber is maintained at a pressure less than a pressure of the first vacuum chamber, and wherein, optionally, a pressure of the second vacuum chamber is at least 10 times less than the pressure of the first vacuum chamber.

5. The ion lens assembly of Claim 4, wherein the last one of said one or more focusing apertures and the at least the first steering element are positioned in the second vacuum chamber.

6. The ion lens assembly of and one of Claims 1 to 5, further comprising a second steering element positioned upstream of the last one of said one or more focusing apertures.

7. The ion lens assembly of Claim 6, further comprising a collision cell positioned upstream of the second steering element.

8. The ion lens assembly of Claim 6, wherein the first and the second steering elements are configured to provide ion steering along two non-parallel directions.

9. The ion lens assembly of Claim 8, wherein the two non-parallel directions are orthogonal to one another.

10. The ion lens assembly of Claim 6, wherein any of the first and the second steering elements is further configured to be switched into a focusing element.

11. The ion lens assembly of Claim 6, wherein each of the first and the second steering elements comprises two electrodes separated by a gap.

12. The ion lens assembly of Claim 11, wherein each of the two electrodes of each of the first and the second steering elements includes a semi-circular profile.

13. The ion lens assembly of Claim 11, further comprising at least a voltage source for applying voltages to said two electrodes of each of the first and the second steering elements.

14. The ion lens assembly of Claim 13, further comprising a controller in communication with said at least the voltage source for controlling application of said voltages to the two electrodes via said at least the voltage source.

15. The ion lens assembly of Claim 14, wherein said controller is configured to apply different voltages to said two electrodes of each of the first and the second steering elements to provide ion steering.

16. The ion lens assembly of Claim 15, wherein said controller is further configured to cause said at least the voltage source to apply common voltages to said electrodes of at least one of the first and the second steering elements to switch that steering element into a focusing element.

17. The ion lens assembly of Claim 6, wherein at least one of the first steering element and the second steering element is configured to simultaneously steer and focus ions passing therethrough.

18. A mass spectrometer, comprising: a time-of-flight (TOF) mass analyzer; and an ion lens assembly including one or more focusing apertures for receiving ions and directing the received ions along an ion path into a time-of-flight mass analyzer, said ion lens assembly comprising: a last one of said one or more focusing apertures positioned at an end of the ion path to receive the ions propagating through the ion path and to generate a focused ion beam, and at least a first steering element positioned to receive the focused ion beam and configured to steer the focused ion beam relative to a downstream pusher electrode of the time-of-flight mass analyzer.

19. The mass spectrometer of Claim 18, wherein the at least the first steering element is configured to steer the focused ion beam across a width of said pusher electrode.

-Tl-

20. The mass spectrometer of Claim 18, further comprising a second steering element positioned upstream of the last one of said one or more focusing apertures.

21. The mass spectrometer of Claim 20, wherein the first and the second steering elements are configured to provide ion beam steering along two non-parallel directions.

22. A method for operating a mass spectrometer, the method comprising: steering an ion beam to a last one of one or more focusing apertures positioned at an ion path of the mass spectrometer; generating, by the last one of the one or more focusing apertures, a focused ion beam; and steering the focused ion beam, using at least a first steering element, relative to a downstream pusher electrode of a time-of-flight mass analyzer.

23. The method of Claim 22, wherein steering the ion beam comprises steering the ion beam to the last one of the one or more focusing apertures using at least a second steering element.

24. The method of Claim 22, wherein at least one of the first steering element and the second steering element is configured to simultaneously steer and focus ions passing therethrough.

25. The method of any one of Claims 22 to 24, wherein steering the focused ion beam relative to the downstream pusher electrode comprises steering the focused beam in a first direction, and wherein steering the ion beam to the last one of the one or more focusing apertures comprises steering the ion beam in a second direction that is orthogonal to the first direction.

6. The method of Claim 25, wherein steering the focused beam in a first direction comprises controllably modulating a first voltage applied to electrodes of the at least the first steering element to steer the focused ion beam in the first direction, and wherein steering the ion beam in the second direction comprises controllably modulating a second voltage applied to electrodes of the at least the second steering element.