Ion routing device

Abstract

An ion routing device is provided that has at least three branches that intersect at the junction. [Solution] Each branch defines an ion path through the ion routing device, and the ion path through each branch defines the longitudinal axis of the branch. Each branch is provided with longitudinally extending electrodes, and the longitudinally extending electrodes of each branch are electrically isolated from the longitudinally extending electrodes of adjacent branches. The ion routing device also includes a controller configured to control the passage of ions through the ion routing device. The controller is configured to provide an RF electrical signal to the longitudinally extending electrodes of each branch and to apply different DC biases to each RF electrical signal between the longitudinally extending electrodes of at least two of the adjacent branches.

Description

Technical Field

[0001] The present disclosure relates to ion routing devices, and more particularly, to ion routing devices that can be used for the manipulation and transfer of ions in a mass spectrometer.

Background Art

[0002] A typical mass spectrometer includes an ion source, an ion processing device, and an ion mass analyzer / detector. The ion source generates a mixture of ionized species from an analyte that passes through the ion processing device and reaches the ion mass analyzer / detector. The ion processing device can include a mass filter, a mass separator, an ion accumulation device, and a reaction cell. The ion mass analyzer / detector is used to detect the number of incident ions as a function of the mass of the ions.

[0003] In the most common mass spectrometer architectures, the ion processing devices are connected continuously, as illustrated in FIG. 1A. With such a continuous architecture, ions can propagate from the ion source to the final detector along only a single path. This restricts the mass spectrometer to having only one ion source and only one dead-end ion detector. Another drawback of the continuous architecture is that ions must pass through all of the ion processing devices, even in operating modes where the ions do not benefit from such passage. For example, a mass filter and an ion fragmentation device function only during an MS2 scan, but ions must pass through these devices while they are deactivated during the acquisition of a panoramic MS1 spectrum. Thus, the continuous architecture suffers from unnecessary ion losses and time delays, which in turn result in sensitivity degradation and longer processing times.

[0004] These problems are exacerbated by the complexity and versatility of mass spectrometers. For example, a mass spectrometer may have several different ion processing devices, such as cells for collisional fragmentation, electron-based fragmentation (ExD), and UV fragmentation. Such a mass spectrometer may suffer additional delays if ions must pass through all ion processing devices, including inactive ones, when arranged in a continuous architecture.

[0005] Some ion processing devices, such as gas-phase reaction cells, ExD cells, and UV fragmentation cells, are relatively slow, requiring up to 100 ms to process an ion population. When such ion processing methods are involved in mass spectrometry scans, mass spectrometers with a continuous architecture are ultimately blocked from other faster scans, such as acquiring panoramic MS1 or MS2 spectra using collision fragmentation, which takes only a few milliseconds to perform.

[0006] To address these shortcomings, flexible ion routing has been employed. For this purpose, a mass spectrometer may be equipped with an ion routing device capable of selectively redirecting an ion flux to one of two or more arbitrary directions. A mass spectrometer having such a branching structure is shown in Figure 1B. Ion processing devices 1 and 2 in Figure 1B can be bypassed by directing incident ions directly to the ion mass spectrometer / detector for fast MS1 spectrum acquisition. To obtain an MS2 spectrum, the ion routing device can first direct the ions to either ion processing device 1 or ion processing device 2 for processing, and once processing is complete, the ion routing device can direct the processed ions to the ion mass spectrometer / detector. While the ion ensemble is being processed, for example, in ion processing device 1, the mass spectrometer can use ion processing device 2 to simultaneously acquire further MS1 or further MS2 spectra.

[0007] High vacuum transport devices (where ions move at speeds substantially exceeding the thermal velocity, essentially without gas collisions) can function as ion routing devices that selectively direct ions along alternative ion pathways using switchable deflectors. However, this approach is inconvenient for ion transfer between gas-filled ion processing devices where low-energy ion transport in gas-filled ion guides is preferred.

[0008] Nevertheless, there are conventional mass spectrometers that have ion routing devices equipped with gas-filled RF multipole and RF carpets capable of selectively transporting ions between different paths. U.S. Patent No. 9,812,311 describes an ion routing device having two parallel planar RF ion carpets separated by a gap. The carpets form tracks from which ions can move while being confined within the volume between the carpets. Segmented DC electrodes are positioned on both sides of the tracks on the same parallel substrate hosting the RF carpets. The DC electrodes are biased with a retarding voltage (e.g., a positive voltage for handling cations) that keeps ions on the RF tracks and also generates a field gradient for propelling ions along the tracks. U.S. Patent Application No. 2021 / 0364467 and U.S. Patent No. 11,119,069 describe similar arrangements but utilize traveling waves for ion propulsion along the tracks between the ion carpets.

[0009] U.S. Patent No. 7,420,161 describes a Y-shaped multipole capable of directing ions to one of two RF quadrupole branches. Its advantage over ion routing devices with RF carpets lies in better ion confinement in the quadrupole field. However, switching between the two branches requires a 180-degree shift in the RF phase on several electrodes, which is a relatively slow process and has the disadvantage of requiring a complex electron supply.

[0010] U.S. Patent No. 7,358,488 describes a cruciform structure of four branches intersecting at right angles to each other, as schematically shown in Figure 2. The four branches comprise RF electrodes that generate four RF multipole (quadrupole or octupole) configurations. The RF electrodes are labeled "A". A pair of blocking electrodes prevent ions from escaping from junction regions where the RF field is weaker (one of which is shown in Figure 2 and labeled "B"). In a quadrupole modification, RF is supplied to eight L-shaped electrodes with two opposite polarities, thereby generating a continuous X-shaped valley of RF dynamic gravity potential, allowing ions to propagate to any of the four branches. The desired ion path is selected by applying axial field gradients along two required branches and blocking DC potentials to the other two branches. Such designs suffer from significant ion loss and delay problems caused by insufficient extraction fields in junction regions, particularly when a 90-degree rotation is required. [Overview of the project]

[0011] According to a first embodiment, an ion routing device is provided having at least three branches that intersect at a junction. Each branch defines an ion path through the ion routing device, and each ion path through a branch defines the longitudinal axis of the branch. Each branch has a longitudinally extending electrode, and the longitudinally extending electrode of each branch is electrically isolated from the longitudinally extending electrode of an adjacent branch. The ion routing device also includes a controller configured to control the passage of ions through the ion routing device. The controller is configured to provide an RF electrical signal to the longitudinally extending electrode of each branch and to apply different DC biases to each RF electrical signal between the longitudinally extending electrodes of at least two of the adjacent branches.

[0012] By applying different DC biases to the bifurcations, ions can be attracted to pass through some bifurcations and repelled from passing through others, thus allowing for the selection of the ion path through the ion routing device. This configuration accelerates and minimizes ion loss while passing through the ion routing device. This shape can be optimized along the entire ion orbit to minimize the quadrupole component of the DC field, which typically leads to increased losses for higher masses.

[0013] The advantage of increased ion transfer speed is particularly beneficial during ion transfer when ions pass through 90-degree bends between branches. Furthermore, this arrangement is highly suitable for use in a very wide range of instrument configurations. This arrangement enables lossless (or very low-loss) ion transfer between different ion processing devices (IPDs) and / or two or more mass sources or mass spectrometers. Different IPDs, mass sources, and mass spectrometers may be arranged to receive ions from different branches of the ion routing device. This arrangement is highly advantageous in mass spectrometers combining high-speed and low-speed IPDs or analyzers because it allows for selective routing of ions to reduce time delays by enabling parallel operation of IPDs. As a result, the overall speed and sensitivity of the mass spectrometer are improved.

[0014] The controller may be configured to provide in-phase RF electrical signals to electrodes extending longitudinally in each branch, such that the electric fields generated in each branch are in phase with each other.

[0015] For example, the controller may be configured to control the passage of ions through an ion routing device from the input branch to the output branch of at least three branches by (i) providing an RF electrical signal to an electrode extending longitudinally in the input branch with a first DC bias, (ii) providing an RF electrical signal to an electrode extending longitudinally in the output branch with a second DC bias having a lower magnitude than the first DC bias, and (iii) providing an RF electrical signal to an electrode extending longitudinally in at least one unused branch with a third DC bias having a higher magnitude than the first DC bias, thereby leaving at least one unused branch.

[0016] The ion routing device may include an RF power supply for providing RF electrical signals. The RF power supply may be configured to provide RF electrical signals to the primary coil of a transformer further comprising secondary coils for each of at least three branches. The ends of each secondary coil may be connected to at least one opposing pair of electrodes extending longitudinally in each branch. The center point of each secondary coil is connected to a DC power supply configured to provide a DC bias to the RF electrical signals. This provides a simple arrangement for providing different DC biases to different branches.

[0017] The ion routing device may include a pair of central electrodes positioned on either side of the junction, and the controller is further configured to supply DC electrical signals to the pair of central electrodes. Conveniently, this makes it possible to bias the central electrodes to prevent ions from escaping from the junction of the ion routing device.

[0018] Optionally, each branch comprises four longitudinally extending electrodes arranged to form two pairs of longitudinally extending electrodes, with each pair of longitudinally extending electrodes positioned on either side of the ion path, thereby forming opposing pairs of at least one pair of opposing longitudinally extending electrodes. Such arrangement results in a quadrupole trapping field that traps ions in the space between the four longitudinally extending electrodes.

[0019] At least three branches can intersect at junctions such that the size of the ion path through each branch (e.g., the cross-sectional area of ​​the ion path) is maintained. For example, the branches and junctions may be free from obstacles that collide with the ion beam passing through the ion routing device. The ion path may extend through junctions without optical apertures configured to limit the size of the ion beam moving along the ion path from one branch to another. An aperture plate or aperture separation wall may be omitted from the junctions where the branches meet.

[0020] The ends of electrodes extending longitudinally from adjacent branches that intersect at the junction may be shaped to form a miter joint angle. This results in better control of the electric field shape at the junction.

[0021] In a currently preferred embodiment, each branch further includes laterally extending electrodes, and the controller is further configured to provide a DC electrical signal to the laterally extending electrodes of each branch. The resulting DC field helps to direct the passage of ions through the ion routing device in a desired direction. For each branch, the controller may be configured to provide a DC electrical signal via a resistor chain such that an electrical signal of varying DC magnitude is provided to the laterally extending electrodes. The laterally extending electrodes of each branch may form a series of longitudinally extending electrodes, and the resistor chain may be configured such that the DC magnitude of the DC electrical signal provided to each laterally extending electrode changes progressively along the series of electrodes. The DC magnitude may change linearly along the series of electrodes or according to a monotonic function.

[0022] The controller may be further configured to apply a traveling wave voltage signal to the electrodes. The traveling wave voltage signal can energize ions through an ion routing device. The controller may be configured to sequentially apply a dynamic or variable DC voltage, amplitude-modulated RF waveform, or frequency-modulated RF waveform to the electrodes. This can form a potential well that moves from one end of the branch to the other. The moving potential well can transport ions through an ion routing device.

[0023] Optionally, longitudinally extending electrodes and transversely extending electrodes are formed on the printed circuit board. This manufacturing method is particularly well suited to forming the electrode arrangements described herein. The longitudinally extending electrodes may be attached to the printed circuit board by soldering, for example. All longitudinally extending electrodes to be attached to a single printed circuit board may be formed as a single component and then attached to the printed circuit board before the gaps between the individual longitudinally extending electrodes are formed, for example, by wire etching. The transversely extending electrodes may be formed directly on the printed circuit board by etching, for example. Electrical contacts connecting to the longitudinally extending electrodes may be provided on the outside of the printed circuit board. A resistor chain used to supply DC electrical signals to the transversely extending electrodes may also be provided on the outside of the printed circuit board.

[0024] According to a second aspect, a method for selectively guiding ions through an ion routing device is provided. The ion routing device includes at least three branches that intersect at a junction. Each branch defines an ion path through the ion routing device, and the ion path through each branch defines the longitudinal axis of the branch. Each branch includes an electrode extending longitudinally. The electrodes extending longitudinally in each branch are electrically insulated from the electrodes extending longitudinally in adjacent branches. The method includes providing an RF electrical signal to each of the electrodes extending longitudinally in each branch and applying different DC biases to each RF electrical signal between at least two of the electrodes extending longitudinally in adjacent branches.

[0025] The in-phase RF electrical signal can be provided to the electrodes extending longitudinally in each branch such that the electric fields generated in each branch are in phase with each other.

[0026] The method can include selectively directing ions through the ion routing device from an input branch of at least three branches to an output branch, thereby leaving at least one unused branch. The RF electrical signal can be provided to the electrode extending longitudinally in the input branch with a first DC bias. The RF electrical signal can be provided to the electrode extending longitudinally in the output branch with a second DC bias that is smaller in magnitude than the first DC bias. The RF electrical signal can be provided to the electrode extending longitudinally in at least one unused branch with a third DC bias that is larger in magnitude than the first DC bias.

[0027] Optionally, the method includes providing an RF electrical signal to a primary coil of a transformer further comprising secondary coils for each of at least three branches using an RF power source. The ends of each secondary coil may be connected to at least one opposing pair of electrodes extending in the longitudinal direction of the respective branch. The center point of each secondary coil may be connected to a DC power source configured to provide a DC bias to the RF electrical signal. Each branch may comprise four longitudinally extending electrodes arranged to form two pairs of longitudinally extending electrodes. Each pair of longitudinally extending electrodes may be positioned on opposite sides of an ion path, thereby forming an opposing pair of at least one opposing pair of longitudinally extending electrodes. Each branch may comprise four longitudinally extending electrodes arranged to form two pairs of longitudinally extending electrodes. Each pair of longitudinally extending electrodes may be positioned on opposite sides of an ion path, thereby forming an opposing pair of at least one opposing pair of longitudinally extending electrodes.

[0028] The ends of the longitudinally extending electrodes of adjacent branches intersecting at the junction may be shaped to form a butt joint angle.

[0029] The method may further include providing a DC electrical signal to a pair of center electrodes positioned on opposite sides of the junction.

[0030] Each branch may further comprise laterally extending electrodes, and the method may further include providing a DC electrical signal to the laterally extending electrodes of each branch. For each branch, the DC electrical signal may be provided via a resistor chain such that a DC magnitude electrical signal that varies is provided to the laterally extending electrodes. The laterally extending electrodes of each branch may form a series of longitudinally extending electrodes, whereby the DC magnitude of the DC electrical signal provided to each laterally extending electrode varies progressively along the series of electrodes. The resistor chain of each branch may be configured such that the DC magnitude of the DC electrical signal provided to each laterally extending electrode varies linearly along the series of electrodes.

[0031] Longitudinal and transverse electrodes may be formed on a printed circuit board. Longitudinal electrodes may be mounted on the printed circuit board, while transverse electrodes may be formed directly on the printed circuit board, for example, by etching. Electrical contacts for connecting to longitudinal and transverse electrodes may be provided on the outside of the printed circuit board. A resistor chain used to supply DC electrical signals to the transverse electrodes may also be provided on the outside of the printed circuit board. [Brief explanation of the drawing]

[0032] To facilitate understanding of the present invention, the accompanying drawings are provided for illustrative purposes only. [Figure 1A] This is a schematic diagram of a conventional mass spectrometer with a continuous arrangement of cells. [Figure 1B] This is a schematic diagram of a conventional mass spectrometer with a discontinuous arrangement of cells, made possible by an ion routing device. [Figure 2] This is a schematic diagram of a conventional ion routing device. [Figure 3A] This is a schematic diagram of an embodiment of an ion routing device. [Figure 3B] Figure 3A is a schematic diagram of an alternative bias configuration for the ion routing device. [Figure 4A] Figure 3A is a schematic diagram of the power supply configuration for supplying electrical signals to the RF electrodes of an ion routing device, such as the ion routing device shown in Figure 3A. [Figure 4B] This is a schematic diagram of an alternative power supply configuration. [Figure 4C] This is a schematic diagram of the power supply configuration for supplying electrical signals to the DC electrodes of an ion routing device, such as the ion routing device shown in Figure 3A. [Figure 5] This is a schematic diagram of an embodiment of an ion routing device mounted using a printed circuit board. [Figure 6A]This is a perspective view of an embodiment of an ion routing device similar to the one shown in Figure 5. [Figure 6B] This is a perspective view of an embodiment of an ion routing device similar to the one shown in Figure 5. [Figure 7] These represent the RF pseudopotential and combined DC field observed within the ion routing device, as shown in Figure 5, for ion transport involving a straight line and a 90-degree rotation through the ion routing device, respectively. [Figure 8] Figures 7A and 7B are graphs showing the ion transport efficiency for straight-line and 90-degree rotational ion transport. [Figure 9] This is a schematic diagram of a mass spectrometer with MS2 capability that uses various fragmentation methods, such as those implemented using an embodiment of an ion routing device. [Figure 10] This is a schematic diagram of a mass spectrometer with MS3 capability implemented using an embodiment of an ion routing device. [Figure 11A] This is a schematic diagram of another mass spectrometer with MS2 capability implemented using an embodiment of an ion routing device. [Figure 11B] This is a schematic diagram of another mass spectrometer with MS2 capability implemented using an embodiment of an ion routing device. [Modes for carrying out the invention]

[0033] An embodiment of the ion routing device 10 according to the present invention is shown in Figure 3A. The ion routing device 10 has four branches 121-12, each equipped with an ion guide. 4IThe ion routing device is provided with the following: Branches 121-124 intersect at the junction 14. Each branch 121-124 has four RF electrodes 16. The plan view in Figure 3A shows only the upper half of the ion routing device 10, i.e., only the upper pairs of RF electrodes 16 of each branch 121-124. As can be seen from the figure, the RF electrodes 16 are electrodes that extend in the longitudinal direction. To indicate the arrangement of adjacent electrodes 16 that terminate adjacent to each other at the junction 14, referred to as “adjacent RF electrodes” 16, one such pair of RF electrodes is labeled 161 and 162.

[0034] An RF waveform is applied to the RF electrode 16 to generate an electric field that moves ions along the central volume of each branch 121-124 within each set of four RF electrodes 16. Alternatively, a DC offset may be applied to the RF electrode 16. The magnitude of the DC offset applied to the RF electrodes 16 of different branches 121-124 can be varied relative to each other, allowing ions to be directed from one particular branch 121-124 to another.

[0035] The RF waveform may be applied to the RF electrode 16 with polarities shown as +RF and -RF in Figure 3A. Using RF electrodes 161 and 162 as examples, adjacent RF electrodes such as 161 and 163 have the same RF polarity (and therefore phase), in this case -RF. The corresponding RF electrodes 16 in the lower half of the ion routing device 10 (not shown in Figure 3A) are supplied with RF waveforms of opposite polarity, i.e., the lower RF electrodes corresponding to 161 and 163 have a +RF polarity. In this way, a desired electric field is generated that holds ions in the space between the RF electrodes 16.

[0036] Figure 3A shows that adjacent RF electrodes, such as RF electrodes 161 and 163, are electrically isolated from each other by a small gap (e.g., 0.5 mm wide) at the junction 14. The ends of adjacent electrodes (such as electrodes 161 and 163) can be shaped to form a miter joint angle where they intersect at the junction 14. Other shapes may be used, but preferably the electrodes are separated by a gap of a constant or substantially constant width. The shape of the gap may deviate from the straight line shown in Figure 3A and can follow any curve, for example. For example, the ends of adjacent RF electrodes 16 can be tapered from a first width of electrode 16 distal to the junction 14 to a second width proximal to the junction 14. In some embodiments, adjacent RF electrodes 16 can be tapered to the point of the junction 14.

[0037] The small gap provides electrical insulation, thereby allowing DC offsets of different magnitudes to be applied to the RF electrodes 16 of each branch 121-124, as described above. All RF electrodes 16 of any particular branch 121-124 are provided with a DC offset of the same magnitude, although this magnitude may differ from branch to branch. The DC offsets applied to branches 121-124 are shown as DC1-DC4 in Figure 3A.

[0038] Therefore, each RF electrode 16 has an applied waveform that includes an RF component and a DC offset. For example, RF electrode 161 is provided with an RF waveform corresponding to -RF+DC1, and RF electrode 162 is provided with an RF waveform corresponding to -RF+DC2. As described above, the RF waveform provides an electric field that radially constrains ions passing along branches 121-124, thereby minimizing lateral leakage of ions from branches 121-124 as ions pass through each branch 121-124. The DC offset provides an overall attractive or repulsive electric field to each branch 121-124 relative to the other branches 121-124. The DC offset is selected according to the desired direction of ion transport through the ion routing device 10. For example, in order to transport ions (e.g., cations) from branch 121, which functions as an input branch, to branch 122, which functions as an output branch (i.e., to pass straight through junction 14), the DC offset is selected to provide a relatively weak DC offset in the electric field within output branch 122 such that DC2 <= DC1. This difference in DC offset ensures that ions are attracted from branch 121 to branch 122. Unused branches 123 and 124 are blocked by providing larger DC offsets to the electric field, setting DC3 > DC1 and DC4 > DC1 for branches 123 and 124, respectively. The stronger DC offsets in the electric field create a potential difference between branches 121 and 124 that repels ions from branches 123 and 124. As another example, setting the DC offset such that DC3 <= DC1, DC2 > DC1, and DC4 > DC1 would result in a potential difference between branches 121 and 124 that induces ions to be injected into branch 121, causing them to rotate 90 degrees and pass through branch 123, while blocking ions from branches 122 and 124.

[0039] Figure 3B shows an alternative RF phase configuration placed on the RF electrode 12 that can be used for linear ion transport where beam rotation is not required (for simplicity, the DC electrode 18 is not shown in Figure 3B). Such a configuration can provide better linear ion transport from branch 121 to 122, for example, as shown in Figure 3B.

[0040] Each branch 121-124 is an open-end structure terminating at the junction 14. In particular, the ion paths in the space between the RF electrodes 16 of each branch 121-124 extend into the junction 14 without any obstructions such as constricted openings defined by separation walls or similar structures. Thus, the ions have an unconstricted path from one branch 121-124 to the next, and the (lateral) size of the ion path is maintained, or substantially maintained, from one branch 121-124 to the next. In this sense, the junction 14 forms an open interface between the four branches 121-124.

[0041] Each branch 121-124 also comprises a series of opposing, laterally extending electrodes 18 biased with a DC voltage only. These electrodes 18 are therefore referred to as DC electrodes 18. Each branch 121-124 comprises one series of DC electrodes 18 above the ion path (shown in Figure 3A) and a second series of DC electrodes 18 below the ion path (not shown in Figure 3A). Each series of DC electrodes 18 extends longitudinally toward the junction 14. A pair of common electrodes 18 are located in the center. c There is a central electrode 18, one of which is directly above the joint and the other is directly below the joint 14. c The DC electrodes 181 in each adjacent row have angled edges so that these DC electrodes 181 intersect at a miter joint angle, as can be best seen by referring to Figure 3A. Other shapes may be used, but preferably the electrodes are separated by a gap of constant or substantially constant width. The shape of the gap may differ from the straight line shown in Figure 3A. These DC electrodes 181 are connected to the pair of central DC electrodes 18 c Surround it.

[0042] The DC-only voltages U0-U4 applied to the DC electrodes 18 are shown in Figure 3A for the upper set of DC electrodes 18. The lower set of DC electrodes 18 corresponds in shape, size, and configuration and is supplied with the same set of DC-only voltages U0-U4. The DC electrodes 18 are supplied with DC-only voltages derived from the four DC voltages U0-U4. The DC electrodes 18 drive ions along each branch 121-124, generating an auxiliary axial electric gradient with respect to the electric field along each branch 121-124. This electric field gradient along each arm 121-124 is achieved by connecting each series of DC electrodes 18 using, for example, a resistor-divided chain configured to apply an electric field gradient of, for example, 0.001-0.5 V / mm, preferably about 0.15 V / mm.

[0043] Therefore, the fields generated by the DC-only voltages U0-U4 provide the propulsion force to move ions along each branch 121-124, while the DC offsets DC1-DC4 are used to create a difference in the DC fields between the different branches 121-124 to steer the ions in the desired direction, and the RF waveforms ±RF are used to constrain the ions using each branch 121-124 and minimize lateral ion leakage.

[0044] Figure 4A shows an exemplary arrangement of how the RF waveform + / -RF and DC offsets DC1-DC4 can be supplied to the RF electrodes 16. Figure 4A shows an RF power supply 20 that is operable to generate an initial RF waveform applied to the primary coil 22 of transformer 24. Transformer 24 generates phase-matched RF voltages with amplitudes equal to the initial RF waveform in four secondary coils 261-264. Each secondary coil 261-264 is connected across the RF electrodes 16 of the corresponding branches 121-124, so that each branch 121-124 receives a phase-matched RF voltage with amplitudes equal to the amplitude of the initial RF waveform generated by its secondary coils 261-264. Individually controlled DC voltages are applied at the midpoint of each secondary coil 261-264, providing DC offsets DC1-DC4 to the RF electrodes 16 within each branch 121-124.

[0045] Figure 4B shows an alternative exemplary arrangement of how the RF waveform + / -RF and DC offsets DC1 to DC4 may be supplied to the RF electrode 16. The figure is simplified in that it shows the connections of two branches 121 and 122. Similar connections are made for branches 123 and 124.

[0046] Similar to Figure 4A, Figure 4B shows an RF power supply 20 that can operate to generate an initial RF waveform applied to the primary coil 22 of transformer 24. Transformer 24 generates phase-matched RF voltages with amplitude equal to the initial RF waveform in four pairs of secondary coils 261-264. Each of the pairs 261-264 secondary coils is connected to the RF electrodes 16 of the corresponding branches 121-124 and individually controlled DC voltages DC1A, DC1B, DC2A, DC2B, DC3A, DC3B, DC4A, and DC4B, providing a DC offset to the RF electrodes 16 within each branch 121-124. It is possible to apply resolved DC components to one or more branches 121-124, providing the possibility of mass filtering. For example, DC1A = DC1 + resolvingDC, DC1B = DC1 - resolvingDC, DC2A = DC2 + resolvingDC, DC2B = DC2 - resolvingDC, etc. In this case, only ions with a mass-to-charge ratio (m / z) that satisfies Mathieu's stability criterion can pass through branches 121-124 (see, for example, U.S. Patent No. 2,939,952). Special shapes or fields (asymmetric rods, multi-frequency RF, etc.) can also be implemented within such guides to improve their performance (see, for example, U.S. Patents No. 7,709,786, No. 11,282,693, No. 12,040,173, and No. 7,633,060). The addition of a decomposed DC component may be useful in applications where only partial transmission over a broad initial m / z range is beneficial.

[0047] Figure 4C shows an exemplary arrangement of how DC-only voltages U0-U4 can be supplied to the DC electrodes 18 of each branch 121-124 using the arrangement of Figure 4A. The DC electrodes 18 are supplied with individually controlled DC voltages defined by voltages U0-U4. Voltage U0 is supplied to the electrode pair 18 located in the upper and lower center of the junction 14. c It is applied directly. In operation using positive ions, the DC-only voltage U0 can be higher than all DC offsets DC1 to DC4 in order to prevent ion leakage from the top and bottom of the junction 14 of the ion routing device 10.

[0048] The DC-only voltages U1-U4 are applied directly to the DC electrodes 181-184 of each branch 121-124, i.e., the DC electrode 184 furthest from the junction 14. To reduce the number of individual DC voltage sources, the other DC electrodes 181-183 within each branch 121-124 are connected via a continuous resistor voltage divider 28 that provides voltage distribution to the DC electrodes 181-183 within each of the branches 121-124. Figure 4B shows two resistor voltage dividers 28 for branches 121 and 122. The corresponding resistor voltage dividers 28 for branches 123 and 124 are not shown for clarity. For example, these distributions may be substantially linear such that each DC electrode 181-184 in the set receives a progressively decreasing voltage. Center electrode 18 c The DC electrodes 181 of each branch 121-124 closest to the center receive the same potential U0. The difference between the central voltage U0 and the voltages applied to the DC electrodes 181-183 relative to U0 generates a field gradient that drives ions along branches 121-124.

[0049] In some embodiments, a traveling wave voltage signal can be applied to the electrode 18 as an alternative to, or in addition to, a gradient DC field, to propel ions through the ion routing device 10. In various embodiments, a dynamic or variable DC voltage, amplitude-modulated RF waveform, or frequency-modulated RF waveform can be sequentially applied to the electrode 18 to generate a potential well that moves from one end of the branch to the other. The moving potential well can transport ions through the ion routing device 10. (See, for example, U.S. Patents 6,812,453, 9,799,503, or 10,692,710).

[0050] In some embodiments, the ion routing device 10 in Figure 3A is gas-filled to a pressure sufficient for ion thermalization along one of the lengths of branches 121 to 124. For example, a branch length of 50 mm provides approximately 5 × 10⁻¹⁶ ions for an ion mass range of less than 1 kDa. -3 5 × 10 for the ion mass range up to mbar and 100 kDa -2 A gas pressure N2 of mbar is required. During operation, the ion routing device 10 is pressurized via a gas inlet capillary tube and can be controlled via a feedback loop based on readings from a Pirani gauge (or similar) directly connected to the ion routing device 10.

[0051] To facilitate ion propagation through the RF quadrupoles within each branch 121-124, the RF electrodes 16 and DC electrodes 18 can be mounted on two dielectric substrates 30, as shown in Figure 5. Each substrate 30 is a printed circuit board (PCB). A pair of RF electrodes 16 are attached to each PCB 30, which may be a PCB plate (e.g., by welding, soldering, or bonding). These RF electrodes 16 do not need to have flat or parallel surfaces, and may have concave or convex shapes, etc. The RF waveform is applied with alternating polarity ±RF to form a quadrupole field distribution that constrains ions near the axis along the RF electrodes 16 perpendicular to the plane of the drawing. The DC electrodes 18 are formed directly on the PCB 30 (e.g., by etching) or formed externally and attached to the PCB 30 to generate an axial gradient that propels ions along the axis. The configuration of the RF electrode 16 and DC electrode 18 is optimized to compensate for the quadrupole DC component, as taught in U.S. Patent No. 9,536,722, thereby maximizing the mass range of ionic stability. However, other configurations are possible if a better quality quadrupole field is required; for example, the RF electrode can be hyperbolic, particularly if additional mass selection is needed within the ion guide 10. Alternatively, additional PCB electrodes can be added to the sides of the RF electrode 16.

[0052] An example of the ion routing device 10 was numerically simulated using MASIM 3D software, and the mechanical design was performed in SolidWorks. The ion routing device 10 was modeled as a sandwich of two parallel PCBs 30 having etched DC electrodes 18 and soldered RF electrodes 16. Electrical contacts for RF and DC voltage supply were mounted on the outside of the PCB 30, as was a resistor chain 28 that distributes an axial gradient voltage between the DC electrodes 18. All RF electrodes 16 can be machined from a single piece of metal to form the overall cross shape and then soldered to each PCB 30 with precise alignment. The central gap between the RF electrodes 16, the top surface of the RF electrodes 16, and the 45-degree slots between adjacent electrodes 16 at the joint 14 can then be precisely machined and finished by wire erosion technique.

[0053] Detailed modeling has shown that it is advantageous to narrow the RF electrode 16 where it intersects at the junction 14 (most commonly seen in Figure 4A). The narrowed portion 31 allows for stronger penetration of the entire DC field into the junction 14, thereby equipping the DC offset at the center point of the ion routing device 10 by reaching the ions in the most efficient manner. It has been found that if the RF electrode 16 is not narrowed in this way, the DC field at the center point becomes non-uniform, potentially forming either a potential barrier or a potential well at the center point. Both adversely affect ion permeability. The resulting quadrupole fields of branches 121-124 provide the strongest compression of the ion beam at the exits of branches 121-124, and thus improve the transfer of ions into and back into the subsequent ion processing device. The narrowed portion 31 of the RF electrode may also be provided by notches 31 formed at the cruciate corners of the RF electrode 16, where they intersect at the junction 14. The notches 31 may be circular as shown in Figure 4A, but other shapes may be used.

[0054] The spacers 34 between the PCBs 30 also form an airtight enclosure for maintaining the gas pressure within the ion routing device 10 at a desired level. The spacers 34 can also be used for aligning the respective ends of the branches 121-124 and for alignment with subsequent devices. In the former case, using the spacers 34 to align the fully open ends of the branches 121-124 at the junction 14 helps maintain, or substantially maintain, the (lateral) size of the ion path from one branch 121-124 to the next. In this sense, the junction 14 forms a non-opening interface between the four branches 121-124. In fact, each branch 121-124 has an internal space with cross-sectional sizes defined on both sides by the spacers 34 and at the top and bottom by the PCBs 30. The cross-sectional size is the same for each branch 121-124, and all of these are open ends that contact each other to define a large opening between each branch 121-124 relative to the size of the ion path between the RF electrodes 16.

[0055] No constricted openings, defined by separation walls or the like, are located between branches 121 and 124, so that ions have an unconstricted path from one branch 121 to 124 to the next branch 121 to 124.

[0056] Figures 6A and 6B show the distribution of the RF-driven pseudopotential and the coupled superimposed DC field on the central plane of the ion routing device 10 in two operating modes. Figure 6A shows an example of linear ion transmission from branch 121 to branch 122, and Figure 6B shows an example of ion transmission with a 90-degree rotation from branch 121 to branch 123.

[0057] Figure 7 shows the simulated ion transport efficiency in the two operating modes shown in Figures 6A and 6B. Figure 7 demonstrates that for ions with m / z above the low mass cutoff, substantially 100% lossless transmission is possible compared to the linear mode in Figure 6A. Figure 7 also shows that in the rotational mode in Figure 6B, nearly 100% transmission is possible over a wide m / z range.

[0058] Several exemplary arrangements of the ion routing device 10 within the mass spectrometer 100 will be presented here.

[0059] Figure 8 shows the ion source 102, the quadrupole mass filter 104, and collision-induced dissociation. dissociation (CID) cell 106, ion routing device 10, ultraviolet photodissociation (ultra-violet) An example of a mass spectrometer 100a is shown, including a photodissociation (UVPD) cell 108, an electron-based dissociation (ExD) cell 110 (such as an electron collision dissociation cell), and a time-of-flight (TOF) mass spectrometer 112. A mass filter 104 is positioned immediately after the ion source 102 to allow separation of a specific m / z interval. A CID cell 106 follows the mass filter 104 and can be activated to fragment selected ions by collision with the gas. An ion routing device 10 contains the same gas as the CID cell 106. The ion routing device 10 receives ions from the CID cell 106 to branch 121, allowing selective routing of ions to one of the following devices, namely, the TOF mass spectrometer 112 via branch 122, the UVPD cell 108 via branch 123, or the ExD cell 110 via branch 124.

[0060] In some modes, ions are linearly transported through the ion routing device 10 to the TOF mass spectrometer 112 via branches 121 and 122, thereby enabling high-speed acquisition of MS2 spectra (with repetition rates up to several kHz). In other modes, fragmented or intact ions are diverted to the UVPD cell 108 via branches 121 and 123, or to the ExD cell 110 via branches 121 and 124, where the ions are stored for, for example, 1 ms to 100 ms and undergo corresponding processing. During UVPD and / or ExD processing of the stored ions, other ions may be linearly transported into the TOF mass spectrometer 112 through the ion routing device 10, ensuring no delay in the TOF processing. Once the UVPD or ExD processing is complete, the processed ions are returned to the ion routing device 10 and transported to branch 122 for forward transmission toward the TOF mass spectrometer 112. During this transfer, the input branch 121 of the ion routing device is kept interrupted by a delayed DC voltage offset DC1.

[0061] The UVPD cell 108 may be replaced by a dead end plate, and the branch 123 may be used to store ions (for example, for subsequent BoxCar acquisition as described in International Publication No. 2018 / 134346, or for subsequent multiplexed SIM as described in U.S. Patent No. 7,880,136).

[0062] Alternatively, the CID cell 106 may be positioned at the rear branch 122 on the way to the TOF mass spectrometer 112, as shown in the mass spectrometer 100b of Figure 9. This architecture allows for arbitrary fragmentation of ions after UVPD or ExD treatment and before mass spectrometry. For this purpose, ions are transferred from branch 123 or 124 to branch 122 and then to the CID cell 106. To enable MS3 analysis (CID-CID, UVPD-CID, or ExD-CID), an ion gate 114 and an ion storage device 116 (e.g., a storage multipole) are introduced between the ion source 102 and the ion routing device 10. During operation, ions from the ion source 102 travel through the open gate 114 and ion storage device 116 without accumulation, are mass-selected in the mass filter 104, and transferred by the ion routing device 10 to one of the following ion processing devices: CID cell 106, UVPD cell 108, or ExD cell 110. After processing using the corresponding fragmentation method, the ions are returned to the ion routing device 10, directed to branch 121, and re-enter the mass filter 104. During this stage, the ion gate 114 is closed to prevent mixing of processed and unprocessed ions. On their way through the mass filter 104, the ions are mass-selected again to select the desired ion species and are accumulated in the ion storage device 116. In the next stage, the accumulated ions are marshalled back towards the TOF mass spectrometer 112 through the mass filter 104, ion routing device 10, and CID cell 106, with any further fragmentation in the CID cell 106.

[0063] Figure 10 shows a mass spectrometer 100c with two mass spectrometers, namely a TOF mass spectrometer 112 and an orbitrap mass spectrometer 118. A branch 124 of the ion routing device 10 may be used to divert some ions to a C-shaped ion trap 120 (C-trap), and the ions are orthogonally accelerated toward the orbitrap mass spectrometer 118. Mass spectrometer 100c of this architecture benefits from the high repeatability of the TOF mass spectrometer 112 and the high resolution of the orbitrap spectrometer 118.

[0064] Figures 11A and 11B give examples of mass spectrometer architectures 100d and 100e with two ion routing devices 10 and multiple ion processing devices. The multiple ion routing devices 10 are preferably fabricated on the same pair of upper and lower PCBs 30 and share one gas supply capillary tube. The RF waveforms ±RF of the ion routing devices 10 preferably have the same frequency and are phase-synchronous to enable aperture-free and lossless ion transfer between the ion routing devices 10. Several different configurations of the ion routing devices 10 are shown in Figures 11A and 11B, but are not limited to these.

[0065] Those skilled in the art will understand that the above embodiments can be modified in many different ways without departing from the scope of the invention as defined by the appended claims.

[0066] For example, the above diagram and description relate to an ion routing device 10 in which all branches 121-124 are in the plane. However, this is not always the case. One or more branches 121-124 may be located out of the plane. This can be used to allow for additional branches 121-124. For example, two further branches 121-124 may be added, 90° out of the plane, so that a 6-branch intersection can be realized. Also, when branches 121-124 are located in the plane, they do not need to extend 90° from each other. For example, an in-plane 6-branch configuration may be implemented in which branches 121-126 are arranged at equal intervals of 60°.

Claims

1. An ion routing device, At least three branches intersecting at the joint, Each branch defines an ion path through the ion routing device, and each ion path through the branch defines the longitudinal axis of the branch. Each branch is equipped with an electrode that extends in the longitudinal direction. Each branch has electrodes extending in the longitudinal direction that are electrically insulated from electrodes extending in the longitudinal direction of adjacent branches, and consists of at least three branches. An ion routing device comprising: a controller configured to control the passage of ions through the ion routing device, wherein the controller is configured to provide an RF electrical signal to the longitudinally extending electrode of each branch and to apply different DC biases to each RF electrical signal between at least two of the longitudinally extending electrodes of the adjacent branches.

2. The ion routing device according to claim 1, wherein the controller is configured to provide a first set of in-phase RF electrical signals to electrodes extending longitudinally in the first set of the branch, and a second set of in-phase RF electrical signals to electrodes extending longitudinally in the second set of the branch, the second set of in-phase RF electrical signals being 180 degrees out of phase with the first set of in-phase RF electrical signals such that the electric fields generated at each branch are in phase with each other.

3. The controller controls the passage of ions through the ion routing device from the input branch to the output branch of the at least three branches, thereby, The RF electrical signal is supplied to the electrodes extending in the longitudinal direction of the input branch using a first DC bias. Using a second DC bias that is smaller in magnitude than the first DC bias, the RF electrical signal is supplied to the electrodes extending in the longitudinal direction of the output branch. The ion routing device according to claim 1 or 2, configured to leave at least one unused branch by providing the RF electrical signal to the longitudinally extending electrode of the at least one unused branch using a third DC bias which is larger in magnitude than the first DC bias.

4. The RF power supply for providing the aforementioned RF electrical signals is provided, The RF power supply is configured to supply the RF electrical signal to the primary coil of a transformer further comprising a secondary coil for each of the at least three branches. The ends of each secondary coil are connected to at least one opposing pair of electrodes extending in the longitudinal direction of each branch. The center point of each secondary coil is connected to a DC power supply configured to provide the DC bias to the RF electrical signal. Or, The RF power supply is configured to supply the RF electrical signal to the primary coil of a transformer further comprising a pair of secondary coils for each of the at least three branches. The ion routing device according to claim 3, wherein each end of each pair of secondary coils is connected to one longitudinally extending electrode of at least one opposing pair of longitudinally extending electrodes of each branch, and the other end of each pair of secondary coils is configured to provide a DC bias, with one secondary coil receiving a DC bias equal to the DC voltage plus the DC decomposition component, and the other secondary coil receiving a DC bias equal to the DC voltage minus the DC decomposition component.

5. The ion routing device according to any one of claims 1 to 4, further comprising a pair of central electrodes positioned on both sides of the junction, wherein the controller is further configured to provide DC electrical signals to the pair of central electrodes.

6. The ion routing device according to any one of claims 1 to 5, wherein each branch comprises four longitudinally extending electrodes arranged to form two pairs of longitudinally extending electrodes, each pair of longitudinally extending electrodes positioned on either side of the ion path, thereby forming one of the at least one opposing pair of longitudinally extending electrodes.

7. The ion routing device according to any one of claims 1 to 6, wherein the at least three branches intersect at the junction such that the size of the ion path through each branch is maintained, and optionally the ion path extends through the junction without an optical aperture configured to limit the size of the ion beam moving along the ion path from one branch to another.

8. The ion routing device according to any one of claims 1 to 7, wherein the ends of electrodes extending in the longitudinal direction of adjacent branches that intersect at the joint are shaped to form a miter joint angle.

9. The ends of the electrodes extending in the longitudinal direction of adjacent branches are formed to contact at the joint and form a notched section between the adjacent branches, optionally, The ion routing device according to any one of claims 1 to 8, wherein the notched section forms a constricted portion of the electrode extending in the longitudinal direction at the joint.

10. Each branch further comprises electrodes extending laterally, The ion routing device according to any one of claims 1 to 9, wherein the controller is further configured to provide a DC electrical signal to the laterally extending electrodes of each branch.

11. The ion routing device according to claim 10, wherein for each branch, the controller is further configured to provide the DC electrical signal via a resistor chain such that the laterally extending electrodes are provided with an electrical signal of varying DC magnitude.

12. For each branch, The aforementioned electrode extending in the lateral direction forms a series of electrodes extending in the longitudinal direction. The resistor chain is configured such that the magnitude of the DC electrical signal provided to each laterally extending electrode changes progressively along the series of electrodes, and optionally, The ion routing device according to claim 11, wherein the resistor chain is configured such that the magnitude of the DC of the DC electrical signal provided to each laterally extending electrode changes linearly along the series of electrodes.

13. The ion routing device according to any one of claims 1 to 12, wherein the controller is further configured to apply a traveling wave voltage signal to the electrode and optionally apply a dynamic or variable DC voltage, an amplitude-modulated RF waveform, or a frequency-modulated RF waveform to the electrode in sequence.

14. The electrodes extending in the longitudinal direction and the electrodes extending in the transverse direction are formed on a printed circuit board, and can be optionally configured as follows: The ion routing device according to any one of claims 10 to 13, wherein the longitudinally extending electrode is attached to the printed circuit board, and the transversely extending electrode is formed directly on the printed circuit board, for example, by etching.

15. The ion routing device according to claim 14, as dependent on claim 11, wherein the printed circuit board is provided with electrodes extending in the longitudinal direction, electrodes extending in the transverse direction, and electrical contacts connected to the resistor chain on the outside of the printed circuit board.

16. A method for selectively directing ions through an ion routing device, wherein the ion routing device comprises at least three branches intersecting at a junction, each branch defining an ion path through the ion routing device, the ion path through each branch defining the longitudinal axis of the branch, each branch comprising a longitudinally extending electrode, the longitudinally extending electrode of each branch being electrically insulated from the longitudinally extending electrode of an adjacent branch, and the method is as follows: To provide an RF electrical signal to each of the electrodes extending in the longitudinal direction of each branch, A method comprising applying different DC biases to each RF electrical signal between at least two longitudinally extending electrodes of the adjacent branches.

17. The method according to claim 16, comprising providing a first set of in-phase RF electrical signals to a first set of electrodes extending in the longitudinal direction of the branch, and a second set of in-phase RF electrical signals to a second set of electrodes extending in the longitudinal direction of the branch, wherein the second set of in-phase RF electrical signals is 180 degrees out of phase with the first set of in-phase RF electrical signals such that the electric fields generated at each branch are in phase with each other.

18. The ion routing device selectively directs ions from the input branch to the output branch of the at least three branches, thereby The RF electrical signal is supplied to the electrodes extending in the longitudinal direction of the input branch using a first DC bias. Using a second DC bias that is smaller in magnitude than the first DC bias, the RF electrical signal is supplied to the electrodes extending in the longitudinal direction of the output branch. The method according to claim 16 or 17, comprising leaving at least one unused branch by providing the RF electrical signal to the longitudinally extending electrode of the at least one unused branch using a third DC bias which is larger in magnitude than the first DC bias.

19. Using an RF power supply to provide the RF electrical signal to the primary coil of a transformer further comprising secondary coils for each of the at least three branches, wherein the end of each secondary coil is connected to at least one opposing pair of electrodes extending longitudinally in each branch, and the center point of each secondary coil is connected to a DC power supply configured to provide the DC bias to the RF electrical signal. Or, The method according to claim 18, comprising using an RF power supply to provide the RF electrical signal to the primary coil of a transformer further comprising a pair of secondary coils for each of the at least three branches, wherein the ends of each pair of secondary coils are connected to one longitudinally extending electrode of at least one opposing pair of longitudinally extending electrodes of each branch, and the other ends of each pair of secondary coils are provided with a DC bias, with one secondary coil receiving a DC bias equal to the DC voltage plus the DC decomposition component, and the other secondary coil receiving a DC bias equal to the DC voltage minus the DC decomposition component.

20. The method according to any one of claims 16 to 19, further comprising providing a DC electrical signal to a pair of central electrodes located on both sides of the joint.

21. The method according to any one of claims 16 to 20, wherein each branch further comprises a laterally extending electrode, and the method further comprises providing a DC electrical signal to the laterally extending electrode of each branch.

22. The method according to claim 21, comprising providing the DC electrical signal via a resistor chain such that, for each branch, the laterally extending electrode is provided with an electrical signal of varying DC magnitude.

23. The method according to claim 22, wherein, for each branch, the laterally extending electrode forms a series of electrodes extending in the longitudinal direction, and the magnitude of the DC of the DC electrical signal provided to each laterally extending electrode changes progressively along the series of electrodes.

24. The method according to claim 23, wherein, for each branch, the resistor chain is configured such that the magnitude of the DC of the DC electrical signal provided to each laterally extending electrode changes linearly along the series of electrodes.

25. The method according to any one of claims 16 to 24, further comprising applying a traveling wave voltage signal to the electrode and optionally applying a dynamic or variable DC voltage, an amplitude-modulated RF waveform, or a frequency-modulated RF waveform to the electrode in sequence.

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