Method for scheduling ions for analysis

Abstract

A method of scheduling ions for analysis by a mass analyzer over a range of mass-to-charge ratios (m / z) of interest is provided herein. The method includes obtaining predicted intensities and associated m / z of ions across a range of masses of interest. The method also includes inputting ions to an ion scheduling device, outputting the ions from the ion scheduling device to the mass analyzer according to m / z or ion mobility of the ions, and selectively attenuating the ions based on the predicted intensities and associated m / z of the ions.

Description

Technical Field

[0001] This disclosure relates to mass spectrometry. In particular, this disclosure relates to a method for manipulating ions to perform mass spectrometry. Background Technology

[0002] US-A-2939952 discloses a tandem mass spectrometer that employs a quadrupole mass filter to isolate target ions before fragmentation and further downstream mass analysis. One characteristic of quadrupole mass filters is that unselected ions bombard the quadrupoles, resulting in the loss of valuable analyte ions and also contaminating and ultimately degrading the electrodes. Depending on the isolation window used, the theoretical sensitivity loss can easily exceed 99%.

[0003] One workaround is to accumulate and separate ions upstream of the quadrupole so that the m / z of the ions delivered to the device roughly matches the range of the isolation window, thus minimizing ion loss and achieving accuracy before separation. Residual loss then becomes a factor affecting the resolution before separation and the quality of alignment with the quadrupole isolation window.

[0004] This method was initially described by Hoyes in GB-A-2442638, in which ions are first loaded into an ion trap. A pseudo-barrier at the RF level prevents the release of ions with lower m / z values ​​unless they are pushed toward the exit by a DC or traveling wave to overcome the RF pseudo-barrier, thus releasing these ions for quadrupole selection / fragmentation, etc. Giles in US-B-6914241B and Bateman in US-B-6838662 further describe methods using a reverse traveling wave and a nonlinear DC gradient to create ion separation within the guide. These ions reach equilibrium positions and can be released in a time-dependent manner through the quadrupole by adjusting the DC or traveling wave amplitude, thus significantly enhancing its efficiency. Figure 1 This illustrates the ion separation under these two opposing forces, and Figure 2 A schematic diagram of an ion dispatching method using an ion dispatching device and a quadrupole is shown.

[0005] Several techniques are available for implementing this "ion scheduling" process. Typical methods involve separating ions under the influence of two different forces, such as DC potential, RF pseudobarrier (or traveling wave), or collision resistance with a buffer gas. US-B-10665441 discloses an ion scheduling method involving parallel ion acquisition followed by serial fragmentation. A parallel accumulation and serial fragmentation method from a Trapped Ion Mobility Spectroscopy (TIMS) device is disclosed in Meier, F. et al., Parallel Accumulation-Serial Fragmentation (PASEF): Multiplying Sequencing Speed ​​and Sensitivity by Synchronized Scans in a Trapped Ion Mobility Device. Journal of Proteome Research 2015, 12, 5378-5387, US9891194B2, and US10794861B2. Other implementations include accumulation in multiple wells, or orthogonally across an RF pseudobarrier (US10199208B2) or via ion mobility (US9607817B1).

[0006] It is also known to use traveling waves to propel ions through ion guides. US-B-7375344 discloses a series of applications of out-of-phase RF potentials, while Giles et al., Applications of a traveling wave-based radio-frequency-only stacked ring ion guide, Rapid Commun. Mass Spectrom. 2004; 18:2401–2414 discloses applying switching DC pulses to a continuous axial segment of an ion guide to generate a potential front that moves downward over time at the center of the guide, thereby dragging ions along with it.

[0007] In a process known as automatic gain control, the mass spectrometer controls ion loading into the trap by varying the ion accumulation time. This process is inevitably disrupted by the ion dispatching mechanism, which converts the continuous ion beam into time-varying concentrated pulses of ions with similar m / z. This problem is believed to be solvable by downstream beam attenuation, and most promisingly by altering the duty cycle of the fast-pulse ion optical gating element. US-B-7960690 has demonstrated this effect using 1kHz switching, where the expected ion packet appears with a pulse width of <2ms.

[0008] Tandem mass spectrometry involves the isolation and fragmentation of eluted analyte material, thereby generating fragment mass spectra for mass analysis to return structural and quantitative information. These MS / MS or MS2 spectra are typically supported by survey spectra of unfragmented precursor ions (referred to as MS1, MS, or full MS spectra), which provide information about their accurate m / z and intensity. This analysis is optional for data-independent acquisition (DIA) methods, but for data-dependent acquisition (DDA) methods, a list of precursor targets for MS2 analysis is required. The dynamic range of MS1 spectra poses a substantial problem. Digested peptide concentrations can vary by up to 10 orders of magnitude, but the dynamic range of a single excitation spectrum (e.g., in an orbital trap mass analyzer) is limited to 4 orders of magnitude. Furthermore, the number of ions that can be injected into an orbital trap mass analyzer can be limited to about 10⁵ by the capacity of the accumulated C-trap, and therefore low-intensity peptide precursor signals can easily be overwhelmed, leading to missed potential fragmentation targets or poor quantification.

[0009] An important approach to improving the dynamic range of MS1 spectra is the High Dynamic Range (HDR) or Boxcar method, in which the wide mass range to be analyzed is subdivided into many narrower isolation windows, and independent injections into the C-trap are made for each isolation window with different fill times depending on the ion current (Meier et al., Nature Methods, 2018, 15, 440-448). The total ion population is then analyzed together, for example in an orbital trap mass analyzer. This method attenuates highly clustered regions while amplifying sparsely clustered mass regions, thereby enhancing many relatively weak peaks and significantly improving the effective dynamic range of the spectrum. The trade-off is a substantial increase in the time required to accumulate ions through multiple fills. Due to the long fill times of the low-level windows and the milliseconds required to switch the quadrupole and ion source voltages, the HDR method rapidly impacts the potential acquisition rate of MS2 spectra.

[0010] In this context, this disclosure provides an improved, or at least commercially relevant, alternative ion dispatching method for mass analysis. Summary of the Invention

[0011] According to a first aspect of this disclosure, a method is provided for scheduling ions for analysis by a mass analyzer within a range of mass-to-charge ratios (m / z) of interest. The method includes: Obtain the predicted intensity and associated m / z of ions across the range of mass-to-charge ratios of interest; Ions are input into the ion dispatching device; Based on the m / z or ion mobility of the ions, the ions are output from the ion dispatching device to the mass analyzer; and The ions are selectively attenuated based on their predicted intensity and associated m / z.

[0012] The first aspect of the approach aims to address the technical challenges associated with: the interaction between ion scheduling and rapid (e.g., 200–400 Hz) spectral acquisition, rapid switching between full MS and MS / MS, and control of ion populations in space charge-constrained downstream trapping regions (e.g., automatic gain control).

[0013] In particular, controlling the ion cluster output from an ion dispatcher can be challenging when there are relatively large variations in abundance within the ion cluster. Typically, the operation of an ion dispatcher amplifies the number of ions output to the downstream mass analyzer by a factor between 3 and >>100, depending on the ion dispatcher used, compared to a typical DIA / DDA method. However, many ions are already very strong and can saturate downstream analyses without the use of an ion dispatcher. Therefore, the ion dispatcher itself can easily become overfilled with relatively strong substances, leading to undesirable space charge effects. Thus, the presence of relatively high-intensity substances within the ion dispatcher can make it more challenging to separate and dispatch relatively low-abundance substances within the ion cluster using this device. Therefore, the first aspect of the method aims to improve the dynamic range of ions output from the ion dispatcher.

[0014] Therefore, the first approach recognizes that, in order to improve the amplification of relatively low-abundance substances within an ion cluster using an ion dispatching device, it is desirable to selectively attenuate relatively strong substances that would otherwise exceed the capacity / dynamic range of the ion dispatching device and / or the mass analyzer. This must be done in an m / z (or ion mobility) dependent manner to preserve the relatively low-abundance substances that the ion dispatching device is intended to amplify.

[0015] According to the method of the first aspect, before analyzing the ions, predicted values ​​of the ion intensities and associated m / z across the mass range of interest are obtained. These predicted intensities are used to inform which m / z (ions) should be selectively attenuated in order to reduce the presence of relatively high-abundance substances in the ions output from the ion dispatching device. According to this disclosure, selective attenuation of ions can be performed upstream of, within, or downstream of the ion dispatching device before analysis by a mass analyzer. Further details of these implementations are provided below.

[0016] In some embodiments, selectively attenuating an ion based on its predicted intensity and associated m / z includes: identifying a list of m / z values ​​for ions with associated predicted intensities higher than a predetermined threshold intensity from the predicted intensities and associated m / z values, and selectively attenuating the ion based on the m / z list. Therefore, the m / z list of ions can identify one or more ionic substances with predicted intensities higher than a predetermined threshold intensity, which can reduce the dynamic range of ions output for mass analysis. Thus, the method according to this disclosure can selectively attenuate or even remove ionic substances with excessively high predicted intensities from the ions output from the ion dispatching device.

[0017] In some embodiments, the ion scheduling device outputs ions sequentially as multiple ion scheduling groups. Ions in each ion scheduling group span an m / z extraction window, such that the multiple ion scheduling groups cover the m / z range of interest. Alternatively, ions in each ion scheduling group may span an ion mobility extraction window. That is, the ion scheduling device may divide ions into multiple groups based on their m / z or ion mobility. These ion groups can then be output sequentially from the ion scheduling device based on their m / z or ion mobility. In some embodiments, ions in the ion scheduling groups may be output sequentially in ascending m / z or ascending ion mobility order. In some embodiments, ions in the ion scheduling groups may be output sequentially in descending m / z or descending ion mobility order.

[0018] In some embodiments, the method of the first aspect can be an ion scheduling method for a data-dependent acquisition (DDA) method. Therefore, in some embodiments, the method may further include obtaining a target m / z list and scheduling ions from the output of an ion scheduling device based on the target m / z list. For example, the DDA method may include obtaining a target m / z list corresponding to an analyte of precursor ions or ions of interest identified in an early mass analysis forming part of the DDA method. Then, according to the ion scheduling method of the first aspect, ions or ion clusters may be output from the ion scheduling device to a mass analyzer based on the target m / z list. According to the method of the first aspect, relatively high-intensity ions or relatively high-intensity ion groups may be selectively attenuated to improve the dynamic range of ions corresponding to the target m / z list.

[0019] In some embodiments, the method of the first aspect may be an ion scheduling method for a data-independent acquisition (DIA) method. Therefore, in some embodiments, as part of a DIA methodology investigation, ions from an ion scheduling group output by the ion scheduling can be directly analyzed by a mass analyzer. Thus, the isolation window for each DIA analysis may be defined by the m / z extraction window of the ion separation device. In some embodiments, the ions of the ion scheduling group may also be mass filtered by a downstream mass filter using another m / z isolation window (e.g., an m / z isolation window narrower than the m / z extraction window of the ion scheduling device). When using ion mobility to separate ions from the ion scheduling group, the ion separation device may use the m / z isolation window to select a subset of ions from the ions of the ion scheduling group. Therefore, in some embodiments, such as in a DIA methodology investigation, the method may include mass filtering of ions from each ion scheduling group output from the ion scheduling device using a downstream mass filtering device, wherein the mass filtering device outputs multiple filtered groups of ions to the mass analyzer, each filtered group of ions spanning the m / z isolation window of the mass filtering device. In such embodiments, the isolation window for each DIA analysis may be defined by the m / z isolation window applied by the mass filtering device.

[0020] In some embodiments, such as in a DIA methodology investigation, the method may require multiple fillings of the ion scheduling device to resolve each m / z isolation window constituting a portion of the DIA methodology investigation. Therefore, in some embodiments, multiple ion scheduling cycles may be executed, wherein in each ion scheduling cycle, ions may be input to the ion scheduling device, and the ion scheduling device sequentially outputs multiple ion scheduling groups for each ion scheduling cycle. Specifically, for a DIA methodology investigation, for each ion scheduling group output from the ion scheduling device, the mass filtering device may update its m / z range such that the multiple filtered ions output from the mass filtering device span the m / z range of interest.

[0021] In some embodiments, ions can be selectively attenuated by an upstream mass selection device before being introduced into the ion dispatching device. By selectively attenuating ions upstream of the ion dispatching device, the space charge effect caused by relatively abundant ionic material within the ion dispatching device can be reduced or eliminated.

[0022] In some embodiments, selectively attenuating ions using an upstream mass filter includes identifying a first m / z associated with ions having a predicted intensity above a predetermined threshold intensity from a predicted intensity and an associated m / z. The upstream mass filter can then selectively attenuate ions having the first m / z, wherein the mass-filtered ions are input to an ion dispatching device. For example, the mass filter may apply a notch or bandpass filter to the ions to mass filter ions having the first m / z. Such a mass filter may be provided, for example, by a quadrupole mass filter, to which one or more additional RF oscillation voltages may be applied. Each RF oscillation voltage may be selected to attenuate or completely remove ions of a specific m / z by resonant ejection of ions from the quadrupole mass filter. By selectively attenuating or removing ions with the first m / z from the ions input to the ion dispatching device, the space charge effect within the ion dispatching device can be reduced, and / or the dynamic range of ions output from the ion dispatching device can be improved.

[0023] In some embodiments, the method of the first aspect may utilize an upstream mass filtering device in different analytical steps. For example, in a first analytical step, the mass filtering device may mass filter ions having a first m / z and input the (filtered) ions to an ion dispatching device. In a second analytical step, ions having the first m / z may be output to a mass analyzer for mass analysis. For example, in the second analytical step, ions having the first m / z may bypass the ion dispatching device or pass through the ion dispatching device between cycles. That is, relatively strong ions with the first m / z can be analyzed separately from the rest of the ion group and may not undergo the ion dispatching step. By analyzing ions with the first m / z separately in the second analytical step, ion optics (e.g., the accumulation time of ions in the mass filtering device) can be controlled to account for the relatively high intensity of ions with the first m / z (e.g., the accumulation time can be shortened).

[0024] In some embodiments, using an upstream mass filter to selectively attenuate ions based on the predicted intensity and associated m / z of the ions includes identifying a first m / z of ions with an associated predicted intensity higher than a predetermined threshold intensity from the predicted intensity and associated m / z. Based on the first m / z, a first passband m / z range of interest with m / z below the first m / z and a second passband m / z range of interest with m / z above the first m / z can be identified. Ions within the first passband m / z range of interest and the second passband m / z range of interest can then be analyzed in a separate ion scheduling cycle of the ion scheduling device. For example, in a first analysis step, the upstream mass filter may provide ions within the first passband m / z range of interest to the ion scheduling device. In a second analysis step, the mass filter provides ions within the second passband m / z range of interest to the ion scheduling device. Therefore, in some embodiments, the m / z range of interest may be divided into two (or more) passband m / z ranges of interest. In some embodiments, one or more steps in the first and second analysis steps may each include multiple ion scheduling cycles. Ions within each passband may have a predicted intensity below a predetermined threshold. By dividing relatively low-intensity ions between two or more passbands, the ion dispatching device can avoid performing an ion dispatching cycle that includes relatively high-intensity ions (e.g., ions of the first m / z) along with relatively low-intensity ions, thereby improving the dynamic range of ions output from the ion dispatching device.

[0025] In some embodiments, a third analysis step may also be provided, wherein ions having a first m / z are provided to the mass analyzer for mass analysis. For example, in the third analysis step, ions having the first m / z may bypass the ion dispatching device or pass through the ion dispatching device between cycles. That is, the relatively strong ions with the first m / z can be analyzed separately from the rest of the ion group and may not undergo the ion dispatching step. By analyzing the ions with the first m / z separately in the third analysis step, ion optics (e.g., the accumulation time of ions in the mass filter) can be controlled to account for the relatively high intensity of the ions with the first m / z (e.g., the accumulation time can be shortened).

[0026] In some embodiments, ion scheduling devices can be used for selective ion attenuation. In some embodiments, an ion scheduling device comprising multiple ion traps can be used to selectively attenuate ions. For example, an ion scheduling device may include multiple ion traps, each having an associated m / z accept window. These multiple m / z accept windows may span a range of interest in m / z. In some embodiments, the m / z accept windows of adjacent ion traps may overlap, allowing some ions to be accepted into each of two adjacent ion traps (i.e., ions at m / z within two accept windows may be shunted between the two adjacent ion traps). The ion scheduling device may also include multiple ion gates. Each ion gate may be associated with a corresponding ion trap. Each ion gate controls the entry of ions within its m / z accept window into its associated ion trap. Thus, each ion gate may operate independently of the other ion gates. Because the m / z accept windows of the ion traps span a range of interest in m / z, the presence of a relatively high-intensity precursor ion with, for example, m / z M1 may affect only one trap (or may affect two ion traps with overlapping m / z accept windows), such that the accumulation of ions in other traps is unaffected by the relatively high-intensity precursor ion. In practice, once the relatively high-intensity precursor ion M1 fills the associated ion trap, the precursor ion M1 may decay, while other ion traps continue to accumulate ions. Therefore, the dynamic range of ions output by the ion dispatching device can be improved. Thus, in some embodiments, each ion gate can be controlled independently to control the number of ions received into the associated ion trap or the duration of ion accumulation in each ion trap (accumulation time).

[0027] For example, selectively attenuating ions includes, for each ion gate, determining an ion accumulation time for ions within the m / z accepting window of the associated ion trap based on the predicted ion intensity and associated m / z. Therefore, if the predicted ion intensity within the m / z accepting window is relatively high, the accumulation time of the associated ion gate can be relatively short. If the predicted ion intensity within the m / z accepting window is relatively low, the duration of the accumulation time can be extended. Thus, in some embodiments, each of the plurality of ion gates can selectively attenuate ions within the m / z accepting window of the associated ion trap based on the predicted ion intensity and associated m / z. For example, each of the plurality of ion gates can selectively control the accumulation time of the associated ion trap to selectively attenuate ions within the associated m / z accepting window.

[0028] In some embodiments, an ion dispatching device may include a single ion trap instead of multiple ion traps. For example, a single-ion-trap ion dispatching device may dispatch ions such that ions are distributed (dispatched) along the ion trap according to their m / z. In some embodiments, an ion dispatching device may include an attenuation electrode associated with a region of the ion dispatching device, the attenuation electrode being configured to attenuate or remove ions from the ion dispatching device when an ion removal voltage is supplied. In some embodiments, selectively attenuating ions includes selectively supplying an ion removal voltage to the attenuation electrode to selectively attenuate ions based on their predicted intensity and associated m / z. Thus, when an ion passes through the region of the ion dispatching device associated with the attenuation electrode, the ion dispatching device may selectively attenuate or remove the ion. Since ions can be distributed (dispatched) within the ion dispatching device according to their m / z, the attenuation electrode can be selectively operated to attenuate only ions with a specified m / z (e.g., the m / z of ions expected to be present at a relatively high intensity).

[0029] In some embodiments, the ion dispatching device outputs ions sequentially as a plurality of ion dispatching groups, each ion dispatching group spanning an m / z extraction window, such that the plurality of ion dispatching groups cover the m / z range of interest. When an ion removal voltage is supplied, an attenuation electrode selectively attenuates or removes ions from the ion dispatching group present in a region of the ion dispatching device. Therefore, as ions from the plurality of ion dispatching groups move through the ion dispatching device, some or all of the ion dispatching groups can pass through the region associated with the attenuation electrode, thereby allowing the attenuation electrode to selectively attenuate the ion dispatching group sequentially.

[0030] In some embodiments, the ion dispatching device may include a plurality of attenuation electrodes. These attenuation electrodes may be distributed throughout the ion dispatching device, each attenuation electrode associated with a different region of the ion dispatching device. When an ion removal voltage is supplied, each attenuation electrode may selectively attenuate or remove ions present in different ion dispatching groups within the ion dispatching device. Therefore, in some embodiments, ions from two or more ion dispatching groups may be selectively attenuated in parallel by the ion dispatching device. Parallel attenuation of ions, relative to sequential attenuation of ion dispatching groups, reduces the number of ion attenuation steps to be performed by the ion dispatching device, thereby improving the throughput of the ion dispatching device.

[0031] In some embodiments, a multi-step method for filling an ion dispatching device can be used to provide (partial) attenuation of ion dispatching groups. For example, in a first filling step, ions may be input into and captured in the ion dispatching device. The ions may then be separated into multiple ion dispatching groups. As part of the first filling step, an ion removal voltage may be supplied to attenuation electrodes (or, for parallel processes, to one or more attenuation electrodes) to selectively attenuate or remove ion dispatching groups from the ion dispatching device. In a second filling step, additional ions may be input into the ion dispatching device and separated into ions from the multiple ion dispatching groups from the first filling step, wherein the ion removal voltage is not applied to the attenuation electrodes. Thus, the second filling step may fill (or only partially fill) the ion dispatching groups attenuated in the first filling step. Ions from the first and second filling steps are then simultaneously output from the ion dispatching device according to their m / z. In other embodiments, three or more filling steps may also be provided before ions are output from the ion dispatching device.

[0032] In some embodiments, ions may also be attenuated after being output from the ion dispatching device. Post-ion dispatching attenuation of ions may be used in conjunction with any other ion attenuation techniques discussed herein (i.e., ion attenuation as part of the ion dispatching device, and / or ion attenuation prior to the ion dispatching device).

[0033] For example, in some embodiments, the method may include outputting ions from an ion scheduling device to a mass analyzer via a decaying ion gate. In some embodiments, the decaying ion gate may selectively decay the ion based on its predicted intensity and associated m / z. For example, the ion scheduling device may output ions as multiple ion scheduling groups, each spanning an m / z extraction window. The decaying ion gate may selectively decay ions within an ion scheduling group, wherein the m / z of ions with relatively high predicted intensities falls within the m / z extraction window of that ion scheduling group. Thus, the dynamic range of the output ions can be improved by selectively decaying relatively high-intensity precursor ions.

[0034] In some embodiments, the selective attenuation of ions utilizes prior knowledge of the m / z and / or intensity of the ions input to the ion dispatching device. In some embodiments, such knowledge can be obtained by performing one or more mass analyses of the ions across the mass range of interest. Thus, in some embodiments, obtaining the predicted intensity and associated m / z of ions across the mass range of interest may include determining the predicted intensity and associated m / z of the ions based on previous mass analyses performed by a mass analyzer. For example, a previous mass analysis may be a mass analysis performed at an earlier time point across the m / z range of interest (e.g., MS1 analysis). In some embodiments, a mass analysis of a group of related ions may be performed at an earlier time period that does not form part of the current mass spectrometry experiment (e.g., MS1 analysis). In some embodiments, a previous mass analysis may be a pre-analysis or an investigative analysis performed by a mass analyzer (e.g., AGC analysis). Thus, a pre-analysis may be performed as part of the current mass spectrometry experiment.

[0035] In some embodiments, particularly for ion scheduling devices that separate ions based on their ion mobility, the pre-analysis or survey analysis may include ion mobility analysis. For example, ion mobility pre-analysis or survey analysis may be performed using the ion scheduling cycle of the ion scheduling device, wherein a mass analyzer or ion mobility analyzer (wherein the instrument includes an ion mobility analyzer) is used to measure the output ions.

[0036] It should be understood that the method according to the first aspect can be used with various ion dispatching devices. For example, in some embodiments, the ion dispatching device may include an ion accumulation region and an ion separation region, in which ions accumulate and ions from the ion accumulation region are separated in the ion separation region according to their m / z. Thus, in some embodiments, as ions are separated, they can move from the ion accumulation region to the ion separation region. The separated ions can then move out of the ion dispatching device sequentially from the ion separation region according to their m / z. In some embodiments, one or more attenuation electrodes may be provided in the ion separation region for selective attenuation of ions within the ion dispatching device.

[0037] In some embodiments, the ion scheduling device may also provide the ability to avoid separating certain groups of ions. For example, in some embodiments, the ion scheduling device may include: an ion separation path along which ions are separated according to their m / z; a bypass path along which ions are not separated according to their m / z; and a path selection region that selects whether ions move along the ion separation path or along the bypass path. By providing a bypass region, the ion scheduling device can allow (unscheduled) ions to bypass the ion scheduling device while the ion scheduling procedure is being performed. Therefore, the bypass region can allow unscheduled ions to be output to the mass analyzer while the ion scheduling procedure is being performed, in order to improve the throughput of the mass analyzer. For example, multiple groups of unscheduled ions can be output, or inserted between ions in the ion scheduling group, for further analysis. This allows various analyses (e.g., pre-analytical scans, survey scans, single-ion monitoring scans, etc.) to be performed using unscheduled ions before, during, or after the method of the first aspect.

[0038] In some embodiments, the ion dispatching device may include a plurality of ion traps. Each ion trap may have an associated m / z receiving window, wherein the plurality of m / z receiving windows span a range of interest in m / z. For example, each receiving window may have an m / z range of at least 50 m / z, 100 m / z, 150 m / z, or 200 m / z. Thus, a plurality of ion traps may be provided that together receive ions across the range of interest in m / z without making the ion dispatching device too large and / or inefficient in manufacturing. The m / z range of each receiving window is no greater than: 500 m / z, 400 m / z, 300 m / z, 250 m / z, or 200 m / z, such that ions are separated into a plurality of ion dispatching groups with different m / z values ​​spanning the range of interest in m / z. In some embodiments, the plurality of ion traps may sequentially output ions, such that the ion dispatching device outputs ions to a mass analyzer according to the m / z of the ions.

[0039] According to a second aspect of this disclosure, a controller is provided for scheduling ions for analysis by a mass analyzer within a range of m / z of interest. The controller is configured to: Obtain the predicted intensity and associated m / z of ions across the mass range of interest; This allows ions to be input into the ion dispatching device; Based on the m / z of the ions, the ions are output from the ion dispatching device to the mass analyzer; and The ions are selectively attenuated based on their predicted intensity and associated m / z.

[0040] Therefore, it should be understood that the controller can be configured to enable the ion dispatching device and the mass analyzer to perform the method of the first aspect. Any optional features and associated advantages of the first aspect also apply to the controller of the second aspect.

[0041] According to a third aspect of this disclosure, a mass spectrometry system is provided for analyzing ions across a range of interest in m / z. The mass spectrometry system may include an ion dispatching device configured to receive ions and output ions to the mass spectrometry system. The mass spectrometry system may be configured to perform the methods of the first aspect. For example, the mass spectrometry system may include a mass analyzer, an ion dispatching device configured to receive ions and output ions to the mass analyzer, and a controller according to a second aspect of this disclosure.

[0042] According to a fourth aspect of this disclosure, a computer program is provided that includes instructions for causing a mass spectrometry system of the third aspect to perform the steps of the method of the first aspect. Therefore, it should be understood that the computer program of the fourth aspect may incorporate any optional features and associated advantages of the first, second, or third aspects discussed above.

[0043] According to a fifth aspect of this disclosure, a computer-readable medium is provided having a computer program of the fourth aspect stored thereon. Therefore, it should be understood that the computer-readable medium of the fifth aspect may incorporate any optional features and associated advantages of the first, second, third, or fourth aspects discussed above.

[0044] As will be understood from the foregoing, aspects of this disclosure provide selective attenuation of ions, including before entering an ion dispatching device and / or after leaving the ion dispatching device. According to a sixth aspect of this disclosure, a decaying ion gate for a mass spectrometry system can be used to provide selective attenuation of ions. The decaying ion gate includes a first ion lens defining a first aperture, a second ion lens defining a second aperture, and a first deflection electrode and a second deflection electrode. The second ion lens is spaced apart from the first ion lens, and the first and second apertures are aligned axially between the decaying ion gate to define an ion channel between the first and second apertures. The first and second deflection electrodes are disposed on opposite sides of the ion channel between the first and second ion lenses. The first and second deflection electrodes are configured to receive a variable alternating deflection voltage across the first and second electrodes to variably attenuate ions passing through the decaying ion gate.

[0045] The sixth aspect, the attenuation ion gate, can provide selective attenuation of, for example, ions from an ion packet (or ion dispatch group) generated by an ion dispatching device according to this disclosure. Conventionally, ion gates can operate in a binary manner (i.e., fully open or fully closed). Therefore, attenuating a portion of the ion packet may involve opening (or closing) the ion gate as the ion packet passes through it, such that only a portion of the ions pass through the gate. Controlling such ion gates requires careful calibration of the timing of the applied on / off voltage to provide the desired attenuation level (e.g., 50% of the ion packet passing through the ion gate). In particular, for the applied voltage, some ion gates may require up to 50 µs to fully open and / or fully close. Therefore, selective attenuation with relatively short pulse widths (e.g., <2 ms pulse width) may require further calibration.

[0046] The sixth aspect of the attenuation ion gate provides a first deflection electrode and a second deflection electrode to which a variable alternating deflection voltage can be applied. The variable AC deflection voltage can be applied via a voltage source that forms part of the attenuation ion gate or is provided as part of the mass spectrometry system. In some embodiments, the voltage source can be configured to apply a frequency- and amplitude-variable AC deflection voltage to the first deflection electrode and an opposite frequency- and amplitude-variable AC deflection voltage to the second deflection electrode. By controlling ion passage through the ion gate using the amplitude of the variable alternating deflection voltage applied to the entire ion bank as ions pass through the ion gate, the calibration and subsequent control of the attenuation ion gate are simplified compared to a binary on / off gate.

[0047] In some embodiments, the AC deflection voltage may have a frequency corresponding to a time period longer than the pulse width entering the ion pack. For example, for ions in an ion dispatch group with a pulse width of approximately 2 ms, the AC deflection voltage may have a frequency of at least 500 Hz. Preferably, the period of the AC deflection voltage should be at least 10 times the pulse width of the ions output by the ion dispatch group (e.g., at least 5 kHz for a 2 ms pulse width). Thus, as the ion dispatch group passes through the attenuating ion gate, the AC deflection voltage may oscillate multiple times relative to the duration (pulse width) of the ions in the ion dispatch group. In turn, this allows the AC deflection voltage to selectively attenuate the ion pack more reliably / more accurately.

[0048] In some embodiments, the amplitude of the alternating deflection voltage can be varied to allow ions to be selectively attenuated by the attenuating ion gate. For example, in some embodiments, a first alternating deflection voltage amplitude can be used for both a first and a second deflection electrode. The first alternating deflection voltage amplitude can be relatively low (but greater than 0V) such that the first alternating deflection voltage substantially does not interfere with the ion transport as it passes through the attenuating ion gate. For example, in some embodiments, the first alternating deflection voltage amplitude is no greater than about 10V or about 5V, allowing about 100% of the ions to pass through the attenuating ion gate. When attenuation of ions is desired, a second alternating deflection voltage amplitude can be applied, wherein the second alternating deflection voltage amplitude is greater than the first alternating deflection voltage amplitude. Using a known relationship between the second alternating deflection voltage amplitude and the amount of ion attenuation (e.g., determined by appropriate calibration measurements), the attenuating ion gate can control ion transport from ion packets (ions in an ion dispatch group) from 100% to 0% with improved resolution. For example, in some embodiments, a second alternating deflection voltage of at least 25V may result in 0% of the ions passing through the attenuating ion gate. Therefore, the voltage source can be configured to vary the amplitude of the alternating deflection voltage between 10V and at least 25V in order to control the decay of ions passing through the ion gate.

[0049] In some embodiments, the frequency of the alternating deflection voltage can be varied to control ion attenuation. For example, in some embodiments, a first alternating deflection voltage frequency can be used for both a first and a second deflection electrode. The first alternating deflection voltage frequency can be relatively low (but greater than 0 Hz) such that the first alternating deflection voltage substantially does not interfere with ion transport as it passes through the attenuating ion gate. For example, in some embodiments, the first alternating deflection voltage frequency is no greater than: about 100 kHz, about 50 kHz, about 20 kHz, or about 10 kHz, allowing approximately 100% of ions to pass through the attenuating ion gate. When ion attenuation is desired, a second alternating deflection voltage frequency, greater than the first alternating deflection voltage frequency, can be applied. Using a known relationship between the second alternating deflection voltage frequency and the amount of ion attenuation (e.g., determined by appropriate calibration measurements), the attenuating ion gate can control ion transport from ion packets (ions in an ion dispatch group) from 100% to 0% with improved resolution. For example, in some embodiments, the voltage source is configured to vary the frequency of the alternating deflection voltage between 100 kHz and at least 1000 kHz in order to control the attenuation of ions passing through the ion gate.

[0050] In some embodiments, it will be understood that both the amplitude and frequency of the alternating deflection voltage can be varied in order to control the decay of ions passing through the decaying ion gate.

[0051] In some embodiments, the attenuation ion gate may further include a shielding electrode defining a shielding aperture, wherein the shielding electrode may be disposed between the first deflection electrode and the second deflection electrode and the second ion lens. The shielding aperture may be aligned with the ion channel. The shielding electrode may be provided to shield the alternating deflection voltage applied to the first deflection electrode and the second deflection electrode from the voltage applied to the second ion lens and other downstream ion optics.

[0052] In some embodiments, a variable DC potential (e.g., a deflection voltage or 0V) may be applied to one or more deflection electrodes to add additional binary on / off control of the decaying ion gate. In some embodiments, a DC potential may be applied to a deflection electrode separate from the first and second deflection electrodes. For example, the decaying ion gate may include a third deflection electrode disposed between the first and second deflection electrodes and the first ion lens, or between the first and second deflection electrodes and the second ion lens. The third deflection electrode may be configured to selectively receive a DC deflection voltage configured to prevent ions from passing through the decaying ion gate.

[0053] In some embodiments, one or more shielding electrodes may also be provided between the first electrode, the second electrode, and the third electrode. Therefore, a shielding electrode defining a shielding aperture may be provided, wherein the shielding electrode is disposed between the first deflection electrode, the second deflection electrode, and the third deflection electrode.

[0054] In some embodiments, each of the first and second ion lenses may be a generally plate-like structure, each plate-like structure defining a corresponding aperture through the thickness of the plate-like structure. Each aperture in the first and second apertures may be generally circular or elliptical. A DC voltage may be applied to each of the first and second ion lenses. The DC voltage may cause ions to be accelerated through a decaying ion gate (e.g., a negative voltage is applied for positively charged ions).

[0055] Specifically, in some embodiments, the second ion lens may include a plate defining a second aperture through the thickness of the plate. In some embodiments, the edge of the plate defining the second aperture may be extruded toward the first ion aperture to define a grazing region of the second ion lens surrounding the second ion aperture. Since ions deflected by the first and second deflection electrodes may be guided toward the edge of the second aperture, the grazing region allows the second ion lens to guide ions away from contact with the inner surface of the second aperture. This, in turn, reduces wear / contamination of the second ion lens, thereby improving the lifespan of the second aperture. Attached Figure Description

[0056] Embodiments of this disclosure will now be described with reference to the following non-limiting drawings, in which: - Figure 1 This is a schematic diagram of separating ions of different m / z along the ion guide by using a variable DC force to counteract the axial pseudoforce. - Figure 2 This is a schematic diagram of an ion dispatching method, which accumulates and releases ions with three different m / z values, consistent with the resolution quadrupole isolation window; - Figure 3 A shows a schematic diagram of an ion dispatching device according to the present disclosure, including a single ion trap ion dispatching device; - Figure 3 B shows a schematic diagram of an ion dispatching device according to the present disclosure, including a bypass; - Figure 3 C shows a schematic diagram of a multi-ion trap ion dispatching device according to the present disclosure; - Figure 4 This is a schematic diagram of a mass spectrometry system according to an embodiment of the present disclosure, the mass spectrometry system including an orbital trap mass analyzer and an MRT-TOF mass analyzer; - Figure 5 This is a schematic diagram of a linear ion dispatching device and a decaying ion gate; - Figure 6 This is a flowchart of a method for operating an ion dispatching device, showing the time during which ions can be selectively decayed; - Figure 7 This is a graph showing the order of analyte m / z targets in the basic DIA cycle of multiple cycles of the combined ion dispatching device; - Figure 8 This is a schematic diagram showing a low-resolution mass filter placed before the ion dispatching device to limit the mass range entering and remove excess ions; - Figure 9 This is a schematic diagram of a multi-well ion scheduling device, where the accumulation time of each well is controlled by a separate ion gate; - Figure 10 A schematic diagram is shown of attenuation electrodes mounted in an RF electrode stack, which can be activated to remove ions in the m / z range associated with their location; - Figure 11 A schematic diagram of a region purging method is shown, in which the protective electrode is deactivated or set to an attracting potential, thereby causing unwanted m / z regions to overflow outside the device; - Figure 12 A schematic cross-sectional view of a decaying ion gate according to an embodiment of the present disclosure is shown; - Figure 13 A schematic diagram of an isometric view of a decaying ion gate according to an embodiment of the present disclosure is shown; - Figure 14ASimulation results show the effect of different alternating deflection voltages (variable amplitude and variable frequency) on the permeability of generated ions within a 1ms time period; - Figure 14B The effect of changing the frequency of the 25V amplitude alternating deflection voltage is shown. - Figure 14C Showing the target Figure 14A and 14B The simulation results show the dependence of transmittance on ion m / z; - Figure 15 A schematic cross-sectional view of a decaying ion gate according to yet another embodiment of the present disclosure is shown; - Figure 16 A schematic cross-sectional view of the second aperture of a decaying ion gate according to an embodiment of the present disclosure is shown. Detailed Implementation

[0057] Throughout this disclosure, the term "intensity," when used in the context of ion aggregation, refers to the quantity or flux of a particular type of ions generated from a common sample and detected by a mass spectrometer operating under controlled conditions (e.g., but not limited to, over a common measurement period). In practice, ion intensity refers to the signal amplitude corresponding to the quantity or flux of a particular type of ions detected. In many cases, as used above, the phrase "specific type" may refer to ions having a specific mass-to-charge (m / z) ratio or a specific range of limited m / z ratios. In many cases, the measured m / z ratio may be related to or indicate the presence of a specific ionic composition (i.e., ionic substance).

[0058] According to this disclosure, an ion scheduling method is provided. The ion scheduling method according to an embodiment of this disclosure can be performed by a mass spectrometry system 1. A schematic diagram of the mass spectrometry system 1 according to this disclosure is shown in... Figure 4 As shown in the figure. Mass spectrometry system 1 can be used to analyze data from chromatographic devices such as liquid chromatography (LC) columns (…). Figure 4 (Not shown in the image) The sample supplied. One such example of an LC column is the Thermo Fisher Scientific, Inc. ProSwift (RTM) monolithic column, which provides high-performance liquid chromatography (HPLC) by forcing a sample carried in the mobile phase through a stationary phase composed of irregular or spherical particles under high pressure. In an HPLC column, sample molecules elute at different rates depending on their degree of interaction with the stationary phase. In other embodiments, sample molecules may be supplied by any other suitable means, such as a gas chromatography column or other sample delivery methods known to those skilled in the art.

[0059] An ion source can be used to ionize sample molecules to generate precursor ions. Figure 4In the embodiments, the ion source is an electrospray ionization source (ESI source) 20 under atmospheric pressure.

[0060] Then, the precursor ions generated by the ESI source 20 can enter the vacuum chamber of the mass spectrometry system 1 and be guided by the capillary 25 to the RF-only lens 30. The precursor ions are focused by the RF-only lens 30 into the implantation flat electrode 40, which implants the precursor ions into the ion dispatching device 50. In some embodiments, the pre-filter 45 ( Figure 4 (Not shown) is placed upstream of the ion dispatching device 50 to selectively attenuate ions.

[0061] Figure 4 The ion scheduling device 50 shown includes an ion separation path 52 along which ions are separated according to their m / z or ion mobility, and a bypass path 54 along which ions are not separated according to their m / z or ion mobility. The ion scheduling device 50 also includes a path selection region 56 that selects whether ions travel along the ion separation path 52 or the bypass path 54. Therefore, Figure 4 The ion control device 50 shown is an ion control device that includes a bypass 300, for example, such as Figure 3 As further illustrated in section B. It should be understood that, Figure 3 A and Figure 3 Ion control devices 200 and 400 of C can also be used as ion control device 50 for mass spectrometry system 1, as further described below. Further details of the ion control device 50 according to this disclosure are discussed in more detail below.

[0062] Ion attenuation device 60 may be located at the distal end of ion dispatching device 50. Ion attenuation device 60 may be configured to control the entry of precursor ions from ion dispatching device 50 into the channel of a downstream mass selector, which is in the form of a quadrupole mass filter 70. Alternatively, ion attenuation device 60 may be composed of a static lens ( Figure 4 Instead of (not shown in the image), the static lens can be configured to guide ions from the ion dispatching device 50 to the quadrupole mass filter 70 without any intentional attenuation of these ions.

[0063] The quadrupole mass filter 70 is typically, but not necessarily, segmented and functions as a bandpass filter, allowing a selected mass number or a limited mass range to pass through while excluding precursor ions of other m / z. The mass filter 70 can also operate in RF-only mode, in which it is not mass-selective, i.e., it substantially allows all m / z precursor ions to pass through. For example, the quadrupole mass filter 70 can be controlled by a controller ( Figure 4(Not shown) Control is used to select the m / z range of precursor ions that are allowed to pass through, while filtering out (disallowing) other ions in the precursor ion stream that are outside that m / z range. For example, a quadrupole mass filter 70 can filter precursor ions based on the m / z range of interest.

[0064] although Figure 4 The quadrupole mass filter 70 is shown, but those skilled in the art will understand that other types of mass selection devices may also be suitable for selecting precursor ions within the mass range of interest. Furthermore, in some embodiments, more than one ion selection device or mass selection device may be provided. For example, another mass selection device may be provided downstream of the ion routing multipole 120. In this way, MS3 or MSn scans can be performed if necessary (mass analysis is typically performed using a time-of-flight (TOF) mass analyzer 150).

[0065] The mass spectrometry system 1 can operate in various operating modes to analyze precursor ions in the MS1 and / or MS2 domains. In a first operating mode, a first mass analyzer can be used to analyze precursor ions in the MS1 domain (e.g., as shown in orbital trap mass analyzer 110). Therefore, according to this disclosure, in the first operating mode, MS1 analysis is performed using orbital trap mass analyzer 110.

[0066] In the first operating mode, precursor ions can exit the quadrupole mass filter 70 through the attenuation ion gate 80 and the transfer multipole 90 and enter the first ion trap 100 (bent trap or C trap). The first ion trap 100 has a longitudinally extending electrode supplied with an RF voltage and an end cap supplied with a DC voltage. The result is a potential well extending along the longitudinal axis of the first ion trap 100. In the first operating mode, ions can be trapped and cooled in the first ion trap 100, or transferred to the ion routing multipole 120, where the ions are cooled. The movement of ions can be controlled by applying a DC end cap voltage to the first ion trap 100. The implantation time (IT) of ions into the first ion trap 100 (or the ion routing multipole 120) determines the amount of precursor ions (ion swarm) available for subsequent analysis. Depending on the analysis to be performed, the precursor ions can be guided from the first ion trap 100 or from the ion routing multipole 120 to different parts of the mass spectrometry system 1.

[0067] When precursor ions are to be analyzed by the orbital trap mass analyzer 110 (first mass analyzer), if the ions are cooled in the ion routing multipole 120, they can then be transferred back to the first ion trap 100 for analysis by the orbital trap mass analyzer 110. The precursor ions can then be orthogonally ejected from the first ion trap 100 toward the orbital trap mass analyzer 110. Figure 4As shown, the orbital capture quality analyzer 110 can be an Orbitrap sold by Thermo Fisher Scientific, Inc. TM Mass Analyzer. The orbit trapping mass analyzer 110 has an eccentric injection port through which precursor ions are coherently injected into the orbit trapping mass analyzer 110. The precursor ions are then trapped within the orbit trapping mass analyzer 110 by a superlog electric field and perform reciprocating motion in the longitudinal direction while orbiting around the internal electrodes.

[0068] The axial component (more or less) of the motion of the ion packet in the orbital trap mass analyzer 110 is defined as simple harmonic motion, where the angular frequency in the z-direction is related to the square root of the mass-to-charge ratio of a given ionic substance. Therefore, as time progresses, the precursor ions separate according to their mass-to-charge ratio.

[0069] Precursor ions in the orbital trap mass analyzer 110 are detected using an image current detector including a barrel-shaped detection electrode 111. The image current detector generates a "transient" in the time domain containing information about all ionic substances as they pass through the image current detector. This transient is then subjected to a Fast Fourier Transform (FFT), resulting in a series of peaks in the frequency domain. From these peaks, a mass spectrum representing the abundance / ion intensity relative to m / z can be generated.

[0070] In the above configuration, precursor ions within the mass range of interest (selected by the quadrupole mass filter 70) are analyzed by the orbital trap mass analyzer 110 without fragmentation. The resulting mass spectrum is denoted as MS1.

[0071] although Figure 4 The orbital trapping mass analyzer 110 is shown, but it should be understood that other mass analyzers may be used as the first mass analyzer according to embodiments of this disclosure. For example, a Fourier transform ion cyclotron resonance (FTICR) mass analyzer may be used as the first mass analyzer to analyze precursor ions in the MS1 domain. Mass analyzers, such as orbital trapping mass analyzers and ion cyclotron resonance mass analyzers, may also be used in this invention, even when obtaining mass spectrometry information from transient signals using other types of signal processing than Fourier transform (see, for example, WO2013 / 171313, ThermoFisher Scientific). In some embodiments, a TOF mass analyzer may also be used instead of the orbital trapping mass analyzer 110 to analyze precursor ions in the MS1 domain.

[0072] In the second operating mode of the mass spectrometry system 1, precursor ions can be analyzed by the TOF mass analyzer 150 (second mass analyzer) in the MS1 domain (MS1 analysis performed by the TOF mass analyzer 150). Precursor ions to be analyzed by the second mass analyzer can be mass filtered by the quadrupole mass filter 70. Therefore, precursor ions can be filtered to include precursor ions from the range of interest or from a sub-range of interest in the m / z range.

[0073] To enable the TOF mass analyzer 150 to analyze precursor ions, the precursor ions can enter the first ion trap 100 from the quadrupole exit lens / tangent lens arrangement 80 and the first transfer multipole 90, and continue their path through the first ion trap 100 and into the ion routing multipole 120. Therefore, the first ion trap 100 can also be effectively operated as an ion guide in the second operating mode. Alternatively, the precursor ions can be cooled in the first ion trap 100 and then ejected axially from the first ion trap 100 into the ion routing multipole 120. The precursor ions can then continue through the ion routing multipole 120 and be ejected from the ion routing multipole 120 at the axial end opposite the first ion trap 100. Therefore, the ion routing multipole 120 can also be effectively operated as an ion guide in the second operating mode.

[0074] The ejected precursor ions enter ion guide 130. Ion guide 130 is configured to guide precursor ions from ion routing multipole 120 to ion processor 140. Ion processor 140 is configured to process the ions into ion packets suitable for injection into TOF mass analyzer 150. Ion processor 140 may include an RF voltage-controlled third ion trap containing a buffer gas. For example, a suitable buffer gas is one with a pressure of 5 x 10⁻⁶. -4 mBar to 1x10 -2 Nitrogen gas in the mBar range. Optionally, an ion processor can be used to induce ion fragmentation for analysis in the MS2 domain. For analysis in the MS1 domain, ion fragmentation is not desired, and ions can therefore be transferred from the fragmentation chamber 141 of the ion processor to the extraction trap 142 of the ion processor. The ion processor 140 has the capability to rapidly cut off the applied RF voltage and apply a DC voltage to extract the captured precursor ions. Suitable flat extraction traps, also known as rectangular ion traps, are further described in US9,548,195(B2).

[0075] Despite Figure 4The embodiment shown depicts an ion processor 140 (third ion trap), but those skilled in the art will understand that other methods for forming ion packets of precursor ions are also available. For example, a relatively slow ion transfer via a multipole can be used to influence ion focusing, which can then be ejected as a single packet to a TOF mass analyzer 150. Alternatively, orthogonal displacement of precursor ions can be used to form ion packets. Further details of these alternatives can be found in US-A-20030001088, which describes a traveling-wave ion focusing method, the contents of which are incorporated herein by reference.

[0076] exist Figure 4 The TOF mass analyzer 150 shown is a multiple reflection time-of-flight mass analyzer (MR-TOF). The TOF mass analyzer 150 is constructed around two opposing ion mirrors 160, 162 that extend in the drift direction. The mirrors are counter-oriented in a direction orthogonal to the drift direction. Ion processor 140 injects ions into the first mirror 160, and the ions then oscillate between the two mirrors 160, 162. The ejection angle of the ions from the extraction trap 140 and the additional deflectors 170, 172 allows control over the ion energy in the drift direction, guiding the ions along the length of the mirrors 160, 162 during oscillation, thus producing a Z-shaped trajectory. The mirrors 160, 162 are tilted relative to each other, creating a potential gradient that slows the ion drift and causes the ions to reflect back in the drift dimension and concentrate on detector 180.

[0077] The precursor ions accumulated in the ion processor 140 are injected as ion packets into the TOF mass analyzer 150 (the second mass analyzer). The time taken for the precursor ions to reach the detector 180 is recorded by the TOF mass analyzer 150 and used to generate an MS1 ​​mass spectrum of the precursor ions.

[0078] In the third operating mode of mass spectrometry system 1, TOF mass analyzer 150 (second mass analyzer) can be used to analyze precursor ions in the MS2 domain (MS2 analysis).

[0079] To analyze precursor ions in the MS2 domain, some precursor ions can be transferred from the quadrupole mass filter 70 to the ion routing multipole 120 in a manner similar to the second operating mode described above. The precursor ions to be transferred can be ions from an ion scheduling group already output from the ion scheduling device 50, or a group of precursor ions that have not yet undergone ion scheduling. The output ions (e.g., ions from the ion scheduling group) can be further mass-selected by the quadrupole mass filter 70. For example, the output ions can be further mass-selected to include target precursor ions, or further mass filtering can be performed using the m / z isolation window of the quadrupole mass filter 70 (e.g., as part of a DIA methodology investigation), as discussed in more detail below.

[0080] The ions can then be transferred to the fragmentation chamber 141 of the ion processor 140. The fragmentation chamber 141 is in... Figure 4 The mass spectrometry system 1 contains a high-energy collisional dissociation (HCD) device. A buffer gas can be supplied to the fragmentation chamber 141. When the precursor ions are to be fragmented, the kinetic energy of the precursor ions may increase, causing the precursor ions that reach the fragmentation chamber 141 and collide with the buffer gas molecules to fragment into fragment ions.

[0081] Despite Figure 4 The ion processor 140 shows an HCD fragmentation chamber 141, but alternatively other fragmentation devices employing methods such as collision-induced dissociation (CID), electron capture dissociation (ECD), electron transfer dissociation (ETD), photodissociation, etc., may be used.

[0082] Fragmented ions can be injected from fragmentation chamber 141 into extraction trap 142 of the ion processor. The ejected fragments can accumulate in extraction trap 142 to form ion packs. The fragmented ions can then be injected into TOF mass analyzer 150 as described above.

[0083] It should be understood that in some embodiments, the first mass analyzer (orbit trap mass analyzer 110) and the second mass analyzer (TOF mass analyzer 150) can operate simultaneously. That is, it should be understood that the mass spectrometry system 1 can operate in the first operating mode simultaneously with a second or third operating mode. According to this disclosure, the ion scheduling device 50 is operable to output multiple sets of ions, enabling the orbit trap mass analyzer 110 and the TOF mass analyzer 150 to operate efficiently and also providing improved dynamic range.

[0084] Mass spectrometry system 1 can be located in the controller ( Figure 4 Under the control of (not shown), the controller is configured, for example, to control the timing of the ejection of the trapping assembly, to control one or more power sources (not shown) to set appropriate potentials on electrodes such as quadrupoles to concentrate and filter ions, thereby capturing mass spectrometry data from the orbital trapping device 110, capturing mass spectrometry data from the orbital trapping device 110 and the TOF mass analyzer 150, controlling the order of MS1 and MS2 analyses, etc. It should be understood that the controller may include a computer operable according to a computer program containing instructions to cause the mass spectrometry system 1 to perform the steps according to the method described herein.

[0085] The method of ion dispatching using ion dispatching device 50 will be described next. Figure 1 This is an illustrative diagram illustrating one possible principle of ion dispatch using traveling waves. Such traveling wave principles of ion dispatch can be derived from... Figure 4 Ion regulation device 50 and Figure 3 A and Figure 3 Ion regulation devices 200 and 300 of B are utilized. Figure 1 In this process, the DC field gradient (opposite potential gradient) and the traveling wave (potential that changes with time) induce ion separation along the length. Figure 1 This shows the traveling wave at a single moment; in fact, the traveling wave is in the first direction (in Figure 1 (From left to right) Proceeding continuously. Opposite DC and pseudoforces cause ions of different m / z to precipitate at different locations.

[0086] In order to achieve Figure 1 The m / z-dependent separation can be achieved by opposing the potential gradient (e.g., a static field) with a pseudo-force generated by a dynamic (time-varying) potential. In some ion dispatching devices 50 of this disclosure, the axial pseudo-potential generated by a traveling wave is opposed to the rising DC gradient. Such a traveling wave can be a multiphase (e.g., four-phase or higher) traveling wave. The pseudo-force propels ions until they reach a region where the DC force is equal to or greater than the pseudo-force, at which point the ions are captured (or, if the DC gradient is insufficient, the ions are ejected from the device). Since the pseudo-force depends on m / z, the ion capture location also depends on its m / z. Therefore, ions can be captured at various different locations in the separation (first) direction.

[0087] Ions can be released from the ion dispatching device 50 in an m / z-dependent manner by scanning / stepping an applied DC potential or traveling wave amplitude / frequency (or duty cycle / pulse velocity of a digital waveform). Alternatively, many other methods of ion extraction from the guide can be applied: the DC gradient and traveling wave can be removed, and the ions are released over time based on their spatial separation / drift time, or a very slow traveling wave can be applied to drive the ions out in a slow beam, and so on. The accumulated ions can then be released to, for example, a quadrupole (or other mass filter) matched to its m / z or ion mobility, and thus losses at the quadrupole can be mitigated.

[0088] Because the application of traveling wave potential usually requires axial segmentation of the electrode, Figure 1 The arrangement can be implemented using stacked ring ion directors and / or related structures. Figure 3 Example a is shown of a linear ion dispatching device 200, which is a device for separating ions, in which implementation can be performed. Figure 1 The method. The linear ion dispatching device 200 includes a separator region 201, a pre-accumulation region 202, a funnel / initial capture region 203, and an ion outlet 204.

[0089] In this particular example, the linear ion dispatcher 200 has a stacked ring structure and also includes an optional section for ion trapping from the inlet capillary and a pre-accumulation region 202 to maximize the duty cycle. A single-ion trap ion dispatcher 200 is shown to include a similar pre-accumulation region 202 for pre-accumulating ions during operation of the separator 201, except for a separation region 201 in which a traveling wave and DC gradient are applied. The ion funnel 203 can draw ions from the inlet capillary or from... Figure 4 The ion gate shown receives ions, and a small funnel-shaped region compresses the extracted ions as they leave the device and reach a higher vacuum (lower pressure) region. The funnel-shaped region 203 and the pre-accumulation region 202 may have their own applied DC offset and gradient, and a controllable (i.e., variable) DC barrier may be provided between the accumulator 202 and the separator 201. A potential (e.g., from an auxiliary electrode, not shown) may be applied within the guide to cause the ions to move laterally (i.e., perpendicular to the axis of the ion guide), allowing a large amount of charge to be distributed over a wider region to reduce the space charge effect. After the ions have passed through the separation region 201, they leave the device through the ion outlet 204, for example, to reach the higher vacuum (lower pressure) ion guide. Therefore, in summary, the separation region and / or accumulation region described herein can be a vacuum region. The separation and / or accumulation regions may be at lower pressures than the upstream regions of the device (i.e., the regions upstream of the separation and / or accumulation regions) and / or at higher pressures than the downstream regions of the device (i.e., the regions downstream of the separation and / or accumulation regions). Various hermetically sealed housings and pumps are available to ensure the formation of a vacuum.

[0090] Preferably, the properties of the traveling wave can be configured such that ions pass through the wave while being affected by a pseudo-force rather than being completely entrained within it. This can be achieved, for example, by altering the frequency and / or voltage amplitude of the traveling wave. In principle, a sufficiently high traveling wave potential will only carry ions and there will be no separation unless the opposite DC is set high enough to balance this effect. Therefore, the opposite potential and the time-varying potential can be fine-tuned to optimize separation performance.

[0091] An operable linear ion dispatching device 200 is available to output ions separated according to their m / z. Figure 4In the mass spectrometry system 1, a linear ion dispatcher 200 is provided instead of ion dispatcher 50. First, ions can be transferred from the implantation flat electrode 40 to a pre-accumulation region 202 via an ion funnel 203. Ions (e.g., mixed m / z ions, if not selectively attenuated before entering the ion dispatcher) can accumulate in the pre-accumulation region to form an ion bag. The ion bag is then transferred from the pre-accumulation region 203 to a separation region 201, which can be achieved by applying a DC gradient / offset or traveling wave across the pre-accumulation region 203 to drive the ions. Once the pre-accumulation region 203 has been emptied of ions, further transfer of ions from the pre-accumulation region 203 is prevented (e.g., by activating an ion gate) to the separation region 201, and the pre-accumulation region 203 begins to accumulate more ions as they enter. Simultaneously, the separation process begins in the separation region 201. The DC potential is reduced (or alternatively, the traveling wave amplitude is increased, or both) to the level required for the first lowest m / z extraction window to exit. After a brief delay (typically on the order of 0.25–5 ms), ions within the first m / z extraction window leave the system and enter a downstream quadrupole (or other mass filter) for finer isolation. The DC potential can then be further reduced to the next m / z extraction window in the sequence, and so on, until the range of interest is exhausted (i.e., each m / z extraction window spanning the range of interest has been emptied of ions). The accumulation region can then be emptied again, and the cycle repeated.

[0092] Therefore, in each cycle of the linear ion scheduling device 200, ions can be output from the linear ion scheduling device 200 according to their m / z. That is, ions can be output from the linear ion scheduling device 200 in generally increasing m / z order. Of course, in other embodiments, ions can be released in descending m / z order. In particular, ions can be output from the linear ion scheduling device 200 in the order of their m / z extraction windows. It should be understood that the general techniques for ion scheduling described with respect to the linear ion trap 200 can also be applied. Figure 3 B's bypass ion regulation device 300 and Figure 3 C. A multi-ion trap ion dispatching device 400. Similarly, ions can also be separated according to their ion mobility, in an order of increasing or decreasing ion mobility.

[0093] Next, the general operation of the ion dispatching device 50 will be described. The following discussion will describe, as follows: Figure 3 The operation of the linear ion dispatching device 200 shown in A is illustrated, but it should be understood that the principles described herein can be applied to other types of ion dispatching devices 50. Figure 5 A schematic diagram of the arrangement of the separation region 201 and ion outlet 204, the quadrupole mass filter 70 and the attenuation ion gate 80 of the linear ion dispatching device 200 is shown.

[0094] like Figure 5 As shown, ions are separated into ion scheduling groups in the separation region 201 of the linear ion scheduling device 200. Figure 5 The diagram illustrates ions in three ion scheduling groups ("a", "b", and "c"), but additional ion groups may be provided. Ions within each group have different m / z values. For example, mass spectrometry system 1 may have a range of m / z of interest from 300 m / z to 900 m / z. Within this range of interest, ions in each ion scheduling group may each span an m / z extraction window. For example, the width of each m / z extraction window may be at least: 50 m / z, 70 m / z, 100 m / z, 150 m / z, and 200 m / z. Ions can be scheduled such that ions in group "a" have relatively low m / z values, followed by ions in group "b" with higher m / z values, ions in group "c" with even higher m / z values, and so on.

[0095] like Figure 5 As shown, ions can be output from the linear ion dispatching device 200 in approximately m / z order, where the ions are further isolated by a quadrupole mass filter 70. Ions from each ion dispatching group pass through an attenuating ion gate 80 before being injected into a mass analyzer (e.g., a TOF mass analyzer 150). The attenuating ion gate 80 is configured to selectively attenuate ions from each ion dispatching group based on their strength. The strength of the ions in the ion dispatching group can be known or can be predicted from previous analysis or survey analysis in the same manner as conventional automatic gain control methods. The attenuating ion gate 80 can attenuate ions from the ion dispatching group by closing the gate for a specific time when ions pass through it. That is, the attenuating ion gate 80 applies or removes a deflection potential during a specific time period, either by repeatedly opening and closing in a pulse-width modulation manner or by applying an RF potential. Therefore, it should be understood that there are various possibilities that allow the attenuating ion gate 80 to allow substantially all ions in the ion dispatching group, some ions, or disallow ions from the ion dispatching group to pass through the attenuating ion gate for further analysis by the mass spectrometry system 1.

[0096] Next, we will refer to Figure 6 The flowchart describes a method 500 for scheduling ions within a range of interest (m / z) for analysis by a mass analyzer. As shown in step 501 of method 500, the method includes measuring m / z-dependent ion currents. Therefore, in the initial step of this method, the mass spectrometry system 1 can perform an investigational analysis of the ions to obtain predicted intensities and associated m / z values ​​of the ions within the range of interest (m / z). Other techniques for obtaining predicted intensities and associated m / z values ​​of ions across the range of interest can also be used instead of the investigational analysis.

[0097] In step 502, the method may optionally include determining the target analyte. For example, in a DDA analysis, step 502 may include determining the target analyte from the predicted intensity and associated m / z of the ions obtained in step 501. Alternatively, the determined target analyte may be provided by referencing an external data source.

[0098] In some embodiments, step 502 may further include identifying one or more relatively strong precursor ions within the m / z range of interest. A relatively strong precursor ion may be defined as any precursor ion having an intensity above a predetermined threshold in the investigational analysis (or any other previously performed analysis, such as an MS1 ​​analysis from an earlier cycle of mass spectrometry system 1). For example, step 502 may include a list of m / z values ​​for ions with associated predicted intensities above a predetermined threshold, identified from predicted intensities and associated m / z values. This list may be used in methods for selectively attenuating the m / z of the identified ions. The intensity threshold may be determined based on, for example, the ion capacity and / or dynamic range of one or more components of the mass spectrometry system.

[0099] In some embodiments, the predicted intensity list may be generated from one or more previous analyses and a prediction algorithm configured to model the elution of chromatographic peaks. Therefore, the prediction algorithm can be applied to model the evolution of chromatographic peaks as they elute from the chromatographic apparatus. It should be understood that a typical ion scheduling cycle can have a duration of, for example, about 100 ms, while a chromatographic peak may elute within a few seconds. Therefore, the prediction algorithm can utilize data from, for example, multiple consecutive ion scheduling cycles to predict the intensity of chromatographic peaks (and associated precursor ions) within subsequent ion scheduling cycles.

[0100] In step 503, ions are input from ESI source 20 to ion dispatching device 50. The ions are then separated into multiple groups by the ion dispatching device, with ions from each group subsequently output (released) by the ion dispatching device 50 according to their m / z (step 504). In step 505, the ions from the ion dispatching groups output from the ion dispatching device 50 are then mass-analyzed using orbital trap mass analyzer 110 or TOF mass analyzer 150. In other mass spectrometry systems, other mass analyzers (such as ion trap mass analyzers and quadrupole mass analyzers) may be used to analyze ions, in addition to or as alternatives to orbital trap mass analyzer 110 and TOF mass analyzer 150.

[0101] like Figure 6 As shown, method 500 includes one or more additional ion attenuation steps 506, 507, 508. (As will be seen from...) Figure 6As understood herein, during method 500, ions may be selectively attenuated at one or more of three points. In optional step 506 (attenuation point 1), the ions may be selectively attenuated before being injected into the ion dispatching device 50. In optional step 507 (attenuation point 2), the ions may be selectively attenuated while they are within the ion dispatching device 50. In optional step 508 (attenuation point 3), the ions may be selectively attenuated after they have been ejected from the ion dispatching device 50. These three attenuation points will be described in further detail below.

[0102] In each of steps 506, 507, and 508, the ion can be selectively decayed based on its predicted strength and associated m / z. Specifically, a list of relatively strong precursor ions can be used to identify specific m / z values ​​or ion scheduling groups containing specific m / z values ​​for selective decay. For example, if the m / z list identifies a relatively strong precursor ion at, for example, 700 m / z, ions in the ion scheduling group including ions at m / z 700 can be selectively decayed.

[0103] According to method 500, in steps 504 and 505, ions from the ion scheduling group are output from the ion scheduling device for m / z analysis. As shown in step 509, steps 504 and 505, which release and analyze ions from the ion scheduling group, can be repeated until the ions in the ion scheduling device 50 within the m / z range of interest are exhausted. At this point, one cycle of operating the ion scheduling device 50 is effectively completed, and method 500 can return to step 501. In some embodiments, method 500 may not perform the investigation analysis between each cycle of the ion scheduling device 50. That is, in some embodiments, steps 501 and 502 may not be performed at the beginning of each cycle. Instead, in some embodiments, once the ions in the ion scheduling device 50 are exhausted in step 508, the method may return to step 503 and load more ions into the ion scheduling device 50 for analysis.

[0104] In some embodiments, method 500 can be used to perform DIA methodological investigations. For example, in a DIA methodological investigation according to this disclosure, a single cycle of the DIA methodological investigation analyzes the ion in the range of m / z of interest, from 300 m / z to 900 m / z. For the DIA methodological investigation, the ion to be investigated is subjected to multiple MS2 analyses, each MS2 analysis having an isolation window of 10 m / z. This DIA methodological investigation can be used for typical proteomics analyses.

[0105] In some methodological investigations (such as the DIA methodological investigation described above), the isolation window for each MS² analysis may be narrower than the m / z extraction window of the ion dispatcher. For example, the ion dispatcher 200 may have an m / z extraction window of approximately 100 m / z. In such cases, the ion dispatch groups output by the ion dispatcher 200 can be further mass-filtered by a quadrupole mass filter 70 to further mass-select ions within each group to the desired m / z isolation window. Accordingly, the quadrupole mass filter 70 can mass-filter the ions of each ion dispatch group output from the ion dispatcher 50. For the ions of each ion dispatch group, the quadrupole mass filter 70 outputs the filtered ions to, for example, a TOF mass analyzer 150, where each filtered ion spans the m / z isolation window used for the DIA methodological investigation.

[0106] Figure 7 The graph shows the m / z of ions from the filtered array analyzed according to the DIA methodological investigation. (The remaining text appears to be a fragment and requires further context for accurate translation.) Figure 7 Understood, the ion dispatching device 200 initially outputs ions from the ion dispatching group with an extraction window of 100 m / z ranging from 300 m / z to 400 m / z. These ions are then further mass-selected by a quadrupole mass filter 70 to an m / z isolation window within the 300-400 m / z range that has not yet been analyzed in the DIA cycle. Figure 7 In one embodiment, a 10 m / z isolation window was applied, such that the ions in the first filtered group (labeled j) ranged from 300 m / z to 310 m / z. Ions in the next ion scheduling group were output by the ion scheduling device 50 with a 100 m / z extraction window ranging from 400 m / z to 500 m / z. A 10 m / z isolation window was then applied to these ions to select isolation windows between 400 m / z and 500 m / z that had not yet been analyzed in the DIA cycle. Figure 7 In the second filtration group, the ions (labeled k) range from 400 m / z to 410 m / z. (The remaining text appears to be incomplete and requires further context.) Figure 6 Understood, the ion scheduling device 50 continues to output ion scheduling groups according to the sequential m / z extraction windows, and then performs further quality filtering on the ion scheduling group to produce filtered ion groups l, m, and n. After this, the ion scheduling device 50 completes one cycle because all ions within the desired m / z range have been output from the ion scheduling device 50. Therefore, the ion scheduling device 50 is refilled, and ions from other ion scheduling groups are output sequentially from the ion scheduling device 50. (The last sentence appears to be incomplete and possibly refers to a different process.) Figure 7 Understood, the quadrupole mass filter 70 then applies 10 m / z isolation to select different m / z ranges not yet analyzed in the DIA cycle. For example, in Figure 7Ions marked with 'o' in the filtered group can be found in the range of 310 m / z to 320 m / z.

[0107] If from Figure 7 Understood, the ion dispatching device 50 may require 10 cycles to output enough ion dispatching groups to cover the desired 300 m / z to 900 m / z range with a 10 m / z isolation window. Although Figure 7 The diagram illustrates one possible order for selecting ions from the ion scheduling group output by the ion scheduling device 50 after filtering, but it should be understood that any suitable order can be used. Therefore, it should be understood that the quadrupole mass filter 70 can be used in conjunction with the ion scheduling device 50 to output sufficiently separated targets simply by scattering relatively narrow 10 m / z wide targets between multiple cycles of the ion scheduling device 50.

[0108] Apart from Figure 7 In addition to the DIA methodological investigation, it should be understood that the ion dispatching methods according to this disclosure can also be applied to the DDA methodological investigation. For example, the above Figure 6 Method 500 can also be applied to DDA methodological investigations. As part of a DDA methodological investigation, the method may further include the step of obtaining a list of target m / z of interest. The list of target m / z of interest may be obtained at the beginning of the method or after the investigational analysis of the ions (step 501). The list of target m / z of interest may include the top N (N=5, 10, 15, etc.) precursors identified in the investigation of spectra or any other suitable DDA methodological investigation used to analyze the sample. Method 500 can then be applied as follows: Figure 6 Continuing as shown, the scheduled ions to be output from the ion scheduler are selected based on a list of target m / z of interest. Similar to the DDA methodology investigations discussed above, in cases where multiple DDA target m / z values ​​are closely spaced (i.e., within the m / z extraction window of the ion scheduler), multiple cycles of the ion scheduler may be required to analyze all target m / z values. Since multiple cycles of the ion scheduler may be performed as part of the DDA methodology investigation, it will be understood that techniques for selectively attenuating ions to improve the dynamic range of the scheduled ions used for analysis can also be applied to the DDA methodology investigation.

[0109] As mentioned above Figure 6 The ion dispatching method discussed according to this disclosure includes one or more additional steps for selectively attenuating ions. It should be understood that such steps for selectively attenuating ions contrast with any mass filtration steps performed by the quadrupole mass filter 70, as further explained below.

[0110] like Figure 5As shown, and as described in step 508 of method 500, in some embodiments, ions may be selectively attenuated after being output from ion dispatching device 50. For example, as Figure 5 As shown, ions can be selectively attenuated via an attenuation ion gate 80 downstream of the ion dispatching device 50. The attenuation ion gate 80 may also be downstream of the quadrupole mass filter 70.

[0111] Therefore, in step 508, the mass spectrometry system 1 can identify ion scheduling groups or relatively strong filtered groups of ions from the obtained predicted intensities and associated m / z. For each identified group of ions, the mass spectrometry system can selectively control the attenuation ion gate 80 to selectively attenuate that group of ions. Figure 5 In this embodiment, the attenuation ion gate 80 selectively attenuates ions identified as relatively strong filtered groups. Filtered ions from relatively low-intensity groups are not attenuated by the attenuation ion gate 80. Therefore, step 508 can be similar to HDR scanning methodology or Boxcar scanning methodology, but provides an improved dynamic range of ion output for analysis in a more efficient or continuous manner using available ions. Since the ion dispatching device 50 outputs ions in m / z or associated mobility order, the downstream attenuation ion gate 80 can operate sequentially on the released ions. This methodology avoids the need to limit injection time during multiple individual injections (as with HDR scanning measurements or Boxcar scanning strategies), thereby improving the use of the ion stream.

[0112] like Figure 6 As shown, in some embodiments of this disclosure, ions may be selectively attenuated before entering the ion dispatching device 50 (step 506). Figure 8 A schematic diagram of an ion control device 50, a quadrupole mass filter 70, and an upstream mass filter 45 is shown. The quadrupole mass filter 70 and the ion control device 50 can be configured as described above regarding... Figure 4 The arrangement is described above. Ion dispatching device 50 can be any of the ion dispatching devices described herein, such as linear ion dispatching device 200. Upstream mass filtration device 45 can be another quadrupole mass filter, commonly referred to as an injection filter or pre-filter.

[0113] According to step 508 above, ions can be selectively attenuated after leaving the ion dispatching device 50. One consequence of this strategy is that, when accumulating in the ion dispatching device, relatively strong ions may be mixed with relatively low-intensity ions. This, in turn, may lead to overfilling of the ion dispatching device, thus affecting a longer accumulation time, which is beneficial for improving the ion count of relatively low-intensity ions.

[0114] In view of this, step 506 of method 500 may provide the exclusion of one or more relatively high-intensity precursors from one or more cycles of ion dispatching device 50. Thus, for example, as part of step 502, method 500 may identify a first m / z of ions having an associated predicted intensity higher than a predetermined threshold intensity from the predicted intensity and the associated m / z. Then, step 506 may mass filter the ions having the first m / z using an upstream mass filtering device 45, wherein the mass-filtered ions are input to ion dispatching device 50. By removing relatively strong ions with the first m / z from the ions input to ion dispatching device 50, relatively low-intensity ions can be accumulated without overfilling ion dispatching device 50, thereby improving the dynamic range of ions output from ion dispatching device 50.

[0115] For example, in the first analysis step, the upstream mass filtration device 45 can perform mass filtration on ions with a first m / z and input the filtered ions to the ion dispatching device 50. In the second analysis step, ions with the first m / z can be output to a mass analyzer (e.g., a TOF mass analyzer 150) for mass analysis. For example, in Figure 4 In one embodiment, the ion dispatching device 50 includes a bypass region 54 through which ions of the first m / z can be output for analysis by the mass spectrometry system 1. In practice, the mass spectrometry system 1 can be configured to perform single-ion monitoring and acquisition of the first m / z ions and exclude the first m / z ions from the ion separation path 52 of the ion dispatching device 50.

[0116] In practice, ions with a first m / z can be excluded from the ions input to the ion separation path 52 using a notch mass filter. Such a device may remove or attenuate a relatively narrow range of m / z, including the first m / z, within the range of interest. Therefore, a notch mass filter can be configured to remove "notches" from the ion pack's m / z range. One such notch mass filter includes an additional RF oscillator applied to a quadrupole ion director or... Figure 8The pre-filter resonates with the oscillation of the target first m / z ion. Such notch mass filtering devices are further described at least in Miller, PE, & Denton, MB (1990), “A notch rejection quadrupole mass filter”, International journal of mass spectrometry and ion processes, 96(1), 17-26). In some embodiments, multiple notches can be applied by applying multiple additional sine waves to remove two or more relatively strong substances from the m / z range of interest. Such waveforms can be used to induce resonant jets of a variety of high-intensity materials without significantly damaging the target material over a wide mass range, as further described in Belov, ME, Nikolaev, EN, Anderson, GA, Auberry, KJ, Harkewicz, R., & Smith, RD (2001), “Electrospray ionization-Fourier transform ion cyclotron mass spectrometry using ion preselection and external accumulation for ultrahigh sensitivity” Journal of the American Society for Mass Spectrometry, 12(1), 38-48.

[0117] As an alternative strategy to using a notch filter, ions input to the ion dispatching device 50 can also be divided into two or more passbands for different cycles of input to the ion dispatching device 50. Therefore, method 500 may include identifying a first m / z of ions with an associated predicted intensity above a predetermined threshold intensity in step 502, and identifying a first passband m / z range of interest with m / z below the first m / z and a second passband m / z range of interest with m / z above the first m / z based on the first m / z. For example, to remove relatively strong precursor ions at m / z 700, the method may... Figure 7A DIA scan may identify a first passband m / z ranging from 300 to 690 m / z and a second passband m / z ranging from 710 to 900 m / z. Therefore, in the first analytical step, the upstream mass filter 45 provides ions within the desired first passband m / z range (300-690 m / z) to the ion dispatching device 50. In the second analytical step, the upstream mass filter 45 provides ions within the desired second passband m / z range (710-900 m / z) to the ion dispatching device. In the third analytical step, ions with the first m / z are provided to the mass analyzer for mass analysis. For example, ions around m / z 700 can bypass the ion dispatching device 50 and be examined by conventional MS2 analysis, or examined within their own short cycles along with any other substance of reasonable strength.

[0118] from Figure 7 As can be understood from the DIA methodology review, each of the first and second analytical steps targeting the first and second passbands may require one or more ion scheduling cycles. The number of ion scheduling cycles for each passband in the first and second passbands may depend on the m / z of the relatively strong ions to be removed. In some embodiments, three or more m / z passband ranges may be provided, wherein selective attenuation will be performed on two or more relatively strong substances.

[0119] like Figure 6 As shown, in some embodiments of this disclosure, ions may be selectively attenuated within the ion dispatching device 50 (step 507).

[0120] For example, for a multi-ion trap ion dispatching device 400, such as... Figure 3 As shown in C), each ion trap can be controlled individually to achieve selective decay. Therefore, instead of sequentially outputting m / z separated ions from the linear ion dispatching device 50 as previously described, Figure 9This illustration shows ions of different m / z that are orthogonally (i.e., orthogonal to the generally linear direction of the ion dispatching device) separated by multiple RF electrodes 406 of the multi-ion trap ion dispatching device 400. The RF electrodes 406 orthogonally separate ions in a manner similar to the RF electrodes 206 of other ion dispatching devices, through a combination of traveling waves and DC potentials. Ions are also guided along the axial length of the multi-ion trap ion dispatching device 400 such that, as these ions pass through the ion separation region 401 of the multi-ion trap ion dispatching device 400, the separated groups of ions are each guided to one of the multiple ion traps 402. Ions of different m / z take different paths through the ion separation region 401 and are thus guided to different ion traps 402. The ions are laterally (transverse to the axial direction of ion movement) constrained by the RF electrodes 406 and DC protection electrodes 410, 412 disposed on opposite sides of the multi-ion trap ion dispatching device 400.

[0121] In summary, each ion trap 402 may define an exit point, allowing ions captured within the ion trap 402 to leave the ion separation region 401. Two, three, four, or more ion traps 402 may exist, each ion trap being used to allow ions within a corresponding m / z acceptance window to leave the ion separation region 401. These multiple m / z acceptance windows provided by the multiple ion traps 402 may span the range of interest in m / z. For example, for the range of interest in 300–900 m / z, five ion traps 402 may have m / z acceptance windows of 300–420 m / z, 420–540 m / z, 540–660 m / z, 660–780 m / z, and 780–900 m / z, respectively.

[0122] The m / z range of ions passing through each ion trap 402 is adjustable or fine-tunable, for example, by appropriately selecting the voltage applied by the electrode assembly and / or by adjusting the gas flow within the separation region. Therefore, ions with a given m / z may be directed to one of the multiple ion traps 402 under certain conditions, but to different ion traps 402 under other conditions.

[0123] The multiple ion traps 402 are preferably spaced apart in a direction transverse to the axial length of the ion dispatching device 400. Therefore, the ions separated in the transverse direction are divided into ion dispatching groups, which correspond to the m / z extraction windows of the ion traps 402 of the ion dispatching device 400, respectively.

[0124] Additional potential (e.g., DC force) can be applied to the multi-ion trap ion dispatching device 400 to propel it along the axial length of the device 400 (i.e., Figure 3 The horizontal direction in C pulls ions toward the outlet. For example, a DC gradient can be applied to a DC-only top plate PCB (in... Figure 3(not shown in C) or a shaped counter electrode (if it is an RF blanket type) or an additional DC electrode mounted between the RF electrodes 406; or achieved by shaping the RF electrodes 406. Figure 3 In embodiment C, each RF electrode 406 extends along the axial length of the ion dispatching device 400, i.e., the electrode extends toward the outlet of the ion trap 402 or perpendicular to the arrangement direction of the multiple ion traps. Therefore, the RF electrode 406 may have a traveling wave / reverse DC applied directly thereto to divide ions into ion dispatching groups. Further configurations of the multi-ion trap ion dispatching device 400 are described in GB 2312733.5, the contents of which are incorporated herein by reference.

[0125] Each of the plurality of ion traps 402 may include an ion gate 407. Each ion gate 407 may be associated with a corresponding ion trap 402. Figure 9 A schematic diagram of a multi-ion trap ion scheduling device 400 is shown, illustrating the ion gate 407 associated with each ion trap 402. Effectively, the plurality of ion gates 407 form an ion gate array for the selective attenuation of ions in the multi-ion trap ion scheduling device 400. Thus, each ion gate 407 controls the entry of ions within its m / z receiving window into its associated ion trap 402. Therefore, based on the predicted intensity of the ions and their associated m / z, each of the plurality of ion gates 407 can selectively attenuate ions within the m / z receiving window of its associated ion trap.

[0126] For example, in the case where the predicted intensity identifies an ion with a first m / z intensity higher than a predetermined threshold, the method can identify an m / z acceptance window associated with the first m / z. For example, if the first m / z is 700 m / z, an ion trap 402 spanning 660-780 m / z can be identified, and the ion gate 407 associated with that ion trap 402 can be controlled to attenuate ions within that m / z acceptance window. In practice, the method can determine the ion accumulation time for each ion gate based on the predicted intensity of the ion and the associated m / z, for ions within the m / z acceptance window of the associated ion trap. Thus, when a single high-intensity precursor is ready to fill an ion trap 402, other ion traps 402 may not be affected by the presence of a relatively high-intensity precursor. Therefore, ion accumulation in other ion traps 402 can continue without attenuating any other m / z acceptance windows. In some embodiments, the ion accumulation time of each ion trap 402 can be determined / controlled individually, such that each ion trap has its own automatic gain control.

[0127] In some embodiments, relatively strong precursor ions may pose a risk of overfilling a single ion trap 402 (or entering an adjacent ion trap 402), and ion gate 407 further provides attenuation of relatively strong precursors, although other nearby m / z substances that fall into the same ion trap 402 will also be attenuated.

[0128] Once a suitable number of ions have accumulated within ion trap 402, the ion trap can be controlled to sequentially output ions in the form of ion scheduling groups, where each ion scheduling group corresponds to ions captured in one (or selected) ion trap within ion trap 402. By selectively attenuating some ion material using ion gate 407, the accumulation time of the ion traps in the ion scheduling device can be extended to allow an improved number of relatively low-intensity precursor ions to accumulate in at least some ion traps 402 without overfilling other ion traps 402 (e.g., due to high-intensity precursor ions) affecting the accumulation.

[0129] If from Figure 9 Understood, ions can be selectively attenuated within a multi-ion-trap ion dispatching device 400 using multiple ion gates and / or ion traps. For a linear ion dispatching device 200 (i.e., where ions are axially separated according to their m / z), selective ion attenuation can also be achieved, as further described below. For example, Figure 10 A schematic diagram of a linear ion dispatching device 200 is shown, which includes one or more attenuation electrodes 207 for selectively attenuating ions. Figure 10 A schematic cross-section of the ion separation region 201 of the linear ion dispatching device 200 is shown. (As will be...) Figure 3 As understood, the ion separation region 201 is downstream of the ion accumulation region. The ion separation region 201 includes a plurality of RF electrodes 206 (e.g., in the form of stacked annular ion directors), each RF electrode 206 being axially spaced from the other RF electrodes 206.

[0130] As described above, ions initially accumulate in ion accumulation region 202 before being transferred to ion separation region 201. In ion separation region 201, ions are separated into different groups based on their m / z or ion mobility. These groups of ions are spatially separated along the axial length of ion separation region 201 due to the interaction of the traveling wave and the applied DC potential. For ease of illustration, Figure 10 The ions after separation are schematically shown above the ion dispatching device 200. For example... Figure 10 As shown, the ion dispatching device 200 includes one or more attenuation electrodes 207. Figure 10In this embodiment, attenuation electrodes 207 are disposed between adjacent RF electrodes 206 along the axial length of the ion dispatching device 200. Each attenuation electrode 207 may be associated with a corresponding region of the ion separation region 201 of the ion dispatching device 200. That is, one or more attenuation electrodes 207 may be provided as part of the ion dispatching device 200 to selectively remove ions present in the associated region of the ion separation region 201.

[0131] exist Figure 10 In one embodiment, a plurality of attenuation electrodes 207 are provided along the axial length of the ion dispatching device 200. One or more attenuation electrodes 207 are configured to attenuate or remove ions from the ion dispatching device 200 when supplied with an ion removal voltage.

[0132] For example, such as Figure 10 As shown, the attenuation electrode 207 can be "activated" by supplying a voltage (e.g., a DC voltage) to it. The DC voltage applied to one or more attenuation electrodes 207 can perturb ions trapped within a traveling wave of a nearby active attenuation electrode 207, causing them to be removed from the device (i.e., removed from ions dispatched to be output by the ion dispatching device 200). For example, an attraction potential (i.e., a potential opposite to the polarity of the ions) can be applied to the attenuation electrode 207 to attract ions toward the attenuation electrode 207 and away from the ion separation region 201. It should be understood that the attenuation electrode 207 can follow the DC gradient of the ion dispatching device 200 such that the applied DC voltage can appropriately perturb the ions. Therefore, one or more attenuation electrodes 207 can be controlled to selectively remove ions of different m / z from the ion dispatching device. Therefore, method step 507 can include selectively attenuating ions by selectively supplying an ion removal voltage to the attenuation electrode 207 to selectively attenuate ions based on their predicted intensity and associated m / z.

[0133] exist Figure 10 In some embodiments, a plurality of attenuation electrodes 207 are arranged along the axial length of the ion separation region 201. Therefore, when ions are separated into multiple spatially separated groups of ions in different regions of the ion separation region 201, each group of ions can approach one or more attenuation electrodes 207. Thus, by applying a suitable potential to one or more attenuation electrodes 207 in the ion separation region that are approaching that group of ions, individual groups of ions can be selectively attenuated, or completely removed from the ion separation region 201. In some embodiments, multiple groups of ions can be removed in parallel by applying potentials to multiple attenuation electrodes in different regions of the ion separation region 201.

[0134] In some embodiments, the ion dispatching device 200 outputs ions sequentially as a plurality of ion dispatching groups, each ion dispatching group spanning an m / z extraction window or an ion mobility extraction window, such that the plurality of ion dispatching groups cover the m / z range of interest. When an ion removal voltage is supplied, the attenuation electrode 207 can selectively attenuate or remove ions present in an associated region of the ion dispatching device 200 from the ion dispatching group. For example, in some embodiments, one or more attenuation electrodes 207 may be located near the ion outlet 204 of the ion dispatching device 200. Thus, ions from each ion dispatching group can pass through the region of the ion dispatching device 200 that may be affected by the attenuation electrode 207. Therefore, one or more attenuation electrodes 207 can selectively attenuate the ion based on a predicted intensity as the ion is about to leave the ion dispatching device 200.

[0135] In some embodiments, a plurality of attenuation electrodes 207 may be distributed in the ion dispatching device 200 (e.g., as shown in the figure). Figure 10 As shown in the diagram, each attenuation electrode is associated with a different region of the ion dispatching device. When an ion removal voltage is supplied, each attenuation electrode 207 can selectively attenuate or remove ions from different ion dispatching groups present in the ion dispatching device. Therefore, multiple attenuation electrodes 207 can affect the selective attenuation of ions from multiple parallel ion dispatching groups. Furthermore, multiple attenuation electrodes 207 can allow the selective removal of said ion dispatching group before the ions of the ion dispatching group reach the ion outlet 204. In other words, selective removal can be achieved during the ion separation process of the ion dispatching device 200. For example, ions can be selectively attenuated as part of a multi-step process for filling the ion separation region 201.

[0136] Therefore, in the first filling step, ions are input into the ion dispatching device 200 and separated into multiple ion dispatching groups in the ion separation region 201. In practice, the separated ions maintain a relatively constant equilibrium position along the ion separation region of the ion dispatching device 200 based on their m / z or ion mobility. An ion removal voltage can then be supplied to one or more attenuation electrodes 207 to selectively attenuate or remove one or more ion dispatching groups from the ion dispatching device 200 (e.g., as shown in the image). Figure 10 (As shown in the diagram). For example, as part of the first filling step, relatively strong precursor ions may be selectively removed to prevent overfilling of the ion dispatching device 200.

[0137] In the second filling step, ions are introduced into the ion dispatching device 200 and separated from ions from multiple ion dispatching groups from the first filling step, wherein no ion removal voltage is applied to the decay electrode. Therefore, ions from the second filling step are added to the ions from the first filling step. In practice, for relatively low-intensity ion dispatching groups, the total accumulation time is the sum of the accumulation times of the first and second filling steps. For ions in the ion dispatching group that are selectively removed in the first filling step, the accumulation time is only the duration of the second filling step. The durations of the first and second filling steps can be adjusted based on the predicted intensity. For example, the first filling step may be longer than the second filling step to allow for additional accumulation time for relatively low-intensity precursors. In some embodiments, three or more filling steps may be provided, wherein only the final filling step does not apply a decay voltage.

[0138] Once all filling steps are completed, ions are output from the ion scheduling device 200 according to their ion scheduling groups. Therefore, ions accumulated from specific ion scheduling groups in the first and second filling steps can be output simultaneously.

[0139] In some embodiments, it may be desirable to selectively attenuate only a portion of the ions in the ion dispatch group. Selective attenuation (i.e., providing the option to remove only a portion of the ions, rather than a binary choice of 0% or 100% of the ions in the ion dispatch group) can be implemented using the multi-fill step strategy described above. Alternatively or additionally, selective attenuation can be implemented within the ion dispatch device 200 using attenuation electrodes 207. Thus, in some embodiments, one or more attenuation electrodes 207 may not extend entirely across the width of the device. Alternatively, one or more attenuation electrodes 207 can be segmented into multiple attenuation electrode segments ( Figure 10 (Not shown in the diagram), where multiple electrode segments are located at axial positions of the ion dispatching device (similar to attenuation electrode 207). These multiple attenuation electrode segments may be spaced apart across the width of the ion dispatching device 200 to form a group of attenuation electrode segments. Each attenuation electrode segment may be supplied with a DC attenuation voltage independently of the other attenuation electrode segments in the group. Therefore, ions in the ion dispatching group that are separated and maintained near an equilibrium position close to attenuation electrode 207 / attenuation electrode segment can be selectively attenuated, with the attenuation proportional to the width of the active attenuation electrode or the width of the active attenuation electrode segment within the group. In other words, the attenuation force is stronger by increasing the number of activated attenuation electrode segments. For example, in some embodiments, a group of four attenuation electrode segments may be provided instead. Figure 10A single attenuation electrode 207. Therefore, by not activating any attenuation electrode segment, 0% of the ions in the local ion dispatch group can be selectively attenuated. As one of the attenuation electrode segments is activated, the selective removal capacity may increase to remove approximately 25% of the ions in the ion dispatch group. Activating additional attenuation electrode segments can subsequently increase the selective removal rate to 50%, 75%, and 100% (with all four attenuation electrode segments activated).

[0140] It should be understood that the selective control of the attenuation electrode segment can be combined with the multi-filling step strategy discussed above to provide further control over the ion population of each group of ions separated by the ion dispatching device 200.

[0141] exist Figure 10 In one embodiment, the attenuation electrode 207 is disposed between adjacent RF electrodes 206 of the ion dispatching device 200. In other embodiments, for example, as Figure 11 As shown, the attenuation electrode 207 can be implemented as part of the DC protection electrode formed at the edge of the ion dispatching device 200. Figure 11 This is a top cross-sectional view of the linear ion dispatching device 200. (See image below.) Figure 11 As shown, the linear ion control device 200 includes a plurality of DC protection electrodes 210, 212 disposed on opposite sides of the linear ion control device 200. The opposing DC protection electrodes 210, 212 are configured to laterally confine ions within the linear ion control device. RF electrodes 206 extend along the length of the linear ion control device 200 between the opposing DC protection electrodes. In some embodiments, a single DC protection electrode may extend along a considerable length of the accumulation region 202 and / or the ion separation region. Figure 11 In one embodiment, the DC protection electrodes on opposite sides are segmented to form two sets of DC protection electrodes 210, 212 on opposite sides of the linear ion dispatching device 200. During normal operation, a DC confinement voltage can be provided to each of the DC protection electrodes 210, 212 to laterally confine ions within the linear ion dispatching device 200.

[0142] like Figure 11 As shown, one or more attenuation electrodes 207 may be provided instead of the DC protection electrodes 210, 212 at the edge of the linear ion dispatching device 200. In practice, one or more DC protection electrodes 210, 212 may be replaced along a portion of the axial length of the linear ion dispatching device 200 to allow selective attenuation of ions. A DC confinement voltage may be supplied to the attenuation electrodes 207 to confine ions within the linear ion dispatching device 200, similar to the operation of the DC protection electrodes 210, 212.

[0143] To induce selective ion decay, a decay voltage can be supplied to decay electrode 207 independently of the DC confinement voltage supplied to DC protection electrodes 210, 212. By varying the voltage supplied to decay electrode 207 (relative to DC protection electrodes 210, 212), some ions can be allowed to escape from the linear ion dispatching device 200 in the region of decay electrode 207. For example, when selective ion decay is required, the decay voltage can be a reduced DC confinement voltage (e.g., 10%, 20%, or 50% of the DC confinement voltage), no voltage, or an attractive DC voltage (i.e., a voltage with an opposite potential to the DC confinement voltage) to cause ions to migrate from the central region of the ion dispatching device and escape via one or more edge regions of the ion dispatching device 200. To achieve selective removal of ions at a desired m / z, decay electrode 207 can be controlled only to remove ions when the desired ions are located in the region near decay electrode 207. For example, decay electrode 207 can be positioned toward the ion outlet 204 of the linear ion dispatching device 200 such that each ion-dispatched ion group passes through decay electrode 207 before leaving the device 200. Therefore, as Figure 11 As shown, one or more attenuation electrodes 207 may be associated with a region of the linear ion dispatching device 200, wherein Figure 11 Each attenuation electrode 207 is configured to selectively attenuate or selectively remove ions from the linear ion dispatching device 200 when supplied with an attenuation voltage.

[0144] In some embodiments, it should be understood that highly clustered groups of ions may have relatively high space charges. This, in turn, can push some of the ions in the highly clustered groups closer to the guard electrodes 210, 212 of the ion dispatching device 200. The relatively high potential applied to the guard electrodes 210, 212 prevents the ion group from expanding further. In some embodiments, one or more guard electrodes 210, 212 may act as attenuation electrodes 207 by having a relatively low order of magnitude of potential applied to them. By maintaining regions of the “weaker” guard electrodes 210, 212, such as near the outlet 204 (where all ions will pass), the relatively high-intensity ions passing through them can be forced across the weakened protective barrier under the influence of space charge. Thus, the ions of the relatively high-intensity groups can be selectively attenuated as they pass through the regions of the weaker guard electrodes 210, 212. Such regions of lower order of magnitude of potential can be maintained throughout each ion dispatching cycle in order to effectively self-regulate the ion group of ions in each ion dispatching group.

[0145] According to embodiments of this disclosure, it should be understood that the attenuation ion gate 80 can provide selective attenuation of ions. Specifically, the attenuation ion gate 80 can be provided for selectively attenuating ions leaving the ion dispatching device 50, as described above. Next, reference will be made to... Figure 12 Describes the attenuation ion gate 80.

[0146] like Figure 12 As shown, the attenuation ion gate 80 includes a first ion lens 82, a second ion lens 84, and a first deflection electrode and second deflection electrodes 86 and 88. An isometric view of the attenuation ion gate 80 is shown below. Figure 13 As shown in the image.

[0147] The first ion lens 82 defines a first aperture 81 through which ions can enter the attenuating ion gate 80. For example... Figure 12 As shown (and also as Figure 4 (As indicated in the text), the attenuating ion gate 80 can receive ions from the quadrupole mass filter 70. (As indicated in the text) Figure 12 and Figure 13 As shown, the first ion lens 82 can be a generally circular (or elliptical) plate. A first hole is formed that penetrates the thickness of the plate. Figure 12 In one embodiment, the first hole is circular, but in other embodiments, plates and holes of other shapes may be used.

[0148] The second ion lens 84 defines a second aperture 83 through which ions can exit the attenuation ion gate 80. For example... Figure 12 As shown (also as Figure 4 As shown in the diagram), the attenuation ion gate 80 can output ions to the transfer multipole 90, for example... Figure 13 The octet 92 is shown. Similar to the first ion lens 82, the second ion lens can be a generally circular (or elliptical) plate. A second hole 83 is formed, penetrating the thickness of the plate. Figure 12 In one embodiment, the second hole 83 is circular, but in other embodiments, plates of other shapes and the second hole 83 may be used.

[0149] like Figure 12 As shown, the second ion lens 84 is spaced apart from the first ion lens 82. Therefore, the first and second ion lenses 82 and 84 form a split lens structure. The first and second apertures 81 and 83 are also aligned axially with the attenuating ion gate 80 to define an ion channel between the first and second apertures. Ions pass through the attenuating ion gate along the ion channel, as... Figure 12 The ion path is shown in the diagram. It should be understood that by applying potentials to the upstream quadrupole mass filter 70, the first ion lens and the second ion lenses 82, 84, and the transfer multipole 90, ions are confined to the substantially central region of the ion path (through the center of the first and second holes).

[0150] like Figure 12 and Figure 13As shown, the first deflection electrode and the second deflection electrode 86, 88 are disposed on opposite sides of the ion channel between the first ion lens 82 and the second ion lens 84. The first deflection electrode and the second deflection electrode 86, 88 may be spaced apart on opposite sides of the ion channel at a distance similar to the diameter of the first hole and the second hole 81, 83. The first deflection electrode and the second deflection electrode 86, 88 are configured to receive a variable alternating deflection voltage across the first deflection electrode and the second deflection electrode to variably attenuate ions passing through the attenuation ion gate. Therefore, an alternating deflection voltage difference may be applied across the first deflection electrode 86 and the second deflection electrode 88. It should be understood that in some embodiments, a common DC offset voltage (e.g., -30V for positive ions) may also be applied to the first deflection electrode and the second deflection electrode 86, 88.

[0151] The alternating deflection voltage difference can be a generally sinusoidal waveform, but other alternative waveforms may be applied in some embodiments. Thus, the alternating potential applied to the first and second deflection electrodes 86, 88 can replace or supplement binary on / off ion gate control to allow for variable attenuation of ions using lower amplitude voltage waveforms (on / off gate control typically utilizes a DC voltage not exceeding 50V).

[0152] like Figure 12 As shown, a shielding electrode 87 may also be provided. The shielding electrode 87 defines a shielding hole 91. The shielding electrode 87 may be disposed between the first deflection electrode and the second deflection electrodes 86, 88 and the second ion lens 84 (along the axial direction). In other embodiments, the shielding electrode 87 may be disposed between the first deflection electrode and the second deflection electrodes 86, 88 and the first ion lens 82. In some embodiments, two shielding electrodes 87 may be provided on opposite axial sides of the first deflection electrode and the second deflection electrodes 86, 88.

[0153] By applying an alternating deflection voltage to the first and second deflection electrodes 86, 88, when the voltage difference between the first and second deflection electrodes 86, 88 is relatively low (e.g., no greater than about 10V), ions will primarily be transported through the ion channel. For example, when the voltage difference is relatively low, ions entering the attenuating ion gate 80 at a potential of about ~40eV can travel through the attenuating ion gate 80. By changing (increasing) the amplitude (or frequency), the ion beam is made to diffuse radially in a manner proportional to the increase in the frequency and amplitude of the alternating deflection voltage. Therefore, the proportion of ions increases and they may then collide with or be deflected by the second (exit) aperture 83 instead of entering the transfer multipole 90.

[0154] The first and second ion lenses 82 and 84 can be spaced apart in a manner similar to existing split-lens designs. To ensure that ions pass through the attenuating ion device 80 under normal (i.e., fully open) operation without significant ion loss, the ions can be accelerated to approximately 40 eV. In some embodiments, the pressure within the ion channel can be relatively low, for example, << 1 x 10⁻⁶ eV. -3 mbar ensures that collisions do not affect ion transport.

[0155] Figure 13 An isometric view of a model of a decaying ion gate 80 constructed using a three-dimensional computer simulation software package (MASIM3D Simulation Suite) for simulating ion trajectories is shown. The decaying ion gate 80 is configured to receive ions from a quadrupole with a 4 mm radius and output ions to an octupole with a 3 mm radius. The simulation suite assumes ions are generated in the quadrupole at a potential of +5 V with an energy of 1 eV, allowing them to be accelerated through a first aperture 81 with a diameter of 2 mm while maintaining a first lens at -35 V. Positive and negative phases of an alternating deflection voltage are applied to opposing first and second deflection electrodes 86, 88, as it was found that using a single RF phase would result in excessive ion energy perturbation. Ions are then directed through a larger aperture of a shielding electrode 87 behind the deflection electrodes 86, 88, and then through a second aperture 83 into an octupole 90 with an inscribed radius of 3 mm, where they are decelerated to 3 eV. Ions that diffused beyond a 2 mm radial displacement were removed from the simulation and assumed to be lost. The proportion of these lost ions determined the transmittance estimates shown in Figure 14 for different simulated alternating deflection voltage ranges.

[0156] Figure 14A , Figure 14B and Figure 14C Simulation results show the effect of different alternating deflection voltages (variable amplitude and variable frequency) on the transmittance of generated ions over a 1 ms time period. Figure 14A In this study, the amplitude of the 10 kHz alternating deflection voltage varies within the range of 0-100 V. For ions with m / z 195, when the voltage amplitude is above approximately 5 V, the ion transmittance begins to decrease from 100%. At an alternating deflection voltage amplitude of approximately 15 V, the ion transmittance has already decreased to 40%, and at an alternating deflection voltage of 20 V, it decreases to approximately 20%. Due to the relatively small pulse width of some ion packets (e.g., <2 ms), it is likely preferable to use an alternating deflection voltage frequency of at least 5 kHz, preferably 10 kHz. For higher frequency alternating deflection voltages, it is expected that the amplitude required to reduce ion transmittance will increase, which is typical of RF-ion interactions.

[0157] Figure 14B This illustrates the effect of changing the frequency of a 25V amplitude alternating deflection voltage. For example... Figure 14BAs shown, the percentage of transmittance increases with increasing alternating deflection voltage frequency.

[0158] Figure 14C The dependence of transmittance on ion m / z is shown. Figure 14C Slightly more than half of the m / z 195 ions were removed using an alternating deflection voltage of 10 kHz and 15 V amplitude. Higher m / z ions reduce transmittance because higher m / z, lower velocity ions are more likely to encounter high deflection potentials more frequently. This is achieved through methods such as... Figure 14C It is understood that within the m / z range of 195 to 2800 m / z, the transmittance variation is only about 20%, and the trend is smooth. Therefore, in some embodiments, the attenuation ion gate can be calibrated to account for the m / z dependence of ion transmittance. For example, the attenuation ion gate 80 can adjust the applied alternating deflection voltage based on the m / z of the ions in the ion dispatch group to be selectively attenuated. Calibration may include adjusting the amplitude of the alternating deflection voltage based on the m / z of the ions to be selectively attenuated and / or adjusting the amplitude of the alternating deflection voltage based on the m / z of the ions to be calibrated.

[0159] Although Figure 12 In some embodiments, the deflected ions are depicted as impacting a second ion lens, but in others, the deflected ions may be directed to a secondary detector, such as a dynamometer electrode. The dynamometer electrode may be positioned off-axis from the second aperture 83. Secondary particles generated by receiving ions at the dynamometer electrode may be directed to a detector or electron multiplier for the secondary particles. In this way, the deflected particles can be used to obtain additional information about the ion beam passing through the attenuating ion gate. Further description of such secondary detectors is available in at least US11,087,969B, the contents of which are incorporated herein by reference.

[0160] Although Figure 12 In some embodiments, an alternating voltage is applied using the first deflection electrode and the second deflection electrode 86, 88. However, in other embodiments, a DC voltage may be applied to further attenuate / deflect ions transported through the ion gate. For example, in some embodiments, a differential DC voltage may be additionally applied to the first deflection electrode and the second deflection electrode 86, 88 to further reduce the permeability of ions passing through the ion gate 80. In some embodiments, such a differential DC voltage may be applied to, for example, completely close the ion gate.

[0161] It should be understood that applying a differential DC voltage to the first and second deflection electrodes 86, 88 reduces the effectiveness of the alternating deflection voltage. In particular, the conventional differential DC voltage used to shut down the ion gate typically exceeds 100V. To address this issue, Figure 15A schematic diagram of a decaying ion gate 80 including a third deflection electrode 85 and a fourth deflection electrode 89 is shown. In fact, the structure of this embodiment is similar to, for example, the dual-gate split lens described in US 8,0264,75B, the contents of which are incorporated herein by reference.

[0162] like Figure 15 As shown, the third and fourth deflection electrodes 85 and 89 may have a structure similar to that of the first and second deflection electrodes 86 and 88. In some embodiments, the third and fourth deflection electrodes 85 and 89 may be (axially) disposed between the first and second deflection electrodes 86 and 88 and the first ion lens 82, or disposed between the first and second deflection electrodes 86 and 88 and the second ion lens 84.

[0163] The third and fourth deflection electrodes 85 and 89 can be configured to selectively receive a DC deflection voltage, which is configured to prevent ion transport through a decaying ion gate. Therefore, the (fully) opening and (fully) closing of the decaying ion gate by the DC voltage can be axially spaced from the variable attenuation provided by the first and second deflection electrodes 86 and 88. In some embodiments, such as Figure 15 As shown, a shielding electrode 87 defining the shielding hole 91 can be provided (axially) between the first deflection electrode and the second deflection electrode 86, 88 and the third deflection electrode and the fourth deflection electrode 85, 89, in order to shield relatively large DC voltages from the effects of low amplitude alternating deflection voltages.

[0164] As described above, when ions leave the attenuation ion gate 80 through the second ion aperture 83, the deflected ions may collide with the second ion lens 82. In order to reduce wear and / or contamination of the second ion aperture 83, in some embodiments, the axial profile of the second ion aperture may be modified to guide (or graze) the deflected ions away from the second ion aperture 83. Figure 16 An example of this type of contour is shown in the image. For example... Figure 16 As shown, the edge of the plate defining the second aperture 83 is extruded toward the first ion aperture 82 to define a grazing region 600 of the second ion lens 82 surrounding the second ion aperture 83. Since ions deflected by the first and second deflecting electrodes 86, 88 can be guided toward the edge of the second aperture 83, the grazing region 600 allows the second ion lens 82 to guide deflected ions away from the inner surface 602 of the second aperture 83, or at least reduces the number of ions in contact with the inner surface 602. This, in turn, reduces wear / contamination of the second ion lens 82, thereby improving the lifespan of the second aperture.

[0165] Therefore, according to this disclosure, a method for scheduling ions for analysis by a mass spectrometry system is provided, wherein ions are selectively attenuated based on their m / z and relative intensity.

[0166] Embodiments of this disclosure will now be described with reference to the following numbered clauses.

[0167] 1. A method for scheduling ions for analysis by a mass analyzer within a range of mass-to-charge ratios (m / z) of interest, the method comprising: Obtain the predicted intensity and associated m / z of ions across the range of mass-to-charge ratios of interest; Ions are input into the ion dispatching device; Based on the m / z or ion mobility of the ions, the ions are output from the ion dispatching device to the mass analyzer; and The ions are selectively attenuated based on their predicted intensity and associated m / z.

[0168] 2. The method according to Clause 1, wherein

[0169] Selectively attenuating the ions based on their predicted intensity and associated m / z includes: A list of m / z values ​​for ions with associated predicted intensities higher than a predetermined threshold, identified from the predicted intensities and associated m / z values; and The ions are selectively attenuated based on the m / z list.

[0170] 3. The method described under Clause 1 or Clause 2 further includes: Obtain the list of target m / z values ​​of interest; and The output of ions from the ion scheduling device is scheduled based on the target m / z list of interest.

[0171] 4. The method according to any of the preceding clauses, wherein

[0172] The ion scheduling device outputs the ions sequentially as multiple ion scheduling groups, wherein each ion scheduling group spans the m / z extraction window, such that the multiple ion scheduling groups cover the m / z range of interest or each ion scheduling group spans the ion mobility range.

[0173] 5. The method described in Clause 4, wherein

[0174] Perform multiple ion scheduling cycles, where in each ion scheduling cycle: Ions are input to the ion scheduling device, and the ion scheduling device sequentially outputs the plurality of ion scheduling groups for each ion scheduling cycle.

[0175] 6. The method according to clause 4 or 5, wherein the method further comprises: A downstream mass filtration device is used to perform mass filtration on ions from each ion scheduling group output from the ion scheduling device, wherein for each ion scheduling group, the mass filtration device outputs filtered ions to the mass analyzer, and each filtered ion crosses the m / z isolation window of the mass filtration device.

[0176] 7. The method described in Clause 6, wherein

[0177] For each ion scheduling group output from the ion scheduling device, the mass filtering device updates the position of the m / z isolation window of the mass filtering device, such that the multiple filtered ions output from the mass filtering device span the m / z range of interest.

[0178] 8. The method according to any of the foregoing clauses, wherein

[0179] The ions are selectively attenuated by an upstream filtration device before being fed into the ion dispatching device.

[0180] 9. The method according to Clause 8, wherein the method further comprises: Selectively attenuating the ions based on their predicted intensity and associated m / z includes: Identify a first m / z associated with an ion having a predicted intensity higher than a predetermined threshold intensity from the predicted intensity and associated m / z; and The upstream mass filtration device is used to selectively attenuate ions having the first m / z, wherein the mass-filtered ions are input to the ion dispatching device.

[0181] 10. The method according to Clause 9, wherein the method further comprises: In the first analysis step, the upstream mass filtration device selectively attenuates ions having the first m / z and inputs the ions to the ion dispatching device, and In the second analysis step, the ions having the first m / z are output to the mass analyzer for mass analysis.

[0182] 11. The method according to Clause 8, wherein

[0183] Selectively attenuating the ions based on their predicted intensity and associated m / z includes: Identify a first m / z associated with an ion having a predicted intensity higher than a predetermined threshold intensity from the predicted intensity and associated m / z, and identify a first passband m / z range of interest with m / z lower than the first m / z and a second passband m / z range of interest with m / z higher than the first m / z based on the first m / z; In the first analysis step, the upstream mass filtration device provides the ion dispatching device with ions within the first passband m / z range of interest, and In the second analytical step, the upstream mass filtration device provides the ion dispatching device with ions within the desired second passband m / z range, and In the third analytical step, the ions having the first m / z are provided to the mass analyzer for mass analysis.

[0184] 12. The method according to Clause 11, wherein

[0185] One or more steps in the first and second analysis steps may each include multiple ion scheduling cycles.

[0186] 13. The method according to any of the preceding clauses, wherein

[0187] The ion control device includes: Multiple ion traps, wherein each ion trap has an associated m / z accepting window or an associated ion mobility accepting window, and Multiple ion gates, each associated with a corresponding ion trap, wherein each ion gate controls the entry of ions within the m / z receiving window or ion mobility receiving window into the associated ion trap.

[0188] 14. The method according to Clause 13, wherein

[0189] Based on the predicted intensity and associated m / z of the ions, each of the plurality of ion gates selectively attenuates the ions within the m / z receiving window or ion mobility receiving window of the associated ion trap.

[0190] 15. The method described in accordance with Clause 14, wherein

[0191] Selectively attenuating the ions includes, for each ion gate, determining the ion accumulation time for ions within the m / z acceptance window or ion mobility acceptance window of the associated ion trap, based on the predicted intensity and associated m / z of the ion.

[0192] 16. The method according to any one of clauses 1 to 12, wherein

[0193] The ion control device includes a decay electrode associated with a region of the ion control device, the decay electrode being configured to decay ions or remove ions from the ion control device when an ion removal voltage is supplied.

[0194] Selectively attenuating the ions involves selectively supplying an ion removal voltage to the attenuation electrode to selectively attenuate the ions based on their predicted intensity and associated m / z.

[0195] 17. The method according to Clause 16, wherein

[0196] The ion scheduling device outputs the ions sequentially as multiple ion scheduling groups, each ion scheduling group spanning an m / z extraction window or an ion mobility extraction window; and

[0197] When the ion removal voltage is supplied, the attenuation electrode selectively attenuates or removes ion-dispatch group ions present in the region of the ion dispatching device associated with the attenuation electrode.

[0198] 18. The method described in accordance with Clause 17, wherein

[0199] Multiple attenuation electrodes are distributed within the ion control device, each attenuation electrode being associated with a different region of the ion control device, and

[0200] When the ion removal voltage is supplied, each attenuation electrode selectively attenuates or removes ions from different ion dispatch groups present in the ion dispatching device.

[0201] 19. The method described pursuant to Clause 17 or Clause 18, wherein

[0202] In the first filling step: Ions are input into the ion dispatching device, separated into multiple ion dispatching groups, and captured by the ion dispatching device; and An ion removal voltage is supplied to the attenuation electrode to selectively attenuate or remove the ion control group from the ion control device; and In the second filling step, ions are input to the ion dispatching device and separated into multiple ion dispatcher groups from the first filling step, wherein the ion removal voltage is not applied to the attenuation electrode. Ions from the first filling step and the second filling step are simultaneously output from the ion dispatching device according to their m / z or ion mobility.

[0203] 20. The method according to any of the preceding clauses, wherein

[0204] Ions from the ion dispatching device are output to the mass analyzer via a decaying ion gate, wherein the decaying ion gate selectively decays the ions based on the predicted intensity and associated m / z of the ions.

[0205] 21. The method according to any of the preceding clauses, wherein

[0206] Obtaining predicted intensities and associated m / z for ions across the mass range of interest includes: The predicted intensity and associated m / z of the ion are determined based on previous mass analysis performed by the mass analyzer.

[0207] 22. The method according to any of the preceding clauses, wherein

[0208] The ion control device includes: an ion accumulation region, wherein ions accumulate; and

[0209] An ion separation region is formed in which ions from the ion accumulation region are separated according to their m / z or ion mobility.

[0210] 23. The method according to any of the preceding clauses, wherein

[0211] The ion control device includes: An ion separation path, wherein ions are separated along the ion separation path according to their m / z or ion mobility; A bypass path, along which ions are not separated according to their m / z or ion mobility; and The path selection region selects whether ions travel along the ion separation path or the bypass path.

[0212] 24. The method according to any of the preceding clauses, wherein

[0213] The ion dispatching device includes multiple ion traps, each ion trap having an associated m / z receiving window or ion mobility receiving window, and

[0214] The multiple ion traps output ions sequentially, so that the ion scheduling device outputs the ions to the mass analyzer according to the ion's m / z or ion mobility.

[0215] 25. A controller for scheduling ions for analysis by a mass analyzer within a range of m / z of interest, the controller being configured to: Obtain the predicted intensity and associated m / z of ions across the mass range of interest; This allows ions to be input into the ion dispatching device; Based on the m / z or ion mobility of the ions, the ions are output from the ion dispatching device to the mass analyzer; and The ions are selectively attenuated based on their predicted intensity and associated m / z.

[0216] 26. A mass spectrometry system for analyzing ions in a range of interest (m / z), the mass spectrometry system comprising: An ion dispatching device, configured to receive ions and output ions to a mass spectrometry system; The mass spectrometry system thereon is configured to perform the method according to any one of clauses 1 to 24.

[0217] 27. A computer program comprising instructions that cause a mass spectrometry system according to Clause 26 to perform the steps of the method according to any one of Clauses 1 to 24.

[0218] 28. A computer-readable medium on which a computer program according to Clause 27 is stored.

[0219] 29. An attenuation ion gate for a mass spectrometry system, the attenuation ion gate comprising: A first ion lens, wherein the first ion lens defines a first aperture; A second ion lens, defining a second aperture, wherein the second ion lens is spaced apart from the first ion lens, and the first and second apertures are aligned axially in the attenuation ion gate to define an ion channel between the first and second apertures; and A first deflection electrode and a second deflection electrode are disposed on opposite sides of the ion channel between the first ion lens and the second ion lens. The first deflection electrode and the second deflection electrode are configured to receive a variable alternating deflection voltage across the first electrode and the second electrode in order to variably attenuate ions passing through the attenuation ion gate.

[0220] 30. The attenuating ion gate according to Clause 29, wherein the attenuating ion gate further comprises: A shielding electrode, defining a shielding aperture, wherein the shielding electrode is disposed between the first deflection electrode and the second deflection electrode and the second ion lens, and The shielding hole is aligned with the ion channel.

[0221] 31. The attenuating ion gate according to Clause 29 or Clause 30, wherein the attenuating ion gate further comprises: A voltage source configured to apply a frequency- and amplitude-converting alternating deflection voltage to the first deflection electrode and an opposite frequency- and amplitude-converting alternating deflection voltage to the second deflection electrode.

[0222] 32. The attenuation ion gate as described in Clause 31, wherein

[0223] The voltage source is configured to vary the amplitude of the alternating deflection voltage between 10V and at least 25V in order to control the attenuation of ions passing through the ion gate.

[0224] 33. The attenuation ion gate as described in Clause 31 or Clause 32, wherein

[0225] The voltage source is configured to vary the frequency of the alternating deflection voltage between 100 kHz and at least 1000 kHz in order to control the attenuation of ions passing through the ion gate.

[0226] 34. The attenuating ion gate according to any one of clauses 29 to 33, wherein the attenuating ion gate further comprises: A third deflection electrode is disposed between the first and second deflection electrodes and the first ion lens, or between the first and second deflection electrodes and the second ion lens. The third deflection electrode is configured to selectively receive a DC deflection voltage, which is configured to prevent ions from passing through the decay ion gate.

[0227] 35. The attenuating ion gate according to Clause 34, wherein the attenuating ion gate further comprises: A shielding electrode, defining a shielding aperture, wherein the shielding electrode is disposed between the first deflection electrode and the second deflection electrode and the third deflection electrode, and The shielding hole is aligned with the ion channel.

[0228] 36. A decaying ion gate according to any one of clauses 29 to 35, wherein

[0229] The second ion lens includes a plate, wherein the plate defines a second hole penetrating the thickness of the plate, wherein optionally, the second hole is generally circular or elliptical.

[0230] 37. The attenuation ion gate as described in Clause 36, wherein

[0231] The edge of the plate defining the second aperture protrudes toward the first ion aperture to define the grazing area of ​​the second ion lens surrounding the second ion aperture.

Claims

1. A method for scheduling ions within a range of mass-to-charge ratios of interest for analysis by a mass analyzer, the method comprising: Obtain the predicted intensity and associated mass-to-charge ratio of ions across the range of mass-to-charge ratios of interest; Ions are input into the ion dispatching device; Based on the mass-to-charge ratio or ion mobility of the ions, the ions are output from the ion dispatching device to the mass analyzer; as well as The ions are selectively attenuated based on their predicted intensity and associated mass-to-charge ratio.

2. The method according to claim 1, characterized in that, Selectively attenuating the ions based on the predicted intensity and associated mass-to-charge ratio of the ions includes: A list of mass-to-charge ratios for ions with associated predicted intensities higher than a predetermined threshold intensity is identified from the predicted intensity and associated mass-to-charge ratio; and The ions are selectively decayed based on the mass-to-charge ratio list.

3. The method according to claim 1, characterized in that, The method further includes: Obtain a list of target mass-to-charge ratios of interest; and The output of ions from the ion scheduling device is scheduled based on the list of target mass-to-charge ratios of interest.

4. The method according to claim 1, characterized in that, The ion dispatching device outputs the ions sequentially as multiple ion dispatching groups. Each ion scheduling group spans a mass-to-charge ratio extraction window, such that the multiple ion scheduling groups cover the range of mass-to-charge ratios of interest, or Each ion scheduling group spans a range of ion mobility.

5. The method according to claim 4, characterized in that, Perform multiple ion scheduling cycles, where in each ion scheduling cycle: Ions are input to the ion scheduling device, and the ion scheduling device sequentially outputs the plurality of ion scheduling groups for each ion scheduling cycle.

6. The method according to claim 4, characterized in that, The method further includes: A downstream mass filtration device is used to perform mass filtration on ions from each ion scheduling group output from the ion scheduling device, wherein for each ion scheduling group, the mass filtration device outputs filtered ions to the mass analyzer, and each filtered ion crosses the mass-to-charge ratio isolation window of the mass filtration device.

7. The method according to claim 6, characterized in that, For each ion scheduling group output from the ion scheduling device, the mass filtering device updates the position of the mass-to-charge ratio isolation window of the mass filtering device, such that the multiple filtered ions output from the mass filtering device span the mass-to-charge ratio range of interest.

8. The method according to claim 1, characterized in that, The ions are selectively attenuated by an upstream filtration device before being fed into the ion dispatching device.

9. The method according to claim 8, characterized in that, The method further includes: Selectively attenuating the ions based on the predicted intensity and associated mass-to-charge ratio of the ions includes: Identify a first mass-to-charge ratio associated with an ion having a predicted intensity higher than a predetermined threshold intensity from the predicted intensity and associated mass-to-charge ratio; and The upstream mass filtration device selectively attenuates ions having the first mass-to-charge ratio, wherein the mass-filtered ions are input to the ion dispatching device.

10. The method according to claim 9, characterized in that, The method also includes In the first analytical step, the upstream mass filtration device selectively attenuates ions having the first mass-to-charge ratio and inputs the ions to the ion dispatching device, and In the second analytical step, ions having the first mass-to-charge ratio are output to the mass analyzer for mass analysis.

11. The method according to claim 8, characterized in that, Selectively attenuating the ions based on the predicted intensity and associated mass-to-charge ratio of the ions includes: The first mass-to-charge ratio associated with an ion having a predicted intensity higher than a predetermined threshold intensity is identified from the predicted intensity and the associated mass-to-charge ratio, and a first passband mass-to-charge ratio range of interest with a mass-to-charge ratio lower than the first mass-to-charge ratio and a second passband mass-to-charge ratio range of interest with a mass-to-charge ratio higher than the first mass-to-charge ratio are identified based on the first mass-to-charge ratio. In the first analytical step, the upstream mass filtration device provides the ion dispatching device with ions within the mass-to-charge ratio range of the first passband of interest, and In the second analytical step, the upstream mass filtration device provides the ion dispatching device with ions within the mass-to-charge ratio range of the second passband of interest, and In the third analytical step, ions having the first mass-to-charge ratio are provided to the mass analyzer for mass analysis.

12. The method according to claim 11, characterized in that, One or more steps in the first and second analysis steps may each include multiple ion scheduling cycles.

13. The method according to claim 1, characterized in that, The ion control device includes: Multiple ion traps, wherein each ion trap has an associated mass-to-charge ratio accepting window or an associated ion mobility accepting window, and Multiple ion gates, each associated with a corresponding ion trap, wherein each ion gate controls the entry of ions within the mass-to-charge ratio receiving window or ion mobility receiving window into the associated ion trap.

14. The method according to claim 13, characterized in that, Based on the predicted intensity and associated mass-to-charge ratio of the ions, each of the plurality of ion gates selectively attenuates ions within the associated mass-to-charge ratio receiving window or ion mobility receiving window of the ion trap.

15. The method according to claim 14, characterized in that, Selectively attenuating the ions includes, for each ion gate, determining the ion accumulation time for ions within the mass-to-charge ratio acceptance window or ion mobility acceptance window of the associated ion trap, based on the predicted intensity and associated mass-to-charge ratio of the ion.

16. The method according to claim 1, characterized in that, The ion control device includes a decay electrode associated with a region of the ion control device, the decay electrode being configured to decay ions or remove ions from the ion control device when an ion removal voltage is supplied. Selectively attenuating the ions involves selectively supplying an ion removal voltage to the attenuation electrode to selectively attenuate the ions based on their predicted intensity and associated mass-to-charge ratio.

17. The method according to claim 16, characterized in that, The ion dispatching device outputs the ions sequentially as multiple ion dispatching groups, each ion dispatching group spanning either a mass-to-charge ratio extraction window or an ion mobility extraction window; and When the ion removal voltage is supplied, the attenuation electrode selectively attenuates or removes ion-dispatch group ions present in the region of the ion dispatching device associated with the attenuation electrode.

18. The method according to claim 17, characterized in that, Multiple attenuation electrodes are distributed within the ion control device, each attenuation electrode being associated with a different region of the ion control device, and When the ion removal voltage is supplied, each attenuation electrode selectively attenuates or removes ions from different ion dispatch groups present in the ion dispatching device.

19. The method according to claim 17, characterized in that, In the first filling step: Ions are input into the ion dispatching device, separated into multiple ion dispatching groups, and captured by the ion dispatching device. as well as An ion removal voltage is supplied to the attenuation electrode to selectively attenuate or remove the ion control group from the ion control device. and In the second filling step, ions are input to the ion dispatching device and separated into multiple ion dispatcher groups from the first filling step, wherein the ion removal voltage is not applied to the attenuation electrode. Ions from the first filling step and the second filling step are simultaneously output from the ion dispatching device according to their mass-to-charge ratio or ion mobility.

20. The method according to claim 1, characterized in that, Ions from the ion dispatching device are output to the mass analyzer via a decaying ion gate, wherein the decaying ion gate selectively decays the ions based on the predicted intensity and associated mass-to-charge ratio of the ions.

21. The method according to claim 1, characterized in that, Obtaining predicted intensities and associated mass-to-charge ratios for ions across the range of masses of interest includes: The predicted intensity and associated mass-to-charge ratio of the ion are determined based on previous mass analysis performed by the mass analyzer.

22. The method according to claim 1, characterized in that, The ion control device includes: an ion accumulation region, wherein ions accumulate; and An ion separation region is where ions from the ion accumulation region are separated according to their mass-to-charge ratio or ion mobility.

23. The method according to claim 1, characterized in that, The ion control device includes: An ion separation path, in which ions are separated according to their mass-to-charge ratio or ion mobility along the ion separation path; A bypass path, in which ions are not separated according to their mass-to-charge ratio or ion mobility along the bypass path; and The path selection region selects whether ions travel along the ion separation path or the bypass path.

24. The method according to claim 1, characterized in that, The ion dispatching device includes multiple ion traps, each ion trap having an associated mass-to-charge ratio receiving window or an ion mobility receiving window, and The multiple ion traps output ions sequentially, so that the ion dispatching device outputs the ions to the mass analyzer according to the ion mass-to-charge ratio or ion mobility.

25. A controller for scheduling ions for analysis by a mass analyzer within a range of mass-to-charge ratios of interest, the controller being configured to: Obtain the predicted intensity and associated mass-to-charge ratio of ions across the mass range of interest; This allows ions to be input into the ion dispatching device; Based on the mass-to-charge ratio or ion mobility of the ions, the ions are output from the ion dispatching device to the mass analyzer; and The ions are selectively attenuated based on their predicted intensity and associated mass-to-charge ratio.

26. A mass spectrometry system for analyzing ions within a range of mass-to-charge ratios of interest, the mass spectrometry system comprising: An ion dispatching device, configured to receive ions and output ions to a mass spectrometry system; The mass spectrometry system is configured to perform the method according to any one of claims 1.

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