Beam homogenization with trapped ion processing of discrete ion packets

Abstract

In one aspect, a mass spectrometer is disclosed, the mass spectrometer comprising: an ion capture device; at least one pressurized ion guide configured to allow an adjustable axial field to be established therein such that the axial field can be adjusted to operate the pressurized ion guide in either of fast and slow operating settings; a mass analyzer for receiving the ions passing through the pressurized ion guide and configured to provide mass analysis of the received ions; and a controller in communication with the at least one pressurized ion guide to cause adjustment of the axial field to switch an operational setting of the pressurized ion guide between a fast and a slow operational setting based on an operational mode of the mass spectrometer.

Description

[0001] Related applications

[0002] This application claims priority to U.S. Provisional Application No. 63 / 462,652, filed April 28, 2023, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This disclosure relates to mass spectrometry, and more specifically, to methods and systems for enhancing the dynamic range of signal acquisition in mass spectrometry. Background Technology

[0004] This teaching generally relates to systems and methods for mass spectrometry, and more specifically, to such systems and methods for enhancing the dynamic range in mass spectrometry analysis, in which fragment ions are generated by the dissociation of precursor ions (e.g., via electronically activated dissociation).

[0005] Mass spectrometry (MS) is an analytical technique used to determine the structure of chemical substances for testing, with both qualitative and quantitative applications. MS can be used to identify unknown compounds, determine the atomic composition of molecules, determine the structure of compounds by observing compound fragmentation, and quantify the amount of a specific compound in a mixed sample. Since mass spectrometry detects chemical entities as ions, a conversion from the analyte to charged ions must occur. Summary of the Invention

[0006] In one aspect, a mass spectrometer is disclosed, comprising: an ion trapping device; at least one pressurized ion guide configured to allow an adjustable axial field (e.g., a DC axial field) to be established therein, such that the axial field can be adjusted to operate the pressurized ion guide in either a fast operating setting or a slow operating setting; a mass analyzer for receiving ions through the pressurized ion guide and configured to provide mass analysis of the received ions; and a controller communicating with the at least one pressurized ion guide to induce adjustment of the axial field, thereby switching the operating setting of the pressurized ion guide between a fast operating setting and a slow operating setting based on the operating mode of the mass spectrometer.

[0007] In some embodiments, the operating mode of the mass spectrometer is characterized by the inter-precursor switching time associated with the analysis of different precursor ions introduced into the mass spectrometer during a single mass analysis run.

[0008] In some embodiments, the controller is configured to operate the ion guide in a fast operation setting when the inter-precursor switching time is less than about 2 ms. Furthermore, in some embodiments, the controller is configured to operate the ion guide in a slow operation setting when the inter-precursor switching time is greater than about 5 ms.

[0009] In some embodiments, the ion trapping device is configured to operate as a flow-through ion guide.

[0010] In some embodiments, where the capture device operates as a flow-through ion guide (also referred to herein as a flow-through device), the controller can be configured to induce adjustment of the axial field such that ions passing through the pressurized ion guide remain substantially (and preferably completely) intact during the rapid operation setup of the ion guide.

[0011] In various embodiments (including embodiments in which the capture device operates as a flow-through ion guide), the controller can be configured to induce adjustment of the axial field in the slow operating setting of the ion guide in order to prevent saturation of the ion detector of the mass analyzer.

[0012] In various embodiments (including embodiments in which the capture device operates as a flow-through ion guide), the controller can be configured to induce modulation of the axial field in a slow operating setting of the ion guide in order to prevent charge distortion effects in one or more mass spectra generated based on data acquired by a mass analyzer.

[0013] In various embodiments, the capture device can be configured to operate as an ion trap to generate multiple ion packets that are different in time. In some such embodiments, the default settings for the operating state of the ion guide can be set based on the time of ion packet generation. For example, in some such embodiments, the ion guide can operate in a default slow operating setting, except for the last set of ion packets (e.g., the last ion packet), in which case the ion guide's operating settings can be switched to a fast operating setting. For example, the controller can be configured to adjust the axial field to select the slow operating setting of the ion guide for one or more ion packets generated during a first data acquisition interval, and to select the fast operating setting of the ion guide for one or more ion packets generated during a second data acquisition interval.

[0014] The mass spectrometer may include a DC voltage source, operated under the control of a controller, for applying at least one DC voltage to an ion guide to generate an adjustable axial field. In some embodiments, the controller may be configured to apply a minimum DC voltage at which the axial field causes ion packets arriving at the mass analyzer to exhibit time broadening (e.g., characterized by full width at half maximum (FWHM)) below a target threshold (e.g., 10 ms). Furthermore, in some such embodiments, the applied voltage may be selected such that the ratio of the time interval between consecutive ion packets arriving at the mass analyzer to the time broadening (e.g., average time broadening) of the ion packets is in the range of about 0 to about 5 ms. As an example, the controller may be configured to determine the minimum DC voltage by continuously increasing the DC voltage applied to the ion guide and monitoring the time broadening of ions arriving at the mass analyzer until a target time broadening (e.g., target average time broadening) and / or a target ratio of the time interval between consecutive ion packets to their time broadening (e.g., their average time broadening) is achieved.

[0015] In some embodiments, the ion guide may include multiple rods arranged in a multi-pole configuration, such as a quadrupole, hexapole, or octupole configuration. In some such embodiments, an RF voltage may be applied to the rods to induce radial confinement of ions, and one or more DC voltages may be applied to the rods to generate a desired axial potential within the ion guide.

[0016] In some embodiments, the mass spectrometer may include a ToF mass analyzer.

[0017] In the practice of this teaching, a variety of ion trapping devices can be used. By way of example, ion trapping devices can be ion-particle reaction devices, ion-ion reaction devices, and ion-radiation reaction devices, such as electron activated dissociation (EAD) devices, proton transfer devices, UV or infrared dissociation devices.

[0018] In some embodiments, the pressurized ion guide can be maintained at a pressure in the range of about 1 mTorr to about 10 mTorr.

[0019] In a related aspect, a method for performing mass spectrometry is disclosed, the method comprising: sequentially introducing ions generated by ionization of a plurality of samples into an ion trapping device; and introducing ions exiting the ion trapping device into a pressurized ion guide, the pressurized ion guide being configured to allow the establishment of an adjustable axial field therein such that the axial field can be adjusted to switch the operation setting of the pressurized ion guide between a fast operation setting and a slow operation setting based on the operating mode of the mass spectrometer.

[0020] As an example, the operating mode of a mass spectrometer can be characterized by the precursor switching time associated with the continuous mass analysis of different precursors during a single mass analysis run.

[0021] In some embodiments, the axial field can be adjusted to operate the pressurized ion guide in a fast operation setting when the precursor switching time is less than about 2 ms, and in a slow operation setting when the sample switching time is greater than 5 ms.

[0022] In some embodiments, the ion guide may operate as an ion flow-through ion guide, wherein ions are not trapped but pass through the ion guide while undergoing, for example, deceleration or acceleration. In some other embodiments, the ion guide may operate as an ion trap, wherein ions are trapped and may undergo processes such as ion-particle reactions, ion-ion reactions, and ion-radiation reactions, resulting in the production of product ions.

[0023] As described above, the ion trapping device can operate as a flow-through ion guide or as an ion trap. In some embodiments (including those in which the ion guide operates as a flow-through device), the axial potential can be adjusted such that ions passing through the ion trapping device remain substantially fragmented. Furthermore, in some embodiments, when the ion guide operates in a slow operating mode, the axial potential can be adjusted to prevent saturation of the ion detector of the mass analyzer. In some embodiments (including those in which the ion trapping device operates as an ion flow-through device), the axial field can be adjusted to prevent charge distortion effects in one or more mass spectra generated based on data acquired by the mass analyzer.

[0024] As described above, in some embodiments, the ion trapping device can operate as an ion trap to generate, for example, multiple ion packets that are different in time, including product ions generated by processing precursor ions introduced into the ion trap. In some such embodiments, the operating settings of the pressurized ion guide can be selected based on the generation time of the different ion packets. By way of example, in some such embodiments, a slow operating setting of the ion guide is selected for one or more ion packets generated during a first data acquisition interval; while a fast operating setting of the ion guide is selected for one or more ion packets generated during a second data acquisition interval, wherein the second data acquisition interval is after the first data acquisition interval.

[0025] In a related aspect, a method for performing mass spectrometry is disclosed, comprising: generating multiple ion packets within multiple different time periods, wherein each ion packet includes product ions associated with the same precursor ion species; introducing each ion packet into a pressurized ion guide; and subjecting each ion packet to an axial potential in the pressurized ion guide. During a data acquisition period, each ion packet passing through the pressurized ion guide is introduced into a downstream time-of-flight (ToF) mass analyzer to generate an ion detection signal corresponding to the ions in that ion packet, and adjusting the axial potential to decelerate at least a first ion packet generated within at least a first time period and to accelerate at least a second ion packet generated within at least a second time period, wherein the at least second time period follows at least the first time period.

[0026] In some cases, at least a first time period overlaps with a first portion of the data acquisition period, and at least a second time period overlaps with a second portion of the data acquisition period, wherein the second portion of the data acquisition period follows the first portion of the data acquisition period. In some such embodiments, the second ion packet includes a plurality of temporally consecutive ion packets. In some cases, temporally consecutive ion packets may include ion packets generated in the last time period of a plurality of different time periods. In some cases, at least the second ion packet includes the last ion packet of a plurality of ion packets.

[0027] In some embodiments, each ion pack can be generated by trapping precursor ions in an ion trap and subjecting the trapped precursor ions to an ion-particle reaction, an ion-ion reaction, or an ion-radiation reaction to generate product ions. In some cases, product ions can be generated via the fragmentation of the precursor ions. In some embodiments, the reaction undertaken by the ions can cause the trapped precursor ions to fragment to generate product ions. By way of example and without limitation, these reactions can include any one of electron-activated dissociation, ultraviolet dissociation, infrared multiphoton dissociation, electron transfer dissociation, and proton transfer reactions.

[0028] In various embodiments, the pressurized ion guide may include a plurality of poles arranged in a multi-pole configuration (e.g., quad, hex, or octagonal configuration). In some such embodiments, a first DC voltage is applied to at least one of the multipole poles to facilitate the generation of an axial DC potential. The pressurized ion guide may also include a plurality of auxiliary electrodes inserted into the plurality of multipole poles. In some such embodiments, a second DC voltage may be applied to at least one of the auxiliary electrodes such that the combination of the first DC voltage and the second DC voltage generates an axial DC potential.

[0029] In a related aspect, a method for performing mass spectrometry is disclosed, comprising: generating a first plurality of ion packets during a first time period, wherein each ion packet includes product ions associated with a first precursor ion species; introducing the first plurality of ion packets into a pressurized ion guide; subjecting the first plurality of ion packets to an axial DC potential in the pressurized ion guide to decelerate the ions in the first plurality of ion packets, thereby generating a first plurality of decelerated ion packets. During a first data acquisition period, introducing the first plurality of decelerated ion packets into a time-of-flight (ToF) mass analyzer to generate ion detection signals corresponding to these product ions. During a second time period, generating a second plurality of ion packets, wherein each of the second plurality of ion packets includes product ions corresponding to a second precursor species. The first data acquisition period and the second time period partially overlap, such that data acquisition associated with the first plurality of decelerated ion packets continues during a portion of the second time period, during which a subset of the second ion packets is generated.

[0030] During the second data acquisition period, a second plurality of ion packs are introduced into the TOF mass analyzer to generate ion detection signals associated with product ions (e.g., fragment ions) in the second plurality of ion packs. In some embodiments, the product ions in the second plurality of ion packs are decelerated by passing through a pressurized ion guide before being introduced into the TOF mass analyzer.

[0031] In various embodiments, the step of generating the first plurality of ion packs includes capturing ions corresponding to a first precursor ion species and subjecting at least a portion of the captured ions to an ion-particle reaction, an ion-ion reaction, or an ion-radiation reaction to generate product ions. Furthermore, the step of generating the second plurality of ion packs includes introducing ions corresponding to a second precursor ion species into an ion trap and subjecting at least a portion of the captured ions to an ion-particle reaction, an ion-ion reaction, or an ion-radiation reaction to generate product ions. By way of example, the reaction may include any one of electron-activated dissociation, ultraviolet dissociation, infrared multiphoton dissociation, electron transfer dissociation, and proton transfer dissociation.

[0032] A further understanding of the various aspects of this teaching can be obtained by referring to the following detailed description in conjunction with the accompanying drawings, which are briefly described below. Attached Figure Description

[0033] Figure 1 An example of the typical arrival time distribution of fragment ions generated via the EAD reaction performed in an ion dissociation device is depicted.

[0034] Figure 2 An example of EAD spectra for single-charged lipid species is shown, where the ratio of typical fragment intensity to precursor intensity is less than 1 / 500;

[0035] Figure 3 An example of unprocessed data collected around a signal associated with a high abundance precursor is shown;

[0036] Figure 4A An example of a mass spectrum of a sample acquired under high-throughput conditions is shown;

[0037] Figure 4B This shows the results obtained under low-throughput conditions and... Figure 4A Mass spectra of the same samples in the sample;

[0038] Figure 4C The mass spectra of the same sample obtained under “slow” ion propagation conditions are shown.

[0039] Figure 4D The mass spectra of the same sample obtained under “fast” ion propagation conditions are shown.

[0040] Figure 4E The distribution of arrival times of multiple ion packets at the ToF mass analyzer is shown;

[0041] Figure 5A It is a flowchart depicting the various steps of a method for performing a mass spectrometry method according to an embodiment of the present teaching;

[0042] Figure 5B It shows the combination with Figure 5A The flowchart discusses an example of a timeline diagram associated with the implementation of the mass spectrometry method;

[0043] Figure 6A This is a partial schematic view of an ion guide applicable to various embodiments, which includes a set of quadrupoles and a plurality of auxiliary electrodes inserted between these poles;

[0044] Figure 6B This is a partial schematic view of an ion guide applicable to various embodiments, which includes a segmented quadrupole assembly to which RF voltage and DC voltage can be applied;

[0045] Figure 6C This is a partial schematic view of an ion guide applicable to various embodiments, which includes multiple stacked rings to which a DC voltage can be applied to generate a DC axial potential;

[0046] Figure 6D This is an example of a traveling voltage wave that can be used, according to this teaching, to slow down or accelerate ions as they pass through an ion guide;

[0047] Figure 7 It is a flowchart depicting various steps of a method according to an embodiment of this teaching;

[0048] Figure 8AThis is a timing diagram of ion processing in one embodiment of this teaching;

[0049] Figure 8B This is a timing diagram of ion processing in one embodiment of this teaching;

[0050] Figure 9A A mass spectrometer according to one embodiment of the present teachings is schematically depicted;

[0051] Figure 9B yes Figure 9A A partial view of the mass spectrometer depicted in the image;

[0052] Figure 9C It describes the conventional axial DC potential and in Figure 9A and Figure 9B A diagram illustrating an example of the axial DC potential generated in various components of a mass spectrometer according to one embodiment;

[0053] Figure 10A , Figure 10B , Figure 10C and Figure 10D The diagram shows the arrival time distribution of multiple temporally distinct ion packets generated in the EAD chamber as they reach the TOF mass analyzer located downstream of the EAD chamber, where L1 represents LINAC1 (pulling ions) and L2 represents LINAC2 (pushing ions), illustrating that a slower axial gradient (smaller L2) results in a larger time broadening within the ion packets; and

[0054] Figure 11 This is a diagram depicting an implementation example of a controller applicable to the practice of this teaching. Detailed Implementation

[0055] It will be understood that, for clarity, the following discussion will set forth various aspects of embodiments of the applicant's teachings, while omitting certain specific details where convenient or appropriate to do so. For example, the discussion of the same or similar features in alternative embodiments may be somewhat simplified. For the sake of brevity, well-known ideas or concepts may also not be discussed in detail. Those skilled in the art will recognize that certain embodiments of the applicant's teachings may not require certain details specifically described in each implementation, which are set forth herein only to provide a thorough understanding of the embodiments. Similarly, it will be clear that modifications or alterations to the described embodiments may be made based on common general knowledge without departing from the scope of this disclosure. The following detailed description of the embodiments should not be construed as limiting the scope of the applicant's teachings in any way.

[0056] As used herein, the terms “about” and “substantially equal to” refer to variations in numerical quantities that may occur, for example, through real-world measurement or processing procedures, unintentional errors in these procedures, differences in the manufacture, origin, or purity of the composition or reagent. Generally, the terms “about” and “substantially” as used herein mean 10% greater or less than the stated value or range of values, or complete conditions or states. For example, a concentration value of about 30% or substantially equal to 30% could mean a concentration between 27% and 33%. These terms also refer to variations that are considered equivalent by those skilled in the art, provided that such variations do not cover known values ​​practiced in the prior art.

[0057] As used herein, the term “and / or” includes any and all combinations of one or more associated listed items and may be abbreviated to “ / ”.

[0058] As used herein, the term "ion trapping device" refers to a device capable of receiving ions and subjecting them to electric and / or electromagnetic fields (e.g., for inducing radial confinement of the ions and / or modulating their kinetic energy), from which those ions and / or their product ions may exit. An ion trapping device may operate in a flow-through mode (also referred to herein as a through-mode), wherein ions remain substantially intact (e.g., without fragmentation) as they pass through the ion trapping device. Alternatively, an ion trapping device may operate as an ion trap, wherein ions may be temporarily trapped and optionally undergo reactions such as ion-particle reactions, ion-ion reactions, and / or ion-radiation reactions to generate product ions (e.g., fragment ions).

[0059] As used herein, the term “electron activated dissociation” and its abbreviation “EAD” refer to electron-mediated processes that lead to the dissociation of species. Some examples of EAD reactions include electron capture dissociation (ECD), such as thermal ECD, negative ECD, electron collision dissociation (EID), electron impact excitation of organic ions (EIEIO), and electron de-electron dissociation of both positively and negatively charged precursor ions.

[0060] Intraspectral dynamic range is a crucial characteristic of mass spectrometers, defined as the ratio of the lowest detectable mass signal to the highest detectable mass signal in a single spectrum. In time-of-flight (ToF) mass analyzers, the lowest detectable signal intensity is limited by the noise level, while the highest detectable signal intensity is often limited by the number of ions that can be detected simultaneously in a single ion detection event. Furthermore, the frequency of ToF extractions performed by ToF mass analyzers is typically very high (e.g., greater than 10 kHz), compared to the typical ion accumulation time of approximately 10 ms (e.g., in an ion trap). For example, in some cases, each ToF spectrum can contain at least 100 ToF extractions, where the upper limit of detection is related to the product of the maximum number of ions that the detection system can handle and the number of ToF extractions.

[0061] However, in some cases, the number of ToF extractions that include a mass signal is not equal to the total number of ToF extractions. In other words, in some cases, not every ToF extraction includes a mass signal. In this case, the multiplier associated with the number of ToF extractions corresponds to the number of ToF extractions that include one or more mass signals. This can happen, for example, when ions are captured and released prior to mass analysis in a ToF mass analyzer, because the frequency of capture / release cycles is often much lower than the speed of the ToF analyzer.

[0062] This capture / release setup is particularly useful in MS / MS analysis, where analytes can be probed via ion-ion reactions, ion-particle reactions, and / or ion-radiation reactions such as ultraviolet photodissociation (UVPD), infrared multiphoton dissociation (IRMPD), electron activated dissociation (EAD), electron transfer dissociation (ETD), and proton transfer reaction (PTR). In this case, the effective number of ToF pulses will be primarily defined by the capture / release cycle frequency, which in turn may impair the intraspectral dynamic range. The need for extended reaction times can stem from the generally poor fragmentation / reaction efficiency inherent in such fragmentation techniques. Consequently, the intraspectral dynamic range is often lower in this case than in beam-collision induced dissociation techniques or those where fragmentation does not occur, such as in ToF MS acquisition.

[0063] In the form of an example, Figure 1 The typical arrival time distribution of fragment ions generated by the EAD reaction performed in the ion dissociation device at the downstream ToF mass analyzer is depicted. This data is obtained using data described in more detail below. Figure 9A and Figure 9BThe mass spectrometer shown is schematically illustrated. In this example, a single charged ion underwent simultaneous loading and reaction for 30 ms, and the ToF mass analyzer was pulsed at a frequency of 13.5 kHz. In this example, less than 30% of the ToF extraction contained any signal, with 90% of the total signal contained in approximately 10% of the ToF extraction.

[0064] In some fragmentation techniques (such as EAD), the total number of possible fragment ion types can be high. Furthermore, in EAD, probing for single-charged ions can lead to precursor-fragment neutralization reactions, which can result in a high ratio of residual precursor ions to fragment ions under optimal reaction conditions. In the case of multi-charged ions, secondary fragmentation can occur in addition to product neutralization, resulting in internal fragment ions that do not provide information. This difference in precursor and fragment abundance can further complicate the tuning of the dynamic range within the spectrum, as it requires the co-detection of strong residual precursor ions and low-intensity fragment ions. To illustrate, Figure 2 An example of EAD spectra for a single-charge lipid species is shown, where the ratio of typical fragment intensity to precursor intensity is less than 1 / 500. This difference between precursor and fragment abundance can further exacerbate the potential problems associated with limited intraspectral dynamic range.

[0065] One drawback of the inherently poor intraspectral dynamic range associated with EAD is that data acquisition at very high ion loads (which is generally preferred for dexterous detection of low-abundance fragment ions) can lead to undesirable data artifacts. To illustrate, Figure 3 An example of unprocessed data acquired around a signal associated with a high-abundance precursor is shown, exhibiting a clipped precursor signal, followed by a silent downswing (no signal detected), and then a significantly elevated baseline that remains above a threshold for more than 10 microseconds. The latter problem (the clipped precursor signal) can occur in conventional data acquisition systems tuned for very high data rates and often include data filtering as a first data processing step. This data filtering is used to detect data points above a threshold and to form data packets based on these points, often supplemented with a limited number of neighboring points. Traditionally, such data packets are associated with a single detection event, ideally corresponding to the detection of ions or groups of ions from the same precursor ion species.

[0066] exist Figure 3 In this study, an example of such a data packet was labeled as a low-abundance ion. However, this conventional data processing presents challenges in handling data with elevated baselines, where wide transport packets may contain multiple detection events. Furthermore, baseline recovery can introduce noise peak artifacts, such as at points where the baseline slowly crosses the discriminator's threshold. Both of these phenomena can lead to undesirable data artifacts.

[0067] Another problem that may arise in EAD (or any other capture technique) MS / MS analysis of high-charge proteins is that total ionic charge may degrade the performance of the mass analyzer when it exceeds a threshold. Figure 4A and Figure 4B An example of this phenomenon is shown, where mass spectra of the same sample were obtained under both high and low ion flux conditions. The mass spectrum derived from the high ion flux conditions shows significant peak broadening.

[0068] It has been found that inhomogeneities in the ion beam can be a cause of this problem when performing MS / MS analyses, such as EAD fragmentation via precursor ions. Conventionally, fragment ions are accelerated by an axial DC potential as they pass through a downstream pressurized ion guide, such as a collision chamber (e.g., the Q2 chamber discussed below). In various embodiments, the typical pressure within such a pressurized ion guide can, for example, range from about 1 mTorr to about 10 mTorr.

[0069] One way to address this inhomogeneity is to slow down the ions in the region between the ion trap and the ToF mass analyzer. As an example, this "slowing down" of the ions can be achieved by applying neutral, reverse, or slightly positive voltages to a pair of tapered electrodes (also referred to herein as LINAC electrodes) and matching the potentials across other components, for example, as discussed in more detail below. Here, a reverse voltage produces an axial potential opposite to the direction of ion motion, a neutral voltage produces no axial potential, and a slightly positive voltage produces an axial potential along the ion motion, which can be no more than one-third of the typical axial potential corresponding to a "positive" voltage. For example, a slightly positive potential would correspond to a total voltage drop of less than 1V on the ion guide. As an example, Figure 4C and Figure 4D Examples of mass spectra of propagating ions acquired under slow and fast ion propagation conditions are shown. Data acquired under slow ion propagation conditions exhibit better quality (e.g., narrower linewidths) than data acquired under fast ion propagation conditions. Similar strategies can also be used to mitigate the space charge effect in MS / MS analysis of highly charged proteins.

[0070] However, a drawback of this approach (i.e., reducing ion propagation speed) is that it can adversely affect system throughput. For example, LC / MS (liquid chromatography / mass spectrometry) is often used to analyze complex mixtures. In such analyses, thousands of analytes need to be analyzed within short timeframes (e.g., per minute of analysis). Because conventional mass spectrometers are sequential devices, analyzing thousands of analytes requires scheduling separate time intervals for analyzing co-eluted analytes. Mass spectrometric experiments measuring ions corresponding to one or more such analytes are sometimes referred to as transitions, following the nomenclature of targeted MRM analysis, where each precursor has a transition to a product ion, and this transition is monitored. It is convenient to extend this term to other conventional mass spectrometric analyses (e.g., data-correlated or data-independent analyses). In many cases, it is important to ensure that crosstalk between transitions is negligible (e.g., <1%, indicating that ions from a transition contribute less than 1% to the analysis associated with subsequent transitions).

[0071] To achieve this goal, after data acquisition for a conversion is completed, the ion guide of the mass spectrometer often removes any remaining ions corresponding to that conversion. The next acquisition begins after a period of ion refilling. Typically, the time required for ion optics equilibration is an undesirable overhead, reducing the total number of conversions that can be measured. To reduce this overhead, the different components of the ion optics are configured to drive ions as quickly as possible while maintaining the integrity of the transported ions. The pressurized ion guide, in which ions tend to lose their kinetic energy through collisions with the bath gas, is considered a bottleneck for rapid ion movement.

[0072] In some pressurized ion guides, an axial DC gradient is established to assist ion movement along the ion guide. For some of these fast ion guides, transition times on the order of 1 ms have been observed, which can result in a total switching time of less than 2 ms between conversions. This gradient is often set in smooth increments to prevent ions from acquiring high kinetic energies, which could lead to ion fragmentation and loss upon collision with the bath gas. This contrasts with other methods, such as altering the collision energy at the inlet of the pressurized ion guide, which induces ion fragmentation and is often used to assist the conversion from precursor ions to product ions.

[0073] Traditionally, based on the recognition that ions need to be driven as quickly as possible while avoiding unwanted fragmentation, modern mass spectrometers employ a fast axial DC gradient, i.e., a DC gradient that accelerates the movement of ions. However, this approach can lead to potential loss of sensitivity and a decrease in data quality, for example, due to a reduction in the dynamic range within the spectrum.

[0074] As recognized in this disclosure, operating the pressurized ion guide of a mass spectrometer in a slow operating setting is advantageous for at least a portion of the data acquisition period associated with mass analysis, to provide significantly improved data quality, although at the cost of some increase in overhead time, particularly for mass analysis in which ions are captured prior to analysis. By way of example, but not limiting, in some embodiments, the transition time of the pressurized ion guide in a slow operating setting can be between about 5 ms and about 20 ms, which can facilitate ion packet diffusion and provide more favorable detection conditions. In various embodiments, by way of example, the typical pressure within such a pressurized ion guide can be in the range of about 1 mTorr to about 10 mTorr.

[0075] In the form of an example, Figure 4E Multiple ion packets detected via a Time-of-Flight (ToF) mass analyzer are shown, where the ion packets are slowed down as they pass through the collision chamber. The last ion packet is only partially captured, and a longer data acquisition period will be required to detect the entire last ion packet. As described below, in some embodiments, the last ion packet can be accelerated to prevent the loss of mass data due to incomplete detection (or lack of detection) of the ion packet.

[0076] As discussed in more detail below, in various embodiments, the axial DC potential in the collision chamber downstream of the ion fragmentation apparatus can be switched between ion deceleration potential and ion acceleration potential in sync with the fragmentation cycle of a particular type of precursor ion to, for example, provide enhanced dynamic range and flux.

[0077] For example, in some of these embodiments in which a series of ion packets corresponding to a specific precursor ion species are generated, all ion packets except the last one in the series can be decelerated, while the last ion packet can be accelerated to improve both the dynamic range and flux of the system.

[0078] In some embodiments, the data acquisition period may be offset relative to the corresponding fragmentation period, in conjunction with the deceleration of the ion pack, to improve both the dynamic range and the flux of the system.

[0079] refer to Figure 5AThe flowchart illustrates that, in one embodiment of the method for performing mass spectrometry according to this teaching, mass analysis of ions corresponding to precursor ion species (i.e., ions of the same precursor ion species) can be performed by capturing a portion of ions in an ion trap, fragmenting the captured ions to generate multiple fragment ions, slowing or accelerating the fragment ions by pressurizing an ion guide (e.g., a collision chamber), and introducing the slowed / accelerated ions into a time-of-flight (ToF) mass analyzer to generate ion detection signals during multiple mass analysis cycles during a data acquisition period (also referred to herein as a data acquisition interval), wherein the ion detection signals can be processed to generate a mass spectrum of the ions.

[0080] In various embodiments, the deceleration or acceleration of ions as they pass through a pressurized ion guide can be achieved via an axial DC potential generated within the pressurized ion guide. In some embodiments, this axial DC potential can be adjusted to switch from an ion deceleration potential to an ion acceleration potential during one or more final cycles of mass analysis of precursor ion species. By way of example, the default setting for the axial DC potential can be a deceleration DC potential to “slow down” the ions introduced into the pressurized ion guide. During one or more final cycles of mass analysis, the axial DC potential can be switched to an acceleration DC potential. By way of example, the axial DC potential can be switched to an acceleration DC potential during the last (final) cycle of mass analysis to, for example, ensure that fragment ions generated during the last cycle reach the downstream ToF mass analyzer before the end of the data acquisition period.

[0081] By way of example, but without limitation, the decelerating axial DC potential can range from about 0 to about 2 volts on the ion guide, while the accelerating axial DC potential can range from about 3 volts to about 5 volts, and can have the opposite polarity to the decelerating axial DC potential. In some embodiments, the deceleration of ion fragments can be achieved primarily via collisions with molecules of a background gas present in a pressurized ion guide (e.g., a collision chamber), while in some other embodiments, the axial electric field associated with the axial DC potential is the primary mechanism for slowing down the ions. In the latter case, in various embodiments, collisions with the bath gas or broadening due to space charge are responsible for the diffuse ion pack.

[0082] Figure 5B This is shown in conjunction with the above. Figure 5A An example of a timing diagram associated with the implementation of the discussed method is provided. This timing diagram shows that in each data acquisition cycle, multiple ion packets generated during the first part of the data acquisition cycle are decelerated (i.e., these ion packets are slowed down), while the last ion packet is accelerated to avoid incomplete data collection associated with that ion packet, thereby improving dynamic range and increasing system throughput.

[0083] In some embodiments, a pressurized ion guide (e.g., a collision chamber) may include multiple rods arranged in a multi-pole configuration (e.g., a quadrupole configuration). As an example, an axial DC potential within the pressurized ion guide may be established using a voltage offset between the multi-pole rods and the rod associated with an upstream ion trap. As an example, the upstream ion trap may be an electron dissociation chamber comprising a pair of L-shaped electrodes axially offset relative to each other to form an ion trap region therebetween, where ions can be captured and undergo fragmentation (e.g., via electron-activated dissociation).

[0084] A DC voltage source operating under the control of a controller can generate a DC offset voltage between the rods of the pressurized ion guide and the rods of the upstream ion trap to decelerate or accelerate ions entering the collision chamber. Furthermore, as discussed in more detail below, a pair of longitudinally tapered auxiliary electrodes (also referred to herein as LINAC electrodes) can also be positioned within the pressurized ion guide. The voltage offset applied between the two pairs of LINAC electrodes can also contribute to the generation of an axial DC potential within the pressurized ion guide. In other words, the offset voltage between the rods of the pressurized ion guide and the rods of the upstream ion trap, as well as the voltage across the LINAC electrode pairs, can synergistically generate an axial DC potential within the pressurized ion guide. In various embodiments, the axial DC potential within the pressurized ion guide is adjusted by regulating the DC offset voltage between the rods of the pressurized ion guide and the rods of the upstream ion trap, rather than the DC offset voltage between the LINAC electrode pairs, so that the axial DC potential switches between deceleration and acceleration potentials.

[0085] In some other embodiments, other types of ion guides may be employed, such as segmented multi-electrode, stacked ring ion guides, or ion guides with segmented auxiliary electrode groups. In some embodiments, an axial field is generated by applying various DC potentials to each segment electrode or ring electrode. In some other embodiments, ions are propelled toward or away from the mass analyzer by applying traveling waves to the segments of the ion guide.

[0086] For example, Figure 6AThis is a partially schematic view of an ion guide 1000 according to one embodiment. The ion guide 1000 includes a set of quadrupoles 1002 (two of which are visible in the figure), to which an RF voltage can be applied to generate a radially confining field for guiding ions through a channel provided between the quadrupoles. The ion guide 1000 also includes five pairs of auxiliary electrodes 1004a, 1004b, 1004c, 1004d, and 1004e, which are interposed between the quadrupoles and axially separated from each other in pairs. A DC voltage can be applied to these auxiliary electrodes to generate a field gradient along the longitudinal axis of the ion guide for accelerating or decelerating ions passing through the ion guide. More specifically, in this example, multiple DC voltage sources (DC1, DC2, DC3, DC4, and DC5) provide different DC voltages to the auxiliary electrode pairs, such that the DC potential difference between those electrode pairs generates a DC axial potential.

[0087] In a further manner, Figure 6B An example of a segmented quadrupole ion guide 2000 is shown, which can be used as a pressurized ion guide in various embodiments of this teaching. The segmented quadrupole ion guide 2000 includes three quadrupole groups 2001, 2002, and 2003, arranged in series relative to each other such that they share a common longitudinal axis. More specifically, each quadrupole group includes four rods arranged in a quadrupole configuration. Multiple axial gaps separate each quadrupole group from adjacent quadrupole groups. In this embodiment, the axial gaps between adjacent quadrupole groups are uniform, while in other embodiments, these gaps may be non-uniform (i.e., they may have different values). In some embodiments, the gaps may range, for example, from about 0.1 mm to about 10 mm.

[0088] Radio frequency (RF) source 2004 is capacitively coupled to the poles of quadrupole groups 2001, 2002, and 2003 via capacitors 2006a, 2006b, 2006c, 2006d, 2006e, and 2006f to apply an RF voltage to these poles. In some embodiments, the frequency of the RF voltage applied to the poles of the quadrupole group may be, for example, in the range of about 200 kHz to 10 MHz, and the amplitude may be in the range of about 100 V to about 10 kV.

[0089] Furthermore, in this embodiment, multiple DC voltage sources 2008a, 2008b, and 2008c are electrically coupled to the rods of the quadrupole assembly via resistors 2010a / 2010b, 2012a / 2012b, and 2014a / 2014b. The DC voltage sources can apply DC voltages to the rods of the quadrupole assembly to, for example, modulate the energy of electrons within the interaction module. In some embodiments, the DC voltage applied to the rods of the quadrupole assembly can be, for example, in the range of about 0 to about 100 volts (in embodiments where negative ions are detected, a negative voltage is used). Additionally, DC voltages can be applied to electrodes 2001 and 2003 to help trap ions within the electron-ion interaction module.

[0090] The controller 2016, which communicates with the RF source 2004 and the DC voltage source, can control the application of RF voltage and / or DC voltage to the poles of the quadrupole group. For example, the controller 2016 can control the application of RF voltage to the poles of the quadrupole group such that the phase of the voltage applied to any pole in the group is opposite to the phase of the RF voltage applied to the corresponding pole in an adjacent group.

[0091] In another example, Figure 6C An ion guide 3000 is shown, comprising multiple stacked rings 3002, 3003, 3004, 3005, 3006, 3007, and 3008, each ring having a central opening through which ions can pass. An RF voltage is applied to the ion rings such that the RF voltages applied to two adjacent ion rings are 180 degrees out of phase with each other. Furthermore, multiple DC voltage sources DC1, DC2, DC3, DC4, DC5, and DC6 apply DC voltages to the ion rings to generate axial potentials for accelerating or decelerating ions passing through the openings of the ion rings.

[0092] exist Figure 6D In another example, schematically illustrated, a traveling wave voltage applied to multiple electrodes (e.g., the ring discussed above) can be used to accelerate or decelerate ions passing through the ion guide.

[0093] In some embodiments, during a data acquisition period associated with a specific precursor ion species, ions are accelerated only during the last mass analysis cycle associated with that specific precursor ion species. In some such embodiments, ions (i.e., fragment ions and any residual precursor ions that may remain after fragmentation) are decelerated, i.e., their propagation velocity is reduced, during one or more mass analysis cycles associated with a portion of the terminal portion of one or more final cycles during which mass analysis is performed, extending from the beginning of the data acquisition period to the end of the data acquisition period. By way of example, in various embodiments, the default setting of the axial DC potential causes ions to be decelerated as they pass through the collision chamber, wherein the default setting of the last cycle (final cycle) of the mass analysis for the analyzed precursor ion species is changed to accelerate ions (fragment ions and any residual precursor ions) in that final cycle.

[0094] In various embodiments, after terminating the data acquisition period for quality analysis of a precursor ion species, another data acquisition period for quality analysis of another precursor ion species is initiated, wherein multiple cycles of quality analysis are performed in the manner discussed above.

[0095] In related aspects, a method for performing mass spectrometry is disclosed, wherein the data acquisition period associated with the detection of fragment ions of different precursor ion species is offset relative to the period of fragmentation of those precursor ion species, in order to, for example, improve data acquisition efficiency. As an example, in some methods, data acquisition for the detection of fragment ions associated with one precursor ion species continues while fragment ions associated with different precursor ion species are being generated.

[0096] refer to Figure 7 The flowchart illustrates that, in one embodiment of this method for performing mass spectrometry, a first plurality of ion packets are generated during a first time period, wherein each ion packet comprises fragment ions associated with a first precursor ion species. The first plurality of ion packets are introduced into a collision chamber and subjected to an axial DC potential within the collision chamber to decelerate the ions within the ion packets, thereby generating a first plurality of decelerated ion packets.

[0097] During the first data acquisition period, the first plurality of decelerating ion packs are introduced into the time-of-flight (ToF) mass analyzer to generate ion detection signals corresponding to the fragment ions within the first plurality of ion packs.

[0098] During the second time period, a second plurality of ion packets are generated, wherein each of the second plurality of ion packets includes fragment ions associated with a second precursor ion species that is different from the first precursor ion species.

[0099] The first data acquisition period partially overlaps with the second time period, such that data acquisition associated with the first plurality of decelerating ion packets continues during a portion of the second time period, within which a subset of the second ion packets is generated. By way of example, the first data acquisition period associated with the first plurality of ion packets can continue while another precursor ion species undergoes fragmentation. In other words, in various embodiments of this aspect of the teaching, the data acquisition period associated with the precursor ion species (i.e., the data acquisition period in which fragment ions associated with the precursor ion species are detected) and the period in which fragment ions are generated do not terminate simultaneously.

[0100] In a further illustrative manner, Figure 8A An example of a timing diagram associated with one implementation of the method described above (in MS / MS analysis of multiple different precursor ion species, offsetting the data acquisition period relative to the period of precursor ion fragmentation and the period of introducing fragment ions into the downstream ToF mass analyzer). In this example, multiple different precursor ion groups are analyzed. Solid and dashed lines indicate which ion group is processed in the corresponding portion of the data acquisition period. In such an embodiment, the fragmentation device (e.g., EAD) is located upstream of the collision chamber and the ToF mass analyzer, and therefore the fragmentation device can be switched to receive the next ion group while continuing to process (e.g., decelerate and / or detect) ions released from the fragmentation device in the previous cycle in parallel.

[0101] The traces, labeled EAD cycles and depicted by solid lines, show the time periods corresponding to the fragmentation of precursor ion species within the ion trap and their extraction from the ion trap and introduction into the collision chamber (e.g., the Q2 collision chamber described below) and subsequent entry into the ToF mass analyzer. The traces depicted as dashed lines instead show the corresponding cycles of fragmentation, introduction into the collision chamber, and detection by the downstream ToF mass analyzer for different precursor ion species. The solid lines following the dashed lines represent another (third) precursor.

[0102] As shown by the second trace labeled “Q2 period”, in all cases, the ions introduced into the collision chamber are slowed down by the axial DC potential present in the collision chamber, for example, in the manner discussed herein.

[0103] The last trace, labeled "Data Period," indicates the time period during which ion detection signals were acquired. The portion of the trace depicted by a solid line represents the data acquisition period associated with one of the precursor ion species (i.e., the precursor ion species used in the solid line in the EAD period trace). The portion of the trace depicted by a dashed line represents the data acquisition period associated with another precursor ion species (i.e., the precursor ion species used in the dashed line in the EAD period trace), with the solid line on the right representing a portion of the period for yet another precursor.

[0104] The timing diagram shows that the data acquisition period for each ion species extends beyond the time it takes for that precursor ion species to complete fragmentation, deceleration, and the introduction of ions into the final cycle of the ToF mass analyzer. In this way, while another precursor ion species is introduced into the ion dissociation device to generate its ion fragments, the detection and analysis of the generated fragment ions can continue during the data acquisition period.

[0105] In some embodiments, the methods described above for improving the dynamic range and flux of the system can be combined. In other words, switching the axial DC potential between deceleration DC potential and acceleration DC potential based on the mass analysis cycle (e.g., accelerating the ion pack during the last cycle as described above) can be combined with corresponding cycle offsets of the data acquisition period relative to fragmentation and the introduction of fragment ions into the collision chamber, such as in the manner discussed above.

[0106] In an explanatory manner, Figure 8B An example of a timing diagram for implementing this aspect of the present teaching is illustrated in one embodiment.

[0107] refer to Figure 9A , Figure 9B and Figure 9C A mass spectrometer 800 according to one embodiment of this teaching may include an ion source (not shown) for generating ions that can be received by an ion guide Qjet via an aperture 802 of the mass spectrometer. The Qjet ion guide includes a set of rods 801 arranged in a quadrupole configuration, with two rods 801a / 801b visible in the figure, and employs a combination of gas dynamics and a radio frequency field to induce ion focusing. Ions exiting the Qjet ion guide are received by an ion guide Q0, which includes a set of quadrupoles 804, with two rods 804a / 804b visible in the figure. An RF voltage can be applied to this set of quadrupoles to induce radial confinement of the ions and generate an ion beam, which is then received by an ion mass filter Q1. The ion guides Qjet, Q0, and mass filter Q1 are disposed within a differential pumping chamber that maintains a gradually decreasing pressure.

[0108] The ion lens IQ0 focuses ions exiting the ion guide Q0 into the mass filter Q1. The mass filter Q1 includes a stubby lens 806 comprising a set of quadrupoles (two of which, 806a / 806b, are visible in the figure), to which an RF field can be applied to induce ion focusing. The mass filter Q1 also includes a set of quadrupoles 810, two of which, 810a / 810b, are visible in the figure, to which a combination of RF and DC voltages can be applied to allow selection of precursor ions with a specific m / z ratio for transport to the downstream electron reactor 812 (also referred to herein as an electron reactor trap), where the precursor ions can undergo electron capture dissociation, as discussed in more detail below. The selected precursor ions exiting the quadrupole set 810 are received by the downstream electron reactor 812 through the ion lens IQ1. The short, thick lens 816 located downstream of the quadrupole assembly 810 helps to focus the selected precursor ions into the downstream electron reaction device 812.

[0109] The electron reaction device 812 includes two sets of L-shaped bars 812a / 812b, which are axially offset relative to each other to provide an ion trapping region 813 between the two sets of L-shaped bars. The combination of the two sets of quadrupoles provides an axial channel 10 and a transverse channel 12, wherein precursor ions can be introduced into the trapping region 813 via the inlet of the axial channel, and product ions generated by electron trapping dissociation of the precursor ions or any other electron-induced fragmentation process (such as EIEIO (electron bombardment excitation of organic ions), EID (electron-induced dissociation)) and any remaining precursor and / or charge-reduced ions can exit the ion reaction device via the outlet of the axial channel. An electron beam 815 can be introduced into the ion trapping region 813 via the inlet of the transverse channel to interact with the ions trapped in the ion trapping region 813, wherein the interaction between electrons and trapped ions can, for example, cause the dissociation of precursor ions via electron trapping dissociation. The electron beam can exit the ion reaction device via the outlet of the transverse channel. Further details regarding the electronic reaction device and its operation can be found, for example, in U.S. Patent No. 10,014,166, the entire contents of which are incorporated herein by reference.

[0110] Fragment ions generated in ion trapping region 813 are received by collision chamber Q2 via ion lens IQ2. Collision chamber Q2 is pressurized by introducing nitrogen gas to allow collision cooling of the ions received in chamber Q2. A pair of LINAC electrodes Q2L1 and Q2L2 are located in the collision chamber and are axially separated from each other, so that a DC potential difference can be maintained between the pair of LINAC electrodes.

[0111] For details, please refer to the following: Figure 9BIn this embodiment, DC / RF voltage sources 819 and 821, operating under the control of controller 823, can apply RF and DC voltages to the rods of the ECD chamber and the collision chamber to generate a quadrupole electric field for providing radial confinement of ions and further providing a DC offset voltage between the rods of the Q2 chamber and the upstream ECD chamber. Another DC voltage source 825, also operating under the control of controller 823, provides a DC voltage across the LINAC electrodes Q2L1 and Q2L2.

[0112] The combination of a DC offset voltage applied between the rods in the upstream ECD chamber and the collision chamber, and a DC voltage applied across the LINAC electrodes, results in an axial DC potential that can either slow down or accelerate ions passing through the collision chamber, thus “slowing down” or “speeding up” the ions. As an example, ion slowing can be achieved by applying a neutral, reverse polarity, or slightly positive LINAC voltage and matching the potential on other components (e.g., ECD, ST2, etc.).

[0113] In an explanatory manner, Figure 9C Two traces are presented, each depicting the axial DC potential along the longitudinal axis of the mass spectrometer from the ST2 lens through the ECD chamber and downstream of the Q2 collision chamber. The solid trace depicts an example of the longitudinal variation of the axial DC potential that causes ions to be accelerated as they pass through the Q2 collision chamber; while the dashed trace depicts an example of the longitudinal variation of the axial DC potential that causes ions to be slowed down as they pass through the Q2 collision chamber. More specifically, in Figure 9C In the illustrated example, the gradient of the axial DC potential within the Q2 collision chamber, depicted by the solid line, results in an electric field within the collision chamber that accelerates the ions as they pass through. Conversely, the gradient of the axial DC potential within the Q2 collision chamber, depicted by the dashed line, essentially disappears.

[0114] Therefore, in this case, the ions are slowed down by collisions with background gas molecules present in the Q2 collision chamber. As discussed above, in various embodiments, during the initial subset of multiple cycles of introducing the precursor ion species into the ion fragmentation device, fragmenting the precursor ion species into multiple ion fragments, and introducing those ion fragments into the downstream ToF mass analyzer, the ions are slowed down as they pass through the Q2 collision chamber, and in the last cycle (or in several consecutive final cycles), the axial DC potential is adjusted to accelerate the ions as they pass through the Q2 collision chamber.

[0115] In various embodiments, the deceleration and / or acceleration of ions as they pass through a pressurized ion guide, which acts as an ion trap, to generate multiple distinct ion packets can be adjusted to obtain a desired ratio of the time difference (time gap between two consecutive ion packets) when they arrive at the downstream TOF mass analyzer to the width of the arriving ion packets (e.g., their full width at half maximum (FWHM)). As an example, the ratio of the time gap to the width of the ion packets can range, for example, from about 0 ms to about 5 ms.

[0116] In an explanatory manner, Figure 10A , Figure 10B , Figure 10C and Figure 10D This shows the effect of TOF mass spectrometry (such as...) Figure 9A The figures depict the arrival time distributions of multiple temporally distinct ion packets generated in the EAD chamber of the mass spectrometer (described as a TOF mass analyzer), measured at the advance electrodes. L1 and L2 refer to the LINAC1 and LINAC2 electrodes, respectively. The data presented in these figures show a larger time broadening of the ion packets observed at the slower axial gradient (i.e., smaller L2).

[0117] The controller 823 can be implemented in hardware, firmware, and / or software, and can be programmed to implement various methods according to this teaching. As an example, Figure 11 An example of such an implementation is schematically depicted, wherein the controller includes a processor 900 that communicates with a permanent memory module 902 and a random access memory (RAM) module 904 via a communication bus 906. The controller may also include a communication module 908 that allows the controller to communicate with a voltage source and other devices. While in some embodiments the controller may be integrated into the mass spectrometer, in other embodiments the controller may be implemented as a stand-alone computer system capable of providing operating instructions to the mass spectrometer.

[0118] Instructions for performing various methods of mass spectrometry according to this teaching can be stored in permanent memory module 902 and can be transferred to RAM module 904 for execution under the control of processor 900. By way of example, these instructions can provide a DC offset voltage for application to the rods and / or other components of the collision chamber (e.g., the rods of the upstream ion trap) for different periods of precursor ion species mass analysis. Furthermore, in some cases, these instructions can provide a time setting for the data acquisition period relative to the fragmentation period of the precursor ion species.

[0119] Refer again Figure 9AIons exiting chamber Q2 are focused by a set of ion-focusing optics 815 into a time-of-flight (ToF) mass analyzer 818, which provides mass analysis of those ions. More specifically, the ToF mass analyzer 818 includes an ion deflector (also referred to herein as an accelerator) 818a that can apply an accelerating voltage to the ion packet, causing the ion packet to pass through the field-free region of the ToF analyzer and travel toward an ion mirror 820, which can deflect the ions to an opposing ion mirror 822, which in turn guides the ions to an ion detector 824, which can generate an ion detection signal in response to the detection of ions. The mass spectrometer 800 may include a dynamic range adjuster 826 for adjusting the dynamic range of the ion detector 824. The ion detection signal can be processed in a manner known in the art to generate a mass spectrum of fragment ions.

[0120] Those skilled in the art will understand that various changes can be made to the above embodiments without departing from the scope of this teaching.

Claims

1. A mass spectrometer, comprising: Ion capture device; At least one pressurized ion guide is configured to allow an adjustable axial field to be established therein, such that the axial field can be adjusted to operate the pressurized ion guide in either a fast operating setting or a slow operating setting. A mass analyzer is used to receive ions passing through the pressurized ion guide and is configured to provide mass analysis of the received ions; as well as The controller communicates with the at least one pressurized ion guide to induce adjustment of the axial field so as to switch the operation setting of the pressurized ion guide between the fast operation setting and the slow operation setting based on the operating mode of the mass spectrometer.

2. The mass spectrometer according to claim 1, wherein, The operating mode of the mass spectrometer is characterized by the inter-sample switching time associated with the introduction of different precursor ions into the mass spectrometer during a single mass analysis run.

3. The mass spectrometer according to claim 2, wherein, The controller is configured to operate the ion guide in the fast operation setting when the sample switching time is less than about 2 ms.

4. The mass spectrometer according to claim 2, wherein, The controller is configured to operate the ion guide in the slow operation setting when the sample switching time is greater than about 5 ms.

5. The mass spectrometer according to any one of the preceding claims, wherein, The ion capture device is configured to operate as a flow-through ion guide.

6. The mass spectrometer according to claim 4, wherein, The controller is configured to induce adjustment of the axial field so that ions passing through the ion guide remain substantially intact during the rapid operation setting of the ion guide.

7. The mass spectrometer according to claim 1, wherein, The controller is configured to induce adjustment of the axial field in the slow operation setting of the ion guide in order to prevent saturation of the ion detector of the mass analyzer.

8. The mass spectrometer according to claim 1, wherein, The controller is configured to induce adjustment of the axial field in the slow operation setting of the ion guide in order to prevent charge distortion effects in one or more mass spectra generated based on data acquired by the mass analyzer.

9. The mass spectrometer according to any one of claims 1 to 4 and 6 to 8, wherein, The capture device is configured to operate as an ion trap.

10. The mass spectrometer according to claim 9, wherein, The controller is configured to operate the axial ion guide in the slow operation setting.

11. The mass spectrometer according to claim 9, wherein, The ion trap is configured to generate ion packets at different times.

12. The mass spectrometer according to claim 11, wherein, The controller is configured to select the operating settings of the ion guide based on the generation time of the different ion packets over the time period.

13. The mass spectrometer according to claim 12, wherein, The controller is configured to select a slow operation setting for an ion guide for one or more ion packs generated during a first data acquisition interval, and a fast operation setting for selecting an ion guide for one or more ion packs generated during a second data acquisition interval, wherein the second data acquisition interval is after the first data acquisition interval.

14. The mass spectrometer according to any one of claims 11, further comprising a DC voltage source operating under the control of a controller for applying at least one DC voltage to the ion guide to generate the adjustable axial field.

15. The mass spectrometer according to claim 14, wherein, The controller causes the DC voltage source to apply a minimum DC voltage, at which the axial field causes the ion packets arriving at the mass analyzer to exhibit a time broadening below the target threshold.

16. The mass spectrometer according to claim 15, wherein, The controller is configured to determine the minimum DC voltage by continuously increasing the at least one DC voltage applied to the ion guide and monitoring the time spread of ions arriving at the mass analyzer.

17. The mass spectrometer according to any one of claims 1 to 4 and 6 to 8, wherein the ion guide comprises a plurality of rods arranged in a multi-pole configuration.

18. The mass spectrometer according to any one of claims 1 to 4 and 6 to 8, wherein the mass analyzer comprises a ToF mass analyzer.

19. The mass spectrometer according to any one of claims 1 to 4 and 6 to 8, wherein the ion trapping device comprises an ion-particle reaction device.

20. The mass spectrometer according to claim 19, wherein the ion-particle reaction device includes an electron activated dissociation (EAD) device.

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