Patent Application
20210202230
The present teachings are generally related to methods and systems for efficient transfer of ions having a wide range of m/z ratios into an ion trap, e.g., a linear ion trap (LIT), in a mass spectrometer.
Mass spectrometry (MS) is an analytical technique for measuring mass-to-charge ratios of molecules, with both qualitative and quantitative applications. MS can be useful for identifying unknown compounds, determining the structure of a particular compound by observing its fragmentation, and quantifying the amount of a particular compound in a sample. Mass spectrometers detect chemical entities as ions such that a conversion of the analytes to charged ions must occur during sample processing.
In tandem mass spectrometry (MS/MS), ions generated from an ion source can be mass selected in a first stage of mass spectrometry (precursor ions), and the precursor ions can be fragmented in a second stage to generate product ions. The product ions can then be detected and analyzed.
In some cases, precursor ions selected by an upstream mass filter can be introduced into an RF ion trap functioning as a collision cell in which they undergo fragmentation. The fragmented ions can then be received by a downstream LIT and released according to their m/z ratios, e.g., via selective mass axial ejection (MSAE), to be detected by a downstream detector.
Conventional linear ion traps can, however, exhibit poor trapping efficiency for large m/z ions at low applied RF voltage(s), due to low effective trapping potential. Increasing the applied RF voltage(s) can increase the trapping efficiency of large m/z ions but could adversely affect the trapping of low m/z ions because at higher applied RF voltage(s) the motion of the low m/z ions can become unstable. As a result, the mass range of linear ion traps is typically parsed using separate sample runs and pieced back together to be able to process ions having a wide range of m/z ratios. Such parsing of the mass range can, however, decrease the duty cycle and sensitivity.
Accordingly, there is a need for improved methods and systems for loading ion traps for use in mass spectrometry.
In one aspect, a method of processing ions in a mass spectrometer is disclosed, which comprises introducing one or more precursor ions into a collision cell so as to cause fragmentation of at least a portion of said ions into a plurality of ion fragments, where the collision cell can have a plurality of rods to at least one of which an RF voltage can be applied for radially confining at least a portion of the ion fragments. By way of example, the collision cell can include a quadrupole rod set to which RF voltages can be applied for radially confining the ions therein. The RF voltage(s) applied to the collision cell are initially selected so as to radially confine ion fragments having m/z ratios above a threshold (which herein are referred to as high m/z fragments). An analyzer ion trap, e.g., a linear ion trap, is positioned downstream of the collision cell, where the analyzer ion trap includes a plurality of rods to at least one of which an RF voltage can be applied for radially confining ions therein. Similar to the collision cell, initially, the RF voltage(s) applied to the analyzer ion trap are selected to radially confine ion fragments having m/z ratios above said threshold, i.e., high m/z ion fragments.
The ion fragments can then be released from the collision cell into the downstream analyzer ion trap. Substantially concurrent with the introduction of the ions into the analyzer ion trap or with a delay relative to such introduction of the ions into the analyzer ion trap, a gas pressure pulse can be applied to the analyzer ion trap so as to expedite cooling of the ion fragments (and in some cases a plurality of precursor ions) received by the analyzer ion trap. In some embodiments, the application of the gas pressure pulse can raise the internal pressure of the analyzer ion trap by at least a factor of about 1.5, e.g., a factor in a range of about 1.5 to about 10.
Subsequently, the RF voltage(s) applied to the collision cell and the downstream analyzer ion trap can be reduced to a level suitable for radially confining ions having m/z ratios below said threshold (which are herein referred to as low m/z fragments).
This can be followed by the introduction of precursor ions into the collision cell to generate a plurality of fragment ions, and releasing the fragment ions from the collision cell into the downstream analyzer ion trap. In this manner, the analyzer ion trap can be efficiently loaded with high m/z and low m/z ions.
Subsequently, the ions contained in the analyzer ion trap can be released, e.g., via selective mass axial rejection (MSAE), to be received by a downstream detector. The ions can be detected by the downstream detector to generate a mass spectrum.
In some embodiments, the high m/z ions have an m/z ratio greater than about 300, e.g., in a range of about 300 to about 1000, and the low m/z ions have an m/z ratio equal to or less than about 300, e.g., in a range of about 50 to about 300.
In some embodiments, the frequency of the RF voltages applied to any of the collision cell and the analyzer ion trap can be, for example, in a range of about 0.3 MHz to about 2 MHz. In some embodiments, the amplitudes of the RF voltages suitable for radially confining the high m/z ions, e.g., m/z ratios greater than about 300, can be, for example, in a range of about 43.5 V0-peak at 0.3 MHz to about 1933 V0-peak at 2 MHz, and the amplitudes of the RF voltages suitable for radially confining the low m/z ions, e.g., m/z ratios in a range of about 50 to about 300, can be, for example, in a range of about 7 to about 322 V0-peak. The above voltages correspond to quadrupole arrays having inscribed r0 radius of 4.17 mm. In some embodiments, the RF voltages applied to the collision cell and the downstream analyzer ion trap for radially confining said high m/z ion fragments are selected to generate a Mathieu parameter (q) greater than about 0.27 for the highest m/z ions in the mass window of interest.
In some embodiments, an axial field can be applied to the collision cell, e.g., via application of a DC voltage to an electrode positioned in the proximity of an exit outlet of the collision cell for axial confinement of ions within the collision cell.
In some embodiments, an ion source, e.g., an atmospheric pressure ionization source, can be employed to generate a plurality of precursor ions. In some such embodiments, a filter, e.g., an RF/DC filter, can be employed to select from the ions generated by the ion source a plurality of precursor ions having m/z ratios in a desired range for introduction into the collision cell.
In a related aspect, a method of processing ions in a mass spectrometer is disclosed, where the mass spectrometer includes a first ion trap and a second analyzer ion trap positioned downstream of said first ion trap, each of said ion traps having a plurality of rods to at least one of which an RF voltage can be applied for radially confining at least a portion of ions within said trap. The method can include applying one or more RF voltage(s) to the first ion trap and the second ion trap so as to radially confine ions having m/z ratios above a threshold (“high m/z ions”). A plurality of ions are introduced into the first ion trap, where in some embodiments, the ions can undergo collisional cooling in the first ion trap. This can be followed by releasing at least a portion of the ions from the first ion trap and introducing those ions into the downstream analyzer ion trap. Substantially concurrent with the introduction of the ions into the analyzer ion trap or with a delay relative to such introduction of ions into the analyzer ion trap, a gas pressure pulse can be applied to the downstream analyzer ion trap to expedite cooling of the ions received by the analyzer ion trap. In some embodiments, the application of the gas pressure pulse to the analyzer ion trap can increase an internal pressure thereof by at least a factor of about 1.5, e.g., a factor in a range of about 1.5 to about 10.
Subsequently, the RF voltage(s) applied to the first ion trap and the downstream analyzer ion trap can be reduced to a level suitable for radially confining ions having m/z ratios below said threshold. In other words, the RF voltage(s) applied to the first ion trap and the downstream analyzer ion trap allow these traps to radially trap high m/z ions while the low m/z ions have a higher probability of being lost, e.g., by striking the rods of the ion traps.
The RF voltages applied to the first ion trap and the downstream analyzer ion trap can then be reduced to a level that would be suitable for radially confining ions having m/z ratios below said threshold, i.e., the low m/z ions. A plurality of ions can then be introduced into the first ion trap, and then released from the first ion trap to be introduced into the downstream analyzer ion trap. Optionally, another gas pressure pulse can be applied to the analyzer ion trap to cause cooling of the ions therein. In this manner, the analyzer ion trap can be loaded with both high m/z and low m/z ions.
Subsequently, the ions can be released from the downstream analyzer ion trap, e.g., via MSAE, to be received by an ion detector, which can detect the ions for generating a mass spectrum.
In a related aspect, a method of introducing ions into a mass analyzer of a mass spectrometer is disclosed, where the mass analyzer includes a plurality of rods, e.g., a set of quadrupole rods, to which one or more RF voltages can be applied for radially confining ions therein. The method can include applying an RF voltage to said at least one rod of the mass analyzer so as to generate an electromagnetic field configured to radially trap ions having m/z ratios above a threshold (i.e., suitable for radially confining high m/z ions), and introducing a plurality of ions into the mass analyzer. A gas pressure pulse can be applied to the mass analyzer to facilitate the cooling of the ions in the mass analyzer. The RF voltage(s) applied to the mass analyzer can then be reduced so as to generate an electromagnetic field that is suitable for radially trapping ions having m/z ratios below said threshold (i.e., suitable for radially confining low m/z ions). A plurality of ions can then be introduced into the mass analyzer. Optionally, another gas pressure pulse can be applied to the mass analyzer to cool the ions contained therein. In this manner, the mass analyzer can be loaded with both high and low m/z ions. The ions can then be released, e.g., via MSAE, from the mass analyzer to be detected by a downstream ion detector.
In a related aspect, a mass spectrometer is disclosed, which comprises a collision cell for receiving a plurality of precursor ions and causing fragmentation thereof to generate a plurality of ion fragments, said collision cell comprising a plurality of rods to at least one of which an RF voltage can be applied to generate an electromagnetic field for radially confining the ion fragments within said collision cell. An analyzer ion trap positioned downstream of the collision cell can receive at least a portion of the ion fragments generated in the collision cell. The mass spectrometer further includes at least one RF voltage source for applying one or more RF voltages to the collision cell and the downstream analyzer ion trap for radially confining ions therein. The mass spectrometer also includes a pulsed gas source that is in fluid communication with said downstream analyzer ion trap for applying a gas pressure pulse to the ion trap to cause cooling of the ions contained therein.
A controller is in communication with the RF voltage source and the pulsed gas source. The controller is configured to perform the following steps for processing the ions: causing the RF voltage source to apply RF voltages to the collision cell and the analyzer ion trap suitable for radially confining high m/z ions therein, causing said pulsed gas source to apply a gas pressure pulse to said downstream analyzer ion trap configured for confining high m/z ions when fragment ions are introduced from the collision cell into said downstream analyzer ion trap to cause cooling of said ions, and subsequently, causing the RF voltage source to reduce said RF voltages applied to said collision cell and said downstream analyzer ion trap to a level suitable for radially confining low m/z ions. The controller is further configured to cause mass selective axial ejection of the ions from the analyzer ion trap, e.g., by effecting an AC voltage source to apply appropriate voltages to the rods of the analyzer, following the performance of the above steps.
The mass spectrometer can further include an ion source for generating ions. A variety of different ion sources can be employed. By way of example, the ion source can be an atmospheric ionization source, an atmospheric pressure photoionization (APPI), an electrospray ionization (ESI), a thermospray ionization, among others.
In some embodiments, a mass filter, e.g., an RF/DC mass filter, can be disposed between the ion source and the collision cell. By way of example, the mass filter can be configured to select precursor ions having m/z ratios within a desired range for introduction into the collision cell.
The collision cell and the analyzer ion trap can be configured in a variety of different ways. By way of example, in some embodiments, the collision cell and the analyzer ion trap can include a set of quadrupole rod sets to which RF voltages can be applied for radially confining ions. In other embodiments, any of the collision cell and the analyzer ion trap can include other multi-pole configurations, such as hexapole. In some embodiments, the collision cell and the downstream analyzer ion trap can be capacitively coupled to one another.
In some embodiments, the ion fragments generated in the collision cell can have m/z ratios in a range of about 50 to about 2000, e.g., in a range of about 50 to about 1000.
In some embodiments of the above mass spectrometer, the collision cell is configured to cause primarily cooling of ions rather than their fragmentation. Further, in some embodiments, the spectrometer may lack a collision cell and the analyzer ion trap can receive ions directly, or via one or more ion guides, from an ion source.
Further understanding of the present teachings can be obtained by reference to the following detailed description in conjunction with the associated drawings, which are described briefly below.
The present teachings are generally related to methods and systems for processing ions in a mass spectrometer. In some embodiments, the methods include loading one or more ion traps with ions having a wide range of m/z ratios, e.g., m/z ratios in a range of about 50 to about 1000, in two or more stages, where in one stage the one or more ion traps are configured to confine ions having high m/z ratios, e.g., m/z ratios greater than about 300, and in at least another stage the one or more ion traps are configured to confine ions having low m/z ratios, e.g., m/z ratios in a range of about 50 and 300. As discussed in more detail below, the present teachings provide certain advantages relative to conventional methods for loading ions into an ion trap, e.g., for both enhanced product ion (EPI) scans and enhanced mass spectrometry (EMS), such as efficient loading of ion traps and an increase in the duty cycle of mass analysis.
In EPI, precursor ions, e.g., precursor ions selected by an upstream filter, can be fragmented in a collision cell and the fragment ions together with any remaining precursor ions can be trapped in a downstream ion trap, where the ions can undergo collisional cooling. Subsequently, the ions can be released from the ion trap, e.g., via mass selective axial ejection (MSAE) to be detected by a downstream detector. Typically, ion traps have a low mass cut-off, which usually corresponds to about one-third of the mass of the precursor ions. For example, if the RF voltage applied to the ion trap is selected to correspond to Mathieu parameter (q) of 0.3 for precursor ions, the low mass cut-off (q of about 0.906) will occur for an m/z ratio of 0.33×m/z (precursor). Alternatively, if the RF voltage applied to the ion trap is set so as to trap low m/z ions, the trapping efficiency for large m/z ions could potentially become poor. Thus, in conventional systems, different mass segments need to be used to obtain a complete spectrum, e.g., a complete collision-induced dissociation (CID) spectrum, e.g., down to an m/z ratio of 50 or 30. The number of segments that may be required for obtaining a complete spectrum can depend, e.g., on the mass range and the mass of the precursor ion. A significant drawback of such conventional methods is that each mass segment requires a full cycle (injection, trapping, cooling and mass analysis), which can significantly increase the duty cycle of both EPI and EMS scans. In contrast, the present teachings can provide methods and systems for generating full spectra, e.g., EPI or EMS spectra, without mass parsing.
With reference to flow chart of
In some embodiments, due to the high pressure of the collision cell, e.g., a pressure in a range of about 1 to about 15 mTorr, ions received by the collision cell are cooled rapidly and no additional cooling time may be needed after the fill period.
In some embodiments, the ion fragments can have m/z ratios in a range of about 50 to about 1000. In some such cases, the high m/z fragments can have m/z ratios greater than about 300, and the low m/z fragments can have m/z ratios equal to or less than about 300, e.g., in a range of about 50 to about 300.
A gas pressure pulse is applied to the analyzer ion trap to expedite cooling of the ion fragments. In some embodiments, the gas pressure pulse can be applied to the analyzer ion trap concurrently with the introduction of the ion fragments into the analyzer ion trap. In other embodiments, the gas pressure pulse can be delayed relative to the introduction of the ions released from the collision cell into the mass analyzer. In other embodiments, the gas pressure pulse can start before the introduction of the ions released from the collision cell into the mass analyzer and can last during the time of ion introduction and beyond ion introduction. In some embodiments, the duration of the gas pulse can be, for example, in a range of about 0.1 ms to about 20 ms, e.g., in a range of about 0.1 ms to about 5 ms. In some embodiments, the duration of the pressure pulse can be between about 0.1 ms to about 20 ms.
In some embodiments, the application of the gas pressure pulse to the analyzer ion trap can increase an internal pressure of the analyzer ion trap by a factor, in a range of about 1.5 to about 10, e.g., about 300%. For example, the application of the gas pressure pulse can increase the internal pressure of the analyzer ion trap from about 2×10−5 Torr to about 8×10−5 Torr. Such increase in the internal pressure of the analyzer ion trap can reduce the energy of the ions entering the mass analyzer, thus increasing the trapping efficiency as well as expedite collisional cooling of the ions contained therein.
Subsequent to the introduction of the ions into the mass analyzer and the application of the gas pressure pulse, the RF voltage(s) applied to the collision cell and the downstream analyzer ion trap can be reduced to a level that would be suitable for radially confining ion fragments having m/z ratios below the aforementioned threshold (which herein are referred to as “low m/z ions”). This is then followed by the introduction of a plurality of precursor ions into the collision cell to generate a plurality of ion fragments.
The ions contained in the collision cell are released from the collision cell and are introduced into the analyzer ion trap. In some embodiments, another gas pressure pulse can be optionally applied to the analyzer ion trap to facilitate cooling of the ions, and particularly, the cooling of the newly-arrived low m/z ions. The cooling of the ions allow efficient trapping of not only the low m/z but also the high m/z ions despite the low RF effective potential (e.g., D=qV/8, where q is the Mathieu parameter, and Vpeak-to-peak is the amplitude of the RF voltage). The ions can then be released from the analyzer ion trap using, e.g., mass selective axial ejection (MSAE), to be detected by a downstream detector.
The increased pressure in the analyzer ion trap due to the application of the gas pressure pulse can significantly reduce the total fill plus cool time of the analyzer ion trap, e.g., about 5 millisecond (msec) or less, which can in turn enhance the duty cycle of mass analysis.
The ions can be generated by an ion source, such as an atmospheric pressure ionization source. In some embodiments, a filter can be positioned between the ion source and the collision cell to select ions having m/z ratios in a particular range. By way of example, such a filter can include a quadrupole rod set to which RF/DC voltages can be applied to allow selecting ions having m/z ratios in a particular range for passage through the filter. In some embodiments, the RF voltages applied to the collision cell and the downstream analyzer ion trap for radially confining said high m/z ion fragments are selected to generate a Mathieu parameter (q) greater than about 0.27.
The present teachings can be employed to obtain not only EPI spectra but also EMS spectra. For example, with reference to the flow chart of
By way of example, the high m/z ions can have m/z ratios greater than about 300, e.g., in a range of about 300 to about 1000.
A plurality of ions are then introduced into the first ion trap, e.g., a collision cell. In this embodiment, the kinetic energy of the ions introduced into the collision cell are selected so as to minimize fragmentation of the ions during their passage through the collision cell, e.g., ion energies less than about 10 eV.
The fill time for trapping ions in the collision cell can be, for example, in a range of about 2 to about 200 msec. At least a portion of the ions in the first ion trap are released and introduced into the downstream analyzer ion trap.
A gas pressure pulse is applied to the downstream analyzer ion trap so as to expedite the cooling of the ions received from the collision cell by the analyzer ion trap. In some embodiments, the gas pressure pulse can be applied to the analyzer ion trap substantially concurrently with the introduction of the ions from the first ion trap into the analyzer ion trap. In other embodiments, the gas pressure pulse can be delayed relative to the introduction of the ions from the first ion trap into the analyzer ion trap. In other embodiments, the gas pressure pulse can start before the introduction of the ions from the first ion trap into the analyzer ion trap. By way of example, in some embodiments the gas pulse can start 1 ms before the ion introduction from the first ion trap into the second ion trap. The increase in the internal pressure of the analyzer ion trap can expedite cooling of the ions received thereby, e.g., typically in about 40 to 60 msec.
Subsequently, the RF voltages applied to the first ion trap and the downstream analyzer ion trap are reduced to a level that would be suitable for radially confining ions having m/z ratios below said threshold (which herein are referred to as low m/z ions). This can be followed by introducing a plurality of ions into the first ion trap. At least a portion of the ions can be released from the first ion trap, e.g., after a desired time period after introduction of the ions into the first ion trap, and the released ions can be introduced into the downstream analyzer ion trap.
Following the introduction of the low m/z ions into the analyzer ion trap, the analyzer ion trap contains both high m/z and low m/z ions. The ions contained in the analyzer ion trap can then be released, e.g., via MSAE, to be detected by a downstream ion detector.
In some embodiments, the present teachings can be applied to an analyzer ion trap that can receive ions from an ion source without the ions first being introduced into an upstream collision cell. Similar to the previous embodiments, the RF voltages applied to the analyzer ion trap can be modulated so as to efficiently trap both high m/z and low m/z ions in the analyzer ion trap prior to releasing those ions from the analyzer ion trap to be detected by a downstream ion detector.
More specifically, with reference to the flow chart of
Subsequently, the ions contained in the analyzer ion trap can be released, e.g., via MSAE, to be detected by a downstream detector.
With reference to
As will be appreciated by a person of skill in the art, the quadrupole rod set Q1 can be operated as a conventional transmission RF/DC quadrupole mass filter that can be operated to select an ion type of interest and/or a range of ion types of interest. By way of example, the quadrupole rod set Q1 can be provided with RF/DC voltages suitable for operation in a mass-resolving mode. As should be appreciated, taking the physical and electrical properties of Q1 into account, parameters for an applied RF and DC voltage can be selected so that Q1 establishes a transmission window of chosen m/z ratios, such that these ions can traverse Q1 largely unperturbed. Ions having m/z ratios falling outside the window, however, do not attain stable trajectories within the quadrupole and can be prevented from traversing the quadrupole rod set Q1. It should be appreciated that this mode of operation is but one possible mode of operation for Q1. By way of example, in some embodiments, the quadrupole rod set Q1 can be operated in RF only mode, thus acting as an ion guide for ions received from Q0.
Ions passing through the quadrupole rod set Q1 can pass through the stubby ST2, also a Brubacker lens, to enter a collision cell 1304 in which at least a portion of the ions undergo fragmentation to generate ion fragments. In this embodiment, the collision cell includes a quadrupole rod set, though other multi-pole rod sets can also be employed in other embodiments. An RF voltage source 1310 operating under the control of a controller 1312 applies RF voltages to the rods of the collision cell to radially confine ions within the collision cell. Further, in this embodiment, IQ2 and IQ3 lenses are disposed in proximity of the inlet and outlet ports of the collision cell. By applying a DC voltage to the IQ3 lens that is higher than the collision cell's rod offset, axial trapping of the ions can be achieved.
Initially, the controller effects the RF voltage source to apply RF voltages to the rods of the collision cell that are suitable for radially confining ions having m/z ratios greater than a threshold, i.e., high m/z ions. By way of example, the RF voltages are selected to radially confine ions having m/z ratios greater than about 300, e.g., in a range of about 300 to about 1000.
With continued reference to
In this embodiment, the fragment ions contained in the collision cell are then released by setting the IQ3 voltage attractive for ions relative to the collision rod offset, and are introduced into the analyzer ion trap. As noted above, the RF voltages applied to the collision cell are selected to confine ions having high m/z ratios. As such, the ion fragments as well as in some cases precursor ions released from the collision cell and introduced into the downstream analyzer ion trap 1308 are primarily high m/z ions. The analyzer ion trap will provide effective confinement of these ions as the RF voltages applied to the analyzer ion trap are selected to provide radial confinement of such high m/z ions.
As shown in
As shown schematically in
Subsequently, the controller 1312 communicates with the RF source 1310 to cause the RF source to reduce the RF voltages applied to the collision cell 1304 and the downstream analyzer ion trap 1308. As noted above, the reduced RF voltages are selected so as to allow radial confinement of ions having m/z ratios below a threshold, i.e., the low m/z ions. By way of example, in some embodiments, the RF voltages, e.g., Vpeak-to-peak amplitude, can be reduced by a factor of about 10, e.g., by factor in a range of about 10 to about 20. The frequency of the RF voltages can remain unchanged. In some such embodiments, the low m/z ions can have, for example, m/z ratios less than about 300, e.g., in a range of about 50 to about 300.
Concurrent with or following the reduction of applied RF voltages to the collision cell and the downstream analyzer, a plurality of ions can be introduced into the collision cell, where they can undergo fragmentation with the low m/z fragment ions having a higher probability of being radially confined in the collision cell. The fragment ions (and in some cases a number of precursor ions) can then be released from the collision cell by reducing the DC voltage applied to IQ3 to a value below the collision cell rod offset, and be received by the downstream analyzer ion trap. Optionally, another gas pressure pulse can be applied to the analyzer ion trap to cause cooling of the ions therein. In this manner, the analyzer ion trap can be loaded with both high and low m/z ions. The ions can be Mass Selective Axially Ejected (MSAE) from the Q3 ion trap in a manner described by Hager in “A new Linear ion trap mass spectrometer,” Rapid Commun. Mass Spectro. 2002; 16: 512-526.
In other embodiments, following the reduction of applied RF voltages to the collision cell and the downstream analyzer, a plurality of ions can be introduced into the collision cell, where they can undergo fragmentation with the low m/z fragment ions having a higher probability of being radially confined in the collision cell and be transmitted toward the analyzer without being axially trapped in the collision cell. Subsequently, the ions contained in the analyzer ion trap can be released therefrom, e.g., via MSAE. The released ions can then be detected by a downstream detector 1314 and a mass spectrum thereof can be generated.
In some embodiments, the collision cell 1304 can be configured so as to cause primarily cooling of the ions and not their fragmentation. For example, the kinetic energy of the ions entering the collision cell can be selected so that the ions will undergo collisional cooling without fragmentation. Similar to the previous embodiment, initially, the collision cell and the downstream analyzer are configured to radially confine low m/z ions. A plurality of precursor ions can enter the collision cell and then be released into the downstream analyzer ion trap where a gas pressure pulse can be applied via the gas source 1316 to the downstream analyzer ion trap 1308 to cause cooling of the ions. Subsequently, the collision cell and the downstream analyzer can be configured to confine low m/z ions. A plurality of ions can be introduced into the collision cell and then released into the analyzer ion trap. In this manner, the analyzer ion trap can be loaded with both high m/z and low m/z ions. The ions can then be released, e.g., via MSAE, from the analyzer ion trap to be detected by the detector 1314.
In some embodiments, the spectrometer system 1300 can lack a collision cell. In such an embodiment, the ions generated by the ion source 1302 are received by the mass analyzer 1308 after passage through the ion guide Q0 and the filter Q1. In such an embodiment, the mass analyzer 1308 can be initially configured to radially confine high m/z ions. Similar to the previous embodiments, a gas pressure pulse can be applied to the mass analyzer to cool the ions received thereby. This can be followed by reducing the RF voltages applied to the mass analyzer to configure it for radially confining low m/z ions. The mass analyzer can receive ions and trap low m/z ions. Optionally, another gas pressure pulse can be applied to the mass analyzer to cool the ions received thereby. Again, in this manner, the mass analyzer can be loaded with both high m/z and low m/z ions. After loading the mass analyzer with both high m/z and low m/z ions, the ions can be released from the mass analyzer, e.g., via MSAE, to be detected by a downstream detector 1314.
The present teachings provide a number of advantages. For example, they allow for efficient trapping of both high m/z and low m/z ions. In other words, they allow for efficient trapping of ions having a wide range of m/z ratios. This can in turn enhance the duty cycle of mass analysis. For example, the implementation of the present teachings can result in at least a factor of 2 improvement in the duty cycle of mass analysis.
The following example is provided for further elucidation of various aspects of the present teachings, and is not necessarily indicative of the optimal ways of practicing the present teachings and/or optimal results that may be achieved.
The above data shows that the methods according to the present teachings can be used to obtain similar mass spectra compared to those obtained using conventional methods, but with a reduced duty cycle.
Those having ordinary skill in the art will appreciate that various changes can be made to the above embodiments without departing from the scope of the invention.
This application claims priority to U.S. provisional application No. 62/728,642 filed on Sep. 7, 2018, entitled “RF Ion Trap Ion Loading Method,” which is incorporated herein by reference in its entirety.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/IB2019/057463 | 9/4/2019 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 62728642 | Sep 2018 | US |
