Expanded dynamic range for attenuation of ion beams - Patents.com

Abstract

In one aspect, a method for modulating the transmission of ions in a mass spectrometer is disclosed, the method including generating an ion beam comprising a plurality of ions; directing the ion beam to ion optics positioned in a path of the ion beam, the ion optics including at least one aperture through which the ions can pass; and applying one or more voltage pulses to the ion optics at a selected duty cycle to obtain a desired attenuation of intensity of the ion beam passing through the ion optics, wherein the pulse width of the voltage pulses at the selected duty cycle is determined by identifying a pulse width on a calibrated normalized ion intensity vs. pulse width relationship for the ions that corresponds to the desired attenuation on an ideal normalized ion intensity vs. pulse width relationship for the ions.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims priority to a provisional patent application, entitled “Increased Dynamic Range for the Attenuation of an Ion Beam,” filed on July 23, 2019, and having application serial number 62 / 877,542, which is incorporated herein by reference in its entirety.

[0002] The present teachings relate generally to methods and systems for modulating the transmission of ions into components of a mass spectrometer, and more particularly to such methods and systems that can be employed to extend the dynamic range for attenuation of an ion beam within a mass spectrometer. [Background technology]

[0003] Mass spectrometry (MS) is an analytical technique for measuring the mass / charge ratio of molecules, in 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 chemicals as ions, so conversion of the analytes to charged ions must occur during sample processing.

[0004] It is often necessary to attenuate the intensity of the ion beam in a mass spectrometer, for example to avoid saturation of the detector, to reduce space charge that can adversely affect the performance of a quadrupole mass filter, or to prevent overfilling of the ion trap, among other things. The ability to reduce the intensity of the ion beam in a predictable manner can also reduce the number of dilutions required for analysis of a sample in the mass spectrometer.

[0005] A conventional technique for reducing the intensity of an ion beam is to vary the potential applied to a lens located near the entrance port of a mass spectrometer component from a transmission mode to a non-transmission mode. The reduction in beam intensity may be proportional to the duty cycle of the potential applied to the lens. For example, such techniques have been used to attenuate ion beams by pulsing the potential applied to the skimmer of a mass spectrometer.

[0006] However, such techniques suffer from nonlinearities at low duty cycles.

[0007] Thus, there is a need for improved methods and systems for attenuating the intensity of an ion beam in a mass spectrometer, and in particular, such methods and systems that allow for linear attenuation of the intensity of an ion beam over a wide range of intensities. Summary of the Invention [Means for solving the problem]

[0008] In one aspect, a method of modulating the transmission of ions in a mass spectrometer is disclosed that includes generating an ion beam comprising a plurality of ions; directing the ion beam to an ion optics positioned in a path of the ion beam, the ion optics including at least one aperture through which the ions can pass; and applying one or more voltage pulses at a selected duty cycle to the ion optics to obtain a desired attenuation of intensity of the ion beam passing through the ion optics, the pulse width of the voltage pulses at the selected duty cycle being determined by identifying a pulse width on a calibrated normalized ion intensity vs. pulse width relationship for the ions that corresponds to the desired attenuation on an ideal normalized ion intensity vs. pulse width relationship for the ions.

[0009] In some embodiments, a calibrated normalized ion intensity versus pulse width relationship is obtained via a linear fit to data corresponding to normalized intensities of the ions transmitted through the ion optics as a function of pulse widths of a plurality of voltages applied to the ion optics at the selected duty cycle.

[0010] As an example, the ideal normalized ionic intensity vs. pulse width relationship can be defined by the following linear relationship: y=m1x1 equation (1) During the ceremony, y represents the normalized ion intensity, x1 represents the ideal pulse width, m1 represents the slope of the linear relationship.

[0011] The calibrated normalized ion intensity vs. pulse width relationship can be defined by the following linear relationship: y=m2x2+b Equation (2) During the ceremony, y represents the normalized ion intensity, x2 represents the pulse width of the voltage pulse applied to the ion optics; m2 represents the slope of the linear relationship, b represents the intercept of the linear relationship.

[0012] Equation (1) and equation (2) above can be employed to determine a pulse width, x2, for application to the ion optics according to the following relationship:

number

[0013] In some embodiments, a calibrated normalized ion intensity for a voltage pulse width associated with multiple voltage pulses applied to the ion optics in the duty cycle is obtained as a ratio of a measured intensity of ions passing through the ion optics at a calibrated voltage pulse width associated with multiple calibration voltage pulses applied to the ion optics in the duty cycle to a measured intensity of ions passing through the ion optics at that voltage pulse width. By way of example, the calibration voltage pulses may have a pulse width of about 200 microseconds and may be applied to the ion optics at a duty cycle of about 5%.

[0014] In some embodiments, the slope (m2) and intercept (b) above can be obtained via a polynomial fit to the measured normalized ion intensities for ions having a number of different m / z ratios. Such a polynomial fit can be used to obtain values ​​of m2 and b for use in equation (3) above when calculating the pulse width for the voltage pulse to be applied to the ion optics.

[0015] In some embodiments, the ion beam can include ions having a plurality of different m / z ratios. In some such embodiments, equation (3) above can be employed to determine a pulse width for one of the m / z ratios. The determined pulse width can then be applied to the ion optics. Although the determined pulse width may differ from the optimal pulse width for an m / z ratio other than the one used to determine the pulse width, the use of the determined pulse width can nevertheless improve the linearity of ion transmission, particularly when the m / z ratios range from values ​​of about 200 Da or less for low (e.g., 50-250 Da) and intermediate (e.g., 600-800 Da) mass ranges, as well as an even wider range (e.g., 300 Da) for higher mass ranges.

[0016] In some embodiments, the pulse width of the voltage pulse applied to the ion-optics can be about 2000 microseconds or less, such as in the range of about 4 microseconds to about 2000 microseconds. Additionally, in some embodiments, the rise time of the voltage pulse applied to the ion-optics can be about 20 microseconds or less. In some embodiments, the voltage pulse has an amplitude selected to suppress transmission of ions, preferably all ions, to components located downstream of the ion-optics during a suppression phase of the voltage pulse.

[0017] The voltage pulses can be applied to the ion optics at a variety of different duty cycles, for example, the duty cycle can be in the range of about 0.1% to about 5%, such as 1%, 2%, 3%, 4%, or other values ​​within this range.

[0018] In some embodiments, the present teachings can be employed to attenuate the brightness of an ion beam in a mass spectrometer by a factor in the range of about 0.1% to about 5%.

[0019] In some embodiments, the method further includes positioning one of the mass filter and the ion trap downstream of the ion optics such that the ion optics is positioned near an entrance to the mass filter or ion trap to modulate the transmission of ions into the mass filter or ion trap. As discussed in more detail below, the ion optics may be positioned in a region where the background gas provides sufficient pressure to cause ions to lose a portion of their axial kinetic energy as a result of collisions with the background gas, thus allowing ions to be captured by the ion optics when the voltage applied to the ion optics is intended to suppress the transmission of ions to downstream components of the spectrometer. By way of example, the background pressure in the region where the ion optics is located may be within a range of about a few millitorr (e.g., 1 millitorr to about 10 millitorr).

[0020] In a related aspect, a method of modulating the transmission of ions in a mass spectrometer is disclosed that includes generating an ion beam comprising a plurality of ions, directing the ion beam to an ion optics positioned in a path of the ion beam, the ion optics including at least one aperture through which the ions can pass, and applying one or more voltage pulses to the ion optics at a selected duty cycle to modulate the passage of the ions through the ion optics, the pulse width of the voltage pulses being determined by calculating an adjustment to the pulse width of an ideal pulse that would result in a desired normalized intensity of ions passing through the ion optics. The step of calculating the adjustment can include utilizing an ideal normalized ion intensity vs. pulse width relationship and a calibrated normalized ion intensity vs. pulse width relationship for the ions.

[0021] In a related aspect, a mass spectrometer is disclosed that comprises an ion source for generating an ion beam comprising a plurality of ions; ion optics positioned in a path of the ion beam, the ion optics comprising at least one aperture through which ions can pass; and a voltage source configured to apply one or more voltage pulses to the ion optics at a selected duty cycle to obtain a desired attenuation of ion beam intensity, the voltage pulses having a pulse width that corresponds to a pulse width on a calibrated normalized ion intensity vs. pulse width relationship for the ions that corresponds to the desired attenuation on an ideal normalized ion intensity vs. pulse width relationship for the ions.

[0022] The mass spectrometer can further include a controller for determining the pulse width of a voltage pulse by identifying the pulse width on the calibrated normalized ion intensity vs. pulse width relationship, the controller can be in communication with a voltage source to communicate the determined pulse width to the voltage source.

[0023] In some embodiments, the voltage pulse has a rise time of less than about 20 microseconds. Additionally, in some embodiments, the voltage pulse has a pulse width in the range of about 4 microseconds to about 200 microseconds. Additionally, the voltage pulse can have an amplitude selected to suppress transmission of ions, preferably all ions, through the ion-optics to which the voltage pulse is applied during the suppression stage of the voltage pulse. By way of example, the voltage pulse can have an amplitude of at least about 50 volts.

[0024] In some embodiments, a controller controls a voltage source to apply the voltage pulses to the ion optics at a duty cycle of less than about 5%, for example, at a duty cycle in the range of about 0.1% to about 5%.

[0025] In some embodiments, the mass spectrometer further includes a mass filter, e.g., a quadrupole mass filter, positioned downstream of the ion optics such that the ion optics is positioned near the entrance port of the mass filter to modulate the transmission of ions into the mass filter. In some embodiments, an ion trap, e.g., a linear ion trap (e.g., a quadrupole linear ion trap), is positioned downstream of the ion optics such that the ion optics is positioned near the entrance port of the ion trap to modulate the transmission of ions into the ion trap. [Brief description of the drawings]

[0026] [Figure 1] FIG. 1 is a flow chart depicting various steps in one embodiment of the present teachings for attenuating an ion beam in a mass spectrometer. [Diagram 2] FIG. 2 diagrammatically depicts a mass spectrometer according to an embodiment of the present teachings. [Diagram 3] FIG. 3 illustrates one embodiment of a controller implementation suitable for use within the mass spectrometer of FIG. [Figure 4]FIG. 4 depicts a partial schematic diagram of a mass spectrometer according to an embodiment in which a doublet lens is positioned between the upstream ion guide and the downstream mass filter. [Figure 5A] FIG. 5A is a schematic partial view of a mass spectrometer in which a doublet lens comprising two lenses is positioned between an ion guide and a mass filter, where application of a voltage pulse to the lens provides modulation of the intensity of the ion beam in accordance with the present disclosure. [Figure 5B] FIG. 5B is a schematic diagram of a modified version of the mass spectrometer depicted in FIG. 5A in which the doublet lens is replaced with a single lens. [Figure 6A] FIG. 6A depicts voltage pulses for application to the lenses shown in FIG. 5A or FIG. 5B. [Figure 6B] FIG. 6B depicts the leading edge of the voltage pulse shown in FIG. 6A. [Figure 7A] FIG. 7A depicts two voltage pulses, one of which has a more rapid rise time. [Figure 7B] FIG. 7B illustrates the leading edge of the voltage pulse illustrated in FIG. 7A. [Figure 8] FIG. 8 shows in three panels (i.e., panels (a), (b), and (c)) different patterns of potentials that can be applied to a lens positioned between the ion guide and a downstream component of the mass analyzer (e.g., a mass filter or ion trap). [Figure 9A] FIG. 9A diagrammatically depicts the trajectories of ions through a lens positioned between the ion guide and the downstream components when the voltage pattern shown in panel (a) of FIG. 8 is applied to the lens. [Figure 9B] FIG. 9B diagrammatically depicts the trajectories of ions through the lens shown in FIG. 9A when the voltage pattern shown in panel (b) of FIG. 8 is applied to the lens. [Figure 9C] FIG. 9C diagrammatically depicts the trajectories of ions through the lens shown in FIG. 9B when the voltage pattern shown in panel (c) of FIG. 8 is applied to the lens. [Figure 10]FIG. 10 shows plots of normalized ion intensity versus duty cycle for an applied voltage pulse having a rise time of 36 microseconds and an amplitude of 30 V for several m / z ratios. [Figure 11] FIG. 11 shows a portion of the plot depicted in FIG. 10 at low duty cycles. [Figure 12] FIG. 12 shows plots of normalized ion intensity versus duty cycle for an applied voltage pulse having a rise time of 14 microseconds and an amplitude of 50 V for several m / z ratios. [Figure 13] FIG. 13 shows a plot of normalized ion intensity versus lens potential for several m / z ratios. [Figure 14A] 14A-14C show plots of normalized ionic intensity versus lens potential for several different compounds. [Figure 14B] 14A-14C show plots of normalized ionic intensity versus lens potential for several different compounds. [Figure 14C] 14A-14C show plots of normalized ionic intensity versus lens potential for several different compounds. [Figure 15A] 15A-15C show plots of normalized ion intensity as a function of DC potential applied to a lens positioned between the ion guide and downstream components for different pressures in the ion guide and downstream components, and for several different m / z ratios. [Figure 15B] 15A-15C show plots of normalized ion intensity as a function of DC potential applied to a lens positioned between the ion guide and downstream components for different pressures in the ion guide and downstream components, and for several different m / z ratios. [Figure 15C] 15A-15C show plots of normalized ion intensity as a function of DC potential applied to a lens positioned between the ion guide and downstream components for different pressures in the ion guide and downstream components, and for several different m / z ratios. [Figure 16A]16A-16D show plots of normalized ion intensity as a function of DC potential applied to a single lens and a doublet lens positioned between the ion guide and downstream components for several different m / z ratios. [Figure 16B] 16A-16D show plots of normalized ion intensity as a function of DC potential applied to a single lens and a doublet lens positioned between the ion guide and downstream components for several different m / z ratios. [Figure 16C] 16A-16D show plots of normalized ion intensity as a function of DC potential applied to a single lens and a doublet lens positioned between the ion guide and downstream components for several different m / z ratios. [Figure 16D] 16A-16D show plots of normalized ion intensity as a function of DC potential applied to a single lens and a doublet lens positioned between the ion guide and downstream components for several different m / z ratios. [Figure 17] FIG. 17 shows a plot of normalized ion intensity as a function of DC potential for the unfragmented ion at m / z 68 and the ion fragments at m / z 59. [Figure 18A] FIG. 18A shows plots of ideal and calibrated normalized ion intensity versus pulse width for a voltage pulse having a rise time of 14 microseconds and an amplitude of 40 V for an ion with m / z 29. [Figure 18B] FIG. 18B shows plots of ideal and calibrated normalized ion intensity versus pulse width for a voltage pulse having a rise time of 14 microseconds and an amplitude of 40 V for an ion with m / z 322. [Figure 18C] FIG. 18C shows plots of ideal and calibrated normalized ion intensity versus pulse width for a voltage pulse having a rise time of 14 microseconds and an amplitude of 40 V for an ion with m / z 29. [Figure 18D]FIG. 18D shows plots of ideal and calibrated normalized ion intensity versus pulse width for a voltage pulse having a rise time of 14 microseconds and an amplitude of 40 V for an ion with m / z 2122. [Figure 19] FIG. 19 shows a plot obtained by fitting the data presented in FIG. 18A to a linear relationship. [Figure 20] FIG. 20 illustrates the use of the plot presented in FIG. 19 to identify a pulse width for a voltage pulse that can result in a desired normalized ionic intensity. [Figure 21A] FIG. 21A shows the slope of a mass-dependent linear relationship for identifying the pulse width of a voltage pulse according to an embodiment of the present teachings as a function of ion mass. [Figure 21B] FIG. 21B shows the intercept of a mass-dependent linear relationship for identifying the pulse width of a voltage pulse according to an embodiment of the present teachings as a function of ion mass. [Figure 22] FIG. 22 shows a plot of normalized ion intensity as a function of the duty cycle of the applied voltage pulse for positive ion mode. [Figure 23] FIG. 23 shows a plot of normalized ion intensity as a function of the duty cycle of the applied voltage pulse for the negative ion mode. [Figure 24] FIG. 24 shows a plot of normalized ion intensity as a function of the duty cycle of the applied voltage pulse for the positive enhanced product ion (EPI) mode. [Diagram 25] FIG. 25 shows an expanded view of the plot presented in FIG. [Figure 26A] FIG. 26A shows a plot of normalized ion intensity as a function of duty cycle for m / z 29 for voltage pulsing to a single lens and a doublet lens. [Figure 26B] FIG. 26B shows a plot of normalized ion intensity as a function of duty cycle for m / z 118 for application of voltage pulses to the single lens and the doublet lens. [Figure 26C] FIG. 26C shows a plot of normalized ion intensity as a function of duty cycle for m / z 922 for application of voltage pulses to the single lens and the doublet lens. [Figure 26D] FIG. 26D shows a plot of normalized ion intensity as a function of duty cycle for m / z 2122 for application of voltage pulses to the single lens and the doublet lens. [Figure 27] FIG. 27 shows normalized ion intensity as a function of duty cycle for multiple m / z ratios, illustrating that the linearity of the duty cycle is maintained not only for singly charged ions, but also for multiply charged ions, according to an embodiment of the present teachings. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0027] The present teachings generally relate to methods and systems for modulating the transmission of ions into a component of a mass spectrometer, such as a mass filter or ion trap (such as a linear ion trap). In some embodiments, one or more voltage pulses are applied to an ion optics, such as an ion lens, positioned in the path of an ion beam of the mass spectrometer to modulate the transmission of ions through the ion optics. The pulse width of the voltage pulses can be determined by using a calibrated ion intensity vs. pulse width relationship and an ideal ion intensity vs. pulse width relationship in a manner discussed in more detail below.

[0028] Various terms are used herein according to their ordinary meaning in the art. The following terms are defined to provide further clarity.

[0029] The term "ion beam brightness" as used herein is a measure of the number of ions passing through a defined area per unit time.

[0030] The term "pulse rise time," as used herein, refers to the time required for a pulse to expand from zero to 90% of its amplitude.

[0031] The term "duty cycle" as used herein refers to the fraction of time that ions are transmitted through the ion-optics system to which a voltage pulse according to the present teachings is applied over a cycle time, which refers to the time interval between successive voltage pulses.

[0032] The term "calibrated normalized ion intensity versus pulse width," as used herein, refers to the ratio of a measured ion intensity to a reference ion intensity as a function of multiple pulse widths applied to the ion optics through which the ions pass.

[0033] The term "ideal normalized ion intensity versus pulse width" as used herein refers to the calculated ratio of ion intensity to a calculated reference ion intensity as a function of multiple voltage pulses having ideal pulse widths characterized by a disappearing rise time and an amplitude high enough to prevent 100% transmission of ions during the ion non-transmission phase.

[0034] The term "about" as used herein refers to up to a + / - 10 percent variation of a numerical value.

[0035] The term "substantially" as used herein refers to a deviation from an absolute state or condition of up to about + / - 10 percent.

[0036] FIG. 1 is a flow chart depicting various steps in an embodiment of a method according to the present teachings for modulating the transmission of an ion beam in a mass spectrometer. The method includes generating an ion beam comprising a plurality of ions (step 1) and directing the ion beam to at least one ion optics positioned in the path of the ion beam, the ion optics including at least one aperture through which the ions can pass (step 2). One or more voltages can be applied to the ion optics at selected duty cycles to obtain a desired attenuation of the brightness of the ion beam (step 3). The pulse width of the voltage pulse can be determined by employing an ideal normalized ion intensity vs. pulse width relationship and a calibrated normalized ion intensity vs. pulse width relationship for the ion. More specifically, the pulse width of the voltage pulse can be determined by identifying a pulse width on the calibrated normalized ion intensity vs. pulse width relationship that corresponds to a desired attenuation on the ideal normalized ion intensity vs. pulse width relationship for the ion.

[0037] As an example, Figure 20 graphically depicts the ideal normalized ion intensity vs. pulse width relationship (A) and the calibrated normalized ion intensity vs. pulse width relationship (B) for an ion with m / z 29. The ideal ion intensity vs. pulse width relationship can be theoretically obtained by assuming that the voltage pulse applied to the ion optics has a vanishing rise time and a sufficiently high amplitude that can suppress the transmission of all ions during the suppression phase of ion transmission.

[0038] A calibration relationship can be obtained by measuring the intensity of ions passing through the ion optics at a selected duty cycle as a function of pulse width for multiple voltage pulses applied to the ion optics and normalizing the measured ion intensities to a reference ion intensity. For example, the calibration normalized ion intensity versus pulse width data depicted in Figure 18 was normalized to ion intensity data obtained via application of a 200 μsec voltage pulse to the ion optics at a 5% duty cycle, as discussed in more detail below.

[0039] In some embodiments, the ideal normalized ion intensity vs. pulse width and the calibrated normalized ion intensity vs. pulse width can both be in the form of a linear relationship. As an example, in some embodiments, the ideal ion intensity vs. pulse width can be defined by the above relationship (1), and the calibrated ion intensity vs. pulse width can in turn be defined by the above relationship (2). As discussed above, the two relationships can be used to provide the above relationship (3), which defines the pulse width of the actual voltage pulse as a function of the pulse width of the ideal voltage pulse.

[0040] The coefficient m1 is mass independent due to the assumed vanishing rise time of an ideal voltage pulse, while the coefficients m2 and b are mass dependent due to the finite rise time of an actual voltage pulse. In addition, as noted above, the kinetic energy of the ions may be affected by some collisions with background gas that the ions experience in the vicinity of the ion optics, which may cause kinetic energy loss. This in turn may result in ions having different axial kinetic energies that also contribute to the mass dependence of m2 and b. In some embodiments, the slope (m2) and intercept (b) above may be obtained via a polynomial fit to normalized ion intensities measured for ions with a number of different m / z ratios. Such a polynomial fit may be used to obtain values ​​of m2 and b for use in equation (3) above when calculating the pulse width for the voltage pulse to be applied to the ion optics. In various aspects, other suitable forms of fits to the data may also be used.

[0041] 21A and 21B show one example of the measured mass dependence of the coefficients m2 and b. In this example, a fit to the measured data can yield the following relationships for m2 and b as a function of ion mass (x):

number

number

[0042] It should be understood that the linear fits in equations (4) and (5) above are for a specific example and that they may vary for other examples of ions due to, for example, variations in pulse rise time, pressure, and spacing between the IQ0 lens and the Q0 ion optics.

[0043] With continued reference to FIG. 18A, in this example, the ideal normalized ion intensity versus pulse width is in the form of relationship (1), and the calibrated normalized ion intensity versus pulse width relationship is obtained by fitting the measured normalized ion intensity to relationship (2).

[0044] 20, by way of example, if a normalized ion intensity of 0.4 is desired, a line can be drawn parallel to the pulse width axis that intersects the ideal relationship at point A1 and the calibrated relationship at point B1, thereby showing that a normalized ion intensity of 0.4 can be achieved with an actual pulse width of about 96.7 microseconds, while for an ideal voltage pulse, a pulse width of about 80 microseconds may be sufficient. In other words, the ideal normalized ion intensity vs. pulse width and the calibrated normalized ion intensity vs. pulse width can be used to identify an adjustment of 16.7 microseconds to the ideal pulse width to obtain an actual pulse width that will achieve the desired normalized ion intensity of 0.4 for ions passing through the ion optics.

[0045] In some embodiments, the ion optics can be in the form of a lens positioned near the entrance port of a mass analyzer component. For example, the ion optics can be in the form of a lens positioned near the entrance port of a mass filter or ion trap (e.g., a linear ion trap) to modulate the transmission of ions into the mass filter or ion trap. In some embodiments, the ion optics can be composed of two or more lenses positioned in tandem to modulate the intensity of an ion beam passing through the ion optics.

[0046] In some embodiments, the duty cycle of the voltage pulses applied to the ion-optics can be, for example, in the range of about 0.1% to about 5%. In some embodiments, the present teachings advantageously enable improved linearity of ion intensity modulation at duty cycles as low as about 0.1%.

[0047] As noted above, the coefficients m2 and b in the above relationship 3 are mass dependent. Thus, relationship 3 defines the pulse width required for a particular ion mass. In some embodiments, the ion beam can include multiple ion types with different m / z ratios. In some such embodiments, the pulse width of the voltage pulse for application to the ion optics can be determined for m / z ratios within the range of m / z ratios exhibited by the ions in the ion beam. Although such pulse widths are determined for only one of the m / z ratios, the advantages associated with the present teachings can still be achieved if the spread of m / z ratios exhibited by the ions is not too wide. For example, in some embodiments where the spread of m / z ratios of the ions in the ion beam is less than about 200 Da, the present approach can result in much improved linear attenuation of the ion beam, especially at low duty cycles of the voltage pulse.

[0048] The present teachings can be implemented in a variety of different mass spectrometers. As an example, FIG. 2 diagrammatically depicts a mass spectrometer 1300 including an ion source 1302 for generating an ion beam comprising a plurality of ions. The ion source can be separated from a downstream section of the spectrometer by a curtain chamber (not shown) in which an orifice plate (not shown) is disposed, providing an orifice through which ions generated by the ion source can enter the downstream section. In this embodiment, an RF ion guide (QJet) can be used to trap and focus ions using a combination of gas dynamics and radio frequency fields. In this embodiment, ions traverse a QJet quadrupole that utilizes a combination of gas dynamics and radio frequency fields to provide improved trapping rates and efficient transport of ions to downstream elements despite the gas load associated with a larger sampling orifice. A lens IQ0 is disposed between the QJet and the downstream Q0 ion guide.

[0049] The ion guide Q0 delivers ions via lens IQ1 and stabilizer ST1 to a downstream quadrupole mass analyzer Q1, which may be mounted in a vacuum chamber that may be evacuated to a pressure that may be maintained below the pressure of the chamber in which the RF ion guide Q0 is located. As a non-limiting example, the vacuum chamber containing Q1 may have a pressure of approximately 1×10 -4 Pressures below 5×10 Torr (e.g., about 5×10 -5 The pressure may be maintained at 100 psi (torr), although other pressures may be used for this or other purposes.

[0050] As discussed in more detail below, multiple voltage pulses in accordance with the present teachings can be applied to lens IQ0 at selected duty cycles to provide a desired attenuation of the ion beam.

[0051] As will be appreciated by those skilled in the art, quadrupole rod set Q1 can be operated as a conventional transmission RF / DC quadrupole mass filter that can be operated to select an ion of interest and / or a range of ions of interest. By way of example, quadrupole rod set Q1 can be provided with RF / DC voltages suitable for operation in a mass-resolved mode. As should be appreciated, taking into account the physical and electrical properties of Q1, parameters for the applied RF and DC voltages can be selected such that Q1 establishes a transmission window for selected m / z ratios, thereby allowing these ions to traverse Q1 largely unperturbed. However, ions with m / z ratios that are outside the window may not acquire a stable trajectory within the quadrupole and may be prevented from traversing quadrupole rod set Q1. It should be appreciated that this mode of operation is only one possible mode of operation for Q1. By way of example, in some embodiments, quadrupole rod set Q1 can be configured as an ion trap. In some aspects, ions can be mass-selectively ejected axially from the Q1 ion trap in the manner described by Hager in "A new Linear ion trap mass spectrometer", Rapid Commun. Mass Spectra. 2002; 16: 512-526.

[0052] Ions passing through the quadrupole rod set Q1 can pass through the stab ST2 and enter the electron capture dissociation cell 1304 according to the present teachings. In some embodiments, the dissociation cell 1304 can include multiple quadrupole rod sets positioned in tandem, and RF voltages can be applied to the multiple quadrupole rod sets to confine electrons near the longitudinal axis of the quadrupole rod sets for efficient interaction of the electrons with precursor ions entering the dissociation module. Capture of one or more electrons by the precursor ions can result in fragmentation of at least a portion of the precursor ions. The fragmented ions can be detected and analyzed by the downstream mass analyzer 1208 in a manner known in the art.

[0053] 2, in this embodiment, a pulsed voltage source 1310 operating under the control of a controller 1312 can apply multiple voltage pulses to lens IQ0 to attenuate the brightness of the ion beam for introduction into the downstream quadrupole rod set Q0. For a desired attenuation of the brightness of the ion beam, the controller can determine the required pulse width and duty cycle of the voltage pulses in accordance with the present teachings, for example by using equation (3) above, and can affect the application of such voltage pulses via the pulsed voltage source to the IQ0 lens.

[0054] By way of example, FIG. 3 diagrammatically depicts one example of an implementation of the controller 1312, which includes a processor 1400 in communication with a random access memory (RAM) module 1404 via a bus 1402, a permanent memory module 1406, a communication interface 1408 providing communication between the controller and a pulsed voltage source, and a user interface 1410. In some embodiments, the permanent memory module 1406 can store information regarding the required pulse width and duty cycle of a voltage pulse that can achieve a desired attenuation of the brightness of the ion beam. The controller can also store information regarding an amplitude or a range of amplitudes for the voltage pulse. Such information can be calculated based on the teachings above. In particular, as discussed in detail above, the calibrated normalized ion intensity vs. pulse width relationship and the ideal normalized ion intensity vs. pulse width relationship can be employed to derive the required pulse width for a voltage pulse applied at a given duty cycle. As discussed above, in some embodiments, the duty cycle of the voltage pulse can be as low as about 0.1%.

[0055] 4, in some embodiments, a doublet lens comprising a lens IQ0A and another lens IQ0B positioned axially alongside lens IQ0A can be placed between the QJet and the Q0 quadrupole. Application of voltage pulses to lenses IQ0A and IQ0B in accordance with the present teachings can attenuate the brightness of the ion beam passing through these two lenses to reach the downstream quadrupole rod set Q0.

[0056] Ions pass through quadrupole ion guide Q0 to quadrupole mass filter Q1. Although not shown in this figure, one or more ion lenses may be positioned between the Q0 and Q1 quadrupoles. In this embodiment, quadrupole rod set Q1 is configured as a mass filter, although in other embodiments it may be configured as a linear ion trap (e.g., a linear ion trap) in a manner known in the art.

[0057] The following examples are provided to further elucidate various aspects of the present teachings. These examples are provided for illustrative purposes only and are not necessarily intended to represent the best way to practice the invention and / or the best results that may be obtained. EXAMPLES

[0058] The data discussed in the following examples were obtained using a hybrid triple quadrupole linear ion trap mass spectrometer modified according to the present teachings. Figures 5A and 5B depict diagrammatically the relevant ion optics. In particular, Figure 5A shows an RF ion guide, designated herein as a QJet, operating at a pressure of 2.8 Torr, followed by a dual IQ0 lens (IQ0A and IQ0B), which then shows the Q0 region, which may be configured as an RF-only ion guide operating at 8.7 millitorr. Lenses IQ0A and IQ0B had aperture diameters of 1.4 mm and 1.5 mm, respectively. In both regions, the pressure is primarily due to nitrogen entering the mass spectrometer through the openings in the orifice plate. Specifically, a gas flow of nitrogen was introduced between the orifice plate and the curtain plate such that the total flow rate exceeded the flow rate of nitrogen into the vacuum chamber through the orifice plate openings. Excess nitrogen flowed outward through the curtain plate openings.

[0059] Figure 5B shows a similar arrangement to that shown in Figure 5A, except that the IQ0A lens has been removed. Removal of the IQ0A lens resulted in an increase in pressure in the Q0 region from 8.7 mTorr to 10.6 mTorr. The increase in pressure was due to the larger 1.5 mm diameter of the opening of the IQ0B lens. Ion Kinetic Energy

[0060] Ions transported through the high pressure region of the QJet ion optics (see FIG. 5A) acquire a gas jet velocity that can lead to ions having an axial kinetic energy that depends on their mass. In the IQ0B lens, the gas undergoes expansion into the lower pressure Q0 region (e.g., 8.7 mTorr in the Q0 region vs. 2.8 mTorr in the QJet region). Using the known free jet expansion equation, the maximum axial velocity can be calculated for a fully expanded expansion. Such a calculation yields a maximum axial gas velocity of 765 m / sec for a pressure of 2.8 mTorr in the QJet region and 8.7 mTorr in the Q0 region. However, in this region, the radial dimension of the gas expansion exceeds the radial dimension of the Q0 ion optics, which can lead to an interruption of the expansion, which can result in ions not acquiring as high a velocity as compared to a fully expanded expansion. The axial kinetic energy of the ions is a function of the velocity they are acquiring. For a maximum velocity of 765 m / sec, an upper limit on the kinetic energy of the ions can be calculated as presented in Table 1 below. Table 1: Ion kinetic energy (V=765m / sec) [Table 1]

[0061] As a result of the different kinetic energies of the ions, their response to the voltage applied to the lens (e.g., IQ0A) located between the QJet and Q0 regions will be mass dependent. The ion kinetic energies can be modified relative to those listed above due to collisions with background gas and by pulsed gradient electric fields applied to the lens, which can cause kinetic energy losses. However, in general, higher potentials are required to stop heavier ions. Figure 6A shows the shape of the voltage pulse applied to the IQ0B lens at a 5% duty cycle. In the ion transmission mode, the DC potential on IQ0B is held at -10V, while in the ion non-transmission mode, the DC potential is reduced to -40V. These values ​​represent the potentials typically employed for positive ion mode.

[0062] Figure 6B shows the leading edge of the voltage pulse depicted in Figure 6 A. With reference to Figure 6B, when an ion transmission voltage pulse is applied to the IQ0B lens, it takes approximately 24 microseconds for the applied DC potential to increase to a level that may allow transmission of the m / z 2122 ion, while for the m / z 322 ion, the time required for transmission is 50 microseconds based on the ion kinetic energy presented in Table 1 above.

[0063] Changing the applied DC potential from ion transmission mode to ion non-transmission mode occurs more quickly because the falling edge of the pulse is more abrupt than the rising edge of the pulse. In other words, in this embodiment, the ion beam can be turned off more quickly than it can be turned on. Also note that the on-axis potential experienced by the ions is different from the potential applied to the lens due to the ion optics located on either side of the lens and the diameter of the lens aperture. Nevertheless, Figures 6A and 6B show that the response of ions to the potential applied to the lens is mass dependent when the ions have different kinetic energies.

[0064] The reduction in the rise time of the voltage pulse applied to the lens increases the speed of the ion's response to the pulse. The more rapid the response, the closer the transmission potential time period is to the desired transmission time period. Figures 7A and 7B compare the voltage pulse depicted in Figures 6A and 6B to a voltage pulse having a more rapid rise and fall time. In particular, the 90% rise time is reduced from about 36 microseconds to about 14 microseconds. The reduced rise time results in a more rapid response of the ion to the pulse. Transmitting lens potential vs. non-transmitting lens potential

[0065] In many embodiments, the ion beam can be turned off by either increasing the DC potential applied to the lens through which the ions pass relative to the adjacent ion optics, or by decreasing the DC potential. For example, Figure 9A diagrammatically depicts a lens IQ0B positioned between the ion guide (QJet) and the quadrupole RF-only ion guide Q0. Figure 8 shows in panels (a), (b), and (c) different patterns of potentials that can be applied to these components.

[0066] Upon application of equal DC potentials to these components, as shown in panel (a), ions are expected to be transmitted in a straight line through the lens, as shown in FIG. 9A.

[0067] When the DC potential applied to the lens is increased as shown in panel (b) of FIG. 8, an electrostatic barrier is generated, leading to the repulsion of ions (in this case positive ions) on the upstream side of the lens, as shown in FIG. 9B.

[0068] When the DC potential applied to the lens is set to an attractive potential, the ions are transmitted through the lens and redirected downstream of the lens where they are neutralized, as shown in Figure 9C. In this case, collisions of the ions with the background gas are required to lower the ion's kinetic energy, allowing them to be attracted back to the lens after passing through it.

[0069] As discussed above, in many embodiments, the amplitude of the DC potential applied to the lens is selected to be high enough to suppress 100% transmission of ions to downstream components. Signal as a function of lens duty cycle

[0070] FIG. 10 shows normalized ion intensity as a function of the duty cycle of the voltage applied to lens IQ0B for ions with m / z ratios of 29, 322, 922, and 2122. The duty cycle was varied from 0 to 100%. The voltage pulses had a rise time of 36 microseconds and an amplitude of 30 V. The pulses were traveling in the negative direction (see, for example, FIG. 9C). Normalization of the ion intensity signal for the data shown in FIG. 10 was based on a duty cycle of 100%.

[0071] The data shown in Figures 11 and 12 was normalized at a 5% duty cycle. This normalization was chosen based on the amount of error in the pulse width compared to the overall cycle time. An error of 14 microseconds makes a voltage pulse with a pulse width of 200 microseconds applied at a 5% duty cycle equivalent to a pulse width of 186 microseconds at a 4.65% duty cycle. This represents an error of 0.35%. Furthermore, note that a 1e7 cps signal at full intensity subject to decay at a 5% duty cycle can result in 1e7cps x 200 microseconds = 2,000 ions. In a pulse counting system, noise is proportional to the square root of the total number of counts. Thus, in this example, the noise is: [ka] The relative noise is then 4 / 2,000×100%=±2.3%. The noise associated with the pulse width (i.e., 0.35%) is less than the signal noise, so normalization at a 5% duty cycle is not expected to significantly affect the signal at lower duty cycle values.

[0072] The plot appears very linear from 0 to 100% duty cycle. However, looking more closely at the region below 5% duty cycle, this shows that the plot is in fact non-linear, as shown in FIG. 11. The intercept of the plot is non-zero and mass dependent, while in the ideal case the plot would be expected to have the same intercept and slope. Reducing the pulse rise time to 14 microseconds improves the linearity of normalized ion intensity versus duty cycle, as shown in FIG. 11.

[0073] It has been observed that increasing the amplitude of the voltage pulse can improve the linearity of the normalized ion intensity versus duty cycle of the applied pulse. Figure 12 presents the normalized ion intensity as a function of the duty cycle of the applied pulse for a pulse with a rise time of 36 microseconds, but with an increase in pulse amplitude from 30V to 50V. Each of the plots shows an extruded intercept where the y-axis is below y=0.

[0074] FIG. 13 shows a plot of normalized ion intensity as a function of the amplitude of the DC potential applied to the IQ0B lens. When the potential is set to −40 V, some ions leak through the lens. At m / z 29 and m / z 322, about 0.13% ion leakage is observed, while at m / z 922, the ion leakage drops to 0.004%, and then rises to 0.23% for m / z 2122. The plot in FIG. 13 shows that the pulse amplitude should be high to reduce the effect of ion leakage. This can also result in improved linearity, as shown in FIG. 12. Lens potential: Compound dependence

[0075] 14A-14C show that the ion transmission characteristics also depend on the analyte (compound) under analysis. These plots depict normalized ionic intensity versus lens potential for PPG (poly(propylene) glycol) and an Agilent prepared mixture (a mixture composed of homogeneously substituted triazatriphosphorine, see U.S. Pat. No. 5,872,3571) with similar mass. The data presented in FIG. 14A-14C show that the transmission characteristics of compounds through the lenses are different. To remedy this difference, the amplitude of the voltage pulse applied to the lens was set to 50V (absolute potential applied to the lens between -10V and -60V), which was the maximum potential provided by the available power supply. Lens potential: Pressure dependence

[0076] 15A-15C show the effect of varying the pressure in the QJet and Q0 ion optics on the shape of the lens potential curve. In these examples, PPG ions were used to collect the data. The pressures shown in each figure represent the pressure in the QJet region, followed by the pressure in the Q0 ion optics region. The data presented show that in each case the lens potential profile becomes broader as the pressure increases. The variations for the positive lens potential are more pronounced relative to those for the negative lens potential. Furthermore, the broadening of the profile becomes greater as the ion mass increases. Lens potential: single vs. double lenses

[0077] 16A-16D show plots providing a comparison of normalized ion intensity versus lens potential for several ions with different m / z ratios when using a single lens versus a dual lens between the QJet and Q0 regions (see FIGS. 5A and 5B). In all cases, the single lens potentials show a more rapid drop in transmission when the lens potential is set to a negative value. However, when the lens potential is set to a positive value, the transmission window expands to more positive lens potentials, and in some cases non-transmission and blocking potentials exist beyond the range provided by the available power supply. The shape of the curves indicates that it may be better to apply a negative lens potential than a positive lens potential with a single lens that turns off the ion beam more completely than a dual lens. Lens potential: fragment ions vs. non-fragment ions

[0078] The data presented in FIG. 17 shows that as ions are formed during their transition along the ion guide, transmission through the lens can occur over a wide range of potentials applied to the IQ0B lens. M / z 59 is known to be a fragment ion that can form along the ion guide in the interface region of the mass spectrometer. FIG. 17 depicts normalized ion intensity as a function of lens potential for fragment ions of m / z 59 and stable ions at m / z 68. Larger ions may be able to transmit through the IQ0B lens if the potential is not sufficient to prevent their transmission. If a larger ion passes through the lens and fragments downstream of the lens in the Q0 ion optics produce an ion fragment of m / z 59, it would appear that m / z 59 was transmitted. In this example, m / z 59 was not transmitted, but rather was generated downstream of the lens. The intensity of the ion fragments is expected to be highly dependent on the ion source and interface conditions. Duty cycle linearity enhancement

[0079] 18A-18D show plots of normalized intensities of ions passing through the IQ0B lens as a function of pulse width of the applied voltage pulse for ions with different m / z ratios. Each plot shows ideal normalized ion intensity vs. pulse width and calibrated normalized ion intensity vs. pulse width fitted to a linear relationship. The ion intensity obtained via application of a 200 microsecond voltage pulse to the lens at a 250 Hz pulse repetition rate corresponding to a 5% duty cycle was taken as the reference intensity to obtain the normalized intensity. That is, the measured or expected ion intensity was divided by the reference intensity to obtain the normalized intensity.

[0080] Each graph depicts a plot representing normalized measured ion intensity as a function of pulse width (referred to herein as calibrated normalized ion intensity versus pulse width) for a voltage pulse having a rise time of approximately 14 microseconds, a linear fit to the measured normalized intensity data as a function of pulse width, and a plot representing ideal normalized intensity as a function of pulse width. The ideal normalized ion intensity is the intensity that would be expected if the voltage pulse applied to the lens had a vanishing rise time and the anti-transmitting potential applied to the lens could completely suppress transmission of ions through the lens.

[0081] A linear fit of the calibrated ion intensity versus pulse width shows a slope and intercept that varies as a function of m / z ratio.

[0082] FIG. 19 shows the fit to the ideal normalized ion intensity vs. pulse width and the calibrated normalized ion intensity vs. pulse width for m / z 29. In this example, the linear fit to the data was normalized to the ideal fit at the 200 microsecond pulse width point. In other words, the above equation (2) was normalized again for a second time. FIG. 20 shows that, for m / z 29, if the pulse width is ideal (i.e., the pulse has a vanishing rise time and can completely suppress the transmission of ions through the lens), to obtain a normalized ion intensity of 0.4, the pulse width of the applied voltage pulse should be about 96.7 microseconds (point B), while a pulse width of 80 microseconds may be required to obtain a normalized ion intensity of 0.4.

[0083] A linear fit to an ideal normalized ion intensity versus pulse width plot can be represented by equation (1) above, which is reproduced below: y=m1x1 Also, a linear fit to the calibrated normalized ion intensity versus pulse width plot can be represented by equation (2) above, which is also reproduced below. y=m2x2+b

[0084] As discussed in detail above, these two equations can be adopted to obtain equation (3) above, which can yield the normalized ionic intensity y, in terms of the pulse width of the applied pulse, as reproduced below:

number

[0085] The mass-dependent coefficients m2 (slope) and b (intercept) for the above calibration data are plotted in Figures 21A and 21B, respectively. In this example, the slope and intercept can be represented by a fit to the following third order polynomial:

number

[0086] If an ideal pulse width defined by x1 is desired, this value can be inserted into equation (3) above to obtain a value for x2 that represents the pulse width of the voltage pulse to be applied to the lens.

[0087] Figures 22-24 show plots of normalized ion intensity passing through lens IQ0B as a function of duty cycle for the positive ion, negative ion, and positive enhanced product ion (EPI) modes of operation, respectively. The duty cycle was 5%, corresponding to a pulse width of 200 microseconds. The pulse amplitude was set to the maximum pulse amplitude that could be delivered by the power supply (i.e., 50V). In the EPI experiments in which a linear ion trap was used, the trap was filled for approximately 4 ms per data point, which allowed the fill time to be matched to the 250 Hz pulse repetition rate.

[0088] Figure 25 shows an expanded view of Figure 22 illustrating the region between 0 and 1% duty cycle. It can be seen that for higher masses there is a region of reduced intensity below about 0.3% duty cycle. Without being limited to any particular theory, this reduced intensity may be due to confinement of ions in the region between the IQ0B lens and the Q0 ion optics as a result of the short transmitted pulse.

[0089] 26A-26D present plots of normalized ion intensity as a function of duty cycle for two cases, namely, (1) when a single IQ0B lens is positioned near the entrance port of the Q0 quadrupole, and (2) when doublet lenses IQ0A and IQ0B are positioned near the entrance port of the Q0 quadrupole, for multiple m / z ratios. In all cases, the amplitude of the voltage pulse was selected to be 50V (i.e., the maximum amplitude provided by the power supply). This data shows that the linearity of ion beam attenuation is maintained in both the single lens and doublet lens cases, thus demonstrating that the present teachings provide a robust method and system for attenuating the brightness of an ion beam in a mass spectrometer.

[0090] Figure 27 shows that the linearity of the duty cycle is maintained for multiply charged ions as well. In this example, ions with charge states of +1, +2, and +3 all display the same linearity. The main difference between multiply charged ions and singly charged ions is the pulse amplitude, which is proportional to the charge state of the ion. Thus, ions with a charge state of +3 experience a pulse with an amplitude of 150V, while singly charged ions experience only a pulse with an amplitude of 50V. The present specification also provides, for example, the following items: (Item 1) 1. A method for modulating the transmission of ions in a mass spectrometer, comprising: generating an ion beam comprising a plurality of ions; directing the ion beam to ion optics positioned in a path of the ion beam, the ion optics including at least one aperture through which the ions can pass; applying one or more voltage pulses at a selected duty cycle to the ion optics to obtain a desired attenuation of the ion beam brightness passing through the ion optics; wherein a pulse width of the voltage pulse at the selected duty cycle is determined by identifying a pulse width on a calibrated normalized ion intensity vs. pulse width relationship for the ion that corresponds to the desired decay on an ideal normalized ion intensity vs. pulse width relationship for the ion. (Item 2) 2. The method of claim 1, wherein the calibrated normalized ion intensity versus pulse width relationship is obtained via a linear fit to data corresponding to normalized intensity of the ions transmitted through the ion optics as a function of pulse width of a plurality of voltages applied to the ion optics at the selected duty cycle. (Item 3) The ideal normalized ionic intensity vs. pulse width relationship is the following linear relationship: y=m 1 x 1 wherein: y represents the normalized ion intensity, x 1 represents the ideal pulse width, m 1 represents the slope of the linear relationship. (Item 4) The calibrated normalized ion intensity vs. pulse width relationship is the following linear relationship: y=m 2 x 2 +b wherein: y represents the normalized ion intensity, x 2 represents the pulse width of the voltage pulse applied to the ion optics; m 2 represents the slope of the linear relationship, 4. The method according to claim 3, wherein b represents the intercept of the linear relationship. (Item 5) The pulse width x 2 is related to the following relationship:

number

Claims

1. 1. A method for modulating the transmission of ions in a mass spectrometer, comprising: generating an ion beam comprising a plurality of ions; directing the ion beam to ion optics positioned in a path of the ion beam, the ion optics including at least one aperture through which the ions can pass; applying one or more voltage pulses at a selected duty cycle to the ion optics to obtain a desired attenuation of the ion beam brightness passing through the ion optics; a pulse width of the voltage pulse at the selected duty cycle is determined by identifying a pulse width on a calibrated normalized ion intensity vs. pulse width relationship for the ion that corresponds to the desired decay on an ideal normalized ion intensity vs. pulse width relationship for the ion; The ideal normalized ionic intensity vs. pulse width relationship is the following linear relationship: y = m1 x 1 wherein: y represents the normalized ion intensity, x 1 represents the ideal pulse width; m 1 represents the slope of the linear relationship; The calibrated normalized ion intensity vs. pulse width relationship is the following linear relationship: y = m2 x2 + b wherein: y represents the normalized ion intensity, x 2 represents the pulse width of the voltage pulse applied to the ion optics; m 2 represents the slope of the linear relationship; b represents the intercept of said linear relationship.

2. The pulse width x ２ is related to the following relationship: [0010] The method of claim 1 , wherein the formula is determined according to:

3. 3. The method of claim 2, further comprising re-normalizing the relationship of claim 2 at a 5% duty cycle point.

4. 2. The method of claim 1 , wherein the calibrated normalized ion intensity for a voltage pulse width associated with a plurality of voltage pulses applied to the ion optics in the duty cycle is obtained as a ratio of a measured intensity of ions passing through the ion optics at a calibrated voltage pulse width associated with a plurality of calibrated voltage pulses applied to the ion optics in the duty cycle to a measured intensity of ions passing through the ion optics at that voltage pulse width.

5. The method of claim 4 , wherein the calibration voltage pulse width is in the range of 4 microseconds to 200 microseconds.

6. The method of claim 1 , wherein the ions comprise a plurality of different m / z ratios.

7. The method of claim 6 , wherein the ideal normalized ion intensity vs. pulse width relationship and the calibrated normalized ion intensity vs. pulse width relationship are determined with respect to at least one of the m / z ratios.

8. 8. The method of claim 7, wherein the ideal normalized ion intensity vs. pulse width relationship and the calibrated normalized ion intensity vs. pulse width relationship determined for the at least one of the m / z ratios are employed to determine the pulse width of the voltage pulse.

9. 7. The method of claim 6, further comprising generating an ideal normalized ion intensity vs. pulse width relationship and a calibrated normalized ion intensity vs. pulse width relationship for ions having each of said m / z ratios.

10. 10. The method of claim 9, further comprising selecting the ideal normalized ion intensity vs. pulse width relationship and the calibrated normalized ion intensity vs. pulse width relationship for ions having one of the m / z ratios to determine a pulse width of the voltage pulse for application to the ion optics as the ions having the different m / z ratios pass through the ion optics.

11. The method of claim 1 , wherein the voltage pulse has a rise time of less than 20 microseconds.

12. The method of claim 1 , wherein the voltage pulse has an amplitude selected to suppress transmission of ions through the ion-optics system during a suppression stage of the voltage pulse.

13. 2. The method of claim 1, wherein the selected duty cycle is less than 5%, or less than 4%, or less than 3%, or less than 2%, or less than 1%, and optionally within the range of 0.1% to 1%.

14. The method of claim 1 , wherein the voltage pulse has a pulse width of less than 200 microseconds, and optionally a pulse width in the range of 4 microseconds to 200 microseconds.

15. 10. The method of claim 1, further comprising positioning one of the RF-only ion guides downstream of the ion-optics such that the ion-optics is located near an entrance to the RF-only ion guide.

16. 1. A method for modulating the transmission of ions in a mass spectrometer, comprising: generating an ion beam comprising a plurality of ions; directing the ion beam to ion optics positioned in a path of the ion beam, the ion optics including at least one aperture through which the ions can pass; applying one or more voltage pulses at a selected duty cycle to the ion-optics to modulate passage of the ions through the ion-optics; wherein the pulse width of the voltage pulse is determined by calculating an adjustment to the pulse width of an ideal pulse that would result in a desired normalized intensity of ions passing through the ion optics; calculating the adjustment value includes utilizing an ideal normalized ion intensity vs. pulse width relationship and a calibrated normalized ion intensity vs. pulse width relationship for the ion; The ideal normalized ionic intensity vs. pulse width relationship is the following linear relationship: y = m1 x 1 wherein: y represents the normalized ion intensity, x 1 represents the ideal pulse width; m 1 represents the slope of the linear relationship; The calibrated normalized ion intensity vs. pulse width relationship is the following linear relationship: y = m2 x2 + b wherein: y represents the normalized ion intensity, x 2 represents the pulse width of the voltage pulse applied to the ion optics; m 2 represents the slope of the linear relationship; b represents the intercept of said linear relationship.

17. The method of claim 16 further comprising re-normalizing the adjustment value at a 5% duty cycle point.

18. 1. A mass spectrometer comprising: an ion source for generating an ion beam comprising a plurality of ions; ion optics positioned in a path of the ion beam, the ion optics comprising at least one aperture through which ions can pass; a voltage source configured to apply one or more voltage pulses to the ion optics at a selected duty cycle to obtain a desired attenuation of the ion beam brightness; the voltage pulse having a pulse width corresponding to a pulse width on a calibrated normalized ion intensity vs. pulse width relationship for the ion that corresponds to the desired attenuation on an ideal normalized ion intensity vs. pulse width relationship for the ion; The ideal normalized ionic intensity vs. pulse width relationship is the following linear relationship: y = m1 x 1 wherein: y represents the normalized ion intensity, x 1 represents the ideal pulse width; m 1 represents the slope of the linear relationship; The calibrated normalized ion intensity vs. pulse width relationship is the following linear relationship: y = m2 x2 + b wherein: y represents the normalized ion intensity, x 2 represents the pulse width of the voltage pulse applied to the ion optics; m 2 represents the slope of the linear relationship; b represents the intercept of the linear relationship.

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