Method of modulating transmission of ions in a mass spectrometer and mass spectrometer

Abstract

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

Description

[0001] Related applications

[0002] This application claims priority to provisional patent application No. 62 / 877,542, filed on July 23, 2019, entitled "Increased Dynamic Range for the Attenuation of an Ion Beam", the entire contents of which are incorporated herein by reference. Technical Field

[0003] This teaching generally relates 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 used to increase the dynamic range of attenuation of the ion beam in a mass spectrometer. Background Technology

[0004] Mass spectrometry (MS) is an analytical technique used to measure the mass-to-charge ratio of molecules, with both qualitative and quantitative applications. MS can be used to identify unknown compounds, determine the structure of specific compounds by observing fragments of those compounds, and quantify the content of specific compounds in a sample. Since mass spectrometry detects chemical entities as ions, the analytes must be converted into charged ions during sample processing.

[0005] It is typically necessary to attenuate the ion beam intensity in a mass spectrometer, for example, to avoid detector saturation, reduce space charge that could adversely affect the performance of a quadrupole mass filter, or prevent overfilling of the ion trap. The ability to reduce the ion beam intensity in a predictable manner can also reduce the number of dilutions required to analyze samples in the mass spectrometer.

[0006] A common technique for reducing ion beam intensity is to change the potential applied to a lens located near the entrance of a mass spectrometer component from transmission mode to non-transmission mode. The reduction in beam intensity can be proportional to the duty cycle of the potential applied to the lens. For example, this technique has been used to attenuate the ion beam by pulsed potential applied to the skimmer of the mass spectrometer.

[0007] However, this technique is affected by nonlinearity at low duty cycles.

[0008] Therefore, there is a need for methods and systems to enhance the intensity of ion beams in attenuated mass spectrometers, and in particular, such methods and systems that allow for linear attenuation of ion beam intensity over a wide intensity range. Summary of the Invention

[0009] On one hand, a method for modulating ion transmission in a mass spectrometer is disclosed, comprising: generating an ion beam containing a plurality of ions; guiding the ion beam to an ion optical device located in the ion beam path, wherein the ion optical device includes at least one opening through which ions can pass; and applying one or more voltage pulses to the ion optical device at a selected duty cycle to obtain a desired attenuation of the brightness of the ion beam passing through the ion optical device, wherein the pulse width of the voltage pulse at the selected duty cycle is determined by identifying a pulse width in a calibrated normalized ion intensity versus pulse width relationship of the ions corresponding to the desired attenuation in the ideal normalized ion intensity versus pulse width relationship of the ions.

[0010] In some embodiments, the calibrated normalized ion intensity versus pulse width relationship is obtained by linear fitting of data corresponding to the normalized intensity of the ions transmitted through the ion optics, which varies with the pulse width of a plurality of voltages applied to the ion optics with the selected duty cycle.

[0011] As an example, the relationship between ideal normalized ion intensity and pulse width can be defined by the following linear relationship:

[0012] y = m1x1, Equation (1)

[0013] in,

[0014] y represents the normalized ionic strength.

[0015] x1 represents the ideal pulse width, and

[0016] m1 represents the slope of the linear relationship.

[0017] The relationship between calibrated normalized ion intensity and pulse width can be defined by the following linear relationship:

[0018] y = m²x² + b, Equation (2)

[0019] in,

[0020] y represents the normalized ionic strength.

[0021] x2 represents the pulse width of the voltage pulse applied to the ion optics device.

[0022] m2 represents the slope of the linear relationship, and

[0023] b represents the intercept of the linear relationship.

[0024] Based on the following relationship, the pulse width x2 to be applied to the ion optics can be determined using the above equations (1) and (2):

[0025]

[0026] In some embodiments, the calibrated normalized ion intensity for the voltage pulse width associated with a plurality of voltage pulses applied to the ion optics at the said duty cycle is obtained as a ratio of the measured intensity of ions passing through the ion optics at that voltage pulse width to the measured intensity of ions passing through the ion optics at the calibration voltage pulse width associated with a plurality of calibration voltage pulses applied to the ion optics at the said duty cycle. As an example, the calibration voltage pulse may have a pulse width of approximately 200 microseconds and be applied to the ion optics at a duty cycle of approximately 5%.

[0027] In some embodiments, the slope (m2) and intercept (b) described above can be obtained by polynomial fitting of the measured normalized ion intensities of ions having multiple different m / z ratios. This polynomial fitting can be used to obtain the values ​​of m2 and b when calculating the pulse width of the voltage pulse to be applied to the ion optics, for use in the above equation (3).

[0028] In some embodiments, the ion beam may include ions having a plurality of different m / z ratios. In some such embodiments, equation (3) above may be used to determine the pulse width for one of the m / z ratios. The determined pulse width may then be applied to the ion optics. While the determined pulse width may differ from the optimal pulse width for the m / z ratio used to determine the pulse width, using the determined pulse width can enhance the linearity of ion transmission, especially when the m / z ratio spans a wider range (e.g., 50 to 250 Da) for low (e.g., 50 to 250 Da) and medium (e.g., 600 to 800 Da) mass ranges, and even for higher mass ranges spanning a wider range (e.g., 300 Da), the m / z ratio is equal to or less than about 200 Da.

[0029] In some embodiments, the pulse width of the voltage pulse applied to the ion optics may be equal to or less than about 2000 microseconds, for example, in the range of about 4 microseconds to about 2000 microseconds. Furthermore, in some embodiments, the rise time of the voltage pulse applied to the ion optics may be equal to or less than about 20 microseconds. In some embodiments, the amplitude of the voltage pulse is selected to suppress the transmission of ions (preferably all ions) to a component disposed downstream of the ion optics during the suppression phase of the voltage pulse.

[0030] Voltage pulses can be applied to ion optics at various duty cycles. For example, the duty cycle can range from about 0.1% to about 5%, such as 1%, 2%, 3%, 4%, or any other value within that range.

[0031] In some embodiments, this teaching can be used to attenuate the brightness of the ion beam in a mass spectrometer by a factor ranging from about 0.1% to about 5%.

[0032] In some embodiments, the method further includes positioning either a mass filter or an ion trap downstream of the ion optics, such that the ion optics is positioned near the inlet of the mass filter or ion trap to modulate the transmission of ions thereto. As discussed in more detail below, the ion optics may be positioned in a region where the background gas provides sufficient pressure, causing ions to lose some of their axial kinetic energy due to 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 mass spectrometer. As an example, the background pressure in the region where the ion optics is positioned can be in the range of approximately a few millitors (e.g., 1 millitor to approximately 10 millitors).

[0033] In a related aspect, a method for modulating ion transmission in a mass spectrometer is disclosed, comprising: generating an ion beam containing a plurality of ions; guiding the ion beam to an ion optical device located in the ion beam path, wherein the ion optical device includes at least one opening through which ions can pass; and applying one or more voltage pulses to the ion optical device at a selected duty cycle to modulate the passage of ions through the ion optical device, wherein the pulse width of the voltage pulses is determined by calculating an adjustment to the pulse width of an ideal pulse that would result in the desired normalized intensity of ions passing through the ion optical device. The step of calculating the adjustment may include: utilizing the ideal normalized ion intensity versus pulse width relationship of the ions and calibrating the normalized ion intensity versus pulse width relationship.

[0034] In a related aspect, a mass spectrometer is disclosed, comprising an ion source for generating an ion beam containing a plurality of ions, an ion optics located in the ion beam path, the ion optics including at least one opening 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 the brightness of the ion beam, wherein the voltage pulses have pulse widths corresponding to pulse widths of calibrated normalized ion strengths on a pulse width relationship corresponding to the desired attenuation on the ideal normalized ion strength of the ions.

[0035] The mass spectrometer may also include a controller for determining the pulse width of the voltage pulse by identifying the pulse width in relation to the calibrated normalized ion intensity versus pulse width relationship. The controller may communicate with a voltage source to transmit the determined pulse width to the voltage source.

[0036] In some embodiments, the voltage pulse has a rise time of less than approximately 20 microseconds. Furthermore, in some embodiments, the voltage pulse has a pulse width ranging from approximately 4 microseconds to approximately 200 microseconds. Additionally, the voltage pulse may have an amplitude selected to suppress ion (preferably all ions) transmission through an ion optics device to which the voltage pulse is applied during the suppression phase of the voltage pulse. As an example, the voltage pulse may have an amplitude of at least approximately 50 volts.

[0037] In some embodiments, the controller controls a voltage source to apply the voltage pulse to the ion optics at a duty cycle of less than about 5% (e.g., a duty cycle in the range of about 0.1% to about 5%).

[0038] In some embodiments, the mass spectrometer may further include a mass filter, such as a quadrupole mass filter, disposed downstream of the ion optics such that the ion optics are located near the inlet port of the mass filter, for modulating the transmission of ions into the mass filter. In some embodiments, an ion trap, such as a linear ion trap (e.g., a quadrupole linear ion trap), is disposed downstream of the ion optics such that the ion optics are located near the inlet port of the ion trap, for modulating the transmission of ions into the ion trap. Attached Figure Description

[0039] Figure 1 This is a flowchart depicting the various steps of using an ion beam in an attenuated mass spectrometer as described in the embodiments of this teaching.

[0040] Figure 2 A mass spectrometer according to an embodiment of this teaching is schematically depicted.

[0041] Figure 3 Depicting applicable Figure 2 An implementation example of a controller for a mass spectrometer.

[0042] Figure 4 A partial schematic diagram of a mass spectrometer according to an embodiment is depicted, wherein a doublet lens is located between an upstream ion guide and a downstream mass filter.

[0043] Figure 5A This is a schematic partial view of a mass spectrometer, including a doublet lens configuration with two lenses positioned between the ion guide and the mass filter, wherein a voltage pulse applied to the lenses according to this teaching provides modulation of the ion beam intensity.

[0044] Figure 5B yes Figure 5A The diagram depicts a modified version of the mass spectrometer, in which the doublet lens is replaced by a single lens.

[0045] Figure 6A Describes the application to Figure 5Aor Figure 5B The voltage pulse of the lens shown.

[0046] Figure 6B Depicting Figure 6A The leading edge of the voltage pulse shown,

[0047] Figure 7A Two voltage pulses are depicted, one of which has a faster rise time.

[0048] Figure 7B Depicting Figure 7A The leading edge of the voltage pulse depicted in the image.

[0049] Figure 8 The different modes of potential that can be applied to a lens located between the ion guide and downstream components (e.g., mass filter or ion trap) of the mass spectrometer are shown in three panels (i.e., panels (a), (b), and (c)).

[0050] Figure 9A It schematically depicts when Figure 8 When the voltage pattern shown in panel (a) is applied to the lens, ions follow the path of the lens located between the ion guide and the downstream component.

[0051] Figure 9B It schematically depicts when Figure 8 When the voltage pattern shown in panel (b) is applied to the lens, ions pass through Figure 9A The trajectory of the lens shown.

[0052] Figure 9C It schematically depicts when Figure 8 When the voltage pattern shown in panel (c) is applied to the lens, ions pass through Figure 9B The trajectory of the lens shown.

[0053] Figure 10 The graph shows the relationship between normalized ion intensity and duty cycle for an applied voltage pulse with a rise time of 36 microseconds and an amplitude of 30V for multiple m / z ratios.

[0054] Figure 11 It shows Figure 10 The portion of the diagram depicted at a low duty cycle.

[0055] Figure 12 The graph shows the relationship between normalized ion intensity and duty cycle for an applied voltage pulse with a rise time of 14 μs and an amplitude of 50 V for multiple m / z ratios.

[0056] Figure 13 The graphs showing the relationship between normalized ion intensity and lens potential for multiple m / z ratios are presented.

[0057] Figures 14A-14C The graphs showing the relationship between normalized ionic strength and lens potential for various compounds are presented.

[0058] Figures 15A-15C The graph shows the relationship between normalized ion intensity as a function of the DC potential applied to the lens located between the ion director and the downstream component for different pressures and for several different m / z ratios.

[0059] Figures 16A-16D The graph shows the relationship between the normalized ion intensity as a function of the DC potential applied to a single lens and a double lens located between the ion guide and the downstream component for several different m / z ratios.

[0060] Figure 17 The graph shows the relationship between normalized ionic strength as a function of DC potential for unfragmented ions at m / z 68 and ionic fragments at m / z 59.

[0061] Figure 18A The graph shows the relationship between ideal and calibrated normalized ion intensity and pulse width for a voltage pulse with a rise time of 14 μs and an amplitude of 40 V, for an ion with m / z 29.

[0062] Figure 18B The graph shows the relationship between ideal and calibrated normalized ion intensity and pulse width for a voltage pulse with a rise time of 14 μs and an amplitude of 40 V, for an ion with m / z 322.

[0063] Figure 18C The graph shows the relationship between ideal and calibrated normalized ion intensity and pulse width for a voltage pulse with a rise time of 14 μs and an amplitude of 40 V, for an ion with m / z 922.

[0064] Figure 18D The graph shows the relationship between ideal and calibrated normalized ion intensity and pulse width for a voltage pulse with a rise time of 14 μs and an amplitude of 40 V, for an ion with m / z 2122.

[0065] Figure 19 It shows how to... Figure 18A The relationship graph presented is obtained by fitting the data to a linear relationship.

[0066] Figure 20 It shows the use of Figure 19 The relationship diagram presented in the figure is used to identify the pulse width of the voltage pulse that will result in the desired normalized ion intensity.

[0067] Figure 21AThe mass correlation slope for identifying the linear relationship between the pulse width of a voltage pulse as a function of ion mass, according to an embodiment of this teaching, is shown.

[0068] Figure 21B The mass-related intercept for identifying the linear relationship between the pulse width of a voltage pulse as a function of ion mass, according to an embodiment of this teaching, is shown.

[0069] Figure 22 The graph shows the relationship between normalized ion intensity and the duty cycle of the applied voltage pulse for positive ion mode.

[0070] Figure 23 The graph shows the relationship between normalized ion intensity and the duty cycle of the applied voltage pulse for negative ion mode.

[0071] Figure 24 The graph shows the relationship between normalized ion intensity and the duty cycle of the applied voltage pulse for the positive enhanced product ion (EPI) mode.

[0072] Figure 25 It shows Figure 24 An expanded view of the relationship diagram presented in the middle.

[0073] Figure 26A The graph shows the relationship between normalized ion intensity as a function of duty cycle for m / z 29 when a voltage pulse is applied to a single lens and a doublet lens.

[0074] Figure 26B The graph shows the relationship between normalized ion intensity as a function of duty cycle for applying a voltage pulse to a single lens and a doublet lens, for m / z 118.

[0075] Figure 26C The graph shows the relationship between normalized ion intensity as a function of duty cycle for m / z 922 when a voltage pulse is applied to a single lens and a doublet lens.

[0076] Figure 26D The graph shows the relationship between normalized ion intensity as a function of duty cycle for m / z 2122 for both single-lens and double-lens systems when a voltage pulse is applied.

[0077] Figure 27 The normalized ion strength for multiple m / z ratios as a function of duty cycle is shown in the embodiments of this teaching, illustrating that duty cycle linearity is maintained not only for single charged ions but also for multiple charged ions. Detailed Implementation

[0078] This teaching generally relates to methods and systems for modulating the transmission of ions into components of a mass spectrometer, such as mass filters or ion traps, such as linear ion traps. In some embodiments, one or more voltage pulses are applied to ion optics, such as ion lenses, positioned in the path of the ion beam of the mass spectrometer to modulate the transmission of ions through ion optics. The pulse width of the voltage pulse can be determined using a calibrated ion intensity versus pulse width relationship and an ideal ion intensity versus pulse width relationship, as discussed in more detail below.

[0079] Various terms are used herein according to their ordinary meaning in the art. The following terms are defined for further explanation:

[0080] As used herein, the term "brightness of an ion beam" is a measure of the number of ions that pass through a specified area per unit time.

[0081] As used herein, the term "pulse rise time" refers to the time required for a pulse to increase from zero to 90% of its amplitude.

[0082] As used herein, the term “duty cycle” refers to the percentage of time an ion is transmitted through an ion optics device by a voltage pulse applied according to the teachings within a cycle time, where the cycle time refers to the time interval between consecutive voltage pulses.

[0083] As used herein, the term "calibrated normalized ion strength to pulse width" refers to the ratio of the measured ion strength to a reference ion strength as a function of the pulse widths applied to the ion optics through which the ions pass.

[0084] As used herein, the term “ideal normalized ion strength to pulse width” refers to the calculated ratio of the ion strength as a function of a plurality of voltage pulses having an ideal pulse width relative to a calculated reference ion strength, characterized by a disappearance rise time and a sufficiently high amplitude to prevent 100% transmission of ions during their nontransmissive phase.

[0085] As used in this article, the term “approximately” refers to a numerical change of up to + / - 10%.

[0086] As used herein, the term “substantially” means a deviation from the complete state or condition of at most approximately + / - 10%.

[0087] Figure 1This is a flowchart depicting the various steps in an embodiment of a method for modulating ion beam transmission in a mass spectrometer according to the present teachings. The method includes generating an ion beam comprising a plurality of ions (step 1) and guiding the ion beam to at least one ion optics located in the ion beam path, wherein the ion optics includes at least one opening through which the ion beam can pass (step 2). One or more voltages may be applied to the ion optics at a selected duty cycle to obtain a desired attenuation of the ion beam brightness (step 3). The pulse width of the voltage pulse can be determined by employing an ideal normalized ion intensity versus pulse width relationship and a calibrated normalized ion intensity versus pulse width relationship. More specifically, the pulse width of the voltage pulse can be determined by identifying the pulse width in the calibrated normalized ion intensity versus pulse width relationship corresponding to the desired attenuation in the ideal normalized ion intensity versus pulse width relationship of the ions.

[0088] As an example, Figure 20 The ideal normalized ion intensity versus pulse width relationship (A) and the calibrated normalized ion intensity versus pulse width relationship (B) are schematically depicted for ions with m / z 29. The ideal ion intensity versus pulse width relationship can theoretically be obtained by assuming that the voltage pulse applied to the ion optics has a vanishing rise time and a sufficiently high amplitude to suppress the transmission of all ions during the suppression phase of all ions.

[0089] The 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 the pulse width of multiple voltage pulses applied to the ion optics and normalizing the measured ion intensity relative to a reference ion intensity. For example, Figures 18A-18D The calibration-normalized ion intensity described herein normalizes the pulse width data relative to the ion intensity data obtained by applying a 200-microsecond voltage pulse to the ion optics at a 5% duty cycle, as discussed in more detail below.

[0090] In some embodiments, both the ideal normalized ion intensity to pulse width and the calibrated normalized ion intensity to pulse width can be linear relationships. As an example, in some embodiments, the ideal ion intensity to pulse width can be defined by the above relationship (1), and the calibrated ion intensity to pulse width can be defined by the above relationship (2). As discussed above, these 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.

[0091] While the coefficient m1 is mass-independent due to the assumed ideal rise time of the voltage pulse, the coefficients m2 and b are mass-dependent due to the finite rise time of the actual voltage pulse. Furthermore, as mentioned above, the kinetic energy of the ions is affected by the number of collisions they undergo with the background gas near the ion optics, resulting in kinetic energy loss. This, in turn, leads to ions having different axial kinetic energies, which also contributes to the mass dependence of m2 and b. In some embodiments, the slope (m2) and intercept (b) described above can be obtained by polynomial fitting of measured normalized ion intensities of ions with multiple different m / z ratios. This polynomial fitting can be used to obtain the values ​​of m2 and b when calculating the pulse width of the voltage pulse to be applied to the ion optics, for use in equation (3) above. Other suitable forms of data fitting can be used in various aspects.

[0092] As an example, Figure 21A and Figure 21B An example of the correlation between the coefficients m2 and b in the measurement mass is shown. In this example, fitting the measurement data can lead to the following relationship between m2 and b as a function of ion mass (x):

[0093] m2=-1.5678×10 -13 x 3 +7.9705×10 -13 x 2 -1.2565×10 -6 x + 5.8566 × 10 -3 Equation (4)

[0094] b = 3.136 × 10 -11 x 3 -1.594×10 -7 x 2 +2.513×10 -4 x-1.713×10 -1 Equation (5)

[0095] It should be understood that the linear fits in equations (4) and (5) above are for a specific example, and for other ion examples, they may differ, for example, due to variations in pulse rise time, pressure, and the spacing between the IQ0 lens and the Q0 ion optics.

[0096] Continue to refer to Figure 18A In this example, the ideal normalized ion intensity versus pulse width is in the form of relation (1), and the calibrated normalized ion intensity versus pulse width relation is obtained by fitting the measured normalized ion intensity to relation (2).

[0097] refer to Figure 20As an example, if a normalized ion intensity of 0.4 is desired, a line parallel to the pulse width axis can be plotted. This line intersects the ideal relationship at point A1 and the calibration relationship at point B1, indicating that a normalized ion intensity of 0.4 can be obtained using an actual pulse width of approximately 96.7 microseconds, while for an ideal voltage pulse, a pulse width of approximately 80 microseconds would be sufficient. In other words, the ideal normalized ion intensity versus pulse width and the calibrated normalized ion intensity versus pulse width can be used to identify an adjustment of 16.7 microseconds to the ideal pulse width to obtain the actual pulse width that will achieve the desired normalized ion intensity of 0.4 for ions passing through the ion optics.

[0098] In some embodiments, the ion optics may be in the form of a lens located near the inlet port of a mass spectrometer component. For example, the ion optics may be in the form of a lens located near the inlet 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 may consist of two or more lenses positioned in series for modulating the intensity of the ion beam passing through them.

[0099] In some embodiments, the duty cycle of the voltage pulse applied to the ion optics can range, for example, from about 0.1% to about 5%. In some embodiments, this teaching advantageously allows for enhanced linearity of ion intensity modulation at duty cycles as low as about 0.1%.

[0100] As described above, the coefficients m2 and b in relation 3 are related to mass. Therefore, relation 3 defines the pulse width required for a specific ion mass. In some embodiments, the ion beam may include multiple ion types with different m / z ratios. In some such embodiments, the pulse width for the voltage pulse applied to the ion optics can be determined for the range of m / z ratios exhibited by the ions within the ion beam. While such a pulse width is determined only for one of the m / z ratios, the advantages associated with this teaching can still be achieved if the spread of the m / z ratios exhibited by the ions is not too wide. For example, in some embodiments where the spread of the m / z ratio of the ions within the ion beam is less than about 200 Da, this approach can result in a significantly enhanced linear attenuation of the ion beam, particularly with voltage pulses at low duty cycles.

[0101] This teaching can be implemented in a variety of different mass spectrometers. As an example, Figure 2A mass spectrometer 1300 is schematically depicted, including an ion source 1302 for generating an ion beam comprising multiple ions. The ion source can be separated from the downstream portion of the mass spectrometer by a curtain chamber (not shown) in which an aperture plate (not shown) is provided, providing an opening through which ions generated by the ion source can enter the downstream portion. In this embodiment, an RF ion guide (QJet) can be used to capture and focus ions using a combination of gas dynamics and a radio frequency field. In this embodiment, ions pass through a QJet quadrupole, which utilizes a combination of gas dynamics and a radio frequency field to provide improved capture rate and efficient ion transport to downstream elements, regardless of the gas load associated with a larger sampling aperture. A lens IQ0 is disposed between the QJet and the downstream Q0 ion guide.

[0102] Ion director Q0 delivers ions to downstream quadrupole mass analyzer Q1 via lens IQ1 and short stud ST1. The quadrupole mass analyzer can be located in a vacuum chamber, which can be evacuated to a pressure maintained below that of the chamber in which the RF ion director Q0 is housed. As a non-limiting example, the vacuum chamber containing Q1 can be maintained at a pressure less than approximately 1 × 10⁻⁶. -4 Torr (for example, approximately 5 × 10) -5 Under Torr pressure, but other pressures can be used for this or other purposes.

[0103] As discussed in more detail below, multiple voltage pulses according to this teaching can be applied to lens IQ0 at a selected duty cycle in order to provide the desired attenuation of the ion beam.

[0104] As those skilled in the art will recognize, the quadrupole assembly Q1 can operate as a conventional transmission RF / DC quadrupole mass filter, which can be operated to select ions of interest and / or a range of ions of interest. As an example, the quadrupole assembly Q1 can be provided with an RF / DC voltage suitable for operation in mass-resolved mode. It should be appreciated that, considering the physical and electrical characteristics of Q1, the parameters of the applied RF and DC voltages can be selected such that Q1 establishes a transmission window with a selected m / z ratio, allowing these ions to pass through Q1 largely undisturbed. However, ions with m / z ratios falling outside the window cannot obtain a stable trajectory within the quadrupole and can be prevented from crossing the quadrupole assembly Q1. It should be appreciated that this operating mode is only one possible operating mode for Q1. As an example, in some embodiments, the quadrupole assembly Q1 can be configured as an ion trap. In some respects, ions can be mass-selectively axially ejected from the Q1 ion trap in the manner described by Hager in “A new Linear ion trap massspectrometer” Rapid Commun. Mass Spectra 2002;16:512-526.

[0105] According to this teaching, ions passing through quadrupole assembly Q1 can pass through short, thick ST2 and enter electron capture and dissociation unit 1304. In some embodiments, dissociation unit 1304 may include a plurality of quadrupole assemblies positioned in series and may be subjected to an RF voltage to confine electrons near the longitudinal axis of the quadrupole assemblies, allowing the electrons to interact efficiently with the precursor ions entering the dissociation module. The capture of one or more electrons by the precursor ions can cause at least a portion of the precursor ions to fragment. Fragment ions can be detected and analyzed by downstream mass analyzer 1208 in a manner known in the art.

[0106] Continue to refer to Figure 2 In this embodiment, the pulsed voltage source 1310, operating under the control of the controller 1312, can apply multiple voltage pulses to the lens IQ0 to attenuate the brightness of the ion beam introduced into the downstream quadrupole assembly Q0. For the desired attenuation of the ion beam brightness, the controller can, for example, determine the required pulse width and duty cycle of the voltage pulses according to the teachings using the above equation (3), and can influence the application of such voltage pulses to the IQ0 lens via the pulsed voltage source.

[0107] As an example, Figure 3An implementation example of controller 1312 is schematically depicted, wherein the controller includes a processor 1400 that communicates via bus 1402 with a random access memory (RAM) module 1404, a permanent memory module 1406, a communication interface 1408 providing communication between the controller and the pulsed voltage source, and a user interface 1410. In some embodiments, the permanent memory module 1406 may store information about the required pulse width and duty cycle of the voltage pulse that can achieve the desired attenuation of the ion beam brightness. The controller may also store information about the amplitude or amplitude range of the voltage pulse. Such information can be calculated based on the teachings above. In particular, as discussed in detail above, the required pulse width of the voltage pulse applied at a given duty cycle can be derived using a calibrated normalized ion intensity versus pulse width relationship and an ideal normalized ion intensity versus pulse width relationship. As discussed above, in some embodiments, the duty cycle of the voltage pulse can be as low as approximately 0.1%.

[0108] like Figure 4 As schematically illustrated, in some embodiments, a doublet lens comprising lens IQ0A and another lens IQ0B axially connected in series with IQ0A can be disposed between QJet and the Q0 quadrupole. Applying voltage pulses to lenses IQ0A and IQ0B according to this teaching can attenuate the brightness of the ion beam passing through these two lenses to reach the downstream quadrupole assembly Q0.

[0109] Ions pass through the quadrupole ion guide Q0 to reach the quadrupole mass filter Q1. Although not shown in the figure, one or more ion lenses may be arranged between the quadrupoles Q0 and Q1. While the quadrupole assembly Q1 is configured as a mass filter in this embodiment, 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.

[0110] The following examples are provided to further illustrate various aspects of this teaching. These examples are provided for illustrative purposes only and are not necessarily intended to indicate the best mode of practicing the invention and / or the best results that can be obtained.

[0111] Example

[0112] The data discussed in the following examples were obtained using a hybrid triple quadrupole linear ion trap mass spectrometer, which has been modified according to this teaching. Figure 5A and 5B The relevant ion optics devices are schematically depicted. In particular, Figure 5AAn RF ion director, designated QJet herein, is shown, operating at a pressure of 2.8 Torr, followed by dual IQ0 lenses (IQ0A and IQ0B), and then a Q0 region that can be configured for RF ion director-only operation at 8.7 mTorr. Lenses IQ0A and IQ0B have apertures of 1.4 mm and 1.5 mm, respectively. In both regions, the pressure is primarily due to nitrogen gas, which enters the mass spectrometer through orifices in the orifice plate. Specifically, a nitrogen gas flow is introduced between the orifice and the curtain plate such that the total flow rate is greater than the nitrogen flow rate entering the vacuum chamber through the orifice plate. Excess nitrogen flows outward through the curtain plate orifices.

[0113] Figure 5B It shows something similar to Figure 5A The arrangement shown differs in that the IQ0A lens has been removed. Removing the IQ0A lens caused the pressure in the Q0 region to increase from 8.7 mTorr to 10.6 mTorr. The increase in pressure is due to the larger 1.5 mm aperture of the IQ0B lens.

[0114] Ion kinetic energy

[0115] Ions transported through the high-voltage region of the QJet ion optics (see...) Figure 5A The velocity of the gas jet will be obtained, which may result in the ions having axial kinetic energy related to their mass. At the IQ0B lens, the gas undergoes expansion into the lower pressure Q0 region (e.g., 8.7 mTorr in the Q0 region versus 2.8 Torr in the QJet region). Using the known free-jet expansion equation, the maximum axial velocity of a fully expanded expansion can be calculated. For a pressure of 2.8 Torr in the QJet region and 8.7 mTorr in the Q0 region, such a calculation yields a maximum axial gas velocity of 765 m / s. However, in this region, the radial scale of the gas expansion is larger than the radial scale of the Q0 ion optics, causing the expansion to be interrupted, which will prevent the ions from reaching high velocities compared to a fully expanded expansion. The axial kinetic energy of the ions is a function of the velocity they achieve. For the maximum velocity of 765 m / s, an upper limit to the ion kinetic energy can be calculated, as shown in Table 1 below:

[0116] Table 1: Ion Kinetic Energy (V = 765 m / s)

[0117] m / z Ion kinetic energy (eV) 29 0.088 322 0.977 922 2.797 2122 6.436

[0118] Due to the varying kinetic energies of the ions, their response to a voltage applied to a lens (e.g., IQ0A) positioned between the QJet and Q0 regions will be mass-dependent. The ion kinetic energy can be modified relative to those listed above due to collisions with the background gas that result in kinetic energy loss, and the gradient electric field generated by the pulse applied to the lens. However, generally, a higher potential is required to stop heavier ions. Figure 6A The shape of a voltage pulse applied to the IQOB lens with a 5% duty cycle is shown. In ion transmission mode, the DC potential on the IQOB remains at -10V, while in ion non-transmission mode, the DC potential drops to -40V. These values ​​represent potentials typically used in positive ion mode.

[0119] Figure 6B It shows Figure 6A The leading edge of the voltage pulse is depicted in the image. (Reference) Figure 6B Based on the ion kinetic energy shown in Table 1 above, once an ion transmission voltage pulse is applied to the IQ0B lens, the applied DC potential takes approximately 24 microseconds to increase to a level that will allow ion transmission at m / z 2122, while the time required for ion transmission at m / z 322 is 50 microseconds.

[0120] When the falling edge of the pulse is steeper than its rising edge, the change from ion transmission mode to ion non-transmission mode occurs more quickly when the applied DC potential is switched on. In other words, in this example, the ion beam can be switched off faster than it can be switched on. It should also be noted that, due to the location of the ion optics on either side of the lens and the diameter of the lens aperture, the on-axis potential experienced by the ions will differ from the potential applied to the lens. Nevertheless, Figure 6A and 6B This indicates that when ions have different kinetic energies, the response of ions to the potential applied to the lens will be mass-dependent.

[0121] Reducing the rise time of the voltage pulse applied to the lens will increase the ion response rate to the pulse. The faster the response, the closer the transmission potential time period will be to the desired transmission time period. Figure 7A and 7B Will Figure 6A and 6B The voltage pulse depicted is compared to a voltage pulse with faster rise and fall times. Specifically, the rise time has been reduced by 90% from approximately 36 microseconds to approximately 14 microseconds. The reduced rise time will result in a faster response of ions to the pulse.

[0122] Transmitting and non-transmitting lens potentials

[0123] In many embodiments, the ion beam can be shut off by increasing the DC potential applied to the lens through which the ions pass relative to adjacent ion optics or by decreasing the DC potential. For example, Figure 9A The lens IQ0B is schematically depicted between the ion guide (QJet) and the quadrupole-only RF ion guide Q0. Figure 8 Different modes of potentials that can be applied to these components are shown in panels (a), (b), and (c).

[0124] After applying equal DC potentials to these components, as shown in panel (a), ions are expected to pass directly through the lens, as... Figure 9A As shown in the image.

[0125] When the DC potential applied to the lens increases, such as Figure 8 As shown in panel (b), an electrostatic barrier is generated, resulting in a repulsive force on the upstream side of the lens for ions (in this case, positive ions), such as Figure 9B As shown in the image.

[0126] When the DC potential applied to the lens is set to the attraction potential, ions will pass through the lens and be redirected to the downstream side of the lens, where they are neutralized, such as... Figure 9C As shown in the diagram. In this case, it is necessary to cause the ions to collide with the background gas to reduce the kinetic energy of the ions and to attract the ions back to the lens after they pass through it.

[0127] 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% of ions from penetrating to downstream components.

[0128] Signal as a function of lens duty cycle

[0129] Figure 10 The normalized ion intensity is shown as a function of the duty cycle of the voltage applied to the lens IQ0B for ions with m / z ratios of 29, 322, 922, and 2122. The duty cycle varies from 0 to 100%. The rise time of the voltage pulse is 36 microseconds, and the amplitude is 30V. The pulse is negative (see, for example,...). Figure 9C ). Figure 10 The ion intensity signals in the data shown are normalized based on a 100% duty cycle.

[0130] Figure 11 and 12The data shown is normalized at a 5% duty cycle. This normalization is chosen based on the amount of error in the pulse width compared to the total cycle time. A 14-microsecond error would result in a voltage pulse with a 200-microsecond pulse width applied at a 5% duty cycle being equivalent to a 186-microsecond pulse width applied at a 4.65% duty cycle. This represents an error of 0.35%. Furthermore, it should be noted that a full-intensity 1e7 cps signal attenuated at a 5% duty cycle would produce 1e7 cps * 200 microseconds = 2000 ions. In a pulse counting system, noise is proportional to the square root of the total count. Therefore, in this example, the noise would be equal to... The count is 4 / 2000 * 100% = ±2.3%. The noise associated with the pulse width (i.e., 0.35%) is less than the signal noise, so normalization with a 5% duty cycle is not expected to have a significant impact on signals with lower duty cycle values.

[0131] These graphs appear quite linear from 0 to 100% duty cycle. However, closer inspection of the areas with duty cycles below 5% reveals that these graphs are actually non-linear, as shown below. Figure 11 As shown in the figure. The intercept of the graph is non-zero and mass-dependent, whereas ideally these graphs are 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 the figure. Figure 11 As shown in the image.

[0132] It has been observed that increasing the amplitude of the voltage pulse can improve the linearity between the normalized ion intensity and the duty cycle of the applied pulse. Figure 12 The normalized ion intensity, as a function of the duty cycle of the applied pulse, is presented for pulses with a rise time of 36 microseconds, but with the pulse amplitude increasing from 30V to 50V. Each plot shows the intercept of the projection with the y-axis below y=0.

[0133] Figure 13 The graph shows the relationship between normalized ion intensity and the amplitude of the DC potential applied to the IQ0B lens. When the potential is set to -40V, some ions leak through the lens. Approximately 0.13% ion leakage is observed at m / z 29 and m / z 322, decreasing to 0.004% at m / z 922, and then increasing to 0.23% for m / z 2122. Figure 13 The relationship diagram indicates that the pulse amplitude should be high to reduce the effects of ion leakage. This can also improve linearity, such as... Figure 12 As shown in the image.

[0134] Lens potential: compound dependent

[0135] Figures 14A-14CThe ion transmission characteristics are shown to also depend on the analyte (compound) being analyzed. These figures depict the normalized ion intensity versus lens potential for PPG (poly(propylene) glycol) and Agilent tuned mixtures (a mixture of homosubstituted triazatriphosphine compounds, see U.S. Patent No. 5,872,3571) of similar mass. Figures 14A-14C The data presented indicate that the compounds exhibit different transmission characteristics through the lens. To mitigate this difference, the amplitude of the voltage pulse applied to the lens was set to 50V (an absolute potential applied to the lens from -10V to -60V), which is the maximum potential available from the power supply.

[0136] Lens potential: pressure dependent

[0137] Figures 15A-15C The effect of varying pressure in QJet and Q0 ion optics on the shape of the lens potential curves is illustrated. In these examples, PPG ions were used for data collection. The pressure shown in each figure represents the pressure in the QJet region, followed by the pressure in the Q0 ion optics region. The presented data show that, in each case, the lens potential distribution becomes wider with increasing pressure. The change in positive lens potential is more pronounced relative to the change in negative lens potential. Furthermore, the increase in distribution width becomes more significant with increasing ion mass.

[0138] Lens potential: single lens and double lens

[0139] Figures 16A-16D This shows the availability in the QJet and Q0 regions (see...) Figure 5A and 5B This graph compares the relationship between normalized ion intensity and lens potential for many ions with different m / z ratios using a single lens and a double lens. In all cases, when the lens potential is set to a negative value, the single lens potential shows a faster decrease in transmittance. However, when the lens potential is set to a positive value, the transmission window increases to a higher positive lens potential, and in some cases, the non-transmitting or blocking potential exceeds the range provided by the available power supply. The shape of the curves indicates that applying a negative lens potential is better than applying a positive lens potential when the single lens completely shuts off the ion beam compared to the double lens.

[0140] Lens potential: fragment ions and non-fragment ions

[0141] Figure 17 The data presented indicate that transmission through the IQOB lens can occur over a wide potential range when ions are formed during transport along the ion guide. M / z 59 is known to be a fragment ion that can be formed in the interfacial region of the mass spectrometer and along the ion guide. Figure 17Normalized ion strength as a function of lens potential is depicted for fragment ions at m / z 59 and stable ions at m / z 68. If the potential is insufficient to prevent the transmission of large ions, then large ions can be transmitted through the IQ0B lens. If large ions pass through the lens and fragments downstream of the lens in the Q0 ion optics, thus generating m / z 59 ion fragments, then it appears that m / z 59 is transmitted. In this example, m / z 59 is not transmitted; instead, it is generated downstream of the lens. The intensity of ion fragments is expected to be highly dependent on the ion source and interface conditions.

[0142] Extension of duty cycle linearity

[0143] Figures 18A-18D The graphs show the relationship between the normalized intensity of ions passing through an IQ0B lens and the pulse width of the applied voltage pulse for ions with different m / z ratios. Each graph shows the ideal normalized ion intensity versus pulse width and the calibrated normalized ion intensity versus pulse width fitted to a linear relationship. The ion intensity obtained by applying a 200-µs voltage pulse to the lens at a pulse rate of 250 Hz corresponding to a 5% duty cycle is used as the reference intensity to obtain the normalized intensity. That is, the measured or predicted ion intensity is divided by the reference intensity to obtain the normalized intensity.

[0144] Each graph depicts a relationship between the normalized measured ion intensity as a function of the pulse width of a voltage pulse with a rise time of approximately 14 microseconds (referred to herein as calibrated normalized ion intensity versus pulse width), a linear fit of the measured normalized intensity data as a function of the pulse width, and a graph representing the ideal normalized intensity as a function of the pulse width. The ideal normalized ion intensity is the predicted intensity if the voltage pulse applied to the lens has a vanishing rise time and the nontransmission potential applied to the lens completely suppresses the transmission of ions through the lens.

[0145] A linear fit of the calibrated ion intensity to the pulse width shows the slope and intercept as a function of the m / z ratio.

[0146] Figure 19 The fit of ideal and calibrated normalized ion strength to pulse width is shown for m / z 29. In this example, the linear fit of the data is normalized to an ideal fit at a pulse width of 200 microseconds. In other words, equation (2) above is renormalized a second time. Figure 20The results show that, for m / z 29, in order to obtain a normalized ion strength of 0.4, the pulse width of the applied voltage pulse should be approximately 96.7 microseconds (point B), while if the pulse is ideal (i.e., if the pulse has a disappearing rise time and completely suppresses the transmission of ions through the lens), then a pulse width of 80 microseconds will be required to obtain a normalized ion strength of 0.4.

[0147] The linear fit of the relationship between ideal normalized ion intensity and pulse width can be represented by the above equation (1), and its reproduction is as follows:

[0148] y = m1x1,

[0149] Furthermore, the linear fit of the relationship between the calibrated normalized ion intensity and the pulse width can be represented by the above equation (2), which is also reproduced as follows:

[0150] y = m²x² + b,

[0151] As discussed in detail above, these two equations can be used to obtain the above equation (3) for the pulse width of the applied pulse that will result in the normalized ion intensity y, which is reproduced as follows:

[0152]

[0153] The quality correlation coefficients m2 (slope) and b (intercept) of the above calibration data are respectively in Figure 21A and Figure 21B The plot is shown in the image. In this example, the slope and intercept can be represented by fitting the following third-order polynomial:

[0154] m2=-1.5678×10 -13 x 2 +7.9705×10 -13 x 2 -1.2565×10 -6 x + 5.8566 × 10 -3 ,

[0155] b = 3.136 × 10 -11 x 3 -1.594×10 -7 x 2 +2.513×10 -4 x-1.713×10 -1

[0156] If an ideal pulse width defined by x1 is desired, then that value can be inserted into equation (3) above to obtain the value of x2, which represents the pulse width of the voltage pulse to be applied to the lens.

[0157] Figure 22-24The graphs showing the normalized ion intensity passing through the aforementioned lens IQ0B as a function of the duty cycle in positive ion mode, negative ion mode, and positive enhanced product ion (EPI) operating mode are presented separately. The duty cycle is 5%, corresponding to a pulse width of 200 microseconds. The pulse amplitude is set to the maximum pulse amplitude that the power supply can deliver (i.e., 50V). In the EPI experiments using a linear ion trap, the trap fill time is approximately 4 ms for each data point, which matches the fill time to a 250 Hz pulse rate.

[0158] Figure 25 It shows Figure 22 The unfolded diagram illustrates the region from 0% to 1% duty cycle. It can be seen that for higher quality, there is a region of reduced intensity below approximately 0.3% duty cycle. Without being limited to any particular theory, this reduced intensity is likely due to the short transmission pulse causing ions to be trapped in the region between the IQ0B lens and the Q0 ion optics.

[0159] Figures 26A-26D The graphs present normalized ion intensity as a function of duty cycle for multiple m / z ratios and in two cases: (1) when a single IQ0B lens is positioned near the inlet port of the Q0 quadrupole, and (2) when a doublet lens IQ0A and IQ0B are positioned near the inlet port of the Q0 quadrupole. In all cases, the amplitude of the voltage pulse is chosen to be 50V (i.e., the maximum amplitude provided by the power supply). This data indicates that both single-lens and doublet lenses maintain the linearity of ion beam attenuation, thus indicating that this teaching provides a robust method and system for attenuating the brightness of an ion beam in a mass spectrometer.

[0160] Figure 27 This demonstrates that the duty cycle linearity of multiple charged ions also remains unchanged. In this example, ions with charge states of +1, +2, and +3 all exhibit the same linearity. The main difference between multiple charged ions and single charged ions is that the pulse amplitude will be proportional to the ion's charge state. Therefore, an ion with a charge state of +3 will experience a pulse with an amplitude of 150V, while a single charged ion will only experience a pulse with an amplitude of 50V.

Claims

1. A method of modulating transmission of ions in a mass spectrometer, comprising: generating an ion beam comprising a plurality of ions, directing the ion beam to an ion optic positioned in a path of the ion beam, wherein the ion optic comprises at least one opening through which ions can pass, applying one or more voltage pulses to the ion optic at a selected duty cycle to obtain a desired attenuation of the brightness of the ion beam passing through the ion optic, wherein a pulse width of the voltage pulse at the selected duty cycle is determined by identifying a pulse width on a calibration normalized ion intensity versus pulse width relationship of the ions that corresponds to the desired attenuation on an ideal normalized ion intensity versus pulse width relationship of the ions.

2. The method of claim 1, wherein the calibration normalized ion intensity versus pulse width relationship is obtained via a linear fit of data corresponding to normalized intensities of the ions transmitted through the ion optic as a function of pulse widths of a plurality of voltages applied to the ion optic at the selected duty cycle.

3. The method of claim 2, wherein the ideal normalized ion intensity versus pulse width relationship is defined by the following linear relationship: y = mlxl, where y represents a normalized ion intensity, xl represents an ideal pulse width, and ml represents a slope of the linear relationship.

4. The method of claim 3, wherein the calibration normalized ion intensity versus pulse width relationship is defined by the following linear relationship: y = m2x2 + b, where y represents a normalized ion intensity, x2 represents a pulse width of a voltage pulse applied to the ion optic, m2 represents a slope of the linear relationship, and b represents an intercept of the linear relationship.

5. The method of claim 4, wherein the pulse width x2 is determined according to the following relationship: x2 = 1 - (1 - D) / ml.

6. The method of claim 5, further comprising renormalizing the relationship in claim 5 at a 5% duty cycle point.

7. The method of claim 1, wherein the calibration normalized ion intensity for a voltage pulse width associated with a plurality of voltage pulses applied to the ion optic at the duty cycle is obtained as a ratio of a measured intensity of ions passing through the ion optic at the voltage pulse width relative to a measured intensity of ions passing through the ion optic at a calibration voltage pulse width associated with a plurality of calibration voltage pulses applied to the ion optic at the duty cycle.

8. The method of claim 7, wherein the calibration voltage pulse width is in a range of 4 microseconds to 200 microseconds.

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

10. The method of claim 9, wherein the ideal normalized ion intensity versus pulse width relationship and the calibration normalized ion intensity versus pulse width relationship are determined for at least one of the m / z ratios. ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ 11. The method of claim 10, wherein the ideal normalized ion intensity versus pulse width relationship and the calibrated normalized ion intensity versus pulse width relationship determined for the at least one of the m / z ratios are used to determine the pulse width of the voltage pulse.

12. The method of claim 9, further comprising: An ideal normalized ion intensity versus pulse width relationship and a calibrated normalized ion intensity versus pulse width relationship are generated for ions having each of the m / z ratios.

13. The method of claim 12, further comprising: When the ions having different ones of the m / z ratios pass through the ion optics, the ideal normalized ion intensity versus pulse width relationship and the calibrated normalized ion intensity versus pulse width relationship for ions having one of the m / z ratios are selected to determine a pulse width for the voltage pulse applied to the ion optics.

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

15. The method of claim 1, wherein an amplitude of the voltage pulse is selected to suppress transmission of ions through the ion optics during a suppression phase of the voltage pulse.

16. The method of claim 1, wherein the selected duty cycle is less than 5%.

17. The method of claim 16, wherein the selected duty cycle is in a range of 0.1% to 1%.

18. The method of claim 1, wherein a pulse width of the voltage pulse is less than 200 microseconds.

19. The method of claim 18, wherein a pulse width of the voltage pulse is in a range of 4 microseconds to 200 microseconds.

20. The method of claim 1, further comprising: Any RF-only ion guide is positioned downstream of the ion optics such that the ion optics are disposed near an entrance of the RF-only ion guide.

21. A method of modulating transmission of ions in a mass spectrometer, comprising: 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, wherein the ion optics comprises at least one opening through which ions can pass, applying one or more voltage pulses to the ion optics at a selected duty cycle to modulate passage of ions through the ion optics, wherein a pulse width of the voltage pulse is determined by calculating an adjustment to a pulse width of an ideal pulse that would result in a desired normalized intensity of ions passing through the ion optics.

22. The method of claim 21, wherein the step of calculating an adjustment comprises: utilizing an ideal normalized ion intensity versus pulse width relationship and a calibrated normalized ion intensity versus pulse width relationship for the ions.

23. The method of claim 22, further comprising: re-normalizing the adjustment at a 5% duty cycle point.

24. A mass spectrometer, comprising: an ion source for generating an ion beam comprising a plurality of ions, an ion optics positioned in a path of the ion beam, the ion optics comprising at least one opening 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 brightness of the ion beam, wherein the voltage pulse has a pulse width corresponding to a pulse width on a calibrated normalized ion intensity versus pulse width relationship for the ion corresponding to the desired attenuation on the ideal normalized ion intensity versus pulse width relationship for the ion.

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