Band-pass mass filter

Abstract

A band-pass mass filter includes: a multi-pole ion guide; a first RF voltage source configured to apply a first RF voltage to an electrode of the multi-pole ion guide to generate an electric field for radially defining ions within the multi-pole ion guide; and a second RF voltage source configured to apply a different second RF voltage to the electrodes of the bandpass mass filter wherein a first phase of the second RF voltage is applied to a first pair of opposing electrodes and a different second phase of the second RF voltage is applied to a second pair of opposing electrodes; wherein the frequency of the second RF voltage is at least 1 / 20 of the frequency of the first RF voltage; and wherein the bandpass mass filter is configured to be maintained at a pressure > = 10 <-4 > mbar.

Description

[0001] Cross - reference to related applications

[0002] This application claims the priority and benefit of UK Patent Application No. 2216612.8, filed on November 8, 2022, the entire content of which is incorporated herein by reference. Technical field

[0003] The present invention generally relates to mass spectrometers and / or mobility spectrometers, and more particularly to an apparatus for such spectrometers that operates as a band - pass mass filter. Background art

[0004] Resolving quadrupole mass filters are well - known devices in which RF and DC voltages are applied to electrodes to select the mass - to - charge ratios that can be transmitted by the filter.

[0005] It is also known to apply opposite phases of an auxiliary RF voltage to opposite electrodes in an RF - only ion guide to form a dipole that resonantly ejects ions with undesired mass - to - charge ratios. Summary of the invention

[0006] According to a first aspect, the present invention provides a band - pass mass filter comprising: a multipole ion guide; a first RF voltage source configured to apply a first RF voltage to the electrodes of the multipole ion guide to generate an electric field for radially confining ions within the multipole ion guide; and a second RF voltage source configured to apply a different second RF voltage to the electrodes of the band - pass mass filter, wherein a first phase of the second RF voltage is applied to a first pair of opposite electrodes and a different second phase of the second RF voltage is applied to a second pair of opposite electrodes.

[0007] The first RF voltage is also referred to herein as the main RF voltage, and the second RF voltage is also referred to herein as the auxiliary RF voltage.

[0008] It has been recognized that applying a first phase of a second (auxiliary) RF voltage to a pair of opposite electrodes and a second phase of the second RF voltage to another pair of opposite electrodes improves the stability profile of an RF ion guide such that it operates as a bandpass filter. This is in contrast to the prior art which applies opposite phases of an auxiliary RF voltage to opposite electrodes, thereby creating a dipole voltage that resonantly excites and ejects ions. The inventors have recognized that using such dipole voltages, particularly at relatively high pressures, can be problematic. For example, such techniques may require large voltage amplitudes to perform mass filtering. In addition, compared to the embodiments described herein, dipole voltages are more difficult to apply to an ion guide both mechanically and electrically. Further, in order to operate the ion guide as a bandpass mass filter, a broadband dipole voltage that is difficult to achieve would be required.

[0009] The inventors have also recognized that applying only a single phase of an auxiliary voltage to the electrodes does not produce a high-quality cutoff voltage for the ion guide. Instead, such techniques would also require the application of a DC voltage in order to form a bandpass mass filter.

[0010] For the avoidance of doubt, the electrodes described herein as opposite electrodes are electrodes that are arranged opposite to each other with respect to a central longitudinal axis passing through the bandpass mass filter (i.e., the axis to which the ions are radially confined).

[0011] A separate first RF voltage can create an electric field within a multipole ion guide that radially confines ions having a mass-to-charge ratio above a threshold (i.e., above a low-mass cutoff voltage value).

[0012] The second RF voltage can be configured such that when it is applied to the electrodes of the bandpass mass filter, the electric field within the multipole ion guide radially confines only ions having a mass-to-charge ratio below a threshold.

[0013] This threshold is a high-quality cutoff voltage value. When the first voltage and the second voltage are applied to the bandpass mass filter, the electric field within the multipole ion guide also radially confines only ions having a mass-to-charge ratio above a threshold (i.e., above a low-mass cutoff voltage value).

[0014] The multipole ion guide can be a multipole rod set ion guide.

[0015] The multipole ion guide can be a quadrupole ion guide, such as a quadrupole rod set ion guide.

[0016] The second RF voltage source can be configured to apply the second RF voltage to the electrodes of the multipole ion guide.

[0017] The first RF voltage source can be configured to apply a first phase of a first RF voltage to a first pair of opposing electrodes of a multipole ion guide and a different second phase of the first RF voltage to a second pair of opposing electrodes of the multipole ion guide; and the second RF voltage source can be configured to apply a first phase of a second RF voltage to the same pair of opposing electrodes to which the first phase of the first RF voltage is applied and a second phase of the second RF voltage to the same pair of opposing electrodes to which the second phase of the first RF voltage is applied.

[0018] The first RF voltage source can be configured to apply a first phase of a first RF voltage to a first pair of opposing electrodes of a multipole ion guide and a different second phase of the first RF voltage to a second pair of opposing electrodes of the multipole ion guide; and the second RF voltage source can be configured to apply a first phase of a second RF voltage to a third pair of opposing electrodes in a bandpass mass filter and a second phase of the second RF voltage to a fourth pair of opposing electrodes in the bandpass mass filter.

[0019] For the avoidance of doubt, all of the electrodes in the first, second, third, and fourth pairs of electrodes are different electrodes (i.e., eight electrodes are required).

[0020] In such embodiments, each electrode to which the second voltage is applied can be circumferentially arranged between and adjacent to the multipole electrodes to which the first phase of the first RF voltage is applied and the multipole electrodes to which the second phase of the first RF voltage is applied.

[0021] The cross-sectional shape (at any given point along the bandpass filter) and / or cross-sectional area (at any given point along the bandpass filter) and / or length of all of the electrodes in the first and second pairs of electrodes and also optionally the third and fourth pairs of electrodes can be the same. For example, the bandpass mass filter can have eight (or more) elongated electrodes such as rod electrodes to which the first and second voltages are applied.

[0022] Alternatively, the cross-sectional shape (at any given point along the bandpass filter) and / or cross-sectional area (at any given point along the bandpass filter) and / or length of the electrodes in the third and fourth pairs of electrodes can be different from the electrodes in the first and second pairs of electrodes. For example, the electrodes in the third and fourth pairs of electrodes can be plate electrodes or blade electrodes. These plate electrodes or blade electrodes can be substantially planar electrodes, where their planar surfaces are arranged in a radial direction with respect to a central longitudinal axis passing through the bandpass mass filter. In contrast, the electrodes in the first and second pairs of electrodes can be rod-shaped (including axially segmented rods) electrodes or can be plate electrodes, where their planes are arranged in an axial direction with respect to the central axis.

[0023] The first and second phases of the first RF voltage can be opposite phases of the first RF voltage and / or the first and second phases of the second RF voltage can be opposite phases of the second RF voltage.

[0024] Alternatively, the first and second phases of the first RF voltage can differ by an amount other than 180 degrees, and / or the first and second phases of the second RF voltage can differ by an amount other than 180 degrees. For example, the multipole can be a higher order multipole than a quadrupole, and different phases on an n-phase first RF voltage source can be applied to different pairs of opposing electrodes, where n > 2. Similarly, different phases on an m-phase second RF voltage source can be applied to different pairs of opposing electrodes in the bandpass mass filter, where m > 2.

[0025] The frequency of the second RF voltage can be lower than the frequency of the first RF voltage.

[0026] The frequency of the second RF voltage can be at least 1 / 20 (or at least 1 / 30, at least 1 / 40, or at least 1 / 50) of the frequency of the first RF voltage.

[0027] In other words, the frequency of the second RF voltage can be ≤ 5% of the frequency of the first RF voltage. This can help avoid relatively large stability regions at low values of the q parameter on the Mathieu stability diagram, which would otherwise prevent the ion guide from having an absolute high mass cut-off voltage.

[0028] The amplitude of the second RF voltage can be lower than the amplitude of the first RF voltage.

[0029] The amplitude of the second RF voltage can be between 1% and 20% of the amplitude of the first RF voltage.

[0030] It has been found that such amplitudes provide a narrow enough stability region to operate a practical bandpass filter, while higher amplitudes place more demands on the voltage source and can cause the stability region to become more discontinuous. The amplitude of the second RF voltage can be ≥ 5% and / or ≤ 10%. For example, the preferred range of the amplitude of the second RF voltage is between 5% and 10% of the amplitude of the first RF voltage.

[0031] The second RF voltage source can be configured to vary the amplitude of the second RF voltage over time to change the range of mass-to-charge ratios that the bandpass mass filter can transmit.

[0032] For example, for given values of the first RF voltage and the second RF voltage, increasing the amplitude of the second RF voltage narrows the range of mass-to-charge ratios that can be transmitted by the bandpass mass filter.

[0033] It has been found that a second RF voltage having a frequency ≤ 5% of the frequency of the first RF voltage and an amplitude between 5% and 10% of the amplitude of the first RF voltage is particularly beneficial for generating a bandpass mass filter with a high-quality cut-off voltage.

[0034] The bandpass mass filter can be configured to be maintained at a pressure selected from: ≥ 10 -4 mbar; ≥ 5 × 10 -4 mbar; ≥ 10 -3 mbar; ≥ 5 × 10 -3 mbar; ≥ 10 -2 mbar; ≥ 5 × 10 -2 mbar; ≥ 10 -1 mbar; ≥ 1 mbar; ≥ 100 mbar; or ≥ 1000 mbar.

[0035] The bandpass mass filter can be arranged in the vacuum chamber of a mass spectrometer so as to be maintained at said pressure.

[0036] Conventional DC resolving quadrupole mass filters are constructed from precisely aligned quadrupole electrodes and operate at pressures below 10 -4 mbar in order to provide a desired ion transmission level and mass resolution. The inventors of the present invention have recognized that a multipole RF ion guide, for example with less precisely aligned electrodes, can be adapted by applying an auxiliary RF voltage to its electrodes such that it operates as a bandpass mass filter with an acceptable ion transmission level and mass resolution even at relatively high pressures.

[0037] The bandpass mass filter can include one or more DC voltage sources configured to apply one or more DC voltages to at least one electrode of the bandpass mass filter in order to generate a DC potential gradient along the longitudinal axis of the bandpass mass filter to drive ions along the bandpass mass filter.

[0038] The multipole ion guide to which the first RF voltage is applied can be a purely RF ion guide.

[0039] The multipole ion guide can be an RF ion guide to which no resolving DC voltage is applied, although one or more DC voltages can be applied to provide an axial DC field for driving ions through the ion guide. In other words, the bandpass mass filter is configured such that the mass-to-charge ratio of the ions transmitted is defined by the first RF voltage and the second RF voltage rather than by a DC voltage. Preferably, no DC potential difference is applied between radially opposite or circumferentially adjacent electrodes of the multipole ion guide.

[0040] The present invention also provides a mass spectrometer and / or an ion mobility spectrometer, the mass spectrometer and / or the ion mobility spectrometer including the bandpass mass filter described herein, wherein the bandpass mass filter is located upstream of a mass analyzer and / or an ion mobility separator, and wherein the bandpass mass filter is configured to limit the range of mass-to-charge ratios that can be transmitted to the mass analyzer and / or the ion mobility separator.

[0041] The mass analyzer can be a resolving quadrupole mass filter and / or the ion mobility separator can be a drift time mobility separator configured to drive ions along its longitudinal axis and through a background gas in order to separate ions by mobility.

[0042] The bandpass mass filter can be located in a first vacuum chamber and the mass analyzer can be located in a second vacuum chamber at a pressure lower than that of the first vacuum chamber.

[0043] For example, the spectrometer can be configured to maintain the first vacuum chamber at a pressure of ≥5×10 -3 mbar; and / or to maintain the second vacuum chamber at a pressure of ≤10 -3 mbar. The second vacuum chamber can be at a pressure of ≤5×10 -4 mbar or ≤10 - 4 mbar.

[0044] The mass analyzer can be a resolving quadrupole mass filter.

[0045] Alternatively or in addition, the bandpass mass filter can be arranged upstream of a differential pumping aperture between two chambers maintained at different pressures. The bandpass mass filter can be configured to limit the range of mass-to-charge ratios that can be transmitted to the differential pumping aperture. This can be used to prevent ions with relatively high mass-to-charge ratios from hitting the differential pumping aperture and to prevent contamination of the aperture and charging of the aperture.

[0046] The present invention also provides a method of mass filtering ions, the method including: providing a bandpass mass filter as described herein; applying a first RF voltage to the electrodes of a multipole ion guide using a first RF voltage source; applying a second RF voltage to the electrodes of the bandpass mass filter using a second RF voltage source, wherein a first phase of the second RF voltage is applied to a first pair of opposing electrodes and a different second phase of the second RF voltage is applied to a second pair of opposing electrodes; and transmitting ions into the bandpass mass filter.

[0047] The present invention also provides a method for a mass spectrometer and / or an ion mobility spectrometer, the method including the method of mass filtering ions as described herein.

[0048] The method may include providing a mass spectrometer and / or an ion mobility spectrometer having a mass analyzer and / or an ion mobility separator, and operating a bandpass mass filter to limit the range of mass-to-charge ratios that can be transmitted to the mass analyzer and / or the ion mobility separator.

[0049] The mass analyzer may be a resolving quadrupole mass filter; and / or the ion mobility separator may be a drift time mobility separator that drives ions along its longitudinal axis and through a background gas to separate ions by mobility. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] Various embodiments of the present invention will now be described by way of example only and with reference to the accompanying drawings, in which:

[0051] Figure 1 shows a Mathieu stability diagram of a quadrupole ion guide;

[0052] Figure 2 shows a cross-sectional view through a quadrupole ion guide according to an embodiment of the present invention;

[0053] Figures 3A to 3C shows simulation results modeling the effect on the Figure 1 stability diagram when auxiliary RF voltages of various different amplitudes are also applied to the quadrupole;

[0054] Figures 4A to 4C shows simulation results modeling the effect on the Figure 3C stability diagram when the frequency of the auxiliary RF voltage is varied;

[0055] Figure 5 shows two mass spectra that illustrate the difference in data obtained when using a conventional RF-only ion guide and an RF-only ion guide as disclosed herein; and

[0056] Figure 6 shows an arrangement in which a bandpass mass filter according to an embodiment of the present invention is provided as a sacrificial filter disposed upstream of an analytical quadrupole mass filter. DETAILED DESCRIPTION

[0057] Figure 1 shows a Mathieu stability diagram of a quadrupole ion guide, where the y-axis represents the parameter a and the x-axis represents the parameter q. As is well known in the art, the region below the curve represents the values of RF voltage and DC voltage that can be applied to the quadrupole electrodes to make the trajectory of ions passing through the ion guide stable, while the region above the curve represents the RF voltage and DC voltage that make the trajectory of ions in the ion guide unstable.

[0058] In a quadrupole set mass filter for discrimination, during an experimental run, the amplitudes of the RF voltage and the DC voltage applied to the quadrupole electrodes are scanned or stepped over time such that the filter transmits different mass-to-charge ratios at different respective times during the experimental run. Typically, the voltages are scanned or stepped such that the ratio of the amplitudes of the RF voltage and the DC voltage remains constant, for example in order to follow a linear scan line in a Mathieu stability diagram, such as Figure 1 scan line 1 as shown.

[0059] Typically, it is desirable to apply the RF voltage and the DC voltage to the quadrupole electrodes of the filter such that the scan line 1 crosses the stability region at a location near the tip of the stable region. This enables the filter to transmit only a narrow range of mass-to-charge ratios at any given time (i.e., for any given combination of the RF voltage and the DC voltage), and thus improves the mass resolution of the filter. Ions with a mass-to-charge ratio higher than this narrow range correspond to the area to the left of the curve in the stability region, such that the filter has a high mass cut-off voltage, while ions with a mass-to-charge ratio lower than this narrow range correspond to the area to the right of the curve in the stability region, such that the filter has a low mass cut-off voltage. When the RF voltage and the DC voltage are varied over time, the values of the mass-to-charge ratios that fall within the stable region also change, thus causing the filter to transmit different mass-to-charge ratios at different respective times.

[0060] In contrast, only a single RF voltage is applied to the electrodes of a conventional RF-only quadrupole ion guide, and no discrimination DC voltage is applied. Thus, in the Mathieu stability diagram, the value of the parameter a is zero. As can be seen from Figure 1 it, the RF-only ion guide would theoretically transmit ions with very low values of the parameter q down to q = 0.9. The q value = 0.9 thus represents a low mass cut-off voltage and is relatively steep. For low masses, the lower limit of the parameter q for stabilizing and transmitting ions can be as high as 0.2, but for high masses, it can be much less than 0.1. Thus, the RF-only ion guide does not have a well-defined high mass cut-off voltage, and thus for a given RF voltage, there is a relatively wide range of mass-to-charge ratios that can be transmitted by the ion guide. Thus, it is not possible to operate a conventional RF-only quadrupole ion guide as a narrow band-pass filter without adding discrimination DC.

[0061] The inventors have recognized that in addition to the main RF voltage conventionally used to radially confine ions, an auxiliary RF voltage can also be applied to the RF-only ion guide in a specific manner in order to cause the ion guide to operate as a band-pass filter.

[0062] Figure 2A cross-sectional view through the quadrupole ion guides 2a to 3d according to an embodiment of the present invention is shown. As with conventional only RF quadrupole ion guides, two opposite rod electrodes 2a, 2b are electrically connected to each other so as to form a first pair of electrodes, where, in use, the same voltage signal will be applied to this first pair of electrodes. The remaining two opposite rod electrodes 2c, 2d are electrically connected to each other so as to form a second pair of electrodes, where, in use, the same voltage signal will be applied to this second pair of electrodes. A first phase of the main RF voltage is applied to the two electrodes 2a, 2b of one of the pairs of electrodes, and an opposite second phase of the main RF voltage is applied to the two electrodes 2c, 2d of the other pair of electrodes for radially confining ions within the ion guide. The auxiliary electrodes 3a to 3d may optionally be provided between circumferentially adjacent quadrupole electrodes 2a to 2d, as will be further described below.

[0063] As described above, an auxiliary RF voltage may also be applied to the rod electrodes 2a to 2d so as to cause the ion guide to operate as a bandpass filter. A first phase of the auxiliary RF voltage may be applied to the two electrodes 2a, 2b of the first pair of electrodes, and an opposite second phase of the auxiliary RF voltage may be applied to the two electrodes 2c, 2d of the second pair of electrodes.

[0064] If the auxiliary electrodes 3a to 3d are provided, a DC voltage may be applied to the auxiliary electrodes so as to generate an axial DC field along the longitudinal axis of the ion guide, for example to drive ions through the ion guide downstream. This may be achieved by providing auxiliary electrodes spaced apart along the longitudinal axis of the ion guide and simultaneously applying different DC voltages to different ones of the auxiliary electrodes so as to generate an axial DC field. Alternatively, one or more DC voltages may be applied successively to successive auxiliary electrodes spaced apart in the axial direction such that one or more corresponding DC electric potentials travel in the axial direction, thereby driving ions in the axial direction. One or more DC electric potentials may travel repeatedly in the axial direction along the device. Alternatively, one or more of the auxiliary electrodes may extend along at least a portion of the length of the ion guide and may have a resistive coating such that when a DC voltage is applied thereto, a DC electric potential gradient along the longitudinal axis of the ion guide is generated. Alternatively, one or more of the auxiliary electrodes may extend along at least a portion of the length of the ion guide, and the distance between the auxiliary electrode and the longitudinal axis of the ion guide may vary with the distance along the longitudinal axis such that when a DC voltage is applied to the auxiliary electrode, a DC electric potential gradient along the longitudinal axis of the ion guide is generated.

[0065] It is conceivable that instead of applying the auxiliary RF voltage to the quadrupole electrodes 2a to 2d, it could be applied to other electrodes. For example, in an embodiment including auxiliary electrodes 3a to 3d, the main RF voltage could be applied to the quadrupole electrodes 2a to 2d in the manner described above, but the auxiliary RF voltage could also be applied to the auxiliary electrodes 3a to 3d. In such an embodiment, two opposite auxiliary electrodes 3a, 3b are electrically connected to each other to form a first pair of auxiliary electrodes, and during use, the same voltage signal will be applied to this first pair of auxiliary electrodes, and the remaining two opposite auxiliary electrodes 3c, 3d are electrically connected to each other to form a second pair of auxiliary electrodes, and during use, the same voltage signal will be applied to this second pair of auxiliary electrodes. The first phase of the auxiliary RF voltage can be applied to the two electrodes 3a, 3b in one of the pairs of auxiliary electrodes of the auxiliary electrode pair, and the opposite second phase of the auxiliary RF voltage can be applied to the two electrodes 3c, 3d in the other pair of auxiliary electrodes. For example, referring to Figure 2 , the positive phase of the main RF voltage can also be applied to the electrodes 2a, 2b in the first pair of quadrupole electrodes, and the positive phase of the auxiliary RF voltage can be applied to the electrodes 3a, 3b in the first pair of auxiliary electrodes, while the negative phase of the main RF voltage can be applied to the electrodes 2c, 2d in the second pair of quadrupole electrodes, and the negative phase of the auxiliary RF voltage can be applied to the electrodes 2c, 3d in the second pair of auxiliary electrodes. In an embodiment where the auxiliary RF voltage is applied to the auxiliary electrodes 3a to 3d, one or more DC voltages may or may not be applied to the auxiliary electrodes to generate a DC potential gradient along the longitudinal axis of the ion guide in the manner described above.

[0066] To avoid doubt, the electrodes described herein as opposite electrodes are arranged opposite to each other with respect to the central longitudinal axis passing through the ion guide (into Figure 2 the page).

[0067] Accordingly, embodiments of the present invention apply a first phase of an auxiliary RF voltage to a pair of opposing electrodes and a second phase of the auxiliary RF voltage to another pair of opposing electrodes. This improves the stability diagram of the ion guide such that it operates as a bandpass filter. This is in contrast to applying opposing phases of the auxiliary RF voltage to the electrodes in each pair of opposing electrodes, which would create a dipole voltage for resonantly exciting ions. The inventors have recognized that using such dipole voltages, especially at relatively high pressures, can cause problems and may require a large voltage amplitude to perform mass filtering. Also, such dipole voltages are more difficult to apply to the ion guide both mechanically and electrically compared to the embodiments described above. Additionally, in order to operate the ion guide as a bandpass mass filter, a broadband dipole voltage that is difficult to achieve would be required. The inventors have also recognized that applying only a single phase of the auxiliary voltage to the electrodes does not produce a high-quality cutoff voltage for the ion guide. Instead, such techniques would also require the application of a DC voltage in order to form a bandpass mass filter.

[0068] Figures 3A to 3C Shows simulation results modeling the effect on Figure 1 the stability diagram when the frequency is 1 / 50 of the main RF voltage and an auxiliary RF voltage with different amplitudes is also applied to the quadrupole set. According to the embodiments described above, the first phase of the auxiliary RF voltage is modeled as being applied to two electrodes in a pair of opposing electrodes in a quadrupole ion guide, and the second phase of the auxiliary RF voltage is modeled as being applied to two electrodes in another pair of opposing electrodes of the ion guide. Figure 3A Shows the stability diagram when the amplitude of the auxiliary RF voltage is 1 / 20 of the amplitude of the main RF voltage. Figure 3B Shows the stability diagram when the amplitude of the auxiliary RF voltage is 3 / 40 of the amplitude of the main RF voltage.

[0069] Figure 3C Shows the stability diagram when the amplitude of the auxiliary RF voltage is 1 / 10 of the amplitude of the main RF voltage. By way of example, the frequency of the main RF voltage can be 1 MHz and the amplitude can be 100 V peak-to-peak.

[0070] From Figures 3A to 3CIt can be seen that significantly varying the amplitude of the auxiliary RF voltage relative to the amplitude of the main RF voltage significantly affects the low-q region of the stability diagram, but has a relatively smaller effect on the high-q region of the stability diagram. This indicates that for a given main RF voltage, the auxiliary RF voltage can be applied to the RF-only ion guide in the manner described herein to vary the range of mass-to-charge ratios that can be transmitted and effectively provide a high-quality cut-off voltage. This effective high-quality cut-off voltage, when combined with the low-quality cut-off voltage already present due to the main RF voltage, provides a band-pass mass filter. It can be seen that for a given main RF voltage, increasing the amplitude of the auxiliary RF voltage narrows the width of the stability region, which effectively reduces the high-quality cut-off voltage value. The amplitude of the auxiliary RF voltage can be selected to define the range of mass-to-charge ratios transmitted by the device.

[0071] Accordingly, embodiments of the present invention may use an auxiliary RF voltage having an amplitude relatively lower than that of the main RF voltage. For example, the amplitude of the auxiliary RF voltage can be 1 / 10 or less of the amplitude of the main RF voltage. It has been found that such amplitudes provide a sufficiently narrow stability region to operate a practical band-pass filter, while higher amplitudes place more demands on the voltage source and may cause the stability region to become more discontinuous. However, higher amplitudes can be envisioned, such as an amplitude of the auxiliary RF voltage up to 20% of the amplitude of the main RF voltage.

[0072] Figures 4A to 4C Shows simulation results modeling the effect on the Figure 3C stability diagram when the frequency of the auxiliary RF voltage is varied. Thus, in Figures 4A to 4C the amplitude of the auxiliary RF voltage is 1 / 10 of the amplitude of the main RF voltage. Figure 4A Shows the stability diagram when the frequency of the auxiliary RF voltage is 1 / 50 of the frequency of the main RF voltage. Figure 4B Shows the stability diagram when the frequency of the auxiliary RF voltage is 1 / 10 of the frequency of the main RF voltage. Figure 4C Shows the stability diagram when the frequency of the auxiliary RF voltage is 1 / 5 of the frequency of the main RF voltage.

[0073] It can be seen from the stability diagrams that as the frequency of the auxiliary RF voltage varies relative to the frequency of the main RF voltage, the stability regions and the intervals between the stability regions change. For a sole RF ion guide, i.e., with its parameter a being zero, it can be seen that as the frequency of the auxiliary voltage changes to be closer to the frequency of the main RF voltage, the stability diagram is divided into more distinct stability islands. More specifically, relatively large stability regions occur at low values of the q parameter. Although the ion guide will operate as a band-pass mass filter in these regions, the stability regions at low values of the q parameter prevent the ion guide from having an absolute high mass cut-off voltage. In addition, larger instability regions start to appear between the instability regions, which limits the size of the mass range over which the filter can operate as a band-pass mass filter. Although the amplitude of the auxiliary RF voltage can be increased to reduce the size of the higher-q stability regions, the low-q stability regions are maintained.

[0074] Those skilled in the art should understand that even when the frequency of the auxiliary RF voltage is a relatively small fraction of the frequency of the main RF voltage, such as in Figure 4A , there will still be small instability islands within a very small mass-to-charge ratio range (e.g., a range of 0.3 Da). In traditional low-pressure DC resolution mass filters, this is problematic because ions with mass-to-charge ratios in these small ranges will be filtered out, and thus the filter cannot operate well as a band-pass mass filter. However, since the embodiments of the present invention operate the band-pass mass filter at relatively high pressures (such as ≥ 10 -4 mbar), the ions collide with background gas molecules more frequently, and thus ions with mass-to-charge ratios in these very small mass instability regions are still transmitted through the filter.

[0075] Therefore, the embodiments of the present invention can use an auxiliary RF voltage with a frequency relatively low relative to the frequency of the main RF voltage. For example, the frequency of the auxiliary RF voltage can be 1 / 20 or less of the frequency of the main RF voltage. In other words, the frequency of the auxiliary RF voltage can be ≤ 5% of the frequency of the main RF voltage.

[0076] It should be noted that each of the stability diagrams shown in FIGS. 3 to 4 has been modeled and thus shows the theoretically stable regions of the ion guide. In reality, the stability regions are not as discrete as shown. For example, misalignment of the ion guide electrodes and / or collisions of the ions with background gas molecules may cause some ions that should not be stable in the ion guide to be transmitted through the ion guide. Therefore, the stability regions in each stability diagram may actually be more blurred and may not be discrete.

[0077] Figure 5Two mass spectra are shown that illustrate the difference in data obtained when using a conventional RF-only ion guide and an RF-only ion guide operating as a bandpass mass filter as disclosed herein. The upper mass spectrum was obtained when monitoring a mass of 145 Da and using a conventional RF-only ion guide to which only the primary RF voltage was applied, where the amplitude of the primary RF voltage was 350 V peak-to-peak and the frequency was 1.65 MHz. The lower mass spectrum was obtained under the same conditions as the upper mass spectrum, except that an auxiliary RF voltage was also applied to the ion guide such that it operated as a bandpass mass filter. The amplitude of the auxiliary RF voltage was 15 V peak-to-peak and the frequency was 32 kHz. As Figure 5 can be seen, the two mass spectra are substantially the same in the lower range of mass-to-charge ratio, where for the ions of interest (i.e., 145 Da), there is substantially no loss of signal intensity. However, as can be seen, the bandpass mass filter used to obtain the lower mass spectrum has filtered out ions above a specific mass-to-charge ratio.

[0078] It should be understood that the bandpass mass filter according to the present invention can be used in various application fields. For example, the bandpass mass filter can be used as a sacrificial mass filter disposed upstream of a resolving mass filter.

[0079] Figure 6 A layout structure is shown in which a bandpass filter 4 according to an embodiment of the present invention is provided as a sacrificial mass filter acting as a resolving quadrupole mass filter disposed upstream of an analytical quadrupole mass filter 5. As should be understood, in the resolving quadrupole mass filter 5, two opposite rod electrodes are electrically connected to each other to form a first pair of electrodes, and the remaining two opposite rod electrodes are electrically connected to each other to form a second pair of electrodes. An RF voltage source 6 and a DC voltage source 7 apply an RF voltage and a DC voltage to the electrodes of the resolving quadrupole mass filter 5, respectively, such that the resolving quadrupole mass filter can only transmit ions within a specific range of mass-to-charge ratio (i.e., within a mass window) at any given time. A controller 8 is provided to control the above voltage sources. Ions with a mass-to-charge ratio outside this mass window are filtered out and do not reach the outlet end of the resolving quadrupole mass filter 5.

[0080] The RF voltage and the DC voltage can be varied over time such that the mass-to-charge ratio that can be transmitted by the resolving quadrupole mass filter 5 varies over time. For example, the RF voltage and the DC voltage are scanned or stepped over time such that the mass-to-charge ratio that can be continuously or discontinuously transmitted by the resolving quadrupole mass filter 5 varies over time.

[0081] An ion detector 9 for detecting ions transmitted by the resolution quadrupole mass filter 5 can be provided downstream of the resolution quadrupole mass filter 5. If the detector 9 detects ions, the spectrometer can determine the mass-to-charge ratio of the ions based on the RF voltage and DC voltage applied to the rod electrodes of the resolution quadrupole mass filter 5 at a time corresponding to the time when the resolution quadrupole mass filter transmits the ions, because the RF voltage and DC voltage determine the mass-to-charge ratio that can be transmitted.

[0082] Additional ion optical components can be provided between the resolution quadrupole mass filter 5 and the ion detector 9. For example, a fragmentation or reaction device for fragmenting or reacting precursor ion species transmitted by the resolution quadrupole mass filter 5 to form fragment ions or product ions can be provided downstream of the resolution quadrupole mass filter 5. Another mass filter for mass-analyzing the fragment ions or product ions can be provided between the fragmentation or reaction device and the detector 9. For example, the mass spectrometer can be a tandem quadrupole mass spectrometer.

[0083] It should be understood that the ions filtered out by the resolution quadrupole mass filter 5 usually impinge on the rod electrodes of the filter 5 and disappear. Over time, the inner surfaces of the rod electrodes are contaminated by ions, and electronic charges accumulate on these contaminated surfaces. Eventually, the local charging of the contaminated surfaces causes a degradation in the performance of the resolution quadrupole mass filter 5. This can lead to ion transmission loss, mass resolution loss, or poor peak shape of the ion signal from the downstream detector 9. If such contamination occurs, the resolution quadrupole mass filter 5 must be removed from the vacuum chamber and cleaned.

[0084] The band-pass mass filter 4 according to the present invention can be used as a sacrificial mass filter arranged upstream of the resolving quadrupole mass filter 5. As described above, the main RF voltage source 10 applies a main RF voltage to the electrodes of the band-pass mass filter 4 to radially confine ions, and the auxiliary RF voltage source 11 also applies an auxiliary RF voltage to the electrodes of the band-pass mass filter 4, such that the mass filter 4 has both a high mass cut-off voltage and a low mass cut-off voltage. Ions with a mass-to-charge ratio higher than the high mass cut-off voltage, and ions with a mass-to-charge ratio lower than the low mass cut-off voltage are unstable in the band-pass mass filter 4 and are thus filtered out and not transmitted to the resolving quadrupole mass filter 5. Ions in the first mass-to-charge ratio range are thus transmitted by the band-pass mass filter 4 into the resolving quadrupole mass filter 5. In contrast, the RF voltage and the DC voltage applied to the resolving quadrupole mass filter 5 only cause ions in the second, narrower mass-to-charge ratio range (i.e., corresponding to a single ion species) to be radially confined and thus transmitted to the outlet of the resolving quadrupole mass filter 5. Ions with a mass-to-charge ratio outside this second range are filtered out by the resolving quadrupole mass filter 5. Thus, the band-pass mass filter 4 filters out some ions with a mass-to-charge ratio outside the second mass-to-charge ratio range at a position upstream of the resolving quadrupole mass filter 5. Thus, these ions do not need to be filtered out by the resolving quadrupole mass filter 5 and thus do not impact the electrodes of the resolving quadrupole mass filter 5. This helps to avoid contamination and surface charging of the electrodes of the resolving quadrupole mass filter 5, which would reduce its ion transmission characteristics.

[0085] The band-pass mass filter 4 can be arranged in a first vacuum chamber, and the resolving quadrupole mass filter 5 can be arranged in a second vacuum chamber, wherein the first vacuum chamber is at a higher pressure than the second vacuum chamber.

[0086] It has been found that the band-pass mass filter 4 disclosed herein is particularly useful at relatively high pressures because, even if the electrodes are slightly misaligned, the performance of these devices at such pressures can be as good as or better than that of DC resolving filters. As described above, the band-pass mass filter 4 can include auxiliary electrodes 3a to 3d, which provide a DC potential gradient to drive ions along the band-pass mass filter 4. Alternatively, the quadrupole ion guide electrodes can be axially segmented, and different DC voltages can be applied to different axial segments of these axial segments to provide a DC potential gradient for driving ions along the band-pass mass filter.

[0087] It is contemplated that the bandpass mass filter described herein can be used upstream of an ion optical device rather than a resolving quadrupole mass filter. For example, the bandpass mass filter described herein can be used as a mass filter disposed upstream of an ion mobility separator (IMS). During a single experimental run, different ion groups can successively enter the ion mobility separation region in order to separate them based on the mobility of the ions in each group through a background gas. However, ions with relatively low mobility may take a relatively long time to traverse the ion mobility separation region, and thus, when analyzing ions from a subsequent second ion group in the ion group, the low-mobility ions from the first ion group may be inadvertently detected. Therefore, these low-mobility ions may cause false artifact peaks to appear in the mobility spectrum.

[0088] The bandpass mass filter described herein can be disposed upstream of the IMS device in order to limit the range of mass-to-charge ratios that can be transmitted to the IMS device. Since the mass-to-charge ratio is related to mobility, at relatively high pressures, the bandpass device can limit the range of mobilities entering the IMS device in order to prevent ions from any given ion group from being detected while analyzing ions from a subsequent ion group in the ion group. For example, the bandpass device can limit the range of mobilities entering the IMS device in order to prevent ions from any given ion group from being present in the ion separation region while ions from another ion group are present in the ion separation region.

[0089] Although the invention has been described with reference to various embodiments, those skilled in the art will understand that various changes can be made in form and detail without departing from the scope of the invention as set forth in the appended claims.

[0090] For example, although an embodiment has been described in which the bandpass mass filter is a quadrupole set ion guide, it is contemplated that the ion guide can alternatively include a higher-order multipole set.

[0091] The quadrupole or higher-order multipole set electrodes can be axially segmented electrodes or can be continuous electrodes. The electrodes can be rod-shaped or other shapes, such as plate-shaped.

[0092] Although an embodiment has been described in which the bandpass mass filter is only an RF ion guide (i.e., an ion guide to which only an AC voltage is applied), it is contemplated that a resolving DC voltage can also be applied to the bandpass mass filter in order to improve the maximum achievable mass resolution of the device. This enables the mass resolution to be higher than that achievable by only an RF device or a conventional DC resolving mass filter.

Claims

1. A bandpass mass filter, the bandpass mass filter comprising: Multipole ion guide; A first RF voltage source configured to apply a first RF voltage to the electrodes of the multipole ion guide to generate an electric field for radially confining ions within the multipole ion guide; and A second RF voltage source configured to apply a different second RF voltage to the electrodes of the bandpass mass filter, wherein a first phase of the second RF voltage is applied to a first pair of opposite electrodes and a different second phase of the second RF voltage is applied to a second pair of opposite electrodes; wherein the frequency of the second RF voltage is at least 1 / 20 of the frequency of the first RF voltage; and wherein, the bandpass mass filter is configured to be maintained under a pressure of ≥ 10 -4 mbar.

2. The bandpass mass filter according to claim 1, wherein, The second RF voltage is configured such that when it is applied to the electrodes of the bandpass mass filter, the electric field within the multipole ion guide radially confines only ions having a mass-to-charge ratio below a threshold.

3. The bandpass mass filter according to claim 1 or 2, wherein, The multipole ion guide is a quadrupole ion guide, such as a quadrupole rod set ion guide.

4. The bandpass mass filter according to any one of the preceding claims, wherein, The second RF voltage source is configured to apply the second RF voltage to the electrodes of the multipole ion guide.

5. The bandpass mass filter according to claim 4, wherein, The first RF voltage source is configured to apply a first phase of the first RF voltage to a first pair of opposite electrodes of the multipole ion guide and a different second phase of the first RF voltage to a second pair of opposite electrodes of the multipole ion guide; and wherein the second RF voltage source is configured to apply the first phase of the second RF voltage to the same pair of opposite electrodes to which the first phase of the first RF voltage is applied and the second phase of the second RF voltage to the same pair of opposite electrodes to which the second phase of the first RF voltage is applied.

6. The bandpass mass filter according to any one of claims 1 to 3, wherein, The first RF voltage source is configured to apply a first phase of the first RF voltage to a first pair of opposite electrodes of the multipole ion guide and a different second phase of the first RF voltage to a second pair of opposite electrodes of the multipole ion guide; and wherein the second RF voltage source is configured to apply the first phase of the second RF voltage to a third pair of opposite electrodes in the bandpass mass filter and the second phase of the second RF voltage to a fourth pair of opposite electrodes in the bandpass mass filter.

7. The bandpass mass filter according to any one of the preceding claims, wherein, The first phase and the second phase of the first RF voltage differ by approximately 180 degrees; and wherein the first phase and the second phase of the second RF voltage differ by approximately 180 degrees.

8. The bandpass mass filter according to any one of the preceding claims, wherein, The frequency of the second RF voltage is at least 1 / 30 of the frequency of the first RF voltage.

9. The bandpass mass filter according to claim 8, wherein, The frequency of the second RF voltage is at least 1 / 50 of the frequency of the first RF voltage.

10. The bandpass mass filter according to any one of the preceding claims, wherein, The amplitude of the second RF voltage is lower than the amplitude of the first RF voltage.

11. The bandpass mass filter according to claim 10, wherein, The amplitude of the second RF voltage is between 1% and 20% of the amplitude of the first RF voltage.

12. The bandpass mass filter according to claim 10 or 11, wherein, The second RF voltage source is configured to vary the amplitude of the second RF voltage over time to change the range of mass-to-charge ratios that the bandpass mass filter can transmit.

13. The bandpass mass filter according to any one of the preceding claims, wherein, The band-pass mass filter is configured to maintain at a pressure of ≥ 10 -3 mbar.

14. The bandpass mass filter according to any one of the preceding claims, the bandpass mass filter comprising one or more DC voltage sources configured to apply one or more DC voltages to at least one electrode of the bandpass mass filter so as to generate a DC potential gradient along a longitudinal axis of the bandpass mass filter to drive ions along the bandpass mass filter.

15. The band-pass mass filter according to any one of the preceding claims, wherein, The multipole ion guide is an RF ion guide to which a resolution DC voltage is not applied.

16. A mass spectrometer and / or an ion mobility spectrometer, the mass spectrometer and / or the ion mobility spectrometer comprising the band-pass mass filter according to any one of the preceding claims, wherein, The band-pass mass filter is located upstream of a mass analyzer and / or an ion mobility separator, and wherein the band-pass mass filter is configured to limit the range of mass-to-charge ratios that can be transmitted to the mass analyzer and / or the ion mobility separator.

17. The spectrometer according to claim 16, wherein, The mass analyzer is a resolution quadrupole mass filter; and / or wherein the ion mobility separator is a drift time mobility separator configured to drive ions along its longitudinal axis and through a background gas so as to separate the ions by mobility.

18. The spectrometer according to claim 16 or 17, wherein, The band-pass mass filter is located in a first vacuum chamber and the mass analyzer is located in a second vacuum chamber at a pressure lower than that of the first vacuum chamber.

19. A method for mass filtering ions, the method comprising: A band-pass mass filter according to any one of claims 1 to 15 is provided; Applying the first RF voltage to the electrodes of the multipole ion guide using the first RF voltage source; Applying the second RF voltage to the electrodes of the band-pass mass filter using the second RF voltage source, wherein the first phase of the second RF voltage is applied to the first pair of opposite electrodes and a different second phase of the second RF voltage is applied to the second pair of opposite electrodes; And Transmitting ions into the band-pass mass filter.

20. A method for a mass spectrometer and / or an ion mobility spectrometer, the method comprising the method according to claim 19.

21. A band-pass mass filter, the band-pass mass filter comprising: A multipole ion guide; A first RF voltage source configured to apply a first RF voltage to the electrodes of the multipole ion guide to generate an electric field for radially confining ions within the multipole ion guide; And A second RF voltage source configured to apply a different second RF voltage to the electrodes of the band-pass mass filter, wherein the first phase of the second RF voltage is applied to a first pair of opposite electrodes and a different second phase of the second RF voltage is applied to a second pair of opposite electrodes.

Images