Mass-resolving high-pressure ion guidance with axial field

Abstract

Mass spectrometer which features the following: a first mass filter comprising several electrodes and a first device, wherein the first device is designed and adapted to maintain an axial DC electric field over at least a section of the axial length of the first mass filter in order to drive at least some ions along at least a part of the axial length, or wherein the first device is designed and adapted to apply one or more transient DC voltages to the several electrodes in order to drive at least some ions along at least a part of the axial length; a second device designed and adapted to apply one or more resolving DC voltages to at least some of the electrodes to cause unwanted ions to be radially ejected from the first mass filter, or a third device designed and adapted to apply RF voltages to at least some of the electrodes to cause unwanted ions to be radially ejected from the first mass filter; and a quadrupole mass filter or mass analyzer arranged downstream of the first mass filter, wherein the quadrupole mass filter or mass analyzer is maintained at a lower pressure than the first mass filter.

Description

Background of the present invention

[0001] The present invention relates to a mass spectrometer and a method for mass spectrometry. A preferred embodiment of the present invention relates to a mass filter arranged upstream of an analytical quadrupole rod set mass filter or mass analyzer.

[0002] Quadrupole rod-set mass filters are well known and contain four rod electrodes. An RF voltage and a resolving DC voltage are applied simultaneously to the rod electrodes, so that the mass filter operates in a mass-resolution or mass-to-charge ratio resolution mode. As those skilled in the art will understand, when a quadrupole rod-set mass filter is in a mass-resolution mode, ions with mass-to-charge ratios within a desired mass-to-charge ratio range are passed forward through the mass filter, while unwanted ions with mass-to-charge ratios outside the mass-to-charge ratio range are significantly attenuated.Ions that are not desired to pass forward through the mass filter are either thinned out by causing the ions to adopt unstable trajectories so that the ions impact the rod electrodes, or otherwise thinned out by ejecting the ions radially from the mass filter.

[0003] A problem with conventional quadrupole rod-set mass filters operating in a mass-resolving mode is that they suffer significantly reduced performance at elevated pressures. This is partly due to the axial cooling of the ions, which results in longer transit times and a correspondingly increased exposure to the resolving electric fields (RF and DC fields). In particular, if ions passing forward through the mass filter remain within the mass filter for too long and experience too many cycles of the applied RF voltage, the ions can be inadvertently radially ejected. As a result, the ion transmission efficiency of the mass filter is significantly reduced for ions that are desired to be forward-passed through the mass filter.

[0004] Another significant problem with conventional arrangements is that analytical quadrupoles can be exposed to relatively high ion currents, resulting in a relatively large number of unwanted ions exhibiting unstable trajectories through the analytical quadrupole. A relatively high proportion of ions that are not forward-passed impinge on the analytical quadrupole rods. As a result, the analytical quadrupole rods can quickly become contaminated, and the analytical quadrupole will suffer a loss of resolution due to surface charging effects.

[0005] As those skilled in the art will understand, cleaning the rods of an analytical quadrupole rod set is a non-trivial task that requires the intervention of a service technician and the shutdown of the mass spectrometer.

[0006] US 6 987 264 B1 (Whitehouse) discloses an arrangement in which at least two multipole ion guides are arranged adjacent to each other. US 6 987 264 B1 (Whitehouse) does not address the problem of contamination of the rods of an analytical quadrupole. DE 103 97 000 B4 relates to a method and apparatus for improving the operating characteristics of mass spectrometers. US 5 847 386 A relates to a mass spectrometer in which an axial field is generated. US 2009 / 0 314 935 A1 relates to a mass analyzer comprising a plurality of electrodes with openings through which ions are transferred during use.

[0007] It is desirable to provide an improved spectrometer and method for mass spectroscopy. Summary of the present invention

[0008] According to the invention, a mass spectrometer and a method for mass spectrometry are provided having the features of the independent claims; dependent claims relate to preferred embodiments.

[0009] According to one aspect of the present invention, there is provided a mass spectrometer comprising: a first mass filter comprising a plurality of electrodes and a first device, the first device being configured and adapted to maintain an axial DC electric field across at least a portion of the axial length of the first mass filter to drive at least some ions along at least a portion of the axial length, or the first device being configured and adapted to apply one or more transient DC voltages to the plurality of electrodes to drive at least some ions along at least a portion of the axial length; a second device designed and adapted to apply one or more resolving DC voltages to at least some of the electrodes to cause unwanted ions to be radially ejected from the first mass filter, or a third device designed and adapted to apply RF voltages to at least some of the electrodes to cause unwanted ions to be radially ejected from the first mass filter; and a quadrupole mass filter or mass analyzer arranged downstream of the first mass filter, wherein the quadrupole mass filter or mass analyzer is maintained at a lower pressure than the first mass filter.

[0010] The present invention solves the problem of contamination of the rods of an analytical quadrupole by providing a (first) mass filter upstream of the analytical quadrupole mass filter or mass analyzer. The (first) mass filter is preferably maintained at a relatively high pressure, and an axial force is preferably maintained along the length of the first mass filter to drive ions axially along the length of the mass filter.

[0011] The present invention is particularly advantageous in that the upstream mass filter is arranged in such a way that it significantly reduces contamination of the rods of the analytical quadrupole rod set.

[0012] The quadrupole mass filter preferably contains an analytical mass filter.

[0013] The first mass filter is preferably arranged and designed to operate in a synchronized manner with the quadrupole mass filter or mass analyzer.

[0014] The first mass filter is preferably arranged and designed to substantially reduce the ion current passed to the quadrupole mass filter or mass analyzer.

[0015] The first mass filter and the quadrupole mass filter or mass analyzer are preferably arranged and designed to operate in a mode in which the first mass filter is designed to mass filter ions having a first mass resolution R1, and wherein the quadrupole mass filter or mass analyzer is designed to mass filter ions having a second mass resolution R2 at the same time T1, where R2 > R1.

[0016] US 6 987 264 B1 (Whitehouse) does not teach or suggest operating a mass filter upstream of an analytical quadrupole with a resolution lower than that of the analytical quadrupole.

[0017] The first mass resolution R1 = (m / z) / W 1 / 2 , where m / z is the mass-to-charge ratio of an ion peak and W 1 / 2 is the half-width of the ion peak and where the second mass resolution R2 = (m / z) / W 1 / 2 , where m / z is the mass-to-charge ratio of an ion peak and W 1 / 2 is the half-width of the ion peak.

[0018] The first mass filter and the quadrupole mass filter or mass analyzer are preferably arranged and designed to operate in a mode in which the first mass filter is designed to pass ions having a first mass-to-charge ratio M1 and in which the quadrupole mass filter or mass analyzer is designed to pass ions having a second mass-to-charge ratio M2 at the same time T1, where M1 = M2.

[0019] US 6 987 264 B1 (Whitehouse) does not teach or suggest operating a mass filter upstream of an analytical quadrupole such that the center of the transmission window of the upstream mass filter coincides with the center of the transmission window of the analytical quadrupole.

[0020] The present invention is particularly advantageous in that the upstream mass filter is designed to significantly reduce contamination of the analytical quadrupole rod set.

[0021] The first mass filter is preferably designed to thin out ions having a mass-to-charge ratio less than and / or greater than M1 at time T1.

[0022] The quadrupole mass filter or mass analyzer is preferably arranged and designed to attenuate ions having a mass-to-charge ratio less than and / or greater than M2 at time T1.

[0023] The first mass filter and the quadrupole mass filter or mass analyzer are preferably arranged and designed to operate in a mode in which the first mass filter is designed to pass ions having a first mass-to-charge ratio or a first mass-to-charge ratio range M1, and wherein the quadrupole mass filter or mass analyzer is designed to pass ions having a second mass-to-charge ratio or a second mass-to-charge ratio range M2 at the same time T1, where M1 - M2 ≤ × Da (1 Da = 1.660 × 10 -27 kg) and wherein × is selected from the following group: (i) 10; (ii) 5; (iii) 1; (iv) 0.5; (v) 0.1; (vi) 0.05; (vii) 0.01; (viii) 0.005; and (ix) 0.001.

[0024] US 6 987 264 B1 (Whitehouse) does not teach or suggest operating a mass filter upstream of an analytical quadrupole such that the center of the transmission window of the upstream mass filter coincides with the center of the transmission window of the analytical quadrupole.

[0025] The present invention is particularly advantageous in that the upstream mass filter is designed to significantly reduce contamination of the analytical quadrupole rod set.

[0026] The first mass filter is preferably designed to thin out ions having a mass-to-charge ratio less than and / or greater than M1 at time T1.

[0027] The quadrupole mass filter or mass analyzer is preferably arranged and designed to attenuate ions having a mass-to-charge ratio less than and / or greater than M2 at time T1.

[0028] The first mass filter and / or the quadrupole mass filter or mass analyzer are preferably designed or adapted to be maintained at a pressure selected from the following group: (i) < 0.0001 mbar; (ii) 0.0001 to 0.001 mbar; (iii) 0.001-0.01 mbar; (iv) 0.01-0.1 mbar; (v) 0.1-1 mbar; (vi) 1-10 mbar; (vii) 10 to 100 mbar; (viii) 100-1000 mbar; and (ix) > 1000 mbar.

[0029] The first mass filter and / or the quadrupole mass filter or mass analyzer preferably have an axial length selected from the following group: (i) < 10 mm; (ii) 10-20 mm; (iii) 20-30 mm; (iv) 30-40 mm; (v) 40-50 mm; (vi) 50-60 mm; (vii) 60-70 mm; (viii) 70-80 mm; (ix) 80-90 mm; (x) 90-100 mm; (xi) 100-110 mm; (xii) 110-120 mm; (xiii) 120-130 mm; (xiv) 130-140 mm; (xv) 140-150 mm; (xvi) 150-160 mm; (xix) 160-170 mm; (xix) 170-180 mm; (xix) 180-190 mm; (xx) 190-200 mm; and (xxi) > 200 mm.

[0030] The first mass filter and / or the quadrupole mass filter or mass analyzer are preferably maintained at a pressure P and have an axial length L for which the product PxL is selected from the following group: (i) < 0.001 mbar-mm; (ii) 0.001-0.01 mbar-mm; (iii) 0.01-0.1 mbar-mm; (iv) 0.1-1 mbar-mm; (v) 1-10 mbar-mm; (vi) 10-100 mbar-mm; (vii) 100-1000 mbar-mm; (viii) 1000-10000 mbar-mm; (ix) 10000-100000 mbar-mm; and (x) > 100000 mbar-mm.

[0031] According to one embodiment, the mass spectrometer preferably further comprises a second device configured and adapted to apply one or more resolving DC voltages to at least some of the electrodes to cause unwanted ions to adopt unstable trajectories through the first mass filter and / or to cause unwanted ions to be radially ejected from the first mass filter.

[0032] The second device is preferably designed and adapted to cause unwanted ions to be substantially attenuated.

[0033] The mass spectrometer preferably further includes a third device configured and adapted to apply RF voltages to at least some of the electrodes to cause unwanted ions to adopt unstable trajectories through the first mass filter and / or to cause unwanted ions to be radially ejected from the first mass filter.

[0034] The third device is preferably designed and adapted to cause unwanted ions to be substantially diluted.

[0035] The plurality of electrodes preferably include a quadrupole rod set.

[0036] The quadrupole rod set preferably contains an axially segmented quadrupole rod set. The axially segmented quadrupole rod set preferably contains at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 segments.

[0037] The plurality of electrodes preferably includes a plurality of ring electrodes or a plurality of other electrodes having at least one opening through which ions are passed during use. According to one embodiment, at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 ring electrodes or other electrodes are preferably provided.

[0038] The plurality of ring electrodes are preferably radially segmented.

[0039] The first device is preferably designed and adapted to maintain an axial DC electric field or DC potential gradient across at least a portion of the axial length of the first mass filter to drive at least some ions along at least a portion of the axial length of the first mass filter to generate the axial force.

[0040] The first device is preferably designed and adapted to apply one or more transient DC voltages to the plurality of electrodes to drive at least some ions along at least a portion of the axial length of the first mass filter to generate the axial force.

[0041] The first mass filter preferably further includes one or more vane electrodes.

[0042] The first device is preferably designed and adapted to apply: (i) a DC voltage to the one or more vane electrodes to drive at least some ions along at least a portion of the axial length of the first mass filter; and / or (ii) one or more transient DC voltages to the one or more vane electrodes to drive at least some ions along at least a portion of the axial length of the first mass filter; and / or (iii) a multi-phase RF voltage to the one or more vane electrodes to drive at least some ions along at least a portion of the axial length of the first mass filter.

[0043] The first device is preferably designed and adapted to apply a multi-phase RF voltage to the plurality of electrodes to drive at least some ions along at least a portion of the axial length of the first mass filter to generate the axial force.

[0044] The first device preferably includes a gas flow device configured and adapted to drive at least some ions along at least a portion of the axial length of the first mass filter to generate the axial force.

[0045] The first mass filter is preferably switchable to operate in a mode in which ions are forwardly passed substantially independent of their mass-to-charge ratio.

[0046] The first mass filter is preferably designed to be switched to operate in an RF-only mode.

[0047] When the first mass filter is operated in RF-only mode, the first mass filter preferably acts as a broadband ion transmission ion guide.

[0048] The mass spectrometer preferably further comprises an ion mobility spectrometer or an ion mobility separator arranged upstream of the first mass filter, wherein the first mass filter is designed and adapted to filter ions by mass that emerge or elute from the ion mobility spectrometer or ion mobility separator.

[0049] The first mass filter and the quadrupole mass filter or mass analyzer are preferably arranged in the same or different vacuum chambers.

[0050] According to a further aspect of the present invention, there is provided a method of mass spectrometry comprising: Providing a first mass filter containing a plurality of electrodes and a quadrupole mass filter or mass analyzer arranged downstream of the first mass filter, wherein the quadrupole mass filter or mass analyzer is maintained at a lower pressure than the first mass filter; Applying one or more resolving DC voltages to at least some of the electrodes to cause unwanted ions to be ejected radially from the first mass filter, or applying RF voltages to at least some of the electrodes to cause unwanted ions to be ejected radially from the first mass filter; and Maintaining an axial DC electric field across at least a portion of the axial length of the first mass filter to drive at least some ions along at least a portion of the axial length, or applying one or more transient DC voltages to the plurality of electrodes to drive at least some ions along at least a portion of the axial length.

[0051] Further disclosed is a method for mass spectrometry comprising: Providing a first mass filter containing a plurality of electrodes and a quadrupole mass filter or mass analyzer arranged downstream of the mass filter; and Generating an axial force that propels at least some ions axially through or along the first mass filter.

[0052] Further disclosed is a mass spectrometer comprising: a first mass filter including a plurality of electrodes and a first device configured and adapted to generate an axial force that propels at least some ions axially through or along the first mass filter; and an analytical quadrupole mass filter or mass analyzer arranged downstream of the first mass filter; wherein the first mass filter is designed and adapted to be operated to substantially limit or reduce the ion current passed to the analytical quadrupole mass filter or mass analyzer; and wherein the first mass filter and the analytical quadrupole mass filter or mass analyzer are designed and adapted to be operated in a mode in which: (i) the first mass filter is adapted to mass-filter ions having a first mass resolution R1, and wherein the quadrupole mass filter or mass analyzer is adapted, at substantially the same time T1, to mass-filter ions having a second mass resolution R2, where R2 > R1; and (ii) the first mass filter is adapted to pass ions having a first mass-to-charge ratio or a first mass-to-charge ratio range M1, and wherein, at substantially the same time T1, the quadrupole mass filter or mass analyzer is adapted to pass ions having a second mass-to-charge ratio or a second mass-to-charge ratio range M2, where M1 - M2 ≤ × Da and where × is selected from the following group: (i) 10; (ii) 5; (iii) 1; (iv) 0.5; (v) 0.1; (vi) 0.05; (vii) 0.01; (viii) 0.005; and (ix) 0.001.

[0053] US 6 987 264 B1 (Whitehouse) does not teach or suggest operating a mass filter upstream of an analytical quadrupole with a resolution lower than that of the analytical quadrupole.

[0054] US 6 987 264 B1 (Whitehouse) does not teach or suggest operating a mass filter upstream of an analytical quadrupole such that the center of the transmission window of the upstream mass filter coincides with the center of the transmission window of the analytical quadrupole.

[0055] The present invention is particularly advantageous in that the upstream mass filter is designed to significantly reduce contamination of the analytical quadrupole rod set.

[0056] Further disclosed is a method for mass spectrometry comprising: Providing a first mass filter containing a plurality of electrodes and a quadrupole mass filter or mass analyzer arranged downstream of the mass filter; and generating an axial force that propels at least some ions axially through or along the first mass filter; Operating the first mass filter to substantially limit or reduce the ion current passed to the analytical quadrupole mass filter or mass analyzer; Operating the first mass filter to mass-filter ions having a first mass resolution R1, and at substantially the same time T1, operating the analytical quadrupole mass filter to mass-filter ions having a second mass resolution R2, where R2 > R1; and Operating the first mass filter to pass ions having a first mass-to-charge ratio or range M1, and at substantially the same time T1, operating the analytical quadrupole mass filter or mass analyzer to pass ions having a second mass-to-charge ratio or range M2, where M1 - M2 ≤ × Da and where × is selected from the group consisting of: (i) 10; (ii) 5; (iii) 1; (iv) 0.5; (v) 0.1; (vi) 0.05; (vii) 0.01; (viii) 0.005; and (ix) 0.001. US 6 987 264 B1 (Whitehouse) does not teach or suggest operating a mass filter upstream of an analytical quadrupole with a resolution lower than that of the analytical quadrupole. US 6 987 264 B1 (Whitehouse) does not teach or suggest operating a mass filter upstream of an analytical quadrupole such that the center of the transmission window of the upstream mass filter coincides with the center of the transmission window of the analytical quadrupole.

[0057] The present invention is particularly advantageous in that the upstream mass filter is designed to significantly reduce contamination of the analytical quadrupole rod set.

[0058] Further disclosed is a mass filter comprising: multiple electrodes; and a first device configured and adapted to generate an axial force that propels at least some ions axially through or along the mass filter.

[0059] According to a preferred embodiment, the mass filter includes an axially segmented quadrupole rod set ion guide. RF voltages are preferably applied to the electrodes forming the quadrupole rod set.

[0060] The mass filter is preferably designed to operate at a relatively high pressure in a mass-resolution or mass-to-charge ratio resolution mode, with both DC and RF voltages applied to the electrodes and with additional or further DC voltages applied to the axial segments of the mass filter. The application of the additional or further DC voltages to the axial segments, which together form a rod electrode, results in the generation of an axial DC electric field that serves to drive the ions along the length of the mass filter and through the mass filter. The axial DC electric field or DC potential gradient, preferably maintained along the axial length of the mass filter, significantly reduces the transit time of the ions through the mass filter.

[0061] The preferred embodiment allows for a relatively high-pressure mass filter to be provided by using an axial DC electric field to reduce the transit time of desired ions to be forwardly transmitted through the mass filter. As a result, the ion transmission efficiency of ions to be forwardly transmitted through the mass filter is significantly improved compared to conventional mass filters.

[0062] A particularly advantageous aspect of the preferred embodiment is that the mass filter is designed to control or reduce the transit time of ions through the high pressure quadrupole or other ion guide to improve the resolution properties of the mass filter.

[0063] The present invention enables a high pressure mass filter to be provided, which is particularly advantageous since conventional mass filters must be operated at relatively low pressures, requiring relatively expensive vacuum pumps.

[0064] In contrast to conventional mass filters, the mass filter according to the preferred embodiment can, for example, be incorporated into a new generation of low-cost and compact mass spectrometers currently being developed. The new generation of low-cost and compact mass spectrometers is designed to operate at relatively higher pressures than conventional high-resolution mass spectrometers. As a result, the new generation of low-cost and compact mass spectrometers does not require high-performance vacuum pumps, which can significantly reduce the cost of the mass spectrometer. The mass filter according to the preferred embodiment is ideally suited for inclusion in one of the new generation of mass spectrometers currently being developed.As will be apparent to those skilled in the art, a conventional quadrupole rod set mass filter would not be suitable for use in a relatively high pressure vacuum chamber such as those used in one of the new generation of mass spectrometers.

[0065] The preferred embodiment therefore enables a mass filter to be provided that effectively mass filters ions at relatively higher pressures than those currently associated with conventional quadrupole mass filters.

[0066] The mass filter according to the preferred embodiment also provides an effective means for protecting the downstream ion-optical devices from excessive charge. For example, the mass filter according to the preferred embodiment can be designed to filter out unwanted ions in a relatively high-pressure vacuum chamber, for example, located adjacent to an atmospheric pressure interface of a mass spectrometer.The mass filter according to the preferred embodiment can therefore be designed to protect ion optical devices such as ion traps, high performance analytical mass filters or mass analyzers or ion detectors provided in a downstream vacuum chamber maintained at a much lower pressure from experiencing a high ion current that could otherwise cause the ion trap, high performance analytical mass filter or mass analyzer or ion detector to suffer from saturation effects.

[0067] According to one embodiment, the preferred mass filter may be provided downstream of an ion mobility spectrometer or ion mobility separator and configured to mass-filter ions exiting or eluting from the ion mobility spectrometer or ion mobility separator.

[0068] The plurality of electrodes preferably form a quadrupole rod set.

[0069] The quadrupole rod set preferably contains an axially segmented quadrupole rod set. The axially segmented quadrupole rod set preferably contains at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 segments.

[0070] The plurality of electrodes preferably includes a plurality of ring electrodes or a plurality of other electrodes having at least one opening through which ions are passed during use. According to one embodiment, at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 ring electrodes or other electrodes are preferably provided.

[0071] The first device is preferably designed and adapted to maintain an axial DC electric field or DC potential gradient across at least a portion of the axial length of the first mass filter to drive at least some ions along at least a portion of the axial length of the mass filter to generate the axial force.

[0072] The first device may preferably be designed and adapted to apply one or more transient DC voltages to the plurality of electrodes to drive at least some ions along at least a portion of the axial length of the first mass filter to generate the axial force.

[0073] According to a less preferred embodiment, the first mass filter may further include one or more vane electrodes.

[0074] The first device may be configured and adapted to apply: (i) a DC voltage to the one or more vane electrodes to drive at least some ions along at least a portion of the axial length of the mass filter; and / or (ii) one or more transient DC voltages to the one or more vane electrodes to drive at least some ions along at least a portion of the axial length of the mass filter; and / or (iii) a multi-phase RF voltage to the one or more vane electrodes to drive at least some ions along at least a portion of the axial length of the mass filter.

[0075] The first device may be configured and adapted to apply a multi-phase RF voltage (e.g., three-phase, four-phase, or higher phase) to the plurality of electrodes to drive at least some ions along at least a portion of the axial length of the mass filter to generate the axial force.

[0076] The first device may include a gas flow device configured and adapted to drive at least some ions along at least a portion of the axial length of the mass filter to generate the axial force.

[0077] The mass filter preferably includes a second device designed and adapted to apply one or more resolving DC voltages to at least some of the electrodes to cause unwanted ions to adopt unstable trajectories through the mass filter and / or to cause unwanted ions to be radially ejected from the mass filter.

[0078] The second device is preferably designed and adapted to cause unwanted ions to be substantially diluted.

[0079] The mass filter preferably further includes a third device designed and adapted to apply RF voltages to at least some of the electrodes to cause unwanted ions to adopt unstable trajectories through the mass filter and / or to cause unwanted ions to be radially ejected from the mass filter.

[0080] The third device is preferably designed and adapted to cause unwanted ions to be substantially diluted.

[0081] The mass filter is preferably designed or adapted to be maintained at a pressure selected from the following group: (i) < 0.0001 mbar; (ii) 0.0001 to 0.001 mbar; (iii) 0.001-0.01 mbar; (iv) 0.01-0.1 mbar; (v) 0.1-1 mbar; (vi) 1-10 mbar; (vii) 10 to 100 mbar; (viii) 100-1000 mbar; and (ix) > 1000 mbar.

[0082] The mass filter preferably has an axial length selected from the following group: (i) < 10 mm; (ii) 10-20 mm; (iii) 20-30 mm; (iv) 30-40 mm; (v) 40-50 mm; (vi) 50-60 mm; (vii) 60-70 mm; (viii) 70-80 mm; (ix) 80-90 mm; (x) 90-100 mm; (xi) 100-110 mm; (xii) 110-120 mm; (xiii) 120-130 mm; (xiv) 130-140 mm; (xv) 140-150 mm; (xvi) 150-160 mm; (xix) 160-170 mm; (xix) 170-180 mm; (xix) 180-190 mm; (xx) 190-200 mm; and (xxi) > 200 mm.

[0083] The mass filter is preferably designed to be maintained at a pressure P and to have an axial length L for which the product PxL is selected from the following group: (i) < 0.001 mbar-mm; (ii) 0.001-0.01 mbar-mm; (iii) 0.01-0.1 mbar-mm; (iv) 0.1-1 mbar-mm; (v) 1-10 mbar-mm; (vi) 10-100 mbar-mm; (vii) 100-1000 mbar-mm; (viii) 1000-10000 mbar-mm; (ix) 10000-100000 mbar-mm; and (x) > 100000 mbar-mm.

[0084] The mass filter is preferably switchable to operate in a mode in which ions are forwardly passed essentially independent of their mass-to-charge ratio.

[0085] The mass filter is preferably designed to be switched to operate in an RF-only mode.

[0086] When the first mass filter is operated in the RF-only mode according to one embodiment, the first mass filter preferably functions as a broadband ion transmission ion guide.

[0087] Further disclosed is a mass spectrometer which includes a mass filter as described above.

[0088] The mass spectrometer preferably further comprises a further mass filter or mass analyzer arranged downstream of the mass filter.

[0089] The further mass filter or mass analyzer preferably comprises a quadrupole mass filter or mass analyzer. The quadrupole mass filter or mass analyzer preferably comprises a quadrupole rod set mass filter or mass analyzer. The quadrupole rod set mass filter or mass analyzer preferably comprises either a non-axially segmented quadrupole rod set mass filter or mass analyzer or an axially segmented quadrupole rod set mass filter or mass analyzer.

[0090] According to a further embodiment, the further mass filter or mass analyzer comprises a time-of-flight mass analyzer.

[0091] According to a further embodiment, the time-of-flight mass analyzer includes an axial acceleration time-of-flight mass analyzer or an orthogonal acceleration time-of-flight mass analyzer.

[0092] The mass spectrometer may further include an ion mobility spectrometer or an ion mobility separator arranged upstream of the mass filter, wherein the mass filter is designed and adapted to mass-filter ions emerging or eluting from the ion mobility spectrometer or ion mobility separator.

[0093] Further disclosed is a method for mass filtering ions comprising: Providing a mass filter; and Generating an axial force that propels at least some ions axially through or along the mass filter.

[0094] Further disclosed is a method of mass spectrometry including a method of mass filtering as described above.

[0095] Further disclosed is a quadrupole rod set mass filter or mass analyzer including a device designed and adapted to accelerate ions axially through the mass filter or mass analyzer or along the mass filter or mass analyzer.

[0096] Further disclosed is a method for mass filtering or mass analyzing ions, comprising: providing a quadrupole rod set mass filter or mass analyzer; and axial acceleration of ions through the mass filter or mass analyzer or along the mass filter or mass analyzer.

[0097] According to one embodiment, the mass spectrometer may further include: (a) an ion source selected from the following group: (i) an electrospray ion source (“ESI” ion source); (ii) an atmospheric pressure photoionization ion source (“APPI ion source”), (iii) an atmospheric pressure chemical ionization ion source (“APCI ion source”), (iv) a matrix-assisted laser desorption ionization ion source (“MALDI ion source”), (v) a laser desorption ionization ion source (“LDI ion source”), (vi) an atmospheric pressure ionization ion source (“API ion source”), (vii) a desorption / ionization on silicon ion source (“DIOS ion source”), (viii) an electron impact ion source (“EI ion source”), (ix) a chemical ionization ion source (“CI ion source”), (x) a field ionization ion source (“FI ion source”), (xi) a field desorption ion source (“FD ion source”), (xii) a Inductively coupled plasma ion source (“ICP ion source”), (xiii) a fast atom bombardment ion source (“FAB ion source”),(xiv) a liquid secondary ion mass spectrometry ion source (“LSIMS ion source”), (xv) a desorption electrospray ionization ion source (“DESI ion source”), (xvi) a radioactive nickel-63 ion source, (xvii) a matrix-assisted atmospheric pressure laser desorption ionization ion source, (xviii) a thermal spray ion source, (xix) an atmospheric sampling glow discharge ionization ion source (“ASGDI ion source”), (xx) a glow discharge ion source (“GD ion source”), (xxi) an impactor ion source, (xxii) a direct analysis in real-time ion source (“DART ion source”), (xxii) a laser spray ionization ion source (“LSI ion source”), (xxiv) a sonic spray ionization ion source (“SSI ion source”), (xxv) a matrix-assisted inlet ionization ion source (“MAII ion source”), (xxvi) a solvent-assisted inlet ionization ion source (“SAII ion source”),(xxvii) a desorption electrospray ionization ion source (“DESI ion source”), (xxviii) a laser ablation electrospray ionization ion source (“LAESI ion source”) and a surface-assisted laser desorption ionization ion source (“SALDI ion source”); and / or, (b) one or more continuous or pulsed ion sources and / or (c) one or more ion guides and / or (d) one or more ion mobility separation devices and / or one or more field asymmetric ion mobility spectrometer devices and / or (e) one or more ion traps or one or more ion confinement regions and / or (f) one or more impact, fragmentation or reaction cells selected from the following group: (i) a collision-induced dissociation fragmentation device (“CID fragmentation device”), (ii) a surface-induced dissociation fragmentation device (“SID fragmentation device”), (iii) an electron transfer dissociation fragmentation device (“ETD fragmentation device”), (iv) an electron capture dissociation fragmentation device (“ECD fragmentation device”), (v) an electron impact or impact dissociation fragmentation device, (vi) a photo-induced dissociation fragmentation device (“PID fragmentation device”), (vii) a laser-induced dissociation fragmentation device, (viii) an infrared radiation-induced dissociation device, (ix) an ultraviolet radiation-induced dissociation device, (x) a nozzle-skimmer interface fragmentation device, (xi) an in-source fragmentation device, (xii) an in-source collision-induced dissociation fragmentation device, (xiii) a thermal or temperature source fragmentation device, (xiv) an electric field induced fragmentation device, (xv) a magnetic field induced fragmentation device, (xvi) an enzyme digestion or enzyme degradation fragmentation device, (xvii) an ion-ion reaction fragmentation device, (xviii) an ion-molecule reaction fragmentation device, (xix) an ion-atom reaction fragmentation device, (xx) an ion-metastable ion reaction fragmentation device, (xxi) an ion-metastable molecule reaction fragmentation device, (xxii) an ion-metastable atom reaction fragmentation device, (xxiii) an ion-ion reaction device for reacting ions to form adducts or product ions, (xxiv) an ion-molecule reaction device for reacting ions to form adducts or product ions, (xxv) an ion-atom reaction device for reacting ions to form adducts or product ions, (xxvi) an ion-metastable ion reaction device for reacting ions to form adducts or product ions, (xxvii) an ion-metastable molecule reaction device for reacting ions to form adducts or product ions, (xxviii) an ion-metastable atom reaction device for reacting ions to form adducts or product ions and (xxix) an electron ionization dissociation fragmentation device (“EID fragmentation device”) and / or (g) a mass analyzer selected from the following group: (i) a quadrupole mass analyzer, (ii) a 2D or linear quadrupole mass analyzer, (iii) a Paul or 3D quadrupole mass analyzer, (iv) a Penning trap mass analyzer, (v) an ion trap mass analyzer, (vi) a magnetic sector mass analyzer, (vii) an ion cyclotron resonance mass analyzer (“ICR mass analyzer”), (viii) a Fourier transform ion cyclotron resonance mass analyzer (“FTICR mass analyzer”), (ix) an electrostatic mass analyzer designed to generate an electrostatic field having a quadrolologarithmic potential distribution, (x) an electrostatic Fourier transform mass analyzer, (xi) a Fourier transform mass analyzer, (xii) a time-of-flight mass analyzer, (xiii) an orthogonal acceleration time-of-flight mass analyzer and (xiv) a linear acceleration time-of-flight mass analyzer and / or (h) one or more energy analyzers or electrostatic energy analyzers and / or (i) one or more ion detectors and / or (j) one or more mass filters selected from the following group: (i) a quadrupole mass filter, (ii) a 2D or linear quadrupole ion trap, (iii) a Paul or 3D quadrupole ion trap, (iv) a Penning ion trap, (v) an ion trap, (vi) a magnetic sector mass filter, (vii) a time-of-flight mass filter and (viii) a Wien filter and / or (k) a device or ion gate for pulsing ions and / or (l) an apparatus for converting a substantially continuous ion beam into a pulsed ion beam.

[0098] The mass spectrometer may also contain: (i) a C-trap and a mass analyzer having an outer tubular electrode and a coaxial inner spindle-like electrode forming an electrostatic field with a quadrolologarithmic potential distribution, wherein in a first mode of operation, ions are passed to the C-trap and then injected into the mass analyzer, and wherein in a second mode of operation, ions are passed to the C-trap and then passed to a collision cell or electron transfer dissociation device, wherein at least some ions are fragmented into fragment ions, and wherein the fragment ions are then passed to the C-trap before being injected into the mass analyzer, and / or (ii) a ring-stack ion guide including a plurality of electrodes each having an aperture through which ions are passed in use, and wherein the distance between the electrodes increases along the length of the ion path, and wherein the apertures in the electrodes in an upstream portion of the ion guide have a first diameter, and wherein the apertures in the electrodes in a downstream portion of the ion guide have a second diameter smaller than the first diameter, and wherein opposite phases of an AC or RF voltage are applied in use to successive electrodes.

[0099] According to one embodiment, the mass spectrometer further includes a device designed and adapted to supply an AC or RF voltage to the electrodes. The AC or RF voltage preferably has an amplitude selected from the following group: (i) < 50 V peak-to-peak, (ii) 50-100 V peak-to-peak, (iii) 100-150 V peak-to-peak, (iv) 150-200 V peak-to-peak, (v) 200-250 V peak-to-peak, (vi) 250-300 V peak-to-peak, (vii) 300-350 V peak-to-peak, (viii) 350-400 V peak-to-peak, (ix) 400-450 V peak-to-peak, (x) 450-500 V peak-to-peak and (xi) > 500 V peak-to-peak.

[0100] The AC or RF voltage preferably has a frequency selected from the following group: (i) < 100 kHz, (ii) 100-200 kHz, (iii) 200-300 kHz, (iv) 300-400 kHz, (v) 400-500 kHz, (vi) 0.5-1.0 MHz, (vii) 1.0-1.5 MHz, (viii) 1.5-2.0 MHz, (ix) 2.0-2.5 MHz, (x) 2.5-3.0 MHz, (xi) 3.0-3.5 MHz, (xii) 3.5-4.0 MHz, (xiii) 4.0-4.5 MHz, (xiv) 4.5-5.0 MHz, (xv) 5.0-5.5 MHz, (xvi) 5.5-6.0 MHz, (xvii) 6.0-6.5 MHz, (xviii) 6.5-7.0 MHz, (xix) 7.0-7.5 MHz, (xx) 7.5-8.0 MHz, (xxi) 8.0-8.5 MHz, (xxii) 8.5-9.0 MHz, (xxiii) 9.0-9.5 MHz, (xxiv) 9.5-10.0 MHz and (xxv) > 10.0 MHz.

[0101] The mass spectrometer may further comprise a chromatography or other separation device upstream of an ion source. In one embodiment, the chromatography separation device comprises a liquid chromatography or gas chromatography device. In another embodiment, the separation device may comprise: (i) a capillary electrophoresis separation device ("CE separation device"), (ii) a capillary electrochromatography separation device ("CEC separation device"), (iii) a separation device comprising a substantially rigid ceramic-based multilayer microfluidic substrate ("ceramic tile"), or (iv) a supercritical fluid chromatography separation device.

[0102] The mass spectrometer may contain a chromatography detector.

[0103] The chromatography detector may comprise a destructive chromatography detector, preferably selected from the following group: (i) a flame ionization detector (“FID”); (ii) an aerosol-based detector or nanoquantity analyte detector (“NQAD”); (iii) a flame photometric detector (“FPD”); (iv) an atomic emission detector (“AED”); (v) a nitrogen-phosphorus detector (“NPD”); and (vi) an evaporative light scattering detector (“ELSD”).

[0104] Additionally or alternatively, the chromatography detector may comprise a non-destructive chromatography detector, preferably selected from the following group: (i) a fixed or variable wavelength UV detector; (ii) a thermal conductivity detector (“TCD”); (iii) a fluorescence detector; (iv) an electron capture detector (“ECD”); (v) a conductivity monitor; (vi) a photoionization detector (“PID”); (vii) a refractive index detector (“RID”); (viii) a radio frequency detector; and (ix) a chiral detector.

[0105] The ion guide is preferably maintained at a pressure selected from the following group: (i) < 0.0001 mbar, (ii) 0.0001-0.001 mbar, (iii) 0.001-0.01 mbar, (iv) 0.01-0.1 mbar, (v) 0.1-1 mbar, (vi) 1-10 mbar, (vii) 10-100 mbar, (viii) 100-1000 mbar and (ix) > 1000 mbar.

[0106] According to one embodiment, analyte ions can be subjected to electron transfer dissociation (“ETD”) fragmentation in an electron transfer dissociation fragmentation device. Analyte ions are preferably caused to interact with ETD reagents within an ion guide or fragmentation device.

[0107] According to one embodiment, to effect electron transfer dissociation, either: (a) analyte ions are fragmented or caused to dissociate and form product or fragment ions after interacting with reagent ions and / or (b) electrons are transferred from one or more reagent anions or negatively charged ions to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions, and / or (c) analyte ions are fragmented or caused to dissociate and form product or fragment ions after interacting with neutral reagent gas molecules or atoms or a non-ionic reagent gas,and / or (d) electrons are transferred from one or more neutral non-ionic or uncharged source gases or vapors to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions, and / or (e) electrons are transferred from one or more neutral non-ionic or uncharged superbase reagent gases or vapors to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions, and / or (f) electrons are transferred from one or more neutral,non-ionic or uncharged alkali metal gases or vapors to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions, and / or (g) electrons are transferred from one or more neutral, non-ionic or uncharged gases, vapors or atoms to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions, wherein the one or more neutral, non-ionic or uncharged gases, vapors or atoms are selected from the following group: (i) sodium vapor or atoms, (ii) lithium vapor or atoms, (iii) potassium vapor or atoms,(iv) rubidium vapor or atoms, (v) caesium vapor or atoms, (vi) francium vapor or atoms, (vii) C60 vapor or atoms, and (viii) magnesium vapor or atoms.

[0108] The multiply charged analyte cations or positively charged ions preferably contain peptides, polypeptides, proteins or biomolecules.

[0109] According to one embodiment, to effect electron transfer dissociation: (a) the reagent anions or negatively charged ions are derived from a polyaromatic hydrocarbon or a substituted polyaromatic hydrocarbon and / or (b) the reagent anions or negatively charged ions are derived from the following group: (i) anthracene, (ii) 9,10-diphenylanthracene, (iii) naphthalene, (iv) fluorine, (v) phenanthrene, (vi) pyrene, (vii) fluoranthene, (viii) chrysene, (ix) triphenylene, (x) perylene, (xi) acridine, (xii) 2,2'-dipyridyl, (xiii) 2,2'-biquinoline, (xiv) 9-anthracenecarbonitrile, (xv) dibenzothiophene, (xvi) 1,10'-phenanthroline, (xvii) 9'-anthracenecarbonitrile and (xviii) anthraquinone and / or (c) the reagent ions or negatively charged ions comprise azobenzene anions or azobenzene radical anions.

[0110] According to a particularly preferred embodiment, the electron transfer dissociation fragmentation process involves the interaction of analyte ions with reagent ions, wherein the reagent ions comprise dicyanobenzene, 4-nitrotoluene or azulene. Brief description of the drawings

[0111] Various embodiments of the present invention will now be described, by way of example only, with reference to the drawings, in which: Fig. 1 shows a segmented quadrupole rod set mass filter according to a preferred embodiment and illustrates the resolving DC / RF voltages applied to the rod electrodes and also additional axial DC voltages applied to the rod electrodes to generate an axial DC electric field that causes ions to be accelerated axially through the mass filter; Fig. 2 shows the results of SIMION modeling (RTM modeling) of the effect on the ion transmission efficiency of ions held within the mass filter for different periods of time, and in particular illustrates how the ion transmission efficiency is significantly improved when ions are held within the mass filter for only a relatively short period of time, as in the preferred embodiment; Fig. 3A shows a mass spectrum obtained according to an embodiment of the present invention, wherein a resolving DC voltage of 36 V in combination with an RF voltage was applied to the electrodes of a preferred mass filter, Fig. Figure 3B shows a mass spectrum obtained according to an embodiment of the present invention, wherein a resolving DC voltage of 34 V in combination with an RF voltage was applied to the electrodes of a preferred mass filter, and Fig. Figure 3C shows a mass spectrum obtained when the preferred mass filter was operated in an RF-only mode (i.e., in a non-resolving mode), with the preferred mass filter effectively operating as a broadband transmission ion guide; and Fig. 4 relative transmission curves based on the mass spectra obtained in Fig. 3A-3C, and in particular illustrates: (i) the relative transmission of ions when 36 V DC resolving voltage was applied to the rods in combination with an RF voltage, relative to when the mass filter was operated in an RF-only mode; and (ii) the relative transmission of ions when 34 V DC resolving voltage was applied to the rods in combination with an RF voltage, relative to when the mass filter was operated in an RF-only mode. Detailed description of the preferred embodiment

[0112] A preferred embodiment of the present invention will now be described with reference to Fig. 1 described.

[0113] According to a preferred embodiment of the present invention, a quadrupole rod set mass filter is provided. The quadrupole rod set mass filter preferably comprises an axially segmented quadrupole rod set, each of the four rods being arranged as shown in Fig. 1 is axially divided into several axial segments.

[0114] According to the preferred embodiment, resolving DC voltages (Res DC) and RF voltages are preferably applied to all of the rod electrodes. According to the preferred embodiment, all of the axial segments that together form a single rod electrode are supplied with the same resolving DC voltage and RF voltage. The same resolving DC voltage and RF voltage are applied to opposite axially segmented rod electrodes. Different resolving DC voltages and the opposite phase of the RF voltage are applied to adjacent axially segmented rod electrodes.

[0115] In addition to applying the resolving DC and RF voltages to the rod electrodes, an axial DC gradient (degrees DC) is preferably maintained along the length of each of the rod electrodes to control the transit time of the ions through the quadrupole. According to the preferred embodiment, different axial segments of a particular rod electrode are maintained at different DC voltages or potentials, thus maintaining an axial DC gradient along the length of the mass filter. Maintaining an axial DC gradient along the length of the mass filter advantageously allows the mass filter to operate with minimal loss in the transmission of ions of interest.The axially segmented nature of the rod electrodes allows DC voltages to be applied to the rod electrodes to drive ions along the length of the mass filter and also allows resolving DC / RF voltages to be applied to the electrodes to generate a substantially axially independent radial resolving DC electric field.

[0116] Although according to the preferred embodiment, axial DC voltages are applied to all four axially segmented rod electrodes, less preferred embodiments are contemplated in which DC voltages are applied to only one, two, or three of the axially segmented rod electrodes.

[0117] The segmented nature of the quadrupole rod set according to the preferred embodiment allows the application of the same phase of an RF voltage to all axial segments of a particular rod electrode. According to the preferred embodiment, opposing rod electrodes are maintained in the same RF phase, and adjacent rod electrodes are preferably maintained in opposite phases of the RF voltage.

[0118] As in Fig. 1, axially adjacent segments of the same rod electrode are preferably maintained at the same RF voltage, and the same resolving DC voltage is preferably applied to all of the axial segments forming a rod electrode. According to a less preferred embodiment, the same resolving RF and DC voltages may be applied to only some of the axial segments forming a rod electrode.

[0119] Different axial-field DC voltages are preferably applied to the segmented rod sections of a rod electrode, such that, in one mode of operation, an axial DC voltage gradient is preferably maintained along the length of the quadrupole. For example, the rod segments closest to an input end of the quadrupole mass filter of all four rod electrodes can be maintained at the same voltage V1, and similarly, all rod segments closest to an output end of the quadrupole of all four rod electrodes can be maintained at the same voltage V2. According to the preferred embodiment, V1 > V2. According to a particularly preferred embodiment, V1 can be positive and V2 can be negative.According to one embodiment, V1 can be in the range 0-10 V, 10-20 V, 20-30 V, V 30-40, 40-50 V, 50-60 V, 60-70 V, 70-80 V, 80-90 V, 90-100 V or > 100 V and / or V2 can be in the range < 0 V, 0 to -10 V, -10 V to -20, -20 to -30 V, -30 to -40 V, -40 to -50 V, -50 to -60 V, - 60 to -70 V, - 70 to -80 V, -80 to -90 V, -90 to - 100 V or <-100 V.

[0120] An ion population or group of ions transmitted to the mass filter and experiencing an axial electric field is preferentially driven through the mass filter or ion guide by the axial DC electric field or the axial DC potential gradient, thereby reducing the transit time of ions, while simultaneously undergoing radial mass-to-charge ratio-based mass filtering or mass-to-charge ratio instability filtering, such that ions with undesirable mass-to-charge ratios are radially excited or otherwise diluted. Ions with undesirable mass-to-charge ratios may impact the segmented rod electrodes and thus be lost to the system or otherwise diluted.

[0121] The mass filter according to the preferred embodiment shows a significant improvement in performance, particularly in terms of ion transmission efficiency, compared to conventional quadrupole mass filters that do not use axial fields, since controlling (reducing) the transit time of the ions of interest is important for at least two reasons.

[0122] First, reducing the transit time improves the performance and especially the duty cycle of the mass filter for fast switching experiments.

[0123] Second, reducing the transit time improves the performance of the device when acting as a mass filter, since without the axial field, the transit time of the ions would otherwise be sufficiently long that ions of interest experience many cycles of the RF electric field, resulting in some ions intended to pass forward through the mass filter being inadvertently ejected radially from the mass filter or ion guide or otherwise lost to the rods.

[0124] Fig. Figure 2 shows the results of a SIMION model (RTM model) showing how ions are inadvertently ejected radially from a quadrupole mass filter when the ions remain inside the mass filter for too long, so that the ions experience too many cycles of the RF electric field, causing at least some of the ions to be ejected radially.

[0125] The SIMION model (RTM model) is based on a quadrupole mass filter with four rods with an inscribed radius r0 of 2.67 mm. An RF voltage applied to the rod electrodes at a frequency of 1 MHz was modeled. The background gas pressure was set to 7.5 × 10 -3 Torr (1 Torr = 133,322 Pascal) Argon modeled.

[0126] The transmission efficiency of singly charged ions with a mass-to-charge ratio of 684 was simulated by scanning the resolution RF voltage amplitude from 328.3 V to 359.0 V RF (0-peak) and the resolution DC voltage amplitude from 50.0 V to 54.7 V DC. The percentage of ions remaining after 1 ms, 5 ms, 10 ms, 15 ms, 20 ms, and 25 ms is shown in Fig. 2 as a function of the mass-to-charge ratio. The results in Fig. 2 show how the ion transmission efficiency of a mass filter varies as a function of the time it takes for the ions to pass through the mass filter.

[0127] The results in Fig. Figure 2 clearly shows that exposing ions to the resolving RF and / or DC voltage within the mass filter for an extended period (e.g., up to 25 ms) in combination with the presence of a background gas leads to an increased probability of ion loss to the rod electrodes. Accordingly, when ions are held in the mass filter for up to 25 ms, the ion transmission efficiency is relatively low (i.e., < 30%). In comparison, when the ions are held within the mass filter for a much shorter time (e.g., 1 ms), the ion transmission efficiency can be very high, e.g., > 95%.

[0128] Fig. 3A-3C show experimental results obtained when using a mass filter according to a preferred embodiment. Fig. Figure 3A shows a mass spectrum obtained when the mass filter was operated in a resolution mode with 36 V DC resolution voltage applied to the rod electrodes. Fig. Figure 3B shows a mass spectrum obtained when the mass filter was operated in a resolution mode with 34 V DC resolution voltage applied to the rod electrodes. Fig. Figure 3C shows a mass spectrum obtained when the mass filter was operated in a non-resolution mode, i.e., without a resolving DC voltage applied to the rod electrodes. As will be understood by those skilled in the art, when the mass filter is operated in a non-resolution mode or an RF-only mode, the mass filter operates or functions like a broadband transmission ion guide, i.e., ions are not actively mass filtered by the ion guide, and essentially all ions received at the entrance to the mass filter or ion guide are forwardly transmitted through the mass filter or ion guide.

[0129] Fig. Figure 4 shows relative transmission curves for the two DC resolution voltages described above with respect to Fig. 3A and Fig. 3B, and shows the relative transmission of ions as a function of mass-to-charge ratio for ions when transmitted through the mass filter operating in a mass-resolution mode compared to ions transmitted through the mass filter when operating in a non-resolution mode (where the ion transmission efficiency should be 100%).

[0130] For the data contained in Fig. 3A to 3C and Fig. 4, the axial DC electric field was set to 1 V across the entire 120 mm length of the device. The inscribed radius of the rods R0 was set to 5.3 mm, and the RF voltage applied to the rod electrodes was 1 MHz at 600 V peak-to-peak. The pressure within the mass filter was set to approximately 1 × 10 -2 mbar argon set.

[0131] According to one embodiment, the preferred mass filter can be used as a low-power, high-pressure mass filter or mass analyzer. In particular, the preferred device can be arranged upstream of a high-performance analytical mass filter or mass analyzer, such as a quadrupole rod-set mass filter or mass analyzer or a time-of-flight mass spectrometer. The preferred mass filter can advantageously be operated or otherwise configured to reduce the ion current reaching the high-performance analytical mass filter or mass analyzer, thus improving the robustness and lifetime of the high-performance analytical mass filter or mass analyzer by reducing loading problems.

[0132] The preferred device can be used downstream of an ion mobility spectrometer or ion mobility separator and can be configured to operate in a coupled scanning mode. For example, according to the preferred embodiment, a mass-to-charge ratio transmission window of the mass filter can be scanned synchronously with the ion mobility spectrometer or ion mobility separator, such that ions eluting from an upstream ion mobility spectrometer or ion mobility separator and received by the mass filter are mass-filtered such that only ions with a particular charge state (e.g., doubly, triply, or higher charged) are forwardly passed, while other ions with different charge states (e.g., singly charged) are significantly diluted.

[0133] The preferred mass filter can be used upstream of a charge-limited device such as an ion trap or an accumulation device to enable a higher duty cycle. The accumulation device can be placed upstream of an ion mobility spectrometer or ion mobility separator.

[0134] According to other less preferred embodiments, alternative methods of axially propelling ions through the mass filter may be used, including applying traveling DC waves or transient DC voltages or potentials to the electrodes forming the mass filter. Other embodiments are contemplated in which one or more vane electrodes may be provided and DC and / or RF voltages are applied to the one or more vane electrodes to axially accelerate ions. According to other embodiments, a multi-phase RF voltage may be applied to the electrodes to axially propel the ions. According to a further embodiment, one or more gas flow actuators or mechanisms may also be used to propel ions along at least a part or section of the mass filter.

[0135] Several preferred devices can be combined to provide multiple stages of mass filtration or mass analysis along with optional fragmentation of ions at relatively high pressures.

[0136] The segmented nature of the preferred mass filter allows for multiple configurations. For example, according to one embodiment, a portion or region of the mass filter may be configured to form an ion-confining region, wherein ions within the ion-confining region or portion of the mass filter may be axially confined by applying one or more DC and / or RF voltages, e.g., to input and / or output electrodes.

[0137] According to one embodiment of the present invention, one or more prefilters and / or one or more postfilters may be provided. The one or more prefilters and / or one or more postfilters may optionally be incorporated within the preferred device or otherwise attached thereto. According to one embodiment, the one or more prefilters and / or one or more postfilters may include a short quadrupole rod set or "stubbie," as is well known in the art.

[0138] Ions can be pulsed into the preferred mass filter. Embodiments are also contemplated in which ions can also be optionally separated according to their mass-to-charge ratio and / or ion mobility in combination with mass filtering while the ions are accelerated axially through the device.

[0139] Other radial ejection mechanisms, such as resonant ejection by applying excitation voltages to the electrodes forming the mass filter, may also be used. According to one embodiment, a broadband excitation voltage with one or more frequency notches may be applied to the electrodes forming the mass filter.

[0140] The preferred device may precede or follow a variety of known ion sources, fragmentation devices, and analyzers.

[0141] Several preferred devices can be combined either in series or in parallel.

[0142] RF devices other than quadrupoles can be used and may provide some degree of mass filtering.

Claims

[1] Mass spectrometer having: a first mass filter comprising a plurality of electrodes and a first device, the first device being configured and adapted to maintain an axial DC electric field across at least a portion of the axial length of the first mass filter to drive at least some ions along at least a portion of the axial length, or the first device being configured and adapted to apply one or more transient DC voltages to the plurality of electrodes to drive at least some ions along at least a portion of the axial length; a second device designed and adapted to apply one or more resolving DC voltages to at least some of the electrodes to cause unwanted ions to be radially ejected from the first mass filter, or a third device designed and adapted to apply RF voltages to at least some of the electrodes to cause unwanted ions to be radially ejected from the first mass filter; and a quadrupole mass filter or mass analyzer arranged downstream of the first mass filter, wherein the quadrupole mass filter or mass analyzer is maintained at a lower pressure than the first mass filter. [2] The mass spectrometer of claim 1, wherein the quadrupole mass filter comprises an analytical mass filter. [3] A mass spectrometer according to claim 1 or 2, wherein the first mass filter is designed and adapted to operate in a synchronized manner with the quadrupole mass filter or mass analyzer. [4] A mass spectrometer according to any one of the preceding claims, wherein the first mass filter is designed and adapted to be operated to substantially restrict or reduce the ion current passed to the quadrupole mass filter or mass analyzer. [5] A mass spectrometer according to any one of the preceding claims, wherein the first mass filter and the quadrupole mass filter or mass analyzer are designed and adapted to be operated in a mode in which the first mass filter is designed to mass filter ions having a first mass resolution R1, and wherein the quadrupole mass filter or mass analyzer is designed to mass filter ions having a second mass resolution R2 at the same time T1, where R2 > R1. [6] Mass spectrometer according to claim 5, wherein the first mass resolution R1 = (m / z) / W 1 / 2 , where m / z is the mass-to-charge ratio of an ion peak and W 1 / 2 is the half-width of the ion peak, and where the second mass resolution R2 = (m / z) / W 1 / 2 , where m / z is the mass-to-charge ratio of an ion peak and W 1 / 2 is the half-width of the ion peak. [7] A mass spectrometer according to any one of the preceding claims, wherein the first mass filter and the quadrupole mass filter or mass analyzer are designed and adapted to be operated in a mode in which the first mass filter is designed to pass ions having a first mass-to-charge ratio M1 and in which the quadrupole mass filter or mass analyzer is designed to pass ions having a second mass-to-charge ratio M2 at the same time T1, where M1 = M2. [8] A mass spectrometer according to claim 7, wherein the first mass filter is configured to thin out ions having a mass-to-charge ratio less than and / or greater than M1 at time T1. [9] A mass spectrometer according to claim 7 or 8, wherein the quadrupole mass filter or mass analyzer is designed and adapted to dilute ions having a mass-to-charge ratio less than and / or greater than M2 at time T1. [10] A mass spectrometer according to any one of the preceding claims, wherein the first mass filter and the quadrupole mass filter or mass analyzer are designed and adapted to be operated in a mode in which the first mass filter is designed to pass ions having a first mass-to-charge ratio or a first mass-to-charge ratio range M1, and wherein the quadrupole mass filter or mass analyzer is designed to pass ions having a second mass-to-charge ratio or a second mass-to-charge ratio range M2 at the same time T1, where M1 - M2 ≤ × Da (1.660 × 10 -27kg) and wherein × is selected from the following group: (i) 10; (ii) 5; (iii) 1; (iv) 0.5; (v) 0.1; (vi) 0.05; (vii) 0.01; (viii) 0.005; and (ix) 0.

001. [11] A mass spectrometer according to claim 10, wherein the first mass filter is configured to thin out ions having a mass-to-charge ratio less than and / or greater than M1 at time T1. [12] A mass spectrometer according to claim 10 or 11, wherein the quadrupole mass filter or mass analyzer is designed and adapted to dilute ions having a mass-to-charge ratio less than and / or greater than M2 at time T1. [13] A mass spectrometer according to any one of the preceding claims, wherein the first mass filter and / or the quadrupole mass filter or mass analyzer are designed and adapted to be maintained at a pressure selected from the following group: (i) < 0.0001 mbar; (ii) 0.0001 to 0.001 mbar; (iii) 0.001-0.01 mbar; (iv) 0.01-0.1 mbar; (v) 0.1-1 mbar; (vi) 1-10 mbar; (vii) 10 to 100 mbar; (viii) 100-1000 mbar; and (ix) > 1000 mbar. [14] A mass spectrometer according to any one of the preceding claims, wherein the first mass filter and / or the quadrupole mass filter or mass analyzer have an axial length selected from the following group: (i) < 10 mm; (ii) 10-20 mm; (iii) 20-30 mm; (iv) 30-40 mm; (v) 40-50 mm; (vi) 50-60 mm; (vii) 60-70 mm; (viii) 70-80 mm; (ix) 80-90 mm; (x) 90-100 mm; (xi) 100-110 mm; (xii) 110-120 mm; (xiii) 120-130 mm; (xiv) 130-140 mm; (xv) 140-150 mm; (xvi) 150-160 mm; (xix) 160-170 mm; (xix) 170-180 mm; (xix) 180-190 mm; (xx) 190-200 mm; and (xxi) > 200 mm. [15] A mass spectrometer according to any one of the preceding claims, wherein the first mass filter and / or the quadrupole mass filter or mass analyzer are adapted to be maintained at a pressure P and to have an axial length L, for which the product PxL is selected from the following group: (i) < 0.001 mbar-mm; (ii) 0.001-0.01 mbar-mm; (iii) 0.01-0.1 mbar-mm; (iv) 0.1-1 mbar-mm; (v) 1-10 mbar-mm; (vi) 10-100 mbar-mm; (vii) 100-1000 mbar-mm; (viii) 1000-10000 mbar-mm; (ix) 10000-100000 mbar-mm; and (x) > 100000 mbar-mm. [16] A mass spectrometer according to any preceding claim, wherein the second device is designed and adapted to cause unwanted ions to be substantially diluted. [17] A mass spectrometer according to any one of claims 1 to 15, wherein the third device is designed and adapted to cause unwanted ions to be substantially diluted. [18] A mass spectrometer according to any one of the preceding claims, wherein the plurality of electrodes form a quadrupole rod set. [19] A mass spectrometer according to claim 18, wherein the quadrupole rod set comprises an axially segmented quadrupole rod set. [20] A mass spectrometer according to any one of the preceding claims, wherein the plurality of electrodes comprises a plurality of ring electrodes or other electrodes having at least one aperture through which ions are passed in use. [21] The mass spectrometer of claim 20, wherein the plurality of ring electrodes are radially segmented. [22] A mass spectrometer according to any one of the preceding claims, wherein the first mass filter further comprises one or more vane electrodes. [23] The mass spectrometer of claim 22, wherein the first device is configured and adapted to apply: (i) a DC voltage to the one or more vane electrodes to drive at least some ions along at least a portion of the axial length of the first mass filter; and / or (ii) one or more transient DC voltages to the one or more vane electrodes to drive at least some ions along at least a portion of the axial length of the first mass filter; and / or (iii) a multi-phase RF voltage to the one or more vane electrodes to drive at least some ions along at least a portion of the axial length of the first mass filter. [24] A mass spectrometer according to any one of the preceding claims, wherein the first device is designed and adapted to apply a multi-phase RF voltage to the plurality of electrodes to drive at least some ions along at least a portion of the axial length of the first mass filter to generate the axial force. [25] A mass spectrometer according to any one of the preceding claims, wherein the first device includes a gas flow device designed and adapted to drive at least some ions along at least a portion of the axial length of the first mass filter to generate the axial force. [26] A mass spectrometer according to any preceding claim, wherein the first mass filter is switchable to operate in a mode in which ions are forwardly passed substantially regardless of their mass-to-charge ratio. [27] A mass spectrometer according to claim 26, wherein the first mass filter is configured to be switched to operate in an RF-only mode. [28] A mass spectrometer according to claim 27, wherein when the first mass filter is operated in the RF-only mode, the first mass filter functions as a broadband ion transmission ion guide. [29] A mass spectrometer according to any one of the preceding claims, further comprising an ion mobility spectrometer or an ion mobility separator arranged upstream of the first mass filter, the first mass filter being designed and adapted to mass-filter ions eluting from the ion mobility spectrometer or ion mobility separator. [30] A mass spectrometer according to any one of the preceding claims, wherein the first mass filter and the quadrupole mass filter or mass analyzer are arranged in the same or different vacuum chambers. [31] A method for mass spectrometry comprising: Providing a first mass filter containing a plurality of electrodes and a quadrupole mass filter or mass analyzer arranged downstream of the first mass filter, wherein the quadrupole mass filter or mass analyzer is maintained at a lower pressure than the first mass filter; Applying one or more resolving DC voltages to at least some of the electrodes to cause unwanted ions to be ejected radially from the first mass filter, or applying RF voltages to at least some of the electrodes to cause unwanted ions to be ejected radially from the first mass filter; and Maintaining an axial DC electric field across at least a portion of the axial length of the first mass filter to drive at least some ions along at least a portion of the axial length, or applying one or more transient DC voltages to the plurality of electrodes to drive at least some ions along at least a portion of the axial length.

Images