Ion transport with travelling potential well

Abstract

An ion transport apparatus comprises a power supply configured to supply RF voltages and AC auxiliary voltages. A plurality of electrodes comprise at least one axially segmented electrode and a plurality of axially non-segmented electrodes. The plurality of electrodes are spatially arranged collectively to define a volume extending along an ion optical axis to form a channel, and at least the plurality of axially non- segmented electrodes are configured to receive respective RF voltages from the power supply for generating a radially-confining electric potential field forming a pseudo-potential within the channel for guiding ions therealong. Each of the at least one axially segmented electrodes comprises an array of separate electrode segments that extends alongside the ion optical axis. The power supply is configured to apply to corresponding electrode segments of each said array a respective said AC auxiliary voltage comprising a temporal phase which differs by a substantially constant phase shift relative to respective temporal phases of AC auxiliary voltages concurrently applied to each neighbouring electrode segment of a given said array, thereby the plurality of electrodes collectively generate within said channel at least one travelling potential well for transporting ions therein along the ion optical axis.

Description

[0001] ION TRANSPORT WITH TRAVELLING POTENTIAL WELL

[0002] Field of the Invention

[0003] The present invention relates to methods and apparatus for ion transport, and particularly, though not exclusively, ion transport for use in a mass spectrometer (MS) such as a time-of-flight (TOF) mass spectrometer.

[0004] Background

[0005] Tandem mass spectrometers are widely used for identification and quantification of compounds.

[0006] Quadrupole time-of-flight (Q-TOF) mass spectrometers are a popular type of the tandem mass spectrometer in which orthogonal acceleration time-of-flight (oaTOF) is usually used due to its high resolution and mass accuracy. It is known that oaTOF suffers from a problem of low duty cycle when used either the continuous ion beam mode or in the ion trapping mode.

[0007] In the continuous ion beam mode, ions continuously travel from an ion guide to the downstream orthogonal acceleration electrodes of the oaTOF such that at any given time only a small fraction of those ions are positioned within the orthogonal acceleration electrodes of the oaTOF when a high-voltage TOF extraction pulse is applied to these electrodes for accelerating ions into the flight tube of the TOF system. The ratio of the number of those ions that can be accelerated by the extraction pulse, by being adjacent to the orthogonal acceleration electrodes at a given instant in time, to the number of those ions that are travelling towards the region of the orthogonal acceleration electrodes, is usually defined as the “TOF duty cycle”. The TOF duty cycle is typically about 20% for ions with m / z = 2000 and decreases for ions with smaller m / z value. This problem limits sensitivity of an oaTOF in the continuous ion beam mode. In the ion trapping mode, one may mitigate this problem to some extent by accumulating and trapping ions in an ion guide prior to injecting the ions to oaTOF. However, ions with varying m / z values travel to the region of the orthogonal acceleration electrodes at different times due to their varying velocities. This limits the m / z spectral range possible to obtain in a single TOF spectrum (i.e., a single shot arising from a single orthogonal acceleration of ions) without any spectrum averaging over multiple successive spectra. In addition, ions with the same m / z can leave the ion guide with a wide time spread, and thus can have a larger spatial distribution than the spatial size of orthogonal acceleration electrodes when the high-voltage extraction pulse is applied. This means that those ions that are outside the region of the orthogonal acceleration electrodes cannot be extracted into the flight tube of the TOF system for mass analysis, and this thereby limits the TOF duty cycle.

[0008] The present invention has been devised in light of the above considerations.

[0009] Summary of the Invention

[0010] The inventors have realised that there is a need to improve the sensitivity of a tandem mass spectrometer employing a TOF system (e.g., a Q-TOF) by enhancing TOF duty cycle. The inventors have realised that8628430

[0011] 2

[0012] an enhancement of the TOF duty cycle and MS sensitivity may be achieved by providing an improved ion transport system / method in an ion guide located upstream of an ion injection system of an oaTOF system. The improved ion transport system / method is not limited to use with a TOF system, of course, and may be used in other applications not involving any TOF system in which improvements on ion transport are desirable.

[0013] In a first aspect, the invention may provide an ion transport apparatus comprising:

[0014] a power supply configured to supply RF voltages and AC auxiliary voltages;

[0015] a plurality of electrodes comprising at least one axially segmented electrode and a plurality of axially non-segmented electrodes, wherein the plurality of electrodes are spatially arranged collectively to define a volume extending along an ion optical axis to form a channel, and at least the plurality of axially nonsegmented electrodes are configured to receive respective RF voltages from the power supply for generating a radially-confining electric potential field forming a pseudo-potential within the channel for guiding ions therealong;

[0016] wherein each of the at least one axially segmented electrodes comprises an array of separate electrode segments that extends alongside the ion optical axis and wherein each electrode segment is elongated to extend alongside the ion optical axis whereby successive electrode segments are separated by a segment separation region and the at least one axially segmented electrode extends alongside at least one said axially non-segmented electrode(s) to position a given segment separation region alongside an axially non-segmented electrode; and,

[0017] the power supply is configured to apply to corresponding electrode segments of each said array a respective said AC auxiliary voltage comprising a temporal phase which differs by a substantially constant phase shift relative to respective temporal phases of AC auxiliary voltages concurrently applied to each neighbouring electrode segment of a given said array, thereby the plurality of electrodes collectively generate within said channel at least one travelling potential well for transporting ions therein along the ion optical axis.

[0018] The axially segmented electrodes may be considered to be segmented in a direction substantially parallel to the ion optical axis. The separate electrode segments may each extend alongside the ion optical axis in a direction substantially parallel to the ion optical axis. The non-segmented electrodes may each extend alongside the ion optical axis in a direction substantially parallel to the ion optical axis. The plurality of electrodes may be linear. For example, each electrode of the plurality of electrodes may be elongated along a linear (straight) axis of the electrode. For example, each electrode of the plurality of electrodes may be shaped to be of unchanging cross-sectional profile in a plane transverse to its linear axis. For example, each electrode of the plurality of electrodes may be shaped to have a cross-sectional profile that is symmetrical about its linear axis in a plane transverse to its linear axis. An example is a linear cylindrical rod electrode.

[0019] In the ion transport apparatus, each of the at least one axially segmented electrode(s) may be configured to receive respective RF voltages from the power supply for generating a radially-confining electric potential field forming a pseudo-potential within the channel for guiding ions therealong.8628430

[0020] 3

[0021] The plurality of axially segmented electrodes may comprise one or more segmented electrode pairs comprising two said axially segmented electrodes spatially arranged to oppose each other across the ion optical axis.

[0022] The plurality of axially non-segmented electrodes may comprise one or more non-segmented electrode pairs comprising two axially non-segmented electrodes spatially arranged to oppose each other across the ion optical axis.

[0023] An amplitude and / or a frequency of a said AC auxiliary voltage may differ from an amplitude and / or a frequency, respectively, of a said RF voltage that is applied simultaneously to the set of electrodes. The simultaneously-applied RF voltage is applied to generate the radial trapping potential field in the ion trapping region.

[0024] The power supply may be configured to apply to electrodes of the plurality of electrodes said RF voltages so as to generate an electric potential field having a quadrupolar component in said channel.

[0025] The at least one axially segmented electrode(s) may be configured to receive respective AC auxiliary voltages from the power supply for generating an electric potential field forming a potential within the channel that is not a pseudo-potential.

[0026] The aforesaid substantially constant phase shift of AC auxiliary voltages may be the same as between each two successive segments in a given array.

[0027] The aforesaid substantially constant phase shift of AC auxiliary voltages may be 2π / n and the segmented electrode(s) may comprise at least n segments.

[0028] The aforesaid substantially constant phase shift of AC auxiliary voltages may be 2π / n where n is an integer such that n ≥ 3.

[0029] The aforesaid substantially constant phase shift of AC auxiliary voltages may be 2π / n where n is an integer such that n ≤ 8.

[0030] The corresponding segments of each array may be located at the same axial position along the ion optical axis and may share the same said substantially constant phase shift of AC auxiliary voltages.

[0031] The ion transport apparatus may comprise a plurality of segmented electrodes, wherein each segment separation region of each array is axially aligned with a corresponding segment separation region of each of the other arrays.8628430

[0032] 4

[0033] The ion transport apparatus may be configured such that, for each segmented electrode, the axial length of the segment separation region is less than the axial length of either of the electrode segments that it separates within the given segmented electrode.

[0034] The segmented electrodes may be arranged radially (e.g., azimuthally) around the ion optical axis in a manner that is symmetrical with respect to a rotation (e.g., azimuthal) about the ion optical axis.

[0035] In the ion transport apparatus, all electrodes of the plurality of electrodes may be arranged radially (e.g., azimuthally) around the ion optical axis in a manner that is symmetrical with respect to a rotation (e.g., azimuthally) about the ion optical axis.

[0036] In the ion transport apparatus, the total number of electrodes, being the sum of all said axially segmented electrode(s) and all said axially non-segmented electrodes comprising the plurality of electrodes, may be an even number.

[0037] The ion transport apparatus may be configured such that the field radius of said non-segmented electrodes, being the shortest distance from the ion optical axis to a given non-segmented electrode, is substantially the same for all non-segmented electrodes of the plurality of electrodes.

[0038] The ion transport apparatus may be configured such that the field radius of said segmented electrodes, being the shortest distance from the ion optical axis to a given segmented electrode, is substantially the same for all segmented electrodes of the plurality of electrodes.

[0039] The ion transport apparatus may be configured such that the field radius of said segmented electrodes differs from the field radius of said non-segmented electrodes.

[0040] The ion transport apparatus may be configured such that the field radius, being the shortest distance from the ion optical axis to a given electrode, is substantially the same for all electrodes of the plurality of electrodes.

[0041] The length of each said segmented electrode, being the sum of the lengths of all segments and segment separation regions thereof, may be substantially the same as the length of any said non-segmented electrode. These lengths may be considered to be in a direction parallel to the ion optical axis.

[0042] Each segment separation region of one segmented electrode of each pair of segmented electrodes may oppose a corresponding segment separation region of the other segmented electrode of the pair of segmented electrodes across the ion optical axis.

[0043] At least one said segmented electrode may extend in parallel alongside at least one said non-segmented electrode to position a given segment separation region alongside a non-segmented electrode.8628430

[0044] 5

[0045] The plurality of electrodes may be disposed inside a collision cell configured for maintaining a buffer gas within said channel such that product ion fragments, that are produced from precursor ions by a process of collision-induced dissociation, CID, with the buffer gas, are guided along the channel.

[0046] The ion transport apparatus may comprise an ion trapping part formed at least in part by a terminal part of the ion transport apparatus. The ion trapping part may comprise an exit lens apparatus arranged upon the ion optical axis adjacent to and downstream from a terminal end of the channel formed by the plurality of electrodes of the ion transport apparatus. The power supply may be configured to apply AC voltages to the exit lens apparatus to reversibly generate in the channel an axially-confining electric potential field forming a potential barrier for releasably trapping ions therein. An AC voltage(s) may be used appropriately for electron-transfer dissociation, ETD, applications to trap both + / - charged ions at the same time (i.e., negative ions and positive ions together). Electron-transfer dissociation, ETD, applications are discussed in more detail below. For general use, such as in collision-induced dissociation, CID, applications (or other applications) a plurality of DC voltage(s) may be used cyclically whereby a DC voltage applied to the exit lens is set to a first (higher) value to trap positively-charged ions and subsequently is set to a second (lower) value to release trapped ions. Thus, the DC voltage(s) may cyclically switch through, or alternate between, two (or more) pre-set DC values. When applied in a CID application I method, preferably a first DC voltage may be applied to the exit lens apparatus for trapping ions, before then a second DC voltage may be applied to the exit lens apparatus (in place of the first DC voltage) to release the trapped ions. When applied in an ETD application I method, preferably, an AC voltage may be applied to the exit lens apparatus (optionally together with a DC offset voltage), as mentioned above.

[0047] In this sense, the power supply may be configured to apply AC voltages two kinds:

[0048] - a first kind may be AC voltage(s) applied to the segmented electrodes;

[0049] - a second kind may be AC voltage(s) applied to the exit lens.

[0050] The two kinds of AC voltages may have different frequencies and / or different amplitudes, relative to each other. The first kind of AC voltage is preferably configured so that it does not provide (or create) a pseudo-potential. The second kind of AC voltage may optionally be configured to provide (or create) a pseudo-potential to confine positively and negatively-charged ions at the same time, or may be configured so that it does not provide (or create) a pseudo-potential.

[0051] In a second aspect, the invention may provide a mass spectrometry apparatus comprising the ion transport apparatus disclosed herein according to the first aspect of the invention.

[0052] The mass spectrometry apparatus may comprise a time-of-flight, TOF, mass analyser and the ion transport apparatus disclosed herein according to the first aspect of the invention arranged upstream of the TOF mass analyser for transporting ions the TOF mass analyser for mass analysis.

[0053] In a third aspect, the invention may provide a tandem mass spectrometry apparatus comprising:

[0054] an ion source for providing precursor ions;8628430

[0055] 6

[0056] a first mass analyser configured to apply a selection of precursor ions according to their mass-to-charge ratios;

[0057] a collision cell for fragmenting at least some of the selected precursor ions to generate product ions of the fragmented precursor ions, the collision cell comprising an ion transport apparatus as disclosed herein according to the first aspect of the invention for transporting the product ions and / or the precursor ions in the collision cell;

[0058] a second mass analyser configured to apply a process of mass analysis to the product ions.

[0059] In a fourth aspect, the invention may provide an electron-transfer dissociation, ETD, apparatus comprising:

[0060] a first ion source for providing precursor ions;

[0061] a second ion source for providing reagent ions bearing a charge that is the opposite sign to the charge of the precursor ions;

[0062] an ion transport apparatus as disclosed herein according to the first aspect of the invention;

[0063] an ion trapping part;

[0064] wherein the ion transport apparatus is configured:

[0065] to receive precursor ions from the first ion source at a first said potential well and to transport the first potential well along the ion optical axis to the ion trapping part; and,

[0066] to receive reagent ions from the second ion source at a second said potential well and to transport the second potential well along the ion optical axis to the ion trapping part thereat to combine precursor ions with the reagent ions to allow a process of electron transfer from reagent ions to precursor ions and ion fragmentation to generate product ions.

[0067] The ion trapping part may be formed at least in part by a terminal part of the ion transport apparatus.

[0068] The electron-transfer dissociation, ETD, apparatus may be configured such that:

[0069] the ion trapping part comprises an exit lens apparatus arranged upon the ion optical axis adjacent to and downstream from a terminal end of the channel formed by the plurality of electrodes; and

[0070] said power supply is configured to apply AC voltages (e.g., sinusoidally alternating, or alternating cyclically through / between DC voltages) to the exit lens apparatus to reversibly generate in the channel an axially-confining electric potential field forming a potential barrier (e.g., pseudo-potential barrier, or non-pseudo-potential barrier) for releasably trapping ions therein. An AC voltage(s) may be used appropriately for this purpose to generate a pseudo-potential barrier to trap both + / - charged ions at the same time (i.e., negative ions and positive ions together). The AC voltage may optionally be configured so that it does not provide (or create) a pseudo-potential.

[0071] In a fifth aspect, the invention may provide a mass spectrometry apparatus comprising a time-of-flight, TOF, mass analyser and the electron-transfer dissociation, ETD, apparatus as disclosed herein according to the fourth aspect of the invention arranged upstream of the TOF mass analyser for releasing product ions to the TOF mass analyser for mass analysis.8628430

[0072] 7

[0073] In a sixth aspect, the invention may provide a method of ion transport comprising:

[0074] providing a power supply configured to supply RF voltages and AC auxiliary voltages;

[0075] providing a plurality of electrodes comprising a plurality of axially non-segmented electrodes and at least one axially segmented electrode, wherein the plurality of electrodes are spatially arranged collectively to define a volume extending along an ion optical axis to form a channel, and each of the at least one axially segmented electrodes comprises an array of separate electrode segments that extends alongside the ion optical axis and each electrode segment is elongated to extend alongside the ion optical axis whereby successive electrode segments are separated by a segment separation region and the at least one axially segmented electrode extends alongside at least one said axially non-segmented electrode to position a given segment separation region alongside an axially non-segmented electrode;

[0076] by the power supply, applying to at least the plurality of axially non-segmented electrodes respective RF voltages from the power supply to generate a radially-confining electric potential field forming a pseudo-potential within the channel for guiding ions therealong; and,

[0077] by the power supply, applying to corresponding electrode segments of each said array a respective said AC auxiliary voltage comprising a temporal phase which differs by a substantially constant phase shift relative to respective temporal phases of AC auxiliary voltages concurrently applied to each neighbouring electrode segment of a given said array;

[0078] thereby, by the plurality of electrodes, collectively generating within said channel at least one travelling potential well for transporting ions therein along the ion optical axis.

[0079] In the method of ion transport, the plurality of electrodes may comprise and at least one pair of said axially segmented electrodes that are arranged to oppose each other across the ion optical axis.

[0080] In a seventh aspect, the invention may provide a method of mass spectrometry comprising the method of ion transport as disclosed herein according to the sixth aspect of the invention.

[0081] In an eighth aspect, the invention may provide a method of mass spectrometry as disclosed herein according to the seventh aspect of the invention, further comprising providing a time-of-flight, TOF, mass analyser and transporting ions to the TOF mass analyser according to the method of ion transport according to the sixth aspect of the invention, for mass analysis.

[0082] In a ninth aspect, the invention may provide a method of tandem mass spectrometry comprising:

[0083] providing precursor ions;

[0084] by a first mass analyser, applying a selection of precursor ions according to their mass-to-charge ratios;

[0085] providing a collision cell comprising an ion transport apparatus as disclosed herein according to the first aspect of the invention;

[0086] fragmenting at least some of the selected precursor ions to generate product ions of the fragmented precursor ions in the collision cell and transporting the product ions and / or the precursor ions in the collision cell according to the method of ion transport as disclosed herein according to the sixth aspect of the invention;8628430

[0087] 8

[0088] by a second mass analyser, applying a process of mass analysis to the product ions.

[0089] In a tenth aspect, the invention may provide a method of electron-transfer dissociation, ETD, comprising:

[0090] providing precursor ions;

[0091] providing reagent ions bearing a charge that is the opposite sign to the charge of the precursor ions; providing an ion transport apparatus as disclosed herein according to the first aspect of the invention; providing an ion trapping part;

[0092] by the ion transport apparatus:

[0093] receiving precursor ions at a first said potential well, transporting the first potential well along the ion optical axis to the ion trapping part and trapping the first precursor ions by the ion trapping part; and,

[0094] receiving reagent ions at a second said potential well, transporting the second potential well along the ion optical axis to the ion trapping part and thereat combining first precursor ions with the second precursor ions to allow a process of electron transfer from reagent ions to precursor ions and ion fragmentation to generate product ions.

[0095] The ion trapping part may be formed at least in part by a terminal part of the ion transport apparatus.

[0096] The electron-transfer dissociation, ETD, method may comprise:

[0097] providing the ion trapping part comprising an exit lens apparatus arranged upon the ion optical axis adjacent to and downstream from a terminal end of the channel formed by the plurality of electrodes; and by said power supply, applying AC voltages (e.g., sinusoidally alternating, or alternating cyclically through / between DC voltages) to the exit lens apparatus to reversibly generate in the channel an axially-confining electric potential field forming a potential barrier (e.g., pseudo-potential barrier, or non-pseudo-potential barrier) and therewith releasably trapping ions therein.

[0098] In an eleventh aspect, the invention may provide a method of mass spectrometry comprising providing a time-of-flight, TOF, mass analyser and providing the electron-transfer dissociation, ETD, apparatus as disclosed herein according to the fourth aspect of the invention arranged upstream of the TOF mass analyser, the method comprising releasing product ions from the electron-transfer dissociation, ETD, apparatus to the TOF mass analyser for mass analysis.

[0099] Multipole Fields, Pseudo-potentials and Fringing Fields

[0100] Quadrupoles and Quadrupole fields

[0101] A quadrupole field is expressed by its linear dependence on the coordinate position. In Cartesian coordinates, the quadrupole electric field is given by:

[0102] E = E0(λx + σy + γz)8628430

[0103] 9

[0104] Here, E0, λ, σ, γ are all position-independent, and Eomay be a function of time. The electric field is uncoupled in the three cartesian directions. Thus, in a quadrupole electric field, the force on a charged particle increases linearly with displacement from the zero position. The electric field is subject to the constrain of Laplace’s equation such that:

[0105] ∇ · E = 0

[0106] This condition is satisfied when λ = − σ, γ = 0. The electrical potential corresponding to this field, obtained by spatially integrating the electric field, is:

[0107] 1 1

[0108] Φ = −(1 / 2)E0(λx2+ σy2+ γz2) = −(1 / 2)E0λ(x2− y2)

[0109]

[0110] The equipotential field lines of this electrical potential field are hyperbolae in the x-y plane. Such a potential field may be generated using four parallel hyperbolic cylinders angularly equally-spaced around a common ion optical axis with one pair of the electrodes that oppose across the axis being equally charged and the other pair opposing across the axis being oppositely charged. If the minimum distance between opposing electrodes is equal to 2r0, where r0is the inscribed radius (also referred as the field radius) of a notional cylindrical volume or channel centred on the axis, and the electrical potential difference (voltage) that is between the two pairs of electrodes is Wo, then:

[0111] 1

[0112] λ = −(1 / r02) HEIGHT="32" WIDTH="49" SRC="imgf000009_0002.tif" / >

[0113] This gives:

[0114] ° y )

[0115]

[0116] 2r02

[0117] When used as a mass filter, the electrical potential (voltage), W / o / 2, is applied to one of the two pairs of electrodes and the electrical potential (voltage), -W / o / 2, is applied to the other one of the two pairs of electrodes. Here, Wois given by:

[0118] W0= 2[U − Vcos(ωt)]

[0119] The quantity V is the ground-to-pole voltage amplitude of a sinusoidal RF potential of angular frequency a), and the quantity U is the value of a “mass discriminating” DC ground-to-pole potential. This applied voltage results in equations of motion for the ion in the potential field as follows:

[0120] d2x / dt2+ (ez / mr02)[U − Vcos(ωt)]x = 0

[0121] at2\mr0 /

[0122] d2v ( az \

[0123] d2y / dt2− (ez / mr02)[U − Vcos(ωt)]y = 0

[0124]

[0125] \mr0 /

[0126] Here, the quantity z is the charge of the ion in question, and e is the elementary charge. By defining the following parameters:8628430

[0127] 10

[0128] ax= −ay= (8eU / mω2r02)

[0129] mw2r02

[0130] qx= −qy= (4eV / mω2r02)

[0131]

[0132] f = a>t / 2

[0133] The equations of motion reduce to:

[0134] d2u

[0135] + [au- 2qucos(2^)]u = 0

[0136]

[0137] dt2

[0138] Here, the symbol u represents either x or y. Only certain values of auand qulead to solutions representing stable ion trajectories within the channel formed by the four electrodes. The so-called “stability diagram” for a quadrupole device is well known in the art. These stable trajectories have values of auand quthat are coordinates constrained to reside within a roughly triangular “stable region” of the “stability diagram”. By controlling the values of the voltages U and V so that the ratio U / V = constant, the result is that the ratio of the ion trajectory parameters, axyand qxy, becomes axy / qxy= constant. This may be represented as a straight line in a graph of parameter axyversus qxy, with the line passing through the origin of coordinates and having a gradient equal to the value of the “constant” noted above:

[0139] ax,y = (constant) ■ qxy

[0140] This straight line defines the “mass scan line”. When the value of the quantity U (the “mass discriminating” DC potential) is zero, the quadrupole device acts as an ion guide or a linear ion trap, and the mass scan line is simply a horizontal line for which all axy= 0, and the maximum range qxyof the parameter qxyis possible. However, when operated as a mass analyser, quantity U (the “mass discriminating” DC potential) must be set to a non-zero value, and the mass scan line acquires a positive gradient of value U / V for which the only permissible values of auare those lying within a finite range axycorresponding to a limited range Δqx,yof permissible values of the parameter qxy. In this sense, the mass analyser is able to discriminate ion masses by transmitting only those selected by the mass scan line.

[0141] Higher-order fields and fringing fields

[0142] The above discussion applies strictly to perfectly quadrupolar fields; that is to say, with electrodes having with perfectly quadrupolar geometry, in receipt of perfectly sinusoidal applied voltages and without the presence of ‘fringing fields’.

[0143] Higher-order Fields

[0144] In the more general case, where multipolar field orders greater than quadrupole are present within the electric field generated by a quadrupole ion guide or ion trap device, and multiple RF potentials of amplitude Vnand frequency nnare present, the electric potential field present within a volume surrounded by the electrodes of the quadrupole device can be expressed as:8628430

[0145] 11

[0146] Z / r \w

[0147] AN— cosN^cp - < / >w) U - ^VncOS(wn)(t - tn)

[0148]

[0149] N

[0150] This general form of equation is discussed in more detail in:

[0151] Peter H Dawson: “Quadrupole Mass Spectrometry and its applications”, 1st Edition - January 1, 1976 - Elsevier, ISBN: 978-0-444-41345-1 - (see equation 5.11)

[0152] Further discussion can be found in:

[0153] Mikhail Yavor: “Optics of Charged Particle Analyzers” in “Advances in Imaging and Electron Physics”, Volume 157, Pages 1-381 (2009) - (e.g., see section 1.1.4.3 and section 9.1.4, e.g., equation 9.8)

[0154] The amplitudes Vnand frequencies a)nmay arise either due to imperfections in drive voltages applied to electrodes, or as deliberate additional field terms arising from additional deliberate drive voltage signals (e.g., supplemental AC signals, or auxiliary voltages) for some purpose.

[0155] Here, the quantity N is a positive integer indicating the “order” of the spatial field component contributing to the overall spatial structure of the potential field generated by 2N electrode pole pieces.

[0156] For example, N = 1 corresponds to the potential field generated by a dipole electrode structure, N = 2 corresponds to the potential field generated by a quadrupole electrode structure, N = 4 corresponds to an octopole, and N = 6 to a dodecapole. The terms r and <p are polar coordinates, ANis a weighting factor and <j)Nand tnare phase factors. In cartesian coordinates, this may be expressed as:

[0157] Z, < PN

[0158] AN — * VnCOS(a)n)(t - tn)

[0159] NroUn

[0160]

[0161] < PN = Re{(x + iy)w]

[0162] Here, i = V-l and the term Re{(x + iy)w] refers to the real component of the complex quantity (x + iy)'v. Notably, for an ideal quadrupole field, and with only a single RF potential present with frequency co, only the terms for N = 2 and n = 1 (i.e., a)1= M,

[0163]

[0164] = F) appear in the equation for the electric potential field 4>, in which we may set A2= 1. All other terms are zero. This gives the quadrupolar potential field structure noted above, namely:

[0165] 2 2

[0166] 4> = - [U - Fco. S'fYjt)]

[0167]

[0168] ro

[0169] Of course, in this example of a quadrupolar rod set, the reduction of the above general multipolar field equation to the much simpler quadrupolar field equation is something of an idealisation in which the quadrupolar rod set is assumed to comprise an array of four rods each of infinite length, of exactly the8628430

[0170] 12

[0171] same shape and dimensions arranged perfectly in parallel and perfectly symmetrically around the central longitudinal axis of the array.

[0172] More generally, deviations from this idealised circumstance lead to the creation of higher-order multipole field terms in the electric potential field of a real quadrupolar rod set. The equations of motion for an ion in a multipolar field generated by a quadrupolar electrode rod set in general may be expressed as:

[0173] d2x ( ze Xr z / ze>.r zV 3< PN — 7 + — 7 [t / - Fcos(wt)]x = - ( — ) [f / - Fco.sTwt)] > AN— —

[0174] \

[0175] vmrn / 'm' Z— < ox

[0176] ' N>3

[0177] d2y ( ze \ / -ze\ v d<pN

[0178] - — 7 tu~ Vcos(a)t)]y = - (— ) [U - Vcos(a)tJ] > AN——

[0179] dt2\mrn / '•m' 2_i oy

[0180]

[0181] V U' N>3

[0182] Here, the quantity z is the charge of the ion in question, and e is the elementary charge, and higher order field effects influence the equations of motion in the form of the spatial differentials (d<pN / dx; d<pN / dy) of multipolar field components, <pN, of order greater than N = 2 (e.g., hexapolar, octopolar, and so on). Note that the influence of the higher-order fields is inversely proportional to the mass-to-charge ratio (m / ze) of the ion in question. These equations return to the idealised case for a perfect quadrupolar rod set when all higher-order terms are neglected such that AN= 0 for all N > 2.

[0183] One example of the presence of higher order field effects in a real (non-idealised) quadrupolar rod set is the so-called ‘Fringing Fields’ at and around the terminal ends of the rods. Here, higher-order fields become significant such that AN> 0 for at least some N > 2.

[0184] Fringing Fields

[0185] In the inner regions of a linear quadrupole ion guide, far from a terminal end of the guide, or far from a terminal end of a segment of a segmented electrode of the guide, the two-dimensional quadrupole potential can be written as:

[0186] 2 2

[0187] 4> = - [U - Fcos(wt)]

[0188]

[0189] ro

[0190] Here, 2r0is the shortest distance between opposing rods of the quadrupole ion guide, and where the expression: U - Vcos(a)f) is the electric potential (voltage), measured with respect to ground, applied with opposite polarity to each of the two pairs of rods. It is a linear combination of DC (i.e. U) and RF (i.e. Vcos(a)t)) components, where w is the angular frequency of the RF signal. This is a somewhat idealised circumstance which is a very good approximation in the inner regions of a linear quadrupole ion guide, far from a terminal end of the guide, or far from a terminal end of a segment of a segmented electrode of the guide, but is increasingly inaccurate at axial positions along the ion guide increasingly close to a terminal end. Furthermore, the potential of the ion guide also extends outside of the ion guide beyond its terminal ends or between successive terminal ends of adjacent segments of a segmented electrode of the ion guide, and does not simply fall away instantaneously to a zero value outside of the terminal ends.8628430

[0191] 13

[0192] Rather, a so-called “fringing field” region exists in which the amplitude or strength of the potential smoothly transitions from the value it would have well within the ion guide to a value it would have well outside of the guide, or to an intermediate value between the ends of two segments of a segmented electrode of the ion guide. It can be shown that the exit fringing-field, 0>FF, may be quantified as:

[0193] 2 2

[0194] 4>FF= 4> / (z) = - ^—[U - Vcos(coty\f(z)

[0195]

[0196] ro

[0197] Here, the diminishing term (z) is a smoothly decreasing amplitude or strength function of the axial distance, z, along the ion guide axis on the approach to, and passing beyond, the exit end of the ion guide. As a consequence of the fringing region at the end of an ion guide, ions upon the central axis (i.e. the z-axis) of the ion guide experience a non-zero quadrupole potential outside of the ion guide that diminishes at increasing distance beyond the terminal end of the ion guide, in a direction along the z-axis. It can be shown that, to a good approximation:

[0198] (z) = 1 - exp (-a[z - z0] - b[z - z0]2)

[0199] Here a and b are positive constants determined by the geometry of the quadrupole ion guide, and z0is an axial position outside the ion guide at a fixed potential (e.g. earthed). So-called “Enge functions” are also descriptive. While the fringing-field between the ends of two adjacent segments of a segmented electrode of an ion guide, or trap, may differ from this form of (z), it is accurate to say that, in this circumstance, the function (z) will also be a smoothly decreasing amplitude or strength function of the axial distance, z, along the ion guide axis on the approach to a mid-point between the ends of two adjacent segments of the ion guide.

[0200] This fringing effect applies equally to the pseudo-potential generated by an RF potential, as discussed below. Fringing fields exist in ion guides, or ion traps, of other than quadrupole geometry (e.g., hexapole, octopole, decapole etc.). One can see that the effect of the fringing field is to diminish the potential within the ion guide adjacent to, and also at, the terminal end of the guide, as well as between the terminal ends of two adjacent segments of a segmented electrode of an ion guide, or trap, and to define a non-zero extension of the potential extending a finite distance beyond the terminal end(s).

[0201] The Pseudo-potential

[0202] The following provides an understanding of the physics of confining charged particles with radio frequency fields, and an outline of the pseudo-potential approach exemplified via the simpler case of the 2D quadrupole mass filter. Consider a counterpart to the purely electrostatic arrangements of ion confinement in RF fields, by considering a mechanical analogue useful for understanding. In particular, consider the trapping of a bead on a rotating saddle surface. The rotating saddle-potential analogue does not exactly correspond to the physics of an RF ion guide / trap, however it will capture the underlying principles in an intuitive and useful way. To confine a particle of mass m stably at a point of space, we require a restoring, i.e., binding force F (cf. Hooke’s law):

[0203] F = — c r

[0204] Here, c is the spring constant, and r the position variable. A conservative force F can always be written in terms of a scalar potential 0>:8628430

[0205] 14

[0206] F = -70

[0207] Given the force, we can calculate the potential by integrating once:

[0208] O(x, y, z) = — (ax2+ / ?y2+ yz2)

[0209]

[0210] where a, / ? and y are constants that play the role of c in three spatial directions. In anticipation of the discussion of trapping charged particles in electrostatic potentials, choose: a = - / ? = l,y = 0. With this choice, O forms a potential that has the shape of a saddle surface:

[0211] c

[0212] «

[0213]

[0214] i>(x,y) = 2- y2)

[0215] Although potentials of this shape will allow to trap the particle along the x-direction, there exists no stable minimum and the particle could always escape along the y- direction. Hence, stable trapping is not possible with these static potentials. However, as we will show now using the example of a gravitational saddle potential, trapping becomes feasible when we introduce a time variation. In a gravitational potential, we can set:

[0216] mgh0

[0217] We obtain the expression of a gravitational saddle potential:

[0218] mgh0

[0219] 4>(x,y) = (x2-y2)

[0220] 2r02

[0221] Here, m is the mass of the bead, g the Earth’s gravitational acceleration, and h0and r0are parameters that shape the curvature of the potential. It is possible to rotate the saddle with a angular frequency w around the vertical axis (z-axis), without applying any other motion to it, in order to ‘balance’ the bead within the saddle. This angular rotation transforms the static gravitational potential into a time-varying potential that can be described by writing the potential in terms of rotating axes x',y' as follows:

[0222] mgh0

[0223] 4>(x',y') = (x'2-y'2)

[0224] 2r2

[0225] The rotating saddle potential may be described in the laboratory frame by applying the standard coordinate transformation given by the rotation matrix:

[0226] (x’\ _ / cos(a>t) -sin(wt)\ / x\

[0227] \

[0228]

[0229] y'J \sin((i)t) cos(wt) / \y)

[0230] This gives:

[0231] 4>(x,y, t) = - — {(x2— y2)cos(a)t) — 2xysin(wt)}

[0232]

[0233] 2r0

[0234] Pictorially, one may visualise the time-variation of this potential as a rotation of the saddle surface around the vertical axis, with a frequency w prevents the bead from rolling off the saddle surface. The faster the saddle rotates, the better the bead is confined within the saddle surface (i.e., gravitational potential surface). It can be shown that the bead may follow stable trajectories confined to the saddle surface if the8628430

[0235] 15

[0236] rotation is fast enough. Although the rotating saddle potential intuitively illustrates the basic physics of trapping particles with a rapidly oscillating potential, it must be noted that the electrical potentials used in in ion trapping / guiding are not exactly of the mathematical form shown above for the gravitational potential saddle surface 0>(x,y,t). Rather, electric potentials in ion guides / traps are typically of a form:

[0237] c'

[0238] (x,y, t)~ — (x2— y2)cos(a)t)

[0239]

[0240] Pictorially, the time-variation of this potential representation would rather resemble a flapping potential, where the curvature oscillates with time and the walls of the saddle potential flap like the wings of a bird. The constant c' is dependent on the voltage that is applied to the ion trap / guide electrodes.

[0241] Rapidly oscillating potentials like the “rotating-saddle” potential or the “flapping” potential can be used to confine particles and this is understood via the concept of the “pseudo-potential”. In the pseudo-potential approximation, one considers the average potential that acts on a particle in a rapidly oscillating potential as an effective potential. It is calculated by taking the time-average over one period of the fast oscillation. To analyse the trajectory of the particles in such potentials, we may write down the equations of motion of the particle in the potential:

[0242] F = mr = — z74>(r)

[0243] Here z is the charge of the particle with mass m. A generic type of electrical potential for ion confinement consists of a stationary, slowly changing or quasi-static part, U(Y), and a fast time-dependent oscillating part, V(Y) cos( ot which oscillates with a frequency w:

[0244] 4>(r) = U(r) + V(Y) cos (c t)

[0245] Assume that the frequency of the oscillating part is much larger than the inverse time scale of one period of motion T the particle would carry out only under the influence of U(r), i.e. w » TT / T. As a result of this assumption, we obtain:

[0246] mf = — z (U(r) + 7(r) cos( lt')') = —zVU(r') — zVV(r)' cos(a>t)' = F0(r') + FRF(r') cos(cot) The smooth particle trajectory due to the force F0(r) is modulated by an oscillating force FRF(r) at frequency co.

[0247] Thus, we may write the total trajectory r(t) as a sum of a smooth part F(t) and rapidly oscillating part (t):

[0248] r(t) = F(t) + f(t)

[0249] Typically, the amplitude of the oscillations will be much smaller than the smooth part of the trajectory R, i.e. | « |F|. This permits us to expand the forces F0(r) and FRF(Y) in a Taylor series up to lowest order in the parameter, as follows:

[0250] F0(R + ) = F0(F) + • 7F0(F) + • • •

[0251] FRF(F + ) = FFF(F) + • 7FFF(F) + • • •

[0252] Omitting negligible parts of the series, the equation of motion becomes:

[0253] m(F(t) + (t)) = F0(F) + (t) • 7F0(F) + [RF( ) + (t) • 7FFF(F)] cos(cot)8628430

[0254] 16

[0255] The result of the equation of motion for the oscillating part of the trajectory is given approximately by:

[0256] m (t) = FRFcos(a)t)

[0257] The solution to this equation is:

[0258] <(t) = - cos(at)

[0259]

[0260] By calculating the time average over: m(F(t) + (t)), over one period 2?r / w, we obtain an expression for a time-averaged pseudo-potential. In doing so, note that terms containing cos(wt) will time-average to zero and only terms with [cos(wt)]2remain. Namely:

[0261]

[0262] f (t))> = Fo(7?) + <<(t)> • 7F0(F) + <[FRF(7?) + <(t) • VFRF(R)] cos(a>t)) Given that:

[0263]

[0264] <<(t)> = = 0, this reduces to:

[0265] ..x< cos2(wt))

[0266] mF(t) = F0(F) - -y— FFF(F) • 7FFF(F)

[0267]

[0268] Remembering that F is a conservative force, and (7 x FRF(R) = 0) this means that:

[0269] FRF(R) ■ VFRF(R) = FRF(R) ■ VFRF(R) + FFF(F) X (7 X FRF(7?)) = | 7(FFF(F) • FFF(F))

[0270]

[0271] As a result, and noting that cos2(at ) = 1 / 2, we may write:

[0272] 1

[0273] mR(t) = Fsec= F0(R) - - - 7(^?

[0274]

[0275] 4mω2F)2= ~zVU^ec

[0276] This means that a “secular” force (Fsec) may be defined as the time-averaged force acting on a particle of charge z in the rapidly oscillating RF potential. In other words, the secular force is proportional to the spatial gradient of a secular potential (Usec)

[0277] (FRF)2

[0278] U

[0279]

[0280] sec= U0+ T 4m^<ir = Uo + Ups

[0281] Here,

[0282] y s =

[0283]

[0284] ps4ma2

[0285] This is the “pseudo-potential” created by the RF field. The time-averaged equation of motion over one period of the fast oscillation shows that, when time-averaged, the secular potential can be written as a sum of the stationary potential and the “pseudo-potential”. For quadrupolar fields etc., the “pseudopotential” is proportional to the square of the magnitude of the oscillating part of the potential because FFFOC URF, and is also inversely proportional to the particle mass-to-charge ratio: m / z. Note also that because FRFOC Z, then Upsoc z2, and the resulting force is independent of the sign of the charge on the charged particle in question.

[0286] The invention includes the combination of the aspects and preferred features described except where such a combination is clearly impermissible or expressly avoided.8628430

[0287] 17

[0288] Summary of the Figures

[0289] Embodiments and experiments illustrating the principles of the invention will now be discussed with reference to the accompanying figures in which:

[0290] Figure 1 shows a schematic view of a tandem mass spectrometer system including an oaTOF system.

[0291] Figure 2 shows (A) a schematic view of an ion transport apparatus, (B) a schematic view of a part of the tandem mass spectrometer system of Figure 1 including the ion transport apparatus, (C) a partial cross-sectional view of electrodes of the ion transport apparatus, and (D) a further cross-sectional view of electrodes of the ion transport apparatus.

[0292] Figure 3 shows (A) a schematic view of a sinusoidal auxiliary voltage at each one of four successive time instants within the cycle, equally spaced in time, and (B) the part of the tandem mass spectrometer system illustrated in Figure 2A.

[0293] Figure 4 shows (A) the part of the tandem mass spectrometer system illustrated in Figure 2A, and (B) a schematic view of a travelling potential well at each one of four successive time instants and axial positions.

[0294] Figure 5 shows (A) a schematic view of a part of the tandem mass spectrometer system including an ion transport apparatus of Figure 1, in an alternative example, (B) a partial cross-sectional view of electrodes of the ion transport apparatus, and (C) a further cross-sectional view of electrodes of the ion transport apparatus.

[0295] Figure 6 shows a graphical view of single cycles on four different periodic auxiliary voltage waveforms including: (A) a sinusoidal waveform; (B) a square waveform; (C) a stepped waveform, and; (D) a triangular waveform.

[0296] Figure 7 shows a cross-sectional view of parts of a tandem mass spectrometer including a mass filter, an ion fragmentation and bunching regions of a collision cell, an ion transfer lens system and an orthogonal extraction electrodes region.

[0297] Figure 8 shows the axial position of ions transported along an ion transport apparatus according to simulations of ions having a mass-to-charge ratio of: m / z = 200 and m / z = 2000.

[0298] Figure 9 shows the axial velocity of ions transported along an ion transport apparatus according to simulations of ions having a mass-to-charge ratio of: m / z = 2000.8628430

[0299] 18

[0300] Figures 10A to 10E show schematically a cross-sectional view an ion transport apparatus and therein the axial position of ions transported along an ion transport apparatus according to simulations of ions at five instants in time.

[0301] Figure 11 shows: (A) a graph of the time distribution of a population of ions within a mass filter of an ion transport apparatus; (B) schematically a cross-sectional view the ion transport apparatus and therein the axial position of ions transported along an ion transport apparatus according to simulations, and; (C) a graph of the time distribution of the population of ions output from the ion transport apparatus.

[0302] Figure 12 shows: (A) a graph of the time distribution of a population of ions output an ion transport apparatus according to three different mass-to-charge ratio of: m / z = 400, m / z = 609 and m / z = 900; (B) a histogram of the axial position of ions adjacent to orthogonal acceleration electrodes of an oaTOF apparatus, having been transported there by an ion transport apparatus according to simulations, and; (C) a graph of the duty cycle as a function of mass-to-charge ratio of, m / z, of a tandem mass spectrometer system of Figure 1 when the oaTOF system thereof is operated in a bunched-beam mode, and a comparison with duty cycles achieved in a continuous beam mode.

[0303] Figure 13 shows an electron-transfer dissociation, ETD, apparatus.

[0304] Detailed Description of the Invention

[0305] Aspects and embodiments of the present invention will now be discussed with reference to the accompanying figures. Further aspects and embodiments will be apparent to those skilled in the art. All documents mentioned in this text are incorporated herein by reference.

[0306] Figure 1 shows a tandem mass spectrometry apparatus comprising an ion transport apparatus 111 disclosed in more detail herein. The mass spectrometry apparatus comprises an orthogonal acceleration time-of-flight, oaTOF, mass analyser 112 (comprising part: 113, 115 and 116) configured to accept ions transported to it by the ion transport apparatus 111 arranged upstream of the oaTOF mass analyser for mass analysis. It is to be understood that this example illustrates components of an apparatus for a tandem mass spectrometry in which certain components, such as a vacuum pump serving the vacuum chamber, are omitted from the illustration merely to aid clarity but are to be understood as being present. The tandem mass spectrometry system comprising an ion source 101 for providing precursor ions of a sample under study, an ion optics assembly 103 arranged to receive precursor ions output by the ion source and to guide the received precursor ions to the first mass analyser 105, the first mass analyser 105 is configured for selecting precursor ions according to their mass-to charge ratios (m / z). A collision cell 111 is arranged along the ion optical axis downstream of the first mass analyser 105 for fragmenting the selected precursor ions into product ions and for transmitting ions into the orthogonal acceleration electrodes 113, and time-of-flight assembly 115 of the oaTOF system 112, for analysing ions according to their flight time along a flight trajectory 114 extending between the orthogonal acceleration electrodes 113 and an ion detector 116 of the oaTOF system. The ion source 101, ion optics assembly 103, first mass8628430

[0307] 19

[0308] analyser 105, and the oaTOF system are aligned in succession, and in ion flow communication, along a linear ion optical axis 119.

[0309] A controller and power supply 117 is configurated for applying appropriate radio-frequency, RF, voltages, alternating-current, AC, auxiliary voltages and direct-current, DC, voltages to electrodes of the ion optics assembly 103, the first mass analyser 105, and the collision cell 111, the orthogonal acceleration electrodes 113, and time-of-flight assembly 115, for the purposes of mass analysis of ions.

[0310] The ion source 101 may be any of the following well-known varieties: Electrospray Ionisation (ESI) source, Atmospheric pressure chemical ionization (APCI) source, Atmospheric Pressure Photoionization Ionization (APPI) source, Desorption electrospray ionization (DESI), Probe Electrospray Ionization (PESI) source, Matrix-assisted laser desorption / ionization (MALDI), and so on. The ion optics assembly 103 may include one or more than one ion guides, e.g., multipole rods or stacked ring ion guides. Differential pumping may be used to produce a pressure gradient extending from an atmospheric pressure to a vacuum pressure in a vacuum region in which mass analysis is to occur.

[0311] The first mass analyser 105 may comprise a mass filter, an ion trap or a magnetic sector mass spectrometer configured to select precursor ions according to their mass-to-charge ratios. When a mass filter is used as the first mass analyser, appropriate quadrupole DC and RF voltages may be applied to quadrupole electrode set (e.g., rod electrodes) to allow ions with selected m / z to pass therethrough and other ions to be filtered by colliding with the electrodes.

[0312] The collision cell 111 comprises an ion fragmentation device 107 and an ion transport apparatus 109 for ion bunching and transportation. The collision cell 111 comprises an ion inlet aperture, an ion outlet aperture, and a gas supply (not shown). Product ions may be generated from fragmentations of precursor ions by collision-induced dissociation inside the ion fragmentation device 107 at relatively high pressure. The unfragmented precursor ions and product ions may be transferred and accumulated in the ion transport apparatus guide 109 before those ions are bunched together and are transported with same velocity along the ion transport apparatus 109, as discussed in more detail herein. The bunched ions are then injected from the ion transport apparatus 109 into the region axially aligned with the orthogonal acceleration electrodes 113, and a high-voltage TOF extraction pulse is applied to the orthogonal acceleration electrodes, by the power supply 117, to extract / eject these ions into flight tube 115 of the oaTOF mass analyser 112 for mass analysis. In this way, the oaTOF mass analyser system112 is used as a second mass analyser. However, in other examples, an ion trap-TOF, or an orbitrap, or a mass filter, or an ion trap and other mass analyser may be used as the second mass analyser in place of the oaTOF mass analyser system 112.

[0313] The present example treats the ion transport apparatus 109 as one part of the collision cell 111 although it is expected that ion fragmentations are not mainly produced in the ion transport apparatus 109. A more accurate description may be that the ion transport apparatus 109 is simply located between a fragmentation device 107 and the second mass analyser system 112. However, it is noted that that the same or similar buffer gas pressures can be used in both the fragmentation device 107 and the ion8628430

[0314] 20

[0315] transport apparatus 109. A suitable buffer gas pressure that can be used in both the fragmentation device 107 and the ion transport apparatus 109 is a pressure selected from a range spanning about 0.5 mTorr to about 20 mTorr. Argon, air or nitrogen may be used as the buffer (collision) gas. In some embodiments, the pressure of the buffer gas in the ion transport apparatus 109 may be set to be a lower pressure than the buffer gas pressure maintained within the fragmentation device 107. This pressure difference may be achieved by implementing a gas conductance restrictor according to principles and methods readily available to the person skilled in the art. The higher pressure in the ion fragmentation device 107 may improve the fragmentation efficiency and thus enhance MS sensitivity.

[0316] In this way, the invention may provide a tandem mass spectrometry apparatus comprising an ion source 101 for providing precursor ions, a first mass analyser 105 configured to apply a selection of precursor ions according to their mass-to-charge ratios, a collision cell 111 comprising an ion transport apparatus 109 as disclosed herein in more detail below, for fragmenting at least some of the selected precursor ions to generate product ions of the fragmented precursor ions, and a second mass analyser system 112 configured to apply a process of mass analysis to the product ions.

[0317] Figure 2A shows a schematic view of the electrodes of the ion transport apparatus 109. The apparatus comprises a set of eight electrodes, 102, 104, 106, 108, 110, 112, 114, and 116, that are spatially arranged collectively to define an elongate volume extending along the ion optical axis 119 to form a channel having a channel entrance end and a channel exit end. The channel entrance end and a channel exit end each share the common field radius 120 of the set of eight electrodes.

[0318] The set of eight electrodes comprises four axially non-segmented electrodes, 102, 106, 110, 114, that are each configured to receive respective RF voltages from the power supply 117 for generating a radially-confining electric potential field forming a pseudo-potential within the channel for guiding ions therealong. The plurality of electrodes are disposed inside the collision cell 111 which is configured for maintaining a buffer gas within the channel such that precursor ions guided along the channel may produce product ion fragments by a process of collision-induced dissociation, CID, with the buffer gas.

[0319] The set of eight electrodes also comprises four axially segmented electrodes, 104, 108, 112, 116, that are each configured to receive respective AC auxiliary voltages from the power supply 117. Each of the four axially segmented electrodes comprises an array of four separate electrode segments that extends alongside the ion optical axis 119. Thus, a first axially segmented electrode 104 comprises a first, 104a, a second, 104b, a third, 104c and a fourth, 104d, electrode segment. A second axially segmented electrode 108 comprises a first, 108a, a second, 108b, a third, 108c and a fourth,108d, electrode segment. A third axially segmented electrode 112 comprises a first, 112a, a second, 112b, a third, 112c and a fourth, 112d, electrode segment. Finally, a fourth axially segmented electrode 116 comprises a first, 116a, a second, 116b, a third, 116c and a fourth,116d, electrode segment.

[0320] The field radius 120 of the non-segmented electrodes, being the shortest distance from the ion optical axis 119 to a given non-segmented electrode, is substantially the same for all non-segmented electrodes.8628430

[0321] 21

[0322] Similarly, the field radius 120 of the segmented electrodes, being the shortest distance from the ion optical axis 119 to a given segmented electrode, is also substantially the same for all segmented electrodes. In some embodiments, the field radius of the segmented electrodes can be the same as the field radius of the non-segmented electrodes. However, in other examples, the field radius of the segmented electrodes may be configured to differ from the field radius of said non-segmented electrodes.

[0323] Each electrode segment is elongated to extend alongside the ion optical axis 119 whereby successive electrode segments are separated by a segment separation region “s” of axial length common to each segmented electrode. The four axially segmented electrode extends alongside a respective two adjacent axially non-segmented electrodes of the four non-segmented electrodes to position a given segment separation region “s” alongside an axially non-segmented electrode. Each segment separation region of each array of electrode segments of a given axially segmented electrode is axially aligned with a corresponding segment separation region of each of the other arrays of the other axially segmented electrodes. For each segmented electrode, the axial length of the segment separation region is less than the axial length of either of the electrode segments that it separates within the given segmented electrode. The length of each segmented electrode, being the sum of the lengths of all segments and segment separation regions thereof, is substantially the same as the length of any non-segmented electrode. These lengths are in a direction parallel to the ion optical axis. The four segmented electrodes are arranged as two pairs whereby two segmented electrodes of a given pair oppose each other across the io optical axis 119. For example, segmented electrodes 104 and 112 form such a pair, as do segmented electrodes 108 and 116. Each segment separation region of one segmented electrode of each pair of segmented electrodes opposes a corresponding segment separation region of the other segmented electrode of the pair of segmented electrodes across the ion optical axis. Each segmented electrode extends in parallel alongside at least one non-segmented electrode to position a given segment separation region alongside a non-segmented electrode. The four axially non-segmented electrodes comprise two non-segmented electrode pairs comprising two axially non-segmented electrodes spatially arranged to oppose each other across the ion optical axis. For example, non-segmented electrodes 106 and 114 form such a pair, as do non-segmented electrodes 102 and 110.

[0324] All of the eight electrodes are linear in their elongate shape, with each one of the non-segmented electrodes, and each one of the electrode segments, being a right-circular cylindrical electrode rod. The cylinder axes of each of the four electrode segments of a given axially segmented electrode are collinear. The axially segmented electrodes are segmented in a direction substantially parallel to the ion optical axis and each extends alongside the ion optical axis in a direction substantially parallel to the ion optical axis. The non-segmented electrodes also each extend alongside the ion optical axis in a direction substantially parallel to the ion optical axis.

[0325] The four segmented electrodes are arranged radially (azimuthally) around the ion optical axis in a manner that is symmetrical with respect to a rotation (azimuthal) about the ion optical axis. In particular, the azimuthal angular separation between successive segmented electrodes is substantially 90 degrees. This defines a quadrupolar segmented rod set arrangement. Similarly, the four non-segmented electrodes are8628430

[0326] 22

[0327] also arranged radially (azimuthally) around the ion optical axis symmetrically with respect to a rotation (azimuthal) about the ion optical axis such that the azimuthal angular separation between successive non-segmented electrodes is also substantially 90 degrees. This defines a quadrupolar non-segmented rod set arrangement. Furthermore, the azimuthal separation between successive electrodes of the set of eight electrodes, going azimuthally between non-segmented and segmented electrodes, is a substantially constant angular separation of about 45 degrees (azimuthally) around the ion optical axis. This, quadrupolar segmented rod set arrangement is interdigitated with the quadrupolar non-segmented rod set arrangement. In the present example of the ion transport apparatus, the total number of electrodes, being the sum of all axially segmented electrode(s) and all axially non-segmented electrodes is eight, but it is to be understood that a greater total number may be used which may be an even number (e.g., an octopolar rod set etc.).

[0328] The power supply is configured to apply to corresponding electrode segments of each array (i.e., each axially segmented electrode) a respective said AC auxiliary voltage comprising a temporal phase which differs by a substantially constant phase shift relative to respective temporal phases of AC auxiliary voltages concurrently applied to each neighbouring electrode segment of a given array. Consequently, the set of eight of electrodes collectively generate within the channel at least one travelling potential well for transporting ions therein along the ion optical axis 119. In this example of the ion transport apparatus, each of the four axially segmented electrodes is configured to receive respective RF voltages from the power supply 117, in addition to the AC auxiliary voltages, for generating a radially-confining electric potential field forming a pseudo-potential within the channel for guiding ions therealong. However, in otter examples, such as discussed below with reference to Figure 5, the four axially segmented electrodes do not receive any RF voltages from the power supply 117, and only receive the AC auxiliary voltages. Figure 2B shows the collision cell 111 and ion transport apparatus 109 in a partial cross-sectional view that includes only one axially segmented electrode, 104, and one axially non-segmented electrode 114 positioned at approximately opposite sides of the ion optical axis. The other electrodes of the set of eight electrodes are omitted for clarity. The ion transport apparatus comprises the power supply 117 which is configured to supply RF voltages and AC auxiliary voltages to a plurality of electrodes of the ion transport apparatus.

[0329] The power supply is configured to apply to all eight electrodes of the set of electrodes the aforementioned RF voltages, and to apply the AC auxiliary voltages to the segmented electrodes alone so as to generate a quadrupolar electric potential field in the channel. The amplitude (UAC^, n = 1,2, 3, 4) and frequency of the AC auxiliary voltage differs from the amplitude, Vrf, and frequency, £1, respectively, of the RF voltage that is applied simultaneously to the set of electrodes to generate the radial trapping potential field in the ion trapping region.

[0330] The axially segmented electrodes receive respective AC auxiliary voltages from the power supply, and in response to the AC auxiliary voltages the electrodes are caused to generate an electric potential field forming a potential within the channel that is not a pseudo-potential. However, in embodiments in which the axially segmented electrodes also receive an RF voltage signal, as shown in the example of Figure 2,8628430

[0331] 23

[0332] then those RF voltages cause the segmented electrodes to also generate a radially-confining pseudopotential which is in addition to the potential generated via the AC auxiliary voltages. The AC auxiliary voltages do not provide the radially-confining potential but do generate an axially-confining potential well. Note that in the embodiment shown in Figure 5, the axially segmented electrodes only receive respective AC auxiliary voltages from the power supply, and do not receive an RF voltage signal, as discussed in more detail below.

[0333] The corresponding segments of each array are located at the same axial position along the ion optical axis and share the same substantially constant phase shift of AC auxiliary voltages supplied to them by the power supply. The constant phase shift of AC auxiliary voltages is the same value as between each two successive segments in a given array of electrode segments of a segmented electrode. The constant phase shift has a value of 2n / n and, in this example, n = 4. Here, the number of electrode segments in each segmented electrode is n = 4 segments. The number of segments can be different from n (number of phase shifts amongst the AC auxiliary voltages) and may be equal to or greater than n.

[0334] For example, referring again to schematic Figure 2B, each one of the four electrode segments of a given axially segmented electrode, such as electrode 104 as shown, is supplied by the power supply with a respective one of four AC auxiliary voltages which each share the same amplitude but respectively have AC waveforms that differ in phase. Axially segmented electrode 104 receives from the power supply 117, at its four separate electrode segments, the following AC auxiliary ad RF voltages:

[0335] Electrode Segment Supplied Voltage (AC auxiliary and RF combined)

[0336] 104a tl^ci + Vrfcosilt

[0337] 104b UAC2+ Vrf cosilt

[0338] 104c UAC3+ Vrf cosilt

[0339] 104d UACA+ Vrf cosilt

[0340]

[0341] The four AC auxiliary voltages, UAC(nn = 1,2, 3, 4, are:

[0342] t

[0343]

[0344] ^C(n) = VAccos(2itfAC■ t -

[0345] The four AC auxiliary voltages share a common amplitude VACand a common frequency fAC, but differ in relative phase according to the four different phases, resulting from a constant relative phase shift of n / 2, as between axially successive (neighbouring) electrode segments, as follows:

[0346] <f>^ = 0, 2n

[0347] <f>^ = it / I

[0348] <f>^ = n

[0349]

[0350] = 3n / 28628430

[0351] 24

[0352] Similarly, the opposing axially segmented electrode 112, that opposes electrode 104 across the ion optical axis 119 (not shown in Figure 2B), simultaneously receives from the power supply 117, at its four separate electrode segments, the following AC auxiliary ad RF voltages, which are the same as those received by the corresponding electrode segments of electrode 104:

[0353] Electrode Segment Supplied Voltage (AC auxiliary and RF combined)

[0354] 112a L^ci + Vrfcosilt

[0355] 112b UAC2+ Vrfcosilt

[0356] 112c UAC2+ Vrfcosilt

[0357] 112d UACA+ Vrf cosilt

[0358]

[0359] However, the axially segmented electrode 108 and opposing electrode 116 (i.e., opposing across the ion optical axis 119, not shown in Figure 2B) simultaneously receive from the power supply 117, at their four separate electrode segments, the following AC auxiliary and RF voltages, which comprise an RF component that differs in sign (i.e., a 180 degree phase shift) relative to those received by the corresponding electrode segments of electrodes 104 and 112, as follows:

[0360] Electrode Segment Supplied Voltage (AC auxiliary and RF combined)

[0361] 108a, 116a L^ci - Vrfcosilt

[0362] 108b, 116b UAC2 ~ Vrf cosilt

[0363] 108c, 116c UAC3 - Vrf COSilt

[0364] 108d, 116d UACA— Vrfcosilt

[0365]

[0366] The result is that the RF component of the supplied voltages permits a radially-confining pseudo-potential to be generated around and along the ion optical axis 119 at the particular spatial segment of the channel located that is surrounded by four corresponding electrode segments - one from each of the four segmented electrodes - whilst simultaneously each receiving the same AC auxiliary voltage (i.e., same amplitude, frequency and phase). For example, all those electrode segments in receipt of AC auxiliary voltage UAC1(namely, 104a, 108a, 112a, 116a) are corresponding electrode segments in the sense that they collectively surround and define one particular spatial segment of the channel. Similarly, all those electrode segments in receipt of AC auxiliary voltage UAC2(namely, 104b, 108b, 112b, 116b) are corresponding electrode segments in the sense that they collectively surround and define an axially adjacent spatial segment of the channel. All those electrode segments in receipt of AC auxiliary voltage (namely, 104c, 108c, 112c, 116c) are also corresponding electrode segments in the sense that they collectively surround and define a further axially adjacent spatial segment of the channel. Finally, all those electrode segments in receipt of AC auxiliary voltage UAC4(namely, 104d, 108d, 112d, 116d) are corresponding electrode segments in the sense that they collectively surround and define final spatial segment of the channel.8628430

[0367] 25

[0368] Simultaneously with the supply of the RF and AC auxiliary voltages to the segmented electrodes, the power supply also applies to the non-segmented electrodes RF voltages having the same amplitude Vrf and frequency fl as is applied to the segmented electrodes. Each electrode in a given pair of two opposing non-segmented electrodes (opposing across the ion optical axis 119) receives an RF voltage of the same amplitude, frequency and phase, however, each one of the two pairs of non-segmented electrodes receives a respective RF voltage having phase differing by 180 degrees relative to that applied to the other pair of such electrodes, resulting in a sign change, as follows:

[0369] Electrode Supplied Voltage (RF only)

[0370] 102 — Vrf coslit

[0371] 106 Vrf coslit

[0372] 110 —Vrf coslit

[0373] 114 Vrf coslit

[0374]

[0375] The result is that a quadrupolar electrical potential field is generated along the channel of the ion transport apparatus by the non-segmented electrodes to form a radially-confining pseudo-potential around and along the ion optical axis 119. This is in addition to the pseudo-potential generated by the axially segmented electrodes, as discussed above.

[0376] Figure 20 shows a cross-sectional view of the ion transport apparatus 109 at the axial position AA’ indicated in Figure 2B and indicates the RF and AC auxiliary voltages applied to the axially segmented electrodes and the non-segmented electrodes there, as discussed above. Figure 2D shows a cross-sectional view of the ion transport apparatus 109 at the axial position BB’ indicated in Figure 2B and indicates the RF voltages applied to the non-segmented electrodes, as discussed above. Figures 5A, 5B and 5C respectively show the same schematic view of a further example of the ion transport apparatus as is shown in Figure 2B, Figure 2C and Figure 2D, however in this further example, the diameter of each one of the axially segmented electrodes (e.g., see segmented electrode 304, and its segments 304a -304d, as well as segments 308a, 312a, 316a of the other three segmented electrodes) is smaller than that of the axially segmented electrodes of the embodiment described with reference to Figure 2C, and the field radius they define is larger than that of the axially segmented electrodes of the embodiment described with reference to Figure 2C. In addition, no RF voltages are applied to any of the axially segmented electrodes of the embodiment described with reference to Figure 2C, with only AC auxiliary voltages being applied in the manner described herein.

[0377] Figure 3 shows a schematic representation of the way in which AC auxiliary voltages having a sinusoidal waveform are applied to electrode segments of a given segmented electrode - segmented electrode 104, in the case - illustrating principles which apply equally to the other three segmented electrodes of the ion transport apparatus. The four AC auxiliary voltages, UACW,n = 1,2,3, 4, are:

[0378] VAccos(2nfAC■ t -8628430

[0379] 26

[0380] The auxiliary voltage applied to each one of the four electrode segments of the segmented electrode, at a respective one of four instants in time equally spaced across one temporal cycle of the waveform, are indicated by the following circular symbols:

[0381] . C: 2nfAC■ t = 0, 2zr

[0382] — * ’ * ’ *. Ofrr r.. «— > • Mnr / / OX

[0383] * 2 JT ’ it M

[0384] ,. — Q-—; 211 fAC■ t 3H / 2

[0385]

[0386] For example, at a time, t, corresponding to the condition 2nfAC■ t = 0, 2n, the value of t / c(n) applied to each electrode segment is indicated by the open circle symbol. Then, at a time, t, corresponding to the condition 2nfAC■ t = n / 2, the value of t 4c(n) applied to each electrode segment is indicated by the halffilled circle symbol. Later, at a time, t, corresponding to the condition 2nfAC■ t = n, the value of UAC^ applied to each electrode segment is indicated by the fully-filled circle symbol. Finally, at a time, t, corresponding to the condition 2nfAC■ t = 3n / 2, the value of t / C(„) applied to each electrode segment is indicated by the grey-filled circle symbol. The constant phase shift, A<>, between the auxiliary voltages applied to axially successive electrode segments is:

[0387] A = ( "-) — (ra-1) = 7T- / 2

[0388] This means that the auxiliary voltage applied to any one electrode segment at a given time, t, corresponds to the auxiliary voltage applied to its neighbouring electrode segment at an earlier or later time, t ± At, given by:

[0389] At = l / (4 / c)

[0390] All of the four electrode segments cycle through the same succession of values but do so with the above relative time (phase) difference. The inventors have found that the effect of having such a constant phase difference applied to the electrode segments of the segmented electrodes, in conjunction with RF voltages applied to the non-segmented electrodes (and optionally RF voltages also applied to the segmented electrodes), causes the electrodes as a whole to generate a travelling potential well within the channel formed by the electrodes of the ion transport apparatus. The potential well travels in a direction along the ion optical axis in response to the temporally changing AC auxiliary potentials. Figure 4 shows an example of the electric potential generated by the electrodes of the ion transport apparatus according to the present example. This electric potential was calculated using simulation software of the type readily available to the person skilled in the art.

[0391] Figure 4A shows the schematic partial cross-section view of Figure 3B alongside a series of calculated electric potentials along the ion optical axis 119, in Figure 4B, corresponding to four successive time instants covering slightly more than one complete cycle of the AC auxiliary waveform, U4cW. At a first time instant, the electric potential forms an axially leading well structure 200a and the beginnings of an axially succeeding well structure 200b, the latter forming at the input end of the ion transport apparatus and shown with a first ion packet contained therein. At a succeeding time instant, the electric potential8628430

[0392] 27

[0393] has transported the axially leading well structure 200a out of the axial end (output end) of the ion transport apparatus whilst it has also transported the axially succeeding well structure 200b, and the first ion packet, along the ion optical axis. At a further succeeding time instant, the electric potential has transported the axially succeeding well structure 200b, and the first ion packet, even further along the ion optical axis. Finally, at a subsequent time instant, the electric potential has transported the axially succeeding well structure 200b, and the first ion packet within it, to the output end of the ion transport apparatus for ion ejection to the TOF system (see Figure 1) whilst it has also formed a new axially succeeding well structure 200c, here containing a second ion packet, at the input end of the ion transport apparatus, for ongoing ion transport.

[0394] It is believed that a combination of the phase difference imposed between the AC auxiliary voltages applied to electrode segments of each segmented electrode, combined with the provision of segment separation regions “s” each of which is positioned to extend alongside a part of a non-segmented electrode, permits higher-order field components of the electric field (e.g., higher than quadrupolar) to play an enhanced role in shaping the electric potential into structures analogous to ‘fringing fields’ forming axially-confining walls of a potential well within the channel of the ion transport apparatus which, in conjunction with the radially-confining RF pseudo-potentials formed using the RF voltages, form one or more travelling axially-confining potential wells that travel along the axis of the apparatus, in conjunction with a static radially-confining potential. A detailed discussion of the nature of higher-order electric potential fields, fringing fields and pseudo-potentials is provided above.

[0395] Figure 6 shows a graphical view of single cycles on four different periodic auxiliary voltage waveforms including which may be used as the AC auxiliary waveform in alternative examples of the invention. Figure 6A shows a sinusoidal AC auxiliary waveform as discussed above. Figure 6B shows a square AC auxiliary waveform. Figure 6C shows a stepped AC auxiliary waveform, and Figure 6D shows a triangular AC auxiliary waveform.

[0396] Figure 7 shows a cross-sectional view of parts of a tandem mass spectrometer including a mass filter, an ion fragmentation region 107 and ion bunching region 109 of a collision cell 111, an ion transfer lens system 113a, and orthogonal extraction electrodes 113 for a TOF system. Ion trajectory simulations are performed based on a “Simsol” computational software model including the collision cell, the transfer lens system and the orthogonal acceleration electrodes illustrated by Figure 7. The ion mirror and the flight tube of the TOF system are not included in Figure 7, for clarity. The model of the collision cell has four axially segmented electrodes and four non-segmented electrodes.

[0397] Each axially segmented electrode comprises 16 electrode segmented rods; the first eight segments of each segmented electrode that are axially closest to the mass filter together with the non-segmented electrodes having the same axial positions, define the ion fragmentation region where precursor ions can be fragmented into product ions; the moving axially-confining potential wells are not generated in the ion fragmentation region. The ion transport apparatus discussed herein is represented by the ion bunching region that includes the other eight electrode segments of each segmented electrode and the non-8628430

[0398] 28

[0399] segmented rods with the same position along the ion optical axis. The four-phase transporting AC auxiliary voltages are applied to these latter eight segmented electrodes in the ion bunching region for generating the moving potential wells.

[0400] The way to apply the four-phase transporting AC auxiliary voltages to the eight sets of segmented electrodes has been described above. The field radius r0of the ion guide was 2.5 mm, the length of each segmented rod was 5mm, and the axial segment separation region “s” between any two adjacent electrode segments was 1 mm. The radially confining RF and the axially confining / transporting AC auxiliary voltages were applied in the manner of the first embodiment of this multipole ion guide, as described above. The frequency and the amplitude of the radially confining RF voltage were, respectively, 2.3MHz and 300V (zero-to peak, pole to ground). The frequency of the transporting AC auxiliary voltages was 1 kHz or 2 kHz and the amplitude was 5V. The DC offsets of the transfer lens system 113a and orthogonal acceleration electrodes 113 relative to the collision cell 111 were set to be suitable values of a typical TOF system. The buffer gas pressure was set to be 5 mTorr, 0.5 mTorr and 0.05 mTorr in the collision cell 111, the first part of transfer lens system 113a near the collision cell, and orthogonal acceleration electrodes 113 respectively. Argon was used as the buffer gas in the simulations. Ions with the m / z range from 200 Th to 2000 Th are initially positioned in the post rods of the mass filter with thermalised radial kinetic energy and their ion trajectories are simulated during their travelling towards oa-TOF. Ion statistics were performed by using virtual detectors that do not produce any electric field.

[0401] Figure 8 shows the axial position of ions transported along an ion transport apparatus according to simulations of ions having a mass-to-charge ratio of: m / z = 200 and m / z = 2000. Figure 9 shows the phase space of axial ion velocity Fz as a function of position z along the ion optical axis, which demonstrates when ions are transported from one set of corresponding electrode segments to the next nearby corresponding set. The ions oscillate in the potential well in the z direction and their velocities Fz gradually decrease due to collisions with buffer gas particles. The ions all have a stepwise motion in the z direction and travel with relatively low velocities Fz corresponding to the averaged velocity of the moving axially-confining potential well. It can be seen that a particular benefit of the invention is the feature that the axial position of an ion bunch within a traveling potential well changes in a step-wise manner whereby a potential well is found to dwell for a period of time (See Figure 8: “Dwell Time”) at successive axial dwell positions (See Figure 8 and Figure 9: “Well Position 1 to 6”) along the axis of the apparatus. Figure 9 shows the axial velocity of ions transported along an ion transport apparatus according to simulations of ions having a mass-to-charge ratio of: m / z = 2000. These results illustrate that the motion of the travelling potential well is a step-wise motion in which the dwelling of the well position allows ions to cool, as evidenced by the rapid decay in the oscillation of the z-position of simulated ions within the travelling well immediately after a step in the position of the well, and during each dwell time. It is found that the overall energy transfer (heating) effects that can result from imparting axial kinetic energy (axial velocity) to ions within a well, is reduced overall.

[0402] Figures 10A to 10E show schematically a partial cross-sectional view the ion transport apparatus of Figure 7, and therein the axial position of ions transported along an ion transport apparatus according to simulations of ions at five instants in time. The apparatus comprises four axially segmented electrodes8628430

[0403] 29

[0404] and four axially non-segmented electrodes arranged in the manner discussed above. For clarity, only one segmented electrode and only one non-segmented electrode are shown, but it is to be understood that the general structure is as shown in Figure 2A, but simply with that structure extended axially fourfold. Thus, each of the axially segmented electrodes comprises sixteen electrode segments, the first eight of these segments (per electrode) are used to form the ion fragmentation region 107, alongside the four non-segmented electrodes including electrode 214, and the final eight segments (per electrode: including segments 204a to 204h), alongside the four non-segmented electrodes, are used as the ion transport apparatus as described above whereby the first four segments (204a to 204d) and the last four segments (204e to 204h) each operate in the manner described above with reference to figures 1 to 5.

[0405] In this example of an ion cloud simulation, it is demonstrated using ions of m / z 609 and AC auxiliary voltages of 1 kHz frequency. Ions can be bunched in the potential wells and then transported with a wave velocity of 24 mm / ms along the ion optical axis with argon buffer gas present at a pressure of 5 mTorr.

[0406] At a first time instant, shown in Figure 10A, at t=0.2ms, ions are transferred from mass filter to the collision cell. The ions 400 are seen in the process of being transferred from a mass filter to the ion fragmentation region 107. At a second time instant, t=0.57ms, shown in Figure 10B, ions 402 passed through the ion fragmentation region 107 are collected within a travelling potential well 410 at a first well position (“Well Position 1 ”) as an ion bunch 402 where the remain with the well while it dwells at that position. The first well position is axially aligned with the group of electrode segments that include segment 204a. The travelling potential well subsequently steps, 412, along the axis of the ion transport apparatus at t=0.65ms as shown in Figure 10C and moves the ion bunch 404 with it until it reaches its next well position (Figure 10D: “Well Position 2”) where it dwells allowing the ion bunch 406 within it to cool and contract. This stepping process continues (not shown) in this way to successive well positions are stepped through to reach a terminal well position 416 at t=2.35ms containing the cooled ion bunch 408 ready for injection into the io lens system 113a. This allows to convert a continuous ion beam into a plurality of discrete ion packets with time width of several microsecond (pis) to match the TOF extraction timescales.

[0407] Figure 11 A shows a graph of the time distribution of a population of ions within a mass filter of an ion transport apparatus shown in Figures 10A to 10E (see Figure 11 B) and shows a partial cross-sectional view the ion transport apparatus and therein the axial position of several ion bunches being transported along the ion transport apparatus according to simulations. Figure 11 C shows a graph of the time distribution of the population of ions output from the ion transport apparatus as ion bunches.

[0408] In this example, the input ion beam had a uniform time distribution with width of 3ms, and was converted into four ion pulses with time width of several ps, as demonstrated shown; each ion pulse travels out of the collision cell every 1 millisecond, which can be matched with 1 kHz TOF acquisition speed. These simulations show that ions with varying m / z can be bunched into the potential wells and then transported through the collision cell with the same velocity. Ions took about 4ms or 2ms to travel through the collision cell for 1 kHz or 2 kHz transporting AC auxiliary voltage frequencies. This can overcome a problem of the8628430

[0409] 30

[0410] ion slow movement and overstay in a collision cell. It can reduce the dead time between two MS1 isolation windows, and thus increase data acquisition speed to match fast separations of modern LC methods. In addition, it allows to apply higher pressure than the conventional collision cell as ions can be transported by the moving potential wells; this can result in higher ion fragmentation efficiency. Therefore, the sensitivity of the mass analysis can be improved.

[0411] Another advantage of the invention is the improvement for ion injection to oaTOF. It can provide a bunched ion cloud with a narrow spatial distribution in the ion optical axis before injecting these ions to oaTOF. The bunched ions can be injected to the oaTOF by both a push force from the transporting AC auxiliary voltages and a pull force from the gating voltage of the exit lens. This allows ions to leave the collision cell with a much narrower time spread than the current ion trapping mode of an oaTOF. The narrow time spread results in a narrow spatial distribution for ions arriving in the orthogonal acceleration electrodes and thus allows more ions to be extracted into the flight tube through the grid of the orthogonal acceleration electrode. In this way, the oaTOF duty cycle can be greatly improved for ions within a limited m / z range.

[0412] Figure 12A shows a graph of the time distribution of a population of ions output an ion transport apparatus according to three different mass-to-charge ratio of: m / z = 400, m / z = 609 and m / z = 900.

[0413] Figure 12B shows a histogram of the axial position of ions adjacent to orthogonal acceleration electrodes of an oaTOF apparatus, having been transported there by an ion transport apparatus according to simulations.

[0414] Figure 12C shows a graph of the duty cycle as a function of mass-to-charge ratio of, m / z, of a tandem mass spectrometer system of Figure 1 when the oaTOF system thereof is operated in a bunched-beam mode, and a comparison with duty cycles achieved in a continuous beam mode.

[0415] Simulations show the mass range in a single oaTOF spectrum depends on the delay time between the oaTOF extraction pulse and the accelerating gating voltage of the exit lens. In simulations, ions of different m / z are accelerated to about 43.5eV in the transfer lens system and these ions have different velocities Fz as well as different arrival times in the orthogonal acceleration electrodes 113. A simulated TOF spectrum is shown in Figure 12A. Here, ions were detected at the acceleration electrodes 113. A bipolar TOF extraction voltage was +Z-2.5 kV, giving a 5 kV potential difference across a 4mm distance. This TOF extraction voltage is applied with delay time of 24.98ps after gating voltage of exit lens is switched to release ions into TOF. About 45% of a total of 5000 reserpine ions (m / z = 609) that were initially positioned in the post rods of the mass filter can be extracted giving a TOF duty cycle of 97.7%. About 53% of reserpine ions were lost in the transfer lens system 113a and about 2% of ions were lost by hitting the acceleration electrodes 113 before TOF extraction. Ions of m / z = 400 and m / z = 900 had 22% and 23% overall efficiency respectively which are about a half of that for ions of m / z = 609.8628430

[0416] 31

[0417] Figure 12B demonstrates the axial, z, distribution of the detected ions at the axial position (within its axial extent) of the acceleration electrodes 113 at the time of applying a TOF extraction voltage and highlights (with cross-hatching) the ions of m / z = 609. The axial, z, distribution of m / z = 609 is in the middle of the axial extent of the acceleration electrodes with a negative skewness relative to the mean, and this explains how a 97.7% TOF duty cycle is achieved.

[0418] As for ions of m / z = 400 and m / z = 900, their axial, z, distributions are near the exit edge and entrance edge of the axial extend of the acceleration electrodes, respectively, and the ions outside of that axial range are lost and cannot be analysed by the oaTOF. If we define the m / z range in a single TOF spectrum as the full width of half maximum efficiency, the m / z range is estimated to be from about 400 Th to about 900 Th in this example, which gives a ratio of about 2.25 times. Three or more spectra with different delay time can be estimated to cover the mass range from m / z = 200 to m / z = 2000. The simulations show that the invention may improve a TOF duty cycle by about 12 times for ions of m / z = 609 within a mass range between about 400 Th to about 900 Th.

[0419] Comparing to a continuous ion beam mode with an 8 kHz TOF extraction rate (that acquires 8000 single TOF spectra per second), the improvement for ions with smaller m / z can be greater, e.g. about 20 times improvement for ions with m / z = 200. This feature can improve sensitivity especially in target analysis (e.g. MRM). Simulations show 45% of m / z = 609 ions can travel from the post rods of the mass filter to the acceleration electrodes if the TOF extraction voltage is well timed; this may result in a comparable sensitivity as triple quadrupole MS. Dynamic range can also be improved by about 10 times or higher for m / z = 609, by switching the operation modes between continuous ion beam and ion bunching for analysing ions with high intensity and low intensity respectively. Another advantage of this method is to simplify the data analysis of data independent acquisition (DIA); it can reduce the mix of the product ions isolated from different MS1 windows and can improve false discovery rate for protein identifications.

[0420] Space charge interactions, ion fragmentations and gas flow were not included in the simulations. The simulation model does not include the fight tube, the ion mirror and the detector of the oaTOF system. An ideal grid is used in the orthogonal acceleration electrode, and the ion loss in the grid was not considered. However, the simulation results clearly show this invention provides a relatively higher TOF duty cycle for ions within a limited m / z range than the continuous ion beam mode. In addition, comparing to the ion trapping mode that injects ions to oaTOF from a conventional collision cell with axial DC, this ion bunching method may provide a higher TOF duty cycle and larger m / z range in a single TOF spectrum. A reason for such improvement is believed to be that the moving potential well generated by the transporting AC auxiliary voltages provides tightly bunched ions to leave the ion guide. A gating signal of an exit lens 113a and the travelling potential well can both accelerate the tight ion bunch. Conventional collision cells typically use a gating signal of an exit lens to accelerate un-bunched accumulated ions having merely a wide spatial distribution in the ion optical axis. Therefore, this invention allows ions to leave the ion transport apparatus, via an exit lens, with a much narrower time spread than existing methods, resulting in a narrow spatial distribution for ions that arrive in the orthogonal acceleration electrodes.8628430

[0421] 32

[0422] The invention may provide a multipole ion guide comprising a plurality of elongate electrodes defining an elongated volume with an ion optical axis, in which one or more of segmented rod electrodes are segmented. The multipole ion guide can work as a collision cell or a part of a collision cell. It can provide one or more moving potential wells to bunch ions and then transport ions at the same velocity. This invention may reduce ion travelling time through a collision cell. It may eliminate (or at least reduce) ion overstay in collision cell and may decrease delay time between two acquisition events of an MRM system. It also allows to apply higher pressure than the conventional collision cell, resulting in higher ion fragmentation efficiency. As a result, higher sensitivity and faster data acquisition may be achieved. The bunched ions can be injected to oaTOF with a narrow time spread, resulting in a much higher TOF duty cycle and sensitivity for ions within a limited m / z range. This method for bunching and transporting ions works for both positively and negatively charged ions, and can be used for operating a reaction cell for ETD.

[0423] It is noted that the invention may provide a tandem mass spectrometry apparatus. The apparatus described above with reference to Figure 1 provides an example. Specifically, this tandem mass spectrometry apparatus comprises an ion source 101 for providing precursor ions, and a first mass analyser 105 configured to apply a selection of precursor ions according to their mass-to-charge ratios. A collision cell 111 is provided and includes a fragmentation device 107 for fragmenting at least some of the selected precursor ions to generate product ions of the fragmented precursor ions. The collision cell also includes an ion transport apparatus 109 as disclosed herein, for transporting precursor ions and product ions from the fragmentation device 107 to a second mass analyser (oaTOF) 112 configured to apply a process of mass analysis to the product ions.

[0424] The invention may also provide an electron-transfer dissociation, ETD, apparatus. An example of an ETD apparatus is illustrated schematically in Figure 13. It comprises an ion multi-source 101 comprising first ion source 101 A for providing precursor ions, and a second ion source 101 B for providing reagent ions bearing a charge that is the opposite sign to the charge of the precursor ions. An ion optics assembly 103 is arranged to receive precursor ions output by the first ion source 101 A and to guide the received precursor ions to a first mass analyser 105. The first mass analyser 105 is configured for selecting precursor ions according to their mass-to charge ratios (m / z). An ion transport apparatus according to an example of the invention is arranged along the ion optical axis downstream of the first mass analyser 105 for fragmenting the selected precursor ions into product ions, as described in more detail below, and for transmitting ions into an oaTOF system 112. The ions are received at the orthogonal acceleration electrodes 113 of the oaTOF system for acceleration into a time-of-flight assembly 115 of the oaTOF system, for analysing ions according to their flight time along a flight trajectory 114 extending between the orthogonal acceleration electrodes 113 and an ion detector 116 of the oaTOF system.

[0425] An ion transport apparatus 109, according to the invention, is arranged downstream of the first mass analyser 105 and upstream of the oaTOF system 112. An ion trapping part 109B is arranged downstream of the ion transport apparatus and upstream of the oaTOF system 112. The ion transport apparatus is8628430

[0426] 33

[0427] configured to receive precursor ions from the first ion source 101 A at a first potential well formed by the ion transport apparatus, as described above, and to transport the first potential well along the ion optical axis, as described above, to the ion trapping part. The ion transport apparatus is also configured to receive reagent ions from the second ion source 101 B at a second potential well formed by the ion transport apparatus, as described above, and to transport the second potential well along the ion optical axis, as described above, to the ion trapping part thereat to combine precursor ions with the reagent ions. This combination of ions allows a process of electron transfer from reagent ions to precursor ions and ion fragmentation to generate product ions. In other words, the ion trapping part is first ‘loaded’ with precursor ions and then further ‘loaded’ with reagent ions while the precursor ions are still present in the ion trapping part. The second ion source 101 B is configured for generating negatively charged reagent ions (e.g., using a high-voltage discharge method such as would be readily available to the skilled person). The two ion sources, 101 A and 101 B, can be used at ambient pressure.

[0428] The ion trapping part is formed at least in part by a terminal part of the ion transport apparatus, such as via the terminal (e.g., exit) end of the channel formed by the plurality of electrodes of the ion transport assembly. This may be implemented using the terminal electrode segment(s), in the array of separate electrode segments of the at least one axially segmented electrodes, in conjunction with the parts of the other electrodes of the ion transport assembly, that are all present at (i.e., terminate at) the exit end of the channel formed by the ion transport apparatus. The controller and power supply 117 is configurated for applying appropriate radio-frequency, RF, voltages, alternating-current, AC, auxiliary voltages and direct-current, DC, voltages to electrodes of the ion transport apparatus that at least in part form the ion trapping part, such that an appropriate trapping electric potential field is formed for radially and axially trapping ions there.

[0429] In the present example, the ion trapping part 109B also comprises an exit lens (transfer lens) apparatus arranged upon the ion optical axis 119 adjacent to and downstream from a terminal end of the channel formed by the plurality of electrodes of the ion transport apparatus. The controller and power supply 117 may be configurated to apply AC voltages to the exit / transfer lens apparatus to reversibly generate in the channel an axially-confining electric potential field forming a potential barrier for releasably trapping ions in the ion trapping part. Thus, the ion trapping part may be formed solely by the last segment (or last few segments) of the array of 109 (close to transfer lens system 113a) where the charge transfer can occur; the exit lens downstream of it can be supplied with an AC voltage to confine both negatively charged and positively charges ions.

[0430] The ion source 101, ion optics assembly 103, first mass analyser 105, the ion transport apparatus 109, the ion trapping part 109B, and the oaTOF system are aligned in succession, and in ion flow communication, along a linear ion optical axis 119. The controller and power supply 117 is configurated for applying appropriate radio-frequency, RF, voltages, alternating-current, AC, auxiliary voltages and direct-current, DC, voltages to electrodes of the ion optics assembly 103, the first mass analyser 105, the ion transport apparatus 109, the ion trapping part 109B, and the orthogonal acceleration electrodes 113, and time-of-flight assembly 115, for the purposes of mass analysis of ions.8628430

[0431] 34

[0432] The controller and power supply 117 is configurated to control the ion multi-source 101 to generate ions from the first ion source 101 A and from the second ion source 101 B, respectively, separately in time, such as alternately or consecutively in time (i.e., as opposed to concurrently). The controller and power supply is configured to control the RF and DC voltages of the ion optics assembly 103 and the first mass analyser 105, that are upstream of the ion transport assembly 109, so as to switch the polarity (sign) of the voltages as appropriate when switching between the handling of ions (e.g., positively charged precursor ions) from the first ion source 101 A over a first time interval, and the handling of ions (e.g., negatively charged reagent ions) from the second ion source 101 B over a second time interval. For example, DC offsets may be switched in polarity for ions with opposite sign.

[0433] The design of the two ion sources may be any suitable source of precursor ions and reagent ions as would be readily apparent and available to the person skilled in the art. As one example, the first and second ion sources (101 A and 101 B) may be according to the arrangements disclosed in United States patent US8624179B2 (reference [3]), such as is shown in Figure 4 of US8624179B2 whereby the capillary (item 14 of Fig. 4 of US8624179B2) of an electrospray ion source may provide the first ion source 101 A, and the reagent source (item 19 of Fig. 4 of US8624179B2) and glow discharge pin (item 18 of Fig. 4 of US8624179B2) may provide the second ion source 101 B.

[0434] The features disclosed in the foregoing description, or in the following claims, or in the accompanying drawings, expressed in their specific forms or in terms of a means for performing the disclosed function, or a method or process for obtaining the disclosed results, as appropriate, may, separately, or in any combination of such features, be utilised for realising the invention in diverse forms thereof.

[0435] While the invention has been described in conjunction with the exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art when given this disclosure. Accordingly, the exemplary embodiments of the invention set forth above are considered to be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention.

[0436] For the avoidance of any doubt, any theoretical explanations provided herein are provided for the purposes of improving the understanding of a reader. The inventors do not wish to be bound by any of these theoretical explanations.

[0437] Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0438] Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise” and “include”, and variations such as “comprises”, “comprising”, and “including” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

[0439] It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range8628430

[0440] 35

[0441] is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedent “about,” it will be understood that the particular value forms another embodiment. The term “about” in relation to a numerical value is optional and means for example + / - 10%.

[0442] References

[0443] A number of publications are cited above in order to more fully describe and disclose the invention and the state of the art to which the invention pertains. Full citations for these references are provided below. The entirety of each of these references is incorporated herein.

[0444] [1] Peter H Dawson: “Quadrupole Mass Spectrometry and its applications”, 1st Edition - January 1, 1976 - Elsevier, ISBN: 978-0-444-41345-1

[0445] [2] Mikhail Yavor: “Optics of Charged Particle Analyzers” in “Advances in Imaging and Electron Physics”, Volume 157, Pages 1-381 (2009)

[0446] [3] US8624179B2

Claims

862843036Claims:

1. An ion transport apparatus comprising:a power supply configured to supply RF voltages and AC auxiliary voltages;a plurality of electrodes comprising at least one axially segmented electrode and a plurality of axially non-segmented electrodes, wherein the plurality of electrodes are spatially arranged collectively to define a volume extending along an ion optical axis to form a channel, and at least the plurality of axially non-segmented electrodes are configured to receive respective RF voltages from the power supply for generating a radially-confining electric potential field forming a pseudo-potential within the channel for guiding ions therealong;wherein each of the at least one axially segmented electrodes comprises an array of separate electrode segments that extends alongside the ion optical axis and wherein each electrode segment is elongated to extend alongside the ion optical axis whereby successive electrode segments are separated by a segment separation region and the at least one axially segmented electrode extends alongside at least one said axially non-segmented electrode(s) to position a given segment separation region alongside an axially non-segmented electrode; and,the power supply is configured to apply to corresponding electrode segments of each said array a respective said AC auxiliary voltage comprising a temporal phase which differs by a substantially constant phase shift relative to respective temporal phases of AC auxiliary voltages concurrently applied to each neighbouring electrode segment of a given said array, thereby the plurality of electrodes collectively generate within said channel at least one travelling potential well for transporting ions therein along the ion optical axis.

2. An ion transport apparatus according to any preceding claim wherein each of the at least one axially segmented electrode(s) is configured to receive respective RF voltages from the power supply for generating a radially-confining electric potential field forming a pseudo-potential within the channel for guiding ions therealong.

3. An ion transport apparatus according to any preceding claim wherein the plurality of axially segmented electrodes comprises one or more segmented electrode pairs comprising two said axially segmented electrodes spatially arranged to oppose each other across the ion optical axis.

4. An ion transport apparatus according to any preceding claim wherein the plurality of axially nonsegmented electrodes comprises one or more non-segmented electrode pairs comprising two axially non-segmented electrodes spatially arranged to oppose each other across the ion optical axis.8628430375. An ion transport apparatus according to any preceding claim wherein the power supply is configured to apply to electrodes of the plurality of electrodes said RF voltages so as to generate an electric potential field having a quadrupolar component in said channel.

6. An ion transport apparatus according to any preceding claim wherein an amplitude and / or a frequency of a said AC auxiliary voltage differs from an amplitude and / or a frequency, respectively, of a said RF voltage that is applied simultaneously to the set of electrodes.

7. An ion transport apparatus according to any preceding claim wherein the at least one axially segmented electrode(s) are configured to receive respective AC auxiliary voltages from the power supply for generating an electric potential field forming a potential within the channel that is not a pseudo-potential.

8. An ion transport apparatus according to any preceding claim wherein said substantially constant phase shift of AC auxiliary voltages is the same as between each two successive segments in a given array.

9. An ion transport apparatus according to any preceding claim wherein said substantially constant phase shift of AC auxiliary voltages is 2π / n and the segmented electrode(s) comprises at least n segments.

10. An ion transport apparatus according to any preceding claim wherein said substantially constant phase shift of AC auxiliary voltages is 2π / n where n is an integer such that n ≥ 3.

11. An ion transport apparatus according to any preceding claim wherein said substantially constant phase shift of AC auxiliary voltages is 2π / n where n is an integer such that n ≤ 8.

12. An ion transport apparatus according to any preceding claim wherein the corresponding segments of each array are located at the same axial position along the ion optical axis and share the same said substantially constant phase shift of AC auxiliary voltages.

13. An ion transport apparatus according to any preceding claim comprising a plurality of segmented electrodes, wherein each segment separation region of each array is axially aligned with a corresponding segment separation region of each of the other arrays.

14. An ion transport apparatus according to any preceding claim wherein, for each segmented electrode the axial length of the segment separation region is less than the axial length of either of the electrode segments that it separates within the given segmented electrode.86284303815. An ion transport apparatus according to any preceding claim wherein the segmented electrodes are arranged radially around the ion optical axis in a manner that is symmetrical with respect to a rotation about the ion optical axis.

16. An ion transport apparatus according to any preceding claim wherein all electrodes of the plurality of electrodes are arranged radially around the ion optical axis in a manner that is symmetrical with respect to a rotation about the ion optical axis.

17. An ion transport apparatus according to any preceding claim wherein the total number of electrodes, being the sum of all said axially segmented electrode(s) and all said axially non-segmented electrodes comprising the plurality of electrodes, is an even number.

18. An ion transport apparatus according to any claim of claims 1 to 17 wherein the field radius of said non-segmented electrodes, being the shortest distance from the ion optical axis to a given nonsegmented electrode, is substantially the same for all non-segmented electrodes of the plurality of electrodes.

19. An ion transport apparatus according to any claim of claims 1 to 17 wherein the field radius of said segmented electrodes, being the shortest distance from the ion optical axis to a given segmented electrode, is substantially the same for all segmented electrodes of the plurality of electrodes.

20. An ion transport apparatus according to claims 18 and 19 wherein the field radius of said segmented electrodes differs from the field radius of said non-segmented electrodes.

21. An ion transport apparatus according to claims 18 and 19 wherein the field radius, being the shortest distance from the ion optical axis to a given electrode, is substantially the same for all electrodes of the plurality of electrodes.

22. An ion transport apparatus according to any preceding claim wherein the length of each said segmented electrode, being the sum of the lengths of all segments and segment separation regions thereof, is substantially the same as the length of any said non-segmented electrode.

23. An ion transport apparatus according to any preceding claim wherein each segment separation region of one segmented electrode of each pair of segmented electrodes opposes a corresponding segment separation region of the other segmented electrode of the pair of segmented electrodes across the ion optical axis.

24. An ion transport apparatus according to any preceding claim wherein at least one said segmented electrode extends in parallel alongside at least one said non-segmented electrode to position a given segment separation region alongside a non-segmented electrode.86284303925. An ion transport apparatus according to any preceding claim wherein the plurality of electrodes are linear.

26. An ion transport apparatus according to any preceding claim wherein the plurality of electrodes are disposed inside a collision cell configured for maintaining a buffer gas with said channel such that product ion fragments, that are produced from precursor ions by a process of collision-induced dissociation, CID, with the buffer gas, are guided along the channel.

27. A mass spectrometry apparatus comprising the ion transport apparatus according to any preceding claim.

28. A mass spectrometry apparatus comprising a time-of-flight, TOF, mass analyser and the ion transport apparatus according to any preceding claim arranged upstream of the TOF mass analyser for transporting ions to the TOF mass analyser for mass analysis.

29. A tandem mass spectrometry apparatus comprising:an ion source for providing precursor ions;a first mass analyser configured to apply a selection of precursor ions according to their mass-to- charge ratios;a collision cell for fragmenting at least some of the selected precursor ions to generate product ions of the fragmented precursor ions, the collision cell comprising an ion transport apparatus according to any of claims 1 to 26 for transporting the product ions and / or precursor ions in the collision cell;a second mass analyser configured to apply a process of mass analysis to the product ions.

30. An electron-transfer dissociation, ETD, apparatus comprising:a first ion source for providing precursor ions;a second ion source for providing reagent ions bearing a charge that is the opposite sign to the charge of the precursor ions;an ion transport apparatus according to any preceding claim;an ion trapping part;wherein the ion transport apparatus is configured:to receive precursor ions from the first ion source at a first said potential well and to transport the first potential well along the ion optical axis to the ion trapping part; and,to receive reagent ions from the second ion source at a second said potential well and to transport the second potential well along the ion optical axis to the ion trapping part thereat to combine precursor ions with the reagent ions to allow a process of electron transfer from reagent ions to precursor ions and ion fragmentation to generate product ions.

31. An electron-transfer dissociation, ETD, apparatus according to claim 30 wherein the ion trapping part is formed at least in part by a terminal part of the ion transport apparatus.86284304032. An electron-transfer dissociation, ETD, apparatus according to claim 30 or 31 wherein:the ion trapping part comprises an exit lens apparatus arranged upon the ion optical axis adjacent to and downstream from a terminal end of the channel formed by the plurality of electrodes; and said power supply is configured to apply AC voltages to the exit lens apparatus to reversibly generate in the channel an axially-confining electric potential field forming a potential barrier for releasably trapping ions therein.

33. A mass spectrometry apparatus comprising a time-of-flight, TOF, mass analyser and the electrontransfer dissociation, ETD, apparatus according to any of claims 30 to 32 arranged upstream of the TOF mass analyser for releasing product ions to the TOF mass analyser for mass analysis.

34. A method of ion transport comprising:providing a power supply configured to supply RF voltages and AC auxiliary voltages;providing a plurality of electrodes comprising a plurality of axially non-segmented electrodes and at least one axially segmented electrode, wherein the plurality of electrodes are spatially arranged collectively to define a volume extending along an ion optical axis to form a channel, and each of the at least one axially segmented electrodes comprises an array of separate electrode segments that extends alongside the ion optical axis and each electrode segment is elongated to extend alongside the ion optical axis whereby successive electrode segments are separated by a segment separation region and the at least one axially segmented electrode extends alongside at least one said axially non-segmented electrode to position a given segment separation region alongside an axially nonsegmented electrode;by the power supply, applying to at least the plurality of axially non-segmented electrodes respective RF voltages from the power supply to generate a radially-confining electric potential field forming a pseudo-potential within the channel for guiding ions therealong; and,by the power supply, applying to corresponding electrode segments of each said array a respective said AC auxiliary voltage comprising a temporal phase which differs by a substantially constant phase shift relative to respective temporal phases of AC auxiliary voltages concurrently applied to each neighbouring electrode segment of a given said array;thereby, by the plurality of electrodes, collectively generating within said channel at least one travelling potential well for transporting ions therein along the ion optical axis.

35. A method of ion transport according to claim 34 wherein said plurality of electrodes comprises and at least one pair of said axially segmented electrodes that are arranged to oppose each other across the ion optical axis.86284304136. A method of mass spectrometry comprising the method of ion transport according to claim 34 or 35.

37. A method of mass spectrometry according to claim 36 further comprising providing a time-of-flight, TOF, mass analyser and transporting ions to the TOF mass analyser according to the method of ion transport, for mass analysis.

38. A method of tandem mass spectrometry comprising:providing precursor ions;by a first mass analyser, applying a selection of precursor ions according to their mass-to-charge ratios;providing a collision cell comprising an ion transport apparatus according to any of claims 1 to 26; fragmenting at least some of the selected precursor ions to generate product ions of the fragmented precursor ions in the collision cell and transporting the product ions and / or precursor ions in the collision cell according to the method of any of claims 34 to 35;by a second mass analyser, applying a process of mass analysis to the product ions.

39. A method of electron-transfer dissociation, ETD, comprising:providing precursor ions;providing reagent ions bearing a charge that is the opposite sign to the charge of the precursor ions;providing an ion transport apparatus according to any of claims 1 to 26;providing an ion trapping part;by the ion transport apparatus:receiving precursor ions at a first said potential well, transporting the first potential well along the ion optical axis to the ion trapping part and trapping the first precursor ions by the ion trapping part; and,receiving reagent ions at a second said potential well, transporting the second potential well along the ion optical axis to the ion trapping part and thereat combining first precursor ions with the second precursor ions to allow a process of electron transfer from reagent ions to precursor ions and ion fragmentation to generate product ions.

40. A method according to claim 38 wherein the ion trapping part is formed at least in part by a terminal part of the ion transport apparatus.

41. An electron-transfer dissociation, ETD, method according to claim 39 or claim 40 comprising:providing the ion trapping part comprising an exit lens apparatus arranged upon the ion optical axis adjacent to and downstream from a terminal end of the channel formed by the plurality of electrodes; and862843042by said power supply, applying AC voltages to the exit lens apparatus to reversibly generate in the channel an axially-confining electric potential field forming a potential barrier and therewith releasably trapping ions therein.

42. A method of mass spectrometry comprising providing a time-of-flight, TOF, mass analyser and providing the electron-transfer dissociation, ETD, apparatus according to any of claims 39 to 41 arranged upstream of the TOF mass analyser, the method comprising releasing product ions from the electron-transfer dissociation, ETD, apparatus to the TOF mass analyser for mass analysis.

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