Ion transport for collision-induced dissociation

Abstract

An ion transport apparatus comprises a power supply configured to supply RF voltages and a plurality of electrodes forming a channel for generating therein a radially-confining pseudo-potential field for guiding ions. The plurality of electrodes comprises axially non-segmented electrodes and axially segmented electrodes. Each segmented electrode comprises an array of separate electrode segments that extends alongside the ion optical axis. Each electrode segment is elongated to extend alongside the ion optical axis. Successive electrode segments are separated by a segment separation region and a segmented electrode extends alongside at least one said non-segmented electrode to position a segment separation region alongside a non-segmented electrode. RF voltages received by the electrodes cause a segment separation region to shape the radially-confining electric potential field within the channel to provide more kinetic energy to ions than is provided by the radially-confining electric potential field present within axially adjacent parts of the channel. This allows ions to experience more RF heating, thereby improving efficiency of collision-induced dissociation.

Description

[0001] ION TRANSPORT

[0002] Field of the Invention

[0003] The present invention relates to methods and apparatus for ion transport, and particularly, although not exclusively, to collision-induced ionisation, CID, such as for use in mass spectrometry.

[0004] Background

[0005] A collision cell is a commonly-used component for a tandem mass spectrometer, and is used to fragment precursor ions and generate product ions. A process of collision-induced dissociation (CID) is the most popular ion fragmentation method, in which ions are accelerated by an electric field to increase the ion kinetic energy and to collide with particles of a buffer gas to generate ion fragments.

[0006] One problem of the CID method is poor fragmentation efficiency, which can depend on the molecular structures, masses and charges of ions involved. For example, fragmentation efficiencies for multiple-charged species in triple-quadrupole instruments are typically 20% or lower. One fundamental cause is that the ion kinetic ion energy in the laboratory frame cannot be effectively transferred into ion internal energy. In other words, the low collision energy in the centre-of-mass frame limits the probability of breaking chemical bonds and thereby limits ion fragmentation efficiency.

[0007] Another problem of the CID method arises from the slowdown of ions due to frequent collisions with buffer gas particles, especially when the buffer gas is at high pressure, resulting in long travelling times for ions to pass through the collision cell. In a typical tandem mass spectrometer, the length of the collision cell is in a range of about 120 mm to about 200 mm, and the pressure of the collision cell is in a range of about 1 mTorr to about 20 mTorr, when the buffer gas is argon or nitrogen. The strong damping of the buffer gas in such conditions can greatly slow ions and require tens of millisecond (ms) travelling time for ions to pass through the collision cell. In the extreme scenario, some ions can stay inside collision cell. Ions may be detected at an inappropriate time to give a so-called “ghost peak”. As a result, a delay time interval (i.e., a “down-time”) is usually applied between the two events of multiple reaction monitoring (MRM) in mass analysis to permit time to clear out the remaining ions of the last event. This delay time is dependent upon the travelling time for ions to pass through the collision cell, and can affect the sensitivity and data acquisition speed of a tandem mass spectrometer.

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

[0009] Summary of the Invention

[0010] This invention provides an ion transport apparatus, suitable for use in a mass spectrometer. In a first aspect, the invention may provide an ion transport apparatus comprising:

[0011] a power supply configured to supply RF voltages;

[0012] a plurality of electrodes spatially arranged collectively to define a volume extending along an ion optical axis to form a channel, and configured to receive respective RF voltages from the power supply for8501652

[0013] 2

[0014] generating a radially-confining electric potential field forming a pseudo-potential within the channel for guiding ions therealong; and,

[0015] the plurality of electrodes comprises at least one pair of axially non-segmented electrodes that are spatially arranged to oppose each other across the ion optical axis, and at least one axially segmented electrode;

[0016] wherein each of the at least one segmented electrode comprises an array of separate electrode segments that extends alongside the ion optical axis in which 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 segmented electrode extends alongside at least one said non-segmented electrode to position a given segment separation region alongside a non-segmented electrode;

[0017] whereby, when said RF voltages are received from the power supply by the plurality of electrodes, the given segment separation region shapes the radially-confining electric potential field within the channel to provide more kinetic energy to ions than is provided by the radially-confining electric potential field present within axially adjacent parts of the channel. In this way, an enhanced RF heating effect may be applied to the ions. The ion transport apparatus may provide a collision cell apparatus.

[0018] The pseudo-potential may be a spatially static pseudo-potential. The RF voltage(s) may be scanned such that, as a consequence, the amplitude of the pseudo-potential is scanned. This may permit an ion transport apparatus to implement a mass filtering process, if desired, in some examples. In such examples, the transport apparatus may provide a mass filtering apparatus in the sense that this may permit an ion transport apparatus to change the transmitted m / z range.

[0019] The disclosed ion transport apparatus can be used as an improved collision cell. The RF pseudopotential field is shaped to vary along the ion optical axis, and this variation is generated by the asymmetric geometry of segmented electrodes and the non-segmented electrodes. This allows ions to experience more RF heating and gain higher kinetic energy in the radial direction. As a result, it is possible to improve ion fragmentation efficiency.

[0020] The ion transport apparatus may thereby comprise a plurality of elongated electrodes defining an elongated volume extending along an ion optical axis. Among these electrodes, one or more electrodes (e.g., rod electrodes) are segmented in the direction of the ion optical axis, and the other electrodes (e.g., rod electrodes) are single non-segmented electrodes. Each segmented electrode may be composed of two or more rod segment electrodes. Successive rod segment electrodes in a segmented electrode may be separated in the direction of the ion optical axis. Such geometry can provide an RF pseudopotential field that varies in direction along the ion optical axis, and may result in higher ion fragmentation efficiency.

[0021] An electric field for accelerating ions to travel along the direction of the ion optical axis may be generated, as desired, by applying appropriate direct current (DC) or RF voltages to segmented rod electrodes. An electric field for accelerating ions towards the ion optical axis can reduce ions’ travelling time through the apparatus. It is possible to prevent a ghost peak caused by the stay of the ions in collision cell, and to8501652

[0022] 3

[0023] decrease a delay time between two events / uses of the device. As a result, higher sensitivity and higher duty cycle can be achieved. An electric field for accelerating ions to travel along the ion optical axis can be provided to moderate the ions' slowdown due to gas damping at high pressure and decrease delay times. It also allows users to apply higher buffer gas pressure in the apparatus, resulting in higher ion fragmentation efficiency. Therefore, the sensitivity of the mass analysis can be improved.

[0024] When the RF voltages are received from the power supply by the plurality of electrodes, the given segment separation region may shape the radially-confining electric potential field within the channel to include a contribution from multipoles exceeding second-order that is greater than the contribution from such multipoles present within axially adjacent parts of the channel. Accordingly, the enhanced contribution from multipoles exceeding second-order may cause an enhanced RF heating effect may be applied to the ions.

[0025] It is to be understood that references herein to “second order” refers to quadrupole, as distinct from dipole, in relation to an electric potential field contributions from multipoles. Thus, a contribution from multipoles exceeding second order means exceeding quadrupole-type order.

[0026] Consequently, an RF pseudopotential field may be provided that varies along the ion optical by comprising high order components of the RF pseudopotential field, and thereby provide more RF heating to ions and thus increases ion kinetic energy in the radial direction. This allows to enhance ion fragmentation efficiency.

[0027] The one or more axially segmented electrodes may comprise one or more pairs of axially segmented electrodes wherein the two axially segmented electrodes of a given pair of axially segmented electrodes are arranged to oppose each other across the ion optical axis. For example, the number of pairs of axially segmented electrodes may match the number of pairs of axially non-segmented electrodes.

[0028] Preferably or optionally, 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. For example, the axial length of a spacing between successive segments may be less than the axial length of the segments it separates. A greater RF heating effect may be found to occur as a result.

[0029] The segmented electrodes may be radially arranged around the ion optical axis in a manner that is symmetrical with respect to a rotation about the ion optical axis. All electrodes may be radially arranged around the ion optical axis in a manner that is symmetrical with respect to a rotation about the ion optical axis. The axially segmented electrodes and the axially non-segmented electrodes may be arranged in a circular array around the ion optical axis. They may be evenly, or regularly, spaced in azimuthal angle (i.e., as between successive electrodes) about the ion optical axis.8501652

[0030] 4

[0031] The total number of electrodes comprising the plurality of electrodes may be an even number (e.g. 4, 6, 8, etc. in number). The array may form a quadrupole array, a hexapole array, or an octupole array, for example.

[0032] The field radius, being the shortest distance from the ion optical axis to a given electrode, may be substantially the same for all electrodes of the plurality of electrodes.

[0033] The length of each given 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 given said nonsegmented electrode. The length of a terminal segment of each segmented electrode may be shorter than the length of all axially preceding segments thereof.

[0034] Each segmented electrode may comprise no more than ten segment separation regions, or may comprise no more than five segment separation regions.

[0035] In some examples or embodiments, when the RF voltages are received from the power supply by the plurality of electrodes, the given segment separation region shapes the radially-confining electric potential field upon the ion optical axis to include a contribution from multipoles exceeding second-order that is greater than the contribution of such multipoles present on adjacent parts of the ion optical axis.

[0036] Each segment separation region of one segmented electrode of each pair of segmented electrodes may be arranged to oppose a corresponding segment separation region of the other segmented electrode of the pair of segmented electrodes across the ion optical axis. At least one of the segmented electrodes may be arranged to extend in parallel alongside at least one of the non-segmented electrode to position a given segment separation region alongside a non-segmented electrode.

[0037] The plurality of electrodes may be linear. For example, the plurality of electrodes may define a linear ion transport apparatus so as to define, and extend along, a linear ion optical axis. For example, each of the electrodes of the plurality of electrodes may be linear (e.g., linearly elongated) so as to extend alongside (e.g., be parallel to) a linear ion optical axis.

[0038] The power supply may be configured to supply further RF voltages and / or DC voltages to the plurality of segmented electrodes to form within the channel an electric field configured for urging ions to travel in a selected direction along the ion optical axis. To this end, different DC voltages may be applied by the power supply to successive segments of at least one segmented electrode, that differ relative to each other so as to form a DC potential gradient along the ion optical axis configured for urging ions to travel in a selected direction along the ion optical axis.

[0039] Alternatively, or in addition, different RF voltages may be applied by the power supply to successive segments of at least one segmented electrode, that differ relative to each other so as to form pseudo-8501652

[0040] 5

[0041] potential gradient along the ion optical axis configured for urging ions to travel in a selected direction along the ion optical axis.

[0042] The plurality of electrodes may be disposed inside a collision cell configured for maintaining a buffer gas with said channel such that precursor ions guided long the channel produce product ion fragments by a process of collision-induced dissociation (CID) with the buffer gas.

[0043] The invention may provide a mass spectrometer comprising the ion transport apparatus.

[0044] In a second aspect, the invention provides a tandem mass spectrometry apparatus comprising:

[0045] an ion source for providing precursor ions;

[0046] a first mass analyser configured to apply a selection of precursor ions according to their mass-to-charge ratios;

[0047] a collision cell comprising an ion transport apparatus according to the invention in its first aspect for fragmenting at least some of the selected precursor ions to generate product ions of the fragmented precursor ions;

[0048] a second mass analyser configured to apply a process of mass analysis to the product ions.

[0049] Of course, it may be that product ions may be accompanied by any remaining unfragmented precursor ions which case the second mass analyser may be configured to apply a process of mass analysis to unfragmented precursor ions.

[0050] In a third aspect, the invention provides a method of ion transport comprising:

[0051] providing a power supply configured to supply RF voltages;

[0052] providing a plurality of electrodes spatially arranged collectively to define a volume extending along an ion optical axis to form a channel, and thereat receiving 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,

[0053] the plurality of electrodes comprises at least one pair of axially non-segmented electrodes that are spatially arranged to oppose each other across the ion optical axis, and at least one axially segmented electrode, wherein each of the at least one segmented electrode comprises an array of separate electrode segments that extends alongside the ion optical axis in which 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 segmented electrode extends alongside at least one said non-segmented electrode to position a given segment separation region alongside a non-segmented electrode;

[0054] thereby, within parts of the channel alongside the given segment separation region, shaping the radially-confining electric potential field to provide more kinetic energy to ions than is provided by the radially-confining electric field present within axially adjacent parts of the channel.8501652

[0055] 6

[0056] As noted above, the pseudo-potential may be a spatially static pseudo-potential. The RF voltage(s) may be scanned such that, as a consequence, the amplitude of the pseudo-potential is scanned. This may permit the method of ion transport to implement a method of mass filtering, if desired, in some examples. In such examples, the method of ion transport may provide a mass filtering method in the sense that this may permit an ion transport apparatus to change the transmitted m / z range.

[0057] The shaping of the radially-confining electric potential field may be such as to include a contribution from multipoles exceeding second-order that is greater than the contribution from such multipoles present within axially adjacent parts of the channel. The plurality of electrodes may comprise at least one pair of axially segmented electrodes, wherein the (each) pair comprises two axially segmented electrodes that are arranged to oppose each other across the ion optical axis.

[0058] The method may comprise supplying further RF voltages and / or DC voltages to the plurality of segmented electrodes to form within the channel an electric field configured for urging ions to travel in a selected direction along the ion optical axis.

[0059] The invention may provide a method of mass spectrometry comprising transporting ions according to the method of ion transport of the third aspect of the invention.

[0060] In a fourth aspect, the invention may provide a method of tandem mass spectrometry comprising:

[0061] providing precursor ions;

[0062] by a first mass analyser, applying a selection of precursor ions according to their mass-to-charge ratios;

[0063] providing a collision cell comprising an ion transport apparatus according to the invention in its first aspect;

[0064] transporting the precursor ions in the collision cell according to the invention in its third aspect, thereby fragmenting at least some of the selected precursor ions to generate product ions of the fragmented precursor ions;

[0065] by a second mass analyser, applying a process of mass analysis to the product ions.

[0066] Of course, it may be that product ions may be accompanied by any remaining unfragmented precursor ions which may also be subject to mass analysis by the second mass analyser.

[0067] Multipole Fields, Pseudo-potentials and Fringing Fields

[0068] Quadrupoles and quadrupole fields

[0069] A quadrupole field is expressed by its linear dependence on the coordinate position. In Cartesian coordinates, the quadrupole electric field is given by:

[0070] E = Eo( + ay + yz)8501652

[0071] 7

[0072] Here, E0,,a,y 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:

[0073] V-E = 0

[0074] This condition is satisfied when = - a,y = 0. The electrical potential corresponding to this field, obtained by spatially integrating the electric field, is:

[0075] 1 1

[0076] <!’ = --E0(Ax2+ cry2+ yz2) = — -E(lA(x2— y2)

[0077]

[0078] 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:

[0079] 1

[0080] A — —

[0081] (>

[0082] This gives:

[0083] w0 2

[0084]

[0085] :2^(x y

[0086] When used as a mass filter, the electrical potential (voltage), Wo / 2, is applied to one of the two pairs of electrodes and the electrical potential (voltage), -Wo / 2, is applied to the other one of the two pairs of electrodes. Here, Wois given by:

[0087] Wo= 2[U - Vcos(cot)]

[0088] 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:

[0089] rf2x / 6Z \

[0090] — - + I - 7 I [U — l / cos(<ijt)]x = 0

[0091] at2\mrg J

[0092] d2y ( cz \

[0093] — - — 2_Vcos(wt)]y = o

[0094]

[0095] dtzymr0)8501652

[0096] 8

[0097] Here, the quantity z is the charge of the ion in question, and e is the elementary charge. By defining the following parameters:

[0098] / QeU \

[0099] _ / 4eV \

[0100] Qx - -<7y- J

[0101]

[0102] / = (nt / 2

[0103] The equations of motion reduce to:

[0104] d2iz

[0105] — + [au- 2qucos(2^)]u = 0

[0106]

[0107] Here, the symbol u represents either x ory. 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 shown schematically in Figure 7. 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, ax yand 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:

[0108] ax y=constant) ■ qxy

[0109] 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 qxyof 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.

[0110] Higher-order fields and fringing fields

[0111] 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’.

[0112] Higher-order Fields

[0113] 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 of8501652

[0114] 9

[0115] amplitude Vnand frequency a>nare present, the electric potential field present within a volume surrounded by the electrodes of the quadrupole device can be expressed as:

[0116] Z / r\N

[0117]

[0118] N °C0SN~XU~ XVnC0S^a>n^t~tn)

[0119] This general form of equation is discussed in more detail in:

[0120] 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)

[0121] Further discussion can be found in:

[0122] 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)

[0123] The amplitudes Vnand frequencies

[0124]

[0125] may 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.

[0126] 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.

[0127] 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 <f> are polar coordinates, ANis a weighting factor and cpNand tnare phase factors. In cartesian coordinates, this may be expressed as:

[0128] U~ X

[0129]

[0130] VnC0S^a>n^t~

[0131] Ntn)

[0132] pN= Re{(x + iy)'v}

[0133] Here, i = V-l and the term Re{(x + iy)w} refers to the real component of the complex quantity ( + iy)'vNotably, for an ideal quadrupole field, and with only a single RF potential present with frequency a>, only the terms for N = 2 and n = 1 (i.e., a)r= a>, Vr= R) appear in the equation for the electric potential field , in which we may set A2= 1. All other terms are zero. This gives the quadrupolar potential field structure noted above, namely:

[0134] <p = - — [U - Vcos(a>t)]

[0135]

[0136] ro8501652

[0137] 10

[0138] 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 the same shape and dimensions arranged perfectly in parallel and perfectly symmetrically around the central longitudinal axis of the array.

[0139] 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:

[0140] d2x ( ze \z / ze\r, V9(PN

[0141] j - Vcos(wt)]x = - ( — ) [U ~ Vcos(a>t)] > AN— —

[0142] dt2\mrA vn' Z_i ox

[0143] d2y ( ze \ / ze\1d<p„ — - - j “ Vcos(wt)]y = - (— ) [U ~ Vcos(a)t)'] y AN— — dt2\mr, “ / \m' Z— i oy

[0144]

[0145] \ u / w>3

[0146] 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 (dpN / dx; dcpN / dy) of multipolar field components, cpN, 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-chare 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 / lw= 0 for all N > 2.

[0147] 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.

[0148] Fringing Fields

[0149] 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:

[0150] o = - — [U - Vcos(a>t)]

[0151]

[0152] ro

[0153] Here, 2r0is the shortest distance between opposing rods of the quadrupole ion guide, and where the expression: U - Vcos(a)t) 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. IT) and RF (i.e. ycos(wt)) components, where 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 terminal8501652

[0154] 11

[0155] 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.

[0156] 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, <t>FF, may be quantified as:

[0157] 2 2

[0158] ‘I’FF = ‘I’ / U) = - IV_Vcos(cot)]f(z)

[0159]

[0160] ro

[0161] 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:

[0162] / (z) = 1 - exp (-a[z - z0] - b[z - z0]2)

[0163] 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.

[0164] 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).

[0165] RF Heating

[0166] It is useful to describe the motion of guided, or trapped, ions in two distinct timescales. These are: RF-motion (also known as “micromotion”), which describes the oscillation synchronous with the RF field; and “secular motion”, which describes the motion in a quasi-static harmonic potential, known as the “pseudopotential”. The pseudo-potential approximation gives reasonable results when the RF motion amplitude is small compared to the characteristic dimension of the RF potential spatial variation. This is described in more detail below.

[0167] The total kinetic energy, ETotal, of an ion can be separated, approximately, into the energies corresponding to these two timescales:8501652

[0168] 12

[0169] ^Total — ERF + ^Secular

[0170] Here, ERFis the kinetic energy due to RF motion, and ESecularis the kinetic energy due to secular motion. The modes of secular motion and micromotion have different frequencies and may remain separated. Typically, the micromotion component of an ion’s motion is often neglected, as an approximation, when considering its dynamics, and this approximation is known as the “secular approximation” whereby the ions motion and energy are treated as if the ion experienced only an effective quasi-static harmonic potential, the pseudo-potential. However, when ions experience aperiodic motion due to irregularities in the pseudo-potential, the frequency spectra corresponding to secular motion and micromotion broaden and overlap. This allows energy from micromotion (see ERFabove) to be transferred to the secular motion (see ESecularabove). Thus, micromotion cannot be neglected in such circumstances, and the pseudopotential approximation is no longer entirely accurate. The transfer of energy from RF motion (micromotion) to secular motion, is known as “RF heating”.

[0171] Collision-induced dissociation, CID, is a mass spectrometry technique to induce fragmentation selected ions in a gas phase. The ions may be accelerated by applying an electrical potential to increase the ion kinetic energy and then allowed to collide with neutral molecules of a buffer gas. During the collision, some of the kinetic energy of a colliding ion is converted into internal energy of the ion, and this may result in the fragmentation of the ion. CID may be induced through the application of a supplemental AC signal in resonance with the secular frequency of the ion to be activated, a technique often termed ‘resonance excitation’. The pseudo-potential approximation gives reasonable results when the RF motion amplitude is small compared to the characteristic dimension of the RF potential spatial variation. The AC signal acts to increase the amplitude of the ion’s harmonic oscillation thereby increasing its maximum displacement from the regions where the pseudo-potential approximation is accurate. As this displacement occurs, the ions visit areas of higher RF field strength where they can absorb power from the RF field, in a process of “RF heating” described above.

[0172] The inventors have realised that an enhancement in the transfer of energy from the RF field to enhance the kinetic energy of a colliding ion, may be achieved without the use of supplemental AC signals in resonance with the secular frequency of the ion. Instead, this may be achieved by structuring the electrodes of an ion guide or ion trap to deliberately introduce irregularities in the pseudo-potential, in the form of higher-order field components, which cause ions to experience aperiodic motion leading to “RF heating”.

[0173] The Pseudo-potential

[0174] 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 underlying8501652

[0175] 13

[0176] 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):

[0177] F = — c r

[0178] 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:

[0179] F = -7

[0180] Given the force, we can calculate the potential by integrating once:

[0181] <$>\x,y,z) = -fax + py + yzz)

[0182]

[0183] where a, f> and y are constants that play the role ofc in three spatial directions. In anticipation of the discussion of trapping charged particles in electrostatic potentials, choose: a = - / ? = l,y = 0. With this choice, <t> forms a potential that has the shape of a saddle surface:

[0184] <t>(x,y) = ^(x2~ y2)

[0185]

[0186] 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:

[0187] mgh0

[0188] We obtain the expression of a gravitational saddle potential:

[0189] <,

[0190] >mgh

[0191] (x,y) =20

[0192] (x2

[0193] z-yz)

[0194] zr0

[0195] 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 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:

[0196] (x,y) = -y^-(xz-yz)

[0197]

[0198] zr0

[0199] The rotating saddle potential may be described in the laboratory frame by applying the standard coordinate transformation given by the rotation matrix:

[0200] / x'\ > / cos(cot) — sin(cot)\ / x\

[0201] \y'J \sin(cot) cos(cot) / \y)

[0202] This gives:8501652

[0203] 14

[0204] <$>(x,y, t) =2° {(x2— y2)cos(cot) — 2xysin(cot)}

[0205]

[0206] 2r0

[0207] Pictorially, one may visualise the time-variation of this potential as a rotation of the saddle surface around the vertical axis, with a frequency co 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 the 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 <t>(x,y, t). Rather, electric potentials in ion guides / traps are typically of a form:

[0208] cf

[0209] r(x,y, t)~ — (x2~ y2)cos(cot)

[0210] 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.

[0211] 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:

[0212] F = mr = —z < P(r)

[0213] 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 orquasi-static part, U(r), and a fast time-dependent oscillating part, V(r) cos(a>t) which oscillates with a frequency ar.

[0214] < I’(r) = t / (r) + V(r) cos(at)

[0215] 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. a> » 2TT / T. AS a result of this assumption, we obtain:

[0216] mr = —zV(U(r + V(r) cos it)) = —zVU(r — zVV(r) cos(a>t) = F0(r) + FKFr) cos( >t) The smooth particle trajectory due to the force F0(r) is modulated by an oscillating force FfiF(r) at frequency >.

[0217] Thus, we may write the total trajectory r(t) as a sum of a smooth part R(t) and rapidly oscillating part (t):

[0218] r(t) = R(t) + (t)8501652

[0219] 15

[0220] Typically, the amplitude of the oscillations will be much smaller than the smooth part of the trajectory R, i.e. | | « |7? |. This permits us to expand the forces F0(r) and FRF(r) in a Taylor series up to lowest order in the parameter as follows:

[0221] F0(R + 0 = F0(R + ■ FF0(R) + ■ ■ ■

[0222] FRFR + 0 = FRF(R) + ■ FFRF(R) + ■ ■ ■

[0223] Omitting negligible parts of the series, the equation of motion becomes:

[0224] m(F(t) + (t)) = F0(R + £(t) ■ FF0(R + [FRF(7?) + £(t) ■ VFRF(R ] cos(a>t) The result of the equation of motion for the oscillating part of the trajectory is given approximately by:

[0225] m^(t) = FRFcos(a>t)

[0226] The solution to this equation is:

[0227]

[0228] f(t)

[0229] By calculating the time average over: m(F(t) + ’(t)), over one period 2TT / < >, 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:

[0230] (

[0231]

[0232] m(F(t) + e(t))> = Fo(fi) + <e(t)> ■ + <\FRF(R) + £(t) ■ 7FRF(F)] cos (cot)) Given that:

[0233]

[0234] = 0, this reduces to:

[0235] ... ( cos2(cot))

[0236] mR(t) = Fo(7?) - FRF(R) ■ VFRF(R)

[0237]

[0238] Remembering that F is a conservative force, and (7 x FRF(R) = 0) this means that:

[0239] 1 FRF(R) ■ VFRF(R) = FRF(R) ■ VFRF(R) + FRF(R) x (7 x FfiF(7?)) = - 7(FRF(7?) • FfiF(7?))

[0240]

[0241] As a result, and noting that ( cos2(cot)) = 1 / 2, we may write:

[0242] 1

[0243] mR(t) = Fsec= F0(R) - -^^ F(FRF)2= -zVUsec

[0244]

[0245] This means that a “secular” force (Fsee) 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)

[0246] (FRF)2

[0247] u

[0248]

[0249] -= u°+^ =U°+ Ups

[0250] Here,

[0251] U

[0252]

[0253] ps4mco2

[0254] 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 “pseudo-8501652

[0255] 16

[0256] potential” is proportional to the square of the magnitude of the oscillating part of the potential because FflFoc uRF, and is also inversely proportional to the particle mass-to-charge ratio: mlz. Note also that because FflFoc z, then Upsoc z2, and the resulting force is independent of the sign of the charge on the charged particle in question.

[0257] The invention includes the combination of the aspects and preferred features described except where such a combination is clearly impermissible or expressly avoided.

[0258] Summary of the Figures

[0259] Embodiments and experiments illustrating the principles of the invention will now be discussed with reference to the accompanying figures in which:

[0260] Figure 1 shows a schematic view of a tandem mass spectrometry system.

[0261] Figure 2A shows a perspective view of the electrodes of an ion transport apparatus of the tandem mass spectrometry system of Fig. 1.

[0262] Figure 2B shows a cross-sectional view of the electrodes of the ion transport apparatus of Fig. 2.

[0263] Figure 2C shows a side view of the electrodes of the ion transport apparatus of Fig. 2.

[0264] Figure 3A shows a cross-sectional view of the electrodes of the ion transport apparatus of Fig. 2B, with voltages applied.

[0265] Figure 3B shows a cross-sectional view of the electrodes of the ion transport apparatus of Fig. 2B, with voltages applied, having a different phase / sign at some electrodes as compared to those shown in Fig.

[0266] 3A.

[0267] Figure 4A shows a cross-sectional view of the electrodes of an ion transport apparatus.

[0268] Figure 4B shows a side view of the electrodes of the ion transport apparatus of Fig. 4A.8501652

[0269] 17

[0270] Figure 5A shows a graphical view of the variation in ion kinetic energy as a function of position along an ion transport apparatus according to an example of the invention.

[0271] Figure 5B shows a graphical view of the variation in ion kinetic energy as a function of position along a conventional ion transport apparatus. These results are generated by numerical simulation of ions in an ion transport apparatus.

[0272] Figure 6A shows a graphical view of the variation in ion travelling time along an ion transport apparatus. These results are generated by numerical simulation of ions in an ion transport apparatus.

[0273] Figure 6B shows a graphical view of the variation in ion travelling time along an ion transport apparatus. These results are generated by numerical simulation of ions in an ion transport apparatus.

[0274] Figure 7 shows a “stability diagram” for a quadrupole device.

[0275] Detailed Description of the Invention

[0276] 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.

[0277] Examples of the invention disclosed herein relate to an ion transport apparatus fortransporting ions at relatively high gas pressure, which can be used to dissociate ions by a collision-induced dissociation, CID. The examples disclosed herein relate to a mass spectrometer.

[0278] Referring to Fig. 1, the ion transport apparatus 107 comprises a plurality of elongate electrodes defining an elongate volume with an ion optical axis 113. Among these electrodes, one or more multi-piece segmented rod electrodes 207, 211 etc., are segmented in the direction of the ion optical axis, and the other rod electrodes 205, 209, etc., are single-piece non-segmented rod electrodes. A controller 111, comprising a power supply, is configured to apply RF and DC voltages to these electrodes, such that an RF pseudo-potential is provided to confine ions radially (in a direction perpendicular to the ion optical axis), and such that an electric field is generated to accelerate ions to travel along the ion optical axis. The segmented rod electrodes and non-segmented rod electrodes may generate an RF pseudo-potential that varies in strength and form along the ion optical axis so as to introduce into the electric potential field of the pseudo-potential an increased amount of high-order field components within and near each one of a plurality of segment separation regions defining gaps, Az, between adjacent electrode segments of the segmented electrodes.8501652

[0279] 18

[0280] Ions may gain additional kinetic energy from an “RF heating” process caused by the high-order field components, and this kinetic energy can be transferred into the internal energies of ions, resulting in higher probability of ion fragmentation by collisions with a buffer gas (“CID gas”) present within the ion transport apparatus 107. This allows better fragmentation efficiency and thus higher sensitivity for mass analysis. In addition, the controller may provide voltages (e.g., DC or RF voltages) to the electrodes (e.g., to the segmented electrodes) to form an electric field for accelerating ions to travel along the ion optical axis. This may be achieved by applying different DC or RF voltages to the different electrode segments of the segmented rod electrodes. This acceleration may moderate the ions' slowdown due to gas damping at high buffer gas pressures.

[0281] The ion transport apparatus may have multipole geometry in which N poles of electrodes are arranged in a rotationally symmetrical manner with respect to the ion optical axis, where N may be integer greater than or equal to two and even number ( e.g. 4, 6, 8, etc) is preferred. The field radius, r0, defined as the shortest distance between the ion optic axis 113 to the electrodes, may be identical to (or approximately the same as) for all of the rod electrodes. The segmented rod electrodes are composed of two or more electrode rod segments that are separated in the direction, Az, of the ion optical axis by either open gaps or gaps filled by spacers (not shown) formed from non-conducting materials. The length of each segmented rod electrode can be defined as the sum of the lengths of its constituent electrode rod segments, and the gaps between the adjacent segments. The length of each segmented electrode may be identical to (or approximately the same as) that of each single-piece non-segmented rod electrode. The lengths of each of the electrode rod segments forming a given segmented electrode may be same as each other, or may be different from one or more of the other electrode rod segments forming the given segmented electrode. In some examples, the electrode rod segment forming a given segmented electrode segmented near the ion outlet of the ion transport apparatus (i.e., ion travel path output end) is shorter than those near the inlet of the apparatus. The number of segmented rod electrodes present in the ion transport apparatus may be equal to or greater than one (1), and smaller than N (where N is total number of the poles). It is preferred that the geometry, or spatial arrangement, of the segmented rod electrodes collectively has a rotational symmetry with respect to the ion optical axis. The rod electrodes, and rod segments, can have cross sectional shapes selected from: cylinder, hyperbola, planar or polygon.

[0282] Figure 1 schematically illustrates a tandem mass spectrometer that uses the disclosed ion transport apparatus as a collision cell 107. It is to be understood that this example illustrates components of an apparatus for tandem mass spectrometry in which certain components, such as a vacuum pump serving a vacuum chamber 115, are omitted from the illustration merely to aid clarity but are to be understood as being present.

[0283] The ion transport apparatus within the collision cell 107 comprises a power supply within, and controlled by, controller 111 to supply RF voltages. A plurality of electrodes 201, 203, 205, 207, 209, 211, 213, 215 (see Fig. 2), are spatially arranged collectively to define a volume extending along an ion optical axis 113 to form a channel. They are configured to receive respective RF voltages from the power supply for8501652

[0284] 19

[0285] generating a radially-confining electric potential field forming a spatially static pseudo-potential within the channel for guiding ions therealong. The plurality of electrodes comprises at two pairs of axially nonsegmented electrodes (201, 209 forming a first pair; 205, 213 forming a second pair - see Fig. 2), that are spatially arranged to oppose each other across the ion optical axis, and two pairs of axially segmented electrodes (207, 215 forming a first pair; 203, 211 forming a second pair - see Fig. 2).

[0286] Each of the segmented electrodes comprises an array of separate electrode segments that extends alongside the ion optical axis in which each electrode segment is elongated to extend alongside the ion optical axis 113 whereby successive electrode segments are separated by a segment separation region, Az. The segmented electrodes each extend alongside two neighbouring non-segmented electrodes to position a given segment separation region Az alongside a non-segmented electrode.

[0287] When the RF voltages are received from the power supply by the plurality of electrodes, the given segment separation region shape the radially-confining electric potential field within the channel to include a contribution from multipoles exceeding second-order that is greater than the contribution from such multipoles present within axially adjacent parts of the channel. Accordingly, the enhanced contribution from multipoles exceeding second-order may cause an enhanced RF heating effect may be applied to the ions.

[0288] Consequently, an RF pseudopotential field may be provided that varies along the ion optical by comprising high order components of the RF pseudopotential field, and thereby provide more RF heating to ions and thus increases ion kinetic energy in the radial direction. This allows to enhance ion fragmentation efficiency.

[0289] When the RF voltages are received from the power supply, from the controller 111, by the plurality of electrodes, a given segment separation region Az shapes the radially-confining electric potential field within the channel to provide more kinetic energy to ions than is provided by the radially-confining electric potential field present within axially adjacent parts of the channel. In this way, an enhanced RF heating effect may be applied to the ions. This ion transport apparatus is located within the collision cell 105 to as to provide a collision cell apparatus.

[0290] Thus, the disclosed ion transport apparatus can be used as an improved collision cell. The RF pseudopotential field is shaped to vary along the ion optical axis, and this variation is generated by the asymmetric geometry of segmented electrodes and the non-segmented electrodes. This allows ions to experience more RF heating and gain higher kinetic energy in the radial direction. As a result, it is possible to improve ion fragmentation efficiency.

[0291] An electric field for accelerating ions to travel along the direction of the ion optical axis may be generated, as desired, by applying appropriate direct current (DC) or RF voltages to segmented rod electrodes. An electric field for accelerating ions towards the ion optical axis can reduce ions’ travelling time through the apparatus. It is possible to prevent a ghost peak caused by the stay of the ions in collision cell, and to8501652

[0292] 20

[0293] decrease a delay time between two events / uses of the device. As a result, higher sensitivity and higher duty cycle can be achieved. An electric field for accelerating ions to travel along the ion optical axis can be provided to moderate the ions' slowdown due to gas damping at high pressure and decrease delay times. It also allows users to apply higher buffer gas pressure in the apparatus, resulting in higher ion fragmentation efficiency. Therefore, the sensitivity of the mass analysis can be improved.

[0294] 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 along a central longitudinal axis of the apparatus to a first mass analyser 105. The first mass analyser 105 is configured for selecting precursor ions according to their mass-to charge ratios. The collision cell apparatus provides a fragmentation device 107 for fragmenting the selected precursor ions into product ions and for transmitting ions along the ion optic axis 113. A second mass analyser 109 is configured for analysing the product ions and the unfragmented precursor ions transmitted by the collision cell apparatus 107. The controller 111 is also configured for applying RF and DC voltages to these components for mass analysis.

[0295] The ion source 101 comprise an electrospray ionisation, ESI, source, or an atmospheric pressure chemical ionisation, APCI, source, or an atmospheric pressure photo-ionisation, APPI, or a desorption electrospray ionisation, DESI, source, for example, or a PESI source or a MALDI ion source. The ion optics 103 may include one or more ion guides, e.g., multipole rods or stacked-ring ion guides. Differential pumping may be used to produce a pressure gradient from an atmospheric pressure region at the ion source to a vacuum region for mass analysis components.

[0296] The first mass analyser 105 may comprise a mass filter, an ion trap or a magnetic sector mass spectrometer that selects precursor ions according to their mass-to-charge ratios. When a mass filter is used as the first mass analyser, quadrupole / resolving DC and RF voltages may be applied to quadrupole rod set to allow ions with a selected m / z to pass through the mass filter, and other ions to be filtered out by colliding with electrodes. The fragmentation device 107 comprises the disclosed ion transport apparatus, an ion inlet aperture, an ion outlet aperture, and a buffer gas supply. Product ions can be generated from fragmentations of precursor ions at relatively high pressure. The second mass analyser 107 may be a mass filter, an ion trap, a magnetic sector mass spectrometer, TOF mass analyser, orbitrap, or other mass analyser.

[0297] Figure 2 schematically illustrates a first embodiment of the ion transport apparatus. It includes eight (8) poles of electrodes surrounding the ion optics axis 113, in which four (4) of the electrodes are segmented rod electrodes (203, 207, 211 and 215) each of which is segmented into a plurality (four in this example) of electrode rod segments separated and arranged in linear succession in the direction of the ion optics axis 113. The other four poles of electrodes (201, 205, 209 and 213) are each single-piece nonsegmented electrodes. The segmented rod electrodes are illustrated in dashed line form in a front view of Fig. 2B, and rod electrode segments of the segmented rod electrodes are shown in the 3D perspective view of Fig. 2A amongst the non-segmented rod electrodes.8501652

[0298] 21

[0299] The segmented rod electrode 207 is segmented into a plurality of short rod electrode segments (207a, 207b, 207c and 207d) in the direction of the ion optics axis 113 in this example of Fig. 2C; the other rod electrode segments (203, 211 and 215) are segmented in the same manner of 207. The segmented rod electrodes (203, 207, 211 and 215) and the non-segmented electrodes (201, 205, 209 and 213) have the same field radius r0and the same axial length along the ion optics axis 113 in this example. RF voltages can be applied in different ways to generate either an octupole or a quadrupole potential field as the main component of RF pseudo-potential to confine ions in the radial direction that is perpendicular to the ion optical axis 113, as illustrated by Fig.3. Here, the symbols “RF+” and “RF-” in Fig. 3 illustrate the two RF voltages that have the same frequency, the same (or very similar) amplitudes, and a phase difference of 180 degrees (denoted by the opposite signs + / -).

[0300] This RF pseudo-potential varies with position of the ion optic axis and thus can generate the field of higher order components (i.e., higher than quadrupole field). As a result, ions can experience more RF heating and gain more kinetic energy when they travel through such ion transport apparatus than a conventional octupole ion guide.

[0301] The increased kinetic energy can be transferred into ion internal energy when ions collide with buffer gases, and thus this allows better fragmentation efficiency. Different DC voltages can be applied to the successive segments of one or more of the segmented rod electrodes thereby providing an electric field for accelerating ions to travel through the apparatus (i.e., a potential gradient along the ion optical axis). For example, when respective DC voltages of 3V, 2V, 1V and 0V are applied to rod segments 207a, 207b, 207c and 207d respectively, and to the other segmented rod electrodes in the same manner, a potential difference of about 1,5V can be generated along the ion optic axis 113. Ions that have large radial displacement may feel a stronger accelerating force than ions in the ion optic axis.

[0302] Alternatively, the electric field for accelerating ions can also be generated by the gradient of the RF pseudo-potential. This may be achieved by applying different RF voltages (e.g., voltage amplitudes) to different respective rod segments of the segmented rod electrodes.

[0303] These electric fields can urge ions to travel more quickly through this apparatus than in a typical I conventional octupole CID cell. This can effectively address the problem of ions slow-down at high buffer gas pressure. In addition, the ion transport apparatus can be operated at higher pressure than a conventional collision cell, which can provide a shorter ion travelling time and higher fragmentation efficiency. A voltage source may be configurated to apply the RF and DC voltages to the electrodes in the manner described above.

[0304] Fig.4 schematically illustrates a second embodiment of the ion transport apparatus. It includes four poles of electrodes surrounding the ion optics axis 113, in which two segmented rod electrodes (303 and 307) are segmented into a plurality (4 in this example) of short rod segments in the direction of the ion optics axis 113. The other two poles of electrodes (301 and 305) are single-piece non-segmented electrodes. Fig. 4A illustrates the segmented rod electrodes (303 and 307) in dashed line form, and Fig. 4B shows that the segmented rod electrode 303 compromises four rod segments: 303a, 303b, 305c and 307d.8501652

[0305] 22

[0306] Although it is not shown, it must be understood that segmented rod electrode 307 is segmented in a similar manner as 303.

[0307] A voltage source (not shown) can be configurated to apply the first RF voltage (RF+) to the pair of two non-segmented rod electrodes 301 and 305, and the second RF voltage (RF-) to all of the segments of the pair of two segmented rod electrodes of 303 and 307, such that a quadrupole RF pseudo-potential can be provided to confine ions in the direction perpendicular to the ion optical axis 113. The first RF voltage (RF+) and second RF voltage (RF-) may have the same frequency, the same (or similar) amplitude, and a phase difference of 180 degrees, which can be generated by one shared RF power supply. In a manner similar to that of the first embodiment, the second embodiment may generate the RF pseudo-potential varying along the ion optic axis 113 and thus can give higher ion kinetic energy than a conventional collision cell based on a quadrupole ion guide. As a result, better fragmentation efficiency can be obtained. Different DC or RF voltages can be applied to the segmented rod electrodes of one or more segmented rod electrodes (e.g. 303a, 303b, 303c and 303d) to provide an electric field for accelerating ions in a similar manner of the first embodiment. The ions slowdown problem can be reduced, and fragmentation efficiency can be improved similarly as the first embodiment. A voltage source can be configurated to apply the RF and DC voltages to the electrodes of the ion transport apparatus.

[0308] In the examples of the first and second embodiment, the segmented rod electrodes, e.g. 207 and 303, are divided into four short rod electrode segments, and each segment (207a, 207b, 207c and 207d) has the same length. It should be understood that the number of rod electrode segments is not limited to four, and the length of these segmented rods can be identical or different to each other. Preferably, the rod electrode segments located at / nearthe outlet aperture of the io transport apparatus are shorter than those located at / nearthe inlet aperture of the apparatus. These rod electrode segments may be separated in the direction of ion optical axis 113 either by material-free gaps or by gap filled with a nonconducting material. The number of segmented rod electrodes (that are segmented in the direction of the ion optic axis) is not limited to two (2) or four (4), and may be equal to or greater than one (1) and smaller than N, where N is the total number of poles surrounding the ion optical axis. It is preferred that the geometry of virtual rod electrodes has a rotational symmetry with respect to the ion optical axis. The two examples illustrate an octupole geometry and a quadrupole geometry that are partially segmented in the direction of the ion optical axis, and other multipole ion guide can also be partially segmented and operated in a similar way, such as hexapole, 12-pole, etc.

[0309] The ion transport apparatus may be operated at relatively high pressure for a collision cell to effectively fragment ions. Atypical pressure range is from about 1 mTorrto about 20 mTorrwith a buffer gas of nitrogen, air or argon. A gas flow can also be generated in the same direction of the ion optical axis to assist ion travel more quickly through this apparatus. When the optimal electric field is provided for accelerating ions, higher pressure can be used than a convention CID cell; the higher pressure can further enhance the ion fragmentation efficiency and improve the sensitivity of the mass analysis.8501652

[0310] 23

[0311] When the ion transport apparatus is used as a collision cell in q-TOF instrument, i.e., quadrupole time-of-flight, ion accumulation can be performed by this apparatus. Take the first embodiment as an example, ions could be accumulated in the region near the rod electrode segment 207d, 211d and so on by applying a DC barrier to the exit aperture of the collision cell. Then this DC barrier can be lowered, and an accelerating voltage can be optionally applied to this exit aperture to allow the accumulated ions to travel through the exit aperture and towards the extraction region of a TOF device. By synchronising the voltage applied to the exit aperture and extraction voltage of TOF, the duty cycle of TOF can be greatly increased, resulting in better sensitivity of mass analysis.

[0312] The invention may thus relate to tandem mass spectrometry comprising providing precursor ions, providing selections of precursor ions according to their mass-to-charge ratios by the first mass analyser, providing the process to fragment some of the selected precursor ions and generate the product ions of the fragmented precursor ions in a collision cell, and applying a process of mass analysis to the product ions and unfragmented precursor ions by the second mass analyser. The collision cell may include the ion transport apparatus disclosed herein.

[0313] In the aforementioned examples, the ion transport apparatus is provided in the collision cell. It is also possible to apply such apparatus to transmit ions at relative high pressure or to fragment ions in the application of in-source fragmentation. In these cases, the apparatus can be used downstream of the ion source and upstream of the first mass analyser. Higher performance can be expected in a similar manner as described above.

[0314] A simulation showing an increase in ion kinetic energy

[0315] An ion transport apparatus of the first embodiment was simulated with the following geometry:

[0316] A field radius of r0= 2.5 mm was used;

[0317] The radius of cylinder rods was 1 mm;

[0318] The length of ion transport apparatus was 150 mm;

[0319] The segmented rod electrodes were segmented into ten (10) short rod segments of 14 mm in length;

[0320] The gap, Az, between the two adjacent rod segments was 1 mm;

[0321] An RF voltage of 2.3 MHz frequency and 275 V (zero-to-peak, ground-to-pole) amplitude was applied to confine ions radially;

[0322] A single ion of reserpine (609 Th) was simulated with 1 eV initial kinetic energy in the radial direction, and collisions with buff gas were disabled to better demonstrate the change of ion kinetic energy.

[0323] Fig. 5A shows the ion kinetic energy in the radial direction when the ion travel to different positions along the ion optic axis. The maximum ion kinetic energy value achieved is about 3.6 eV.8501652

[0324] 24

[0325] Fig. 5B shows similar data of Fig. 5A based on a conventional collision cell. The maximum kinetic energy in the radial direction is about 2 eV, which is much smaller than that of the present ion transport apparatus, which lacks the effects of RF heating occurring in the circumstances of the present ion transport apparatus as described with reference to Fig. 5A.

[0326] A simulation showing a reduction in ions slow-down at high pressure

[0327] An ion transport apparatus of the first embodiment was simulated with the following geometry:

[0328] A field radius of r0= 2.5 mm was used;

[0329] The radius of cylinder rods was 1 mm;

[0330] The length of ion transport apparatus was 150 mm;

[0331] The segmented rod electrodes were segmented into ten (10) short rod segments of 14 mm in length;

[0332] The gap, Az, between the two adjacent rod segments was 1 mm;

[0333] An RF voltage of 2.3 MHz freguency and 275 V (zero-to-peak, ground-to-pole) amplitude was applied to confine ions radially;

[0334] Reserpine ions, 609 Th and 610 Th, were simulated, which had a Normal / Gaussian distribution of time of birth with an average of 3 ms and 4 ms respectively, and a standard deviation of 0.2 ms. The arrival time of these ions that pass though the ion transport apparatus was recorded. Argon was used as buff gas at a pressure of 5 mTorr, and the collision energy was 30 eV.

[0335] When a zero (0) Volt DC gradient voltage is applied to the segmented rod electrodes, ions can take tens of ms to travel through the apparatus, as shown by Fig. 6A. Ions also have wide spread of travelling time, and more than half of ions still stay in the ion transport apparatus when the simulation stops at 20 ms. It should be understood that the conventional collision cell suffers from the same problem of ions’ slowdown and has a similar ion travelling time in this condition.

[0336] Fig. 6B shows simulation results when a 4V DC gradient voltage is applied to the segmented rods, ions take about averaged 1 ms to travel though the 150 mm long apparatus and the peak width at half maximum is about 1.2 ms (initial ion distribution has 0.48 ms peak width for the distribution of the birth time). Each ion has averaged 180 collisions with argon gas before passing through the apparatus, which provides a good probability to generate product ions. Comparing with Fig. 6A, the ion travelling time can be greatly reduced with a much narrower spread in this condition. By tuning the DC gradient voltage and the pressure, the fragmentation efficiency may be further improved.

[0337] When the ion transport apparatus is operated as a collision cell, a pressure range from 1 mTorr to 20 mTorr should be used with buff gas of nitrogen, air or argon.

[0338] The pressure of the ion transport apparatus should be between 1 mTorr to 20 mTorr when nitrogen or argon is used as buff gas. The optimal pressure is estimated in a range between 3 mTorr to 15 mTorr.8501652

[0339] 25

[0340] The length of the ion transport apparatus should be in the range of 100 mm to 250 mm. The filed radius, r0, of the ion transport apparatus should be between 1 mm to 10 mm. The length of the segmented rod electrodes can be from 2r0to 50ro.

[0341] 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.

[0342] 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.

[0343] 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.

[0344] Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0345] 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.

[0346] 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 range 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%.

[0347] References

[0348] 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.

[0349] [1] Peter H Dawson: “Quadrupole Mass Spectrometry and its applications”, 1st Edition - January 1, 1976 - Elsevier, ISBN: 978-0-444-41345-18501652

[0350] 26

[0351] [2] Mikhail Yavor: “Optics of Charged Particle Analyzers” in “Advances in Imaging and Electron Physics”, Volume 157, Pages 1-381 (2009)

Claims

850165227Claims:

1. An ion transport apparatus comprising:a power supply configured to supply RF voltages;a plurality of electrodes spatially arranged collectively to define a volume extending along an ion optical axis to form a channel, and 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; and,the plurality of electrodes comprises at least one pair of axially non-segmented electrodes that are spatially arranged to oppose each other across the ion optical axis, and at least one axially segmented electrode;wherein each of the at least one segmented electrode comprises an array of separate electrode segments that extends alongside the ion optical axis in which 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 segmented electrode extends alongside at least one said non-segmented electrode to position a given segment separation region alongside a nonsegmented electrode;whereby, when said RF voltages are received from the power supply by the plurality of electrodes, the given segment separation region shapes the radially-confining electric potential field within the channel to provide more kinetic energy to ions than is provided by the radially-confining electric potential field present within axially adjacent parts of the channel.

2. An ion transport apparatus according to any preceding claim wherein when said RF voltages are received from the power supply by the plurality of electrodes, the given segment separation region shapes the radially-confining electric potential field within the channel to include a contribution from multipoles exceeding second-order that is greater than the contribution from such multipoles present within axially adjacent parts of the channel.

3. An ion transport apparatus according to any preceding claim comprising and at least one pair of said axially segmented electrodes that are arranged to oppose each other across the ion optical axis.

4. 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.8501652285. 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.

6. 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.

7. An ion transport apparatus according to any preceding claim wherein the total number of electrodes comprising the plurality of electrodes is an even number.

8. An ion transport apparatus according to any preceding claim 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.

9. 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.

10. An ion transport apparatus according to any preceding claim wherein the length of a terminal segment of each segmented electrode is shorter than the length of all axially preceding segments thereof.

11. An ion transport apparatus according to any preceding claim wherein each segmented electrode comprises no more than ten segment separation regions.

12. An ion transport apparatus according to any preceding claim wherein each segmented electrode comprises no more than five segment separation regions.

13. An ion transport apparatus according to any preceding claim wherein, when said RF voltages are received from the power supply by the plurality of electrodes, the given segment separation region shapes the radially-confining electric potential field upon the ion optical axis to include a contribution from multipoles exceeding second-order that is greater than the contribution of such multipoles present on adjacent parts of the ion optical axis.

14. 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.85016522915. 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.

16. An ion transport apparatus according to any preceding claim wherein the plurality of electrodes are linear.

17. An ion transport apparatus according to any preceding claim wherein the power supply is configured to supply further RF voltages and / or DC voltages to the plurality of segmented electrodes to form within the channel an electric field configured for urging ions to travel in a selected direction along the ion optical axis.

18. An ion transport apparatus according to claim 17 wherein the power supply is configured to supply different DC voltages to successive segments of at least one segmented electrode that differ relative to each other so as to form a DC potential gradient along the ion optical axis configured for urging ions to travel in a selected direction along the ion optical axis.

19. An ion transport apparatus according to claim 17 wherein the power supply is configured to supply different RF voltages to successive segments of at least one segmented electrode that differ relative to each other so as to form pseudo-potential gradient along the ion optical axis configured for urging ions to travel in a selected direction along the ion optical axis.

20. 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 precursor ions guided long the channel produce product ion fragments by a process of collision- induced dissociation (CID) with the buffer gas.

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

22. 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 comprising an ion transport apparatus according to any preceding claim, for fragmenting at least some of the selected precursor ions to generate product ions of the fragmented precursor ions;a second mass analyser configured to apply a process of mass analysis to the product ions.85016523023. A method of ion transport comprising:providing a power supply configured to supply RF voltages;providing a plurality of electrodes spatially arranged collectively to define a volume extending along an ion optical axis to form a channel, and thereat receiving 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,the plurality of electrodes comprises at least one pair of axially non-segmented electrodes that are spatially arranged to oppose each other across the ion optical axis, and at least one axially segmented electrodes, wherein each of the at least one segmented electrode comprises an array of separate electrode segments that extends alongside the ion optical axis in which 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 segmented electrode extends alongside at least one said non-segmented electrode to position a given segment separation region alongside a non-segmented electrode;thereby, within parts of the channel alongside the given segment separation region, shaping the radially-confining electric potential field to provide more kinetic energy to ions than is provided by the radially-confining electric potential field present within axially adjacent parts of the channel.

24. A method of ion transport according to claim 22 when said RF voltages are received from the power supply by the plurality of electrodes, the given segment separation region shapes the radially- confining electric potential field within the channel to include a contribution from multipoles exceeding second-order that is greater than the contribution from such multipoles present within axially adjacent parts of the channel.

25. A method of ion transport according to any of claims 23 and 24 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.

26. A method of ion transport according to any of claims 23 and 25 comprising supplying further RF voltages and / or DC voltages to the plurality of segmented electrodes to form within the channel an electric field configured for urging ions to travel in a selected direction along the ion optical axis.

27. A method of mass spectrometry comprising the method of ion transport according to any of claims 23 to 26.85016523128. 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 22; transporting the precursor ions in the collision cell according to the method of any of claims 23 to 26, thereby fragmenting at least some of the selected precursor ions to generate product ions of the fragmented precursor ions;by a second mass analyser, applying a process of mass analysis to the product ions.

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