Mass spectrometry in mass filter mode or linear ion trap mode

Abstract

A mass spectrometer apparatus comprising a power supply (119), first and second sets of electrodes (107, 109) defining first and second channels, and a control unit (117). The power supply is controlled to switch selectively between first and second modes. In the first mode, a mass-resolving DC voltage is combined with RF voltages to constrain the mass-to-charge ratio of ions transmitted via the first channel. Ions selectively transmitted are subsequently received in the second channel for transmission. In the second mode, a DC voltage is applied to the ion lens to define an electric potential field configured to combine with a fringing field component of the second channel to form a potential barrier to trap ions within the second channel. Changing the radially-confining electric potential of the second channel increases the kinetic energy of trapped ions to overcome the potential barrier selectively according to their mass-to-charge ratio, m / z, thereby mass-selectively axially ejecting trapped ions.

Description

[0001] MASS SPECTROMETRY

[0002] Field of the Invention

[0003] The present invention relates to mass spectrometry.

[0004] Background

[0005] A mass selective axial ejection method for a linear ion trap (LIT) may use fringing fields near the exit end of LIT to couple the various degrees of freedom of ion motion and to perform axial ejections of excited ions. The fringing fields allow radial energy of ions can be transferred into axial energy. Ions may be resonantly excited into large radial displacements to gain axial kinetic energy sufficient to overcome the barrier potential at the end of LIT and to escape from it. However, the optimal electrode axial length of a mass filter and that of a linear ion trap can be quite different (e.g., the length of a quadrupole rod set). A mass filter requires ions to experience a sufficient number if cycles of an RF confining field in order to be able to achieve good mass resolution, and thus typically has electrodes of axial length of between 120mm and 200 mm for use in a mass range from 50 Th to 2000 Th.

[0006] By contrast, a linear ion trap with axial ejection, electrodes of axial length of 120 mm or longer can be expected to decrease ion ejection efficiency and sensitivity because only ions near the fringing fields are likely to be ejected. The optimal axial length for electrodes of a LIT is estimated to be not more than about 90mm, and typically shorter depending upon the scan speed of the LIT operation.

[0007] This means that the requirements of a mass filter often conflict with those of an LIT.

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

[0009] Summary of the Invention

[0010] In a first aspect, the invention may provide a mass spectrometer apparatus comprising:

[0011] a power supply;

[0012] a first set of electrodes spatially arranged collectively to define a volume extending along an ion optical axis to form a first channel, and configured to receive respective first RF voltages from the power supply for defining a radially-confining electric potential field within the first channel for guiding ions therealong;

[0013] a second set of electrodes spatially arranged collectively to define a volume extending along the ion optical axis to form a second channel spaced from the first channel for receiving ions transmitted by the first channel, and configured to receive respective second RF voltages from the power supply for defining a radially-confining electric potential field within the second channel for guiding ions therealong;

[0014] an ion lens arranged upon parts of the ion optical axis extending from the second channel and configured to define an electric potential field for manipulating ions guided by the second channel when in receipt of a voltage from the power supply;8451551

[0015] 2

[0016] a control unit configured to control the power supply to switch selectively between:

[0017] a first mode in which a mass-resolving DC voltage is combined with the first RF voltages to constrain the mass-to-charge ratio of said ions transmitted by the first channel, whereby only those ions selectively transmitted by the first channel are subsequently received in the second channel for transmission thereby; and,

[0018] a second mode in which a DC voltage is applied to the ion lens to define an electric potential field configured to combine with a fringing field component of the electric potential field of the second channel to form a potential barrier configured to trap ions within the second channel, and in which a change in the radially-confining electric potential of the second channel is applied to increase the kinetic energy of trapped ions so as to overcome the potential barrier selectively according to their mass-to-charge ratio, m / z, thereby mass-selectively axially ejecting trapped ions through the potential barrier.

[0019] The dynamics of mass-resolving ion transmission and mass-selective axial ejection of trapped ions is discussed in detail below in terms of Multipole Fields, Pseudo-potentials and Fringing Fields.

[0020] The control unit may be configured to control the power supply in the second mode for a first time period to maintain the radially-confining electric potential field within the second channel without applying the change thereto such that ions are accumulated in the second channel without axial ejection therefrom, and for a subsequent second time period to apply said change to the radially-confining electric potential field within the second channel.

[0021] The control unit may be configured to control the power supply in the second mode to apply one or more AC auxiliary voltages to electrodes of the second set of electrodes therewith to apply said change to the radially-confining electric potential field within the second channel to excite radial motion of trapped ions therein.

[0022] The control unit may be configured to control the power supply in the second mode to apply to electrodes of the second set of electrodes said one or more AC auxiliary voltages so as to generate a dipolar electric potential field in the second channel.

[0023] An amplitude and / or the frequency of said one or more AC auxiliary voltages may differ from an amplitude and / or a frequency, respectively, of said second RF voltages applied simultaneously to the second set of electrodes to generate the radial trapping potential field in the second channel.

[0024] The control unit may be configured to control the power supply in the second mode to apply to electrodes amongst the second set of electrodes said one or more AC auxiliary voltages having a frequency that corresponds to a frequency of resonant ion motion in the second channel thereby to excite such resonant ion motion.

[0025] The control unit may be configured to control the power supply such that in the second mode a DC offset voltage is applied, to one or more of the first set of electrodes and the second set of electrodes thereby to8451551

[0026] 3

[0027] generate, together with said DC voltage applied to the ion lens, a trapping potential field configured to trap ions in the axial direction within the second channel.

[0028] The control unit may be configured to control the power supply such that in the second mode no massresolving DC voltage is applied to second set of electrodes.

[0029] The second set of electrodes and the ion lens may define a linear ion trap when the control unit is switched to the second mode.

[0030] The axial length of the first set of electrodes may be greater than the axial length of the second set of electrodes such that the length of the first channel may exceed the length of the second channel.

[0031] The axial length of the first set of electrodes may be between about 100mm to about 250mm.

[0032] The axial length of the second set of electrodes may be between about 20mm and about 90 mm.

[0033] In the first mode, the control unit may be arranged to control the mass-resolving DC voltage and the first RF voltages applied thereto to provide a mass filter having a mass transmission range of between about 50 Th and about 8000 Th.

[0034] The mass spectrometer apparatus may further comprise a third set of electrodes spatially arranged collectively to define a volume extending along the ion optical axis to form a third channel spaced from the second channel for receiving ions transmitted by the second channel and configured to receive respective third RF voltages from the power supply for defining a radially-confining electric potential field within the third channel for guiding ions therealong.

[0035] The first set of electrodes and / or the second set of electrodes and / or the third set of electrodes may each comprises a quadrupole rod set.

[0036] The control unit may be configured to control the power supply to switch selectively between said first mode, said second mode and a third mode in which both the first mode and the second mode are implemented simultaneously thereby to provide a mass filter in the first channel and concurrently a linear ion trap in the second channel.

[0037] In a second aspect, the invention may provide a method for mass spectrometry comprising:

[0038] providing a power supply;

[0039] providing a first set of electrodes spatially arranged collectively to define a volume extending along an ion optical axis to form a first channel, and configured to receive respective first RF voltages from the power supply for defining a radially-confining electric potential field within the first channel for guiding ions therealong;8451551

[0040] 4

[0041] providing a second set of electrodes spatially arranged collectively to define a volume extending along the ion optical axis to form a second channel spaced from the first channel for receiving ions transmitted by the first channel, and configured to receive respective second RF voltages from the power supply for defining a radially-confining electric potential field within the second channel for guiding ions therealong;

[0042] providing an ion lens arranged upon parts of the ion optical axis extending from the second channel and configured to define an electric potential field for manipulating ions guided by the second channel when in receipt of a voltage from the power supply;

[0043] controlling the power supply to switch selectively between:

[0044] a first mode in which a mass-resolving DC voltage is combined with the first RF voltages to constrain the mass-to-charge ratio of said ions transmitted by the first channel, whereby only those ions selectively transmitted by the first channel are subsequently received in the second channel for transmission thereby; and,

[0045] a second mode in which a DC voltage is applied to the ion lens to define an electric potential field configured to combine with a fringing field component of the electric potential field of the second channel to form a potential barrier configured to trap ions within the second channel, and in the second mode changing the radially-confining electric potential of the second channel to increase the kinetic energy of trapped ions so as to overcome the potential barrier selectively according to their mass-to-charge ratio, m / z, thereby mass-selectively axially ejecting trapped ions through the potential barrier.

[0046] The method may comprise controlling the power supply in the second mode for a first time period to maintain the radially-confining electric potential field within the second channel without applying said change thereto such that ions are accumulated in the second channel without axial ejection therefrom, and for a subsequent second time period to apply said change to the radially-confining electric potential field within the second channel.

[0047] The method may comprise controlling the power supply in the second mode to apply one or more AC auxiliary voltages to electrodes of the second set of electrodes therewith to apply said change to the radially-confining electric potential field within the second channel to excite radial motion of trapped ions therein.

[0048] The method may comprise controlling the power supply in the second mode to apply to electrodes of the second set of electrodes said one or more AC auxiliary voltages so as to generate a dipolar electric potential field in the second channel.

[0049] In the method, desirably, an amplitude and / or the frequency of said one or more AC auxiliary voltages differs from an amplitude and / or a frequency, respectively, of said second RF voltages applied simultaneously to the second set of electrodes to generate the radial trapping potential field in the second channel.8451551

[0050] 5

[0051] The method may comprise controlling the power supply in the second mode to apply to electrodes amongst the second set of electrodes said one or more AC auxiliary voltages having a frequency that corresponds to a frequency of resonant ion motion in the second channel thereby to excite such resonant ion motion.

[0052] The method may comprise controlling the power supply such that in the second mode a DC offset voltage is applied, to one or more of the first set of electrodes and the second set of electrodes thereby to generate, together with said DC voltage applied to the ion lens, a trapping potential field configured to trap ions in the axial direction within the second channel.

[0053] The method may comprise controlling the power supply such that in the second mode no mass-resolving DC voltage is applied to second set of electrodes.

[0054] In the method, desirably, the second set of electrodes and the ion lens define a linear ion trap when the control unit is switched to the second mode. In the method, desirably, the axial length of the first set of electrodes is greater than the axial length of the second set of electrodes such that the length of the first channel exceeds the length of the second channel. In the method, desirably, the axial length of the first set of electrodes is between about 100mm to about 250mm. In the method, desirably, the axial length of the second set of electrodes is between about 20mm and about 90 mm.

[0055] The method may comprise controlling, when in the first mode, the mass-resolving DC voltage and the first RF voltages applied thereto to provide a mass filter having a mass transmission range of between about 50 Th and about 8000 Th.

[0056] The method may comprise providing a third set of electrodes spatially arranged collectively to define a volume extending along the ion optical axis to form a third channel spaced from the second channel for receiving ions transmitted by the second channel and thereat receiving respective third RF voltages from the power supply defining a radially-confining electric potential field within the third channel for guiding ions therealong.

[0057] In the method, desirably, the first set of electrodes and / or the second set of electrodes and / or the third set of electrodes each comprises a quadrupole rod set.

[0058] The method may comprise controlling the power supply to switch selectively between said first mode, said second mode and a third mode in which both the first mode and the second mode are implemented simultaneously thereby to provide a mass filter in the first channel and concurrently a linear ion trap in the second channel.8451551

[0059] 6

[0060] Multipole Fields, Pseudo-potentials and Fringing Fields

[0061] Quadrupoles and quadrupole fields

[0062] A quadrupole field is expressed by its linear dependence on the coordinate position. In Cartesian coordinates, the quadrupole electric field is given by:

[0063] E = Eo(Ax + cry + yz)

[0064] Here, E0, A,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:

[0065] V-E = 0

[0066] This condition is satisfied when A = - o,y = 0. The electrical potential corresponding to this field, obtained by spatially integrating the electric field, is:

[0067] 1 1

[0068] <!’ = — — E0(Ax2+ cry2+ yz2) = — — E0A(x2— y2)

[0069] 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:

[0070]

[0071] This gives:

[0072] w0 2

[0073]

[0074] :2^(x y

[0075] 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:

[0076] w0= [u - ycos(wt)]

[0077] The quantity V is the ground-to-pole voltage amplitude of a sinusoidal RF potential of angular frequency o>, and the quantity U is the value of a “mass discriminating” DC ground-to-pole potential.8451551

[0078] 7

[0079] This applied voltage results in equations of motion for the ion in the potential field as follows:

[0080] / CZ \

[0081] — - + I - 7 I [U — ycos(ftjt)]x = 0

[0082] at2\mr / )

[0083] d2y i cz \

[0084] — + — 2_Vcos(wt)]y = o

[0085]

[0086] dt2\mrg J

[0087] Here, the quantity z is the charge of the ion in question, and e is the elementary charge. By defining the following parameters:

[0088] / QeU \

[0089] _ / 4eV \

[0090] Qx - -<7y- ^^^2 J

[0091]

[0092] / =

[0093] The equations of motion reduce to:

[0094] d2u

[0095] — + [au- 2qucos(2f)]u = 0

[0096]

[0097] 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 5. 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:

[0098] axy=constant) ■ qxy

[0099] 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.8451551

[0100] 8

[0101] Higher-order fields and fringin fields

[0102] 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’.

[0103] Higher-order Fields

[0104] 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, the electric potential field present within a volume surrounded by the electrodes of the quadrupole device can be expressed as:

[0105] Z / r \wbnVcos(no) / 2')(t — tn)

[0106]

[0107] N °C0SN~X

[0108] n

[0109] 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. 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, ANand bnare weighting factors and cpNand tnare phase factors. In cartesian coordinates, this may be expressed as:

[0110] u - bnVcos(n<x> / 2}(t — tn)

[0111] N '0

[0112] Nz

[0113]

[0114] cp = Re{(x + iy)'v}

[0115] Here, i = V-l and the term Re{z} refers to the real component of the quantity z. Notably, for an ideal quadrupole field, only the terms for N = 2 appear in the equation for the electric potential field <t>, in which we may set A2= b2= 1. All other terms are zero. This gives the quadrupolar potential field structure noted above. 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.

[0116] 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:

[0117] d2x ( ze \z / ze\r, V9(PN

[0118] j - Vcos(wt)]^ = - ( — ) [U ~ Vcos(o>t)] ) AN— —

[0119] dt2\mr,1 w Z_i ox

[0120]

[0121] V U 7N>38451551

[0122] 9

[0123] d2y ( ze \ rze\1d(i)rj— + - j “ Vcos(at)]y = - ( — ) [U - Vcos(a)f)] > AN— — dt2\mrn / Z_i dy

[0124]

[0125] Here, 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-charge ratio (m / ze) of the ion in question. Here, the quantity z is the charge of the ion in question, and e is the elementary charge. These equations return to the idealised case for a perfect quadrupolar rod set when all higher-order terms are neglected such that

[0126]

[0127] = 0 for all N > 2.

[0128] 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.

[0129] Fringing Fields

[0130] In the inner regions of a linear quadrupole ion guide, far from a terminal end of the guide, the two-dimensional quadrupole potential can be written as:

[0131] 7 7

[0132] o = - — [U - Vcos(a>t)]

[0133]

[0134] ro

[0135] 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, 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 and does not simply fall away instantaneously to a zero value outside of the terminal ends. 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. It can be shown that the exit fringing-field, <t>FF, may be quantified as:

[0136] 2 2

[0137] ‘I’FF = ‘I’ / U) = - IV_Vcos(<x>ty]f(z')

[0138]

[0139] ro

[0140] 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.8451551

[0141] 10

[0142] It can be shown that, to a good approximation:

[0143] / (z) = 1 - exp (~a[z - z0] - b[z - z0]2)

[0144] 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. This fringing effect applies equally to the pseudo-potential generated by an RF potential, as discussed below. Fringing fields exist in ion guides 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 and to define a non-zero extension of the potential extending a finite distance beyond the terminal end.

[0145] Mass-Selective Axial Ion Ejection

[0146] A method of mass scanning is possible with linear quadrupolar devices (e.g., quadrupole rods) employing quadrupole fields known as mass-selective axial ejection (MSAE). This method uses the fringing field at the exit of the quadrupolar device where the otherwise independent ion motions in the x, y and z directions become coupled by the fringing field. This is due to the significant contribution of higher-order field components present within the fringing field. A quadrupolar device may be operated by applying to the electrodes (e.g., rod set) of the device only an RF voltage. An end plate or exit lens arrangement may be disposed at the exit end of the device and may have a voltage applied to it which is set to a value relative to the potentials applied to the electrodes of the device so as to define a stopping potential, or potential barrier to ions within the device.

[0147] Within the fringing field, radial energy of the ions is converted into axial energy due to the coupling effect of the higher-order field components (i.e., with N > 2) present in the fringing field. If ions have sufficient radial energy then this may be converted into an axial energy sufficient to surmount the potential barrier generated by the end plate or exit lens of the device. Ions possessing a greater radial energy are able to acquire a greater radial displacement which permits those ions to occupy regions of the multipolar field in which the effects of the higher-order field components are relatively larger - as compared to their effects at the central axis of the device - and the consequential coupling or radial motion to axial motion is greater.

[0148] The principle underlying MSAE is to deliberately excite ions within such a device, using bespoke excitation potentials, to increase their radial displacements in a mass-selective manner such that ions with a selected mass-to-charge ratio will achieve the radial displacement necessary for radial-to-axial energy conversion needed to surmount the potential barrier. As a result, axial ejection becomes mass-selective.

[0149] A bespoke excitation potential (voltage) may take the form of auxiliary AC voltages applied either to electrodes of the quadrupolar rod set, in addition to (i.e., superimposed upon) the existing RF potentials applied to the electrodes of the rod set, such as shown in Figure 6, or to separate auxiliary electrodes provided forthat purpose. Auxiliary electrodes may be disposed between, and aligned parallel to, the main electrodes of the rod set.

[0150] Typically, the excitation potential (voltage) may be selected so as to generate a dipolar electric potential field at least in the region of the fringing field. This may be achieved by applying an AC excitation voltage8451551

[0151] 11

[0152] to each of two electrodes forming a pair of electrodes that oppose each other across the longitudinal axis of the device. This enables dipole excitation to take place. Figure 6 shows an example of this in which the auxiliary AC excitation voltage, VAux, is of the form:

[0153] VAux= V'cos(ω't)

[0154] Here, the amplitude V of the auxiliary AC voltage and its frequency, a>', may (and generally do) differ from the amplitude and frequency of the quadrupolar field-generating potentials: U - Vcos(Mt), that are applied simultaneously to the rod set. The motion of a pendulum can serve as a simplified analogy to the radial motion of an ion in the quadrupole field. Just as in the case of a pendulum that has a force applied to it once per period synchronously with the pendulum’s motion, whereby the height of the pendulum swing increase, so too does the amplitude of the ion radial oscillatory motion. Thus, resonant excitation of ions can be achieved in this way by adding the auxiliary excitation voltage of angular frequency a>’ to the basic RF quadrupole field of angular frequency a>. The amplitude V of the excitation voltage may be much less than the amplitude V of the RF voltage which confines ions. In this so-called “dipole excitation” method, the electric potential of the excitation field is directly proportional to the coordinates, and the electric field magnitude does not depend on coordinates. This corresponds to a forced harmonic oscillator and resonant motion occurs when the frequency, a>’, of the applied force coincides with one of the following ion oscillation frequencies:

[0155] ω' = (2l + β)ω / 2 ; l = 0, ±1, ±2, ±3 ...

[0156] Here, p is a dimensionless parameter. The auxiliary AC voltage may be used to excite this resonant ion motion.

[0157] Ion trajectories are influenced by axial fields in the fringing region. An increasing axial electric field arises at and close to the ends of the quadrupole rods due to a spatial gradient in the diminishing RF quadrupole potential there. Additionally, an exit lens arrangement may be provided which creates an axial field when an electric potential is applied to it. These two axial electric fields may be balanced by applying a suitable static positive DC potential to the exit lens such that the total axial field experienced by an ion, averaged over one RF cycle has the effect of generating a potential barrier at the exit of the rod set. This potential barrier may be surmounted by mass-selective excitation of radial ion motion. The spatial shape and position of the potential barrier is schematically shown as a function of axial position in Figure 8. The loci of points at which the net spatial gradient, over one RF cycle, of the potential barrier changes sign (i.e., passes through a zero-value at the ‘peak’ of the barrier) is represented by dash-double-dot lines. Ions positioned at points in space axially behind the barrier peak experience a net negative axial force, over one RF cycle and are reflected axially back into the rod set unless they are able to overcome the barrier. Conversely, ions positioned at points in space axially in front of the barrier peak, having been able to overcome the barrier, experience a net positive axial force, over one RF cycle. When the exit lens DC potential is appropriately chosen, ions with a radial motion having sufficient energy are able to penetrate this potential barrier, and be ejected axially, while all others are reflected axially back into the rod set. Due to the axial shape of the loci of points defining the axial position of the barrier peak, this shape is known as the “cone of reflection”, being rotationally symmetric about the axis of the rod set. The following8451551

[0158] 12

[0159] reference provides additional details: F. A. Londry, James W. Hager, “Mass selective axial ion ejection from a linear quadrupole ion trap”, Journal of the American Society for Mass Spectrometry, Volume 14, Issue 10, 2003, pp 1130-1147. Figure 7 schematically shows a “cone of reflection” 304 formed in the region adjacent to the output end of a quadrupole rod set 300 (two of four rods shown) and an exit lens unit 302 of an ion guide.

[0160] The Pseudo-potential

[0161] 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):

[0162] F = — c r

[0163] 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:

[0164] F

[0165]

[0166] =

[0167] Given the force, we can calculate the potential by integrating once:

[0168] < I’( / x, y, z X) = -C( Zax 7z+ 7 7

[0169] py + yzzX)

[0170]

[0171] where a, / ? 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:

[0172] < I’(x, y) = -(x2 —T2)

[0173]

[0174] 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:

[0175] mgh0

[0176] We obtain the expression of a gravitational saddle potential:

[0177] , mgh0 2

[0178] < P(x,y) =2(xz- yz)

[0179] zr08451551

[0180] 13

[0181] 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:

[0182] . z,

[0183] <&(x,y ) = ~ y )

[0184]

[0185] zr0

[0186] The rotating saddle potential may be described in the laboratory frame by applying the standard coordinate transformation given by the rotation matrix:

[0187] / x'\ > / cos(cot) — sin(cot)\ / x\

[0188] \ y'J \sin(cot) cos(cot) / \y)

[0189] This gives:

[0190] <$>(x,y, t) =2° {(x2— y2)cos(cot) — 2xysin(cot)}

[0191]

[0192] 2r0

[0193] 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:

[0194] cf

[0195] r(x,y, t)~ ~ (x2— y2)cos(cot)

[0196] 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.

[0197] 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:

[0198] F = mr = — zV< P(r)

[0199] 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 a>

[0200] < I’(r) = t / (r) + V (r) cos(a>t)8451551

[0201] 14

[0202] 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. » 1 / T. As a result of this assumption, we obtain:

[0203] mr = —zF U(r) + V(r) cos(ilt)) = —zVU(r) — zVV(r) cos(a t) = F0(r) + FRF(r) cos( )t) The smooth particle trajectory due to the force F0(r) is modulated by an oscillating force FRF(r) at frequency < D.

[0204] Thus, we may write the total trajectory r(t) as a sum of a smooth part 7?(t) and rapidly oscillating part £(t):

[0205] r(t) = F(t) + (t)

[0206] 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:

[0207] F0(F + 0 = F0(F) + ■ VF0(R) + ■ ■ ■

[0208] FRF(F + 0 = FRF(R) + ■ FFRF(R) + ■ ■ ■

[0209] Omitting negligible parts of the series, the equation of motion becomes:

[0210] 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:

[0211] m^(t) = FRFcos(a>t)

[0212] The solution to this equation is:

[0213]

[0214] f(t)

[0215] 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:

[0216] (m(F(t) + (t))> = Fo(F) + < (t)> ■ VF0(R + <[FRF(7?) + £(t) ■ 7FRF(F)] cos cot)) Given that:

[0217]

[0218] = 0, this reduces to:

[0219] ... (cos2(cot))

[0220] mR(t)= Fo(7?) - FRF(R) ■ VFRF(R)

[0221]

[0222] Remembering that F is a conservative force, and (7 x FRF(R) = 0) this means that:

[0223] 1 FRF(R) ■ VFRF(R) = FRF(R) ■ VFRF(R) + FRF(R) x (7 x FfiF(7?)) = - 7(FRF(7?) • FfiF(7?))

[0224]

[0225] As a result, and noting that ( cos2(cot)) = 1 / 2, we may write:

[0226] 1

[0227] mR(t) = Fsec= F0(R) - -^^ F(FRF)2= -zVUsec

[0228]

[0229] 8451551

[0230] 15

[0231] 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 (Usecy.

[0232] (FRFY

[0233] U

[0234]

[0235] -= Uo +^=Uo + U^

[0236] Here,

[0237] u

[0238]

[0239] ps4miu2

[0240] 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 FflFoc uRF, and is also inversely proportional to the particle mass-to-charge ratio: mlz. Note also that because FflFoc z, then \Jpsoc z2, and the resulting force is independent of the sign of the charge on the charged particle in question.

[0241] The invention includes the combination of the aspects and preferred features described except where such a combination is clearly impermissible or expressly avoided.

[0242] Summary of the Figures

[0243] Embodiments and experiments illustrating the principles of the invention will now be discussed with reference to the accompanying figures in which:

[0244] Figure 1 shows a mass spectrometer apparatus.

[0245] Figure 2 shows a TOF mass spectrometer apparatus.

[0246] Figures 3A and 3B show cross sectional views of quadrupole electrode rod sets of a mass spectrometer apparatus and the voltages applied thereto.

[0247] Figure 4 shows a simulated mass spectrum generated by a mass spectrometer apparatus.

[0248] Figure 5 shows a “stability diagram” for a quadrupole device.8451551

[0249] 16

[0250] Figure 6 shows a schematic diagram of a quadrupole device provided with a power unit configured to supply an RF voltage and a mass-discriminating DC voltage and configured to supply an auxiliary RF voltage forexcitation of radial ion motion.

[0251] Figure 7 shows a “cone of reflection” for a quadrupole device comprising an end plate or exit lens arrangement.

[0252] Detailed Description of the Invention

[0253] 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.

[0254] In examples of the invention, a segmented multipole mass spectrometer is disclosed which comprises two or more multipole electrode rod sets. The segmented multipole mass spectrometer can either use a first multipole electrode rod set as a mass filter to provide a mass analyser or use a second downstream multipole electrode rod set as a linear ion trap to provide a mass analyser with mass selective axial ejection. Figures 1 and 2 each show a respective example of a triple quadrupole mass spectrometer comprising a linear ion trap with axial ejection in the second stage of mass analysis. This may provide higher resolution than that provided by a mass filter, and has the added benefit of allowing an MS3 functionality. This may improve the ion ejection efficiency and sensitivity of a linear ion trap by using an electrode set (e.g., a quadruple rod set) with the optimal axial length.

[0255] In particular, three multipole electrode rod sets comprise “pre-rods” 105 or 205, “main rods” 107 or 207, “post rods” 109 or 209, and an ion optic lens behind post rods 111 or 211 positioned in succession along the ion optical axis 400 of the system. The segmented multipole rod sets, including pre-rods 105 or 205, main rods 107 or 207 and post rods 109 or 209, comprise electrodes with geometries of either hyperbolic cross-sectional shape or circular cross-sectional shape. These shapes are found to provide good quadrupole potential field structures. The segmented multipole mass spectrometer permits mass analysis in either a mass filter mode or a linear ion trap mode. In the mass filter mode, the main rods 107 or 207 can be operated as an accurate analytical mass filter to perform mass analysis, and in this mode quadrupole / resolving DC and RF voltages are applied to main rods 107 or 207 and scanned to allow ions with selected m / z to pass through and other ions to be filtered out. The pre-rods 105 and 205, and post rods 109 and 209, may be controlled to operate as RF-only ion guides to transmit ions. In the linear ion trap mode, ions may be accumulated and cooled in the post rods 109 and 209, and then mass selectively ejected therefrom toward the downstream lens 111 or 211.

[0256] The post rods 109 or 209 are downstream of the main rods 107 or 207 along the ion path (and along the ion optical axis 400) and may be operated as a linear ion trap in this mode. The lens 111 or 211 has an aperture to transmit ions and provides a DC potential barrier to assist the mass analysis implemented by8451551

[0257] 17

[0258] the post rods 109 or 209. To provide a good mass resolution as a mass filter, the main rods 107 or 207 may have a length of between 100 mm to 250 mm for a mass range between 50 Th to 2000 Th. The post rods 109 or 209 may have a length in the range of 20 mm to 90 mm that gives good ejection efficiency and ion capacity for a linear ion trap with axial ejection and the optimal length can depend on the scan speed of the ion trap.

[0259] This segmented multipole mass spectrometer arrangement can be used as the first mass analyser or the second mass analyser in a tandem mass spectrometer system.

[0260] In more detail, Figure 1 shows a first embodiment of a tandem mass spectrometer system in which the segmented multipole mass spectrometer acts as the second mass analyser. In particular, the mass spectrometer apparatus comprises a power supply 119 and a control unit 117 configured to control the power supply. A first set of electrodes 107 is spatially arranged collectively to define a volume extending along an ion optical axis 400 to form a first channel, and configured to receive respective first RF voltages from the power supply 119 for defining a radially-confining electric potential field within the first channel for guiding ions therealong. A second set of electrodes 109 is spatially arranged collectively to define a volume extending along the ion optical axis 400 to form a second channel spaced from the first channel for receiving ions transmitted by the first channel, and configured to receive respective second RF voltages from the power supply for defining a radially-confining electric potential field within the second channel for guiding ions therealong. An ion lens 111 is arranged upon parts of the ion optical axis 400 extending from the second channel and is configured to define an electric potential field for manipulating ions guided by the second channel when in receipt of a voltage from the power supply 119.

[0261] The control unit 117 is configured to control the power supply 119 to switch selectively between:

[0262] a first mode in which a mass-resolving DC voltage is combined with the first RF voltages to constrain the mass-to-charge ratio of said ions transmitted by the first channel, defined by electrodes 107, whereby only those ions selectively transmitted by the first channel are subsequently received in the second channel, defined by electrodes 109, for transmission thereby; and,

[0263] a second mode in which a DC voltage is applied to the ion lens 111 to define an electric potential field configured to combine with a fringing field component of the electric potential field of the second channel to form a potential barrier configured to trap ions within the second channel, and in which a change in the radially-confining electric potential of the second channel is applied to increase the kinetic energy of trapped ions so as to overcome the potential barrier selectively according to their mass-to-charge ratio, m / z, thereby mass-selectively axially ejecting trapped ions through the potential barrier.

[0264] The tandem mass spectrometer system comprises an ion source 101 for providing precursor ions, ion optics 103 to transfer ions from an atmospheric pressure region to a vacuum region, a first mass filter device 113 (typically a first quadrupole mass filter), a fragmentation device 115 that fragments the precursor ions, and a segmented multipole rod sets including pre-rods 105, main rods107, post rods 109, and a downstream lens 111. The precursor ion source 101 may comprise an electrospray ionisation, ESI, source, or an atmospheric pressure chemical ionisation, APCI, source, or an atmospheric pressure photoionisation, APPI, or a desorption electrospray ionisation, DESI, source, for example. The ion optics 1038451551

[0265] 18

[0266] may include one or more than one ion guides, e.g., multipole electrode rods or stacked-ring ion guides. Differential pumping (not shown) may be used to produce a pressure gradient extending from an atmospheric pressure at the location of the precursor ion source 101 to the location of a vacuum region of a vacuum system 410 housing the first mass filter device 113, the fragmentation device 115, the segmented multipole rod sets 105, 107, 109, and the downstream lens 111.

[0267] The first mass filter device 113 may comprise one or more quadrupole electrode rod sets, and quadrupole / resolving DC and RF voltages are applied to at least one quadrupole electrode rod set to allow ions with selected m / z to pass through and other ions to be filtered by colliding with electrodes. The fragmentation device 115 may comprise multipole electrode rods or a stack ring ion guides, and provides a collision cell where product ions can be produced from fragmentations of precursor ions at a relatively high buffer (collision) gas pressure. An ion detector 420 is connected in communication with a data acquisition system (not shown) for this tandem mass spectrometer system, for collecting ion detection data for analytical use. This embodiment allows the functions and operations of a conventional triple quadrupole in the sense that it provides an enhancement mode to operate the segmented multipole mass spectrometer in a linear ion trap mode. When the segmented multipole mass spectrometer is operated as a linear ion trap, it may provide much higher mass resolution than is possible using a mass filter at a low scan speed. The linear ion trap can also provide an MS3 function and enhance identification power for the compounds in a complex sample.

[0268] Figure 2 shows the second embodiment of a tandem mass spectrometer system that uses the segmented multipole mass spectrometer as the first mass analyser. In particular, the mass spectrometer apparatus once more comprises a power supply 119 and a control unit 117 configured to control the power supply. A first set of electrodes 207 is spatially arranged collectively to define a volume extending along an ion optical axis 400 to form a first channel, and configured to receive respective first RF voltages from the power supply 119 for defining a radially-confining electric potential field within the first channel for guiding ions therealong. A second set of electrodes 209 is spatially arranged collectively to define a volume extending along the ion optical axis 400 to form a second channel spaced from the first channel for receiving ions transmitted by the first channel, and configured to receive respective second RF voltages from the power supply for defining a radially-confining electric potential field within the second channel for guiding ions therealong. An ion lens 211 is arranged upon parts of the ion optical axis 400 extending from the second channel and is configured to define an electric potential field for manipulating ions guided by the second channel when in receipt of a voltage from the power supply 119.

[0269] The control unit 117 is configured to control the power supply 119 to switch selectively between:

[0270] a first mode in which a mass-resolving DC voltage is combined with the first RF voltages to constrain the mass-to-charge ratio of said ions transmitted by the first channel, defined by electrodes 207, whereby only those ions selectively transmitted by the first channel are subsequently received in the second channel, defined by electrodes 209, for transmission thereby; and,

[0271] a second mode in which a DC voltage is applied to the ion lens 211 to define an electric potential field configured to combine with a fringing field component of the electric potential field of the second channel8451551

[0272] 19

[0273] to form a potential barrier configured to trap ions within the second channel, and in which a change in the radially-confining electric potential of the second channel is applied to increase the kinetic energy of trapped ions so as to overcome the potential barrier selectively according to their mass-to-charge ratio, m / z, thereby mass-selectively axially ejecting trapped ions through the potential barrier.

[0274] The tandem mass spectrometer system comprises an ion source 201, ion optics 203 to transfer ions from an atmospheric pressure region to the vacuum region 410, the segmented multipole rod sets (including pre-rods 205, main rods 207 and post rods 209 and lens 211), an intermediate interface 219, a fragmentation device 215 that fragments the precursor ions, and a TOF mass analyser 217. The intermediate interface 219 is optional, but recommended, and can be implemented between the segmented multipole rod sets and the fragmentation device 215. The intermediate interface 219 may comprise one or more static DC ion lenses, and one or more ion guides, e.g., multipole electrode rods or stacked ring ion guides. The intermediate interface 219 may be used to cool the ions transmitted from the post rods 209 and transfer these ions into the fragmentation device 215. It may effectively reduce ion loss of precursor ions when the segmented multipole rod sets are operated in a linear ion trap mode.

[0275] In this way, the mass spectrometer apparatus may further comprise a third set of electrodes 219 spatially arranged collectively to define a volume extending along the ion optical axis 400 to form a third channel spaced from the second channel, defined by post rods 209, for receiving ions transmitted by the second channel and configured to receive respective third RF voltages from the power supply 119 for defining a radially-confining electric potential field within the third channel for guiding ions therealong. The first set of electrodes 207 and / or the second set of electrodes 209 and / or the third set of electrodes 219 may each comprise a quadrupole rod set.

[0276] A high resolution TOF mass analyser 217 may be provided in the form of an orthogonal extraction type comprising a pusher region 432, an ion mirror 434 and a TOF ion detector 430. Of course, other TOF types and other high resolution mass analysers (e.g., orbitrap, FTICR) could be used in alternative, similar embodiments. A q-TOF mass spectrometer is an instrument combining quadrupole technologies with a time-of-flight mass analyser. When operated as a q-TOF instrument implementing a data-independent acquisition methodology, DIA, this embodiment allows the user to perform precursor isolation by using the post rods 209 as a linear ion trap and thus improves the duty cycle, sensitivity and selectivity of DIA mass analysis.

[0277] Figures 3A and 3B show the application of quadrupole / resolving DC, RF and AC auxiliary / excitation voltages for the multipole rods.

[0278] Figure 3A shows how, when the segmented multipole mass spectrometer is operated in a mass filter mode, a voltage of: +([ / - Vcos t) is applied to one pair of opposing electrodes (denoted the “X” electrodes) of the main rods 107, and a voltage of: -(U - Vcos t) is applied to the other pair of opposing electrodes (denoted the “Y” electrodes) of the main rods 107. Here, U and V are the direct current (referred as quadrupole / resolving DC) and the amplitude of RF voltage with angular frequency The values of U and V are scanned together to allow only target ions having a specific mass-to-charge ratio m / z to pass through the channel defined by the main rods 107. The pre-rods 105 and the post rods8451551

[0279] 20

[0280] 109 are operated as RF only ion guides, and an RF voltage is applied to them in the similar way as it is applied to the main rods 107, but a quadrupole / resolving DC voltage is not applied.

[0281] When the segmented multipole mass spectrometer is operated in a linear ion trap mode, RF voltages are applied to the pre-rods 105, the main rods 107, and the post rods 109 in the similar way as described above and this allows ions to be confined in the radial direction. A quadrupole / resolving DC is not used. Proper DC offset voltages are applied to the pre-rods 105, the main rods 107, the post rods 109, and to the ion lens 111 to trap ions inside the post rods 109 in the axial direction. For positive ions, the DC offset voltages applied to the post rods 109 should be lower than the DC offset voltages applied to the main rods 107 and to the ion lens 111.

[0282] A dipole excitation may be used to axially eject ions. This may be achieved by applying two different phases of AC auxiliary voltage respectively to each one of two opposing electrodes of the post rods 109. This is illustrated in Figure 3B whereby an AC auxiliary voltage of a first phase: +(Vaccos ωact) is applied to one electrode of a pair of two opposing electrodes (denoted the “X1” electrode of the pair) of the post rods 109, and simultaneously an AC auxiliary voltage of a second phase: -(Vaccos ωact) is applied to the other one electrode of the pair of two opposing electrodes (denoted the “X2” electrode of the pair) of the post rods 109. The AC auxiliary voltages applied to two electrodes should be out of phase, and are in fact in anti-phase. Other excitation methods, e.g. quadrupole excitation, boundary excitations and so on, are not illustrated as examples in Figure 3B, but they are also possible to allow axial ejection.

[0283] Mass analysis can be performed by scanning the amplitude or the frequency of the RF voltages to bring ions to be reasonably excited with the dipole AC auxiliary voltage or other excitation signals (or conditions). Ions can be excited increasingly or decreasingly according to their m / z during the mass scanning. The basic operation of a linear ion trap is taught by the prior art publication: Hager, J. W., “A New Linear Ion Trap Mass Spectrometer”; Rapid Commun. Mass Spectrom, 2002; 16:512-526.

[0284] The control unit 117 may be configured to control the power supply 119 in the second mode for a first time period to maintain the radially-confining electric potential field within the second channel without applying the change thereto such that ions are accumulated in the second channel without axial ejection therefrom, and for a subsequent second time period to apply said change to the radially-confining electric potential field within the second channel.

[0285] The control unit 117 may be configured to control the power supply in the second mode to apply one or more AC auxiliary voltages to electrodes of the second set of electrodes therewith to apply said change to the radially-confining electric potential field within the second channel to excite radial motion of trapped ions therein. The control unit may be configured to control the power supply in the second mode to apply to electrodes of the second set of electrodes said one or more AC auxiliary voltages so as to generate a dipolar electric potential field in the second channel.

[0286] This segmented multipole mass spectrometer can allow to users operate the main rods 107 as a mass filter and the post rods 109 as a linear ion trap at the same time. In this operation, only ions within a m / z window selected by the main rods 107 can be transmitted through the channel defined by the main rods,8451551

[0287] 21

[0288] and then accumulated and trapped in the channel defined by the post rods 109. This operation can be used to enrich low abundant compounds by reducing other interference ions and can find good applications fortrace analysis. Such operation also allows to reduce space charge effects in the channel defined by the post rods 109 by filtering ions in the channel defined by the main rods 107. The main rods 107 may be driven / operated to implement a unit mass resolution or lower mass resolution for this purpose.

[0289] Simulation of the segmented multipole mass spectrometer in a linear ion trap mode gives a resolution of 1730, or FWHM=0.35 Th, for m / z = 609 at a pressure of 0.05 mTorr of nitrogen buffer gas, with a 1000 Th / s scan speed, as shown in Figure 4. Such resolution is much high than the resolution of conventional mass filter. The improved mass resolution can better meet demands of analysis in some applications. When electrode post rods, 109 or 209, of length 40mm are used as the linear ion trap, the segmented multipole rods give ejection efficiency of about 43%. By comparison, prior art devices that use rods of length 120mm or longer, both as a linear ion trap and also as a mass filter, have limited ion ejection efficiency and sensitivity as a linear ion trap because only ions that are near the end of the rods have a sufficiently high possibility to be axially ejected. A simulation under the same conditions but using electrode rods of 120mm length indicates merely 11% ejection efficiency with similar mass resolution. The present invention allows optimisations of the length (and other geometries) of the linear ion trap and the mass filter separately, and thus improves the performance.

[0290] The pressure in the segmented multipole mass spectrometer may be in the range from 0.01 mTorr to 1 mTorr. The optimal pressure of the segmented multipole rods should be between 0.03 mTorr to 0.3 mTorr when nitrogen or air is used as buffer gas. A buffer gas may be used and may be selected from: helium, nitrogen, air or argon. Nitrogen or air is desirable to reduce costs.

[0291] An amplitude and / or the frequency of said one or more AC auxiliary voltages may differ from an amplitude and / or a frequency, respectively, of said second RF voltages applied simultaneously to the second set of electrodes to generate the radial trapping potential field in the second channel. The amplitude of AC auxiliary voltage for ion excitations may be from Vac= 0.2V to Vac= 20V. The control unit 117 may be configured to control the power supply 119 in the second mode to apply to electrodes amongst the second set of electrodes said one or more AC auxiliary voltages having a frequency that corresponds to a frequency of resonant ion motion in the second channel thereby to excite such resonant ion motion. The control unit 117 may be configured to control the power supply 119 such that in the second mode a DC offset voltage is applied, to one or more of the first set of electrodes and the second set of electrodes thereby to generate, together with said DC voltage applied to the ion lens, a trapping potential field configured to trap ions in the axial direction within the second channel. The frequency of AC auxiliary voltage for ion excitations may be from 0.05-times to 0.5-times the frequency of the main driving RF voltage (e.g., 0.05& J < o>ac< 0.5w). The driving RF voltage, a>, may have a frequency in the range from 0.5 MHz to 3 MHz, and 1.2MHz. The control unit may be configured to control the power supply such that in the second mode no mass-resolving DC voltage is applied to second set of electrodes. The second set of electrodes and the ion lens may define a linear ion trap when the control unit is switched to the second8451551

[0292] 22

[0293] mode. The control unit 117 may be configured to control the power supply 119 to switch selectively between the first mode, the second mode and a third mode in which both the first mode and the second mode are implemented simultaneously thereby to provide a mass filter in the first channel and concurrently a linear ion trap in the second channel.

[0294] The axial length of the first set of electrodes may be greater than the axial length of the second set of electrodes such that the length of the first channel may exceed the length of the second channel. Thus, the length of the main rods, 107 or 207, may be in the range of 100 mm to 250 mm for a mass range between 50 Th to 2000 Th. The length of the post rods, 109 or 209, may be in the range of 20 mm to 90 mm.

[0295] Improved data-independent acquisition, DIA, methods are possible according to the invention, such as in the context of quadrupole time-of-flight, q-TOF, techniques and instruments. The conventional DIA methods suffer from drawbacks including low duty cycle (or low sensitivity), slow acquisition speed and a large MS1 isolation window due to the use of a mass filter in the MS1 stage. Using a linear ion trap in place of a mass filter for the purposes of precursor selection can help to solve such problems and improve. This also keeps all the functions of a mass filter in the MS1 stage, and thus provides a flexibility for users to choose the most suitable operation mode for different applications.

[0296] 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.

[0297] 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.

[0298] 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.

[0299] Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0300] 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.

[0301] 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 range8451551

[0302] 23

[0303] 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%.

[0304] References

[0305] 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.

[0306] [1] US6177668B1

[0307] [2] F. A. Londry, James W. Hager, “Mass selective axial ion ejection from a linear quadrupole ion trap”, Journal of the American Society for Mass Spectrometry, Volume 14, Issue 10, 2003, pp 1130-1147.

[0308] [3] Hager, J. W., “A New Linear Ion Trap Mass Spectrometer”; Rapid Commun. Mass Spectrom, 2002; 16: pp 512-526.

Claims

845155124Claims:

1. A mass spectrometer apparatus comprising:a power supply;a first set of electrodes spatially arranged collectively to define a volume extending along an ion optical axis to form a first channel, and configured to receive respective first RF voltages from the power supply for defining a radially-confining electric potential field within the first channel for guiding ions therealong;a second set of electrodes spatially arranged collectively to define a volume extending along the ion optical axis to form a second channel spaced from the first channel for receiving ions transmitted by the first channel, and configured to receive respective second RF voltages from the power supply for defining a radially-confining electric potential field within the second channel for guiding ions therealong;an ion lens arranged upon parts of the ion optical axis extending from the second channel and configured to define an electric potential field for manipulating ions guided by the second channel when in receipt of a voltage from the power supply;a control unit configured to control the power supply to switch selectively between:a first mode in which a mass-resolving DC voltage is combined with the first RF voltages to constrain the mass-to-charge ratio of said ions transmitted by the first channel, whereby only those ions selectively transmitted by the first channel are subsequently received in the second channel for transmission thereby; and,a second mode in which a DC voltage is applied to the ion lens to define an electric potential field configured to combine with a fringing field component of the electric potential field of the second channel to form a potential barrier configured to trap ions within the second channel, and in which a change in the radially-confining electric potential of the second channel is applied to increase the kinetic energy of trapped ions so as to overcome the potential barrier selectively according to their mass-to-charge ratio, m / z, thereby mass-selectively axially ejecting trapped ions through the potential barrier.

2. A mass spectrometer apparatus according to any preceding claim wherein the control unit is configured to control the power supply in the second mode for a first time period to maintain the radially-confining electric potential field within the second channel without applying said change thereto such that ions are accumulated in the second channel without axial ejection therefrom, and for a subsequent second time period to apply said change to the radially-confining electric potential field within the second channel.8451551253. A mass spectrometer apparatus according to any preceding claim wherein the control unit is configured to control the power supply in the second mode to apply one or more AC auxiliary voltages to electrodes of the second set of electrodes therewith to apply said change to the radially-confining electric potential field within the second channel to excite radial motion of trapped ions therein.

4. A mass spectrometer apparatus according to claim 3 wherein the control unit is configured to control the power supply in the second mode to apply to electrodes of the second set of electrodes said one or more AC auxiliary voltages so as to generate a dipolar electric potential field in the second channel.

5. A mass spectrometer apparatus according to claim 3 or claim 4 wherein an amplitude and / or the frequency of said one or more AC auxiliary voltages differs from an amplitude and / or a frequency, respectively, of said second RF voltages applied simultaneously to the second set of electrodes to generate the radial trapping potential field in the second channel.

6. A mass spectrometer apparatus according to any of claims 3 to 5 wherein the control unit is configured to control the power supply in the second mode to apply to electrodes amongst the second set of electrodes said one or more AC auxiliary voltages having a frequency that corresponds to a frequency of resonant ion motion in the second channel thereby to excite such resonant ion motion.

7. A mass spectrometer apparatus according to any preceding claim wherein the control unit is configured to control the power supply such that in the second mode a DC offset voltage is applied, to one or more of the first set of electrodes and the second set of electrodes thereby to generate, together with said DC voltage applied to the ion lens, a trapping potential field configured to trap ions in the axial direction within the second channel.

8. A mass spectrometer apparatus according to any preceding claim wherein the control unit is configured to control the power supply such that in the second mode no mass-resolving DC voltage is applied to second set of electrodes.

9. A mass spectrometer apparatus according to any preceding claim wherein the second set of electrodes and the ion lens define a linear ion trap when the control unit is switched to the second mode.

10. A mass spectrometer apparatus according to any preceding claim wherein the axial length of the first set of electrodes is greater than the axial length of the second set of electrodes such that the length of the first channel exceeds the length of the second channel.

11. A mass spectrometer apparatus according to claim 10 wherein the axial length of the first set of electrodes is between about 100mm to about 250mm.84515512612. A mass spectrometer apparatus according to claim 10 or claim 11 wherein the axial length of the second set of electrodes is between about 20mm and about 90 mm.

13. A mass spectrometer apparatus according to any preceding claim wherein when in the first mode, the control unit is arranged to control the mass-resolving DC voltage and the first RF voltages applied thereto to provide a mass filter having a mass transmission range of between about 50 Th and about 8000 Th.

14. A mass spectrometer apparatus according to any preceding claim comprising a third set of electrodes spatially arranged collectively to define a volume extending along the ion optical axis to form a third channel spaced from the second channel for receiving ions transmitted by the second channel and configured to receive respective third RF voltages from the power supply for defining a radially- confining electric potential field within the third channel for guiding ions therealong.

15. A mass spectrometer apparatus according to any preceding claim wherein the first set of electrodes and / or the second set of electrodes and / or the third set of electrodes each comprises a quadrupole rod set.

16. A mass spectrometer apparatus according to any preceding claim wherein the control unit configured to control the power supply to switch selectively between said first mode, said second mode and a third mode in which both the first mode and the second mode are implemented simultaneously thereby to provide a mass filter in the first channel and concurrently a linear ion trap in the second channel.

17. A method for mass spectrometry comprising:providing a power supply;providing a first set of electrodes spatially arranged collectively to define a volume extending along an ion optical axis to form a first channel, and configured to receive respective first RF voltages from the power supply for defining a radially-confining electric potential field within the first channel for guiding ions therealong;providing a second set of electrodes spatially arranged collectively to define a volume extending along the ion optical axis to form a second channel spaced from the first channel for receiving ions transmitted by the first channel, and configured to receive respective second RF voltages from the power supply for defining a radially-confining electric potential field within the second channel for guiding ions therealong;845155127providing an ion lens arranged upon parts of the ion optical axis extending from the second channel and configured to define an electric potential field for manipulating ions guided by the second channel when in receipt of a voltage from the power supply;controlling the power supply to switch selectively between:a first mode in which a mass-resolving DC voltage is combined with the first RF voltages to constrain the mass-to-charge ratio of said ions transmitted by the first channel, whereby only those ions selectively transmitted by the first channel are subsequently received in the second channel for transmission thereby; and,a second mode in which a DC voltage is applied to the ion lens to define an electric potential field configured to combine with a fringing field component of the electric potential field of the second channel to form a potential barrier configured to trap ions within the second channel, and in the second mode changing the radially-confining electric potential of the second channel to increase the kinetic energy of trapped ions so as to overcome the potential barrier selectively according to their mass-to-charge ratio, m / z, thereby mass-selectively axially ejecting trapped ions through the potential barrier.

18. A method according to claim 17 comprising controlling the power supply in the second mode fora first time period to maintain the radially-confining electric potential field within the second channel without applying said change thereto such that ions are accumulated in the second channel without axial ejection therefrom, and for a subsequent second time period to apply said change to the radially- confining electric potential field within the second channel.

19. A method according to any of claims 17 to 18 comprising controlling the power supply in the second mode to apply one or more AC auxiliary voltages to electrodes of the second set of electrodes therewith to apply said change to the radially-confining electric potential field within the second channel to excite radial motion of trapped ions therein.

20. A method according to claim 19 comprising controlling the power supply in the second mode to apply to electrodes of the second set of electrodes said one or more AC auxiliary voltages so as to generate a dipolar electric potential field in the second channel.

21. A method according to claim 19 or claim 20 wherein an amplitude and / or the frequency of said one or more AC auxiliary voltages differs from an amplitude and / or a frequency, respectively, of said second RF voltages applied simultaneously to the second set of electrodes to generate the radial trapping potential field in the second channel.

22. A method according to any of claims 19 to 21 comprising controlling the power supply in the second mode to apply to electrodes amongst the second set of electrodes said one or more AC auxiliary845155128voltages having a frequency that corresponds to a frequency of resonant ion motion in the second channel thereby to excite such resonant ion motion.

23. A method according to any of claims 17 to 22 comprising controlling the power supply such that in the second mode a DC offset voltage is applied, to one or more of the first set of electrodes and the second set of electrodes thereby to generate, together with said DC voltage applied to the ion lens, a trapping potential field configured to trap ions in the axial direction within the second channel.

24. A method according to any of claims 17 to 23 comprising controlling the power supply such that in the second mode no mass-resolving DC voltage is applied to second set of electrodes.

25. A method according to any of claims 17 to 24 wherein the second set of electrodes and the ion lens define a linear ion trap when the control unit is switched to the second mode.

26. A method according to any of claims 17 to 25 wherein the axial length of the first set of electrodes is greater than the axial length of the second set of electrodes such that the length of the first channel exceeds the length of the second channel.

27. A method according to claim 26 wherein the axial length of the first set of electrodes is between about 100mm to about 250mm.

28. A method according to claim 26 or 27 wherein the axial length of the second set of electrodes is between about 20mm and about 90 mm.

29. A method according to any of claims 17 to 28 comprising controlling, when in the first mode, the mass-resolving DC voltage and the first RF voltages applied thereto to provide a mass filter having a mass transmission range of between about 50 Th and about 8000 Th.

30. A method according to any of claims 17 to 29 comprising providing a third set of electrodes spatially arranged collectively to define a volume extending along the ion optical axis to form a third channel spaced from the second channel for receiving ions transmitted by the second channel and thereat receiving respective third RF voltages from the power supply defining a radially-confining electric potential field within the third channel for guiding ions therealong.

31. A method according to any of claims 17 to 30 wherein the first set of electrodes and / or the second set of electrodes and / or the third set of electrodes each comprises a quadrupole rod set.

32. A method according to any of claims 19 to 31 comprising controlling the power supply to switch selectively between said first mode, said second mode and a third mode in which both the first mode and the second mode are implemented simultaneously thereby to provide a mass filter in the first channel and concurrently a linear ion trap in the second channel.

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