Ion transport with orthogonal extraction

Abstract

An ion transport apparatus comprises a plurality of electrodes including a set of axial confinement electrodes, a set of radial confinement electrodes, and an orthogonal extraction part. The electrodes collectively to define a volume extending along an ion optical axis to form a channel. The radial confinement electrodes and the orthogonal extraction part are configured to receive RF voltages to generate a radially-confining electric pseudo-potential within the channel. The axial confinement electrodes receive DC voltages for generating an axially-confining electric potential field forming a potential well within the channel for axially confining ions therein. The orthogonal extraction part is configured for transmission therethrough of ions from the channel in a direction transverse to the ion optical axis. The angled axial confinement electrodes define an axially varying field radius that changes with increasing axial proximity to the orthogonal extraction part to align the potential well with the orthogonal extraction part.

Description

[0001] ION TRANSPORT WITH ORTHOGONAL EXTRACTION

[0002] Field of the Invention

[0003] The present invention relates to methods and apparatus for ion transport and / or trapping, such as linear ion transport and / or trapping, and particularly, though not exclusively, linear ion transport and / or trapping for use in a mass spectrometer (MS) such as an extraction linear ion trap for use with time-of-flight (TOF) mass spectrometers.

[0004] Background

[0005] Tandem mass spectrometers are widely used for identifications and quantifications of compounds, and the quadrupole time-of-flight (Q-TOF) mass spectrometer is one popular type of the tandem mass spectrometer. In a Q-TOF system, orthogonal acceleration time-of-flight (oaTOF) is usually used due to the high resolution and mass accuracy that this technique allows. However, it is known that oaTOF methods have the drawbacks of low duty cycle and low sensitivity.

[0006] Ion trap time-of-flight TOF systems, whereby ions are released from an ion trap into a TOF analyser, may improve upon the low duty cycle and lower sensitivity of a conventional Q-TOF. However, ion trap TOF systems have a disadvantage of a slow data acquisition speed, or the long cycle time for acquiring a single TOF spectrum. As a result, such systems have difficulty in meeting the demand of modern fast liquid chromatography methods that sufficient spectral data points can be obtained in each chromatography spectral peak. For ion trap TOF, it may take about 10ms or longer for ions to be transferred from an upstream device to the ion trap for extracting ions to the TOF device. This can limit the data acquisition speed of TOF systems. There is a need to improve the data acquisition speed of ion trap TOF systems

[0007] The present invention has been devised in light of the above considerations.

[0008] Summary of the Invention

[0009] In a first aspect, the invention may provide an ion transport apparatus comprising:

[0010] a power supply configured to supply RF voltages and DC voltages;

[0011] a plurality of electrodes comprising: a set of axial confinement electrodes, a set of radial confinement electrodes, and an orthogonal extraction part, wherein the plurality of electrodes are spatially arranged collectively to define a volume extending along an ion optical axis to form a channel;

[0012] the set of radial confinement electrodes and the orthogonal extraction part are configured to receive one of more 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 set of axial confinement electrodes is configured to receive one or more DC voltages from the power supply for generating an axially-confining electric potential field forming a potential well within the channel for axially confining ions therein. The orthogonal extraction part is arranged along the ion optical axis and comprises an ion extraction port configured for transmission therethrough of ions from the channel in a directiontransverse to the ion optical axis, and the axial confinement electrodes define an axially varying field radius that changes with increasing axial proximity to the orthogonal extraction part so as to align the potential well with the orthogonal extraction part. The power supply is configured selectively to apply one or more orthogonal extraction voltages to the orthogonal extraction part therewith to eject said axially confined ions from the potential well and through the ion extraction port. The orthogonal extraction voltages may be configured to create a dipolar electric field within the channel directed transversely (e.g., perpendicular) to the ion optical axis towards the ion extraction port to urge ions towards the ion extracting port with sufficient energy imparted to those ions that they may pass through the ion extraction port with an onward velocity suitable for inputting the ions to a TOF analyser. The power supply may be configured to apply DC offset voltages to the radial confinement electrodes. Note that the DC offset voltages in question do not provide a “mass discriminating” DC potential (see below). Preferably, the radial confinement electrodes are not operated to provide mass discrimination amongst ions within the ion transport apparatus.

[0013] The invention may provide a linear ion trap (LIT) fortrapping ions within the orthogonal extraction part for subsequent orthogonal extraction as desired in a direction transverse to the ion optical axis. The invention may provide an ion transport apparatus for use as a linear ion trap for rapid ion transportation and cooling. The ion transport apparatus may be operated with a buffer gas present within the channel and maintained (e.g., by suitably controlled vacuum pumps) at a pressure suitable for cooling axially confined ions in the potential well. The buffer gas pressure may be maintained at a gas pressure in a range from about 0.2 mTorrto about 5 mTorr.

[0014] It is to be understood that a reference to “orthogonal extraction” includes a reference to extraction of trapped ions in a direction transverse to the ion optical axis such that the direction in question comprises at least a component which is orthogonal to the ion optical axis. For example, the direction transverse to the ion optical axis may be a direction which has substantially no (or negligible) axial component and is wholly orthogonal to the ion optical axis. Alternatively, the direction transverse to the ion optical axis may comprise a non-zero axial component as well as a non-zero orthogonal so as to be oblique to the ion optical axis, but not orthogonal to it.

[0015] The invention may improve the sensitivity of an oaTOF method and / or system by the use therein as an ion trap time-of-flight (IT-TOF) arrangement in which an ion trap is used for accumulating ions and extracting the accumulated ions into the flight path of a TOF analyser. The ion trap may comprise a linear ion trap (LIT). The ions (e.g., product ions and / or precursor ions in a tandem mass spectrometry system) can be trapped and cooled in the ion trap before they are extracted from the ion trap to the TOF analyser. An IT-TOF may allow a large fraction of ions over a wide m / z range to be extracted into a TOF analyser, resulting in higher TOF duty cycle. In an IT-TOF system, a linear ion trap (LIT) may be used as an ion extraction region / trap. This may provide an improved trapping efficiency and a larger ion capacity as compared to a three-dimensional (3D) ion trap. When used in a tandem mass spectrometry system, product ions (and / or precursor ions) may be transferred from an upstream device (e.g. a collision cell configured for collision-induced dissociation, CID) into the ion transport device fortrapping and subsequent orthogonal extraction. The ions may be radially trapped by a pseudopotential generated byradio frequency (RF) voltages applied to electrodes of the ion transport apparatus and axially trapped by direct current (DC) voltages applied to electrodes of the ion transport apparatus. The trapped ions may be cooled to near the thermal energy by collisions with molecules of a buffer gas, if desired, before they are orthogonally extracted (e.g., to a TOF analyser) so that improvements in mass resolution can be obtained.

[0016] Space charge effects are an important factor that limits the mass accuracy and sensitivity of IT-TOF. When too many ions are trapped in the ion trap and then are extracted to the TOF analyser, mass accuracy and mass resolution can be degraded due to Coulomb repulsion between ions: this effect is known as the ‘space charge effect’. Ion capacity is usually defined as the maximum number of ions stored in the ion trap that does not significantly degrade the mass accuracy. In a single TOF spectrum (single shot without averaging data over multiple shots), the number of the detected ions can be limited by the ion capacity and this can lead to difficulties in analysing ions with low abundance. A solution is to increase the data acquisition speed of an IT-TOF system so that more ions can be analysed per unit time, resulting in higher sensitivity. In aspects of the invention, the number of the accumulated ions in the linear ion trap may be regulated by an automatic gain control method for reducing the degradation of mass accuracy caused by the space charge effect.

[0017] The invention may provide a novel linear ion trap comprising a plurality of elongate electrodes defining an elongated volume with an ion optical axis, in which a DC accelerating field is provided in its entrance region and a retarding filed is provided in its rear region. The invention may thereby provide an extraction ion trap for a TOF analyser with the feature of rapid ion transportation and cooling. This may improve data acquisition speed and sensitivity of IT-TOF. It has been found that this may reduce a travelling time of ions into the linear ion trap (e.g., from a collision cell) and may reduce the time required to cool the trapped ions to near the thermal energy. Therefore, the data acquisition speed and the sensitivity of IT-TOF may be improved.

[0018] High trapping efficiency may be achieved for a mass range from 200 Th to 2000 Th using the same voltage settings applied to the electrodes of the system when transporting ions to the orthogonal extraction part for trapping there before subsequent extraction. This may allow a wide m / z range for a single TOF spectrum (i.e., as obtained via a single TOF ‘shot’).

[0019] The linear ion trap may provide a DC electrical field in its entrance region for accelerating ions being transported to the orthogonal extraction part fortrapping, and a DC electrical field in its rear region for retarding ions that have been transported to the orthogonal extraction part fortrapping them there. Both the accelerating field and the retarding field are configured to urge ions into the orthogonal extraction part fortrapping them there, ready for cooling and / or orthogonal extraction. The accelerating field and the retarding field may be generated by applying a DC voltage(s) to axial confinement electrodes (e.g., rods) configured to provide a changing field radius. It allows rapid ion transportation and cooling without limiting the m / z range of trapped ions.When the ion guide apparatus is used as a linear ion trap as a part of a tandem mass spectrometer apparatus, comprising a collision cell (e.g., CID cell) upstream of the ion guide, the ion guide allows ion processing to occur in parallel in the sense that a first group of ions may be trapped (and preferably cooled) and extracted orthogonally from the linear ion trap and to simultaneously accumulate a second group of ions in the upstream collision cell. This may greatly improve ion usage and mass spectral sensitivity.

[0020] The axial confinement electrodes may define an axially varying field radius that increases with increasing axial proximity to the orthogonal extraction part so as to align the potential well with the orthogonal extraction part. This allows an axial variation in the proximity to the ion optical axis of the nearest surface of electrodes (i.e., nearest to the ion optical axis) amongst the axial confinement electrodes. As a result, an axial variation in a strength of contribution to the electrical potential field, at successive positions along the ion optical axis, arises when voltages are applied to the axial confinement electrodes. This axial variation is thereby achieved without requiring a similar axial variation in the voltages applied to axial confinement electrodes. An electrical potential well may thereby be formed having a depth that increases steadily with increasing axial proximity to the orthogonal extraction part.

[0021] This spatial geometry of the axial confinement electrodes permits an electric field component within the channel that is directed generally along the ion optical axis, e.g., along a ‘z’ coordinate axis in a Cartesian coordinate system (x,y,z), and also permits the spatial differentials (e.g., ∂φN / ∂x ; ∂φN / ∂y, see below) of multipolar field components to shape the electrical potential field in forming an electrical potential well having a depth that increases steadily with increasing axial proximity to the orthogonal extraction part. Put in other words, because the field radius of the axial confinement electrodes is made a function of axial position fz’), this allows the electrical potential field strength within the channel to vary as a function of axial position (‘z’) along the channel in such a way as to define a spatial potential gradient defining an electric force configured to accelerate / decelerate ions along the channel so as to urge them to a position at the bottom of the potential well so formed for axially confining ions therein.

[0022] The axial confinement electrodes may comprise one or more axially segmented axial confinement electrodes each of which comprises an array of separate axial confinement electrode segments that extends alongside the ion optical axis and wherein each axial confinement electrode segment is elongated to extend alongside the ion optical axis whereby successive axial confinement electrode segments are axially separated by a segment separation region that is aligned with the orthogonal extraction part. The corresponding segments of each said array may be located at the same axial position along the ion optical axis.

[0023] This spatial geometry of the axial confinement electrodes and their segment separation regions, permits the spatial differentials (e.g., ∂φN / ∂x ; ∂φN / ∂y, see below) of multipolar field components to shape the electrical potential field the channel in and around the orthogonal extraction part. Put in other words, the electrical potential field formed in the channel adjacent to (or aligned with) segment separation regions includes local ‘fringing field’ regions (see below) extending from axial confinement electrode segments that are axially adjacent to (preceding / succeeding) the orthogonal extraction part which act collectivelywith the orthogonal extraction part to form a continuous bridging electrical potential field within parts of the channel that span a given segment separation region, that transitions between an electrical potential field formed in the channel by axial confinement electrode segments and an electrical potential field formed in the channel by the orthogonal extraction part.

[0024] The radial confinement electrodes may comprise one or more axially segmented radial confinement electrodes each of which comprises an array of separate radial confinement electrode segments that extends alongside the ion optical axis and wherein each radial confinement electrode segment is elongated to extend alongside the ion optical axis whereby successive radial confinement electrode segments are axially separated by a segment separation region that is aligned with the orthogonal extraction part. The corresponding segments of each said array may be located at the same axial position along the ion optical axis. The power supply may be configured to apply RF voltages to electrode segments amongst the array of separate radial confinement electrode segments, and separately to apply orthogonal extraction voltages to the orthogonal extraction part to eject said axially confined ions from the potential well.

[0025] Each segment separation region of each array may be axially aligned with a corresponding segment separation region of each of the other arrays. For each segmented axial confinement electrode and / or each segmented radial confinement electrode, the axial length of the respective segment separation region may be less than the axial length of either of the electrode segments that it separates within the given segmented electrode.

[0026] In some embodiments, the length of each said segmented electrode, being the sum of the lengths of all segments and segment separation regions thereof, may be substantially the same as the length of any said non-segmented electrode. Each said segment separation region of one segmented electrode of each pair of segmented electrodes may oppose a corresponding segment separation region of the other segmented electrode of the pair of segmented electrodes across the ion optical axis.

[0027] The orthogonal extraction part may comprise a plurality of extraction electrodes that are spatially arranged collectively to define a part of said volume extending along an ion optical axis forming said channel. The plurality of extraction electrodes may comprise one or more of said axially segmented radial confinement electrodes, and the power supply may be configured to supply said RF radial confinement voltages to the plurality of extraction electrodes, and selectively to supply said orthogonal extraction voltages to one or more of the plurality of extraction electrodes. In this way, the plurality of extraction electrodes may be utilised for forming an RF pseudo-potential within the orthogonal extraction part for radial trapping of confined ions in the potential well, and selectively utilised for orthogonal extraction of the confined ions via the ion extraction port independently of the supply of RF radial confinement voltages to other electrodes amongst the axially segmented radial confinement electrodes. In addition, the power supply may be configured selectively to vary said RF radial confinement voltages supplied to the plurality of extraction electrodes thereby selectively to vary a depth of an RF pseudo-potential formed thereby within the orthogonal extraction part. In this way, one may selectively vary a depth of the potential well formed within the orthogonal extraction part as a combination of the RF pseudo-potential - a radially-confining potential well - and the axially-confining potential well formed using the axial confinement electrodes. In this sense, the apparatus may provide an axially narrower inner potential well aligned with the orthogonal extraction part, within an axially greater outer potential well. The depth of the inner potential well, may be selectively varied without interfering with the overall structure of the outer potential well. This may be useful when wishing to manipulate confined ions (e.g., compressing confined ions by making the inner well deeper without changing its axial or radial dimensions / extent) within the orthogonal extraction part, without wishing to alter the axially greater outer potential well.

[0028] The radial confinement electrodes may comprise one or more axially non-segmented radial confinement electrodes each of which comprises one continuous radial confinement electrode piece that is elongated to extend alongside the ion optical axis whereby one of said axially non-segmented radial confinement electrodes comprises a through hole forming the ion extraction port of the orthogonal extraction part. In this way, radial confinement electrodes may form the orthogonal extraction part as well as other parts of the apparatus configured for radial ion confinement at other parts of the channel. The power supply may be configured to apply RF voltages to one or more said axially non-segmented radial confinement electrodes, and separately to apply orthogonal extraction voltages to at least one said axially nonsegmented radial confinement electrode to eject said axially confined ions from the potential well via said through hole.

[0029] The one or more axial confinement electrodes may comprise one or more electrode pairs comprising two said axial confinement electrodes spatially arranged to oppose each other across the ion optical axis. For example, axial confinement electrodes may comprise a plurality of electrode pairs arranged to form a multi-polar electrode array (e.g., a quadrupolar array, and octupolar array, etc.). A multi-polar electrode array of axial confinement electrodes may comprise four poles to which the same DC potential (or at least the same sign I polarity of voltage) is applied such that the electrical potential field generated by the array is not a quadrupole electric potential field. The axial confinement electrodes may be arranged at respective positions located azimuthally around the ion optical axis that are collectively symmetrical with respect to an azimuthal rotation about the ion optical axis. All electrodes of the plurality of electrodes may be arranged at respective positions located azimuthally around the ion optical axis that are collectively symmetrical with respect to an azimuthal rotation about the ion optical axis. The total number of electrodes comprising the plurality of electrodes may be an even number.

[0030] The one or more radial confinement electrodes may comprise one or more electrode pairs comprising two said radial confinement electrodes spatially arranged to oppose each other across the ion optical axis. For example, radial confinement electrodes may comprise a plurality of electrode pairs arranged to form a multi-polar electrode array (e.g., a quadrupolar array, and octupolar array, etc.). The power supply may be configured to apply RF voltages to electrode pairs to form a quadrupolar electrical potential field within the channel. The radial confinement electrodes may define an axially non-varying field radius that that is substantially unchanging with increasing axial proximity to the orthogonal extraction part. The set of radial confinement electrodes may comprise one or more non-segmented electrode pairs comprising two axially non-segmented electrodes spatially arranged to oppose each other across the ion optical axis. The powersupply may be configured to apply to the set of radial confinement electrodes and to the orthogonal extraction part, said RF voltages so as to generate a quadrupolar electric potential field in said channel.

[0031] Each electrode of the plurality of electrodes may be linear.

[0032] In a second aspect, the invention may provide a mass spectrometry apparatus comprising the ion transport apparatus according to the invention in its first aspect.

[0033] In a third aspect, the invention may provide a mass spectrometry apparatus comprising a time-of-flight, TOF, mass analyser and the ion transport apparatus according to the invention in its first aspect arranged upstream of the TOF mass analyser for transporting ions the TOF mass analyser for mass analysis.

[0034] The mass spectrometry apparatus may comprise an ion optical assembly arranged upon the ion optical axis for receiving ions and transmitting the ions in a direction along the ion optical axis towards the ion transport apparatus wherein the TOF analyser is configured to receive (and analyse) ions orthogonally extracted from the ion transport apparatus. The mass spectrometry apparatus may comprise a controller configured to change an ion transmission efficiency of the ion optical assembly according to a preselected property of a TOF spectrum of orthogonally extracted ions detected by the TOF analyser.

[0035] The pre-selected property may be a total number of detected ions contributing to the spectrum when generated from detected corresponding to a same single orthogonal extraction (i.e., same single ‘shot’) of ions from the ion transport apparatus. For example, the spectrum of ions detected by the TOF analyser may be observed to degrade, due to the ‘space charge effect’ noted above, thereby leading to a degradation of the accuracy with which ion mass (m / z ratios) can be derived from the TOF spectrum. Occurrence of such an observation indicates that the number of ions trapped within the ion transport (trap) apparatus is greater than the ion capacity of apparatus. Operating parameters of the ion optical assembly may then be adjusted to decrease ion transmission efficiency of the ion optical assembly and thereby reduce the rate at which ions enter into, and are accumulated by, the ion transport apparatus (trap). This will reduce the number of ions trapped within the ion transport (trap) apparatus between successive orthogonal extraction events and, consequently, reduce ‘space charge effects’ amongst trapped and extracted ions.

[0036] For example, if the total number of detected ions exceeds a first pre-set threshold then operating parameters of the ion optical assembly may be adjusted to decrease ion transmission efficiency of the ion optical assembly and thereby decrease the ion current or transmission at which ions enter into, and are accumulated by the ion transport apparatus (trap). As an alternative or in addition, if the total number of detected ions is less than a second pre-set threshold then operating parameters of the ion optical assembly may be adjusted to increase ion transmission efficiency of the ion optical assembly and thereby increase the ion current or transmission at which ions enter into, and are accumulated by the ion transport apparatus (trap). In this way, an optimal ion transmission efficiency of the ion optical assembly may be found which finds an acceptably high rate of ion throughput (and therefore a better spectrum) whilst avoiding the unwanted ‘space charge effect’ to an acceptable degree.The mass spectrometry apparatus may be configured to apply the one or more orthogonal extraction voltages to the orthogonal extraction part, to eject axially confined ions through the ion extraction port as an orthogonal extraction event (i.e., that gives a single TOF transient), after a pre-set ion accumulation time interval spanning between successive such orthogonal extraction events. This pre-set ion accumulation time interval may be held constant over a plurality of successive orthogonal extraction events. This means that the pre-selected property of the spectrum of ions detected by the TOF analyser according to a given one of these orthogonal extraction events can be compared directly to the same preselected property of the spectrum of ions detected by the TOF analyser according to a succeeding one of those orthogonal extraction events, for the purposes of assessing whether to change an ion transmission efficiency of the ion transport apparatus.

[0037] In a fourth aspect, the invention may provide a tandem mass spectrometry apparatus comprising:

[0038] an ion source for providing precursor ions;

[0039] a first mass analyser configured to apply a selection of precursor ions according to their mass-to-charge ratios;

[0040] a collision cell for fragmenting at least some of the selected precursor ions to generate product ions of the fragmented precursor ions;

[0041] an ion transport apparatus according to the invention in its first aspect, for receiving and transporting product ions from the collision cell;

[0042] a second mass analyser configured to receive product ions extracted from the ion transport apparatus via the ion extraction port thereof, and configured to apply a process of mass analysis to the product ions.

[0043] In a fifth aspect, the invention may provide a method of ion transport comprising:

[0044] providing a power supply configured to supply RF voltages and DC voltages;

[0045] providing a plurality of electrodes comprising: a set of axial confinement electrodes, a set of radial confinement electrodes, and an orthogonal extraction part, wherein the plurality of electrodes are spatially arranged collectively to define a volume extending along an ion optical axis to form a channel and wherein the orthogonal extraction part is arranged along the ion optical axis and comprises an ion extraction port configured for transmission therethrough of ions from the channel in a direction transverse to the ion optical axis; and,

[0046] by the power supply:

[0047] applying to the set of radial confinement electrodes and the orthogonal extraction part, one or more RF voltages to generate a radially-confining electric potential field forming a pseudo-potential within the channel for guiding ions therealong;

[0048] applying to the set of axial confinement electrodes one or more DC voltages to generate an axially-confining electric potential field forming a potential well within the channel for axially confining ions therein, wherein the axial confinement electrodes define an axially varying field radius that changes with increasing axial proximity to the orthogonal extraction part so as to align the potential well with the orthogonal extraction part; and,

[0049] selectively applying one or more orthogonal extraction voltages to the orthogonal extraction part thereby ejecting axially confined ions from the potential well and through the ion extraction port.In the method, the axial confinement electrodes may define an axially varying field radius that increases with increasing axial proximity to the orthogonal extraction part so as to align the potential well with the orthogonal extraction part.

[0050] In the method, the plurality of electrodes may comprise and at least one pair of said axially segmented electrodes that are arranged to oppose each other across the ion optical axis.

[0051] In a sixth aspect, the invention may provide a method of mass spectrometry comprising the method of ion transport according to the invention in its fifth aspect.

[0052] In a seventh aspect, the invention may provide a method of mass spectrometry according to the invention in its sixth aspect and further comprising providing a time-of-flight, TOF, mass analyser and transporting ions to the TOF mass analyser according to the method of ion transport of the fifth aspect of the invention, for mass analysis.

[0053] The method of mass spectrometry may comprise providing an ion optical assembly arranged upon the ion optical axis for receiving ions and transmitting the ions in a direction along the ion optical axis towards the plurality of electrodes wherein the TOF analyser is configured to receive ions orthogonally extracted by the orthogonal extraction part, the method comprising:

[0054] determining a pre-selected property of a TOF spectrum of orthogonally extracted ions detected by the TOF analyser; and,

[0055] changing an ion transmission efficiency of the ion optical assembly according to the pre-selected property so determined.

[0056] The pre-selected property may be a property selected from the following properties:

[0057] a mass resolution (e.g., according to a spectral peak width of a selected spectral peak); and / or, a total number of detected ions contributing to the TOF spectrum when generated from detected orthogonally extracted ions corresponding to a same single orthogonal extraction (i.e., same single ‘shot’) of ions by the orthogonal extraction part.

[0058] In an eighth aspect, the invention may provide a method of tandem mass spectrometry comprising: providing precursor ions;

[0059] by a first mass analyser, applying a selection of precursor ions according to their mass-to-charge ratios;

[0060] providing a collision cell and therewith fragmenting at least some of the selected precursor ions to generate product ions of the fragmented precursor ions;

[0061] providing an ion transport apparatus according to the invention in its first aspect;

[0062] transporting the product ions (and / or precursor ions) in the ion transport apparatus according to the method of the invention in its fifth aspect;

[0063] by a second mass analyser, applying a process of mass analysis to the product ions.Multipole Fields, Pseudo-potentials and Fringing Fields

[0064] Quadrupoles and quadrupole fields

[0065] A quadrupole field is expressed by its linear dependence on the coordinate position. In Cartesian coordinates, the quadrupole electric field is given by:

[0066] E = E0(λx + σy + γz)

[0067] Here, E0, λ, σ, γ are all position-independent, and E0may 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:

[0068] ∇ · E = 0

[0069] This condition is satisfied when λ = − σ, γ = 0. The electrical potential corresponding to this field, obtained by spatially integrating the electric field, is:

[0070] 1 1

[0071] <!’ = — — E0(Ax2+ cry2+ yz2) = — — E0A(x2— y2)

[0072] 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:

[0073]

[0074] This gives:

[0075] w0 2

[0076]

[0077] :2^(x y

[0078] 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:

[0079] W0= 2[U − Vcos(ωt)]

[0080] The quantity V is the ground-to-pole voltage amplitude of a sinusoidal RF potential of angular frequency co, 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:x ( ez \

[0081] —— + I — 7 I [U — Vcos(eot)]x = 0

[0082] dtzymrQ J

[0083] d2y / 6Z \

[0084] — - — 2_Vcos(wt)]y = o

[0085]

[0086] at2\mr(f 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] dyy I ymco 7^rg 2 J I

[0090] _ / 4e7 \

[0091] Qx - -<7y- ^^^2 J

[0092]

[0093] ( = (nt [2

[0094] The equations of motion reduce to:

[0095] d2iz

[0096] — + [au- 2qucos(2^)]u = 0

[0097]

[0098] 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 well known in the art. These stable trajectories have values of auand quthat are coordinates constrained to reside within a roughly triangular “stable region” of the “stability diagram”. By controlling the values of the voltages U and V so that the ratio U / V = constant, the result is that the ratio of the ion trajectory parameters, axyand qxy, becomes axylqxy= 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:

[0099] ax y=constant) ■ qxy

[0100] 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 t 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.

[0101] Higher-order fields and fringing 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’.Higher-order Fields

[0103] In the more general case, where multipolar field orders greater than quadrupole are present within the electric field generated by a quadrupole ion guide or ion trap device, and multiple RF potentials of amplitude Vnand frequency enare present, the electric potential field present within a volume surrounded by the electrodes of the quadrupole device can be expressed as:

[0104] Z / r \w

[0105] Vncos(a>n)(t - tn)

[0106]

[0107] N °C0SN~Xz

[0108] This general form of equation is discussed in more detail in:

[0109] 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)

[0110] Further discussion can be found in:

[0111] 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)

[0112] The amplitudes Vnand frequencies enmay 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.

[0113] 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.

[0114] 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:

[0115]

[0116] U~ XVnC0S^a>n^t~

[0117] Ntn)

[0118] pN= Re{(x + iy)'v}

[0119] Here, i = V-l and the term Re{( + iy)w} refers to the real component of the complex quantity ( + iy)w. Notably, 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= V) 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:

[0120] o = - — [U - Vcos(a>t)]

[0121]

[0122] ro

[0123] 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.

[0124] 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:

[0125] d2x ( ze \z / ze\r, V9(PN

[0126] j - Vcos(wt)]x = - ( — ) [U ~ Vcos(a>t)] > AN— —

[0127] dt2\mr, w Z_i ox

[0128] d2y ( ze \ / ze\1d<p„ — - - j “ Vcos(wt)]y = - (— ) [U ~ Vcos(a)t)'] y AN— — dt2\mr, “ / oy

[0129]

[0130] 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-charge ratio (m / z) of the ion in question. These equations return to the idealised case for a perfect quadrupolar rod set when all higher-order terms are neglected such that AN= 0 for all N > 2.

[0131] 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.

[0132] Fringing Fields

[0133] 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:

[0134] o = - — [U - Vcos(a>t)]

[0135]

[0136] ro

[0137] 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 idealisedcircumstance which is a very good approximation in the inner regions of a linear quadrupole ion guide, far from a terminal end of the guide, or far from a terminal end of a segment of a segmented electrode of the guide, but is increasingly inaccurate at axial positions along the ion guide increasingly close to a terminal end. Furthermore, the potential of the ion guide also extends outside of the ion guide beyond its terminal ends or between successive terminal ends of adjacent segments of a segmented electrode of the ion guide, and does not simply fall away instantaneously to a zero value outside of the terminal ends.

[0138] 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:

[0139] 2 2

[0140] ‘I’FF = ‘I’ / U) = - IV_Vcos(cot)]f(z)

[0141]

[0142] ro

[0143] 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:

[0144] / (z) = 1 - exp (-a[z - z0] - b[z - z0]2)

[0145] 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.

[0146] 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).

[0147] The Pseudo-potential

[0148] 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 underlyingprinciples 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):

[0149] F = — c r

[0150] 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:

[0151] F = -7

[0152] Given the force, we can calculate the potential by integrating once:

[0153] <$>\x,y,z) = -fax + py + yzz)

[0154]

[0155] 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:

[0156] <t>(x,y) = ^(x2~ y2)

[0157]

[0158] 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:

[0159] mgh0

[0160] We obtain the expression of a gravitational saddle potential:

[0161] <,

[0162] >mgh

[0163] (x,y) =20

[0164] (x2

[0165] z-yz)

[0166] zr0

[0167] 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:

[0168] (x,y) = -y^-(xz-yz)

[0169]

[0170] zr0

[0171] The rotating saddle potential may be described in the laboratory frame by applying the standard coordinate transformation given by the rotation matrix:

[0172] x'\ > / cos(cot) — sin(cot)\ / x\

[0173] y’ J \sin(cot) cos(cot) / \y)

[0174] This gives:<$>(x,y, t) =2° {(x2— y2)cos(cot) — 2xysin(cot)}

[0175]

[0176] 2r0

[0177] 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:

[0178] cf

[0179] r(x,y, t)~ — (x2~ y2)cos(cot)

[0180] 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.

[0181] 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:

[0182] F = mr = —z < P(r)

[0183] 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.

[0184] < I’(r) = t / (r) + V(r) cos(at)

[0185] 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:

[0186] mr = —zV(U(r + V(r) cos it)) = —zVU(r — zVV(r) cos(a>t) = F0(r) + FRFr) cos( >t) The smooth particle trajectory due to the force F0(r) is modulated by an oscillating force FfiF(r) at frequency >.

[0187] Thus, we may write the total trajectory r(t) as a sum of a smooth part 7?(t) and rapidly oscillating part £(t):

[0188] r(t) = F(t) + (t)

[0189] 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:F0(R + 0 = F0(R + ■ FF0(R) + ■ ■ ■

[0190] FRFR + 0 = FRF(R) + ■ FFRF(R) + ■ ■ ■

[0191] Omitting negligible parts of the series, the equation of motion becomes:

[0192] m(F(t) + (t)) = F0(R + £(t) ■ FFO(F) + [FRF(7?) + £(t) ■ 7FRF(7?)] cos(a)t) The result of the equation of motion for the oscillating part of the trajectory is given approximately by:

[0193] m^(t) = FRFcos(a>t)

[0194] The solution to this equation is:

[0195] f

[0196]

[0197] (t)

[0198] By calculating the time average over: m(F(t) +

[0199]

[0200] over one period 2TT / < >, we obtain an expression for a time-averaged pseudo-potential. In doing so, note that terms containing cos (cut) will time-average to zero and only terms with [cos(wt)]2remain. Namely:

[0201] (

[0202]

[0203] m(F(t) + e(t))> = FO(F) + <e(0> ' + <\FRF(R) + e(t) ' FFRF(F)] cos (cot)) Given that:

[0204]

[0205] = 0, this reduces to:

[0206] ... (cos2(cot))

[0207] mR(t)= Fo(7?) - FRF(R) ■ VFRF(R)

[0208]

[0209] Remembering that F is a conservative force, and (7 x FRF(R) = 0) this means that:

[0210] 1 FRF(R) ■ VFRF(R) = FRF(R) ■ VFRF(R) + FRF(R) x (7 x FfiF(7?)) = - 7(FRF(7?) • FfiF(7?))

[0211]

[0212] As a result, and noting that ( cos2(cot)) = 1 / 2, we may write:

[0213] 1

[0214] mR(t) = Fsec= F0(R) - -^^ F(FRF)2= -zVUsec

[0215]

[0216] 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)

[0217] (FRF)2

[0218] u

[0219]

[0220] -= u°+^ =U°+ Ups

[0221] Here,

[0222] U

[0223]

[0224] ps4mco2

[0225] 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 FRFO URF, and is also inversely proportional to the particle mass-to-charge ratio: mlz. Note also that because FRFOC Z, then \Jpsoc z2, and the resulting force is independent of the sign of the charge on the charged particle in question.The invention includes the combination of the aspects and preferred features described except where such a combination is clearly impermissible or expressly avoided.

[0226] Summary of the Figures

[0227] Embodiments and experiments illustrating the principles of the invention will now be discussed with reference to the accompanying figures in which:

[0228] Figure 1 shows a schematic view of a time-of-flight (TOF) spectrometer apparatus comprising a linear ion trap (LIT).

[0229] Figure 2 shows: (A) schematic view of a linear ion trap (LIT) used in the spectrometer apparatus; and, (B) a graphical view of the strength of an electrical potential field at points along the ion optical axis of the LIT.

[0230] Figure 3 shows: (A) a cross-sectional view of the linear ion trap (LIT) of Figure 2; (B) a side view of the LIT; (C) a first cross-sectional view of the linear ion trap (LIT); and, (D) a second cross-sectional view of the linear ion trap (LIT).

[0231] Figure 4 shows: (A) a cross-sectional view of the linear ion trap (LIT); (B) a side view of the LIT; (C) a first cross-sectional view of the linear ion trap (LIT); and, (D) a second cross-sectional view of the linear ion trap (LIT).

[0232] Figure 5 shows: (A) a graph of the results of a calculation (simulation) of ion axial position in the linear ion trap (LIT) of Figure 2 as a function of time; (B) a graph of the results of a calculation (simulation) of ion radial (x) position in the linear ion trap (LIT) of Figure 2 as a function of time; (C) and (D) a graph of the results of a calculation (simulation) of ion axial velocity in the linear ion trap (LIT) of Figure 2 as a function of axial position.

[0233] Figure 6 shows: (A) a graph of the results of a calculation (simulation) of standard deviation of an ion cloud in ion radial position in the linear ion trap (LIT) of Figure 2 as a function of time; (B) a graph of the results of a calculation (simulation) of standard deviation in ion axial position in the linear ion trap (LIT) of Figure 2 as a function of time; (C) a graph of the results of a calculation (simulation) of standard deviation in ion radial velocity in the linear ion trap (LIT) of Figure 2 as a function of time; and, (D) a graph of the results of a calculation (simulation) of standard deviation in ion axial velocity in the linear ion trap (LIT) of Figure 2 as a function of time.

[0234] Figure 7 shows steps in a method for controlling the time-of-flight (TOF) spectrometer apparatus of Figure 1.Detailed Description of the Invention

[0235] 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.

[0236] Figure 1 shows a schematic (part cross-sectional) view of a time-of-flight (TOF) spectrometer apparatus comprising an ion transport apparatus operating as a linear ion trap (LIT). Figure 2A, Figure 3A and Figure 3B show the ion transport apparatus in top-down view based on Figure 3C (corresponding to the view of Figure 1) and a cross-section view and side view, respectively.

[0237] The ion transport apparatus comprises a power supply 113 configured to supply RF voltages and DC voltages to electrodes of the ion transport apparatus. The electrodes in question include a plurality of electrodes comprising: a set of axially segmented axial confinement electrodes (104a, 108a, 112a, 116a and 104c, 108c, 112c, 116c), and a set of axially-segmented radial confinement electrodes (102a, 106a, 110a, 114a and 102b, 106b, 110b and 114b and 102c, 106c, 110c, 114c). An orthogonal extraction part is formed by an intermediate segment of the radial confinement electrodes (102b, 106b, 110b and 114b). The plurality of electrodes are spatially arranged collectively to define a volume extending along an ion optical axis 119 to form a channel for ion transport and trapping.

[0238] The set of axially-segmented radial confinement electrodes, and the orthogonal extraction part they define, are configured to receive RF voltages from the power supply 113 for generating a radially-confining electric potential field forming a pseudo-potential within the channel for guiding ions therealong. The set of axial confinement electrodes is configured to receive DC voltages from the power supply 113 for generating an axially-confining electric potential field forming a potential well within the channel for axially confining ions therein. An example of such a potential well is shown in Figure 2B.

[0239] The orthogonal extraction part (102b, 106b, 110b and 114b) is arranged along the ion optical axis and comprises an ion extraction port 106d configured for transmission therethrough of ions from the channel in a direction transverse to the ion optical axis 119. The axial confinement electrodes (104a, 108a, 112a, 116a and 104c, 108c, 112c, and 116c) define an axially varying field radius that changes with increasing axial proximity to the orthogonal extraction part so as to align the potential well with the orthogonal extraction part. This is shown in Figure 2B.

[0240] The power supply is configured selectively to apply one or more orthogonal extraction voltages to the orthogonal extraction part therewith to eject said axially confined ions from the potential well and through the ion extraction port. The orthogonal extraction voltages may be configured to create a dipolar electric field within the channel directed transversely (e.g., perpendicular) to the ion optical axis towards the ion extraction port to urge ions towards the ion extracting port with sufficient energy imparted to those ions that they may pass through the ion extraction port with an onward velocity suitable for inputting the ions to a TOF analyser. This is used as an extraction ion trap for the oaTOF mass analyser 111. The plurality of elongate electrodes of the ion transport apparatus 109 define an elongated volume stretching along theion optical axis 119 as a channel so that quadrupole RF fields can confine ions in the two-dimensional space that is orthogonal to ion optical axis, and a DC accelerating field and a DC retarding field can transport and trap ions in the direction of the ion optical axis. The accelerating field is generated in the entrance region of the linear ion trap and a retarding field is generated in the rear region along the ion optical axis, with the orthogonal extraction part / region being sandwiched between them along the ion optical axis. This linear ion trap can receive ions from an upstream collision cell to cool these ions to near the thermal energy and then orthogonally extract these ions into the oaTOF mass analyser 111.

[0241] The confining RF voltages may, when applied to the radially-confining electrodes, form a quadrupole, hexapole, octupole or other higher order multipole field; a quadrupole field is usually preferred to provide a narrow ion beam in the two-dimensional space that is orthogonal to ion optical axis. The DC accelerating field and DC retarding field allow ions to be transported rapidly from an upstream device to the extraction region of the linear ion trap and to be cooled to near thermal energy. This linear ion trap may provide high ion trapping efficiency over a wide m / z range with the desired feature of rapid ion transportation and cooling, so that the data acquisition speed and sensitivity of IT-TOF can be improved.

[0242] In this way, the ion transport apparatus forms a linear ion trap (LIT) that provides fortrapping ions within the orthogonal extraction part for subsequent orthogonal extraction as desired in a direction transverse to the ion optical axis. The ion transport apparatus is operated with a buffer gas present within the channel and maintained by suitably controlled vacuum pumps (not shown) at a pressure suitable for cooling axially confined ions in the potential well. The buffer gas pressure is maintained at a gas pressure in a range from about 0.2 mTorrto about 5 mTorr.

[0243] This example of a use of the linear ion trap receives ions from an upstream device (e.g. a collision cell) to trap and cool those ions before orthogonally extracting these ions from the extraction region into the oaTOF mass analyser. In more detail, Figure 1 schematically illustrates a tandem mass spectrometer that implements the disclosed linear ion trap 109 and an oaTOF mass analyser 111. It is to be understood that this example illustrates components of an apparatus for a tandem mass spectrometry in which certain components, such as a vacuum pump serving the vacuum chamber, are omitted from the illustration merely to aid clarity but are to be understood as being present.

[0244] The tandem mass spectrometry system comprising an ion source 101 for providing precursor ions of a sample under study, an ion optics assembly 103 arranged to receive precursor ions output by the ion source and to guide the received precursor ions to a first mass analyser 105, a first mass analyser 105 for selecting precursor ions according to their mass-to charge ratios (m / z), a collision cell 107 for fragmenting the selected precursor ions into product ions and the linear ion trap 109 for receiving these ions. The oaTOF 111 is configured to receive orthogonally-ejected ions for analysis according to their flight time.

[0245] The ion source 101 may comprise any of the following known ion source types: ESI, APCI, APPI, DESI, PESI, MALDI. 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 atmospheric pressure to a vacuum region for mass analysis.The first mass analyser 105 may be a mass filter, an ion trap or a magnetic sector mass spectrometer configured to select precursor ions according to their mass-to-charge ratios. When a mass filter is used as the first mass analyser, quadrupole DC and RF voltages may be applied into quadrupole rod set to allow ions with selected m / z to pass through and other ions to be filtered by colliding with electrodes of the first mass analyser. A collision cell 107 may comprise an ion guide with an ion inlet aperture, an ion outlet aperture, and a gas supply. Product ions may be generated from fragmentations of precursor ions by collision-induced dissociation inside the collision cell 107 at relatively high pressure.

[0246] Product ions and any unfragmented precursor ions, may be accumulated in the collision cell 107 near its ion outlet aperture before they are injected into the linear ion trap 109. The accumulated ions from the collision cell 107 may be received and trapped in the linear ion trap 109 and may be cooled to near thermal energy in the extraction region of 109 before they are orthogonally extracted into the oaTOF mass analyser 111.

[0247] Ion orthogonal extraction may be performed by switching off the radially-confining RF voltages applied to the linear ion trap 109 and immediately applying a high-voltage dipole extraction pulse to a pair of electrodes of the orthogonal extraction part, including the electrode 106b containing the orthogonal extraction port 106d, that oppose each other across the ion optical axis so that ions can be orthogonally accelerated to pass from through the orthogonal extraction port 106d (formed as a through-hole or slot) from within the LIT, and into the oaTOF mass analyser 111. Whereas an oaTOF analyser 111 is illustrated in this example, it is to be understood that another type of mass analyser, e.g. Fourier-transform mass spectrometer and orbitrap, can also be implemented in place of the oaTOF device. Buffer gas pressure is controlled within the LIT 109 so as to reside within a pressure range of between 0.2 mTorrto 5 mTorr. Argon, air or nitrogen can be used as the buffer gas. This pressure range has been found to be particularly effective at cooling trapped ions.

[0248] Figure 2 and Figure 3 schematically illustrate one embodiment of the said linear ion trap 109. Figure 2A illustrates a 3D model (generated using ‘Simion’ software well known in the art) of the linear ion trap 109. Figure 2B shows a calculated DC potential along the ion optical axis (z axis) of this linear ion trap. The z position of the DC potential is axially aligned with the 3D model of Figure 2A.

[0249] The linear ion trap 109 includes three sets of multipole rods that are separated in the direction of the ion optical axis 119. A first set defines an ion entrance region for receiving and accelerating ions, a middle set defines an ion extraction region fortrapping and extracting ions received from the ion entrance region, and last set defines a rear region for decelerating ions to urge them into the ion extraction region. The three sets of multipole rods define eight axially segmented electrodes, four of which form an array of radial confinement electrodes each comprising three electrode segments, and the other four defining an array of axial confinement electrodes each comprising two segments. In this way, each one of the three sets of multipole rods comprises four axial segments each one of which is one electrode segment from a respective one of four radial confinement electrodes positioned at a common axial position along the ion optical axis but separated by 90 degrees in azimuthal angle around the ion optical axis. Similarly, a firstone (at the entrance region) and a last one (at the rear region) of the three sets of multipole rods comprises a further four axial segments each one of which is one electrode segment from a respective one of four axial confinement electrodes positioned at a common axial position along the ion optical axis but separated by 90 degrees in azimuthal angle around the ion optical axis. The azimuthal angular separation between radial confinement electrode segments and axial confinement electrode segments within a given one of the first and last sets of multipole rods, is 45 degrees.

[0250] The electrodes of the three sets are labelled with ‘a’, ‘b’ and ‘c’ to denote belonging to one of these three regions (see: 104a, 108a, 112a, 116a and 102a, 106a, 110a, 114a and 102b, 106b, 110b and 104c, 108c, 112c, 116c and 102c, 106c, 110c, 114c). Ions can be transferred from an upstream device to enter the entrance region of 109 before they are finally trapped in the extraction region that is between the entrance region and the rear region. A DC accelerating field is provided in the entrance region and a DC retarding field is provided in the rear region. The calculated DC potential along its ion optical axis is shown by Figure 2B. This design can allow ions to be transported rapidly and trapped in the extraction region (the centre set of multipole rods).

[0251] After ions are cooled to near the thermal energy in the extraction region, ions are orthogonally extracted into a oaTOF mass analyser for mass analysis by passing through a slot 106d of the electrode 106b. Other ion optics that are omitted in Figure 2 and 3 may be employed to direct ejected ions into the oaTOF device as appropriate.

[0252] The geometry of the linear ion trap 109 and its voltage applications is illustrated in Figure 3. Figure 3A illustrates a cross-sectional view of the linear ion trap 109, the view is from the top-down view according to Figure 3C showing the plane containing the ion optical axis 119. For clarity all other electrodes are omitted from the view other than those crossing the plane containing the ion optical axis. The same is true for the cross-sectional view of Figure 1. Figure 3B shows a right side view according to Figure 3C view. Figure 3C shows a cross-sectional view at the position BB’ in the entrance region shown in Figure 3A and Figure 3B. Figure 3D shows a cross-sectional view at the position CC’ immediately before the axial extraction part. One can see that at the position BB’ in the entrance region farthest from the axial extraction part, the field radius, raBB’, of the axial confinement electrodes 104a, 108a, 112a and 116a, is the same as the field radius, ro, of the radial confinement electrodes 102a, 106a, 110a and 114a.

[0253] However, at an axial position in the entrance region closer to the orthogonal ejection / extraction part, at the position CC’, the field radius, racc’, of the axial confinement electrodes 104a, 108a, 112a and 116a, is greater than the field radius, ro, of the radial confinement electrodes 102a, 106a, 108a and 112a. The field radius of the auxiliary confinement rods increases with increasing proximity to the orthogonal ejection / extraction part: raBB’ < racc’.

[0254] Similarly, the field radius of the axial confinement electrodes 104c, 108c, 112c and 116c in a part of the rear region farthest from the axial extraction part, is the same as the field radius, ro, of the radial confinement electrodes 102c, 106c, 110c and 114c. However, at an axial position in the rear region that is closer to the orthogonal ejection / extraction / ejection part, the field radius of the axial confinement electrodes 104c, 108c, 112c and 116c, is greater than the field radius, ro, of the radial confinementelectrodes 102c, 106c, 110c and 114c. The field radius of the auxiliary confinement rods in the rear region thus increases with increasing proximity to the orthogonal ejection / extraction / ejection part.

[0255] The entrance region includes eight electrode pole pieces surrounding the ion optical axis 119. Four of the eight electrode poles are respective segments of four axially segmented radial confinement electrodes, and the other four electrode poles are axial respective segments of four axially segmented axial confinement electrodes. An RF voltage, Vrfcos Ωt, is supplied by the power supply 113 to two of the radial confinement electrodes, 106a and 114a, which oppose each other across the ion optical axis. Simultaneously, an RF voltage, -Vrfcos Ωt, is supplied by the power supply 113 to another two of the radial confinement electrodes, 102a and 110a, which oppose each other across the ion optical axis. This application of RF voltages generates a quadrupole pseudo-potential in the volume of space surrounded by the electrodes so that ions can be confined in the two-dimensional space that is orthogonal to ion optical axis 119. The two RF voltages have the same frequency, Ω, the same amplitudes, Vrf, and a phase difference of π radians, whereby this phase difference accounts for the opposite signs of the voltages. The RF voltages are referred to herein as the confining RF voltages and the electrodes to which the RF voltages are applied (e.g. 102a, 106a, 110a and 114a) are referred herein as the RF rods.

[0256] The frequency, Ω, of the confining RF voltage may be in a range from 500kHz to 5MHz, and the RF amplitude, Vrf, may be in a range of 10V to 1000V. The value if this voltage may be adjusted / scanned as desired with the transmitted m / z range. A DC offset U1is applied to the four RF rods of the entrance region. This quantity is not a “mass discriminating” DC ground-to-pole potential (see above) such that when U1T 0 the radial confinement electrodes do not provide mass discrimination amongst ions transported and trapped within it. U1is a DC offset does not introduce a mass discriminating DC. To introduce mass discriminating DC, if wanted, +U can be applied to electrodes 102 and 110 and -U can be applied to electrodes 114 and 106.

[0257] The field radius of the RF rods, r0, defined as the shortest distance from the ion optical axis 119 to facing surfaces of the RF rods, should be in a range of 1mm to 5mm. The value of r0does not change with axial position along the ion optical axis 119. The other four electrodes 104a, 108a, 112a and 116a receive only a DC voltage, UA, from the power supply, and are referred to herein as “auxiliary rods”, this being a reference to axial confinement electrodes. A DC voltage, UA, is applied to the four auxiliary rods in the entrance region. UAand U1may have different values DC voltage values.

[0258] The field radius, ra, of the auxiliary rods, defined as the shortest distance from the ion optical axis 119 to facing surfaces of the auxiliary rods, is configured to vary with axial position along the ion optical axis 119 such that rais a function of axial position z. The field radius may increase linearly or decrease linearly in the entrance region. Here, the field radius increases linearly with increasing proximity to the extraction region. Preferably, ramay be configured to vary through a range from about 0.2roto about 5r0. In the example shown in figures 3C and 3D, the field radius of the auxiliary rods linearly increases along the ion optical axis 119, e.g. raat position BB’ is smaller than that at CC’. A DC accelerating field is formed in the entrance region by setting UAand U1appropriately, as shown by Figure 2B. The projection of the length ofthe auxiliary rods (axial confinement electrodes) on the direction of the ion optical axis 119 may be the same or slightly shorter than the length of the RF rods (radial confinement electrodes) in the entrance region. The rear region also has eight electrodes including four RF rods (radial confinement electrodes) and four auxiliary rods (axial confinement electrodes), similarly as the entrance region.

[0259] A quadrupole pseudo-potential is provided by applying RF voltages to the RF rods (radial confinement electrodes), and the same RF voltages may be supplied to the radial confinement electrodes in the entrance region, the extraction region and the rear region. The power supply provides DC voltages to the axial confinement electrodes in the rear region to generate a retarding field in the rear region in a similar manner by varying the field radius of the auxiliary rods with the position along the ion optical axis 119. The field radius, ra, of the auxiliary rods in the rear region is configured to vary with axial position along the ion optical axis 119 such that rais a function of axial position z. The field radius may increase linearly or decrease linearly in the rear region. Here, the field radius increases linearly with increasing proximity to the extraction region. Preferably, ramay be configured to vary through a range from about 0.2roto about 5r0.

[0260] The extraction region comprises four radial confinement electrodes to which RF voltages are applied for providing a quadrupole pseudopotential. The auxiliary rods do not extend to (i.e., alongside) the extraction region and, instead, segment separation regions 117, are formed between axially successive axial confinement electrodes such that radial confinement electrodes (102b, 106b, 110b and 114b) of the extraction region are aligned with the segment separation regions 117.

[0261] In the extraction region, one electrode 106b has an open slot 106d for ion extraction to the oaTOF analyser. The width of the slot may be in a range of 0.02roand 0.4ro, and the length of the slot in a direction parallel to the ion optical axis 119, may be in a range of 0.8roand 10ro. Different DC voltages may be applied to the three sets of the RF rods (radial confinement electrodes) in the entrance region (DC voltage U, the extraction region (DC voltage U2), and rear region (DC voltage U3), respectively. By optimising the DC voltages applied to the three set of RF rods (radial confinement electrodes) the DC voltages applied to the two sets of the auxiliary rods (axial confinement electrodes), ions can be quickly transported to and trapped in the extraction region. After ions are trapped and effectively cooled in the extraction region, the radially confining RF voltages can be switched off and a bipolar extraction DC voltage can be applied immediately to the electrodes of 106b and 114b to provide a dipole accelerating field to orthogonally extract the trapped ions into a oaTOF mass analyser.

[0262] For example, 500V and -500V extraction pulses may be applied, by the power supply, to radial confinement electrodes 114b and 106b in the extraction region, respectively, for extracting positively-charged ions. The two bipolar extraction DC voltages can be in a range between + / -300V to + / -4000V. The extracted ions may thereby be caused to pass through the open slot of the electrode 106b and any subsequent other ion optics (not shown) and travel to the flight path of oaTOF analyser for mass analysis. For improved mass resolution, it is preferred to cool the trapped ions in the (trapping) extraction region to nearthe thermal energy. The length of the entrance region, the extraction region and the rear region each may be in a range of about 2r0to about 50ro. The gas pressure of a buffer gas provided in the iontransport apparatus at a pressure range is between 0.2 mTorrto 5 mTorr, and argon, air or nitrogen may be used as buffer gas.

[0263] Ion compression may be optionally applied to ions within the ion transport apparatus, such as during the process of cooling ions trapped within the extraction region. The aim of compression is to compress a spatial distribution of an ion cloud in the direction of the ion optical axis 119 so as to increase the number of ions that can be orthogonally extracted into the oaTOF analyser for higher sensitivity. For a positively-charged ions, the power supply may be configured to implement ion compression by increasing simultaneously the DC voltages (U1, U3) applied both to the RF rods (radial confinement electrodes) of the entrance region and to the RF rods (radial confinement electrodes) of the rear region by tens of Volts to hundreds of Volts at the same time. In addition, or in the alternative, the power supply may be configured to implement ion compression by increasing simultaneously the DC voltages applied both to the auxiliary rods (axial confinement electrodes) of the entrance region and to the auxiliary rods (axial confinement electrodes) of the rear region to provide the same effect. Alternatively, the power supply may be configured to implement ion compression by reducing the DC voltage (e.g. a negative voltage) applied to the RF rods (radial confinement electrodes) of the extraction region by tens of Volts to hundreds of Volts.

[0264] The power supply may be configured to vary (e.g., to scan) the values of the DC voltages used for ion compression, as described above, at a predetermined rate of variation (e.g., a rate of 1 V / ps or smaller) in order to reduce possible ion loss due to the ion compression. For negatively-charged ions, the same operation can be performed by reversing the polarity of these DC voltages. Ion compression is desirable to be applied after most ions are axially trapped in the extraction region of the ion transport apparatus 109. Ions may gain energy due to the ion compression and thus collisional cooling is preferred for ions to reach near the thermal energy after ion compression.

[0265] Figure 4 schematically illustrates the second embodiment of the said linear ion trap. It has a similar working principle as the first embodiment. Figure 4A shows the liner ion trap in a cross-sectional view in which, for clarity, only the radial confinement electrodes that reside in a plane containing the ion optical axis 319 are shown, and all other electrodes are omitted from the view. Figure 4B shows a side view including all electrodes visible from that viewpoint. Figures 4C and 4D each show (Figure 4C) a crosssection view at the position DD’ in the entrance region, and (Figure 4D) a cross-section view at EE’ in the extraction region.

[0266] A quadrupole RF pseudo-potential is provided to confine ions radially within the ion transport apparatus, and a DC accelerating field is provided axially in the entrance region, and a DC retarding field is provided axially in the rear region. The main difference from the first embodiment described herein with reference to Figure 2A and Figure 3, is that the RF rods (radial confinement electrodes) are not segmented in a direction parallel to the ion optical axis 319. In other words, only one set of the RF rods (radial confinement electrodes) is used and shared by the entrance region, the extraction region and the rear region. Such design can lower the cost for electrode manufacture and reduce the number of power supplies. Two sets of the auxiliary rods are used in the entrance region and in the rear region respectively, and each set of the auxiliary rods has four rods with varying field radius along the ion opticalaxis 319. In a similar manner, different DC voltages are supplied by the power supply be applied to the RF rods (radial confinement electrodes) and the auxiliary rods (axial confinement electrodes) so that an accelerating field can be formed in the entrance region and a retarding field can be provided in the rear region.

[0267] In the example of Figure 4, the field radius of the auxiliary rods in the entrance region and in the rear region, linearly increases with increasing proximity (the axial position) to the extraction region, along the ion optical axis. The field radius r0of the RF rods (radial confinement electrodes) has a constant value and does not change with the position along the ion optical axis 319. In the extraction region, one radial confinement electrodes 306 has an open slot 306d for ion extraction to the oaTOF analyser. The sizes of the electrodes of the second embodiment and the operating parameters including RF voltages, DC voltages and buffer gas pressure may be the same or similar as those in the first embodiment. Ion compression may be optionally applied during the step of ion cooling by either changing the DC voltages applied to the two set of auxiliary rods (axial confinement electrodes) in the entrance region and rear region and / or by changing the DC voltage applied to the RF rods (axial confinement electrodes), in the manner described above with reference to Figure 2A and Figure 3.

[0268] It should be noted that the present embodiments are mere examples, and any change, modification or addition appropriately made within the spirit of the present invention will evidently fall within the scope of claims of the present patent application. In the examples above, a sinusoidal wave is used as the confining RF voltages. Sinusoidal wave is the most used analogue AC signal, but this invention is not limited to sinusoidal wave and should include other possible waveforms. For example, a rectangular wave can be used to create a quadrupole pseudopotential for confining ions for confining ions radially.

[0269] A rectangular wave Ur(t) that can be defined as:

[0270] f. > (UH, for remainder of t / T < d

[0271]

[0272] {UL, for remainder of t / T > d

[0273] where UHand ULare different voltages, T is the period Ur(t) and d is a parameter with a numerical value chosen by the user to be between 0 and 1. Such a waveform may be generated in a digital form, for example, if the power supply is configured as a digital power supply. This has advantages of rapid switching on / offwith precise control of RF phases before orthogonal ion extraction.

[0274] In the examples of the first and the second embodiments, a set of the auxiliary rods has four rod electrodes (e.g. 104a, 108a, 112a and 116a in the entrance region shown by Figure 3) for providing the axial confinement DC field. Four auxiliary rods allow a maximal m / z range of trapped ions. It is possible to use one, two or other number of rod electrodes (axial confinement) for providing similar effects and reducing manufacturing cost. In the present examples, the cross sections of the auxiliary rods (axial confinement) are smaller than those of the RF rods (radial confinement) to enhance the effective confining force of the quadrupole RF field. In some embodiments, the same cross sections can be used for both auxiliary rods (axial confinement) and RF rods (radial confinement) to reduce the manufacturing costs. In the present examples, the field radius of one set of the auxiliary rods (axial confinement) changes as a linear function of axial position. It should be understood that the field radius may alsochange with the axial position in a manner described by other (non-linear) monotonically increasing or monotonically decreasing function.

[0275] In the examples above, a quadrupole RF field is used to confine ions radially and it is also possible to use other higher order multipole RF field (see discussion of higher-order fields, above) in a similar way, such as hexapole, octupole, decapole, dodecapole, etc. The two examples use cylindrical rods (confinement electrodes) for demonstration purpose. It should be understood that other shapes of electrodes, including semicircle shape, arc shape, hyperbolic shape, planar shape, polyhedron and so on, are also possible to provide the similar quadrupole or other higher order RF fields. In practice, planer electrodes may be employed in the extraction region, such as at least the electrode containing the ion extraction port and the electrode opposing it across the ion optical axis, as this may provide a more uniform dipole electric field for orthogonal ion extraction, and thus may have an advantage over other electrode shapes.

[0276] Ion trajectory simulations were performed based on a computational model implemented using “Simsol” software readily available to the person skilled in the art. The simulations included a collision cell 107 and the linear ion trap 109 according to the first embodiment. The linear ion trap had three sets of multipole rods, as described above with reference to Figure 3, with axial lengths of 55 mm, 10 mm and 25 mm, respectively for the entrance region, the extraction region and the rear region. The field radius of ion guide electrodes (not shown) in the collision cell was 2.5mm. For the linear ion trap, 109, the field radius r0of the RF rods (radial confinement electrodes) was 2.5mm in the three respective regions. The field radius of the auxiliary rods (axial confinement electrodes) linearly increases from 2.5mm to 3.75mm in the entrance region in an axial direction towards the extraction region, and increases from 2.5mm to 3.75mm in the rear region in an axial direction towards the extraction region.

[0277] The confining RF voltages had a frequency of 2.3MHz and an amplitude of 300V (zero-to peak, pole to ground), and this RF voltage was used to drive both the ion guide electrodes (not shown) in the collision cell 107 and the ion transport (trap) apparatus 109 with a phase difference of zero radians. DC voltages were tuned to give a DC potential along the ion optical axis shown by Figure 2B whereby ions gain about 2 eV / charge during their transportation from the collision cell 107 to the extraction region of the ion transport (trap) apparatus. The pressure of a buffer gas within the ion transport (trap) apparatus was set to be 0.75 mTorr and a buffer gas pressure was set to be 5 mTorr in the collision cell. Argon was used as the buffer gas and a hard sphere model was used as the gas collision model in the simulations.

[0278] Ions are born in the collision cell 107 at an axial position of about 4mm from the exit aperture of the collision cell. Ions were assumed to have thermalised kinetic energy at temperature of 300K and a Gaussian distribution of x and y position with standard deviation of 0.04mm. The birth time of ions had a uniform distribution to reduce the effects of the RF phase. Reserpine ions (m / z = 609) and ions with m / z = 200 and m / z = 2000 were used as examples in the simulations. The ion travelling from the collision cell 107 to the linear ion trap 109 and ion cooling were investigated by considering ion trajectories. Ion compression was included. A gas flow due to the pressure gradient as between the collision cell and the ion transport apparatus was not included in this study.A single ion trajectory of ins wit m / z = 609 is demonstrated by Figure 5. Figure 5A shows an ion trajectory in the axial (z) direction from a simulation time from 0ms to 2.49ms and Figure 5B illustrates an ion trajectory in x direction, transverse to the ion optical axis. Figure 5C and 5D show a phase space plot of ion velocities in the axial (z) direction, Vz, with respect to the axial (z) coordinate before and after ion compression, respectively. It can be seen that the ion first travels from the collision cell to the ion transport apparatus (linear ion trap), then turns around in the rear region, subsequently travels towards the entrance region and thereafter oscillates back and forth in the axial (z) direction until it is finally trapped in the extraction region with an axial position (z) in the range from about 158.6mm to about 168.6mm. In Figure 5B a rapid reduction in ion oscillation amplitude in the x direction is seen to occur at a time of about 2356ps, and the is the result of a collision of an ion with a buffer gas molecule during the cooling process. The ion starts to be trapped inside the extraction region after about 1,1ms. Ion compression is performed at time t =2.5ms by decreasing the DC voltage of the RF rods (radial confinement electrodes) in the extraction region. This DC voltage is linearly scanned over a time interval from t = 2.5ms to t = 2.6ms with a voltage step of-1V step every 1ps and is ultimately reduced by 100V. The Figure 5D shows the compression reached when the DC voltage of the RF rods has been changed by -100V, and it can be seen that ion compression greatly reduces the amplitude of oscillation in axial (z) direction and increases ion velocity Vz. Ions are then gradually cooled to a steady state.

[0279] Ion statistics were studied based on a simulation of 5000 ions of m / z = 609. Ion compression was applied at time t = 2.5ms by steadily changing the DC voltage applied to radial confinement electrodes of the extraction region by -100V (i.e., reducing by 100V). The distributions of ion positions: x,y,z, and ion velocities: Vx, Vy and Vz for the simulated ions were determined at different simulation times. The data of standard deviation (Std) in these six parameters are shown in Figure 6. It can be seen that the ion compression process narrows ion axial spatial distribution and increases mean kinetic energy in the axial (z) direction. The ion compression process does not strongly affect ion motion in the x and y directions and does not cause ion loss for m / z = 609. The ion cloud can reach a steady state at about 5ms, which can allow 200Hz oaTOF acquisition speed for maximal mass resolution. Ion statistics were further studied for ions of m / z = 200 and m / z = 2000 by using the same voltage setting as was used for ions of m / z = 609 in order to demonstrate a mass range from 200 Th to 2000 Th for this ion transport apparatus (linear ion trap), across a x10 ratio of maximum m / z to minimum m / z. A larger m / z range is possible. Ion statistics at simulation time t = 5ms is listed in Table 1 which lists ion statistics of 5000 ions at for kinetic energy (kx,ky and fcz) resolved in the x,y and z directions, respectively, and:

[0280] kr = kx + ky

[0281] while

[0282] k = kx + ky + kz.

[0283] The units of x, Vx and kx are mm, mm / ps and eV, respectively. Ions are not fully thermalised to the gas temperature of 300K. The mean total kinetic energies (Mean_k) of m / z = 200 and m / z = 2000 are slightly higher than m / z = 609. Ions of m / z = 200 are expected to be cooled more quickly than m / z = 609, and are surprisingly found to have higher radial kinetic energy kr. Ions of m / z = 2000 have much higher axial kinetic energy kz, which can be assumed to be the result of ion compression.Table 1

[0284] m / z 200 609 2000

[0285] Std_x 0.0473 0.0930 0.2393

[0286] Std_y 0.0770 0.1060 0.2511

[0287] Std_z 0.1648 0.1565 0.2033

[0288] Std_Vx0.1663 0.0710 0.0376

[0289] Std_Vy0.1021 0.0609 0.0360

[0290] Std_Vz0.1222 0.0673 0.0477

[0291] Mean_kx0.0287 0.0159 0.0147

[0292] Mean_ky0.0108 0.0117 0.0134

[0293] Mean_kz0.0155 0.0143 0.0236

[0294] Mean_kr0.0395 0.0276 0.0281

[0295] Mean_k 0.0549 0.0419 0.0517

[0296] Table 2 shows overall efficiency, and source of ion loss. The overall efficiency, defined as the ratio of the number of ions that are trapped in the ion transport apparatus (linear ion trap) after ion axial compression to the number of ions born in the collision cell, is determined by simulations. It includes ion trapping and ion compression effects. The ions of m / z = 200, m / z = 609 and m / z = 2000 give the overall efficiency of 91.8%, 97.2% and 85.2% respectively. The ion loss of m / z = 200 and m / z = 609 is a result of ions hitting an exit lens with an aperture of 2.4mm diameter. The major loss of m / z = 2000 is caused by the -100V ion compression; if the ion compression is applied later (e.g. at t =4ms), the ion loss of m / z = 2000 can be reduced at cost of longer cycle time.

[0297] Table 2

[0298] m / z 200 609 2000

[0299] Overall efficiency 91.8% 97.2% 85.2%

[0300] Ion loss at exit lens 8.2% 2.8% 0.6%

[0301] Ion loss from compression 0 0 14.1%

[0302] Note that the simulation used a pressure of 0.75mTorr in the ion transport apparatus (linear ion trap) with argon gas used as a buffer gas, and demonstrates the possibility to operate as an ion trap-TOF (IT-TOF) system at 200Hz cycle rate. If higher buffer gas pressure is used in the ion transport apparatus (linear ion trap) or a lower ion compression voltage is applied, the cycle time for acquiring a single TOF spectrum can be further reduced, resulting in higher data acquisition speed and sensitivity for IT-TOF.

[0303] In summary, ion trajectory simulations show the ion transport apparatus (linear ion trap) can provide rapid ion transportation and cooling by using the axial DC electric field. A cycle time of 5ms (including ion compression) is demonstrated for acquiring a single TOF spectrum at buffer gas pressure of 0.75mTorr, which can increase TOF acquisition speed to 200Hz or higher. High overall efficiency (>85%) is achieved for a m / z range from 200 Th to 2000 Th. The ion transport apparatus (linear ion trap) may be implemented as a high-performance extraction ion trap for a TOF analyser for enhancing the sensitivity and acquisition speed of IT-TOF mass spectrometer.This invention also relates to a method for operating the ion transport apparatus as a linear ion trap in conjunction with a TOF analyser including an automatic gain control method, as described by Figure 7. The fast data acquisition speed allows the ion processing in parallel to cool and extract a first group of ions in the linear ion trap and to accumulate a second group of ions in the collision cell simultaneously without discarding ions on purpose. This can greatly improve ion usage and MS sensitivity. Figure 7 illustrates an operating workflow diagram for controlling the operation of the apparatus of Figure 1, including the linear ion trap and ao-TOF mass analyser. The controlling operation may include the following steps:

[0304] STEP S1:

[0305] Inject a first group of ions from an upstream device into the linear ion trap 109 for a time interval Δt1. Typically, Δt1may be about 1ms. Accumulate a second group of ions in the upstream device after Δt1has elapsed.

[0306] STEP S2:

[0307] Cool the injected ions in the linear ion trap for a for a time interval Δt2(e.g., about 4ms). Optionally apply ion axial compression by increasing the depth of the axial potential well (e.g., by tuning DC voltages of segments without changing RF voltages, such as by increasing the value of the DC axially-confining potential of either side of the radially-confining RF pseudo-potential well) without increasing the radial or axial length of the electrical potential well;

[0308] STEP S3:

[0309] Extract the cooled ions from the linear ion trap into the aoTOF analyser for a time interval Δt3( e.g. Δt3< 0.1ms).

[0310] STEP S4:

[0311] Determine whether a mass accuracy degradation has occurred in the spectral data generated by the oaTOF system from using ions extracted from the linear ion trap. If a mass accuracy degradation has not occurred, then:

[0312] go back to STEP S1 directly, and inject the second group of ions into the linear ion trap 109: else,

[0313] go to STEP S5 and, by the controller 113, decrease an ion transmission efficiency of an ion optic system 103 upstream of the linear ion trap 109, and then go back to STEP 1 and inject the second group of ions into the linear ion trap 109.

[0314] Such operation can aim to analyse as many ions as possible by the oaTOF system without discarding ions on purpose so that the MS sensitivity may be improved. However, when too many ions are stored in the linear ion trap 109 and are analysed by the oaTOF 111, mass accuracy may be degraded due to the ‘space charge effect’. There is a need to control the ion number trapped within the linear ion trap so that higher mass accuracy can be obtained. The automatic gain control STEP S5, as shown by Figure 7, permits this control. The number of ions stored in LIT can be controlled by changing ion transmissionefficiency of the upstream ion optic system 103 without changing Δt1and the cycle time of single oaTOF spectrum so that mass accuracy is not significantly degraded by the ‘space charge effect’.

[0315] There are several ways to change the ion transmission of an upstream ion optic system, such as:

[0316] tuning RF voltages applied to an ion guide of an upstream an ion optic system within the upstream ion guide 103 and / or any ion optics within the upstream collision cell 107;

[0317] applying ion isolation by the mass filter 105 with an m / z transmission window;

[0318] changing the ESI voltages applied in the ion source 101, etc.

[0319] Such working parameters can be dynamically optimised according to the number of the detected ions in oaTOF spectra and desired m / z range for analysis. For example, if a degradation of mass accuracy is observed in the TOF spectra, this suggests the ion number is higher than the ion capacity of LIT 109 and these working parameters should be tuned to decrease ion transmission efficiency upstream of the LIT and reduce the number of ions in LIT. On the other hand, if the number of detected ions is lower than the threshold ion number for causing degrading mass accuracy, then these working parameters can be tuned to give higher ion transmission if possible.

[0320] Alternatively, the injection time Δt1can also be controlled / tuned by the controller 113 to control the number of ions stored in the linear ion trap. In SETP S2, ion compression can be optionally applied to reduce ion cloud spatial distribution in the direction of the ion optical axis of LIT.

[0321] 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.

[0322] 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.

[0323] 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.

[0324] Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0325] 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.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%.

[0326] References

[0327] 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.

[0328] [1] Peter H Dawson: “Quadrupole Mass Spectrometry and its applications”, 1st Edition - January 1, 1976 - Elsevier, ISBN: 978-0-444-41345-1

[0329] [2] Mikhail Yavor: “Optics of Charged Particle Analyzers” in “Advances in Imaging and Electron Physics”, Volume 157, Pages 1-381 (2009)

Claims

Claims:

1. An ion transport apparatus comprising:a power supply configured to supply RF voltages and DC voltages;a plurality of electrodes comprising: a set of axial confinement electrodes, a set of radial confinement electrodes, and an orthogonal extraction part, wherein the plurality of electrodes are spatially arranged collectively to define a volume extending along an ion optical axis to form a channel;the set of radial confinement electrodes and the orthogonal extraction part are configured to receive one or more 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 set of axial confinement electrodes is configured to receive one or more DC voltages from the power supply for generating an axially-confining electric potential field forming a potential well within the channel for axially confining ions therein;wherein the orthogonal extraction part is arranged along the ion optical axis and comprises an ion extraction port configured for transmission therethrough of ions from the channel in a direction transverse to the ion optical axis, and the axial confinement electrodes define an axially varying field radius that changes with increasing axial proximity to the orthogonal extraction part so as to align the potential well with the orthogonal extraction part; and,the power supply is configured selectively to apply one or more orthogonal extraction voltages to the orthogonal extraction part therewith to eject said axially confined ions from the potential well and through the ion extraction port.

2. An ion transport apparatus according to any preceding claim wherein the axial confinement electrodes define an axially varying field radius that increases with increasing axial proximity to the orthogonal extraction part so as to align the potential well with the orthogonal extraction part.

3. An ion transport apparatus according to any preceding claim wherein the axial confinement electrodes comprise one or more axially segmented axial confinement electrodes each of which comprises an array of separate axial confinement electrode segments that extends alongside the ion optical axis and wherein each axial confinement electrode segment is elongated to extend alongside the ion optical axis whereby successive axial confinement electrode segments are axially separated by a segment separation region that is aligned with the orthogonal extraction part.

4. An ion transport apparatus according to any preceding claim wherein the radial confinement electrodes comprise one or more axially segmented radial confinement electrodes each of which comprises an array of separate radial confinement electrode segments that extends alongside the ion867178634optical axis and wherein each radial confinement electrode segment is elongated to extend alongside the ion optical axis whereby successive radial confinement electrode segments are axially separated by a segment separation region that is aligned with the orthogonal extraction part.

5. An ion transport apparatus according to any of claims 1 to 3 wherein the radial confinement electrodes comprise one or more axially non-segmented radial confinement electrodes each of which comprises one continuous radial confinement electrode piece that is elongated to extend alongside the ion optical axis whereby one said axially non-segmented radial confinement electrode comprises a through hole forming the ion extraction port of the orthogonal extraction part.

6. An ion transport apparatus according to any preceding claim wherein the one or more axial confinement electrodes comprise one or more electrode pairs comprising two said axial confinement electrodes spatially arranged to oppose each other across the ion optical axis.

7. An ion transport apparatus according to any preceding claim wherein the one or more radial confinement electrodes comprise one or more electrode pairs comprising two said radial confinement electrodes spatially arranged to oppose each other across the ion optical axis.

8. An ion transport apparatus according to any preceding claim wherein the radial confinement electrodes define an axially non-varying field radius that that is substantially unchanging with increasing axial proximity to the orthogonal extraction part.

9. An ion transport apparatus according to any preceding claim wherein the set of radial confinement electrodes comprises one or more non-segmented electrode pairs comprising two axially nonsegmented electrodes spatially arranged to oppose each other across the ion optical axis.

10. An ion transport apparatus according to any preceding claim wherein the power supply is configured to apply to the set of radial confinement electrodes and to the orthogonal extraction part, said RF voltages so as to generate a quadrupolar electric potential field in said channel.

11. An ion transport apparatus according to any preceding claim when dependent upon claim 3 or claim 4 wherein the corresponding segments of each said array are located at the same axial position along the ion optical axis.

12. An ion transport apparatus according to any preceding claim when dependent upon claim 3 or claim 4, wherein each segment separation region of each array is axially aligned with a corresponding segment separation region of each of the other arrays.

13. An ion transport apparatus according to any preceding claim when dependent upon claim 3 or claim 4 wherein, for each segmented axial confinement electrode and / or each segmented radial confinement867178635electrode, the axial length of the respective segment separation region is less than the axial length of either of the electrode segments that it separates within the given segmented electrode.

14. An ion transport apparatus according to any preceding claim when dependent upon any of claims 3 to 5 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 nonsegmented electrode.

15. An ion transport apparatus according to any preceding claim when dependent upon claim 6 or claim 7 wherein each said 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.

16. An ion transport apparatus according to any preceding claim when wherein the axial confinement electrodes are arranged at respective positions located azimuthally around the ion optical axis that are collectively symmetrical with respect to an azimuthal rotation about the ion optical axis.

17. An ion transport apparatus according to any preceding claim wherein all electrodes of the plurality of electrodes are arranged at respective positions located azimuthally around the ion optical axis that are collectively symmetrical with respect to an azimuthal rotation about the ion optical axis.

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

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

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

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

22. A mass spectrometry apparatus according to claim 21 comprising:an ion optical assembly arranged upon the ion optical axis for receiving ions and transmitting the ions in a direction along the ion optical axis towards the ion transport apparatus wherein the TOF analyser is configured to receive ions orthogonally extracted from the ion transport apparatus; and, a controller configured to change an ion transmission efficiency of the ion optical assembly according to a pre-selected property of a TOF spectrum of orthogonally extracted ions detected by the TOF analyser.86717863623. A tandem mass spectrometry apparatus comprising:an ion source for providing precursor ions;a first mass analyser configured to apply a selection of precursor ions according to their mass-to- charge ratios;a collision cell for fragmenting at least some of the selected precursor ions to generate product ions of the fragmented precursor ions;an ion transport apparatus according to any preceding claim, for receiving and transporting product ions from the collision cell;a second mass analyser configured to receive product ions extracted from the ion transport apparatus via the ion extraction port thereof, and configured to apply a process of mass analysis to the product ions.

24. A method of ion transport comprising:providing a power supply configured to supply RF voltages and DC voltages;providing a plurality of electrodes comprising: a set of axial confinement electrodes, a set of radial confinement electrodes, and an orthogonal extraction part, wherein the plurality of electrodes are spatially arranged collectively to define a volume extending along an ion optical axis to form a channel and wherein the orthogonal extraction part is arranged along the ion optical axis and comprises an ion extraction port configured for transmission therethrough of ions from the channel in a direction transverse to the ion optical axis; and,by the power supply:applying to the set of radial confinement electrodes and the orthogonal extraction part, one or more RF voltages to generate a radially-confining electric potential field forming a pseudopotential within the channel for guiding ions therealong;applying to the set of axial confinement electrodes one or more DC voltages to generate an axially-confining electric potential field forming a potential well within the channel for axially confining ions therein, wherein the axial confinement electrodes define an axially varying field radius that changes with increasing axial proximity to the orthogonal extraction part so as to align the potential well with the orthogonal extraction part; and,selectively applying one or more orthogonal extraction voltages to the orthogonal extraction part thereby ejecting axially confined ions from the potential well and through the ion extraction port.

25. An ion transport apparatus according to claim 24 wherein the axial confinement electrodes define an axially varying field radius that increases with increasing axial proximity to the orthogonal extraction part so as to align the potential well with the orthogonal extraction part.86717863726. A method of ion transport according to claim 24 or 25 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.

27. A method of mass spectrometry comprising the method of ion transport according to any of claims 24 to 26.

28. A method of mass spectrometry according to claim 27 further comprising providing a time-of-flight, TOF, mass analyser and transporting ions to the TOF mass analyser according to the method of ion transport, for mass analysis.

29. 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 and therewith fragmenting at least some of the selected precursor ions to generate product ions of the fragmented precursor ions;providing an ion transport apparatus according to any of claims 1 to 23;transporting the product ions and / or precursor ions in the ion transport apparatus according to the method of any of claims 24 to 26,;by a second mass analyser, applying a process of mass analysis to the product ions.

30. A method for mass spectrometry according to claim 28 comprising:providing an ion optical assembly arranged upon the ion optical axis for receiving ions and transmitting the ions in a direction along the ion optical axis towards the plurality of electrodes wherein the TOF analyser is configured to receive ions orthogonally extracted by the orthogonal extraction part, the method comprising:determining a pre-selected property of a TOF spectrum of orthogonally extracted ions detected by the TOF analyser; and,changing an ion transmission efficiency of the ion optical assembly according to the pre-selected property so determined.

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