WO2006105994A2

WO2006105994A2 - Faims apparatus with an on-axis ion inlet and method thereof

Info

Publication number: WO2006105994A2
Application number: PCT/EP2006/003362
Authority: WO
Inventors: Axel Kurt Mie
Original assignee: Axel Kurt Mie
Priority date: 2005-04-06
Filing date: 2006-03-30
Publication date: 2006-10-12
Also published as: WO2006105994A3

Abstract

Disclosed is a cylindrical geometry FAIMS apparatus with an improved ion inlet designed for efficiently transporting ions in the gas phase into the analyser region of the FAIMS apparatus. Ions are focussed into a region close to the tip (22a) of the inner electrode (22) carrying an asymmetric high voltage waveform and a compensation voltage, rather than colliding with the tip or other members in the vicinity. The focussing takes place in accordance with the ion focussing effect known from high-field asymmetric waveform ion mobility spectrometry (FAIMS). High electric field gradients occur in the vicinity of a tip carrying a voltage, and these high field gradients are used in the instant invention to yield a strong focussing effect. The main improvements lie in decreased ion losses with subsequently increased ion throughput and more sensitive ion detection, and in the increased flexibility in the design and position of ion sources.

Description

FAIMS apparatus with on-axis ion inlet and method therefor

AREA OF INVENTION

The instant invention relates generally to high-field a≤yπuuecric waveform ion mobility spectrometry (FAIMS), more particularly the instant invention relates to a low- diameter cylindrical FAIMS apparatus having an on-axis ion inlet.

BACKGROUND OF INVENTION

Ion mobility spectrometry (IMS) and high-field asymmetric waveform ion mobility spectrometry (FAIMS) are both based on ion mobility, which means that electric fields are employed to drag ions through a gas which is dense enough that the ions rapidly reach a terminal velocity. For example, atmospheric pressure offers such conditions, but gas pressures higher or lower can be used as well. In IMS, differences in ion mobility between different ion species are employed to separate ion species from each other. Different ion mobilities reflect different "size", i.e. different orientationally averaged collision cross-sections, of different ion species. Usually, IMS is performed at comparatively low electric field, and the ion mobility of any ion is constant, i.e. it is not a function of the electric field strength.

FAIMS uses a different aspect of ion mobility. At higher electric fields, the ion mobility k of an ion is no longer independent of the electric field strength. This fact has been known for a long time. Throughout this document, the term FAIMS apparatus refers to apparatuses featuring either an ion focussing effect according to FAIMS principles or an ion separation effect according to FAIMS principles or both.

FAIMS apparatuses have an analyser region where ion separation takes place. Most commonly, the analyser region is a region between a first and a second spaced-apart electrode. The first electrode is kept at a certain dc voltage, e.g. at ground potential. The second electrode is supplied with an asymmetric waveform, which contains a high voltage component. High voltage in this case means a voltage high enough to create an electric field in the analyser region that is high enough to let an ion's mobility k become a function of the electric field. Ions will oscillate between the electrodes, but as each ion species' mobility depends in a characteristic way on the electric field, after each cycle of the waveform the ions will not be positioned at the same distance from the electrodes, but rather be shifted towards one of the electrodes in a way that is characteristic for the ion species at the experimental conditions.

Carnahan and Tarassov describe in US patent No. 5,420,424, issued on May 30 1995, a FAIMS apparatus with cylindrical electrode geometry. The first electrode is a hollow cylinder, enclosing the second cylindrical electrode spaced-apart in a concentric way. The analyser region in between first and second electrode thus has an annular shape of a certain thickness; in many reported cases it is 2 mm thick. Ions are introduced into the analyser region by a stream of carrier gas. Once inside the analyser region, ions will be distributed around the inner electrode as a consequence of coulomb repulsion between ions, and of the carrier gas distributing itself into the entire analyser region .

The asymmetric waveform could, for example, be a repeating rectangular wave comprising a high-voltage component Vi during a short time ti, followed by a low- voltage component V₂ during a longer time t₂, in such a way that the time-averaged voltage is zero: Vi*ti+V₂*t₂=0. For example, V_high could be -4000V, t_high lμs, Vi_ow +1000V, and ti_ow 4μs. The peak voltage of the waveform, in this case

V_hi_gh=-4000V, is referred to as the Dispersion Voltage (DV) .

Now considering a positively charged ion species with a certain low-field ion mobility ki_ow, valid during the low- voltage part t of the waveform and a lower high-field ion mobility k_hi_gh, valid during the high-voltage part of the waveform. ki_ow is constant at all low electric fields, while k_hi_gh is a function of the electric field strength E and is in this example decreasing with higher electric field strength E. A first ion Ii is initially positioned in the middle of the gap defined by the cylindrically shaped inner and outer electrode. Now a waveform as mentioned above with a negative DV, e.g. DV=V_high= -4000V, t_hig_h = lμs and Vi_ow=+1000V, and ti_ow=4μs is applied to the second (inner) electrode, while the first (outer) electrode is kept at ground potential. During ti_ow, the positive ion will be repelled from the inner electrode and move towards the outer electrode. During t_high, the positive ion will be attracted by the inner electrode and move towards it . Those two movements will not cancel out each other, because the ion's mobility is decreased during thigh, (i.e. k_high < kiow) • After a number of waveform cycles, the ion will hit the outer electrode, be neutralised and thus "disappear" from the system. A negative direct current voltage can be applied to the inner cylinder together with the DV in order to compensate for the ions net motion towards the outer electrode, and keep it balanced in the middle of the analyser region. This direct current voltage is referred to as compensation voltage. Other ion species may not be balanced at this specific CV and thus hit either electrode. This is the principle of separation in FAIMS.

Now it is important to know that the absolute strength of an electric field in an annular space as defined by the two electrodes here, is decreasing with the distance from the inner electrode, given that there is a potential difference between the two electrodes.

A second ion I₂ of the same species in the same system is positioned closer to the outer electrode. During thighs it experiences a lower electric field and thus has a higher ion mobility, compared to Iχ. It will thus experience a net movement towards the inner electrode. The opposite is true for a third ion I₃ of the same species in the same system, which is positioned closer to the inner electrode. I₃ experiences a net movement towards the outer electrode. The ions are subjected to a focussing effect. If this were not counteracted by diffusion, Coulomb ion-ion repulsion (referred to also as space charge effects), and turbulences in the stream of carrier gas, the ions of this species would eventually form a very thin circular layer in between the two electrodes.

In the case of cylindrical FAIMS devices, the focussing effect and the separation effect are counteracting forces. As easily can be understood of one skilled in the art, the focussing effect will be stronger when the electric field has a higher gradient. Cylindrical FAIMS devices with lower electrode diameter have a higher electric field gradient and thus a better focussing effect and worse separation of ions of different species, provided that all other factors including the electrode spacing are equal .

One distinct region of interest is the ion inlet of FAIMS devices. In FAIMS, ions are commonly generated outside the actual FAIMS apparatus and enter the analyser region through some kind of ion inlet aperture, for example a hole in the outer electrode. Around this aperture, the electric fields governing the FAIMS separation and focussing effects are disturbed by fringe fields from the ion source and by the discontinuity of the outer electrode, because the electrode surface is interrupted. This can lead to ion collisions with surfaces. Thus, the size of the ion inlet aperture must be determined carefully; it must be small enough in order to prevent strong fringe fields to enter. However, a too small aperture will obviously also decrease the ion throughput of the FAIMS apparatus .

Depending on the choice of ion source with FAIMS, the position and design of the different features of the ion source must be controlled thoroughly in order to ensure an efficient transport of ions from the ion source into the analyser region.

Other apparatuses have been proposed and built. A prior art cylindrical FAIMS apparatus used for comparative measurements for this invention comprises an outer electrode and an inner electrode made from stainless steel. The outer electrode has an inner diameter of the cylindrical region of 20 mm. The inner electrode has a diameter in the cylindrical region of 16 mm. The electrodes define an analyser region of 2 mm width. The terminal parts of the electrodes have approximately hemispherical shape. Ions are generated from an ion source, for example an electrospray needle. Ions pass through a front plate orifice into a desolvation chamber. Through a carrier gas inlet the desired carrier gas is delivered into desolvation chamber at a flow rate in excess of the gas flow rate through the analyser region, in order to enforce a counter current of gas through the front plate orifice to keep the carrier gas inside the analyser region clean and well- defined. Ions then enter the FAIMS analyser region through an ion inlet orifice in the outer electrode. The ion inlet orifice has a rather small diameter of approximately 1 mm.

Ions are transported along the analyser region towards an ion outlet orifice in the outer electrode by a stream of carrier gas, the total longitudinal distance between the ion inlet and outlet orifices being approximately 37 mm. During the ions' residence time in the analyser region, ions are separated in accordance with the principles described above. Ions then leave the analyser region through ion outlet orifice towards mass spectrometer.

Of interest is international patent application WO0169216, published 2001, in which Purves and Guevremont describe a FAIMS apparatus made of three stacked parallel plates. The high voltage asymmetric waveform applied to the middle plate focuses ions in the vicinity of its edge and enables their transport into the two analytical gaps.

In international patent application WO0008455, published 2000, Purves and Guevremont describe a cylindrical FAIMS apparatus ("FAIMS-Rl prototype") where the ion source and the tip of the inner FAIMS electrode are in juxtaposition. The high-voltage asymmetric waveform is applied to the outer electrode. In the same patent, proposed is ion focussing in the vicinity of a round tip carrying a high-voltage asymmetric waveform ("FAIMS-R2 prototype") , being positioned close to the ion outlet of the cylindrical FAIMS apparatus.

In European patent application 0 679886, Carnahan and Tarassov generate ions on-axis with respect to the inner cylinder. In their preferred embodiment in accordance with their figure no. 2, corona discharge wire (60) is driven with an asymmetric high voltage waveform and generates ions. However not explicitly stated, there may occur ion focussing in the vicinity of the tip of the said corona discharge needle (60), ion source and focussing electrode being identical.

In International Patent Application WO 03/067624, Guevremont et al propose the idea of several prior art FAIMS devices being connected to one "central" FAIMS apparatus .

It is a limitation of the prior art FAIMS devices that ion throughput is restricted by the small size of the ion inlet necessary in order to prevent ion loss through fringe fields. Wider ion inlets will carry along a higher efficiency in ion transport from the ion source towards into the analyser region.

It is a limitation of the prior art FAIMS devices that the position of different features of the ion source must be controlled thoroughly. Weaker constraints will carry along higher flexibility with the design of the ion source, which will be beneficial e.g. for design MALDI interfaces to mass spectrometers and FAIMS apparatuses.

SUMMARY OF THE INVENTION Generally, the present invention provides a means for efficiently transporting ions from an ion source into an apparatus for further ion manipulation. In a first preferred embodiment, a cylindrical high-voltage asymmetric waveform ion mobility spectrometry (FAIMS) apparatus with small diameters of the cylindrical electrodes (1 and 5 mm diameter) and a wide on-axis ion inlet (5mm diameter) enables an active collection of ions from the ion source using an ion focussing effect, rather than relying on a carrier gas to drag in ions into the apparatus. In the first preferred embodiment, the invention comprises a first electrode, having essentially cylindrically shaped bore, and a second essentially cylindrical electrode with a rounded tip, the second electrode being positioned centred at least partly inside the first electrode. The first electrode provides a sample inlet, being identical with the end of the bore and being in communication with an ion source, and a sample outlet orifice, being in communication with a means of ion detection, for example a mass spectrometer .

The first and second electrodes define an analyser region, through which ions are transported longitudinally by means of a carrier gas flow. In the first preferred embodiment, the carrier gas is added to the system close to the ion inlet at the end of the first electrode, the carrier gas supply being shielded by a flat third electrode .

An ion source is positioned close to the ion inlet. Upon application of an asymmetric high voltage waveform to the second electrode, an ion focussing effect will focus ions in the vicinity of the rounded tip of the second electrode. Ions are then transported into the analyser region by the flow of carrier gas. Inside the analyser region, ions are separated under the influence of the asymmetric high voltage waveform. The separation is governed by the composition of the carrier gas, the shape, polarity and amplitude of the high voltage waveform, and an additional direct current voltage applied to first or second electrode. After separation, ions exit the analyser region through the ion outlet for detection.

In a second preferred embodiment, the ion outlet of a first FAIMS apparatus, in accordance with the first preferred embodiment, is in communication with a second cylindrical FAIMS apparatus. The first FAIMS apparatus achieves good ion input, whilst the second FAIMS apparatus achieves good separation.

BRIEF DESCRIPTION OF DRAWINGS

Figure 1 shows a drawing of a cylindrical FAIMS device according to a first preferred embodiment of the invention.

Figure 2 shows a drawing of a tandem cylindrical FAIMS device according to a second preferred embodiment of the invention.

Figure 3a shows a mass spectrum from a KCIO₃ solution, obtained with a prior art FAIMS apparatus.

Figure 3b shows a mass spectrum from a KCIO₃ solution, obtained with FAIMS apparatus of this invention.

DETAILED DESCRIPTION OF EMBODIMENTS Throughout this document, it is assumed that all electrodes have appropriate contacts to provide them with all necessary potentials. Also, it is assumed that an electrical controller is connected, which is able to produce all necessary potentials. The gas pressure all embodiments of the instant invention work at is commonly ambient pressure, but higher or lower pressures are also suitable, as long as FAIMS focussing and separation effects occur, as described above.

Referring to figure 1, the FAIMS apparatus of a first preferred embodiment of the current invention comprises outer electrode (21) and inner electrode (22) made from an electrically conducting material such as for example stainless steel, or from an insulating material such as for example glass, covered with a conductive layer. Outer electrode (21) has an inner diameter in the cylindrical region of 5.0 mm. Inner electrode (22) has a diameter in its cylindrical region of 1.0 mm, and has a rounded tip. Electrodes (21) and (22) define an analyser region of 2.0 mm width. The diameter of inner electrode (22) could be between 0.5 and 10 mm, preferably between 0.5 and 3 mm and most preferably between 1 and 2 mm. Inner diameter of outer electrode (21) will be of a size defined by the gap between inner electrode (22) and outer electrode (21), said gap could be from 0.5 to 4 mm, preferably between 1 an 3 mm and most preferably 2 mm. The axial position of electrode (22) inside electrode (21) can be adjusted. Support member (23) is machined from insulating material, e.g. PEEK. Outer electrode (21) has a first terminus (21a) facing an ionisation source, and a second terminus (21b) . Inner electrode (22) has a first terminus (22a) facing an ionisation source, and a second terminus (22b) . A DV and CV are applied to inner electrode (22), while outer electrode (21) is kept at ground potential. Ions are generated from at least one ion source, using for example electrospray ionisation (ESI) , photoionisation, beta-emission, thermal ionisation, atmospheric pressure chemical ionisation (APCI) or MALDI. For example, a potential difference between an electrospray needle (24) and a front plate electrode (25) drives the generation of ions. Ions pass through a front plate opening (26) of 5 mm diameter, the diameter optionally being adjustable e.g. by means of an adjustable iris aperture or a front plate with different diameter, into a desolvation chamber (27). Through a carrier gas inlet (28), drilled into insulating support member (29) , the desired carrier gas is delivered into the desolvation chamber at a flow rate in excess of the gas flow rate through the analyser region, in order to enforce a counter current of gas through front plate orifice (26) to keep the carrier gas inside the analyser region clean and well-defined. Instead of a carrier gas inlet (28), other ways of supplying a carrier gas can be envisualised; alternatively, it is possible that no defined carrier gas is added, and air form the ambient atmosphere is used instead.

Due to the very high curvature of electric field around first terminus (22a) of inner electrode (22), the ion focussing effect generated by the asymmetric waveform supplied to inner electrode (22) is very strong. A layer (14) in which one species of ions could be focussed in the vicinity of the tip is indicated. Thus, the focussing effect is not easily disturbed by fringe fields, so a small diameter ion inlet orifice preventing fringe fields is not necessary. Instead, the ion inlet (31) is identical with the end of the outer electrode (21), the ion inlet consequently having a diameter of 5 mm. Optionally, ion inlet (31) is adjustable to yield smaller diameters, e.g. by means of an adjustable iris aperture or an additional plate with an aperture of the desired diameter.

Consequently, in contrast to prior art FAIMS apparatuses, in the FAIMS apparatus of the current invention ions come shortly after their generation into the influence of the strong focussing field, because the focussing effect protrudes into desolvation chamber (27) . In order to maximise the benefits of this effect, the ion source should be in juxtaposition with the front plate opening (26) or, if no front plate is used, with the ion inlet (31) .

Advantages of this focussing lie in reduced ion loss during transfer from the ion source to the analyser region, with a subsequent improvement of ion throughput, a high flexibility in the positioning of the ion source relative to the ion inlet (31), and a higher flexibility in ion source and desolvation chamber design. It seems advantageous to use the instant invention together with a MALDI ion source.

A person skilled in the art will easily see that the exact form of first terminus (22a) of inner electrode (22) is not of importance. A somewhat convexly rounded tip, e.g. hemispherically or ellipsoidally shaped, will result in high field gradients in all directions. In fact, for small diameter inner electrodes, the tip could be flat as well without losing too much performance, resulting in a cylindrically shaped tip, but keeping it round and smooth decreases the risk of a corona discharge at the tip. Combinations of the mentioned geometries are of course possible as well. Analogous to the prior art apparatus, ions are transported along the analyser region (30) towards the ion outlet orifice (32) by a stream of carrier gas, the total longitudinal distance between ion inlet (31) and ion outlet orifice (32) being approximately 30 mm. During the ions' residence time in the analyser region (30), ions are separated in accordance with the principles described above. Ions then leave analyser region (30) through ion outlet orifice (32) towards mass spectrometer that is indicated with the end of its inlet capillary (33) .

In this design, desolvation chamber (27) is not a well-defined region as is desolvation chamber in some prior art FAIMS apparatuses. It is rather an open region that cannot be clearly marked off with respect to analyser region (30) .

Referring now to figure 2, there is shown a second preferred embodiment of the instant invention, comprising a tandem FAIMS-FAIMS apparatus. Ions enter after ionisation a first FAIMS apparatus according to figure 1, and subsequently a second FAIMS apparatus (34) according to the prior art through ion inlet (35) . The second FAIMS apparatus (34) shown in figure 2 is referred to as "side- to-side" FAIMS in the literature. In the second preferred embodiment according to the instant invention, the first FAIMS apparatus is mainly used for ensuring a high ion input, whilst the second FAIMS apparatus, having cylindrical electrodes with higher diameter and thus having the ability of better ion separation, is used for the actual separation of ions. Usually, focussing effect and separation effect are regarded as counteracting each other in FAIMS apparatuses. This tandem embodiment presents a beneficial combination of strong focussing and strong separation effects. In a ramification of the second preferred embodiment in accordance with figure 2, the second "high-radius" FAIMS apparatus (34) has a plurality of ion inlets (35) and is connected to a plurality of first "on-axis inlet" FAIMS apparatuses according to the first preferred embodiment of the instant invention, which each is in communication with an ion source. A further increase of ion throughput can be achieved that way. Also, different ion sources, e.g. electrospray ionisation (ESI) and atmospheric pressure chemical ionisation (APCI) can be used at different "on- axis inlet" FAIMS apparatuses in order to yield complimentary ionisation of a sample. Prior art devices carrying a plurality of FAIMS apparatuses on a "central" FAIMS apparatus suffer from the shortcoming that ion transport into the FAIMS analyser region solely relies on carrier gas flow. The total gas flow into all connected FAIMS devices is normally determined by the gas flow into the mass spectrometer, if a mass spectrometer is used as a means of detection. With several ion inlets, the carrier gas flow per ion inlet is reduced, which will lead to declined ion throughput per inlet. The benefits from having several ion inlets are thus at least partly cancelled out. This fact can be avoided using a number of FAIMS apparatuses of the first preferred embodiment of the current invention connected to one "central" FAIMS apparatus, because then ion transport into the FAIMS system not exclusively relies on gas flow but also on ion focussing .

Referring now to figure 3a, there is shown a mass spectrum obtained with a nano-electrospray ion source and a prior art FAIMS apparatus, using negative ionisation and a solution of 1 mg/L potassium chlorate (KCIO₃) , dissolved in a mixture of 80% and 20% water, the mixture also containing 0.2mM ammonium acetate. The signals at m/z=83.1 and 85.1 originate from chlorate (ClO₃ ^") ions. The FAIMS operating parameters were DV=-3500V, the waveform following the equation U = (2 sin (ωt ) +sin (2ωt -φ) ) *1166V, the frequency being approximately 75OkHz, and phase shift φ being π/2. The carrier gas was pure nitrogen. The CV has been optimised for the response of m/z=83.1 and was +36V. The y- axis of the mass spectrum shows ion intensities at arbitrary units.

Referring now to figure 3b, there is shown a mass spectrum that is obtained with the same solution and in the same way as the mass spectrum in figure 3a, except that a FAIMS apparatus in accordance with the first preferred embodiment of the instant invention, shown in figure 1, is used instead of a prior art FAIMS apparatus. DV was varied and then set to -4000V in order to result in a CV optimum comparable to the measurements of figure 3a. As the compared interfaces have a different geometry, it has to be made sure that comparable electric field conditions rule inside the analyser region. A way of calibrating FAIMS analysers is to adjust DV until the CV of the compound of interest has the same CV as in a reference system. The CV has then been optimised for the response of m/z=83.1 and was +34V. Comparing figure 3a to figure 3b, it can be seen that in figure 3b, there is a clear increase of signal intensity at m/z=83.1 and 85.1 compared to figure 3a. This increase can be attributed to the strong ion focussing effect around the tip of the inner electrode in the case of figure 3b.

The increased signal intensity is of value for e.g. FAIMS-MS/MS experiments. In MS/MS experiments, a noisy mass spectrum is in many cases not so much of a problem; the sensitivity-limiting factor is rather the total number of ions of the species of interest entering the mass spectrometer. This number is in the example of figures 3a and 3b increased when using the first preferred embodiment of the current invention, compared to a prior art FAIMS device.

Comparing the regions close to the x-axis of figures 3a and 3b, one can see that the mass spectrum in figure 3b contains a lot more signals that cannot be attributed to the CIO₃ ^" ions. In other words, the ion separation in the

"on-axis inlet" apparatus of the first preferred embodiment shown in figure 1 is inferior to the ion separation in the prior-art FAIMS apparatus. This is expected, because ion focussing and ion separation are counteracting effects; and small diameter FAIMS devices like in the first preferred embodiment of the instant invention feature strong focussing and thus decreased separation.

This fact can be used in cases where a high separation is not desired. For example, when analysing peptides from a tryptic digest of a protein, separated by high-performance liquid chromatography (HPLC) or other separation technique, and coupled to a mass spectrometer via a prior art FAIMS apparatus, different CVs must be monitored in order to see all generated peptide ions. This can be accomplished by choosing a small number of distinct CVs and cycling between them, as has been reported in the literature. However, the number of CVs must be small, because otherwise there is a risk of missing eluting peptides. Also, using for example four distinct CVs and cycling between them, will result in an averaged signal loss of a factor of four for all detected peptides, because the FAIMS analyser is only looking at a specific CV a fourth of the time. Using a small diameter FAIMS in accordance with the first preferred embodiment of the instant invention will decrease the separation to the extent that a smaller number, possibly only one, of CVs must be monitored. The background noise will, due to the decreased separation, be higher than using a prior art FAIMS, but the signal will also be higher, and the risk of missing peptides will be lower.

The separation of the apparatus according to the first preferred embodiment of the instant invention can be improved by applying an additional ripple voltage of a suitable frequency and amplitude to the inner or outer electrode. For example, a cloud of an ion species which is well focussed in the middle between inner electrode and outer electrode will oscillate between inner and outer electrode upon application of the additional ripple voltage, while other ion species may hit either electrode and be removed from the analyser region, resulting in a mass spectrum with less noise peaks.

Generally, all terms used in the claims are to be interpreted according to their ordinary meaning in the technical field, unless explicitly defined otherwise herein. All references to "a/an/the [element, device, component, means, step, etc]" are to be interpreted openly as referring to at least one instance of said element, device, component, means, step, etc., unless explicitly stated otherwise. The steps of any method disclosed herein do not have to be performed in the exact order disclosed, unless explicitly stated.

The invention has mainly been described above with reference to a few embodiments. However, as is readily appreciated by a person skilled in the art, other embodiments than the ones disclosed above are equally possible within the scope of the invention, as defined by the appended patent claims.

Claims

1. A FAIMS apparatus for separating ions, including a) an annular analyser region (30) defined by an outer electrode (21) and an inner electrode (22), the inner electrode being cylindrical along the analyser region, the outer electrode having a cylindrical inner surface along the analyser region, the inner electrode being concentrically positioned inside the outer electrode, the outer electrode extending over at least a portion of the inner electrode, and the outer and inner electrodes each having a first and a second terminus, b) at least one ion outlet orifice (32), c) at least one contact on the inner electrode for receiving an asymmetric waveform and optionally additional voltages such as a compensation voltage or a ripple voltage, and at least one contact on the outer electrode for receiving voltages, d) an ion inlet (31) in the first terminus (21a) of the outer electrode (21) being positioned on-axis with respect to the inner electrode, the ion inlet being in communication with an ion source, characterised by e) first terminus (22a) of inner electrode (22) being generally flat or of convex shape, and f) said terminus (22a) being in communication with the ion source through an ion inlet (31), said inlet (31) being sufficiently large to permit the electric field generated by the high voltage waveform applied to inner electrode (22) to protrude through said ion inlet (31) with a strength sufficiently high to create an ion focussing effect outside outer electrode (21), thus focusing ions in the vicinity of first terminus (22a) and facilitate the ions transport into analyser region (30) .

2. An apparatus according to claim 1 wherein the ion source is one of the group of electrospray ioniser, photoioniser, beta-emitter, thermal ioniser or MALDI.

3. An apparatus according to claims 1-2 wherein ion outlet (32) is in communication with a mass spectrometer.

4. An apparatus according to claims 1-3 wherein ion inlet (31) has a higher diameter than inner electrode (22) .

5. An apparatus according to claims 1-4 wherein the inner electrodes (22) longitudinal position inside outer electrode (21) is adjustable.

6. An apparatus according to claims 1-5 comprising a carrier gas inlet (28) for providing a flow of gas through the analyser region.

7. An apparatus according to claims 1-6 wherein the ion source is juxtaposed with the ion inlet (31) .

8. An apparatus according to claims 1-7 wherein first terminus (22a) of inner electrode (22) has has a generally convex rounded shape, e.g. the shape of one of the group of a) ellipsoid, b) hemisphere, c) cylinder.

9. An apparatus according to claims 1-8 comprising a front plate electrode (25) with a front plate opening (26), mounted on first terminus (21a) of outer electrode (21) , the front plate electrode having at least one contact for receiving a voltage.

10. An apparatus according to claims 1-9 wherein at least one ion outlet orifice (32) is in communication with a second FAIMS apparatus (34).

11. A system comprising a plurality of apparatuses according to claims 1-10, each apparatus being in communication with a second FAIMS apparatus (34), said second FAIMS apparatus having plurality of ion inlets (35) .

12. An apparatus according to claims 1-11 wherein the ion source is positioned outside outer electrode (21) .

13. An apparatus according to claims 1-12 wherein the diameter of the inner electrode is smaller than 10mm.

14. An apparatus according to claims 1-13 wherein a plurality of ion sources is in communication with ion inlet (31).

15 A method for focussing and separating ions, comprising the steps of a) providing at least one ionisation source for generating ions in the gas phase, b) providing a FAIMS analyser region defined by a generally annular region between first and second spaced-apart generally cylindrical electrodes, said analyser region having an ion inlet and an ion outlet, said ion inlet being positioned on-axis with respect to said inner electrode and said ion inlet being sufficiently large to allow FAIMS focussing fields to protrude through said ion inlet, in order to focus ions outside the immediate analyser region c) providing an asymmetric high-voltage waveform to the inner electrode and a direct current voltage to at least one of inner and outer electrodes, all voltages being provided by an electrical controller and supplied through suitable contacts, d) adjusting said high-voltage asymmetric waveform and said direct current potentials to focussing an ion species of interest, e) transferring said ion species through said ion outlet into a mass spectrometer.