ION TRANSFER APPARATUS

20180350581 ยท 2018-12-06

Assignee

Inventors

Cpc classification

International classification

Abstract

An ion transfer apparatus for transferring ions from a first pressure controlled chamber at a first pressure, which first pressure is lower than 10000 Pa, along a path to an adjacent second pressure controlled chamber at a second pressure that is lower than the first pressure. The ion transfer apparatus includes: the first pressure controlled chamber and the second pressure controlled chamber, wherein each pressure controlled chamber includes an ion inlet opening for receiving ions on the path and an ion outlet opening for outputting the ions on the path, wherein the ion outlet opening of the first pressure controlled chamber is in flow communication with the ion inlet opening of a the second pressure controlled chamber; and an RF focusing device configured to focus ions towards the path, the RF focusing device including a plurality of RF focusing electrodes, wherein each RF focusing electrode of the RF focusing device is configured to receive an RF voltage so as to produce an electric field that acts to focus ions towards the path, wherein each RF focusing electrode of the RF focusing device has a shape that extends circumferentially around the path. The first and second pressure controlled chambers each include RF focusing electrodes of the RF focusing device. Each RF focusing electrode of the RF focusing device has a thickness in the direction of the path and a thickness in a direction radial to the path that is less than a distance separating the RF focusing electrode from an adjacent RF focusing electrode of the RF focusing device.

Claims

1-20. (canceled)

21. An ion transfer apparatus for transferring ions from a first pressure controlled chamber at a first pressure, which first pressure is lower than 10000 Pa, along a path to an adjacent second pressure controlled chamber at a second pressure that is lower than the first pressure, the ion transfer apparatus including: the first pressure controlled chamber and the second pressure controlled chamber, wherein each pressure controlled chamber includes an ion inlet opening for receiving ions on the path and an ion outlet opening for outputting the ions on the path, wherein the ion outlet opening of the first pressure controlled chamber is in flow communication with the ion inlet opening of a the second pressure controlled chamber; and an RF focusing device configured to focus ions towards the path, the RF focusing device including a plurality of RF focusing electrodes, wherein each RF focusing electrode of the RF focusing device is configured to receive an RF voltage so as to produce an electric field that acts to focus ions towards the path, wherein each RF focusing electrode of the RF focusing device has a shape that extends circumferentially around the path; wherein the first and second pressure controlled chambers each include RF focusing electrodes of the RF focusing device; wherein each RF focusing electrode of the RF focusing device has a thickness in the direction of the path and a thickness in a direction radial to the path that is less than a distance separating the RF focusing electrode from an adjacent RF focusing electrode of the RF focusing device.

22. An ion transfer apparatus as set out in claim 21, wherein for each RF focusing electrode of the RF focusing device, the thickness of the RF focusing electrode in the direction of the path and the thickness of the RF focusing electrode in a direction radial to the path is less than half of a distance separating the RF focusing electrode from an adjacent RF focusing electrode of the RF focusing device.

23. An ion transfer apparatus as set out in claim 21, wherein for each RF focusing electrode of the RF focusing device, the RF focusing electrode is separated from an adjacent RF focusing electrode of the RF focusing device by a distance that is between 3 and 7 times the thickness of the RF focusing electrode in the direction of the path.

24. An ion transfer apparatus as set out in claim 21, wherein for each RF focusing electrode of the RF focusing device, the thickness of the RF focusing electrode in a direction radial to the path is between 0.5 and 1.5 times the thickness of the RF focusing electrode in the direction of the path.

25. An ion transfer apparatus as set out in claim 21, wherein, for each RF focusing electrode of the RF focusing device, the internal width of an aperture of the RF focusing electrode at its maximum extent is between 1.5 and 10 times a distance separating the RF focusing electrode from an adjacent RF focusing electrode of the RF focusing device.

26. An ion transfer apparatus as set out in claim 21 wherein, for each RF focusing electrode of the RF focusing device, an aperture of the RF focusing electrode has an internal width that is dependent on the position of the RF focusing electrode along the path such that the internal widths of the RF focusing electrodes reduce progressively with position along at least a portion of the path.

27. An ion transfer apparatus as set out in claim 21, wherein for each RF focusing electrode of the RF focusing device, the RF focusing electrode is part of a metal sheet.

28. An ion transfer apparatus as set out in claim 27, wherein each metal sheet includes an outer support structure connected to the RF focusing electrode that is part of the metal sheet via at least one supporting limb.

29. An ion transfer apparatus as set out in claim 28, wherein, for each metal sheet, the/each supporting limb connected to the RF focusing electrode that is part of the metal sheet has a thickness in a direction circumferential to the path that is no more than 3 times the thickness of the RF focusing electrode in the direction of the path.

30. An ion transfer apparatus as set out in claim 28, wherein, for each metal sheet, a distance from the outer support structure to the RF focusing electrode that is part of the metal sheet is, at its minimum extent, greater than an internal width of an aperture of the RF focusing electrode at its maximum extent.

31. An ion transfer apparatus as set out in claim 21, wherein if the second chamber has a pressure of more than 1000 Pa, the ratio of the pressure in the first chamber to the pressure in the second chamber is less than 2.

32. An ion transfer apparatus as set out in claim 21, wherein if the second chamber has a pressure of less than 1000 Pa, the ratio of the pressure in the first chamber to the pressure in the second chamber is less than 5.

33. An ion transfer apparatus as set out in claim 21, wherein the path in the first pressure controlled chamber is inclined relative to the path in the second pressure controlled chamber.

34. An ion transfer apparatus as set out in claim 21, wherein the ion transfer device includes more than two pressure controlled chambers that each include RF focusing electrodes of the RF focusing device.

35. An ion transfer apparatus as set out in claim 21, wherein the ion transfer device is for transferring ions from an ion mobility spectrometry device or a differential mobility spectrometry device at an IMS/DMS pressure, along a path towards a mass analyser at a mass analyser pressure that is lower than the IMS/DMS pressure.

36. An ion transfer apparatus as set out in claim 21, wherein: the ion transfer apparatus is for transferring ions from an ion source at an ion source pressure, which ion source pressure is greater than 500 mbar, along a path towards a mass analyser at a mass analyser pressure that is lower than the ion source pressure.

37. An ion transfer apparatus as set out in claim 21, wherein: the ion transfer device includes a plurality of pressure controlled chambers, wherein each pressure controlled chamber in the ion transfer apparatus includes an ion inlet opening for receiving ions from the ion source on the path and an ion outlet opening for outputting the ions on the path, wherein the first and second pressure controlled chambers are included in the plurality of pressure controlled chambers; the plurality of pressure controlled chambers are arranged in succession along the path from an initial pressure controlled chamber to a final pressure controlled chamber, wherein an ion outlet opening of each pressure controlled chamber other than the final pressure controlled chamber is in flow communication with the ion inlet opening of a successive adjacent pressure controlled chamber; the ion transfer apparatus is configured to have, in use, at least one pair of adjacent pressure controlled chambers for which a ratio of pressure in an upstream pressure controlled chamber to pressure in a downstream pressure controlled chamber is set such that there is substantially subsonic gas flow in the downstream pressure controlled chamber.

38. An ion transfer apparatus as set out in claim 37, wherein: a subset of the pressure controlled chambers each include one or more DC focusing electrodes configured to receive one or more DC voltages so as to produce an electric field that acts to focus ions towards the path; a subset of the pressure controlled chambers each include one or more RF focusing electrodes, each RF focusing electrode being configured to receive an RF voltage so as to produce an electric field that acts to focus ions towards the path.

39. A mass spectrometer including: an ion source at an ion source pressure; a mass analyser at a mass analyser pressure; an ion transfer apparatus for transferring ions from a first pressure controlled chamber at a first pressure, which first pressure is lower than 10000 Pa, along a path to an adjacent second pressure controlled chamber at a second pressure that is lower than the first pressure, the ion transfer apparatus including: the first pressure controlled chamber and the second pressure controlled chamber, wherein each pressure controlled chamber includes an ion inlet opening for receiving ions on the path and an ion outlet opening for outputting the ions on the path, wherein the ion outlet opening of the first pressure controlled chamber is in flow communication with the ion inlet opening of a the second pressure controlled chamber; and an RF focusing device configured to focus ions towards the path, the RF focusing device including a plurality of RF focusing electrodes, wherein each RF focusing electrode of the RF focusing device is configured to receive an RF voltage so as to produce an electric field that acts to focus ions towards the path, wherein each RF focusing electrode of the RF focusing device has a shape that extends circumferentially around the path; wherein the first and second pressure controlled chambers each include RF focusing electrodes of the RF focusing device; wherein each RF focusing electrode of the RF focusing device has a thickness in the direction of the path and a thickness in a direction radial to the path that is less than a distance separating the RF focusing electrode from an adjacent RF focusing electrode of the RF focusing device.

40. A method of making an ion transfer apparatus for transferring ions from a first pressure controlled chamber at a first pressure, which first pressure is lower than 10000 Pa, along a path to an adjacent second pressure controlled chamber at a second pressure that is lower than the first pressure, the ion transfer apparatus including: the first pressure controlled chamber and the second pressure controlled chamber, wherein each pressure controlled chamber includes an ion inlet opening for receiving ions on the path and an ion outlet opening for outputting the ions on the path, wherein the ion outlet opening of the first pressure controlled chamber is in flow communication with the ion inlet opening of a the second pressure controlled chamber; and an RF focusing device configured to focus ions towards the path, the RF focusing device including a plurality of RF focusing electrodes, wherein each RF focusing electrode of the RF focusing device is configured to receive an RF voltage so as to produce an electric field that acts to focus ions towards the path, wherein each RF focusing electrode of the RF focusing device has a shape that extends circumferentially around the path; wherein the first and second pressure controlled chambers each include RF focusing electrodes of the RF focusing device; wherein each RF focusing electrode of the RF focusing device has a thickness in the direction of the path and a thickness in a direction radial to the path that is less than a distance separating the RF focusing electrode from an adjacent RF focusing electrode of the RF focusing device; wherein the method includes forming each RF focusing electrode of the RF focusing device from a metal sheet by chemical etching.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0101] Examples of these proposals are discussed below, with reference to the accompanying drawings in which:

[0102] FIG. 1 shows a schematic diagram of an interface between a region at atmospheric pressure and one at low pressure comprising a plurality of chambers connected in series via sets of apertures, to provide a flow of gas from one chamber the next.

[0103] FIG. 2 shows a DSMC (direct simulation Monte-Carlo) simulation of the gas flow field for a series of pressure-controlled chambers, along with a table displaying data from the simulation.

[0104] FIG. 3(a)-(e) show possible electrode configurations for a focusing device (ion guide).

[0105] FIG. 4(a) shows a simulation ion trajectories passing through a pressure-controlled chamber with a focusing device (ion guides).

[0106] FIG. 4(b) shows a three-dimensional illustration of a focusing device (ion guides) in a pressure-controlled chamber.

[0107] FIG. 5(a) shows pictures of a gas transparent focusing device formed from a stack of chemically etched sheets of stainless steel with gradually reducing radius of apertures along the path and subsequently gold plated.

[0108] FIG. 5(b) shows a three-dimensional image of a focusing device used in a series of chambers, the first of which is pictured in FIG. 5(a).

[0109] FIG. 6(a) shows a table which gives the required number of apertures and length of the interface for a given aperture radius, assuming a gas acceptance flow rate of 460 mbar.Math.l/s.

[0110] FIG. 6(b) shows a cross-sectional view as viewed from the front of an interface with sixteen apertures in each stage of the interface.

[0111] FIG. 6(c) shows a cross-sectional view as viewed from the side of an interface with sixteen apertures in each stage of the interface.

[0112] FIG. 7-FIG. 11 are drawings relating to an Annex, described in more detail below.

DETAILED DESCRIPTION

[0113] In general, the following discussion describes examples of our proposals that relate generally to mass spectrometry and apparatuses and methods for use in mass spectrometry. In particular, though not exclusively, the examples relate to the transmission of gaseous ionic species generated in a region of relatively high or higher pressure (e.g. at or near atmospheric pressure) into a relatively lower or low pressure region.

[0114] The term ion transfer device and interface may be used interchangeably herein.

[0115] In the examples discussed below, an ion transfer apparatus has a focusing device (sometimes referred to herein as a gas transparent ring guide or ion guide) for transporting ions between pressure regions, via a plurality of chambers, and in which a gas jet flows through said chambers. The pressure in each chamber is set to control the jet velocity on the axis to be subsonic in all chambers. An RF focusing field formed within the ion guide for confining ions against the expanding gas jet. A method of construction for the above is also disclosed.

[0116] Beneficial effects of the ion transfer apparatus may include efficient and effective means to transport ions from a high pressure device, such as an ion mobility spectrometry (IMS) device or a differential mobility spectrometry (DMS) device operating at a typical pressure of 2000 Pa to lower pressure region, typically at 1 Pa.

[0117] In the examples discussed below, there is disclosed a gas transparent ring guide extending between multi pressure controlled chambers having a means to focus ions against the expanding gas jet thus providing a method of concentrating the ion flow with respect to the gas flow.

[0118] A starting point for the examples discussed below was a desire to improve the transport ions within the interface region of an API source efficiently, which interface region may include a differential mobility spectrometry (DMS) device e.g. according to U.S. Pat. No. 8,610,054, located in the interface region of a mass spectrometer. A DMS device typically operates in a pressure range 1500 to 5000 Pa. It is desirable that ions exiting the DMS device are transported from this relatively high pressure to a lower pressure region, typically <1 mbar with high efficiency and having a wide range of m/z. This was a motivating factor behind the present invention. At pressure <1 mbar traditional RF multipoles are effective.

[0119] The present inventors intended to develop a vacuum DMS device, and observed that: [0120] Losses in prior art device may be due to high gas speed, and specifically supersonic speed. The gaseous ions entrained within a high speed gas flow are effectively bound to follow that flow and electrical fields are ineffective or partially ineffective to influence the ion flow in opposition to the gas flow. Furthermore high supersonic gas speed results in high turbulence, this turbulence may also reduce ion transmission. [0121] This motivation was to find a method more effective than prior art devices to transport ions from a DMS device, e.g. as described in U.S. Pat. No. 8,610,054. [0122] In support of the invention iterative simulations were undertaken to investigate gas dynamic effects in the interface and conditions preferred to reduce the gas velocity the separate the gas gradually from the main jet.

[0123] In devising the present invention, the present inventors were trying to achieve: [0124] a) An increase in the ion current that may be transmitted from the DMS device. [0125] b) An increase in the transmission efficiency of ions transmitted from the DMS device.

[0126] Potential advantages to a user may include: [0127] a) A wider range of ion mass and mobility may be transmitted simultaneously through the device. [0128] b) A lower level of concentration of sample ions may be analysed; that is a lower limit of detection (LOD) or instrument detection limit (IDL)

[0129] The studies referred to above led to the realisation that it is preferable to maintain the gas velocity subsonic, and allow expansion of the gas jet radially through the ion guide structure. It was found that the control of jet pressure ratio (JPR) between subsequent pressure controlled chambers allows for gradual and controlled separation of the ions from the gas flow, and further allows the use of RF electrical fields, i.e. pseudo potential to effectively confine ions towards the central axis of the device.

[0130] Thus the jet pressure ratio (JPR) may be defined to limit the gas speed. As a consequence one may define a sequence of pressure controlled chambers having small pressure drop between chambers so to transport ions from an initial (high) pressure to a final (low) pressure.

[0131] Here is a non-exhaustive list of what is considered to be new and clever aspects of the present disclosure: [0132] 1. Imposed fixed pressure ratios to maintain the gas flow subsonic in a device for transporting ions [0133] 2. A focusing device, which can be referred to as a gas transparent ring guide (funnel, tunnel or other), implemented within a plurality of interconnected pressure controlled chambers. The ring guide is preferably made from multiple ring electrodes, where each ring electrodes and the chamber end walls are formed from thin metal sheets by the process of chemical etching. [0134] 3. A device for transporting ions comprising a plurality of interconnected pressure controlled chambers having a plurality of parallel channels. [0135] 4. The stacked ring guides located in adjacent pressure controlled chambers may be set at a small angle to each other.

[0136] Preferably: [0137] The velocity of the gas jet is kept sufficiently slow through the transport device. [0138] The jet pressure ratio between adjacent chambers is maintained within certain limits. [0139] A geometry of the pressure controlled chambers and stacked ring guide is correctly defined.

[0140] As a result, it is preferred that: [0141] A defined proportion of gas may be removed from the main jet at each pressure controlled chamber. [0142] A sufficiently low outward radial flow from a gas jet is achieved to allow focusing of ions against the flow for ions having a wide range of mobility values.

[0143] Slow gas flow through the transport device prevents the formation of Mach regions and provides a reduction of the turbulence within the downstream jet. Turbulence in the gas jet may result in high ion losses through the device.

[0144] FIG. 1 shows a plurality of chambers (numbered 1 to 29). Chamber 1 has an entrance aperture 82 and exit aperture 84. Gas flows into chamber 1 from a higher pressure region (P <10 kPa). The pressure of gas in chamber 1 is lower and is determined by aperture 41. The pressure in chamber 3 is further lower than the pressure in chamber 1, and the pressure in chamber 5 is further lower than chamber 3. The ratio of the gas pressure between consecutive chambers is referred to as the jet pressure ratio (JPR). Gas flow enters chamber 1 as a confined jet and goes through the consecutive chambers from chamber 1 to chamber 29. The mass flow rate of jet is gradually reduced as the gas flows from chamber 1 towards chamber 29.

[0145] With reference to FIG. 2 there is shown sequence of 8 pressure controlled chambers (note that the pressures stated are the pressures for the downstream chamber corresponding to the stated pressure ratio). The chambers 1223 and 1225 have a length of 20 mm and chambers 1227 to 1237 all have length of 30 mm. In this embodiment the diameter of the apertures between chambers are all 2 mm.

[0146] Ion optic focusing elements with each chamber are not shown in FIG. 2. Also shown in FIG. 2, is the velocity of the gas jet calculated by the method of direct simulation Monte Carlo (DSMC). Also shown is jet pressure ratio (JPR) between chambers which is defined by the set pressure in the pressure control chambers. The JPR increases from 1.52 between the high pressure region and chamber 101 to 5 between chambers 1133 and 1135. This choice of JPR is sufficiently low to prevent the formation of a shock wave within each chamber and that the gas flow remains subsonic in all chambers but chamber 1235, which has a Mach number of 1.17. However, as the jet does not reach the chamber end wall and the pressure is already reduced to 12 Pa, there is no loss of ions.

[0147] In practice the JPR may be decided by the pumping speed applied to each pressure controlled chamber. Chambers may be pumped independently or may be pumped by a single pump or through chamber 1237. In the latter case the conductance between chambers may be adjusted to provide the required pressure in each chamber.

[0148] It can be seen from FIG. 2 that gas expands in each chamber in radial direction. In chambers 1223, 1225, 1227 and 229 there is a significant radially outwards flow on the surface of the chamber end walls. The proportion of gas flowing radially and not passing into the adjacent downstream chamber may be controlled by a combination of the JPR and the geometry of the chamber. More specifically the ratio of spacing between chamber walls, l and the diameter of the aperture, d, may be chosen to determine the proportion of gas to be removed in each chamber. In this embodiment the value of l/d is 10 and 15. Thus JPR may be used to vary the amount of gas removed in each chamber but the higher will be the ions losses.

[0149] The amount of gas removed in each chamber influences the strength of focusing needed to maintain ions closer to the axis of the gas jet.

[0150] With reference to the theory, the velocity of an ion in the gas media within the 1.sup.st part of the device may be described by the following equation:

[00001] v .fwdarw. = u .fwdarw. + 10 5 .Math. K o .Math. E .fwdarw. P Equation .Math. .Math. 1

K.sub.o is the ion mobility coefficient at pressure atmospheric pressure (110.sup.5 Pa) and P is the local gas pressure in Pascal. Eq. 1 holds in the region of continuum physics. A typical value for K.sub.o in LCMS applications is of 0.0001 m.sup.2/(V.Math.s)

[0151] At a pressure of 110.sup.3 Pa an electrical field of 210.sup.5 V/m field causes the ion to drift at a maximum velocity for the ion of 2,000 m/s, for this field is a maximum theoretical limit, in practice one is able to use significantly lower fields as ions would be caused to fragment at such field strength (the electrical field is so strong that heats up the ion causing fragmentation). A practical limit may be defined by the E/N value (Electrical field divided by the number density of the gas), usually measured in units of Townsend (Td), where 1 Td=110.sup.21 V/m.sup.2. Ions may fragment at E/N>100 to 300 Td. In this example of 110.sup.3 Pa (10 mbar) a maximum field strength is 510.sup.4 V/m, it corresponds to an ion drift velocity of (the ion having a reduced mobility value of 0.01 m.sup.2/Vs) of 200 m/s. This corresponds to Mach numbers of 0.55. A further restriction on the electrical field strength that may be employed for an interface to be employed as a general ion transmission device comes from the consideration that one must transmit ions having a range of mobility values. Typically in the range K.sub.o610.sup.5 to 310.sup.4 m.sup.2/(V.Math.s), that is a factor of 5. This imposes some further lowering of the upper limits of ion drift velocity and thus gas velocity that may be tolerated. Eq. 1 is a very simple expression employed to describe the ion drift velocity in ion mobility devices. To understand ion motion in the present device, a more detail analysis of the ion interface is insightful. Eq. 1 is more generally expressed as:


{right arrow over (v)}.sub.j={right arrow over (u)}+K.sub.j{right arrow over (E)}(1/.sub.j)(D.sub.j grad .sub.j) Equation 2

[0152] Where {right arrow over (v)}.sub.j (x,y,z,t) is the velocity of ion of type j at point x,y,z at time t, K.sub.j is the reduce mobility of ion of type j, D.sub.j(x,y,z,t) is the diffusion coefficient for the charged particles of type j which depends, in particular, on gas pressure and temperature at point x, y, z. {right arrow over (u)}(x, y, z) is the velocity of the neutral gas at point x, y, z and {right arrow over (E)}(x, y, z, t)=grad U(x, y, z, t) is the electric field intensity where U(x, y, z, t) is the electric potential.

[00002] j t + div ( j .Math. v .fwdarw. j ) = 0 Equation .Math. .Math. 3 div ( .Math..Math. 0 .Math. E .fwdarw. ) = div ( - .Math..Math. 0 .Math. grad .Math. .Math. U ) = j Equation .Math. .Math. 4

[0153] These equations may be solved as a system using numerical methods. Software was developed by the inventors for this purpose. Such a system of equations takes into account not only the gas flow and electrical field, but also the influence of diffusion and the total space charge density .sub.j. This system of equations has validity only in the continuum flow regime, and when the external variables change with respect to time and space coordinates only slowly. Furthermore, implicit in Equation 2 is that the ion velocity is constant, or rather changes slowly compared to the characteristic relaxation time of the ions. For the purposes of describing the current invention the system of equations is valid to a pressure range to 1000 Pa, and is valid assuming no shock waves in the gas flow are formed. Thus only valid for chambers 1225 and 1227.

[0154] In the example shown in FIG. 2, a gas jet continues to be established through chambers 1225, 1227, 1229, 1231, 1233 which as demonstrated by the DSMC calculation. The jet becomes progressively more divergent as the pressure is reduced and thus the JPR is increased. In pressure control chamber 1235 the jet no longer persist and the gas flow reduces practically to stand still at the midpoint of chamber 1235. The JPR between chamber 1233 and 1235 is 5 and the pressure in chamber 1235 is 12 Pa (0.12 mbar). The flow is divergent and gas speed reduces rapidly in all directions. The JPR between chamber 1235 and 1237 is 12 and the pressure in chamber 1237 is 1 Pa (0.01 mbar). The gas flowing into chambers 1235 and 1237 approaches that of a cosine distribution as expected for molecular flow conditions.

[0155] To study the transmission of ions through chambers 1223 to 1237 of the current embodiment, a particle tracking Monte Carlo method was used. The Monte Carlo simulation tracks individual ions using the gas flow field obtained by the direct simulation Monte Carlo (DSMC) method and calculation of the electrical field by a finite difference method. Considering the chamber 1225 of FIG. 2, the pressure is 1420 Pa giving a reduce mobility is 0.0071 m.sup.2/Vs (K.sub.o=0.0001 m.sup.2/Vs). The drift velocity whilst maintaining the applied field within the low field limit (E/N<10 Td) provides an ion drift velocity of 25 ms.sup.1. The diffusion coefficient D.sub.j also scales with pressure, as D.sub.j may be expressed in terms of the reduce mobility (see Equation 5). D.sub.o=2.6*10.sup.6 [m.sup.2/s] for K.sub.o=0.0001 [m.sup.2/Vs]. So in chamber 1225 diffusion is a factor 70 larger than at atmospheric pressure. DC fields can be used to focus ions towards the axis, but they cannot reduce the diffuse scattering of the ions that is pronounced in the lower pressure regions. However RF fields work well under low pressure providing the means to repel ions towards the axis, i.e. focusing them. Thus the present invention is most effective when RF fields are used. Additional DC focusing can optionally be used.

[00003] D = k b .Math. T e .Math. K Equation .Math. .Math. 5

[0156] As found by the inventors, the key aspect of the stacked ring guide, when applied to an interface having a plurality of pressure controlled chambers, is the aspect of gas transparency. A gas transparent ion guide has a structure which is effective to allow gas to escape or flow out radially largely unhindered through the walls of the ion guide. This type of focusing device (ion guide) is described further with reference to FIG. 3. Structures (a) and (c) represent structures of the prior art. In (c) the electrodes are spaced by insulating rings, and it is clear that no gas is able to pass out radially and so all gas passing into the input will pass out the output, that is the gas throughput at the input is equal to that of the output. In the context of the multi-chamber interface, this causes a build-up of the gas pressure at the exit aperture of the chamber a high radial flow at the chamber end wall and consequently high ions losses. Although structure (a), also described in the prior art, provides gaps between the electrodes, a study of the gas dynamics shows that this structure is equivalent to (c) and no significant amount of gas is able to pass out of the structure radially. Note that structure (a) is characterised by L>>d, and df (f is the electrode spacing). Here L is the thickness of the electrodes in radial direction, d is thickness of the electrodes in axial direction. In FIG. 3, Structure (a) f=2.65 d, the gap between the electrode is thus 1.65d. Structure (b) is an improvement on (a) in respect of the expected gas transparency. In thus structure L=d and f=2.65 d. However, this structure also has limited gas transparency and is not a preferred embodiment. Structure (d) is characterised by the L=d, and the f>>d, it is drawn as 9.3 d. This structure has very good gas transparency, but due to the large spacing the pseudo potential between the rings created by application of RF voltage to the rings, will not retain the ions inside the structure. Structure (e) provides L=d and f=5d and D=2f, where D is the inner diameter of the structure and represents a preferred embodiment for the stacked ring guide. Structure (e) will provide both transparency to the gas, also confine ions by the pseudo potential. The diameter of the D is preferably chosen to be comparable to the diameter of the gas jet.

[0157] An ion simulation of a preferred embodiment is shown in FIG. 4, which shows ion trajectories passing through chamber 1225 (see FIG. 2). In this simulation L=d=0.2 mm, f=1 mm and D=3 mm. The trajectories are plotted in the mass range m/z=200 Th to 1000 Th, with the collision cross section adjusted appropriately to the mass of the ions. The simulation shows there are no ions losses, all ions entering through the input aperture to chamber 1225 pass through the exit aperture, the transmission is 100%. Similar simulations, performed for chambers 1227, 1229, 1231, 1235 and 1237, show the same result of 100% ion transmission. As the pressure is reduced through chambers 1225 to 1237, the RF focusing becomes more effective at moving ions against the radial gas flow. As ions approach the exit, they are converged by the radially inward gas flow.

[0158] The focusing device is preferably constructed from chemically etched sheets of stainless steel which provides a fine pitch of the ring guide and simultaneously provides high gas transparency. The transparent ring ion guide may have an ID comparable to the pressure limiting apertures used for separating the pressure controlled chambers.

[0159] A device according to the current invention formed from chemically etched sheets is shown in FIG. 5(a) and FIG. 5(b). FIG. 5(a) shows a focusing device, which may be referred to as a gas transparent ion funnel, formed from a stack of chemically etched sheets of stainless steel and subsequently gold plated. This is shown as the 1.sup.st chamber of the focusing device (ion guide) in FIG. 5(b). The same method of construction is used to form further chambers of the device shown here as transparent stacked ring ion tunnels in each of the 5 chambers. The same construction methods may be used to form devices having multiple channels and or converging channels, i.e. several channels converging to a single channel.

[0160] The transparent stacked ring ion guide transports ions through several pressure controlled chambers. It is not necessary to provide pumping to each of the pressure controlled chambers as is required by U.S. Pat. No. 7,064,321B, but in embodiments the conductance between chambers may be adjusted by setting a conductance pathway be chambers. Pumping arrangements as discussed in PCT/GB2015/051569 (currently unpublished, but relevant extracts from which are included in the present disclosure as an Annex) are applicable.

[0161] In other preferred embodiments the axis of (i.e. the path towards which ions as focused by) the stacked ring guides may be set at an angle to each other to as shown by FIG. 5(b). This provides a further means to control gas separation from ions and also provides a method to remove fast neutral particles from the gas jet. Fast neutral particles may take the form of solvent droplets originating in the ESI spray plume that have not fully evaporated. These droplets are harmful to the limit of detections of the downstream mass analyser, and are preferably removed in the ion transport channel.

[0162] Ions may be supplied to the device from an ESI probe according to the prior art for creating a plume or spray of charged droplets containing sample ions, and including a means to evaporate the droplets to generate gaseous sample ions at the ion source region (usually operating under atmospheric pressure) or within an upstream interface according to the prior art, and a means for transporting sample ions to a differential mobility device according to prior art.

[0163] The described ion transfer device has general application as an ion transport device directed to transporting ions efficiently between pressure regions, where the gas flow is reduced within each stage. For example, it may be employed instead of an ion funnel or other stacked ring device, and may operate with improved efficiency and at higher pressure than the prior art devices. It may be used to transport ions from analytical devices which operate at pressures higher than traditional prior art devices that work effectively at 1 Pa or lower. Analytical devices are DMS and IMS operating within intermediate pressure, typically 1000 to 10000 Pa and within the interface region of an atmospheric pressure ionisation source of a mass spectrometer.

[0164] The following represents preferred features/conditions/operating ranges for implementing the present proposals (of course, these values/ranges may depend upon individual application requirements and size constraints): [0165] JPR profile The JPR profile set out above is only one example. Many other examples may be considered provided that the gas jet velocity does not exceed Mach 1, and is preferably significantly less than Mach 1. Preferably, the pressure in the pressure control chamber does not fall below 100 Pa. [0166] % gas removed: The gas flow removed from the gas jet per chamber may be in the range 5% to 50%. [0167] Chamber geometry: The ratio of spacing between chamber walls, l and the diameter of the aperture, h, in the end walls of the chamber may be chosen to determine the proportion of gas to be removed in each chamber. Generally the value of l/h may vary from 5 to 50. This ratio may be constant throughout the device, or most generally may be varied along the device. [0168] Diameter h: h may be typically in the range 0.1 mm to 5 mm. [0169] Focusing: The device may have RF focusing only or DC and RF focusing. [0170] Pressure range: The device is useful for transporting ions from high pressure to low pressure Typically the upper pressure range is 10000 Pa and the lower pressure limit is 1 Pa. [0171] Gas transparent stacked ring device: L=0.5 d to 1.5 d and f=3 d to 6 d and D=1.5 f to 10 f.

Multi-Channel Device (Parallel Embodiment):

[0172] Prior discussion was limited to an interface with a single channel (single path). A single channel system however suffers a number of restrictions. In order to achieve enhanced gas throughput one must have set apertures as large as possible. However, as has been described this determines the length of the device. In preferred embodiments this requires a device length that is too long for some potential applications.

[0173] The present disclosure allows for increases in gas throughput or intake compared to prior art devices, and is limited only by the investment in the pumping system and the size of the device. The diameter of the aperture h in each pressure controlled chamber in turn determines l the spacing between chamber walls. Thus simply increasing the diameter h of a single aperture will lead to a device that is longer than to be viable for use in some commercial LCMS system. Although feasible for high end bespoke instrumentation, ultimately the length may become a disadvantage in commercial implementation. An effective alternative is a multiple chamber (MC) interface having a number of parallel channels. An MC interface having a plurality of channels thus falls within the scope of the invention. As the size of the gas jet scales with the diameter of the inlet aperture, the overall length of the structure may be scaled with aperture size. Gas throughput may be maintained by increasing the number of apertures. FIG. 6(a) gives the radius and number of apertures assuming the device required 10 chambers to deliver ions between from the initial to final pressure. For example a reduction of the apertures to radii from 1 mm to 0.2 mm would require 25 parallel channels. The length of the device would reduce from 300 mm to 60 mm. Such a parallel embodiment of the MC interface would provide acceptable dimension to the application of commercial LCMS instrumentation and could feasibly be produced from a stack of chemically etched sheets. An example of a structure having a plurality of chambers is shown in FIG. 6(b) and FIG. 6(c). FIG. 6(b) shows the cross sectional view as viewed from the front of the device. FIG. 6(c) shows the cross sectional view as viewed from the side of the device, only a proportion of 45 pressure controlled chambers are shown. The device shown has 16 apertures 5, in each stage of the device. The pressure control chamber is divided into equal 16 segments 3, each of which is in fluid communication with pumped region 1. Each pressure controlled chamber 9, is formed from conducting sheets 11, which form the chamber endplates and insulating spacers 9. The insulating spacers have apertures to determine the pressure in the pressure controlled chambers. Optionally the endplates may have formed grooved for guiding the gas to the exit apertures, e.g. as described in PCT/GB2015/051569 (currently unpublished, but relevant extracts from which are included in the present disclosure as an Annex). The chambers may contain focusing elements in each chamber as described above. Optionally the endplates may be formed from PCBs and may be used to deliver voltages to the lens electrodes. These are not shown in FIG. 6. An additional advantage of the parallel embodiment of the MC device is that focusing may be achieved with reduced voltages applied to the electrodes.

[0174] The apparatus as described above is intended for use in any LCMS instrumentation, it could be fitted to any instrument with hardware modifications. It is also applicable to any ionisation method taking place at atmospheric pressure such as nanospray, direct ionisation methods, AP-MALDI. It is expected that the device would be used for next generation instrument only, although a factory retrofit would in principle be possible.

[0175] When used in this specification and claims, the terms comprises and comprising, including and variations thereof mean that the specified features, steps or integers are included. The terms are not to be interpreted to exclude the possibility of other features, steps or integers being present.

[0176] 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.

[0177] 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.

[0178] 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.

[0179] All references referred to above are hereby incorporated by reference.

ANNEXEXTRACTS FROM PCT/GB2015/051569

[0180] These extracts from PCT/GB2015/051569 are included to provide background as regards the possible construction and operation of an ion transfer apparatus including a plurality of pressure-control chambers.

[0181] In this Annex, the figures have been renumbered to avoid conflict with the other figures in this patent application, and the claims have been relabelled as statements to avoid confusion with the claims of this patent application.

[0182] Examples of preferred embodiments of the invention will now be described for the purposes of illustrating the invention in some implementations. It should be understood that the invention is not limited to any one of these embodiments.

[0183] FIG. 7 is a schematic illustration of a generalized arrangement of a skimmer-electrode array according to an embodiment of the invention;

[0184] FIG. 8 is a schematic illustration of a generalized arrangement of a skimmer-electrode array according to an embodiment of the invention;

[0185] FIG. 9 is a schematic illustration of a generalized arrangement of an array designed with off-axis skimmer-electrodes according to an embodiment of the invention;

[0186] FIG. 10 is a schematic illustration of a generalized arrangement of an array equipped with focusing electrodes to collimate the ions and simultaneously channel the flow.

[0187] FIG. 11 is a schematic illustration of a skimmer (which may also serve as an electrode) machined with slots extending radially outwards to collect and direct the gas toward respective pressure exhaust openings.

[0188] An illustrative example of an embodiment is described with reference to FIG. 7. A skimmer-shaped electrode 101 is positioned at the entrance of the array to sample ions produced in the ionization source. Ions are preferably produced by electrospray ionization although other ionization methods readily apparent to those skilled in the art can also be employed. A proportion of an electrospray plume of charged droplets is directed towards or orthogonal to the first skimmer electrode 101 with a circular inlet aperture or ion inlet opening that may greater than 2 mm in diameter. A series of similarly shaped skimmer electrodes is positioned further downstream using insulating rings 103. Region 102 established between the first two skimmer-electrodes defines the pressure control chamber volume which is partially evacuated through a series of pressure exhaust openings or orifices 104 arranged symmetrically on the first insulating ring 103. Region 102 is therefore in fluid communication with the pumping line 105 connected to a vacuum pump through port 106.

[0189] The gas load presented to the second skimmer electrode is reduced by an amount equivalent to the amount of mass flow rate subtracted by the suctioning action of orifices 104 while pressure in the second region or second pressure-control chamber established between the second and third skimmer electrodes positioned by the second insulating ring is lower. A second set of orifices on the second insulating ring removes part of the remaining gas load to reduce pressure in the third region of the array further. Pressure is therefore reduced progressively from the entrance to the exit of the array thus permitting the use of wide aperture sizes to be employed as a means to enhance ion conductance. Pressure levels in each of the regions established between neighbouring skimmer electrodes is controlled by adjusting the dimensions of the skimmer aperture sizes and the dimensions of the orifices within insulating rings 103 used for pumping gas. Electrostatic focusing can be employed by application of appropriate DC potentials to the skimmer electrodes to focus ions in-through the apertures with high transmission efficiency. The entire array is preferably operated at elevated temperature to promote desolvation of charged droplets.

[0190] The skimmer array of FIG. 7 can form an integral part of a mass spectrometer interface where the final stage or region of the array is operated at a pressure of approximately 1 mbar. Subsequent vacuum regions equipped with standard RF ion optical elements typical to those employed in modern mass spectrometers and operated at pressure below 1 mbar can be connected at the far end of the array. In another preferred embodiment the final stage is maintained at an elevated pressure, for example at a pressure of 100 mbar, and the array is coupled to the standard inlet of a mass spectrometer equipped with conventional ion optical systems, for example RF ion optical devices such as the ion funnel or other types of RF ion guides devices operated at approximately 10 mbar and readily known to those skilled in the art. In this preferred embodiment the gas load presented to the entrance of the 10 mbar vacuum region is reduced considerably compared to existing interface designs where pressure is reduced from 1 bar in a single step, therefore the dimensions of the inlet can be increased significantly.

[0191] FIG. 7. is a schematic illustration of a generalized arrangement of an atmospheric pressure mass spectrometer interface comprising of a skimmer-electrode array designed to reduce pressure from the ionization source pressure to a lower pressure level in a progressive manner whilst ion transmission is enhanced compared to existing interface technology.

[0192] A method for the parameterization of the device in order to specify the dimensions of the apparatus is made with reference to FIG. 8. In this preferred embodiment the apparatus consists of a number of consecutive skimmers and ring spacers forming successive regions 201, 202, 203 and 210 designated with [A.sub.1], [A.sub.2], [A.sub.3] and [A.sub.n] respectively. An array design with additional stages between regions 203 and 210 can be implemented but only four regions are shown for simplicity. The skimmer electrodes and ring spacers are shaped into a primary conduit 211 designated with [A] with a predetermined diameter. A secondary conduit 212 designated with [A.sub.o] is arranged coaxially and externally to the primary conduit 211 to produce an inner gap, which defines the pumping line 213 designated with [B]. This is the lowest pressure region evacuated using a vacuum pump. All regions 201, 202, 203 and up to the final stage here designated with 210 are in communication with the pumping line 213 through a series of orifices on the insulating ring spacers, similar to the orifices 104 presented in FIG. 7. The method disclosed herein is concerned with the determination of the internal radius of the orifices that must be employed in order to obtain a desired progressive reduction in pressure for an array configuration with a predetermined number of stages.

[0193] For the following calculation procedure region 201 will be referred to as [A.sub.1], region 202 as [A.sub.2] and so forth up to the final stage designated with [A.sub.n]. Pressure in region [B] is always lower than the lowest pressure in region [A.sub.n], and in case of sonic conditions (choked flow) established through the pressure exhaust openings at least by a fraction . For the parameterization method presented the requirement is that sonic conditions are always established at the exit of each opening (the mean value of the Mach number at the exit of each aperture is always equal to 1.0, which means that a chocked flow is formed). Although the parameterization method disclosed is concerned with the formation of chocked flow conditions at the orifices used for pumping gas it is by no means limited to such. Other parameterization procedures can be devised readily apparent to those skilled in the art, for example different array configurations are envisaged where the flow through the orifices on the insulating rings is not chocked and/or the pumping line [B] is further sub-divided into regions which may be individually connected to one or more pumps, and each region in communication with only a fraction of the skimmer array through the corresponding orifices on the ring spacers.

[0194] For chocked flow conditions the internal radius of each of the orifices is computed by defining (a) the mass flow rate m, that is desired to be subtracted from each region [A.sub.i], i=1, . . . , n, (b) the average static pressure P.sub.i in each region [A.sub.i], i=1, . . . , n, (c) the average total pressure P.sub.t, in each region [A], i=1, . . . , n, (d) the average total temperature T.sub.ti in each region [A.sub.i], i=1, . . . , n, and finally (e) the number of orifices C.sub.i where i=1, . . . , n, distributed circumferentially on each of the ring spacers connecting each region with the pumping line region [B].

[0195] The following definitions are introduced for conciseness. Here n refers to the number of the consecutive regions, M is the mach number, R is the gas constant, y is the ratio of specific heats of the gas (y=C.sub.p/C.sub.v) where C.sub.p is the heat capacity at constant pressure and C.sub.v is the heat capacity at constant volume. The speed of sound .sub.ci, the gas density .sub.ci and the average static temperature T.sub.ci are determined at the exit of the orifices. T.sub.ti is the average total temperature in each region [A.sub.i]. The average total pressure at the exit of each orifice is P.sub.cti and P.sub.ci is the average static pressure for each region [A.sub.i]. A coefficient C.sub.pl,i to account for the total pressure losses through the orifices is also introduced with a value of 0.99. Finally, the mass flow rate to be subtracted from each region [A.sub.i] is denoted with m.sub.i. The number of openings C.sub.i in each region [A.sub.i] have identical geometric characteristics, but may differ to those in other regions.

[0196] We then define the function for the Mach number:

[00004] f ( M ) = 2 [ ( - 1 ) .Math. M 2 + 2 ]

[0197] For choked flow conditions the value of the Mach number is unity (M=1) and the expression reduces to:

[00005] f ( M ) = 2 [ ( - 1 ) + 2 ]

[0198] Then assuming perfect gas conditions and one-dimensional flow inside each orifice the following computations can be used in each region [A.sub.i]. The average total temperature at the exit of the orifice is set equal to the average total temperature T.sub.ti of the upstream region [A.sub.i].

[0199] The average static temperature T.sub.i, the average total pressure P.sub.cti and the average static pressure P.sub.ci at the exit of each orifice are related respectively as:

[00006] T ci = T ti .Math. f ( M ) .Math. P cti = P ti .Math. C pti P ci = P cti .Math. f ( M ) - 1

[0200] The average gas density is then calculated using the perfect gas law as follows:

[00007] ci = P ci RT ci

and the average speed of sound at the exit of each orifice is given by:


.sub.ci={square root over (RT.sub.ci)}

[0201] The total cross sectional area for all the orifices arranged circumferentially on each of the ring spacers positioned in regions [A.sub.i] is then given by:

[00008] E i = m i ci .Math. ci

[0202] It follows that the radius R.sub.ci for each of the orifices can be calculated using the following expression:

[00009] R ci = E i C i .Math.

[0203] In the first preferred embodiment discussed using FIG. 7 and the parameterization method presented with reference to FIG. 8 a common axis is shared between the skimmer electrodes. It is also desirable to design an array where skimmers are progressively displaced off-axis to re-direct a greater portion of the gas flow toward the pumping orifices and into the pumping line to reduce the gas load presented to the apertures further downstream. Reducing the gas load to the skimmer apertures allows for reducing the number of skimmers employed and/or allows for a reduced spacing between skimmers and/or increasing the size of the apertures to enhance ion transmission. FIG. 9 shows an illustrative example where the first 301 and second 302 skimmers are arranged with an offset in the radial direction and an increased portion of the gas flow, indicated by arrows 303 is directed toward the pumping line 304. Side-ways subtraction of a proportion of the gas load can also be achieved by shaping the skimmer electrodes appropriately to help channel the gas toward the pumping line.

[0204] This effect could alternatively or additionally be achieved by other methods of displacing the gas, for example arranging the skimmers along a curved path, or introducing an inclination between skimmers.

[0205] With reference to the off-set design shown in FIG. 9, ions can be maintained near the ion optical axis by compensating electrostatic potentials applied to the skimmer electrodes. Deflection and focusing fields can also be used to counter-act the force on the ions due to the gas flow field. Mass discrimination effects in terms of differences in ion mobility may be minimised by ensuring that the aperture displacement is small, of the order of a few mm down a fraction of a millimetre.

[0206] FIG. 9 is a schematic illustration of a generalized arrangement of an array designed with off-axis skimmer-electrodes.

[0207] Skimmer apertures can be reduced in size progressively to further reduce the gas load at the inlet of the mass spectrometer. In other embodiments aperture sizes are uniform throughout the array or can be increased with distance. The actual aperture sizes can be carefully selected by taking into consideration the dimensions of the orifices on the ring spacers connecting the skimmer array to the pumping line. Here too the final pressure presented at the inlet of the mass spectrometer may range from a fraction of an atmosphere to a few mbar. Also the device can be operated at elevated temperatures to promote desolvation of charged droplets (or prevent re-clustering of previously desolvated ions) produced by electrospray ionization or other types of atmospheric pressure ionization sources.

[0208] Auxiliary gas flows can be envisaged to enhance ion transmission, for example a jet of gas introduced coaxially to the electrospray nebulizer gas to direct the entire spray into the apparatus, or a counter gas flow to support redirection of gas flow toward the pumping line. Electrodes additional to the skimmer electrodes are desirable for providing electrostatic focusing and collimation of ions more effectively. FIG. 10 shows the focusing electrode 403 positioned between the first 401 and second 402 skimmers to form an electrostatic lens controlled by adjusting the potential applied. It is also preferable to machine the rear side of the focusing electrodes to form slots extending radially outwards and aligned with the orifices on the ring spacers.

[0209] FIG. 10 is a schematic illustration of a generalized arrangement of an array equipped with focusing electrodes to collimate the ions and simultaneously channel the gas flow. Electrode shapes departing from the standard skimmer-based coaxial design described so far may equally be used. For example electrodes can be machined flat or take forms where the coaxial symmetry is broken to include channels for the gas to flow outwardly. The thickness of the electrodes can also be varied substantially to affect conductance. The apertures can also be tapered to shape the gas jets discharging into each of the consecutive regions of the apparatus.

[0210] An example of a skimmer shaped electrode machined to form channels to direct the deflected portion of the gas outwardly to the pressure exhaust openings is shown in FIG. 11. The skimmer 101 comprises a circular disk the front face of which bears a frusto-conical projection 530 the top of which presents an ion inlet opening 520 for a given pressure-control chamber, for receiving ions entrained within a flow of gas. Four gas guides (500, 510) are arranged symmetrically radially around the frustum 530. Each gas guide comprises a radial channel formed within the front face and extending generally linearly from a proximal end 500 adjacent to a base part of the frustum, to a distal open end 510 at the peripheral edge of the disk 101. The proximal end of the channel defines gas capture region in which the channel is wider than the distal end. This assists in capturing a greater proportion of gas deflected by the frustum 530. The width of the channel decreases gradually (tapers) along a part of the length of the channel extending away from the gas capture region in the direction towards the distal end such that the width of the channel remains substantially constant towards and at the distal end. The depth of each gas guide is substantially constant along the width and length of the channel. In use, gas deflected by the frustum, which does not pass through the inlet opening 520, is deflected towards a gas capture region 500 of one or more gas guides, where it is channelled along the channel of the gas guide(s) towards a pressure exhaust opening 104. The distal ends of the channels of the gas guides are preferably positioned in register with a respective pressure exhaust opening to permit efficient output of the guided gas.

[0211] The discussion included in this Annex is intended to serve as a basic description. Although the present has been described in accordance with the various embodiments shown and discussed in some detail, one of ordinary skill in the art will readily recognize that there could be variations to the embodiments and those variations would be within the scope and spirit of the present invention. The reader should be aware that the specific discussion may not explicitly describe all embodiments possible; many alternatives are implicit. For instance the number of regions the interface apparatus is comprised of, the range of operating pressures, the nature of the electric fields, DC or RF or combinations thereof, including the shape of the electrodes and the design of the pumping line together with the off-set configuration and broken symmetry electrodes can all be combined and varied to a great extent.