WO2015181564A1

WO2015181564A1 - Improvements in and relating to mass spectrometry

Info

Publication number: WO2015181564A1
Application number: PCT/GB2015/051569
Authority: WO
Inventors: Emmanuel Raptakis; Dimitris Papanastasiou; loannis K. NIKOLOS; Roger Giles
Original assignee: Shimadzu Corporation; WEBSTER, Jeremy
Priority date: 2014-05-30
Filing date: 2015-05-29
Publication date: 2015-12-03
Also published as: GB201409604D0

Abstract

An ion transfer apparatus for transferring ions from an ion source at a first pressure, which first pressure is >500 mbar, suitably atmospheric pressure, along a path towards a mass spectrometer at a lower second pressure, comprising a plurality of pressure- control chambers each comprising an ion inlet opening for receiving therein ions from said ion source on said path and an ion outlet opening for outputting said ions on said path; wherein said plurality of pressure-control chambers are arranged in succession along said path whereby a said ion outlet opening of each pressure-control chamber is in flow communication with a said ion inlet opening of a successive adjacent pressure- control chamber; a pump apparatus in flow communication with each said pressure- control chamber via a respective plurality of pressure exhaust openings formed within each said pressure-control chamber, and arranged to control the pressure in each respective pressure-control chamber to be lower than the pressure in a preceding adjacent pressure-control chamber such that the pressure in a last of said pressure- control chambers is the lowest amongst the plurality of pressure-control chambers.

Description

IMPROVEMENTS IN AND RELATING TO MASS SPECTROMETRY

FIELD OF THE INVENTION

The present invention relates generally to mass spectrometry and apparatus and method thereof. In particular, though not exclusively, the invention relates 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. BACKGROUND OF THE INVENTION

Atmospheric pressure ionization has evolved into an indispensible analytical tool in mass spectrometry and applications in life sciences with a significant impact in areas spanning from drug discovery to protein structure and function as well as the emerging field of systems biology applied to biomedical scientific research. The advent of atmospheric pressure ionization and particularly electrospray enabled the analysis of intact macromolecular ions under native conditions which offers a wealth of information to many different disciplines of science. The generation of intact ionic species is accomplished at or near atmospheric pressure whereas the determination of molecular mass is accomplished at high vacuum. Therefore transfer efficiency of ions generated at high pressure toward consecutive regions of the mass spectrometer operated at reduced pressure is a critical parameter, which determines instrument performance in terms of sensitivity.

Electrospray ionization (ESI) is the prevailing method for generation of gas phase ions where ions in solution are sprayed typically under atmospheric pressure and in the presence of a strong electric field. Charged droplets released from the ESI emitter tip undergo a recurring process of evaporation and fission ultimately releasing ions sampled by an inlet capillary or other types of inlet apertures. The inlet aperture forms the interface of the instrument and represents a physical barrier between the high pressure ionization region and the fore vacuum region normally operated at 1 mbar background pressure. The size of the inlet aperture or capillary employed to admit ions in the fore vacuum is limited to -0.5 mm in diameter to establish the pressure differential necessary for the existing ion optical components to be operable and transport ions to subsequent lower pressure vacuum regions efficiently. Consequently, sampling efficiency of the spray containing charged droplets and bare ions using standard interface designs is limited to < 1% and has a profound effect on instrument sensitivity.

The design of a high transmission interface for efficient transportation of ions from atmospheric pressure into the fore vacuum region of a mass spectrometer has grown into a challenging problem yet no decisive solution has been brought forward. One approach involves increasing pumping speed to accommodate relatively small increments in the size of the inlet aperture. Although increasing the inlet aperture appears a rather straight forward solution the inefficient heat transfer and incomplete ion desolvation are not easily addressed. Furthermore, the cost related to the increased pumping speed becomes considerable. Efforts for improved ion transfer efficiency are also directed toward the development of novel ion optical devices operable at elevated pressure. The ion funnel has been operated successfully at pressures as high as 30 mbar, nevertheless increments in the size of the inlet aperture remain marginal. In yet another design of an interface a multi-inlet capillary configuration is implemented in an effort to sample a larger area of the electrospray plume. Using this type of a novel multi- inlet system enhanced transfer efficiency is claimed, however, the ion losses at the interface are still severe since the reduction in pressure from atmospheric to near or below 0 mbar requires the cross sectional area of the inlet to be kept small. Reducing pressure by approximately two orders of magnitude in a single step is inevitably associated with severe ion losses due to the narrow aperture or other types of multi-inlet system configurations employed. Indeed, these approaches do not address the underlying loss mechanisms arising from diffusion losses, space charge losses, and high gas velocity at the exit of the capillary/capillaries or skimmer. This latter problem can result in a high value for the turbulent velocity ratio (TVR) and the high gas speed prevents effective focusing via an electrical field.

In an entirely different approach a multi-chamber configuration has been disclosed to operate using enlarged apertures and where pressure is reduced progressively from the fore vacuum pressure of -5 mbar to regions of lower pressure. Over this pressure range ions can be guided by RF electrical fields. Whilst use of a series of vacuum regions to reduce pressure progressively may enhance ion transfer efficiency to the high vacuum region, it does not address the problem of the majority of the ions being lost at the interface where a single inlet aperture is employed to sustain a large drop in pressure which is typically from 1 bar down to 5 mbar. Despite the different approaches to interface design the ion transfer efficiency from the high pressure region into the fore vacuum is still limited by the narrow inlet apertures or narrow capillaries with internal diameters restricted to a fraction of a millimetre. Enhanced transfer efficiency is achieved by using multi-inlet aperture configurations, however, this approach is limited too by the large drop in pressure hence the requirement to maintain the overall cross sectional area of the inlet small. Thus, there is still a general need for an improved interface design capable of transferring ions into the fore vacuum region with greater efficiency while maintaining effective desolvation of charged droplets.

SUMMARY OF THE INVENTION

The present invention relates generally to an apparatus and method of operation suitable e.g. for improving transmission efficiency of gaseous ionic species generated at or near atmospheric pressure into a relatively low pressure region. More specifically, the invention in preferred embodiments utilizes consecutive regions separated by enlarged orifices/apertures (e.g. on/in electrodes) (e.g. one or more aperture(s) in each electrode) and maintained at progressively lower pressure to enhance ion throughput in the presence of external electric fields.

In a first aspect, the invention provides an ion transfer apparatus for transferring ions from an ion source at a first pressure (suitably atmospheric pressure) along a path towards a mass spectrometer at a lower second pressure, comprising: a plurality of pressure-control chambers each comprising an ion inlet opening (one or more openings) for receiving therein ions from said ion source on said path and an ion outlet opening (one or more openings) for outputting said ions on said path; wherein said plurality of pressure-control chambers are arranged in succession along said path whereby a said ion outlet opening (one or more openings) of each pressure-control chamber is in flow communication with a said ion inlet opening (one or more openings) of a successive adjacent pressure-control chamber; a pump apparatus in flow communication with each said pressure-control chamber via a respective plurality of pressure exhaust openings formed within each said pressure-control chamber, and arranged to control the pressure in each respective pressure-control chamber to be lower than the pressure in a preceding adjacent pressure-control chamber such that the pressure in a last of said pressure-control chambers is the lowest amongst the plurality of pressure-control chambers.

Thus, the arrangement of successive pressure-control chambers can be regarded as an array of pressure-control chambers.

Suitably the first pressure-control chamber receives ions from an ion source which is at or around atmospheric pressure (~1000mbar). In embodiments, the ion source is at a pressure of >500 mbar, >600 mbar, >700mbar, >800 mbar or >900 mbar. Suitably the ion source pressure is <1500 mbar, <1300 mbar, <1100mbar, or no greater than about 1000 mbar. Thus, suitably, the first pressure-control chamber is configured to operate at a pressure close to or at atmospheric pressure, typically >200 mbar, >100 mbar or >50 mbar. In this way, a plurality of pressure exhaust openings may efficiently and effectively control pressure levels within the successive pressure-control chambers. Furthermore, the plurality of pressure exhaust openings within a given pressure-control chamber may preferably be spaced from each other to prevent, inhibit or at least reduce the possibility of the formation of significant asymmetrical gas flows within the chamber. Such asymmetrical flows may otherwise occur when gas within a chamber forms a significant flow stream towards a single pressure exhaust opening - the flow stream can disturb and distort the flow of gas-entrained ions passing from the ion inlet opening to the ion outlet opening of the chamber. This is highly undesirable as it may result in ions being misdirected and not reaching the ion outlet opening. By providing a plurality of pressure exhaust openings, spaced apart, this effect is reduced or inhibited.

The plurality of exhaust openings in one, some or each pressure control chamber may be arranged substantially symmetrically or be uniformly spaced around the chamber, e.g. forming a regular pattern, for example an annulus. Exhaust openings of the plurality of exhaust openings may be arranged at opposite sides of the pressure control chamber. The plurality of exhaust openings may include pairs of such openings arranged such that one opening of the pair generally opposes the other opening of the pair across the pressure-control chamber (e.g. at opposite sides of the chamber). This enables a substantially spatially uniform pumping/pressure-exhaust to be applied within the pressure control chamber and avoid the formation of an asymmetrical gas flow field with the disadvantages that it can bring - e.g. gas reflections and recirculation phenomena that can deflect ions from the desirable ion path through the ion outlet openings.

It is also desirable to employ ion outlet openings shaped/machined to present a surface bearing gas guiders (e.g. slots, grooves, ridges, fins or channels) that extend radially outwardly from the opening to collect and direct toward the pressure exhaust openings those parts of the gas that do not pass through the ion outlet opening. The gas guiders are preferably formed on the front surface of the inner wall of a given pressure control chamber at the periphery of its ion outlet opening. The ion outlet opening may include a skimmer, and the gas guiders may be formed on the front surface of the skimmer. The skimmer may be an electrode to which an electrical potential is to be applied for electrically directing ions entrained within the gas to pass through the ion outlet opening. Other means of applying an electrical field are possible.

In this way, the present invention addresses the issue of providing high sampling efficiency through a novel design of inlet/outlet openings and pressure-control chambers arranged in a consecutive order to form multiple regions where the gas is removed progressively at each pressure-control chamber through pressure exhausts. Pressure is reduced gradually whilst ions are maintained along the ion path/optical axis of the apparatus. This path may be maintained using electrical fields. The inlet/outlet openings may serve as electrodes used to define regions of different pressure are preferably skimmer-shaped. The inlet/outlet openings may have relatively large aperture sizes. The inlet/outlet openings may be arranged (e.g. shaped) to direct gas sideways (or radially outwards) towards the pressure exhaust openings of a pressure- control chamber to a pumping line (e.g. pumping port). With this design configuration the standard pressure drop of approximately two (e.g. two to three) orders of magnitude normally performed in a single step may now be accomplished over a greater number (plurality) of pressure-control chambers and pumping regions in stages. This allows for increased aperture sizes thereby increasing ion current and number of ions that may be transported from the atmospheric pressure region and with greater efficiency than prior art systems. For example, in embodiments pressure can be reduced from 1 bar to 100 mbar over (via) ten consecutive pressure-control chambers, which permits ion inlet/outlet openings with aperture sizes with diameters of about 2 mm to be utilized increasing ion throughput considerably.

Furthermore, in embodiments an electrospray plume may be entirely directed through the first aperture of the array and thereby addresses the issue of low sampling efficiency of prior art systems. The diameter of the apertures of ion inlet/outlet openings employed in the plurality (array) of pressure control chambers is preferably at least 0.6 mm in diameter, and preferably may be not greater than about 3 mm.

In embodiments and in an aspect of the invention the pressure-control chamber array may enable a reduction in the gas load presented to the inlet of a mass spectrometer hence allow the use of significantly larger inlet apertures or capillaries in order to enhance ion transmission. In this configuration the final region of the array can be preferably but not exclusively adjusted to operate at a pressure of approximately 100 mbar.

In another aspect of the invention the pressure-control chamber array may enable a reduction in pressure in stepwise manner from an initial pressure of about 1 bar to a pressure of about 1 mbar where conventional ion optics can be employed. Suitably the pressure within each pressure-control chamber is substantially uniform. That is, there is substantially no variation in pressure within the chamber.

The design of the pressure-control chamber array is preferably configured to establish a desired pressure drop across the ion inlet/outlet openings (e.g. skimmer-shaped or other types) by subtracting gas from the main gas flow progressively and directing the subtracted gas toward a pumping line. The excess gas load may be evacuated through the pressure exhaust openings in each pressure-control chamber. The pressure control chambers may comprise two consecutive walls (e.g. two ends walls) each containing a respective one of the ion inlet and ion outlet openings (each of the ion inlet and ion outlet being one or more openings), and both separated by an insulating ring used to provide seal between consecutive walls and thereby form regions of different pressure. Pressure exhaust openings may be formed in the insulating rings of a given pressure- control chamber. The wall of a given pressure-control chamber containing the ion outlet opening thereof may simultaneously define the wall of a successive pressure-control chamber and the ion inlet opening thereof. A single pumping line may preferably be used and maintained at a lower pressure using a single vacuum pump. Additional vacuum pumps can also be employed to increase pumping speed and reduce the number of regions necessary to reduce pressure in a stepwise manner. Additional vacuum pumping lines may also be provided to evacuate different regions of the pressure control chamber array operated at substantially different pressure. For example a first vacuum pump may be dedicated to the first one or several few pressure control chambers where pressure is the highest and a second vacuum pump may be connected to the majority of the remaining pressure control chambers of the array further downstream where pressure is lower. As noted above, the pressure-control chambers are suitably configured (e.g. by their size, shape, configuration and location of walls, configuration and location of openings, and/or provision of pumping lines/pumps) so as to achieve in use a substantially uniform pressure within each chamber.

Different types of pumps may be used to evacuate the different pressure regions, for example, rotary pumps, jet pumps or cascades thereof, ejector pumps, rotary vain pumps, side channel blowers, radial fans, screw pumps, rotary lobe and claw vacuum pump, and turbo pumps. Typically the first several chambers (i.e. the first several chambers in the array) should be pumped by a pump capable of high gas throughput but at relatively high pressure. Latter (subsequent) pumps in the array require reduced gas throughput, but must be capable of operation at reduced vacuum pressure.

The reduction in pressure across the array of pressure control chambers may be achieved by controlling the size of the apertures of the ion inlet/outlet openings and the pumping speed through the pressure exhaust openings of the pressure control chamber in question. The pumping speed through the pressure exhaust openings is largely dependent on the characteristic dimensions of the openings, for example, the shape and the cross sectional area as well as the depth of the opening. Restricting the pumping speed is made possible by utilizing a fewer number of openings, as desired, preferably arranged symmetrically around the pressure control chamber (e.g. in a ring array) and having smaller cross sectional areas and/or greater depth. This design may be desirable in the final stages of the array of pressure-control chambers where the gas load to each of the apertures of the ion inlet/outlet openings along the ion path has been reduced. In contrast, a greater gas throughput may be desirable in the first stages of the array and this may be achieved preferably by increasing the number and size of the pressure exhaust openings (e.g. in the ring array), and/or working with relatively smaller aperture sizes for the ion inlet/outlet openings along the first stages of the ion path.

It may also be desirable to establish choked flow conditions in each of the pressure exhaust openings to maximize throughput. This is made possible by maintaining pressure in the pumping line near or below the pressure in the last pressure control chamber. In case the pumping line across the array is divided into more than one region chocked flow conditions are established by adjusting pressure to fall below the pressure in the last pressure control chamber in flow communication with the sub-region of the pumping line. Additional control of the background pressure across the one or more regions of the pumping line is possible by using control valves to adjust pumping speed.

Choked flow is a fluid dynamic condition associated with the Venturi effect. Fluid velocity increases when a flowing fluid at a given temperature and pressure passes through a restriction into a lower pressure environment. At initially subsonic upstream conditions, the conservation of fluid mass ensures that the fluid velocity increases as it flows through the smaller cross-sectional area of the restriction. The Venturi effect causes the static pressure, and therefore the density, to decrease downstream past the restriction. Choked flow is a limiting condition which occurs when the mass flow rate will increase no further even when a further decrease in the downstream pressure occurs, while upstream pressure is fixed. For homogeneous fluids, choking occurs when the exit velocity is at sonic conditions or at a Mach number of 1.

The respective plurality of pressure exhaust openings are preferably arranged within the pressure-control chamber substantially symmetrically around said ion outlet thereof.

The respective plurality of pressure exhaust openings may include at least two pressure exhaust openings disposed within the pressure-control chamber at substantially opposite sides of the ion outlet thereof. The ion transfer apparatus may include a pumping conduit in flow communication with each said pressure exhaust opening and with said pump apparatus.

The pumping conduit preferably comprises a bore within which said plurality of pressure-control chambers are located and said pressure exhaust openings are in flow communication with said bore.

Some or each of the ion outlet openings may be arranged mutually in register and substantially coaxially.

Some or each of the ion outlet openings may be arranged to intersect a common axis of the apparatus, but are not centred, or not all centred, upon said axis.

The plurality of pressure exhaust openings are preferably arranged circumferentially within a respective pressure-control chamber. For example, the outlet openings may be formed in a peripheral wall of the pressure-control chamber which separates two opposing walls of the chamber containing the ion inlet and outlet openings respectively.

One, some or each said pressure-control chamber may comprise a skimmer therein defining the ion outlet thereof. The skimmer forming the ion outlet of one pressure- control chamber may also define the ion inlet opening of the next, successive pressure- control chamber.

One some or each skimmer may be an electrode arranged to receive an electrical potential for directing said ions when thereat.

The ion transfer apparatus may include a voltage source for applying an electrical potential to one, some or each skimmer collectively or independently. Direct (DC) electrical potentials may be applied to some or each of the ion inlet/outlet openings (e.g. skimmer-shaped) independently to focus ions in-through the openings. The ion transfer apparatus may include one or more additional focusing electrodes arranged to receive an electrical potential therewith to collimate, in use, said ions therein. The additional focusing electrodes can be disposed in the vicinity of the ion inlet/outlet openings (e.g. skimmer-shaped) to form strong lenses and further enhance transmission.

A skimmer(s) within a pressure-control chamber may be shaped to direct gas flow towards a/the pressure exhaust opening(s) thereof.

The ion transfer apparatus may include a controller arranged to control the pump means to maintain, in use, a flow through the pressure exhaust openings to be a choked flow with a Mach number substantially equal to unity.

In a second aspect, the invention may provide a mass spectrometer comprising the ion transfer apparatus of any preceding claim.

The mass spectrometer may include a vacuum interface in flow communication with said last of said pressure-control chambers wherein the vacuum interface comprises an inlet skimmer with an aperture size, or an inlet capillary, or a multi-capillary configuration with a cross sectional area greater than 0.7 mm².

In a third aspect, the invention may provide a mass spectrometer interface comprising: an ionization source for generating ions at elevated pressure; a vacuum interface for admitting ions to a lower pressure region; an array of successive openings (e.g. skimmers) in series defining an inlet and an outlet region wherein said inlet region is in communication with said ionization source and said outlet region in communication with said vacuum interface; wherein said array of successive openings further comprises a series of insulating rings each defining and sealing the spacing between adjacent successive openings of the array of openings (e.g. skimmers) to form a first conduit, and a second conduit external to first conduit forming a substantially concentric gap in- between said conduits, and a vacuum pump arranged to evacuate said gap to a lowest pressure attainable throughout the array of openings (e.g. skimmers); and wherein one or more orifices are formed on each of said ring spacers which allow for evacuating the regions between openings (e.g. skimmers) thereby reducing pressure progressively from the ionization source pressure to a lower interface pressure.

Direct (DC) electrical potentials are supplied to each skimmer of said skimmer array independently. The skimmer array may comprise at least two skimmers arranged off- axis. The vacuum pump is preferably controllable to form a choked gas flow through the orifices formed in the ring spacers having a Mach number equal to unity. The concentric gap preferably comprises at least two regions in communication with at least one orifice. Preferably, at least two orifices are formed in each of the ring spacers, e.g. arranged circumferentially.

The vacuum interface may comprise an inlet skimmer with an aperture size, or an inlet capillary, or a multi-capillary configuration with a cross sectional area greater than 0.7 mm².

The one, some or all of the openings of the array of openings may be electrodes which may be skimmer shaped. One or more additional focusing electrodes may be provided (e.g. within the first conduit) to collimate a stream of charged droplets and/or ions when therein, in use.

The skimmers and/or the focusing electrode(s) may be shaped to direct the gas toward the orifices on the ring spacers.

The additional focusing electrodes may be rings or short tubes, the internal diameter of the ring is preferably greater than the aperture in the skimmers.

The device is preferably operated in a mode in which all skimmer electrodes have a common potential, and the DC potentials are applied to each of the additional focusing electrodes.

The additional focusing electrodes are preferably formed with minimal cross section presenting minimal obstruction to the outward radial gas flow.

In a further aspect, the invention may provide a method for transferring ions from an ion source at a first pressure along a path towards a mass spectrometer at a lower second pressure, comprising: directing ions from said ion source into a plurality of pressure- control chambers each comprising an ion inlet opening for receiving there ions on said path and an ion outlet opening for outputting said ions on said path wherein said plurality of pressure-control chambers are arranged in succession along said path whereby ions at an ion outlet opening of each pressure-control chamber flow to an ion inlet opening of a successive adjacent pressure-control chamber; pumping gas from each pressure-control chamber via a respective plurality of pressure exhaust openings formed within each said pressure-control chamber, thereby to control the pressure in each respective pressure-control chamber to be lower than the pressure in a preceding adjacent pressure-control chamber such that the pressure in a last of said pressure- control chambers is the lowest amongst the plurality of pressure-control chambers; outputting ions from the ion outlet opening of said last of said pressure-control chambers towards said mass spectrometer. The method may include removing gas from a said pressure control chamber substantially symmetrically about said ion outlet opening thereof via said plurality of pressure exhaust openings arranged within the pressure-control chamber substantially symmetrically around said ion outlet thereof. The method may include removing gas from a said pressure control chamber substantially at opposite sides of (relative to) said ion outlet opening thereof via at least two pressure exhaust openings disposed within the pressure-control chamber at substantially opposite sides of the ion outlet thereof. Said pumping may include pumping said gas via a pumping conduit in flow communication with each said pressure exhaust opening and with said pumping apparatus.

Some or each of the ion inlet/outlet openings may be arranged mutually in register and substantially coaxially, and the method includes directing said ions therethrough.

Some or each of the ion outlet openings may be arranged to intersect a common axis of the apparatus, but are not centred, or not all centred, upon said axis, and the method includes directing said ions therethrough.

Some or each of said plurality of pressure exhaust openings may be arranged circumferentially within a respective pressure-control chamber, and the method includes pumping said gas therethrough. One, some or each said pressure-control chamber may comprise a (at least one) skimmer therein defining the ion outlet thereof, and the method includes skimming said gas therewith towards a pressure exhaust opening. One some or each skimmer may be an electrode arranged to receive an electrical potential for directing said ions when thereat, and the method includes directing said ions therewith.

The method may include directing ion flow towards successive skimmer by means of gas flow and electrical potentials.

The pumping is preferably controlled to maintain a choked flow through the pressure exhaust openings with a Mach number substantially equal to unity. The method may include providing one or more focusing electrodes arranged to receive an electrical potential and collimating said ions therewith.

BRIEF DESCRIPTION OF THE DRAWINGS

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.

FIG. 1 is a schematic illustration of a generalized arrangement of a skimmer-electrode array according to an embodiment of the invention;

FIG. 2 is a schematic illustration of a generalized arrangement of a skimmer-electrode array according to an embodiment of the invention;

FIG. 3 is a schematic illustration of a generalized arrangement of an array designed with off-axis skimmer-electrodes according to an embodiment of the invention;

FIG. 4 is a schematic illustration of a generalized arrangement of an array equipped with focusing electrodes to collimate the ions and simultaneously channel the flow. FIG. 5 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. DESCRIPTION OF EMBODIMENTS

An illustrative example of an embodiment is described with reference to FIG. 1. 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. 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. The skimmer array of FIG. 1 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.

FIG 1. 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.

A method for the parameterization of the device in order to specify the dimensions of the apparatus is made with reference to FIG. 2. 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 [Ai], [A₂], [A₃] and [An] 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 [AJ 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. 1. 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.

For the following calculation procedure region 201 will be referred to as [Ai], region 202 as [A₂] and so forth up to the final stage designated with [A_n]. Pressure in region [B] is always lower than the lowest pressure in region [A_n], and in case of sonic conditions (choked flow) established through the pressure exhaust openings at least by a fraction 1/2. 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. 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], i=1 ,...,n, (b) the average static pressure P, in each region [A], i=1 ,...,n, (c) the average total pressure P_ti in each region [A], i=1 , ..., ?, (d) the average total temperature Tu in each region [A], i=1 n, and finally (e) the number of orifices C, where i=1 ,...,n, distributed circumferentially on each of the ring spacers connecting each region with the pumping line region [B].

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, γ is the ratio of specific heats of the gas {y=Cp/C_v) where C_p is the heat capacity at constant pressure and Cv is the heat capacity at constant volume. The speed of sound _α, the gas density pci and the average static temperature T_Ci are determined at the exit of the orifices. 7~_f, is the average total temperature in each region [A]. The average total pressure at the exit of each orifice is P_ct; and P_a- is the average static pressure for each region [A]. A coefficient C_p/,, 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,] is denoted with m,. The number of openings C, in each region [A] have identical geometric characteristics, but may differ to those in other regions.

We then define the function for the Mach number: f(M) = —₂

[(r- l)M² + 2]

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

Kr -i) + 2]

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

The average static temperature T_i: the average total pressure P_cu and the average static pressure P_a- at the exit of each orifice are related respectively as:

T_cl = T (M) P_cti = P_tiC_≠

The average gas density is then calculated using the perfect gas law as follows: P_ci =

RT_ci

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

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

It follows that the radius R_c, for each of the orifices can be calculated using the following expression:

In the first preferred embodiment discussed using FIG. 1 and the parameterization method presented with reference to FIG. 2 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. 3 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. Sideways 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.

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.

With reference to the off-set design shown in FIG. 3, 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.

FIG. 3 is a schematic illustration of a generalized arrangement of an array designed with off-axis skimmer-electrodes.

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.

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. 4 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.

FIG. 4 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.

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. 5. 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.

The discussion included in this application 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 without departing from scope of the invention.

Claims

CLAIMS:

1.An ion transfer apparatus for transferring ions from an ion source at a first pressure, which first pressure is >500 mbar, suitably atmospheric pressure, along a path towards a mass spectrometer at a lower second pressure, comprising: a plurality of pressure-control chambers each comprising an ion inlet opening for receiving therein ions from said ion source on said path and an ion outlet opening for outputting said ions on said path; wherein said plurality of pressure-control chambers are arranged in succession along said path whereby a said ion outlet opening of each pressure-control chamber is in flow communication with a said ion inlet opening of a successive adjacent pressure-control chamber; a pump apparatus in flow communication with each said pressure-control chamber via a respective plurality of pressure exhaust openings formed within each said pressure-control chamber, and arranged to control the pressure in each respective pressure-control chamber to be lower than the pressure in a preceding adjacent pressure-control chamber such that the pressure in a last of said pressure-control chambers is the lowest amongst the plurality of pressure- control chambers.

2. An ion transfer apparatus according to claim 1 , wherein the pressure within each of the plurality of pressure-control chambers is substantially uniform.

3. An ion transfer apparatus according to any preceding claim in which said respective plurality of pressure exhaust openings are arranged within the pressure-control chamber substantially symmetrically around said ion outlet thereof.

4. An ion transfer apparatus according to any preceding claim in which said respective plurality of pressure exhaust openings include at least two pressure exhaust openings disposed within the pressure-control chamber at substantially opposite sides of the ion outlet thereof.

5. An ion transfer apparatus according to any preceding claim including at least one pumping conduit in flow communication with each said pressure exhaust opening and with said pump apparatus.

6. An ion transfer apparatus according to claim 5 in which said pumping conduit comprises a bore within which said plurality of pressure-control chambers are located and said pressure exhaust openings are in flow communication with said bore.

7. An ion transfer apparatus according to any preceding claim in which some or each of the ion outlet openings are arranged mutually in register and substantially coaxially.

8. An ion transfer apparatus according to any preceding claim in which some or each of the ion outlet openings are arranged to intersect a common axis of the apparatus, but are not centred, or not all centred, upon said axis.

9. An ion transfer apparatus according to any preceding claim in which said plurality of pressure exhaust openings are arranged circumferentially within a respective pressure-control chamber.

10. An ion transfer apparatus according to any preceding claim in which one, some or each said pressure-control chamber comprises a skimmer therein defining the ion outlet thereof.

11. An ion transfer apparatus according to claim 10 in which one some or each skimmer is an electrode arranged to receive an electrical potential for directing said ions when thereat.

12. An ion transfer apparatus according to claim 11 including a voltage source for applying an electrical potential(s) to one, some or each skimmer collectively or independently.

13. An ion transfer apparatus according to any of claims 10 to 12 wherein a skimmer(s) within a pressure-control chamber is/are shaped to direct ion flow towards a/the pressure exhaust opening(s) thereof.

14. An ion transfer apparatus according to any preceding claim including a controller arranged to control the pump apparatus to maintain, in use, a flow through the pressure exhaust openings to be a choked flow with a Mach number substantially equal to unity.

15. An ion transfer apparatus according to any preceding claim including one or more focusing electrodes arranged to receive an electrical potential different to the electrical potential of the ion outlet opening and therewith to collimate, in use, said ions therein.

16. A mass spectrometer comprising the ion transfer apparatus of any preceding claim.

17. A mass spectrometer according to claim 16 including a vacuum interface in flow communication with said last of said pressure-control chambers wherein the vacuum interface comprises an inlet skimmer with an aperture size, or an inlet capillary, or a multi-capillary configuration with a cross sectional area greater than 0.7 mm².

18. A method for transferring ions from an ion source at a first pressure, which first pressure is >500 mbar, suitably atmospheric pressure, along a path towards a mass spectrometer at a lower second pressure, comprising: directing ions from said ion source into a plurality of pressure-control chambers each comprising an ion inlet opening for receiving therein ions on said path and an ion outlet opening for outputting said ions on said path wherein said plurality of pressure-control chambers are arranged in succession along said path whereby ions at an ion outlet opening of each pressure-control chamber flow to an ion inlet opening of a successive adjacent pressure-control chamber; pumping gas from each pressure-control chamber via a respective plurality of pressure exhaust openings formed within each said pressure-control chamber, thereby to control the pressure in each respective pressure-control chamber to be lower than the pressure in a preceding adjacent pressure-control chamber such that the pressure in a last of said pressure-control chambers is the lowest amongst the plurality of pressure-control chambers; outputting ions from the ion outlet opening of said last of said pressure-control chambers towards said mass spectrometer.

19. A method according to claim 18, wherein the method includes maintaining a substantially uniform pressure within each of the plurality of pressure-control chambers.

20. A method according to claim 19 including removing gas from a said pressure control chamber substantially symmetrically about said ion outlet opening thereof via said plurality of pressure exhaust openings arranged within the pressure- control chamber substantially symmetrically around said ion outlet thereof.

21. A method according to any of claims 18 to 20 including removing gas from a said pressure control chamber via at least two pressure exhaust openings disposed within the pressure-control chamber at substantially opposite sides of the ion outlet thereof.

22. A method according to any of claims 18 to 21 wherein said pumping includes pumping said gas and/or ions via a pumping conduit in flow communication with each said pressure exhaust opening and with said pump apparatus.

23. A method according to any of claims 18 to 22 in which some or each of the ion outlet openings are arranged mutually in register and substantially coaxially, and the method includes directing said ions therethrough.

24. A method according to any of claims 18 to 23 in which some or each of the ion outlet openings are arranged to intersect a common axis of the apparatus, but are not centred, or not all centred, upon said axis, and the method includes directing said ions therethrough.

25. A method according to any of claims 18 to 24 in which some or each of said plurality of pressure exhaust openings are arranged circumferentially within a respective pressure-control chamber, and the method includes pumping said gas therethrough.

26. A method according to any of claims 18 to 25 in which one, some or each said pressure-control chamber comprises a skimmer therein defining the ion outlet thereof, and the method includes skimming said gas therewith.

27. A method according to any of claims 18 to 26 in which one some or each skimmer is an electrode arranged to receive an electrical potential for directing said ions when thereat, and the method includes directing said ions therewith.

28. A method according to any of claims 26 to 27 including directing gas flow towards a/the pressure exhaust opening(s) using said skimmers.

29. A method according to any of claims 18 to 28 in which said pumping is controlled to maintain a flow through the pressure exhaust openings to be a choked flow with a Mach number substantially equal to unity.

30. A method according to any of claims 18 to 28 including providing one or more focusing electrodes are arranged to receive an electrical potential different to the electrical potential of the ion outlet opening, and collimating said ions therewith.