apparatus

Abstract

An apparatus for ion analysis or an Electrospray Ionisation, ESI, interfacing apparatus comprising a virtual impactor comprising a minor flow part configured for directing towards a downstream region a part of a received flow of a gas entrained with ions as a minor flow of the gas containing at least a majority of the ions. A major flow part is configured for directing away from the downstream region a part of the received flow of gas as a major flow of the gas containing not more than a minority of the ions.

Description

[0001] APPARATUS

[0002] Field of the Invention

[0003] The present invention relates to apparatus for use in ion analysis. Examples of ion analysis include mass spectrometry. For example, the present invention may relate to apparatus for use in ion analysis such as mobility spectrometry (IMS) for example, and particularly, although not exclusively, to Field Asymmetric IMS (FAIMS), and / or differential mobility spectrometry (DMS). The present invention also relates to apparatus for use in electrospray ionisation (ESI) processes. The present invention also relates to particle (e.g., powder) separation apparatus and methods.

[0004] Background

[0005] The sensitivity of ion analysis methods and apparatus depends on many factors. Amongst those factors is the need to control (e.g., increase) the quantity of ions of an analyte within an ion analysis apparatus at any one time. By increasing the number of ions available for analysis, one may increase the throughput of ions to a detector of the analysis apparatus and, consequently, improve the sensitivity of the analysis apparatus. The present invention has been devised in light of the above considerations.

[0006] An ion analysis apparatus may have several stages including, for example, a stage at which ions of an analyte are generated and output, an intermediate downstream stage (or stages) for receiving the ions output by the ion source and for guiding them towards one or more subsequent stages (further downstream) of ion analysis. For example, ions passing from any one such stage to a subsequent downstream stage may often be conveyed by a carrier gas. One example, but not the only example, is electrospray ionisation (ESI) processes. Another example is ion mobility spectrometry. The term ion mobility spectrometry (IMS) refers to the methods and apparatus used to characterise ions from sample substances in terms of the speed at which ensembles of those ions progress through a supporting gas atmosphere when urged through it by an applied electric field. Ion mobility measurements involve injecting an ion ensemble into a “drift region”. An ion detector, or simply an ion outlet, may be provided at the output end of the drift region. While within the drift region, the ion ensemble moves longitudinally towards an output end of the drift region e.g., within a flow of purified neutral support gas (e.g., molecular Nitrogen), also known as a “buffer gas”, in which it is entrained. Simultaneously, in one IMS technique for example, the ion ensemble moves transversely to the buffer gas flow direction under the urging force of an applied electric field, E, generated by an appropriate voltage gradient applied transversely to the buffer gas flow direction.

[0007] Notably, ion mobility measurements pertain only to ion ensembles and not to individual ions for which the speeds can be comparatively large. For example, the median speed between collisions for molecular Nitrogen ions at ambient pressure and at a temperature of 25 degrees Celsius is about 450 metres per second. By comparison, as an example, an ion ensemble may typically be urged by the applied electric field, E, to move transversely to the buffer gas flow direction with a velocity of, say, v = 4 m / s.

[0008] It is established practice to normalise such an ion ensemble velocity value, v, by dividing it with the value of the electric field strength, E, applied transversely to the buffer gas flow direction. This normalisation 8539918

[0009] 2 produces an ion mobility coefficient, K = v / E, which is the measure of the ion ensemble velocity per unit field strength. The relationship between ion ensemble velocity, v, and electric field strength, E, is valid for an ion ensemble at thermal energies measured in a buffer gas atmosphere of constant composition, pressure, and temperature. The value of an ion mobility coefficient is dependent upon buffer gas temperature, T, and pressure, P, inside the drift region. Importantly, the value of an ion mobility coefficient is dependent upon the collision cross-section of the ion under study and an ion mobility coefficient, K, for a given ion is sensitive to fluctuations in this quantity.

[0010] A distinction of IMS in contrast to mass spectrometry (MS) is that ions are characterised in a supporting buffer gas atmosphere, also called a drift gas, that is refreshed continuously. A main practical purpose of this gas is to maintain a purified and constant atmosphere for collision-based movement of the ion ensemble.

[0011] Field asymmetric IMS, differential mobility spectrometry, or ion drift spectrometry are different names given to the same process, which is a type of IMS. An ion mobility measurement begins when ions formed from components in a sample, called product ions, are injected into the drift region. These methods are based on ions undergoing changes in ion mobility coefficients, K, as a result of changes in the applied transverse electric field, E, at constant buffer gas particle number density, N, i.e., the number of buffer gas particles per unit volume. An approach in IMS technology has enabled studies of field dependence using a Field Asymmetric Ion Mobility Spectrometer (FAIMS) or DMS. The method of high field asymmetric IMS for ion separations is based on a non-linear, high-field dependence of ion mobility coefficients. In particular:

[0012] Here, a(E / N) = <z2x (E / / V)2+ <z4x (E / / V)4+ - + a2nx (E / / V)2n

[0013] This function describes the non-linear electric field dependence of ion mobility of an ion. The terms a2n(n = 1, 2, ...) are constant coefficients the values of which are particular to a given combination of ion and buffer gas set-up. The function a E / N') is a function describing the dependence of ion mobility on the ratio, E / N, of the electric field strength to neutral gas density. The units of E / N are Townsends (Td) where 1 Td = 10-17Vcm2.

[0014] In this method, termed variously Field Asymmetric IMS (FAIMS), or Differential Mobility Spectrometry (DMS), ions are contained in a gas, e.g., entrained by a gas flow, extending along a drift space between conducting surfaces (e.g., electrodes). The space between the electrodes defines an “analytical gap”. The drift space can be defined between parallel curved or flat electrodes (e.g., plates). A transverse electric field, E, is applied across this analytical gap using an asymmetric voltage waveform known as a “dispersion voltage” (FD), which generates a corresponding dispersion electric field, EDe.g., of ED= +20,000 V / cm or greater in the positive amplitude part of the asymmetric wave cycle and ED= -1,000 V / cm in the negative amplitude part of the asymmetric wave cycle. Ion ensembles move with a speed v within the electric field E according to equations: 8539918

[0015] 3 v = K x ED

[0016] K = K(ED / N = K0(l + a(ED / N~)~)

[0017] Of course, the value of EDchanges in magnitude and polarity as the wave cycle switches between its positive and negative amplitude parts. As a result, the value of K(ED / NJ' is different during these two different parts of a wave cycle for ions for which a(ED / Nj' 0. The asymmetric voltage waveform of the dispersion voltage (VD) is designed so that the time integrals of these two parts of the wave cycle are equal. Notably, ions with mobility coefficients, K(ED / NJ' , that are independent of ED, (i.e., such that a(ED / Nj' « 0 even at high field values) are able to pass through the drift region and emerge from it to be detected. In contrast, ions with a dependence of K on ED(i.e., a(ED / Nj' 0) undergo a net displacement towards a surface of an electrode with repeated exposure of the ion ensemble to the periodic changes in direction and strength of the electric field, ED. The magnitude of displacement depends on the differences in mobility, K(ED / l\r) = K0(l + a ED / N')'), at electric field extremes i.e., the “high-field” amplitude, ED!Hi, and “low-field” amplitude, E^Lparts of the asymmetric wave cycle. In other words:

[0018] The “high-field” amplitude, EDHi, and “low-field” amplitude parts of the waveform have opposite polarity with the “high-field” amplitude, EDHi, conventionally being denoted as having positive polarity. The immediate effects of dispersion electric field, ED, in DMS or FAIMS are revealed in the dependence of the mobilities, K(ED / Nj', of ions on dispersion electric field strength, ED, at the two extremes of the asymmetric waveform. The waveform is designed in field strength, ED, and duty cycle (as between durations of positive polarity and negative polarity parts) so that an ion with little or no dependence of mobility on dispersion electric field strength, ED, will pass through the centre of the analyser by being carried by a flow of buffer gas. Ions that do have a dependence of mobility on dispersion electric field strength, ED, will undergo with each complete cycle of the dispersion voltage waveform, successive net displacements from the central ion axis of ion flow. Eventually, the ion ensemble will collide with an electrode defining the analytical gap and will be discharged and removed from the measurement process. When a direct current (DC) “compensation voltage” (Vc) is applied to the electrodes of the analyser, the effects of the dispersion electric field may be compensated, and ion motion can be restored to the centre of the analyser.

[0019] A comparatively low direct current (DC) “compensation voltage” (Vc) may be added to the electrodes or plates defining the analytical gap so as to superimpose that DC electric field (compensation field, Ec) upon the dispersion electric field, ED, to enable control or “compensation” of ion motion towards an electrode. Ions restored to the centre of the analytical gap will be made able to pass through the drift region. A sweep of this compensation voltage, often 10V to 40V in size (producing compensation electric fields of typically 100V / cm to 500V / cm), provides a means to measure mobility of all ions in the analyser for a given dispersion voltage wave form. This method provides ion mobility filtering, and ion separations 8539918

[0020] 4 are based on differences in ion mobility, leading to the name “Differential Mobility Spectrometry”, also known as FAIMS.

[0021] To achieve high quality (e.g., sensitivity) measurements, the ions under study should preferably undergo a sufficiently large number of complete cycles of the dispersion voltage waveform such that ions with even a relatively small dependence of K on EDmay undergo a sufficiently large number of successive net displacements, per cycle of the dispersion waveform, from the central ion axis of ion flow, that they too collide with an electrode defining the analytical gap. Consequently, only those ions with mobility coefficients, K(ED / NJ' , that are closer to being truly independent of ED, (i.e., such that a(ED / Nj' « 0) are able to pass through the drift region and emerge from it to be detected.

[0022] However, the number of complete cycles of the dispersion voltage waveform that an ion can experience whilst within the drift region, is limited by the duration of time for which the ion is present there. That duration of time is influenced by the speed of flow of the buffer gas within which the ion is entrained. A higher buffer gas flow speed through the drift region reduced that duration of time, thereby reducing quality (e.g., sensitivity) of measurements. References [1] to [8] listed below, represent background art useful for understanding.

[0023] The present invention has been devised in light of the above considerations.

[0024] Summary of the Invention

[0025] Ions passing from any one stage of a mass spectrometry apparatus to a subsequent downstream stage may often be conveyed by a carrying gas. The inventors have realised that a careful manipulation of the carrying gas, at one or more of the various stages of a mass spectrometry apparatus, may increase the sensitivity or performance of such a mass spectrometry apparatus. In some aspects, the invention proposes the use of a virtual impactor in an ion analysis apparatus in separating a majority of a carrying gas (e.g., “buffer” gas) from ions of a sample (or droplets of a sample for ionisation) entrained within it, resulting in slower flow speeds of ion-entrained (or droplet-entrained) gas delivered downstream in the ion analysis apparatus.

[0026] The term “inertial impactor”, which includes conventional impactors and virtual impactors, refers to a device that can classify particles into different size ranges based on particle inertia. In an inertial impactor, a gas flow entrained with particles is forced rapidly to change direction, such that those particles with sufficient inertia escape (i.e., “over-shoot”) the turning gas flow while those particles with less inertia remain in the turning gas flow. This results in a particle size-based separation. A conventional impactor consists of a gas flow outlet nozzle and an impaction plate below the outlet nozzle. When the particle- entrained gas flow exits the nozzle and makes a turn in direction above the obstructing impaction plate, larger particles with sufficient inertia are unable to follow the turning streamlines of gas flow above the impaction plate and impact upon the impaction plate (sometimes referred to as a collection plate). By contrast, smaller particles with less inertia are able to follow the turning streamlines of gas flow above the 8539918

[0027] 5 impaction plate so as to avoid impact with the impaction plate and, instead to flow out of the impactor to be either collected by a filter for further analyses or measured directly.

[0028] Known limitations of the conventional impactor include effects known as “particle bounce” and “particle overloading”. Particle bounce occurs when the impaction plate is unable to absorb the kinetic energy of incident particles completely. Those particles are not retained by the surface of the impaction plate, resulting in the lower particle collection efficiency for larger particles. Particle overloading occurs when too many particles are collected on the impaction plate after a long sampling period. When the impaction plate is loaded heavily with particles, the incident particles strike on previously deposited particles rather than the impaction plate, resulting in particle bounce.

[0029] By contrast, a virtual impactor is a device used to separate particles by size into two gas streams. It is similar to a conventional impactor, but the impaction surface is replaced with a collection inlet defining a space of slower-moving gas. Larger particles are captured in a collection inlet rather than impacted onto an impaction surface.

[0030] Deflected gas streamlines are similar to those in conventional impactors. The smaller particles follow the deflected streamlines of a “major flow” of gas, while the larger particles, with greater inertia, pass through the collection inlet in a forward “minor flow” of gas. Both size fractions can, subsequently, be ducted for any desired methods of analysis or collection. A virtual impactor does not collect particles on an impaction surface, but merely redirects them into two different gas streams according to their size. The working principle of the virtual impactor is, therefore, that when particles flow into the virtual impactor, the majority particles larger than a certain size (known as the “cut-off size”) continue to the “minor channel”, and the majority particles smaller than the cut-off size are re-directed to the “major channel”. The minor flow may be, for example, about 5-20 % of the total gas flow or the major flow may be, for example, about 80-95 % of the total gas flow. A characteristic of a virtual impactor is that particles smaller than the “cut-off size” of the impactor remain in both the major and minor flows. Another characteristic is that particles larger than the cut-off size become concentrated in the minor flow.

[0031] The flow speed of gas within a minor flow is lower than the flow speed of gas within a major flow. The inventors have realised that this property of the virtual impactor may be used advantageously in an apparatus for Ion Mobility Spectrometry by delivering a flow of buffer gas entrained with ions for analysis, to a virtual impactor configured to implement a particle “cut-off size” that is smaller than the size of ions entrained within the buffer gas. Consequently, a lower flow speed of buffer gas entrained with ions, may be created as the minor flow of gas.

[0032] For example, in a first aspect, the invention may provide an ion analysis apparatus comprising: an ion source for generating ions from a sample; an upstream region for providing a flow of a buffer gas containing the ions from the ion source; a virtual impactor for receiving the flow of buffer gas from the upstream region; a downstream region for receiving ions in a minor flow of the buffer gas output from the virtual impactor, the downstream region comprising; an ion analysis assembly configured to receive therein said minor flow of buffer gas; wherein the virtual impactor comprises: 8539918

[0033] 6 a minor flow part configured for directing towards the downstream region a part of the received flow of buffer gas as said minor flow of the buffer gas containing at least a majority of the ions; and, a major flow part configured for directing away from the downstream region a part of the received flow of buffer gas as a major flow of the buffer gas containing not more than a minority of the ions.

[0034] The ion analysis apparatus may comprise an apparatus for Ion Mobility Spectrometry, IMS, or an apparatus for mass spectrometry. In examples where the ion analysis apparatus comprises an apparatus for mass spectrometry, it may comprise one or more ion guides and / or one or more ion focusing assemblies, and / or one or more collision-induced dissociation (CID) assemblies, and / or one or more mass analysers, for receiving ions from the minor flow of the buffer gas. In examples where the ion analysis apparatus comprises an apparatus for Ion Mobility Spectrometry, IMS, it may comprise an ion mobility assembly for receiving ions from the minor flow of the buffer gas. The upstream region may comprise an upstream chamber (e.g., an ESI chamber). The downstream region may comprise a downstream chamber (e.g., a vacuum chamber). The upstream region and the downstream region may be separated by a wall of a vacuum chamber.

[0035] The virtual impactor may be connected to the spray output end of an Electrospray Ionisation Source, ESI, for receiving an electrospray plume directly from the spray output end and for delivering the minor flow of the electrospray plume directly into an ESI chamber of the downstream region. The virtual impactor may be separated from the spray output end of an Electrospray Ionisation Source, ESI, and may be directly connected to an opening / inlet of the desolvation tube for receiving a part of the electrospray plume output from the spray output end into the ESI chamber, and for delivering the minor flow of the electrospray plume directly into the opening / inlet of the desolvation tube. The virtual impactor may be directly connected to an opening / inlet of the downstream region (e.g., an opening / inlet in a vacuum chamber wall separating the upstream region from the downstream region) for receiving from the upstream region a flow of the buffer gas containing the ions, and for delivering the minor flow of the buffer gas containing the ions directly into the ion analysis apparatus in the downstream region.

[0036] Consequently, a flow speed of buffer gas within the ion-enhanced minor flow of the buffer gas, as received by the downstream region, may be lower than the flow speed of buffer gas within the ion- depleted major flow of the buffer gas. Consequently, from the buffer gas received from the upstream region, a lower flow speed of buffer gas entrained with at least a majority of the ions may be created as the minor flow of gas. The density of the ions within the minor flow of the buffer gas may be greater than the density of the ions within the major flow of the buffer gas.

[0037] In some examples, the minor flow of the buffer gas may contain substantially all of the ions from within the buffer gas received from the upstream region, such that substantially all ions in the buffer gas from the upstream region are delivered to the downstream region by the minor flow of the buffer gas. For example, the virtual impactor may be configured to implement a particle “cut-off size” that is smaller than the size of ions generated by the ion source, to be entrained within the buffer gas. 8539918

[0038] 1

[0039] The virtual impactor may comprise a gas flow receiving channel for conducting the received flow of buffer gas, and the major flow part may define one or more channels or ducts extending in a direction that is substantially perpendicular to the direction in which the gas flow receiving channel extends. The one or more channels or ducts may thereby force the creation of deflected streamlines of a “major flow” of buffer gas which extend in a direction that is substantially perpendicular to the direction in which the streamlines of the received flow of buffer gas extends.

[0040] The virtual impactor may be configured to direct the received flow of buffer gas, entrained with ions, to pass through an outlet opening towards a flow control aperture part (e.g., defining the collection inlet) of the virtual impactor. At this point a major portion of the flow is deflected and diverted (e.g., by about 90°) away from the collection inlet. This is where the ion separation takes place. Small particles with low inertia follow the flow streamlines and are carried away radially with the major flow. Large particles, such as the ions from the ion source, with greater inertia deviate from the flowlines and continue moving axially in their forward path through the collection inlet with the minor flow. For example, the minor flow part may comprise a flow control aperture part configured to admit a part of the received flow of buffer gas therefrom to form the minor flow of the buffer gas, and simultaneously to deflect all other parts of that received flow of buffer gas away from the flow control aperture part thereby directing the major flow of the buffer gas away from the downstream region.

[0041] The apparatus may be configured for providing the flow of buffer gas from the upstream region at a gas pressure exceeding a gas pressure provided within the downstream region thereby providing a gas pressure difference therebetween. The virtual impactor may comprise a gas jet outlet opening for forming a jet of the buffer gas received from the upstream region in response to the gas pressure difference. The flow control aperture part may comprise a minor flow aperture (e.g., defining the collection inlet) in communication with the gas jet outlet opening and configured to admit inner parts of the jet of buffer gas through the minor flow aperture to form the minor flow of the buffer gas therefrom, and to deflect all other parts of the jet of buffer gas to form the major flow of the buffer gas therefrom.

[0042] The gas jet outlet opening may be formed in a gas jet outlet part defining a first surface extending from a periphery of the gas jet outlet opening. The flow control aperture part may define a second surface extending from a periphery of the minor flow aperture in spaced opposition to the first surface for deflecting parts of the received flow of buffer gas. The first and second surfaces may define between them a gas flow gap forming the major flow part for directing the major flow of the buffer gas away from the minor flow aperture and away from the downstream region. The gas flow gap forming the major flow part may define a duct for ducting the major flow away from the minor flow aperture (collection inlet). For example, the gas flow gap may have a width / diameter in the range of about 0.1 mm to about 5mm, and more preferably in the range of about 0.1 mm up to 3 mm, or about 1 mm to about 3mm. For example, the gas flow gap may have a width / diameter of about 1 mm, or about 1 .5mm, or about 2mm. The gas flow gap may have a width / diameter exceeding about 0.1 mm or exceeding about 0.5mm. 8539918

[0043] 8

[0044] The first and second surfaces may be substantially mutually parallel. The first and second surfaces may be substantially planar. The second surface may be a surface of a plate (e.g., a circular plate or disk) arranged in spaced parallel opposition to a flat first surface. The gas flow gap may comprise an annular space of uniform width (i.e. , the gap / spacing between the opposing surfaces) that extends radially in all directions from the minor flow aperture (collection inlet) to form the duct of the major flow part for ducting the major flow.

[0045] The first surface may extend (e.g., radially) from all parts of the periphery of the gas jet outlet opening thereby to fully surround the periphery of the gas jet outlet opening. For example, the gas jet outlet opening may be an opening formed in, and fully surrounded by, the first surface.

[0046] The second surface may extend from all parts of the minor flow aperture (collection inlet) thereby to fully surround the periphery of the minor flow aperture. For example, the minor flow aperture may be an opening formed in, and fully surrounded by, the first surface.

[0047] Alternatively, the first surface may extend only from two separated parts of the periphery of the gas jet outlet opening which oppose each other across the gas jet outlet opening. For example, the first surface may be elongated in a first dimension and relatively narrow in a second dimension that is perpendicular to the first dimension (e.g., an area rectangular in shape). The gas jet outlet opening may be formed to extend fully across the first surface in the second dimension so as to separate the first surface into two separate parts which each extend (in the first dimension) from a respective one of the two separated parts of the periphery of the gas jet outlet opening. The gas flow gap may thereby comprise an elongated space of uniform width (i.e., the gap / spacing between the opposing surfaces) that extends radially in two opposite directions from the gas jet outlet opening to form the duct of the major flow part for ducting the major flow.

[0048] Similarly, the second surface may extend only from two separated parts of the periphery of the minor flow aperture which oppose each other across the minor flow aperture. For example, the second surface may be elongated in a first dimension and relatively narrow in a second dimension that is perpendicular to the first dimension (e.g., an area rectangular in shape). The minor flow aperture may be formed to extend fully across the second surface in the second dimension so as to separate the second surface into two separate parts which each extend from a respective one of the two separated parts of the periphery of the minor flow aperture. The gas flow gap may thereby comprise an elongated space of uniform width (i.e., the gap / spacing between the opposing surfaces) that extends radially in two opposite directions from the minor flow aperture (collection inlet) to form the duct of the major flow part for ducting the major flow.

[0049] In some examples, substantially all parts of the first surface that are not opposed by the minor flow aperture are opposed by the second surface.

[0050] In some examples, a width of the minor flow aperture exceeds a width of the gas jet outlet opening. For example, a width of an aperture may refer to a diameter of the aperture. 8539918

[0051] 9

[0052] In some examples, the virtual impactor may comprise a plurality of concatenated virtual impactor stages whereby the minor flow aperture (collection inlet) of an upstream virtual impactor stage defines a gas jet outlet opening of the next downstream virtual impactor stage. This concatenation of virtual impactor stages may assist in further reducing a speed of buffer gas flow in the final minor flow of the buffer gas output by the virtual impactor. For example, the virtual impactor may comprise: a first major flow part configured for directing away from the downstream region a part of the received flow of buffer gas as a first major flow of the buffer gas containing not more than a minority of the ions; an intermediate minor flow part configured for directing towards the downstream region a part of the received flow of buffer gas as an intermediate minor flow of the buffer gas containing at least a majority of the ions; a terminal minor flow part disposed downstream of the intermediate minor flow part and configured for receiving the intermediate minor flow of the buffer gas and for directing towards the downstream region said minor flow of the buffer gas containing at least a majority of the ions; wherein the intermediate minor flow part and the terminal minor flow part collectively form a second major flow part configured for directing away from the downstream region a part of the intermediate minor flow of the buffer gas as a second major flow of the buffer gas containing not more than a minority of the ions.

[0053] In examples where the ion analysis apparatus comprises an apparatus for Ion Mobility Spectrometry, IMS, then the ion analysis assembly may comprise: a differential ion mobility assembly comprising a drift region defined between electrodes separated by an analytical gap wherein the drift region extends along a direction transverse to the analytical gap, and configured to provide therein said minor flow of buffer gas along the drift region; a voltage source configured to apply a dispersion voltage waveform comprising a dispersion voltage portion to one or more of the electrodes thereby to generate a dispersion electric field across the analytical gap containing the minor flow of the buffer gas.

[0054] A reduced flow speed of the minor flow of the buffer gas may thereby permit ions entrained therein to take more time to traverse the drift region and thereby improve the sensitivity of the IMS apparatus.

[0055] In a second aspect, the invention may provide an Electrospray Ionisation, ESI, interface comprising: an input port for receiving a liquid solution containing an analyte, and an output port for outputting droplets and / or ions of the analyte; and, a pneumatically-assisted sprayer in fluid communication with the input port and comprising: a spray capillary for supporting a flow of the liquid solution to a spray output end of the pneumatically-assisted sprayer; and, a nebulizer gas duct for supporting a flow of a nebulizing gas to the spray output end for nebulizing the liquid solution thereat to produce an electrospray plume comprising the nebulizing gas containing droplets of said liquid solution and / or ions of the analyte; 8539918

[0056] 10 a voltage source configured to apply a voltage to the spray capillary for generating an electric field at the spray output end for inducing a charge accumulation at the surface of the liquid solution; a virtual impactor for receiving at least a part of the electrospray plume from the spray output end, wherein the virtual impactor comprises: a minor flow part configured for directing towards the output port a part of the received electrospray plume as a minor flow of the electrospray plume containing at least a majority of the analyte; and, a major flow part for directing away from the output port a part of the received electrospray plume as a major flow of the electrospray plume containing not more than a minority of the analyte.

[0057] The output port of the virtual impactor may be configured to be disposed, in use, within an Electrospray Ionisation, ESI, chamber. The ESI chamber may be configured to maintain a pre-set desired gas pressure therein. The ESI chamber may comprise a desolvation tube configured in communication with the output port of the virtual impactor for receiving at least a part of the minor flow of the electrospray plume therefrom. Consequently, from the nebulizer gas received from the upstream region, a lower flow speed of nebulizer gas entrained with at least a majority of the droplets / ions may be created as the minor flow of gas (i.e. , may be lower than the flow speed of nebulizer gas within the droplet / ion-depleted major flow of the nebulizing gas).

[0058] The virtual impactor may be connected to the spray output end of the pneumatically-assisted sprayer for receiving at least a part of (or substantially all of) the electrospray plume directly from the spray output end and for delivering the minor flow of the electrospray plume directly into the ESI chamber.

[0059] Alternatively, the virtual impactor may be separated from the spray output end of the pneumatically- assisted sprayer, and may be directly connected to an opening / inlet of the desolvation tube for receiving a part of the electrospray plume output from the spray output end into the ESI chamber, and for delivering the minor flow of the electrospray plume directly into the opening / inlet of the desolvation tube.

[0060] The virtual impactor may provide a first virtual impactor connected to the spray output end of the pneumatically-assisted sprayer for receiving at least a part of (or substantially all of) the electrospray plume directly from the spray output end and for delivering the minor flow of the electrospray plume directly into the ESI chamber, and the ESI interface may comprise a second virtual impactor separated from the first virtual impactor and directly connected to an opening / inlet of the desolvation tube for receiving a part of the minor flow of the electrospray plume provided by the first virtual impactor.

[0061] The second virtual impactor may comprise: a minor flow part configured for directing towards the opening / inlet of the desolvation tube a part of the received electrospray plume as a minor flow of the electrospray plume containing at least a majority of the analyte; and, 8539918

[0062] 11 a major flow part for directing away from the opening / inlet of the desolvation tube a part of the received electrospray plume as a major flow of the electrospray plume containing not more than a minority of the analyte.

[0063] The density of the analyte (droplets / ions) within the minor flow of the nebulizer gas (as produced by the virtual impactor, and / or the first virtual impactor and / or the second virtual impactor) may be greater than the density of the analyte (droplets / ions) within the major flow of the nebulizer gas. The lower flow speed of nebulizing gas within the droplet / ion-enhanced minor flow of the nebulizing gas, as received by the downstream region of the ESI chamber or of the desolvation tube, permits a greater intake of the droplets / ions into the opening / inlet of the desolvation tube. This increase in ion intake is beneficial.

[0064] The virtual impactor (or the first virtual impactor) may be mounted coaxially to, and concentrically around, the pneumatically-assisted sprayer. The virtual impactor (or the second virtual impactor, as the case may be) may be mounted coaxially to, and concentrically around, the desolvation tube.

[0065] The Electrospray Ionisation, ESI, interface may comprise a heater for heating the spray capillary to desolvate droplets of said liquid solution, and / or a heater for heating the desolvation tube to desolvate droplets of said liquid solution.

[0066] The minor flow part may comprise a flow control aperture part configured to admit a part of the received electrospray plume therefrom to form the minor flow of the electrospray plume, and simultaneously to deflect all other parts of that received electrospray plume away from the flow control aperture part thereby directing the major flow of the electrospray plume away from the output port (e.g., away from the opening / inlet of the desolvation tube, as the case may be).

[0067] The virtual impactor may comprise a gas jet outlet opening for forming a jet of the nebulizing gas received from the pneumatically-assisted sprayer in response to a gas pressure difference formable between the input port and the virtual impactor. For example, the output port of the Electrospray Ionisation interface may be configured to be disposed, in use, within an Electrospray Ionisation chamber configured to maintain a pre-set desired gas pressure therein.

[0068] The flow control aperture part may comprise a minor flow aperture in communication with the gas jet outlet opening and is configured to admit inner parts of the jet of nebulizing gas through the minor flow aperture to form the minor flow of the electrospray plume therefrom, and to deflect all other parts of the jet of nebulizing gas to form the major flow of the electrospray plume therefrom.

[0069] The gas jet outlet opening may be formed in a gas jet outlet part defining a first surface extending from a periphery of the gas jet outlet opening, and the flow control part defines a second surface extending from a periphery of the minor flow aperture in spaced opposition to the first surface for deflecting parts of the received flow of nebulizing gas, whereby the first and second surfaces define between them a gas flow 8539918

[0070] 12 gap forming the major flow part for directing the major flow of the electrospray plume away from the minor flow aperture and away from the output port.

[0071] The first and second surfaces may be substantially mutually parallel. The first and second surfaces may be substantially planar. The first surface may extends from all parts of the periphery of the gas jet outlet opening thereby to fully surround the periphery of the gas jet outlet opening. The first surface may extend only from two separated parts of the periphery of the gas jet outlet opening which oppose each other across the gas jet outlet opening. The second surface may extend from all parts of the minor flow aperture thereby to fully surround the periphery of the minor flow aperture. The second surface may extend only from two separated parts of the periphery of the minor flow aperture which oppose each other across the minor flow aperture. In some examples, substantially all parts of the first surface that are not opposed by the minor flow aperture may be opposed by the second surface.

[0072] A width of the minor flow aperture may exceed a width of the gas jet outlet opening.

[0073] The virtual impactor of the Electrospray Ionisation, ESI, interface may comprise: a first major flow part configured for directing away from the output port a part of the received flow of nebulizing gas as a first major flow of the electrospray plume containing not more than a minority of the ions; an intermediate minor flow part configured for directing towards the output port a part of the received flow of nebulizing gas as an intermediate minor flow of the electrospray plume containing at least a majority of the ions; a terminal minor flow part disposed downstream of the intermediate minor flow part and configured for receiving the intermediate minor flow of the electrospray plume and for directing towards the output port said minor flow of the electrospray plume containing at least a majority of the ions; wherein the intermediate minor flow part and the terminal minor flow part collectively form a second major flow part configured for directing away from the output port a part of the intermediate minor flow of the electrospray plume as a second major flow of the electrospray plume containing not more than a minority of the ions. In examples where the Electrospray Ionisation, ESI, interface comprises the first virtual impactor and the second virtual impactor, then either one of, or each of, the first virtual impactor and the second virtual impactor may be configured in this way. Alternatively, only the second virtual impactor may be configured in this way, if desired.

[0074] The major flow part(s) may define one or more channels extending in a direction that is substantially perpendicular to the direction in which the pneumatically-assisted sprayer extends.

[0075] For example, in a third aspect, the invention may provide a method for ion analysis comprising: generating ions from a sample in an ion source; providing an upstream region and therein providing a flow of a buffer gas containing the ions from the ion source; providing a virtual impactor and receiving therein the flow of buffer gas from the upstream region; 8539918

[0076] 13 providing a downstream region comprising an ion analysis assembly; and, by the virtual impactor: directing towards the downstream region a part of the received flow of buffer gas as a minor flow of the buffer gas containing at least a majority of the ions to provide the minor flow of buffer gas to the ion analysis assembly; and, directing away from the downstream region a part of the received flow of buffer gas as a major flow of the buffer gas containing not more than a minority of the ions.

[0077] The ion analysis method may comprise a method for Ion Mobility Spectrometry, IMS, or a method for mass spectrometry.

[0078] In examples where the method for ion analysis comprises a method for mass spectrometry, it may comprise directing ions from the minor flow of the buffer gas to: one or more ion guides; and / or one or more ion focusing assemblies; and / or one or more collision-induced dissociation (CID) assemblies; and / or one or more mass analysers. In examples where the method for ion analysis apparatus comprises a method for Ion Mobility Spectrometry, IMS, it may comprise directing ions from the minor flow of the buffer gas to an ion mobility assembly.

[0079] In examples where the ion analysis method comprises method for Ion Mobility Spectrometry, IMS, then the ion analysis method may comprise: providing a downstream region comprising a differential ion mobility assembly comprising a drift region defined between electrodes separated by an analytical gap wherein the drift region extends along a direction transverse to the analytical gap; and, by the virtual impactor: directing towards the downstream region a part of the received flow of buffer gas as a minor flow of the buffer gas containing at least a majority of the ions to provide the minor flow of buffer gas along the drift region; and, directing away from the downstream region a part of the received flow of buffer gas as a major flow of the buffer gas containing not more than a minority of the ions; the method further comprising applying a dispersion voltage waveform comprising a dispersion voltage portion to one or more of the electrodes thereby to generate a dispersion electric field across the analytical gap containing the minor flow of buffer gas.

[0080] For example, in a fourth aspect, the invention may provide a method for Electrospray Ionisation, ESI, interfacing comprising: providing a pneumatically-assisted sprayer in fluid communication with the input port and comprising: a spray capillary for supporting a flow of the liquid solution to a spray output end of the pneumatically- assisted sprayer; and, a nebulizer gas duct for supporting a flow of a nebulizing gas to the spray output end for nebulizing the liquid solution thereat to produce an electrospray plume comprising the nebulizing gas containing droplets of said liquid solution and / or ions of the analyte; 8539918

[0081] 14 applying a voltage to the spray capillary to generate an electric field at the spray output end thereby inducing a charge accumulation at the surface of the liquid solution; and, providing a virtual impactor for receiving the electrospray plume from the spray output end, and by the virtual impactor: directing towards the output port a part of the received electrospray plume as a minor flow of the electrospray plume containing at least a majority of the analyte; and, directing away from the output port a part of the received electrospray plume as a major flow of the electrospray plume containing not more than a minority of the analyte.

[0082] For example, in a fifth aspect, the invention may provide a virtual impactor for separating particles (e.g., particles of a powder) comprising: an input port for receiving an input flow of gas entrained with particles for separation; first minor flow port for forming a first minor flow of gas from the input flow of gas containing at least a majority of particles of a size exceeding a first particle size from amongst the entrained particles; and, a second minor flow port downstream of the first minor flow port for forming a second minor flow of gas from gas received from the first minor flow port and containing at least a majority of particles of a size exceeding a second particle size from amongst the entrained particles; wherein the virtual impactor further comprises: a first major flow part configured for directing away from the first minor flow port a portion of the input flow of gas as a first major flow of gas containing not more than a minority of particles of a size exceeding the first particle size from amongst the entrained particles; a second major flow part configured downstream of the first minor flow port for directing away from the second minor flow port a portion of the first minor flow of gas as a second major flow of gas containing not more than a minority of particles of a size exceeding the second particle size from amongst the entrained particles; wherein the second particle size exceeds the first particle size thereby to separate entrained particles into the first major flow of gas, the second major flow of gas and the second minor flow of gas according to particle size.

[0083] The first minor flow part may comprise a first flow control aperture part configured to admit a portion of the received flow of gas and therefrom to form the first minor flow of the gas, and simultaneously to deflect all other parts of that received flow of gas away from the first flow control aperture part thereby directing the first major flow of the gas away from both the second major flow part and the second minor flow port.

[0084] The second minor flow part may comprise a second flow control aperture part configured to admit a portion of the first minor flow of gas and therefrom to form the second minor flow of the gas, and simultaneously to deflect all other parts of first minor flow of gas away from the second flow control aperture part thereby directing the second major flow of the gas away from both the second minor flow of gas. 8539918

[0085] 15

[0086] In another aspect, the invention may provide a particle separator apparatus comprising the virtual impactor described above and comprising an upstream region and a downstream region, wherein the upstream region is configured to provide the input flow of gas to the input port at a first gas pressure and the downstream region is configured at a second gas pressure lower than the first gas pressure for receiving the second minor flow of gas thereby providing a gas pressure difference between the upstream region and the downstream region, wherein the virtual impactor comprises a first gas jet outlet opening for forming a first jet of the input gas received from the upstream region in response to the gas pressure difference, wherein the first flow control aperture part comprises a first minor flow aperture in communication with the first gas jet outlet opening and is configured to admit inner parts of the first jet of gas through the first minor flow aperture to form the first minor flow of the gas therefrom, and to deflect all other parts of the first jet of gas to form the first major flow of the gas therefrom.

[0087] The first minor flow aperture may provide a second gas jet outlet opening for forming a second jet of the input gas received from the first gas jet outlet opening in response to the gas pressure difference, wherein the second flow control aperture part comprises a second minor flow aperture in communication with the first gas jet outlet opening and is configured to admit inner parts of the second jet of gas through the second minor flow aperture to form the second minor flow of the gas therefrom, and to deflect all other parts of the second jet of gas to form the second major flow of the gas therefrom.

[0088] Each of the first and second gas jet outlet openings may be formed in a respective gas jet outlet part defining a first surface extending from a periphery of the respective gas jet outlet opening, and the respective flow control part may define a second respective surface extending from a periphery of the respective minor flow aperture in spaced opposition to the respective first surface for deflecting parts of the received flow of gas, whereby the respective first and second surfaces define between them a respective gas flow gap forming a respective one of the first and second major flow parts for directing the respective major flow of the gas away from the respective minor flow aperture.

[0089] Each of the respective first and second surfaces may be substantially mutually parallel. Each of the respective first and second surfaces may be substantially planar.

[0090] Each respective first surface may extend from all parts of the periphery of the respective gas jet outlet opening thereby to fully surround the periphery of the gas jet outlet opening.

[0091] Each respective first surface may extend only from two separated parts of the periphery of the respective gas jet outlet opening which oppose each other across the gas jet outlet opening.

[0092] Each respective second surface may extend from all parts of the respective minor flow aperture thereby to fully surround the periphery of the minor flow aperture.

[0093] Each respective second surface may extend only from two separated parts of the periphery of the respective minor flow aperture which oppose each other across the minor flow aperture. 8539918

[0094] 16

[0095] Optionally, substantially all parts of each respective first surface that are not opposed by the respective minor flow aperture are opposed by the second surface.

[0096] A width of each respective minor flow aperture may exceeds a width of the respective gas jet outlet opening.

[0097] The virtual impactor may comprise a gas flow receiving channel for received the input flow of gas entrained with particles for separation, and each respective major flow part may define one or more channels extending in a direction that is substantially perpendicular to the direction in which the gas flow receiving channel extends.

[0098] The invention includes the combination of the aspects and preferred features described except where such a combination is clearly impermissible or expressly avoided.

[0099] Summary of the Figures

[0100] Embodiments and experiments illustrating the principles of the invention will now be discussed with reference to the accompanying figures in which:

[0101] Figure 1A shows an apparatus for ion analysis.

[0102] Figure 1B shows an apparatus for Ion Mobility Spectrometry, IMS.

[0103] Figure 2A shows an ion source in perspective view with an attached virtual impactor shown in cross- sectional view.

[0104] Figure 2B shows an exploded view of the virtual impactor of Figure 2A shown in cross-section.

[0105] Figures 3A, 3B and 3C show elements of a mass spectrometry (MS) system, in perspective view, and cross-sectional views.

[0106] Figure 4 shows a cross-sectional view of an inertial impactor.

[0107] Figure 5 shows a cross-sectional view of the virtual impactor.

[0108] Figures 6A, 6B and 6C show cross-sectional views of parts of a virtual impactor 8539918

[0109] 17

[0110] Figures 7A and 7B show a cross-sectional side view and a plan end view of a virtual impactor.

[0111] Figure 8 shows a perspective (transparent) view of a virtual impactor.

[0112] Figure 9 shows a perspective (transparent) view of a virtual impactor.

[0113] Figure 10 shows experimental data.

[0114] Figure 11 shows experimental data.

[0115] Figures 12A and 12B shows results calculated using a CFD simulation.

[0116] Figure 13 shows results calculated using a CFD simulation used to simulate a movement of ions according to a “hard sphere collisions” simulation method.

[0117] Figure 14 shows a virtual impactor used for particle separation.

[0118] Figure 15 shows a virtual impactor used for particle separation.

[0119] Figure 16 shows a virtual impactor used for particle separation.

[0120] Figures 17A, 17B and 17C show views of a virtual impactor connected to the input end of a desolvation tube.

[0121] Figures 18A and 18B show experimental results from use of a desolvation tube of Figures 17A, 17B and 17C.

[0122] Detailed Description of the Invention

[0123] Aspects and embodiments of the present invention will now be discussed with reference to the accompanying figures. Further aspects and embodiments will be apparent to those skilled in the art. All documents mentioned in this text are incorporated herein by reference. 8539918

[0124] 18

[0125] Figure 1 A shows an apparatus 2A for Ion Mobility Spectrometry, IMS, comprising Electrospray Ionisation, ESI, ion source 6 within an ESI chamber 4 and an ESI interface between the ESI chamber and downstream spectrometry chamber 9 containing a differential ion mobility spectrometry (DMS) assembly 10. The ESI interface comprises an ion source 6 for generating ions from a sample. It defines an upstream region and provides a flow of a nebulizer gas 5 containing ions from the ion source. The ion source comprises an input port shown notionally / schematically as item 11 in Figure 2B, for receiving a liquid solution containing an analyte, and an output port 7 for outputting droplets and / or ions of the analyte. The ion source comprises a pneumatically-assisted sprayer (336, 338 and 338A; Figure 2B) in fluid communication with the input port 11 and comprising a spray capillary 336 for supporting a flow of the liquid solution to a spray output end 338A of the pneumatically-assisted sprayer. A nebulizer gas duct part 338 sheaths the spray capillary 336 along its longitudinal axis within a gas nebulizer gas duct extending along the axis of the gas duct part for supporting a flow of a nebulizing gas to the spray output end 338A for nebulizing the liquid solution thereat to produce an electrospray plume comprising the nebulizing gas containing droplets of said liquid solution and / or ions of the analyte.

[0126] A gap is provided between the spray capillary 336 and the nebulizer gas duct part 338 where compressed nebulizer gas is pumped. A voltage source (not shown) is configured to apply a voltage to the spray capillary 336 for generating an electric field at the spray output end 338A for inducing a charge accumulation at the surface of the liquid solution. This is in accordance with known ESI methods. The invention aims to remove the fast nebulizer gas from ions and droplets created by the ESI pneumatically- assisted sprayer, as discussed herein. Accordingly, a virtual impactor 332 is provided for receiving the electrospray plume from the spray output end 338A. In particular, the virtual impactor comprises a minor flow part 342 configured for directing towards the output port 7 a part of the received electrospray plume as a minor flow of the electrospray plume containing at least a majority of the analyte. The virtual impactor also comprises a major flow part, 340 and 342 collectively, for directing away from the output port 7 a part of the received electrospray plume as a major flow of the electrospray plume containing not more than a minority of the analyte. The operation of the virtual impactor is discussed in more detail below.

[0127] The ESI chamber 4, in addition to providing the ion source, also serves as an upstream region for providing a flow 8 of a buffer gas to a downstream spectrometry region 9 of the apparatus. The flow of buffer gas 8 contains the ions from the ion source that are contained within the of the electrospray plume 12 output by the virtual impactor 332 within the ESI chamber 4, as its minor flow. A downstream spectrometry virtual impactor 354 is provided within the downstream spectrometry region 9 for receiving the flow of buffer gas 8 from the upstream region 4. In particular, the downstream IMS spectrometry region 9 receives ions in a minor flow of the buffer gas output from the virtual impactor 332. The downstream spectrometry region comprises a differential ion mobility, DMS, assembly 10 comprising a drift region 13 defined between electrodes 15 separated by an analytical gap (d). The drift region extends along a direction transverse to the analytical gap. The virtual impactor 354 is configured to provide therein 8539918

[0128] 19 the minor flow 18 of buffer gas along the drift region 13 for onward delivery from the DMS assembly, via a downstream focusing optics assembly, to an ion detector 17 for detection and measurement. In other examples, mass spectrometry apparatus (not shown) may be provided between the focusing optics assembly and the ion detector for implementing ion analysis and mass spectrometry as desired.

[0129] A voltage source 16 is configured to apply a dispersion voltage waveform comprising a dispersion voltage portion to one or more of the electrodes 15 thereby to generate a dispersion electric field across the analytical gap (d) containing the minor flow 18 of the buffer gas. The downstream mass spectrometry virtual impactor 354 comprises a minor flow part 371 configured for directing buffer gas through an outlet opening 370 towards the downstream region a part of the received flow of buffer gas as the minor flow of the buffer gas containing at least a majority of the ions. The downstream mass spectrometry virtual impactor 354 also comprises a major flow part 372 (see Figure 3C) which defining together with the minor flow part 371 a major flow duct 366 that is configured for directing away from the downstream mass spectrometry region a part of the received flow of buffer gas 8 as a major flow of the buffer gas containing not more than a minority of the ions. The major flow duct 366 is inherently a pumped space by virtue of the radial expansion of the major flow of gas within it, as discussed in more detail below with reference to Figure 7B. Tube connection 368 is also provided for major flow duct 366 for connection to a pump (not shown) to assist in removal of the major gas flow therefrom.

[0130] The virtual impactor 354 may further reduce a gas load into the MS vacuum chamber 9, relative to a nominal gas load, while keeping same number of ions as would be present in the nominal gas load. Alternatively, the virtual impactor 354 may enable a gas load into the MS vacuum chamber 9 that is not reduced relative to the nominal gas load, but which is derived from an increased gas load input to the desolvation tube 356 containing more ions than would be present in the nominal gas load, in order to increase ion intake.

[0131] Returning to the ESI chamber 4, a virtual impactor 332 is connected to the spray output end 338A of the pneumatically-assisted sprayer for receiving at least a part of (or substantially all of) the electrospray plume directly from the spray output end and for delivering the minor flow 12 of the electrospray plume directly into the ESI chamber 4. This provides a first virtual impactor of a double virtual impactor assembly comprising which also comprises a second virtual impactor 352 separated from the first virtual impactor 332 and directly connected to an opening / inlet 356A of a desolvation tube 356 for receiving a part of the minor flow 12 of the electrospray plume provided by the first virtual impactor 332. The second virtual impactor comprises a minor flow part 361 configured for directing towards the opening / inlet 356A of the desolvation tube a part of the received electrospray plume 12 as a minor flow of the electrospray plume containing at least a majority of the analyte. A major flow part 362 is provided for directing away from the opening / inlet of the desolvation tube a part of the received electrospray plume 12 as a major flow of the electrospray plume containing not more than a minority of the analyte. 8539918

[0132] 20

[0133] Thus, the apparatus 2A for IMS comprises a combination three elements 332, 352 and 354 each using a respective virtual impactor according to an example of the invention to achieve higher ion intake efficiency and by this increasing mass spectrometry sensitivity. In the second upstream virtual impactor 352 gas speed is reduced still keeping same amount of generated droplets and ions, that improves intake of them by the desolvation line. Also, the duration of time that droplets spend between the first virtual impactor 332 and the second virtual impactor 352 is longer due to slower gas speed, allowing them more time to form ions. The use of the final virtual impactor 354 within the mass spectrometry chamber 9 allows one to use a desolvation tube having a larger bore diameter and consequently this increases the intake of gas form ESI chamber 4 with more droplets and ions. The amount gas taken by mass spectrometry chamber 9 is still low thanks to the use of the final virtual impactor, and number of ions is not reduced.

[0134] Figure 1 B shows an apparatus 2B for ion analysis in which the downstream spectrometry chamber 9 contains a mass spectrometry apparatus 406 for receiving the minor flow 18. The mass spectrometry apparatus 406 may comprise one or more quadrupole electrode assemblies for use in focusing or otherwise guiding ions within the received minor flow 18, and / or for use in applying a mass analysis to those ions. The mass spectrometry apparatus 406 is configured to output ions from the minor flow 18, for onward delivery to the ion detector 17. Additional downstream mass analysis devices may be provided between the mass spectrometry apparatus 406 and the ion detector 17 for implementing any further ion analysis and mass spectrometry as desired. For example, ions from the minor flow 18 of the buffer gas may be directed downstream to: one or more ion guides; and / or one or more ion focusing assemblies; and / or one or more collision-induced dissociation (CID) assemblies; and / or one or more mass analysers.

[0135] Item 402 of Figure 3A denotes a desolvation line assembly comprising the desolvation tube 356 noted above in an alternative embodiment in which the second virtual impactor is omitted. The ESI chamber may be maintained at atmospheric pressure, if desired. Item 404 of Figure 1A or Figure 1 B denotes a chamber wall separating atmospheric pressure ESI chamber from the mass spectrometry, MS, vacuum chamber 9. Item 404 of Figure 1 A or Figure 1 B denotes a quadrupole lens system (Q-array type) for focusing ions ejected from the final virtual impactor 354.

[0136] Figures 2A, 2B and Figures 3A, 3B and 3C show the examples of the invention in a mass spectrometer in perspective view and in cross-sectional views. Figure 2A shows the ion source 6 in perspective view with the attached virtual impactor 332 shown in cross-sectional view. Figure 2B shows an exploded view of the virtual impactor 332 shown in cross-section.

[0137] Figures 3A and 3B show an example of the use of two of the three virtual impactors described above, with Figure 3B being a cross-sectional view of the perspective view of Figure 3A. A first one 352 of these two virtual impactors is installed in the ESI chamber pressure side, and a second (final) one 354 of these two virtual impactors is installed in the MS vacuum chamber. Additionally, the first 332 virtual impactor 8539918

[0138] 21 may be installed in the ESI chamber too. Application of the first 332 virtual impactor in the electrospray ion source (ESI), reduces gas flow without removing ions and droplets generated by ESI.

[0139] The void volume 358 allows the virtual impactor connected to the input port of the desolvation tube to continue to provide the standard function of providing a “drying gas”. In existing instruments, a desolvation tube is surrounded by an output of drying gas that blows air against larger droplets. In examples of the present invention, in order to retain that functionality, void volume 358 provides a bypass for routing a drying gas. However, this routing feature may be omitted if desired. The entrance 360 to the second virtual impactor 352 on ESI chamber pressure side, is enlarged increasing suction of ions into the desolvation tube. The major flow parts 362 of the second virtual impactor are connected to a vacuum pump (not shown) are correspond to the example of the invention as presented in Figure 16. The inlet gas is sucked from these major flow parts 362. Gas flow in let / outlet connection ports 364 are provided for access to the major flow spaces 362 to enable pumping of gas therefrom. By doing this, a larger volume of gas is taken with ions, but same amount gas delivered into desolvation tube 356. By doing this, ions become more concentrated in gas when entering desolvation tube.

[0140] Virtual Impactors

[0141] Figure 4 shows a cross-sectional view of an inertial impactor designed to implement a “conventional impactor” principle. By contrast Figure 5 shows a modification to the inertial impactor design of Figure 4 to as to realise a virtual impactor.

[0142] A conventional impactor design of Figure 4 consists of a gas flow nozzle part 106 and an impaction plate 108 below the outlet end of the nozzle part. A particle-entrained gas 102 is delivered into a gas flow receiving channel 110 of the nozzle part to form flow streamlines of gas which exit the outlet end of the gas flow channel and makes a 90-degree turn 114 in direction above the obstructing impaction plate 108. Larger entrained particles with sufficient inertia are unable to follow the turning streamlines 116 of gas flow above the impaction plate and impact upon the impaction plate where they collect. By contrast, smaller entrained particles with less inertia are able to follow the turning streamlines of gas 116 and flow above the impaction plate so as to avoid impact with the impaction plate and, instead to flow 112 out of the impactor, as an output gas flow 104.

[0143] By contrast, the virtual impactor of Figure 5 is achieved by providing a collection inlet 122 opposite the outlet of the gas flow receiving channel 110 in the nozzle part, in place of the impaction surface there. Impaction plate is thereby replaced by a flow control aperture part 108B defining the collection inlet of the virtual impactor. The collection inlet defines a space of slower-moving gas 124 providing a minor flow 126 entrained with larger particles captured in a collection inlet rather than impacted onto an impaction surface. The larger particles comprise ions (or droplets) generated by the ion source as described above. Deflected gas streamlines 118 convey the smaller particles to define a “major flow” of gas 104, while the larger particles, with greater inertia, pass through the collection inlet along non-deflected streamlines of gas 120 in the forward “minor flow” of gas 126. This principle is applied in the virtual impactors 332, 362 8539918

[0144] 22 and 372 described above. A characteristic of these virtual impactors is that ions and / or droplets greater in size than the “cut-off size” of the impactor in question become concentrated in the minor flow. If all ions and droplets are greater in size than the “cut-off size” then all will concentrate in the minor flow. The flow speed of gas within a minor flow 126 is lower than the flow speed of gas within a major flow 118.

[0145] This is schematically illustrated by the distance of separation between successive flow direction arrowheads upon a given gas flow streamline indicating a notional position of a particle of gas at successive time steps (of equal size) as the particle of gas moves along the streamline in question. The width (diameter) of the collection inlet 122 is larger than the width (diameter) of the output end of the gas flow receiving channel 110 opposing it, enabling a greater throughput of the minor flow. However, former width could be smaller than the latter, if desired, channel but also larger. The minor flow stream 124 provides a gas supply 126 to a downstream system (e.g., desolvation tube, or MS chamber), and could be pumped with negative pressure if desired. The gas pressure in the downstream minor flow 126 is less than the pressure in the major flow 104.

[0146] The virtual impactor of Figure 5 comprises a gas flow receiving channel 110 for conducting the received flow 102 of buffer gas, and a major flow part is defined between opposing surfaces of the flow control aperture part 118B and the output end of the gas flow nozzle part 106, as a duct extending in a direction that is substantially perpendicular to the direction in which the gas flow receiving channel extends. The duct forces the creation of the deflected streamlines 118 of the major flow of buffer gas which extend in a direction that is substantially perpendicular to the direction in which the streamlines of the received flow of buffer gas extends along the gas flow receiving channel 110. In this way, the gas flow receiving channel 110 of the virtual impactor directs the received flow of buffer gas 102, entrained with ions, to pass through an outlet opening of the gas flow receiving channel towards the collection inlet of the opposing flow control aperture part of the virtual impactor. Here, a major portion of the flow 118 is deflected and diverted (e.g., by about 90°) away from the collection inlet 122. The flow control aperture part is configured to admit a part 120 of the received flow of buffer gas 102 to form the minor flow 124 of the buffer gas, and simultaneously to deflect all other parts of that received flow of buffer gas away from the collection inlet of the flow control aperture part (see streamlines 118) and subsequently away from the flow control aperture part 108B as a whole (see streamlines 112) thereby directing the major flow of the buffer gas away from the downstream region.

[0147] Gas Jets

[0148] Figures 6A, 6B and 6C, and Figures 7A and 7B show the principle of spontaneous pumping action around collection inlet 122. This is a significant benefit of examples of the invention because it provides that deflected gas 164 (see Figure 7A) is efficiently evacuated from the duct of the major flow part.

[0149] The flow of gas 102 is provided to the virtual impactor from the upstream region at a gas pressure exceeding a gas pressure provided within the downstream region where the minor flow is output. This gas 8539918

[0150] 23 pressure difference permits the formation of a gas jet at the outlet end of the gas flow receiving channel 110 of the virtual impactor. The outlet end thereby defines a gas jet outlet opening 110B for forming a jet of the gas received from the upstream region. The collection inlet of the flow control aperture part serves as a minor flow aperture in communication with the gas jet outlet opening to admit inner parts of the jet of buffer gas through the minor flow aperture to form the minor flow of the buffer gas. All other parts of the jet of buffer gas are deflected to form the major flow of the buffer gas from the jet.

[0151] The gas jet outlet opening 110B is formed in the terminal end of gas flow nozzle part 106, the nozzle part thereby defining a gas jet outlet part having a first surface 106B extending from a periphery of the gas jet outlet opening 110B. The flow control aperture part defines a second surface via the opposing surface of the flow control aperture part 118B extending from a periphery of the minor flow aperture defining the collection inlet 112 in spaced opposition to the first surface. The second surface deflects parts of the received flow of buffer gas. The first and second surfaces define between them the gas flow gap forming the duct of the major flow part for directing the major flow of the buffer gas away from the minor flow aperture. The first and second surfaces are each planar and are substantially mutually parallel. The second surface is provided by a surface of a circular plate 108B arranged in spaced parallel opposition to a flat first surface 106B. The first surface 106B extends radially from all parts of the periphery of the gas jet outlet opening 110B thereby to fully surround the periphery of the gas jet outlet opening. The second surface also extends from all parts of the minor flow aperture 110B (collection inlet) thereby to fully surround the periphery of the minor flow aperture. Consequently, the gas flow gap is an annular space of uniform width along the gap / spacing between the opposing surfaces, that extends radially in all directions from the minor flow aperture 110B (collection inlet) to form the duct of the major flow part for ducting the major flow. Substantially all parts of the first surface that are not opposed by the minor flow aperture are opposed by the second surface thereby maximizing opposing coverage of the first surface in forming the major flow duct.

[0152] Figure 6A shows a notional scenario 152 where the second surface is absent and the gas jet outlet opening 11 OB is unopposed thereby creating an unobstructed gas jet 156. The gas jet comprises a Mach disk 158 and a portion of jet gas 160 processed by barrel shock. A “region of silence” 162 of the jet is shown. Figures 6B and 6C shows a scenario, 192 and 194, in which the radial extent of the second surface from minor flow aperture (collection inlet), is increased in stages. This shows the deflection of gas 164 from the gas jet. The deflected gas is kept between surfaces of parts 106B and 108B.

[0153] Figures 7A and 7B show a cross-sectional side view (154: Fig. 7A) and a plan view of an end (182: Fig. 7B) of the virtual impactor of Figure 5 with a gas jet present. Impingement points 166 of the gas jet 160 cause deflection of gas 164 into a major flow. The unobstructed parts 168 of the gas jet 160 form a minor flow as a jet of reduced gas speed as compared to the gas speed of in the fast gas jet 160 of Figure 6A, for example a supersonic jet. A first spontaneous pumping region 184, of annular area A1 , is formed in the major flow duct between opposing surfaces 106B and 108B. A second spontaneous pumping region 8539918

[0154] 24

[0155] 186, of annular area A2 (A2>A1) is also formed in the major flow duct between opposing surfaces 106B and 108B and surrounds the first spontaneous pumping region 184. Due to the annular geometry of the major flow duct, and the radial divergence of major gas flow streamlines 164 within it, a negative pressure gradient arises between radially successive annular areas (e.g., A1 and A2) which effectively serves to spontaneously pump the major flow of gas through the major flow duct.

[0156] Figure 8 shows a transparent view 252 of the virtual impactor of Figure 7A and 7B possessing cylindrical symmetry around the axis of the gas flow receiving channel 110. Figure 9 shows a transparent view 254 of an example of the virtual impactor of Figure 5 in a planar form possessing reflection symmetry about the axis of the gas flow receiving channel 110. The first surface extends only from two separated parts of the periphery of the gas jet outlet opening which oppose each other across the gas jet outlet opening 110B. The first surface is rectangular in shape and elongated in a first dimension parallel to the plane of symmetry, and relatively narrow in a second dimension that is perpendicular to the plane of symmetry. The gas jet outlet opening extends fully across the first surface in the second dimension so as to separate the first surface into two separate parts which each extend from a respective one of the two separated parts of the periphery of the gas jet outlet opening. In other words, the gas flow gap comprises an elongated space of uniform width (bore diameter) that extends radially in two opposite directions from the gas jet outlet opening 110B to form the duct of the major flow part for ducting the major flow. The same geometry is present in the second surface, which extends only from two separated parts of the periphery of the minor flow aperture 122 (collection inlet) which oppose each other across the minor flow aperture. The second surface is rectangular in shape and elongated in the first dimension and relatively narrow in the second dimension that is perpendicular to the first dimension. The direction of elongation of the second surface is parallel to that of the first surface. The minor flow aperture extends fully across the second surface in the second dimension so as to separate the second surface into two separate parts which each extend from a respective one of the two separated parts of the periphery of the minor flow aperture 122 (collection inlet). Consequently, the gas flow gap comprises an elongated space of uniform width (bore diameter) that extends radially in two opposite directions from the gas jet outlet opening 110B to form the duct of the major flow part for ducting the major flow.

[0157] Figure 10 and Figure 11 show experimental results of optimising the separation of the opposing first and second surfaces forming the gas flow gap in the virtual impactor of the form shown in Figures 7A and 7B, consisting of these two surfaces forming the major flow duct. The virtual impactor was implemented as the virtual impactor 354 configured to deliver ions to a vacuum chamber 9 containing a mass spectrometry device such as shown in Figure 1 A. Ions are taken from an atmospheric pressure upstream region into the low pressure MS vacuum region 9. An asymmetric voltage waveform was applied by a power source 16 to the planar electrodes 15, to obtain ion separation.

[0158] Graph 502 of Figure 10 shows results derived using a Shimadzu MS2020 device equipped with a low pressure differential mass spectrometry, DMS, device. Gas velocity of the buffer gas passing along the drift region of the DMS device, is plotted as a function of pressure within the low pressure MS vacuum region 9. The “Signal” data shown in the graph 506 of Figure 11 was obtained from the ion detector of the 8539918

[0159] 25

[0160] DMS device for detecting ions of Papaverine. This data is plotted as a function of pressure within the low pressure MS vacuum region 9.

[0161] In each graph, several curves are plotted each of which corresponds to a repeat of the experiment in which the width / diameter of the gas flow gap in the virtual impactor (“Gap” in the graphs) takes a different value as annotated in the graphs. As the size of the gap is increasing, the gas velocity of the buffer gas passing along the drift region of the DMS device is recued for a wide range of pressures. That decrease of the gas speed is important for DMS separation because ions stay longer between separating electrodes. High gas velocity would reduce DMS separation efficiency.

[0162] The inset graph 504 corresponds to a case where the gap size was too small such that fast gas entered vacuum region. The graph 506 shows how the DMS detector signal corresponding to different gas flow gap widths (i.e., separations between elements 106B and 108B). When compared with the data of graph 502 of Figure 10, one can see that the detector signal levels stay on similar level across the range of gap widths, for a given pressure.

[0163] For example, the gap width may be in the range of about 1 mm to about 5mm, and more preferably in the range of about 1 mm to about 3mm, such as in the range of about 1 mm to about 2mm.

[0164] Figures 12A, 12B and 13 show results of a simulation of gas flow in a virtual impactor comprising a between elements equivalent to gas flow nozzle part 106 and collection inlet 108, including particle motion. Here the gas jet outlet opening is formed in the terminal end of gas flow nozzle part 558, the nozzle part thereby defining a gas jet outlet part having a first surface extending from a periphery of the gas jet outlet opening. The flow control aperture part is formed in the opposing surface of the flow control aperture part 560 defining the collection inlet. The flow control aperture part deflects parts 118 of the received flow of buffer gas into the gas flow gap forming the duct of the major flow part for directing the major flow of the buffer gas away from the minor flow aperture. A minor flow 124 is formed along the collection inlet 108.

[0165] This Computational Fluid Dynamics, CFD, simulation simulated nitrogen gas flow from an atmospheric pressure upstream region to a 30mbar downstream vacuum region. The heatmap of figure 12A shows horizontal gas velocity in a direction parallel to the direction of the minor flow 124. The heatmap of figure 12B shows vertical gas velocity in a direction parallel to the direction of the major flow 118. A gas shock barrel and region of silence 562 are indicated.

[0166] Figure 13 shows a graphic 556 from a CFD simulation of nitrogen gas flow between an atmospheric pressure upstream region and a 30mbar vacuum region downstream, combined with a particle motion simulation (hard sphere collisions). Heavy particles, 566, due to their inertia they were transmitted in the minor flow streams 563. Light particles, 568, were deflected by the major flow gas streams 564. 8539918

[0167] 26

[0168] The virtual impactor may be used not only in mass spectrometry and / or ESI applications but may also be applied to the field particle separation. For example, the virtual impactor as described above with reference to the drawings, may be applied in this way. For example, Figure 14 shows an example of the invention providing a virtual impactor as described above with reference to Figure 5 and Figures 7A and 7B. However, in the example of Figure 14, the virtual impactor is used for separating different sizes of particles (e.g., particles of a powder). Here, a separation of particles of two size types (A and B) is shown, but the invention may be applied where there is only one type of particle (A) and it is the carrier gas that is separated from particles A, such as the separation of a nebulising gas or a buffer gas from particles in the form of droplets or ions of an analyte discussed above. In Figure 14, a mixture 202 of two types of particles A and B (or different size) is present in an input carrier gas received by the virtual impactor. The major flow 104 contains a majority of the particles 204 of type B (smaller) separated particles of type A, which comprise the majority of the particles 206 of type A (larger) are taken by the minor flow 126.

[0169] Figure 15 shows a variant of the virtual impactor which may be used for separating a mixture 304 of three different types (sizes) of particles: A, B and C, within a carrier gas. This may also be used as any of the virtual impactors 332, 354 and 364, discussed above with reference to figures 1 , 2A, 2B, and 3A to 3C for the separation of a nebulising gas or a buffer gas from particles in the form of droplets or ions of an analyte. In particular, the virtual impactor 362 of Figure 3C may take the form described below with reference to Figure 15.

[0170] In particular, this example of the virtual impactor comprises: an input port 110 for receiving an input flow of gas 102 entrained with particles of three different types (sizes): A, B and C, for separation in ascending order of particle size; and, first minor flow port 122A for forming a first minor flow 126A of gas from the input flow 102 of gas containing at least a majority of particles of type B and type C having a size exceeding a first particle size from amongst the entrained particles; and, a second minor flow port 122B downstream of the first minor flow port 122A for forming a second minor flow 126B of gas from gas 126A received from the first minor flow port 122A and containing at least a majority of particles of type C having a size exceeding a second particle size from amongst the entrained particles. The second particle size (C) exceeds the first particle size (A).

[0171] The virtual impactor further comprises: a first major flow part, formed between opposing plane-parallel surface parts 106B and 108B, that is configured for directing away from the first minor flow port 122A a portion of the input flow of gas 102 as a first major flow of gas 104 containing not more than a minority of particles of type B and type C having a size exceeding the first particle size from amongst the entrained particles; and, a second major flow part, formed between opposing plane-parallel surface parts 106C and 108C, that is configured downstream of the first minor flow port 122A for directing away from the second minor flow port 122B a portion of the first minor flow of gas 126A as a second major flow of gas 310 containing not 8539918

[0172] 27 more than a minority of particles of type C having a size exceeding the second particle size from amongst the entrained particles.

[0173] Because the second particle size exceeds the first particle size the effect of the virtual impactor is to separate entrained particles of type A, B and C respectively into: the first major flow of gas; the second major flow of gas; and the second minor flow of gas according to particle size.

[0174] Alternatively, if the carrier gas contains only particles of type A (e.g., ions and / or droplets) the virtual impactor may be used to enhance the concentration of those particles within the second minor flow 126B of gas by diverting a proportion of the carrier gas via the first and second major flows of gas. This implementation may be made by the virtual impactor 362 shown in Figure 3C.

[0175] Figure 16 shows an example of the virtual impactor according to an aspect of the invention. Such as when used as a particle separator, for example a powder separator for drug production or food industry. It may be used for separation of molecules that have a macroscopic size.

[0176] The virtual impactor comprises an outlet 452 for pumping and filtering particles type A, an outlet 454 for pumping and filtering particles type B, and an outlet 456 for pumping and filtering particles type C. Compressed air 458 is supplied to a compressed air inlet port of a Venturi tube 470. A mixture 462 of particles A, B and C are drawn into a particle intake port of the Venturi tube 470, within an intake airflow 460 by virtue of a Venturi effect generated in the Venturi tube. By virtue of the processes described above with reference to Figure 15, separated particles 464 of type A, separated particles 466 of type B, and separated particles 468 of type C are output in gas flows 456 (minor flow), 454 (major flow), and 452 (minor flow), respectively.

[0177] The parts of the particle separator shown within the dashed box marked “X” are the same as virtual impactor of Figure 15. A gas input flow duct 472 of the particle separator is equivalent to part 106 of the virtual impactor of Figure 15. A first major flow duct 474 of the particle separator is equivalent to part 108 of the virtual impactor of Figure 15, a second major flow duct 476 of the particle separator is equivalent to part 302 of the virtual impactor of Figure 15, and a minor flow outlet 478 of the particle separator that is equivalent to part 122B of the virtual impactor of Figure 15.

[0178] 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.

[0179] 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 8539918

[0180] 28 be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention.

[0181] 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.

[0182] Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0183] Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise” and “include”, and variations such as “comprises”, “comprising”, and “including” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

[0184] It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedent “about,” it will be understood that the particular value forms another embodiment. The term “about” in relation to a numerical value is optional and means for example + / - 10%.

[0185] Examples

[0186] The virtual impactor employed in aspects of the invention differs for a gas jet separator because a jet separator relies on natural gas expansion, whereby lighter particles in a gas jet expand radially faster than heavier particles. In the present invention, a virtual impactor forms gas streamlines that are forced to rapidly change direction by gas ducting. The gas drag force is considered to be larger than in the case of a jet separator as separation occurs over a smaller distance. Additionally, rejected gas (major flow) is naturally taken away by the Bernoulli effect and gas momentum, creating a spontaneous pumping force stimulating light gas and molecule removal from the mains gas flow streams.

[0187] The proposed invention can control gas speeds delivered into an analytical gap between electrodes of a DMS device of Figure 1 A. The gas speed defines the DMS resolution. In standard MS the gas is delivered as a supersonic gas jet directed between electrodes of a quadrupole array, 406 of Figure 1 B, that is responsible for capturing ions. The main difficulty in optimising that part is related to the supersonic jet dragging away ions with different masses and / or cross-sections with different forces what is detrimental to ion capture by the quadrupole array. As the result, the mass spectrum is affected by mass bias, not uniform sensitivity over m / z scale. Simple way to improve quadrupole array efficiency in capturing ions from the gas jet is to make that gas jet less violent. The present invention addresses this problem. Both problems may be addresses by the present invention, by separating a large part of carrying gas from ions resulting ions being delivered into a vacuum / low pressure of the device with a slow gas. 8539918

[0188] 29

[0189] In many devices, like MS, ions of an analyte are delivered from an ion source device, for example ESI, working in an atmospheric pressure (AP) environment, but delivering the ions into a vacuum environment through a small capillary (for example a desolvation line (or tube) “DL”). After ion extraction from a carrying gas, the remaining carrying gas needs to be evacuated by an efficient pumping system. For example, in MS this takes place in the front vacuum chamber equipped with for example a quadrupole ion guide system to capture ions and transport them to the next vacuum chamber. The capillary diameter of the DL provides gas intake from the AP region and with that droplets / ions are carried into the first MS vacuum chamber. The number of ions delivered to the MS region is one of the parameters defining instrument sensitivity. To increase sensitivity, it is preferential to have a capillaries / DL possessing a large opening diameter that can provide larger gas intake. However, a larger gas intake requires a more efficient pumping system. The proposed invention can reduce gas load into the first chamber by taking out a large part of carrying gas. It is more efficient to pump the gas separated into a major flow using a virtual impactor of the present invention, as opposed to pumping the large front chamber of an analytical device, for the following reasons:

[0190] Gas that is pumped out as a major flow using a virtual impactor according to the present invention would stay at higher pressure than it would be in the front chamber.

[0191] Gas is locked between two surfaces forming a major flow duct of the virtual impactor according to the present invention with the large momentum towards pumping direction.

[0192] Expanding gas between two surfaces when it is pumped would go through an increasing volume.

[0193] ESI carrier gas reduction and DL intake improvements may arise as follows. In ESI, a liquid sample is separated from a needle with a strong carrying / nebulizing gas jet and droplets are formed. The needle is kept under high voltage. When fast carrier gas with droplets / ions arrives on front of DL due to its speed the intake is limited. By using a virtual impactor according to the present invention, one may to remove a large part of the carrying gas from ESI after droplets are formed. Because droplets / ions generated by ESI are carried by slow gas due to implementation of the virtual impactor according to the present invention, the intake by capillary / DL is improved and due to that more ions are delivered into the MS device. Larger ion intake is directly related with higher sensitivity.

[0194] Instead of reducing gas load into the front vacuum chamber of an MS device, one may retain the same pumping efficiency and increase the capillary / DL diameter. That may result in an increase of ion intake which would improve MS sensitivity, while maintaining manageable intake of gas.

[0195] Figure 5 shows a simple implementation of the virtual impactor according to the present invention that allows to separate partially ions / neutrals from the carrying gas. Carrying gas with ions / neutrals (droplets) is pumped in 102 into narrow channel 110. Carrying gas splits and is locked between elements 106 and 108 due to its speed and Bernoulli’s principle. Carrying gas 112 is pumped out 104. Part of the carrying gas 110 passes through the opening 122 with lower velocity 124 for delivery downstream. The carrying 8539918

[0196] 30 gas is later evacuated form the vacuum / low pressure front chamber of the analytical device, and an ion extraction device for example quadrupole 406 (Fig. 1 B) may be used to capture ions from within the downstream area.

[0197] Figures 7A and 7B are applicable to the case, for example, where the gas jet enters from atmospheric pressure into a vacuum region of an MS device creating supersonic gas jet 156. It is important that the gas barrel shock gas part 160 of the supersonic jet is aligned with the aperture 110B such that that it gets reflected 164 and most of the gas 168 forming the minor flow originates from the region of silence 162. This part 168 is passed to the vacuum part of MS. In this case a sudden change of gas motion by the barrel shock causes ions with larger momentum and / or smaller cross-section to follow into a region of silence 162. In this way most of the ions are moved into the vacuum region with minimum gas load. The virtual impactor according to the present invention may be optimised to promote passing of ions and reduce passage of carrying gas. The optimisation can be done by varying the size of the minor flow aperture 122 and the major flow gap between 106 and 108.

[0198] In general terms, in preferred examples, the virtual impactor according to the present invention may be considered as follows. Two parallel plates with a pumped gap and aligned apertures are used. Fast carrier gas jet enters through a first aperture, expands and becomes locked between two plates due to Bernoulli’s effect. A second aperture allows part of gas to escape. Ions and / or neutrals possessing larger momenta than that of the gas particles go through the second aperture. Consequently:

[0199] • Ions and / or neutrals become separated from majority of carrying gas in atmospheric pressure - vacuum MS interface

[0200] • Gas jet shock is still in place promoting change of droplets to ions

[0201] • ion capture efficiency by a downstream MS quadrupole array improves due to smaller gas jet

[0202] • Due to smaller gas jet, gas speed in low pressure DMS addon to MS can be achieved improving separation resolution or additional devices can be used for further gas speed reduction

[0203] In general terms, in preferred examples, the virtual impactor according to the present invention may be considered as follows. Two parallel plates with a pumped gap and aligned apertures are used. Fast carrier gas powder enters through a first aperture, expands and become locked between two plates due to Bernoulli’s effect. A second aperture allows part of gas to escape. Powder with lower momenta and / or cross section is taken between plates where powder with larger momenta and / or cross section goes through the second aperture. Consequently:

[0204] • Powder molecules having different mass and / or cross section are separated

[0205] • Locking carrying gas between two plates due to Bernoulli’s effect and use it for powder separation

[0206] In general terms, in preferred examples, the virtual impactor according to the present invention may be considered as follows. Two parallel plates with a pumped gap and aligned apertures are used for ESI and DL regions of MS. In the case of ESI they are used to separate droplets, after formation, from a fast 8539918

[0207] 31 carrier gas, which improves DL intake. In the case of the DL, a majority of gas carrier ions is separated allowing to increase aperture of DL and its intake without increasing need for larger pumping speed. Consequently:

[0208] • ESI droplets formation remains undisturbed

[0209] • Fast spraying gas is separated from droplets

[0210] • Gas carrying droplets / ions around DL intake is low improving its intake

[0211] • Gas jet shock in MS vacuum part is still in place promoting change of droplets to ions

[0212] • DL aperture can be increased without increasing gas intake by MS pumping system improving droplets / ions intake

[0213] • Locking carrying gas between two plates due to Bernoulli’s principle effect and use it to slow down droplets / ions carrying gas to improve DL intake that is equivalent to higher sensitivity

[0214] • Locking carrying gas between two plates due to Bernoulli’s principle effect and use it to increase DL aperture without changing vacuum gas load and by this improving DL intake that is equivalent to higher sensitivity

[0215] Figures 17A, 17B and 17C show views of a virtual impactor connected to the input end of a desolvation tube. The virtual impactor 602 as depicted on Figure 5 is connected with its minor flow outlet in fluid communication to the flow inlet opening of a desolvation tube 356 and with its gas flow inlet in fluid communication with an ESI ion source in an ESI chamber at higher pressure, for receiving a plume of nebulized analyte and ions from the ESI ion source. The virtual impactor has a relatively large gas and ion flow inlet opening 608, a major flow duct 609, and a minor flow opening 611 defining the flow inlet opening of a desolvation tube 356. Part of the gas is diverted into the major flow duct as the major flow, while keeping ions concentrated in the minor flow directed into the desolvation tube. More ions per gas volume are provided in the minor flow. The version of a virtual impactor 362 shown in Figure 3C has the same purpose and principles, but possesses two concatenated major flow ducts as discussed above with reference to Figure 15. Void region 610 provides a connection to pumping apparatus (not shown) for pumping gas of the major flow. The output end of the desolvation tube comprises a standard nozzle 604 for coupling the output end of the desolvation tube to the downstream vacuum region, and has a standard ejection of gas outlet 606 for outputting ions into an MS vacuum chamber of an MS instrument containing an ion detector for detecting ions delivered into an MS vacuum chamber by the desolvation tube.

[0216] Figures 18A and 18B show experimental results from use of a desolvation tube of Figures 17A, 17B and 17C. Graph 652 shows the detected quantity of ions into an MS vacuum chamber, as a function of time (minutes). The virtual impactor 602 was not attached to the input end of the desolvation tube 356 when conducting these experiments. Ion intensities 652a were detected as a result of a sequence of five separate injections of analyte (Papaverine LC) into the MS instrument, each of 10 nM, followed by five separate subsequent injections 652b of the analyte, each of 100 nM, into the MS instrument. The injections each result in a detected spike in ion intensity at the ion detector of the MS device. The five 8539918

[0217] 32 separate subsequent injections of the analyte, 652b, each peak at approximately the same peak intensity value 656.

[0218] By contrast, graph 654 shows the detected quantity of ions into an MS vacuum chamber, as a function of time (minutes). The virtual impactor 602 was attached to the input end of the desolvation tube 356 when conducting these experiments. Ion intensities 654a were detected as a result of a sequence of five separate injections of analyte (Papaverine LC) into the MS instrument, each of 10 nM, followed by five separate subsequent injections 654b of the analyte, each of 100 nM, into the MS instrument. The injections each result in a detected spike in ion intensity at the ion detector of the MS device. The five separate subsequent injections of the analyte, 654b, each peak at approximately the same peak intensity value 657, which shows more than a 70% signal increase and, consequently, a higher sensitivity.

[0219] References

[0220] A number of publications are cited above in order to more fully describe and disclose the invention and the state of the art to which the invention pertains. Full citations for these references are provided below. The entirety of each of these references is incorporated herein.

[0221] [1] US20080315087

[0222] [2] WO2010125357

[0223] [3] US3425736

[0224] [4] US3936374

[0225] [5] EP2864998B1

[0226] [6] US8026477B2

[0227] [7] US8987663B2

[0228] [8] US20110095095A1

Claims

853991833Claims:1 . An ion analysis apparatus comprising: an ion source for generating ions from a sample; an upstream region for providing a flow of a buffer gas containing the ions from the ion source; a virtual impactor for receiving the flow of buffer gas from the upstream region; a downstream region for receiving ions in a minor flow of the buffer gas output from the virtual impactor, the downstream region comprising an ion analysis assembly configured to receive therein said minor flow of buffer gas; wherein the virtual impactor comprises: a minor flow part configured for directing towards the downstream region a part of the received flow of buffer gas as said minor flow of the buffer gas containing at least a majority of the ions; and, a major flow part configured for directing away from the downstream region a part of the received flow of buffer gas as a major flow of the buffer gas containing not more than a minority of the ions.

2. An apparatus according to any preceding claim wherein the minor flow part comprises a flow control aperture part configured to admit a part of the received flow of buffer gas therefrom to form the minor flow of the buffer gas, and simultaneously to deflect all other parts of that received flow of buffer gas away from the flow control aperture part thereby directing the major flow of the buffer gas away from the downstream region.

3. An apparatus according to claim 2 configured for providing the flow of buffer gas from the upstream region at a gas pressure exceeding a gas pressure provided within the downstream region thereby providing a gas pressure difference therebetween, wherein the virtual impactor comprises a gas jet outlet opening for forming a jet of the buffer gas received from the upstream region in response to the gas pressure difference, wherein the flow control aperture part comprises a minor flow aperture in communication with the gas jet outlet opening and is configured to admit inner parts of the jet of buffer gas through the minor flow aperture to form the minor flow of the buffer gas therefrom, and to deflect all other parts of the jet of buffer gas to form the major flow of the buffer gas therefrom.

4. An apparatus according to claim 3 wherein the gas jet outlet opening is formed in a gas jet outlet part defining a first surface extending from a periphery of the gas jet outlet opening, and the flow control part defines a second surface extending from a periphery of the minor flow aperture in spaced opposition to the first surface for deflecting parts of the received flow of buffer gas, whereby the first and second surfaces define between them a gas flow gap forming the major flow part for directing the853991834 major flow of the buffer gas away from the minor flow aperture and away from the downstream region.

5. An apparatus according to claim 4 wherein the first and second surfaces are substantially mutually parallel.

6. An apparatus according to claim 4 or claim 5 wherein the first and second surfaces are substantially planar.

7. An apparatus according to any of claims 4 to 6 wherein the first surface extends from all parts of the periphery of the gas jet outlet opening thereby to fully surround the periphery of the gas jet outlet opening.

8. An apparatus according to any of claims 4 to 6 wherein the first surface extends only from two separated parts of the periphery of the gas jet outlet opening which oppose each other across the gas jet outlet opening.

9. An apparatus according to any of claims 4 to 8 wherein the second surface extends from all parts of the minor flow aperture thereby to fully surround the periphery of the minor flow aperture.

10. An apparatus according to any of claims 4 to 8 wherein the second surface extends only from two separated parts of the periphery of the minor flow aperture which oppose each other across the minor flow aperture.11 . An apparatus according to any of claims 4 to 10 wherein substantially all parts of the first surface that are not opposed by the minor flow aperture are opposed by the second surface.

12. An apparatus according to any of claims 3 to 11 wherein a width of the minor flow aperture exceeds a width of the gas jet outlet opening.

13. An apparatus according to any of claims 3 to 12 wherein the virtual impactor comprises: a first major flow part configured for directing away from the downstream region a part of the received flow of buffer gas as a first major flow of the buffer gas containing not more than a minority of the ions; an intermediate minor flow part configured for directing towards the downstream region a part of the received flow of buffer gas as an intermediate minor flow of the buffer gas containing at least a majority of the ions; a terminal minor flow part disposed downstream of the intermediate minor flow part and configured for receiving the intermediate minor flow of the buffer gas and for directing towards the downstream region said minor flow of the buffer gas containing at least a majority of the ions;853991835 wherein the intermediate minor flow part and the terminal minor flow part collectively form a second major flow part configured for directing away from the downstream region a part of the intermediate minor flow of the buffer gas as a second major flow of the buffer gas containing not more than a minority of the ions.

14. An apparatus according to any preceding claim wherein virtual impactor comprises a gas flow receiving channel for received the flow of buffer gas, and the major flow part defines one or more channels extending in a direction that is substantially perpendicular to the direction in which the gas flow receiving channel extends.

15. An Electrospray Ionisation, ESI, interface comprising: an input port for receiving a liquid solution containing an analyte, and an output port for outputting droplets and / or ions of the analyte; and, a pneumatically-assisted sprayer in fluid communication with the input port and comprising: a spray capillary for supporting a flow of the liquid solution to a spray output end of the pneumatically-assisted sprayer; and, a nebulizer gas duct for supporting a flow of a nebulizing gas to the spray output end for nebulizing the liquid solution thereat to produce an electrospray plume comprising the nebulizing gas containing droplets of said liquid solution and / or ions of the analyte; a voltage source configured to apply a voltage to the spray capillary for generating an electric field at the spray output end for inducing a charge accumulation at the surface of the liquid solution; a virtual impactor for receiving the electrospray plume from the spray output end, wherein the virtual impactor comprises: a minor flow part configured for directing towards the output port a part of the received electrospray plume as a minor flow of the electrospray plume containing at least a majority of the analyte; and, a major flow part for directing away from the output port a part of the received electrospray plume as a major flow of the electrospray plume containing not more than a minority of the analyte.

16. An Electrospray Ionisation, ESI, interface according to claim 15 wherein the virtual impactor is mounted coaxially to, and concentrically around, the pneumatically-assisted sprayer.

17. An Electrospray Ionisation, ESI, interface according to any of claims 15 and 16 comprising a heater for heating the spray capillary to desolvate droplets of said liquid solution.

18. An Electrospray Ionisation, ESI, interface according to any of claims 15 to 17 wherein the minor flow part comprises a flow control aperture part configured to admit a part of the received electrospray plume therefrom to form the minor flow of the electrospray plume, and simultaneously to deflect all853991836 other parts of that received electrospray plume away from the flow control aperture part thereby directing the major flow of the electrospray plume away from the output port.

19. An apparatus according to claim 18 wherein the virtual impactor comprises a gas jet outlet opening for forming a jet of the nebulizing gas received from the pneumatically-assisted sprayer in response to a gas pressure difference formable between the input port and the virtual impactor, wherein the flow control aperture part comprises a minor flow aperture in communication with the gas jet outlet opening and is configured to admit inner parts of the jet of nebulizing gas through the minor flow aperture to form the minor flow of the electrospray plume therefrom, and to deflect all other parts of the jet of nebulizing gas to form the major flow of the electrospray plume therefrom.

20. An apparatus according to claim 19 wherein the gas jet outlet opening is formed in a gas jet outlet part defining a first surface extending from a periphery of the gas jet outlet opening, and the flow control part defines a second surface extending from a periphery of the minor flow aperture in spaced opposition to the first surface for deflecting parts of the received flow of nebulizing gas, whereby the first and second surfaces define between them a gas flow gap forming the major flow part for directing the major flow of the electrospray plume away from the minor flow aperture and away from the output port.

21. An apparatus according to claim 20 wherein the first and second surfaces are substantially mutually parallel.

22. An apparatus according to claim 20 or claim 21 wherein the first and second surfaces are substantially planar.

23. An apparatus according to any of claims 20 to 22 wherein the first surface extends from all parts of the periphery of the gas jet outlet opening thereby to fully surround the periphery of the gas jet outlet opening.

24. An apparatus according to any of claims 20 to 23 wherein the first surface extends only from two separated parts of the periphery of the gas jet outlet opening which oppose each other across the gas jet outlet opening.

25. An apparatus according to any of claims 20 to 24 wherein the second surface extends from all parts of the minor flow aperture thereby to fully surround the periphery of the minor flow aperture.

26. An apparatus according to any of claims 20 to 25 wherein the second surface extends only from two separated parts of the periphery of the minor flow aperture which oppose each other across the minor flow aperture.85399183727. An apparatus according to any of claims 20 to 26 wherein substantially all parts of the first surface that are not opposed by the minor flow aperture are opposed by the second surface.

28. An apparatus according to any of claims 19 to 27 wherein a width of the minor flow aperture exceeds a width of the gas jet outlet opening.

29. An apparatus according to any of claims 15 to 28 wherein the virtual impactor comprises: a first major flow part configured for directing away from the output port a part of the received flow of nebulizing gas as a first major flow of the electrospray plume containing not more than a minority of the ions; an intermediate minor flow part configured for directing towards the output port a part of the received flow of nebulizing gas as an intermediate minor flow of the electrospray plume containing at least a majority of the ions; a terminal minor flow part disposed downstream of the intermediate minor flow part and configured for receiving the intermediate minor flow of the electrospray plume and for directing towards the output port said minor flow of the electrospray plume containing at least a majority of the ions; wherein the intermediate minor flow part and the terminal minor flow part collectively form a second major flow part configured for directing away from the output port a part of the intermediate minor flow of the electrospray plume as a second major flow of the electrospray plume containing not more than a minority of the ions.

30. An apparatus according to any preceding claim wherein the major flow part(s) define one or more channels extending in a direction that is substantially perpendicular to the direction in which the pneumatically-assisted sprayer extends.

31. A method for ion analysis comprising: generating ions from a sample in an ion source; providing an upstream region and therein providing a flow of a buffer gas containing the ions from the ion source; providing a virtual impactor and receiving therein the flow of buffer gas from the upstream region; providing a downstream region comprising an ion analysis assembly; and, by the virtual impactor: directing towards the downstream region a part of the received flow of buffer gas as a minor flow of the buffer gas containing at least a majority of the ions to provide the minor flow of buffer gas to the ion analysis assembly; and,853991838 directing away from the downstream region a part of the received flow of buffer gas as a major flow of the buffer gas containing not more than a minority of the ions.

32. A method for Electrospray Ionisation, ESI, interfacing comprising: providing a pneumatically-assisted sprayer in fluid communication with the input port and comprising: a spray capillary for supporting a flow of the liquid solution to a spray output end of the pneumatically-assisted sprayer; and, a nebulizer gas duct for supporting a flow of a nebulizing gas to the spray output end for nebulizing the liquid solution thereat to produce an electrospray plume comprising the nebulizing gas containing droplets of said liquid solution and / or ions of the analyte; applying a voltage to the spray capillary to generate an electric field at the spray output end thereby inducing a charge accumulation at the surface of the liquid solution; and, providing a virtual impactor for receiving the electrospray plume from the spray output end, and by the virtual impactor: directing towards the output port a part of the received electrospray plume as a minor flow of the electrospray plume containing at least a majority of the analyte; and, directing away from the output port a part of the received electrospray plume as a major flow of the electrospray plume containing not more than a minority of the analyte.

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