Patent Application
20150108347
The invention relates to an improved interface between an ionizer and an analyzer. More specifically, the invention teaches how to desolvate analyte ions at atmospheric pressure and to improve the transmission of analyte ions form the ionization source to the analyzer, while avoiding contamination produced by low mobility charged particles.
Electro-Spray Ionization (ESI) and Secondary Electro-Spray Ionization (SESI) are powerful tools, which are used for the ionization and further chemical analysis of complex samples from the liquid and the vapor phases, including the effluent of liquid cromatography, gas chromatography and electrophoresis separators. These ionization techniques typically operate at near atmospheric pressure, and they produce a rich variety of (i) analyte ions, (ii) charged droplets of the electrosprayed liquid, which contains the analytes, the solvents, and other contaminants, (iii) clusters, which might contain analytes, contaminants and solvent molecules, and (iv) vapors (for the clarity of the exposition, this mixture will be here referred to as the electrospray mist). However, very often only the analyte ions are of interest for the analytical applications.
Desolvation of Ions:
When coupled with mass spectrometers (MS), the electrospray mist must be dried prior to being analyzed, and the analyte ions must be separated from the rest of the contaminants so that their mass can be measured. Furthermore, it is important to reduce the content of condensable vapors when the mixture of charged particles is transferred from the atmospheric pressure side to the vacuum side of the mass spectrometer through the, so called, Atmospheric Pressure Interface (API). Otherwise, due to the rapid expansion of the supersonic jet, which drags the electrospray mist through the MS inlet (an orifice or a capillary), vapors would tend to condense on the majority of the ions, thus forming big droplets that would not be detected by the MS. Pneumatically assisted electrospray [See U.S. Pat. No. 4,861,988 A] improves the robustness of the ionization, but the increased liquid flow rates produce more and bigger droplets, which are more difficult to desolvate.
By means of an axial counterflow, Fenn and colleagues [U.S. Pat. No. 4,531,056] eliminate a sufficient amount of droplets and vapors prior to the inlet orifice of the MS, which enables a safe supersonic expansion, and a further mass analysis. However, ions are not completely dried by this counterflow feature.
Also, the low pressures of the MS enhance diffusion, which facilitates evacuation of unwanted neutrals. As a result, due to the low pressure of operation of the MS, the API dries the analyte ions very efficiently. Indeed, other configurations do not use the counterflow feature described by Fenn. Instead, they heat the gas to prevent droplet condensation in the expanding jet. For instance, U.S. Pat. No. 4,977,320, U.S. Pat. No. 5,298,744, and U.S. Pat. No. 5,504,327 describe a heated capillary which heats the electrospray mist, evaporates the solvents, and passes the whole mixture to the low pressure side of the MS. In this region, the neutral species are pumped away in the subsequent pumping stages, and the ions are further dried by the heat of the charged particles, which is produced by means of electric fields, either by Direct Current (DC) potentials between electrodes or by the Radio frequency (RF) of quadrupoles, multipoles, and ion funnels used in the ion optics region. U.S. Pat. No. 5,756,994, U.S. Pat. No. 4,999,493 and U.S. Pat. No. 6,700,119 B1 describe an atmospheric pressure ionization interface for MS analysis in which the stream of gas and charged particles enter in a heated chamber, and where the path of the ions, as they pass though the subsequent pumping stages is angled so as to minimize the passage of droplets. These systems overcome the complications associated with the counterflow feature. However, drying the ions at low pressure has other drawbacks, high amounts of contaminants produced by the electrospray can enter the low pressure region of the MS, and these contaminants tend to deposits on the inner walls of the MS and the electrodes, which need to be cleaned. Cleaning the low pressure side of the MS becomes increasingly necessary if one needs to analyze complex samples incorporating low volatility species. And, because these parts are in the low pressure side of the MS, cleaning them is a time consuming operation, which typically requires stopping the vacuum system of the MS, filling the MS with high purity gas until it reaches atmospheric pressure, opening the MS, cleaning the parts which are contaminated, and re-starting the vacuum system (which might take up to one day or even one week, depending on the vacuum level required by each MS). Moreover, this operation must be performed carefully to avoid entrance of dust and other contaminants in the MS, which could impair its operation. As a result, the cleaning procedure, which would take only a few minutes if it was performed at atmospheric pressure, becomes a mayor maintenance operation.
Off-axis electrospray injection [See U.S. Pat. No. 5,750,988] also allows the quantity of ingested droplets to be reduced, but it does not eliminate completely the unwanted big droplets. U.S. Pat. No. 5,412,208 describes a configuration incorporating turbulent hot gas jets aiming at the electrospray plume upstream of the counterflow region. This configuration dries the droplets more quickly and, as a result, fewer droplets and more ions reach the counterflow region. However, the turbulent flow cannot improve the separation capacity of the counterflow, which inevitably passes clusters and traces of vapors to the downstream side of the orifice plate. The invention described in U.S. Pat. No. 7,145,136 B2 utilizes a modified counterflow configuration in which part of the counterflow gas is diverted towards the electrospray plume to enhance the drying process. Enhanced turbulent configurations are also used to promote droplet evaporation [See U.S. Pat. No. 6,700,119 B1 for instance].
In U.S. Pat. No. 7,534,997 B2, a flow of drying gas circulates between to plates, and the ion pathway, as defined by two orifices, has an offset that precludes the passage of big droplets, which follow a straight trajectory that would otherwise reach the orifice communicating with the MS. Smaller droplets reach the second orifice, but they travel a longer distance and are thus more desolvated. However, this system does not separate ions and droplets, likely because the flow is turbulent to enhance heat transfer to the droplets.
A system capable of completely drying the analyte ions at atmospheric pressure and of separating them from other vapors produced by the ionizer would eliminate the need to clean the low pressure side of the MS, and would thus greatly improve its robustness and maintenance costs. However, all the previous configurations described require the ions to be further dried in the low pressure region of the MS, which eventually gets contaminated. Consequently, one goal of the present invention is to provide a solution to the problem of desolvating the ions and separating them at atmospheric pressure (or at least above 100 Torr) from the droplets and vapors produced by the ionizer.
Ion Mobility Spectrometry (IMS) followed by MS analysis is an emerging and very powerful technique that provides extra structural information and separation capacity. According to their principle of operation, there are various IMS techniques, which will be all referred to as IMS in the context of this description. These techniques include Drift Tube IMS (DTIMS), Travelling Wave IMS (TWIMS), Field Asymmetric IMS (FAIMS), Differential Mobility Analysis (DMA), and Variable Electric Field Mobility Analysis (VEFMA). When the IMS is operated downstream of the API interface, it has the advantage that the ions previously pass through the API, and are thus well desolvated due to low pressures of operation of the API. However, these architectures have the disadvantage that the IMS cell needs to be integrated within the low pressure system of the MS, thus requiring a specific design. In contrast, IMS systems operating at higher pressures can operate upstream of the inlet of the MS, and can be developed independently. As a result, the IMS operating at atmospheric or near atmospheric pressures can be added to pre-existing mass spectrometers, as an add on gadget, which enables the user to independently choose the best MS and the IMS for each application, thus maximizing the flexibility of the IMS-MS system and the acquisition economical costs. Although these systems can be more cost effective, a new requirement arises: the analyte ions must be desolvated and separated from the other contaminants prior to their introduction in the IMS separation cell. DTIMS are used at atmospheric pressure in security applications in combination with radioactive ionization sources, which provide a particularly clean sample, which is free from solvents, and which is only useful for a limited family of species. However, these systems are not used with other ion source producing more complex samples because it cannot handle the vapors and incompletely desolvated samples produced by other ion sources.
Achieving a complete desolvation of analyte ions at atmospheric pressure is a complicated task for various reasons: (i) electrostatic ion heating is very low because, at atmospheric pressure, the mean free path of the ions (the averaged distance between collisions with other molecules of the gas) is very low, and hence the extra kinetic energy added by the electric fields onto the ion between collisions is very low; (ii) diffusion is low (in first approximation, it is inversely proportional to the pressure of the gas) and, as a result, vapors released by the droplets remain in the vicinity of the droplet, causing the local vapor pressure near the droplet to be very high. Moreover, due to the fact that ions are continuously colliding with molecules, the gas must be very pure because, otherwise, ions would collide with contaminants and could form new clusters even if one initially managed to completely dry the ions. To give an estimation of the required gas purity, an ion having a residence time of 1 ms in an IMS cell operated at atmospheric pressure will collide with a neutral molecule approximately 4·106 times (every 0.2 ns in average), which means that it will very likely collide at least once with all contaminants present at a concentration in the order of one ppm. These collisions are not important if the contaminants do not react with the ions. However, if the contaminant forms a cluster with the ion, the mobility of the resulting charged particle will change in the middle of the analysis, leading to background signals, tails, and not well defined peaks in the mobility spectrum. Furthermore, if the presence of contaminants is not well controlled, they will lead to non repeatable results.
An attempt to dry ions at atmospheric pressure prior to IMS analysis is described in U.S. Pat. No. 7,351,960 B2. U.S. Pat. No. 7,351,960 B2 discloses a heated capillary, which situated between an ion source and the inlet of a FAIMS device, while this capillary can effectively desolvate droplets, the solvent vapors and the contamination produced during desolvation is conducted towards the FAIMS separation cell. Although ions can be desolvated in the capillary, they can be affected in the cell by the presence of said vapors within the FAIMS cell. As a result, the spectra produced by this system are subjected to poor resolving power and repeatability, and the peaks tend to produce long tails, which in turn lead to a high and undesired background signal level.
U.S. Pat. No. 7,005,633 B2 discloses a desolvation system comprising an axial counterflow which helps to dry droplets and which sweeps away the neutral molecules from the FAIMS device. U.S. Pat. No. 7,189,966 B2 describes an alternative axial counterflow configuration, which incorporates a porous diffuser to laminarize the flow fed to the counterflow chamber. Although these systems reduce the entrance of contamination in the separation cell, the axial counterflow configuration cannot efficiently remove charged droplets which have a sufficiently high mobility to travel against the counterflow current, and which tend to complete their drying process in the separation cell, thus releasing vapors in this region. As a result, although the concentration of contaminants is reduced, said concentration remains above the threshold required to operate the IMS system. This problem arises from the fact that the velocity profile of axial counterflow is not uniform, and partially clustered droplets can pass towards the analyzer through the regions of low velocity (such as the boundary layers, and recirculation regions). Also, the counterflow configuration tends to be turbulent, and some transient eddies can temporally facilitate the passage of droplets to the analyzer, which becomes contaminated for long periods of time.
In summary, regular counterflow is incapable of providing the required desolvation level, and no known desovation system is capable of (i) drying the analyte ions and (ii) eliminating the neutral vapor species as well as incompletely desolvated ions, such that ion mobility spectrometry systems (IMS), including DTIMS, TWIMS, FAIMS, DMA and VEFMA, can safely operate at atmospheric pressure with ion sources producing high amounts of solvents and contamination, such as ESI, nano-ESI, SESI, nebulizer assisted ESI, and other ion sources which can be easily identified by those skilled in the art. Consequently, another goal of the present invention is to provide a solution to the problem of desolvating the ions and separating them at atmospheric pressure from the droplets and vapors produced by the ionizer so as to allow the coupling of ionization systems with IMS systems operating at pressures close to the atmospheric pressure (or at least above 100 Torr).
Planar Differential Mobility Analyzer:
Planar Differential Mobility Analyzers (DMA) operated at high Reynolds Numbers and at near atmospheric pressure are used to select ions according to their mobility and, in tandem with a Mass Spectrometer (MS), they increase the overall selectivity of the compounded analyzer. In a DMA, a drifting gas flows between two parallel electrodes that produce a perpendicular electric field. Ions are driven by the fluid velocity in one direction and by the electric velocity, which is proportional to their mobility, in the perpendicular direction. All ions are introduced through an inlet slit (in the upper electrode), each following a different trajectory, and only ions having the selected mobility reach the outlet slit (in the lower electrode). J. Fernandez de la Mora and coworkers first introduced the use of planar DMA for tandem with MS in U.S. Pat. No. 5,869,831, where the planar DMA geometry allowed for very accessible inlet and outlets.
An improved configuration, taught by Rus et al. in U.S. Pat. No. 7,928,374, uses a specifically designed channel with an elongated shape in the DMA exit side that becomes round in the MS inlet side. Rus also teaches a specific mechanical design that precludes leaks that tend to arise in the geometry proposed in U.S. Pat. No. 5,869,831. He also teaches how to run the DMA drift flow in closed circuit with a gas tight pump so as to control the composition and purity of the gas utilized. Working in closed circuit is very important to reduce background contaminants naturally present in the ambient air, and also because the MS actually ingests part of the drift flow through said specific channel. Clean flow is inputted in the closed recirculation circuit to compensate for the flow ingested by the MS and also to produce a counterflow of gas through the inlet slit if the DMA that is required to ensure that the drift gas of the DMA remains clean when operating in closed recirculation circuit.
The advantages of planar DMA-MS over other IMS-MS configurations are: (i) compared to drift tube Ion Mobility Spectrometer (IMS) having typical duty cycles around 1%, the DMA can be tuned at a fixed mobility, allowing a continuous output of mobility selected ions; (ii) compared to cylindrical DMAs, the planar DMA outlet slit is very accessible, and coupling the DMA to an MS inlet is straightforward and allows high ionic transmission; and (iii) DMAs can handle relatively high ionic flow, which is directly related to the sensitivity.
The DMA transmission is mostly limited when ions pass through the DMA inlet slit. In the region downstream this slit, the electric field is produced by the voltage difference between the upper electrode and the lower electrode, and it effectively pushes the ions forward, but the upstream side of the DMA inlet slit is usually influenced by much lower electric fields. In the description of U.S. Pat. No. 7,928,374 an electrospray (ESI) is located in front of the inlet slit for the purposes of (i) generating the ions to be further analyzed, and (ii) generating the electric fields required to drive ions trough the DMA inlet slit. One first problem of this configuration is that the electric field generated by the electrospray near the DMA inlet slit is very low, and the resulting transmission is very poor. The problem of the configuration of U.S. Pat. No. 7,928,374 is even more pressing if the DMA is operated in closed circuit mode and if the specific ionization source also produces contaminants because then a counterflow has to be used exiting through the DMA inlet slit. This counterflow, as proposed in U.S. Pat. No. 7,928,374, is used to sweep away low mobility species and neutral species that, if entering in the closed DMA circuit, would contaminate it and impair its normal functioning.
A detail of the counterflow configuration of U.S. Pat. No. 7,928,374 is illustrated in
Vapor Ionization:
The analysis of species existing in a gas by virtue of their finite volatility is of interest in the resolution of many analytical problems. Ionizing the vapors directly at atmospheric pressure and then introducing the resulting ions into a mass spectrometer with an atmospheric pressure source (API-MS) is today the fastest approach for vapor analysis. This approach was pioneered by the TAGA system developed at Sciex [1], where vapor ionization was achieved by means of an electrical discharge. A significant advance towards the development of detectors for trace gases was taken in U.S. Pat. No. 4,531,056. The electrospray mass spectrometry method introduced by Fenn and Colleagues in U.S. Pat. No. 4,531,056 involves the use of a counterflow dry gas interposed between the atmospheric pressure inlet of the mass spectrometer and the electrospray source. The counterflow gas impinged frontally against the electrospray cloud, offering an excellent contacting area between the dry gas and the charged drops and electrospray ions. This useful feature was used in [2, 3] for volatile charging by feeding controlled quantities of vapor mixed with the counterflow gas. An important problem of this approach, when used for the analysis of ambient species, is that the sample ambient gas is generally not clean, whereby the analyzer would be rapidly contaminated. Independently, Wu et al. [4] also obtained similar results with an electrospray charger which they referred to as secondary electrospray ionization (SESI).
One solution to sidestep this contamination problem is proposed by Martinez-Lozano et al. [See US Patent Application Publication No. US 2010/0264304 A1], where the contaminated flow carrying the sample is fed through a secondary port into a chamber also enclosing the electrospray plume, and connected with the counterflow gas coming from the curtain plate orifice. This system contributed various improvements over prior art taught in [2, 3], whose combination enabled detection levels as small as 0.2 ppt for trace vapor species [5], while also moderating the ingestion of dust, water vapor and other contaminants into the mass spectrometer. Briefly, the vapors to be analyzed are ionized by contact with a source of charge, and then the ionized vapors are transferred to the analyzer by the electric field produced by the electrospray, while the majority of neutral vapors are swept away by the counterflow gas.
However, this configuration is not very efficient. In order to facilitate ionization of the sample and the ingestion of the resulting sample ions into the analyzer, the sample gas and the ionizing agents emitted by the electrospray must coexist in a volume (termed ionization volume) where the ions thus formed can reach the entrance of the analyzer. In order for the sample gas to be ionized, it must reach the ionization volume, but the ionization volume tends to be substantially occupied by the clean counterflow gas. The sample flow can reach the ionization volume either weakly by diffusion across the counterflow jet, or more vigorously by having sufficient momentum to deflect the counterflow jet away from part of the effective ionization volume. In this configuration, the electrospray tip must be maintained at a certain distance from the curtain plate orifice, such that the counterflow jet is sufficiently weakened to be deflected. But this also weakens the electric fields produced by the electrospray, and the ionic flow rate quickly decreases. Experimental results show that, at a tradeoff distance of around 2 cm between the electrospray and the curtain gas plate, this configuration produces the best results. Furthermore, the unbounded lateral impaction between the counterflow jet and the sample flow is typically unstable and leads to mixing and dilution. To counteract dilution, and to partially deflect the counterflow jet away from the ionization volume, the sample flow rate clearly needs to be higher than the counterflow. But such high sample flow rate implies a very low ionization efficiency (defined as the ratio of sample ions produced to sample molecule introduced).
A solution to sidestep this dilution problem, termed Low Flow SESI, is taught in U.S. Pat. No. 8,217,342 B2 and U.S. Pat. No. 8,461,523 B2, where sample dilution and loss of useful ionization volume associated with the counterflow jet are virtually eliminated by performing the functions of the ionizer and the counterflow gas in two different regions. The approach is particularly advantageous in situations where the available vapor sample is limited. The ionizer isolates the ionization region from the counterflow region by placing them in separate chambers: an ionization chamber and a clean gas chamber. The sample flow enters the ionization chamber where it is mixed with the electrospray plume, producing SESI sample ions at a uniform concentration resulting from the equilibrium between the counterbalancing effects of (i) the chemical reaction by which charging ions transfer their charge to the sample species, and (ii) the coulombic repulsion that dilutes the newly formed ions [6-8]. Electric fields drive the sample ions through the impaction orifice communicating the ionization chamber with the clean gas chamber. Sample flow is also accelerated through the impaction orifice and forms a jet that precludes counterflow clean gas from entering the ionization chamber. Penetration of the counterflow gas into the ionization region and dilution of the sample are averted by using a sufficiently small impaction orifice. Once in the clean gas chamber, ions are pushed towards the analyzer by the electric fields, while the counterflow jet emerging from the curtain plate orifice minimizes the passage of vapors towards the analyzer. Finally, ions along with clean gas are sampled by the analyzer. As shown in
The fluid flow in the impaction region (17) needs to be stable to avoid convective penetration of counterflow gas (1) into the ionization chamber (16). From this perspective, the impaction orifice (14) should be as small as possible. But it should not be made too small. The sample ions (19) have to be extracted from the ionization chamber (16) by the electric field. Using very intense electric fields and a very thin impaction plate (20) to allow passage of the electric streamlines allows the required ionic flow rate to be produced, while minimizing the diameter of the impaction orifice (14). A jet of sample flow (13) is used to sweep those instabilities away from the ionization region, and thus the minimum sample flow that the ionizer can work with is limited by those instabilities in this region. Real samples are often collected in traps or cloths and then vaporized for further analysis, and introducing these off-line samples often requires opening and closing the leak-tight sample flow circuit whose pressure is above the atmospheric pressure because of the pressure drop along the outlet tubes used to evacuate the sample and the counterflow gas. This pressure difference initiates transient pressure variation within the ionizer when an off-line sample is introduced, that induce uncontrolled variations in the flows that perturb the delicate fluid flow configuration required in the impaction region. This effect can be reduced by pumping out the outlet (counterflow plus sample) flow by means of a downstream pump that reduces the pressure of the ionizer until it equals the atmospheric pressure, but the pump still produces instabilities that, after traveling upstream, also affect the impaction region stability. As a consequence, a minimum sample flow is necessary to sweep those instabilities, therefore limiting the ionization efficiency that can be achieved.
As discussed in U.S. Pat. No. 8,217,342 B2 and U.S. Pat. No. 8,461,523 B2, no new sample ions (19) can be produced in the clean region (18) downstream the impaction region because it is free from vapors, but space charge, basically produced by the concentration of the charging agents (21), still tends to dilute ions. In order to minimize dilution of sample ions in this region, passage of ions through this region should be made as fast as possible, and this is achieved by means of intense electric fields and very short paths. But these intense electric fields also force low mobility particles (5), such as charger droplets (produced for instance if the charging agent is an electrospray) to travel against the counterflow gas, thus introducing big contaminants into the analyzer. As a result, the ionizer of U.S. Pat. No. 8,217,342 B2 and U.S. Pat. No. 8,461,523 B2 is subjected to an inconvenient tradeoff between transmission of sample ions and transmission of contaminants which can be specially harmful if the ionizer is coupled with an IMS operating at atmospheric pressure (or at pressures higher than 100 Torr). Consequently, one objective of the invention is to teach how to desolvate the analyte ions and to separate the sample ions from other contaminants, including partially desolvated charged droplets and big clusters, prior to their analysis by and analytical instrument, where said ions are produced by means of a Low Flow SESI ionizer, as described in U.S. Pat. No. 8,217,342 B2 and U.S. Pat. No. 8,461,523 B2.
Coupling the Planar DMA with the Low Flow SESI Vapor Ionizer:
The problem of contaminating the DMA is even more significant if the source of ions is a Low Flow SESI as taught in U.S. Pat. No. 8,217,342 B2 and U.S. Pat. No. 8,461,523 B2. Real word analysis requires a tradeoff between sensitivity and selectivity. The Low Flow SESI increases sensitivity, and thus it also increases the number of species that produce detectable signals. A Low Flow SESI in combination with a Planar DMA in tandem with a MS (including also MS-MS) also increases the capacity of the analyzer to differentiate species (compared to MS alone). Coupling the Low Flow SESI with a Planar DMA is proposed in U.S. Pat. No. 8,217,342 B2 and U.S. Pat. No. 8,461,523 B2. According to it, this can be achieved simply by putting the Impaction slit facing the DMA inlet slit such that ions exiting the impaction slit are guided by means of electric fields toward the DMA, the scheme is illustrated in
The transmission through the inlet of DMAs, including planar DMA, operated with a counterflow of gas exiting through the inlet slit is poor because the counterflow forms a lateral wall jet that diverts low mobility charged particles and neutral species that could contaminate the DMA very inefficiently and, as a consequence, the electric fields near the inlet slit have to be weakened so as to avoid forcing contaminating particles trough the inlet slit. As a result, the transmission of the ions of interest is also weakened and, if one decided to increase deliberately the electric field intensity near the DMA inlet slit, as proposed in the coupling a Low Flow SESI with the DMA, low mobility contaminants would inevitably by entered in the DMA drift flow. Consequently, another purpose of the present invention is to teach how to prevent contamination of the DMA due to charged particles and neutral species produced in the ionization source, while increasing transmission through the inlet slit of the DMA. Another purpose of the present invention is to teach how to optimize the interface of the DMA with a vapor ionizer; and more particularly, other purposes of the present invention are to teach:
A method and an apparatus are described to desolvate ions at near atmospheric pressure, and to transmit the analyte ions from an ionization source to an analyzer, said ionization source producing charged particles of interest, charged droplets, and other low mobility charged particles and neutral species that could contaminate the analyzer if introduced in it. The new invention uses a High pressure Desolvation Sweep Flow (HPD Sweep Flow) that is provided by means of a clean gas source. The HPD Sweep Flow passes through a heating stage, a laminarizing stage, optionally, an acceleration stage, and it finally passes through a channel defined between a pair of electrodes that separate the ionizer from the analyzer, and which are respectively named HPD inlet electrode and HPD outlet electrode. Charged particles and other neutral species produced in the ionization source are introduced trough a slit defined through said HPD inlet electrode. Once in the High pressure Desolvation channel, droplets are subjected to a high temperature gas, the temperature of which is higher than the boiling point of the liquid forming said droplets. This temperature is not limited by the stability of the ion source because the HPD sweep flow does not impinge on the ion source. As a result, higher temperatures can be achieved and droplet evaporation is faster than it would be if the drying gas was aimed directly towards the source of ions. Moreover, said HPD sweep flow, in combination with the electric field produced between said HPD inlet and outlet electrodes, push the analyte ions such that they follow an oblique trajectory and reach the outlet slit of the HPD, while said low mobility charged particles and neutral species, which could otherwise contaminate the analyzer, are swept away by the sweeping flow, thus preventing them from reaching the analyzer inlet. Because, in the new configuration, the neutral gas does not obstruct the passage of said analyte ions, and also because the HPD sweep flow sweeps low mobility particles very efficiently starting at the very moment they leave the impaction slit, the electric fields within the desolvation and separation region can be augmented such that the flow of said analyte ions through said analyzer inlet slit is maximized, while contaminating species are not allowed to pass through an inlet of an associated analyzer.
In one embodiment of the present invention, a flow of laminar and high temperature gas (termed HPD sweep flow) evaporates a fraction of the droplets and sweeps the surviving droplets laterally, as illustrated in
The HPD can be operated in an open circuit, where the gas is directly provided by means of a clean gas generator or a clean gas container (including gas cylinders and other suitable containers), and it can also be re-circulated in order to obtain higher flows, which provide a better separation capacity. In contrast with conventional planar DMAs, the HPD performs the tasks of separating droplets and ions, and desolvating ions in one single stage (while the DMA is designed only to separate ions according to their mobility). In order to achieve the extra task of drying the droplets and desolvating the ions, the HPD operates at much higher temperatures, and it is able to ingest the complete electrospray mist, which cannot be handled by the DMA because vapors would tend to accumulate within the recirculation circuit. This it does at the cost of a lower resolving power by operating with lower flow rates, which enables renewing a higher fraction of the HPD sweep flow (at least 10% or 20% or 50% or 100%) so as to maintain a higher standard of purity even when the HPD is ingesting the complete electrospray mist. Also, the HPD sweep flow utilized allows for; heating the gas with moderate power input (lower than 5 kW) prior to its entrance into the HPD desolvation and separation region, and/or cooling the gas downstream the desolvation and separation region by means of a passive radiator or a heat exchanger—hence eliminating the complications associated with operating the pumps at high temperature (either by eliminating the requirement of a pump or by enabling the pump to be operated at moderated temperatures while operating the HPD at high temperatures).
The HPD can be coupled with an MS. In such a case, it is preferable to shape the outlet slit of the HPD so that the side facing the HPD desolvation and separation region has the shape of an elongated slit, while the side facing the MS inlet is a round orifice.
In another embodiment of the present invention, and with reference to
In another embodiment of the present invention, as shown in
Another embodiment of the new invention utilizes the High Pressure Desolvation described in the present description, an ionizer, which can be the Low Flow SESI taught in U.S. Pat. No. 8,217,342 B2 and U.S. Pat. No. 8,461,523 B2, among others, and the Planar DMA taught in U.S. Pat. No. 7,928,374, the contents of which are incorporated herein by reference, and further provides a HPD sweep gas (27) flowing in the space between the impaction plate (HPD impaction plate) and the upper electrode of the DMA, this space termed now the sweeping channel.
In order to take full advantage of the Low flow SESI, the sample flow (15) has to be as low as possible, and the passage of the HPD sweep flow (27) through the HPD impaction slit (38) has to be avoided. This is achieved by passing the HPD sweep flow through a laminarizing stage (24) right after it is heated in a heating stage (23), and, optionally, accelerating the HPD sweep flow though a smooth geometry so as to minimize turbulence (termed the acceleration stage (25)), and by passing the sample flow (15) through the HPD impaction slit (38). Laminarization meshes can be used in the laminarizing stage to minimize turbulence.
The HPD sweep flow outlet (29) is highly contaminated because it receives the big droplets, and the sample gas. And thus the gas exiting through the outlet of the sweeping flow channel is usually evacuated and cannot be reused, in contrast with the drift flow of the DMA, which is usually recirculated. Nevertheless, in an embodiment of the invention, this gas can be cleaned and reutilized. In one embodiment of the invention, the HPD sweep flow (27) is continuously provided by a source of clean gas (22). Examples of clean gas sources include cylinders, dewars, nitrogen and/or air purifiers and generators, as well as other sources, all included in the present invention, that can be easily identified by those skilled in the art.
The gas is re-circulated in the DMA by means of a re-circulation circuit (43) and a re-circulation pump (44) because the high resolution requires high Reynolds Numbers, and thus it also requires very high flow rates. To give an idea, the planar DMA described in in U.S. Pat. No. 7,928,374 achieves a resolution of almost 80 using a drift flow of approximately 1000 lpm. Purifying the required flow rate in an open loop circuit would be prohibitive. For this reason, an extra inlet (45) is provided to at least renew the re-circulating flow by inputting a flow equivalent to the flow outputted through the DMA inlet and outlet slits, which is much lower than the DMA drift flow (9). In contrast, for the purpose of the present invention, the sweeping channel (39) does not require a high resolution, it only needs to separate big droplets from the ions of interest. In general, there are two main factors limiting the resolution of DMAs: (i) the resolution limit produced by diffusion that scales with the square-root of the applied voltage; and (ii) resolution limit produced by the ratio of the drift flow (or the sweeping flow in our case) to the flow of ions, which scales with the drift flow. By using a high voltage within the sweeping channel (39), diffusion effects are minimized. A sweeping flow of 10 lpm can be easily handled by commercial and portable gas purifiers, and it produces a resolution nearing 2, which is limited by the ratio of the drift flow (or the HPD sweep flow in our case) to the flow of ions. This low resolution is very poor for a DMA, but it is enough to ensure that the HPD separates analyte ions from contaminants and droplets. Advantageously, the relatively low sweeping flow required implies also much lower Reynolds Number configurations that tend to be less turbulent. Moreover, because diffusional effects are minimized, and also because a relatively wide flow of ions is produced (hence the relatively low resolving power of the configuration), the transmission of the ions of interest through the sweeping channel (39) can easily approach 100%.
By introducing the clean HPD sweep flow, the gas reaching the DMA inlet slit is clean, and thus counterflow through this slit is no longer required. More advantageously, part of the HPD sweep flow can be introduced through the DMA inlet slit to facilitate passage of ions through said slit and improve transmission. By operating the DMA in closed circuit and by not adding any extra gas to the re-circulation circuit, the flow ingested by the MS automatically drives the required flow through the DMA inlet slit, such that a perfect match between the two slits (DMA inlet and outlet) is accomplished.
An optional diffuser (41) located in the sweeping channel (39) downstream the impaction and the DMA inlet slits can be used for pressure recovery. The overall pressure drop from the HPD impaction slit (38) to the outlet of the sweeping channel (39), that includes the pressure drop through the ducts and the pressure recovery in the diffuser, can be balanced by means of a valve (42) so as to maintain the HPD impaction slit (38) at atmospheric pressure. This feature allows for minimizing transient pressure evolutions produced when working in off-line mode without the need of a suctioning pump. This pressure regulation system is much more stable than the suctioning pump, and improves the stability of the delicate impaction region, thus enabling the ionizer to work more efficiently with lower sample flows.
The DMA voltage and the voltage applied to the HPD impaction plate (here termed HPD Voltage) can be controlled independently to ensure that the bands of mobilities transferred by the two filters are coincident. Usually, since the band of mobilities passed through the HPD desolvation and separation region is much wider than that of the DMA, the HPD voltage can simply be left at a constant value, and only change the voltage of the DMA. However, in order to ensure that ions go over exactly the same trajectory when they are selected, the HPD Voltage can be varied proportionally with the DMA voltage. Finally, to ensure that ions behave similarly in both the DMA and in the sweeping flow channel, the electric intensity field and the temperature can be tuned similar in both filters.
Providing similar temperatures can be accomplished by two alternative ways, both included in the present invention: (i) the temperature of the sweeping flow can be homogenized by thermally isolating all the channel walls except the wall that is in contact with the upper electrode of the DMA such that heat is transferred from the DMA gas to the sweeping flow by conduction trough the upper electrode until the equilibrium is reached; (ii) the temperature can also be controlled independently in the DMA re-circulating circuit and in the HPD sweep flow by using one or more external active heater(s), preferably also measuring the temperatures and controlling said heaters by a closed loop control scheme, such as a Proportional Integral Derivative controller.
Providing similar electric fields in the DMA and in the HPD requires a more careful design of the interface. One would first think that providing similar electric fields is as easy as providing the right voltages, but we also need to do it in such a way that ions are transferred simultaneously through the HPD and through the DMA, and this mode of operation requires a more refined design. Provided that the DMA fluid speed is optimized and fixed, and that its internal geometry is also fixed, the electric component of the velocity (VE) of the selected ions is also fixed. With reference to
Recirculating the sweep flow with a pump limits the maximum temperature of the flow because some parts of the pump, or even the lubricants of the motor, release vapors and aerosol particles that ca bind with the ions, thus hindering desolvation. In order to recirculate the flow, a stream of high velocity gas is inputted in the recirculating circuit, as illustrated in
In a preferred embodiment of the present invention, and with reference to
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This application claims the benefit of priority to U.S. Provisional Patent Application No. 61/891,967, filed on Oct. 17, 2013, the entire contents of which are incorporated by reference herein.
| Number | Date | Country | |
|---|---|---|---|
| 61891967 | Oct 2013 | US |
