Elimination of the helium requirement in high-field asymmetric waveform ion mobility spectrometry (FAIMS): beneficial effects of decreasing the analyzer gap width on peptide analysis

Cylindrical geometry high-field asymmetric waveform ion mobility spectrometry (FAIMS) focuses and separates gas-phase ions at atmospheric pressure and room (or elevated) temperature. Addition of helium to a nitrogen-based separation medium offers significant advantages for FAIMS including improved resolution, selectivity and sensitivity. Aside from gas composition, ion transmission through FAIMS is governed by electric field strength (E/N) that is determined by the applied voltage, the analyzer gap width, atmospheric pressure and electrode temperature. In this study, the analyzer width of a cylindrical FAIMS device is varied from 2.5 to 1.25 mm to achieve average electric field strengths as high as 187.5 Townsend (Td). At these electric fields, the performance of FAIMS in an N(2) environment is dramatically improved over a commercial system that uses an analyzer width of 2.5 mm in 1:1 N(2) /He. At fields of 162 Td using electrodes at room temperature, the average effective temperature for the [M+2H](2+) ion of angiotensin II reaches 365 K. This has a dramatic impact on the curtain gas flow rate, resulting in lower optimum flows and reduced turbulence in the ion inlet. The use of narrow analyzer widths in a N(2) carrier gas offers previously unattainable baseline resolution of the [M+2H](2+) and [M+3H](3+) ions of angiotensin II. Comparisons of absolute ion current with FAIMS to conventional electrospray ionization (ESI) are as high as 77% with FAIMS versus standard ESI-MS.     

Evaluation of high-field asymmetric waveform ion mobility spectrometry coupled to nanoelectrospray ionization for bioanalysis in drug discovery

The potential of high-field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to nanoelectrospray ionization (nanoESI) as a method to improve sample throughput for bioanalysis in a discovery pharmaceutical setting was explored in this work. The ability of FAIMS to separate gas-phase ions in the millisecond timescale was exploited to eliminate the need for liquid chromatography. Samples were introduced into the FAIMS electrodes/mass spectrometer using offline nanoESI at 20 nL/min and 1.5 kV. Signals were averaged for 30 s after which the next sample could be analyzed. The separation of simple mixtures, e.g., the removal of metabolite and endogenous interferences from parent drug, was demonstrated. Moreover, the application of nanoESI attenuated the ion suppression effects that normally plague conventional electrospray. On average, approximately two-thirds of the neat sample signal intensity was preserved in extracted plasma samples. Standard curves were prepared for several compounds and linearity was obtained over approximately two to three orders of magnitude. This methodology was further tested with the analysis of plasma samples from a mouse pharmacokinetic study. Concentration values determined using nanoESI-FAIMS were comparable to those determined using conventional LC/MS as demonstrated by percent differences of less than 30%. This work demonstrated the proof of concept that the combination of FAIMS and nanospray ionization can be a potentially useful tool to improve the throughput of discovery bioanalysis.     

Behaviour of tetraalkylammonium ions in high‐field asymmetric waveform ion mobility spectrometry

High‐field asymmetric waveform ion mobility spectrometry (FAIMS) is an ion‐filtering technique recently adapted for use with liquid chromatography/mass spectrometry (LC/MS) to remove interferences during analysis of complex matrices. This is the first systematic study of a series of singly charged tetraalkylammonium ions by FAIMS‐MS. The compensation voltage (CV) is the DC offset of the waveform which permits the ion to emerge from FAIMS and it was determined for each member of the series under various conditions. The electrospray ionization conditions explored included spray voltage, vaporizer temperature, and sheath and auxiliary gas pressure. The FAIMS conditions explored included carrier gas flow rate, electrode temperature and composition of the carrier gas. Optimum desolvation was achieved using sufficient carrier gas (flow rate ≥2 L/min) to ensure stable response. Low‐mass ions (m/z 100–200) are more susceptible to changes in electrode temperature and gas composition than high mass ions (m/z 200–700). As a result of this study, ions are reliably analyzed using standard FAIMS conditions (dispersion voltage ?5000 V, carrier gas flow rate 3 L/min, 50% helium/50%nitrogen, inner electrode temperature 70°C and outer electrode temperature 90°C). Variation of FAIMS conditions may be of great use for the separation of very low mass tetraalkylammonium (TAA) ions from other TAA ions. The FAIMS conditions do not appear to have a major effect on higher mass ions. Copyright © 2010 John Wiley & Sons, Ltd.     

High field asymmetric waveform ion mobility spectrometry-mass spectrometry: an investigation of leucine enkephalin ions produced by electrospray ionization

High field asymmetric waveform ion mobility spectrometry (FAIMS) provides atmospheric pressure, room temperature, low-resolution separation of gas-phase ions. The FAIMS analyzer acts as an ion filter that can continuously transmit one type of ion, independent of m/z. The combination of FAIMS with electrospray ionization and mass spectrometry (ESI-FAIMS-MS) is a powerful technique and is used in this study to investigate the cluster ions of leucine enkephalin (YGGFL). Separation by FAIMS of leucine enkephalin ions having the same m/z (m/z 556.5), [M + H]⁺ and [2M + 2H]²⁺, was observed. In addition, four complex ions of leucine enkephalin, [2M + H]⁺, [4M + 2H]²⁺, [6M + 3H]³⁺, and [8M + 4H]⁴⁺, all having m/z 1112, were shown to be separated in FAIMS. Fragmentation of ions as the result of harsh conditions within the mass spectrometer interface (FAIMS-MS) was shown to provide similar information to that obtained from MS/MS experiments in conventional ESI-MS.     

Comparison of experimental and calculated peak shapes for three cylindrical geometry FAIMS prototypes of differing electrode diameters

High-field asymmetric waveform ion mobility spectrometry (FAIMS) separates ions at atmospheric pressure and room temperature based on the difference of the mobility of ions in strong electric fields and weak electric fields. This field-dependent mobility of an ion is reflected in the compensation voltage (CV) at which the ion is transmitted through FAIMS, at a given asymmetric waveform dispersion voltage (DV). Experimental CV, relative peak ion intensity, and peak width data were compared for three FAIMS prototypes with concentric cylindrical electrodes having inner/outer electrode radii of: (1) 0.4/0.6 cm, (2) 0.8/1.0 cm, and (3) 1.2/1.4 cm. The annular analyzer space was 0.2 cm wide in each case. A finite-difference numerical computation method is described for evaluation of peak shapes and widths in a CV spectrum collected using cylindrical geometry FAIMS devices. Simulation of the radial distribution of the ion density in the FAIMS analyzer is based upon calculation of diffusion, electric fields, and the electric fields introduced by coulombic ion-ion repulsion. Excellent agreement between experimental and calculated peak shapes were obtained for electrodes of wide diameter and for ions transmitted at low CV.     

High-field asymmetric waveform ion mobility spectrometry: a new tool for mass spectrometry

High-field asymmetric waveform ion mobility spectrometry (FAIMS) is a new technology for ion separation at atmospheric pressure. This review introduces the reader to FAIMS, covering topics ranging from the fundamentals and extraction of physical parameters from the raw data, to applications of FAIMS extending from homeland security to environmental analysis to proteomics. The investigation of FAIMS as an ion pre-processing tool for mass spectrometry is in its infancy, but reports in the literature illustrate that FAIMS separates isobaric ions including diastereoisomers, separates isotopes, reduces background ions by isolating ions of interest, and simplifies spectra of complex mixtures by dividing the mixture into a series of simpler subsets of ions. Applications ranging from quantitative analysis of inorganic and organometallic compounds, to studies of the conformers of intact proteins, have been reported. This review is a launching point for further exploration of FAIMS.     

Compensation voltage (CV) peak shapes using a domed FAIMS with the inner electrode translated to various longitudinal positions

High-field asymmetric waveform ion mobility spectrometry (FAIMS) separates ions at atmospheric pressure based on the difference in the mobility of an ion in a strong electric field and in a weak electric field. This field-dependent mobility of an ion is reflected in the compensation voltage (CV) at which the ion is transmitted through FAIMS at an applied asymmetric waveform dispersion voltage (DV). In this report, we show that experimental CV peak shapes using dome tipped inner electrode FAIMS prototypes with inner/outer electrode radii of: (1) 0.2/0.4 cm and (2) 0.4/0.6 cm are a function of the longitudinal position of the inner electrode. Varying the longitudinal position of the inner electrode modifies the electric fields between the surfaces of the hemispherical shaped inner electrode and the outer electrode in the vicinity of the ion outlet. In this region the position-dependent electric field strength (E/N) effectively forms a second tandem FAIMS analyzer region having differing ion separation properties. The final tandem FAIMS separation is the intersection of the CV windows of these two differing FAIMS separations and, therefore, the peak width in the CV scan is dependent on the longitudinal tip displacement (LTD) of the inner electrode. CV scans are shown for a LTD range of 0.14 to 0.4 cm. These scans illustrate that it is possible to control the FAIMS resolution (CV/peak width) from about 1 for the 0.2/0.4 cm electrode set at intermediate longitudinal position to over 10 at the narrowest distance between the inner electrode and the ion outlet.     

Development of medium pressure laser ionization,MPLI. Description of the MPLI ion source

A novel pulsed valve/ion source combination capable of time-resolved sampling from atmospheric pressure has been developed for use with laser ionization time of flight mass spectrometry. The source allows ionization extremely close to the nozzle of the pulsed valve, enabling ultra-sensitive detection of a number of compounds, e.g., NO, at mixing ratios <1 pptV. Furthermore, at analyte mixing ratios in the ppbV range, the temporal resolution of the system is in the sub-second regime, allowing time-resolved monitoring of highly dynamic and complex mixtures, e.g., human breath or reacting chemical mixtures in atmospheric smog chamber experiments. Rotational temperatures of approximately 50 K have been observed for analytes seeded in the supersonic jet expansion at a distance of 1 mm downstream of the nozzle orifice. The refinement of the original ion source has drastically reduced the impact of reflected laser light and the resultant electron impact signals previously observed. The general applicability of this technique is demonstrated here by coupling the source to commercially available as well as home-built time-of-flight mass spectrometers. Finally, we discuss the MPLI technique in view of the very recently introduced atmospheric pressure laser ionization (APLI) as well as the traditional jet-REMPI approach.     

Development of a multipurpose ion source for LC-MS and GC-API MS

Over the past decade, multimode ion sources operating at atmospheric pressure (i.e., more than one ionization method is operative in the ion source enclosure) have received considerable interest. Simultaneous operation of different ionization methods targeting different compound classes within one analysis run has several advantages, including enhanced sample throughput and thus significant laboratory cost reductions. Potential drawbacks are enhanced ion suppression and other undesirable effects of the simultaneous operation of ionization methods. In this contribution we present an alternative approach-the development and characterization of a widely applicable, multipurpose ion source operating at atmospheric pressure. The optimized source geometry allows rapid changing from LC-API methods (ESI, APCI, APLI) to GC-API methods (APCI, APLI, DA-APLI) along with the appropriate coupling of chromatographic equipment required. In addition, true multimode operation of the source is demonstrated for LC-ESI/APLI and LC-APCI/APLI.     

Atmospheric pressure ion trapping in a tandem FAIMS-FAIMS coupled to a TOFMS: Studies with electrospray generated gramicidin S ions

A tandem FAIMS–FAIMS system for ion trapping at room temperature and atmospheric pressure is described. The first FAIMS device consisted of a side-to-side configuration (sFAIMS) suitable for ion separation, whereas the second FAIMS device was appropriate for ion trapping (tFAIMS). Ions pre-selected by the sFAIMS entered the tFAIMS and were captured by virtual trapping fields at the hemispherical tip of the inner electrode. The use of the sFAIMS, with wider electrode diameters, and consequently better ion separation efficiency than the tFAIMS, lowered the number of background ions captured in the trapping region of tFAIMS, and thus reduced the space charge effects in the trap. This tandem device was coupled to a laboratory built time-of-flight mass spectrometer and was evaluated using the electrospray generated [M + 2H]²⁺ ion of gramicidin S. The half-time (t_1/2) of the exponential decay of the ion cloud in tFAIMS, determined by monitoring the residual intensity of ions extracted from the ion trapping region of tFAIMS after various delay times, was about 2 s.     

The distribution of ion acceptance in atmospheric pressure ion sources: Spatially resolved APLI measurements

It is demonstrated that spatially resolved mass selected analysis using atmospheric pressure laser ionization mass spectrometry (APLI MS) represents a new powerful tool for mechanistic studies of ion-molecule chemistry occurring within atmospheric pressure (AP) ion sources as well as for evaluation and optimization of ion source performance. A focused low-energy UV laser beam is positioned computer controlled orthogonally on a two-dimensional grid in the ion source enclosure. Resonance enhanced multiphoton ionization (REMPI) of selected analytes occurs only within the confined volume of the laser beam. Depending on the experimental conditions and the reactivity of the primary photo-generated ions, specific signal patterns become visible after data treatment, as visualized in, e.g., contour or pseudo-color plots. The resulting spatial dependence of sensitivity is defined in this context as the distribution of ion acceptance (DIA) of the source/analyzer combination. This approach provides a much more detailed analysis of the diverse processes occurring in AP ion sources compared with conventional bulk signal response measurements.     

一种微型FAIMS传感器芯片的研制

基于微机电系统(MEMS)技术,研制了一种微型高场非对称波形离子迁移谱(FAIMS)传感器芯片.芯片尺寸为18.8mm×12.4mm×1.2mm,由离子化区、迁移区、离子检测区组成.采用真空紫外灯离子源在大气压环境下对样品进行离子化,经过离子化区中聚焦电极的电场作用,实现离子在进入迁移区之前的聚焦,提高离子信号的强度.通过在上下玻璃上溅射Au/Cr(300nm/30nm)金属,并与厚度为200μm、采用感应耦合等离子体(ICP)工艺刻蚀的硅片键合,形成迁移区的矩形通道,尺寸为10mm×5mm×0.2mm.离子检测区为三排直径200μm、间距100μm交错排列的圆柱阵列式微法拉第筒,能同时检测正负离子.采用频率为2MHz,最大电压为364V,占空比为30%的高场非对称方波电压进行FAIMS芯片实验.以丙酮和甲苯为实验样品,载气流速80L·h-1,补偿电压从-10V到3V以0.1V的步长进行扫描,得到了丙酮和甲苯的FAIMS谱图,验证了FAIMS芯片的性能.丙酮和甲苯的FAIMS-MS实验进一步表明FAIMS系统实现了离子分离和过滤功能.     

Gas chromatography coupled to atmospheric pressure ionization mass spectrometry (GC-API-MS): Review

Although the coupling of GC/MS with atmospheric pressure ionization (API) has been reported in 1970s, the interest in coupling GC with atmospheric pressure ion source was expanded in the last decade. The demand of a “soft” ion source for preserving highly diagnostic molecular ion is desirable, as compared to the “hard” ionization technique such as electron ionization (EI) in traditional GC/MS, which fragments the molecule in an extensive way. These API sources include atmospheric pressure chemical ionization (APCI), atmospheric pressure photoionization (APPI), atmospheric pressure laser ionization (APLI), electrospray ionization (ESI) and low temperature plasma (LTP). This review discusses the advantages and drawbacks of this analytical platform. After an introduction in atmospheric pressure ionization the review gives an overview about the history and explains the mechanisms of various atmospheric pressure ionization techniques used in combination with GC such as APCI, APPI, APLI, ESI and LTP. Also new developments made in ion source geometry, ion source miniaturization and multipurpose ion source constructions are discussed and a comparison between GC-FID, GC-EI-MS and GC-API-MS shows the advantages and drawbacks of these techniques. The review ends with an overview of applications realized with GC-API-MS.     

Modeling the resolution and sensitivity of FAIMS analyses

Field asymmetric waveform ion mobility spectrometry (FAIMS) is rapidly gaining acceptance as a robust, versatile tool for post-ionization separations prior to mass-spectrometric analyses. The separation is based on differences between ion mobilities at high and low electric fields, and proceeds at atmospheric pressure. Two major advantages of FAIMS over condensed-phase separations are its high speed and an ion focusing effect that often improves sensitivity. While selected aspects of FAIMS performance are understood empirically, no physical model rationalizing the resolving power and sensitivity of the method and revealing their dependence on instrumental variables has existed. Here we present a first-principles computational treatment capable of simulating the FAIMS analyzer for virtually any geometry (including the known cylindrical and planar designs) and arbitrary operational parameters. The approach involves propagating an ensemble of ion trajectories through the device in real time under the influence of applied asymmetric potential, diffusional motion incorporating the high-field and anisotropic phenomena, and mutual Coulomb repulsion of ionic charges. Calculations for both resolution and sensitivity are validated by excellent agreement with measurements in different FAIMS modes for ions representing diverse types and analyte classes.     

Ion mobility spectrometer—field asymmetric ion mobility spectrometer-mass spectrometry

Since the development of electrospray ionization (ESI) for ion mobility spectrometry mass spectrometry (IMMS), IMMS have been extensively applied for characterization of gas-phase bio-molecules. Conventional ion mobility spectrometry (IMS), defined as drift tube IMS (DT-IMS), is typically a stacked ring design that utilizes a low electric field gradient. Field asymmetric ion mobility spectrometry (FAIMS) is a newer version of IMS, however, the geometry of the system is significantly different than DT-IMS and data are collected using a much higher electric field. Here we report construction of a novel ambient pressure dual gate DT-IMS coupled with a FAIMS system and then coupled to a quadrupole ion trap mass spectrometer (QITMS) to form a hybrid three-dimensional separation instrument, DT-IMS-FAIMS-QITMS. The DT-IMS was operated at ~3 Townsend (electric field/number density (E/N) or (Td)) and was coupled in series with a FAIMS, operated at ~80 Td. Ions were mobility-selected by the dual gate DT-IMS into the FAIMS and from the FAIMS the ions were detected by the QITMS for as either MS or MSⁿ. The system was evaluated using cocaine as an analytical standard and tested for the application of separating three isomeric tri-peptides: tyrosine-glycine-tryptophan (YGW), tryptophan-glycine-tyrosine (WGY) and tyrosine-tryptophan-glycine (YWG). All three tri-peptides were separated in the DT-IMS dimension and each had one mobility peak. The samples were partially separated in the FAIMS dimension but two conformation peaks were detected for the YWG sample while YGW and WGY produced only one peak. Ion validation was achieved for all three samples using QITMS.     

Spherical FAIMS: comparison of curved electrode geometries

High-field asymmetric waveform ion mobility spectrometry (FAIMS) can operate at atmospheric pressure to separate gas-phase ions on the basis of a difference in the mobility of an ion at high fields relative to its mobility at low field strengths. Several novel cell geometries have been proposed in addition to the commercially available planar and cylindrical designs. Nevertheless, there is still much to explore about three-dimensional (3-D) curved cell geometries (spherical and hemispherical) and comparison to two-dimensional (2-D) curved geometries (cylindrical). The geometry of a FAIMS cell is one of the essential features affecting the transmission, resolution, and resolving power of FAIMS. Electric fields in a spherical design allow advantages such as virtual potential wells that can induce atmospheric-pressure near-trapping conditions and help reduce ion losses. Curvature of electrodes enables the ions to remain focused near the gap median, which help to improve sensitivity and ion trapping at higher pressures. Here we detail the design and characterization of a novel FAIMS cell having spherical electrode geometry and compare it to hemispherical and cylindrical cells. These FAIMS cells were interfaced with a quadrupole ion trap mass spectrometer in this study. Several structural classes of common explosives were employed to evaluate the separation power of these geometries. FAIMS spectra were generated by scanning the compensation voltage (CV) while operating the mass spectrometer in total ion mode. The identification of ions was accomplished through mass spectra acquired at fixed values of CVs. The performance of FAIMS using cylindrical, hemispherical, and spherical cells was compared and trends identified. For all trials, the best transmission was obtained by the spherical FAIMS cell while hemispherical FAIMS provided the best resolution and resolving power.     

Optimization of the atmospheric pressure chemical ionization liquid chromatography mass spectrometry interface

Use of optimized instrument parameters that result from statistical experimentation revealed that the sensitivity of atmospheric pressure chemical ionization (APCI) liquid chromatography-mass spectrometry (LC/MS) is greater than the sensitivity of an optimized Thermabeam? LC/MS interface by about 3 orders of magnitude, when tested on aromatic compounds. APCI is one of the few LC/MS techniques in which the chromatogram is directly comparable with liquid chromatographs that use ultraviolet detection. The optimum instrument parameters for a Finnigan SSQ-7000 APCI LC/MS interface were found at low flow rates (e. g., 0. 1 mL/min), relatively low capillary heat (e. g., 225 °C), and high sheath-gas pressure (e. g., 60 lb/in²). The optimization was achieved by monitoring the responses of sensitivity, fragmentation, and cluster ion formation. The fine tuning for high sensitivity calls for a high percentage of water in the mobile phase. In contrast, a high percentage of organic content in the mobile phase is required to obtain abundant protonated molecular ions with respect to fragmentation and clustering. This is an important consideration for analyses of unknowns.     

Compensation voltage shifting in high-field asymmetric waveform ion mobility spectrometry-mass spectrometry

The separation and ion focusing properties of High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) depend on desolvated ions entering the device, leading to a compound-specific, reproducible compensation voltage (CV) for each ion. This study shows that the conditions identified for stable spray and satisfactory ion desolvation in normal electrospray ionization mass spectrometry (ESI-MS) operation might significantly differ from those required for FAIMS-MS. In a typical setup with high-flow electrospray conditions, ions could be incompletely desolvated, resulting in the formation of unidentified clusters with differing behavior in a FAIMS environment. This causes compound-specific shifts of as much as 10 V in CV values when the mobile phase composition and/or flow rate are varied. The shifts diminish and finally disappear when the flow rate of methanol, used as mobile phase, is reduced to 40 microL/min and that of acetonitrile to 20 microL/min. The reproducibility of the observed CV was determined by scanning the CV while infusing a five-component mixture into a 400 microL/min flow of methanol or 50:50 acetonitrile/water. The relative standard deviation (RSD) for these multiple scans ranged from 0.7% to 6%. Therefore, under a constant set of experimental parameters, the CV does not shift appreciably. These observations have an impact on method development strategies. High flow rates can be used with the FAIMS device, since the CV values are reproducible, but it is likely that clusters are forming. Therefore, CV scans should be performed under conditions which mimic the chromatographic elution or flow injection analysis conditions, including matrix composition, to minimize errors in CV determination. An alternative approach is to determine the liquid flow rate at which the CV becomes compound-specific and to split the mobile phase stream accordingly. These experimental results may be specific to the setup used for this study and may not be directly applicable to other instrument FAIMS devices.     

Thin‐layer chromatography and mass spectrometry coupled using proximal probe thermal desorption with electrospray or atmospheric pressure chemical ionization

An atmospheric pressure proximal probe thermal desorption sampling method coupled with secondary ionization by electrospray or atmospheric pressure chemical ionization was demonstrated for the mass spectrometric analysis of a diverse set of compounds (dyestuffs, pharmaceuticals, explosives and pesticides) separated on various high‐performance thin‐layer chromatography plates. Line scans along or through development lanes on the plates were carried out by moving the plate relative to a stationary heated probe positioned close to or just touching the stationary phase surface. Vapors of the compounds thermally desorbed from the surface were drawn into the ionization region of a combined electrospray ionization/atmospheric pressure chemical ionization source where they merged with reagent ions and/or charged droplets from a corona discharge or an electrospray emitter and were ionized. The ionized components were then drawn through the atmospheric pressure sampling orifice into the vacuum region of a triple quadrupole mass spectrometer and detected using full scan, single ion monitoring, or selected reaction monitoring mode. Studies of variable parameters and performance metrics including the proximal probe temperature, gas flow rate into the ionization region, surface scan speed, read‐out resolution, detection limits, and surface type are discussed. Published in 2010 by John Wiley & Sons, Ltd.     

Improving FAIMS sensitivity using a planar geometry with slit interfaces

Differential mobility spectrometry or field asymmetric waveform ion mobility spectrometry (FAIMS) is gaining broad acceptance for analyses of gas-phase ions, especially in conjunction with largely orthogonal separation methods such as mass spectrometry (MS) and/or conventional (drift tube) ion mobility spectrometry. In FAIMS, ions are filtered while passing through a gap between two electrodes that may have planar or curved (in particular, cylindrical) geometry. Despite substantial inherent advantages of the planar configuration and its near-universal adoption in current stand-alone FAIMS devices, commercial FAIMS/MS systems have employed curved FAIMS geometries that can be more effectively interfaced to MS. Here we report a new planar (p-) FAIMS design with slit-shaped entrance and exit apertures that substantially increase ion transmission in and out of the analyzer. The entrance slit interface effectively couples p-FAIMS to multi-emitter electrospray ionization (ESI) sources, improving greatly the ion current introduced to the device and allowing liquid flow rates up to ∼50 μL/min. The exit slit interface increases the transmission of ribbon-shaped ion beams output by the p-FAIMS to downstream stages such as a MS. Overall, the ion signal in ESI/FAIMS/MS analyses increases by over an order of magnitude without affecting FAIMS resolution.