Monte Carlo simulation of ion transport in non-linear ion mobility spectrometry

A program for Monte Carlo simulation of ion transport in non-linear ion mobility spectrometry, also known as field asymmetric ion mobility spectrometry (FAIMS) or differential mobility spectrometry (DMS), has been developed. Simulations are based on elastic collisions between the ions and the gas particles, and take into account the effects of flow dynamics and asymmetric electric fields. Using this program, the separation and diffusion of the ions moving in a planar DMS filtration gap are demonstrated. Ion focusing in a cylindrical filtration gap is also confirmed. A characteristic compensation voltage is found to provide insight for understanding separation in non-linear ion mobility spectrometry. The simulation program is used to study the characteristics of non-linear ion mobility spectrometry, the effect of the carrier gas flow, and the dependence of the compensation voltage and nonlinear mobility coefficient (α) on the applied asymmetric electric field.     

Differential mobility spectrometry of chlorocarbons with a micro-fabricated drift tube

Chlorocarbons were ionized through gas phase chemistry at ambient pressure in air and resultant ions were characterized using a micro-fabricated drift tube with differential mobility spectrometry (DMS). Positive and negative product ions were characterized simultaneously in a single drift tube equipped with a 3 mCi (63)Ni ion source at 50 degrees C and drift gas of air with 1 ppm moisture. Scans of compensation voltage for most chlorocarbons produced differential mobility spectra with Cl(-) as the sole product ion and a few chlorocarbons produced adduct ions, M (.-) Cl(-). Detection limits were approximately 20-80 pg for gas chromatography-DMS measurements. Chlorocarbons also yielded positive ions through chemical ionization in air and differential mobility spectra showed peaks with characteristic compensation voltages for each substance. Field dependence of mobility was determined for positive and negative ions of each substance and confirmed characteristic behavior for each ion. A DMS analyzer with a membrane inlet was used to continuously monitor effluent from columns of bentonite or synthetic silica beads to determine breakthrough volumes of individual chlorocarbons. These findings suggest a potential of DMS for monitoring subsurface environments either on site or perhaps in situ.     

Analysis of explosives using differential mobility spectrometry

Characterization of ions from eight explosives (2,4,6-trinitrotoluene, pentaerythritol tetranitrate, 2,4,6-trinitrophenol, 2,4-dinitrotoluene, erythritol tetranitrate, hexamethylene triperoxide diamine, 2,4,6-trinitrophenylmethylnitramine and 1,3,5-trinitro-perhydro-1,3,5-triazine) using differential mobility spectrometry (DMS) with ⁶³Ni as an ionization source was performed. Presented results of explosive analysis have been evaluated by use of special software tool which communicates with DMS in real time. This tool was developed for visualization, identification and comparison of measured data. Each explosive provides characteristic signal at a specific compensation voltage under a fixed dispersion field. Peaks in DMS spectra for these ions were confined to a range of compensation voltages between ?1.61 to +1.71 V at RF = 1060 V. We calculated specific alpha coefficients (α₂ and α₄) to obtain a nonlinear function of explosives, based on their DMS spectra. Dependence of mobility for measured explosives ions in electric field at E/N values between 0 to 120 Td were used to inspectional graphical differentiation of explosives.     

Altering the mobility-time continuum: nonlinear scan functions for targeted high resolution trapped ion mobility-mass spectrometry

Trapped ion mobility spectrometry (TIMS) is a versatile high resolution technique that provides the user with the flexibility to adjust the mobility range of interest, duty cycle (up to 100 %), and resolving power (up to ~300) according to the application requirements. Furthermore, TIMS offers the flexibility of operating as either a mobility-selective or conventional ion funnel, thus permitting ion mobility separations to be turned on or off. Here, we extend the flexibility of TIMS by introducing multilinear and nonlinear scanning methods that allow enhanced resolution in user-defined mobility regions. The performance of the new method is demonstrated using a variety of nonlinear scan functions that allow the resolving power to be continuously varied across the mobility spectrum. Further, we demonstrate that mobility analysis can be targeted over disparate regions using a multilinear scan function. In this example, high resolution mobility analysis is targeted on two analytes on opposite ends of a mobility range, while other ions that fall between the regions of interest remain unanalyzed. Using this approach, the resolving power for targeted species was increased by a factor of two over the conventional linear scanning approach (R ~60 versus ~120) without reducing the duty cycle of the TIMS measurement. Importantly, in such an analysis, ions in the untargeted regions are not mobility analyzed, however, they are also not discarded. Rather, these ions are ejected for downstream mass analysis. In this sense, TIMS bridges the gap between dispersive and scanning mobility techniques. That is, TIMS disperses ions according to their elution voltage, however, TIMS can also perform target mobility analyses without eliminating untargeted ions.     

Analysis of bacterial strains with pyrolysis-gas chromatography/differential mobility spectrometry

Eight vegetative bacterial strains and two spores were characterized by pyrolysis-gas chromatography with differential mobility spectrometry (py-GC/DMS) yielding topographic plots of ion intensity, retention time, and compensation voltage simultaneously for ions in positive and negative polarity. Biomarkers were found in the pyrolysate at characteristic retention times and compensation voltages and were confirmed by standard addition with GC/MS analyses providing discrimination between Gram negative and Gram positive bacterial types, but no recognition of individual strains within the Gram negative bacteria. Principal component analysis was applied using two dimensional data sets of ion intensity versus retention time at five compensation voltages including the reactant ion peaks all in positive and negative ion polarity. Clustering was observed with compensation voltage (CV) chromatograms associated with ion separation in the DMS detector and little or no clustering was observed with the reactant ion peaks or CV chromatograms where ion separation is poor. Consistent clustering of Gram positive B. odysseyi and Gram negative E. coli in both positive and negative polarities with the reactant ion peak chromatograms and key CV chromatograms suggests common but unknown common chemical compositions in the pyrolysate.     

Quantitative determination of n-alkanethiols in air and in a blended gas mixture of methane with air by gas chromatography/differential mobility spectrometry

Mixtures of n-alkanethiols, in solution with equi-molar amounts from 0.5 to 360 ng per compound, were determined using gas chromatography (GC) with a differential mobility spectrometer, operated with a flow of air at ambient pressure, as the GC detector. A homologous series of n-alkanethiols with carbon number from two to six showed baseline resolution in the GC separation and positive and negative ion chromatograms were produced simultaneously for the alkanethiols. Differential mobility spectra showed compensation voltages characteristic of each alkanethiol and plots of ion intensity, retention time, and compensation voltage yield contour plots illustrating the second dimension of analytical selectivity provided by the detector. Another yet undeveloped dimension of analytical information was found in the dependence of mobility coefficients on electric field. Mass-analysis of ions from thiols showed a hydrogen abstracted ion, protonated monomers, and proton bound dimers. Linear ranges were narrow and the minimum detectable limits were ~1 ng. Response in positive polarity provided a ten-fold improvement in detection limits though spectra were more complex than for negative ions. In a methane-rich air atmosphere, intended to simulate ambient air or the detection of leaks from natural gas pipelines, the response to thiols with negative ions was not degraded by the methane up to 50% v/v, the highest level tested.     

Tandem differential mobility spectrometry with chemical modification of ions

A tandem ion mobility spectrometer with two sequential differential mobility spectrometry (DMS) drift tubes and with detectors at ambient pressure is described and modes of operation are demonstrated. Separate but coordinated electronic control for each drift tube allows several modes of operation including: all ions passing; compensation voltage (CV) scanning; and ion selection over a narrow CV range. Any of these modes can be applied to each drift tube allowing several combinations of analytical measurements, analogous to tandem mass spectrometry, with ions entered into a gas atmosphere containing reagents between the mobility regions. Ions may be changed by cluster or displacement reactions and characterized in the second DMS analyzer. Proton bound dimers of compounds appearing near 0?V CV in DMS1 were isolated in DMS1, introduced into 1?% isopropanol vapors, and resolved at characteristic CV values in the DMS2. This is achieved with analyzer dimensions little greater than a single DMS instrument.     

Effect of moisture on the field dependence of mobility for gas-phase ions of organophosphorus compounds at atmospheric pressure with field asymmetric ion mobility spectrometry

The electric field dependence of the mobilities of gas-phase protonated monomers [(MH+(H2O)n] and proton-bound dimers [M2H+(H2O)n] of organophosphorus compounds was determined at E/N values between 0 and 140 Td at ambient pressure in air with moisture between 0.1 and 15 000 ppm. Field dependence was described as alpha (E/N) and was obtained from the measurements of compensation voltage versus field amplitude in a planar high-field asymmetric waveform ion mobility spectrometer. The alpha function for protonated monomers to 140 Td was constant from 0.1 to 10 ppm moisture in air with onset of effect at approximately 50 ppm. The value of alpha increased 2-fold from 100 to 1000 ppm at all E/N values. At moisture values between 1000 and 10 000 ppm, a 2-fold or more increase in alpha (E/N) was observed. In a model proposed here, field dependence for mobility through changes in collision cross sections is governed by the degree of solvation of the protonated molecule by neutral molecules. The process of ion declustering at high E/N values was consistent with the kinetics of ion-neutral collisional periods, and the duty cycle of the waveform applied to the drift tube. Water was the principal neutral above 50 ppm moisture in air, and nitrogen was proposed as the principal neutral below 50 ppm.     

膜萃取-气相色谱/微分离子迁移谱检测水中的1,4-二恶烷

利用膜萃取-气相色谱/微分离子迁移谱（ME-GC/DMS）对水中的1,4-二恶烷污染物进行了检测。考察了射频电压、采样流速、膜渗透时间、Trap预富集时间等参数对检测二恶烷的影响规律。结果显示：在优化条件下,二恶烷的定量线性范围为2.0~20.0 μg/L,检出限为0.67 μg/L。实验证明,二恶烷与5种氯代烃的混合物在ME-GC/DMS的二维分离谱图中得到特异性响应,增加了识别的准确性。该研究为发展现场实时监测地下水中污染物的方法提供了重要参考。     

Constituents with independence from growth temperature for bacteria using pyrolysis-gas chromatography/differential mobility spectrometry with analysis of variance and principal component analysis

Four bacteria, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus warneri, and Micrococcus luteus, were grown at temperatures of 23, 30, and 37 degrees C and were characterized by pyrolysis-gas chromatography/differential mobility spectrometry (Py-GC/DMS) providing, with replicates, 120 data sets of retention time, compensation voltage, and ion intensity, each for negative and positive polarity. Principal component analysis (PCA) for 96 of these data sets exhibited clusters by temperature of culture growth and not by genus. Analysis of variance was used to isolate the constituents with dependences on growth temperature. When these were subtracted from the data sets, Fisher ratios with PCA resulted in four clusters according to genus at all temperatures for ions in each polarity. Comparable results were obtained from unsupervised PCA with 24 of the original data sets. The ions with taxonomic features were reconstructed into 3D plots of retention time, compensation voltage, and Fisher ratio and were matched, through GC-mass spectrometry (MS), with chemical standards attributed to the thermal decomposition of proteins and lipid A. Results for negative ions provided simpler data sets than from positive ions, as anticipated from selectivity of gas phase ion-molecule reactions in air at ambient pressure.     

Differential mobility spectrometer: optimization of the analytical characteristics

Differential mobility spectrometer is a powerful tool used for detection, filtration and characterization of ions in gas-phase. DMS instrumentation analytical performance is a matter of importance for practical application. This paper is devoted to the improving of the planar DMS analytical characteristics. The goal is to optimize ion transmission and separation efficiency for the best possible DMS performance, balanced between sensitivity and selectivity. Analytical characteristics of the DMS instrument depend on a number of interrelated parameters. Present paper focuses on the sensor geometry and transport gas flow rate and its influence on the DMS performance. To find optimal sensor design parameters a systematic approach to the DMS performance is provided and evaluated both theoretically and experimentally. To facilitate DMS optimization special criterion quantitatively describing DMS analytical quality is proposed. DMS instrumental parameters maximizing analytical quality are determined. Theoretical analysis is validated by comparison with experimental data. Practical recommendations following from these finding are presented.     

Resistively heated temperature programmable silicon micromachined gas chromatography with differential mobility spectrometry

A microfabricated electromechanical system based on radio frequency modulated ion mobility spectrometry (MEMS-RFIMS), also known as differential ion mobility spectrometry (DMS) has been successfully interfaced to a custom-fabricated resistively heated temperature programmable micromachined gas chromatograph. In contrast to a conventional time-of-flight ion mobility spectrometer, the DMS uses the non-linear mobility dependence in strong radio frequency electric fields for ion filtering. Selective and sensitive detection of targeted analytes of interest can be achieved by using different transport gases, radio frequencies, and associated compensation voltages. In addition, the detection of both positive and negative ions, depending on the ionization mechanism favorable to the analytes involved is achieved. When compared to a stand-alone GC with a non spectrometric detector or a stand-alone DMS, GC-DMS as a hyphenated technique offers two competitive advantages; two orthogonal separating methods in a single analytical system and the resolving power of gas chromatography to minimize charge exchange in the ionization chamber of the detector. In this article, a portable, resistively heated temperature programmable silicon machined gas chromatograph with differential mobility detection is introduced. The performance of the instrument is illustrated with examples of difficult industrial applications.     

Time-of-flight ion mobility spectrometry and differential mobility spectrometry: A comparative study of their efficiency in the analysis of halogenated compounds

The ion mobilities of halogenated aromatics which are of interest in environmental chemistry and process monitoring were characterized with field-deployable ion mobility spectrometers and differential mobility spectrometers. The dependence of mobility of gas-phase ions formed by atmospheric-pressure photoionization (APPI) on the electric field was determined for a number of structural isomers. The structure of the product ions formed was identified by investigations using the coupling of ion mobility spectrometry with mass spectrometry (APPI-IMS-MS) and APPI-MS. In contrast to conventional time-of-flight ion mobility spectrometry (IMS) with constant linear voltage gradients in drift tubes, differential mobility spectrometry (DMS) employs the field dependence of ion mobility. Depending on the position of substituents, differences in field dependence were established for the isomeric compounds in contrast to conventional IMS in which comparable reduced mobility values were detected for the isomers investigated. These findings permit the differentiation between most of the investigated isomeric aromatics with a different constitution using DMS.     

Development of rapid methodologies for the isolation and quantitation of drug metabolites by differential mobility spectrometry – mass spectrometry

Clinical and forensic toxicology laboratories are inundated with thousands of samples requiring lengthy chromatographic separations prior to mass spectrometry. Here, we employ differential mobility spectrometry (DMS) interfaced to nano-electrospray ionization-mass spectrometry to provide a rapid ion filtration technique for the separation of ions in gas phase media prior to mass spectral analysis on a DMS-integrated AB SCIEX API 3000 triple-quadrupole mass spectrometer. DMS is efficient at the rapid separation of ions under ambient conditions and provides many advantages when used as an ion filtration technique in tandem with mass spectrometry (MS) and MS/MS. Our studies evaluated DMS-MS/MS as a rapid, quantitative platform for the analysis of drug metabolites isolated from urine samples. In targeted applications, five metabolites of common drugs of abuse were effectively and rapidly separated using isopropanol and ethyl acetate as transport gas modifiers, eliminating the gas chromatography or liquid chromatography-based separations commonly employed in clinical and forensic toxicology laboratories. Calibration curves were prepared for the selected drug metabolites utilizing deuterated internal standards for quantitative purposes. The feasibility of separating and quantitating drug metabolites in a rapid fashion was evaluated by compensation voltage stepping followed by multiple reaction monitoring (MRM) detection. Rapid profiling of clinical and forensic toxicology samples could help to address an urgent need within the scientific community by developing high-throughput analytical methodologies, which could reduce significant case backlogs present within these laboratories.     

Ion mobility-mass spectrometry

This review article compares and contrasts various types of ion mobility-mass spectrometers available today and describes their advantages for application to a wide range of analytes. Ion mobility spectrometry (IMS), when coupled with mass spectrometry, offers value-added data not possible from mass spectra alone. Separation of isomers, isobars, and conformers; reduction of chemical noise; and measurement of ion size are possible with the addition of ion mobility cells to mass spectrometers. In addition, structurally similar ions and ions of the same charge state can be separated into families of ions which appear along a unique mass-mobility correlation line. This review describes the four methods of ion mobility separation currently used with mass spectrometry. They are (1) drift-time ion mobility spectrometry (DTIMS), (2) aspiration ion mobility spectrometry (AIMS), (3) differential-mobility spectrometry (DMS) which is also called field-asymmetric waveform ion mobility spectrometry (FAIMS) and (4) traveling-wave ion mobility spectrometry (TWIMS). DTIMS provides the highest IMS resolving power and is the only IMS method which can directly measure collision cross-sections. AIMS is a low resolution mobility separation method but can monitor ions in a continuous manner. DMS and FAIMS offer continuous-ion monitoring capability as well as orthogonal ion mobility separation in which high-separation selectivity can be achieved. TWIMS is a novel method of IMS with a low resolving power but has good sensitivity and is well intergrated into a commercial mass spectrometer. One hundred and sixty references on ion mobility-mass spectrometry (IMMS) are provided.     

Evaluation of a differential mobility spectrometer/miniature mass spectrometer system

A planar differential mobility spectrometer (DMS) was coupled to a Mini 10 handheld rectilinear ion trap (RIT) mass spectrometer (MS) (total weight 10 kg), and the performance of the instrument was evaluated using illicit drug analysis. Coupling of DMS (which requires a continuous flow of drift gas) with a miniature MS (which operates best using sample introduction via a discontinuous atmospheric pressure interface, DAPI), was achieved with auxiliary pumping using a 5 L/min miniature diaphragm sample pump placed between the two devices. On-line ion mobility filtering showed to be advantageous in reducing the background chemical noise in the analysis of the psychotropic drug diazepam in urine using nanoelectrospray ionization. The combination of a miniature mass spectrometer with simple and rapid gas-phase ion separation by DMS allowed the characteristic fragmentation pattern of diazepam to be distinguished in a simple urine extract at lower limits of detection (50 ng/mL) than that achieved without DMS (200 ng/mL). The additional separation power of DMS facilitated the identification of two drugs of similar molecular weight, morphine (average MW = 285.34) and diazepam (average MW = 284.70), using a miniature mass spectrometer capable of unit resolution. The similarity in the proton affinities of these two compounds resulted in some cross-interference in the MS data due to facile ionization of the neutral form of the compound even when the ionic form had been separated by DMS.     

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.     

Applications of a travelling wave-based radio-frequency-only stacked ring ion guide

The use of radio-frequency (RF)-only ion guides for efficient transport of ions through regions of a mass spectrometer where the background gas pressure is relatively high is widespread in present instrumentation. Whilst multiple collisions between ions and the background gas can be beneficial, for example in inducing fragmentation and/or decreasing the spread in ion energies, the resultant reduction of ion axial velocity can be detrimental in modes of operation where a rapidly changing influx of ions to the gas-filled ion guide needs to be reproduced at the exit. In general, the RF-only ion guides presently in use are based on multipole rod sets. Here we report investigations into a new mode of ion propulsion within an RF ion guide based on a stack of ring electrodes. Ion propulsion is produced by superimposing a voltage pulse on the confining RF of an electrode and then moving the pulse to an adjacent electrode and so on along the guide to provide a travelling voltage wave on which the ions can surf. Through appropriate choice of the travelling wave pulse height, velocity and gas pressure it will be shown that the stacked ring ion guide with the travelling wave is effective as a collision cell in a tandem mass spectrometer where fast mass scanning or switching is required, as an ion mobility separator at pressures around 0.2 mbar, as an ion delivery device for enhancement of duty cycle on an orthogonal acceleration time-of-flight (oa-TOF) mass analyser, and as an ion fragmentation device at higher wave velocities.     

Using a nanoelectrospray-differential mobility spectrometer-mass spectrometer system for the analysis of oligosaccharides with solvent selected control over ESI aggregate ion formation

Differential mobility spectrometry (DMS), also commonly referred to as high field asymmetric waveform ion mobility spectrometry (FAIMS) is a rapidly advancing technology for gas-phase ion separation. The interfacing of DMS with mass spectrometry (MS) offers potential advantages over the use of mass spectrometry alone. Such advantages include improvements to mass spectral signal/noise, orthogonal/complementary ion separation to mass spectrometry, enhanced ion and complexation structural analysis, and the potential for rapid analyte quantitation. In this report, we demonstrate the successful use of our nanoESI-DMS-MS system, with a methanol drift gas modifier, for the separation of oligosaccharides. The tendency for ESI to form oligosaccharide aggregate ions and the negative impact this has on nanoESI-DMS-MS oligosaccharide analysis is described. In addition, we demonstrate the importance of sample solvent selection for controlling nanoESI oligosaccharide aggregate ion formation and its effect on glycan ionization and DMS separation. The successful use of a tetrachloroethane/methanol solvent solution to reduce ESI oligosaccharide aggregate ion formation while efficiently forming a dominant MH(+) molecular ion is presented. By reducing aggregate ion formation in favor of a dominant MH(+) ion, DMS selectivity and specificity is improved. In addition to DMS, we would expect the reduction in aggregate ion complexity to be beneficial to the analysis of oligosaccharides for other post-ESI separation techniques such as mass spectrometry and ion mobility. The solvent selected control over MH(+) molecular ion formation, offered by the use of the tetrachloroethane/methanol solvent, also holds promise for enhancing MS/MS structural characterization analysis of glycans.     

Separation of Ions from Volatile Organic Compounds Using High-Field Asymmetric Waveform Ion Mobility Spectrometry-Mass Spectrometer

A combination of high-field asymmetric waveform ion mobility spectrometry (FAIMS) with mass spectrometer (MS) was analyzed. FAIMS separates ions from the volatile organic compounds in the gas-phase as an ion-filter for MS. The sample ions were created at ambient pressure by ion source, which was equipped with a 10.6 eV UV discharge lamp (λ=116.5 nm).The drift tube of FAIMS is composed of two parallel planar electrodes and the dimension is 10 mm×8 mm×0.5 mm. FAIMS was investigated when driven by the high-filed rectangular asymmetric waveform with the peak-to-peak voltage of 1.36 kV at the frequency of 1 MHz and the duty cycle of 30%. The acetone, the butanone, and their mixture were adopted to characterize the FAIMS-MS. The mass spectra obtained from MS illustrate that there are ion-molecular reactions between the ions and the sample neutral molecular. And the proton transfer behavior in the mixture of the acetone and the butanone is also observed.With the compensation voltage tuned from -30 V to 10 V with a step size of 0.1 V, the ion pre-separation before MS is realized.