Field induced displacement reactions with proton bound dimers of organophosphorus compounds in a tandem differential mobility spectrometer.

Endothermic displacement reactions between proton bound dimers of organophosphorus compounds (OPCs) and isopropanol (IPA) were enabled in air at ambient pressure with tandem differential mobility spectrometry (DMS). Proton bound dimers (M2H+) were mobility isolated in purified air with a first DMS stage, mixed with IPA at ≥100 ppm in a middle reactive stage at 106 to 160 Td from a symmetrical 4 MHz waveform, and mobility analyzed in a second DMS stage. Although the enthalpy for displacement of M by IPA in M2H+ is unfavorable by +44 to 50 kJ mol-1, formation of the heterogenous proton bound dimer, MH+(IPA) arises from field induced dissociation of M2H+ to MH+ and addition of IPA. While peak dispersion for M2H+ of OPCs is limited to -2.25 to -0.5 V compensation voltage, peaks for MH+(IPA) were located at -10.5 to -8.25 V through a combination of ion transformation and mobility-based vapor modification. This inaugural use of ion reactions in air at ambient pressure demonstrates that multi-stage sequential processing of ions can improve significantly the analytical performance in a mobility spectrometer.

Quantitative response to nitrite from field-induced decomposition of the chloride adduct of RDX by reactive stage tandem ion mobility spectrometry.

An additional dimension of selectivity for the determination of RDX by ion mobility spectrometry (IMS) was introduced through field-induced decomposition of RDX·Cl- to NO2- on a spectral baseline free of interfering peaks. In this variant of reactive stage tandem IMS, the explosive ion is decomposed selectively in the presence of an interferent and from significantly convolved peaks which were mobility isolated within a narrow range of drift times using dual ion shutters. Field-induced decomposition at 170 °C and field strength of 112 Td (∼16 kV cm-1) provided 15% decomposition yield and RDX, amid interferent, was detected decisively even when peaks differed in reduced mobility coefficients (Ko) by only 0.02 cm2 V-1 s-1. A nitrite peak with S/N of 8.5 was observed with vapour concentrations of 54 ppb for RDX and 329 ppb for Interferent A in the ionization volume corresponding to 2 ng of RDX and 100 ng of Interferent A deposited on sample traps in the thermal desorption inlet. Findings on quantitative response suggest the presence of excessive amounts of interferent caused ionization suppression of RDX. Still, RDX was determined quantitatively using sequential processing of ions by mobility isolation, selective field induced decomposition, and mobility analysis in a second drift region.

Field Induced Fragmentation (Fif) Spectra of Oxygen Containing Volatile Organic Compounds with Reactive Stage Tandem Ion Mobility Spectrometry and Functional Group Classification by Neural Network Analysis.

Mobility isolated spectra were obtained for protonated monomers of 42 volatile oxygen containing organic compounds at ambient pressure using a tandem ion mobility spectrometer with a reactive stage between drift regions. Fragment ions of protonated monomers of alcohols, acetates, aldehydes, ketones, and ethers were produced in the reactive stage using a 3.3 MHz symmetrical sinusoidal waveform with an amplitude of 1.4 kV and mobility analyzed in a 19 mm long drift region. The resultant field induced fragmentation (FIF) spectra included residual intensities for protonated monomers and fragment ions with characteristic drift times and peak intensities, associated with ion mass and chemical class. High efficiency of fragmentation was observed with single bond cleavage of alcohols and in six-member ring rearrangements of acetates. Fragmentation was not observed, or seen weakly, with aldehydes, ethers, and ketones due to their strained four-member ring transition states. Neural networks were trained to categorize spectra by chemical class and tested with FIF spectra of both familiar and unfamiliar compounds. Rates of categorization were class dependent with best performance for alcohols and acetates, moderate performance for ketones, and worst performance for ethers and aldehydes. Trends in the rates of categorization within a chemical family can be understood as steric influences on the energy of activation for ion fragmentation. Electric fields greater than 129 Td or new designs of reactive stages with improved efficiency of fragmentation will be needed to extend the practice of reactive stage tandem IMS to an expanded selection of volatile organic compounds.

Quantitative response in ion mobility spectrometry with atmospheric pressure chemical ionization in positive polarity as a function of moisture and temperature.

Response of an ion mobility spectrometer at ambient pressure was quantitatively determined for fourteen chemicals from five chemical families spanning a range of proton affinities and temperature from 30 to 175 °C with moisture from 1 to 1 × 104 ppmv in purified air. Peak intensities, drift times and reduced mobility coefficients were determined for hydrated protons from a63Ni ion source and for protonated monomers and proton bound dimers of alcohols, aldehydes, acetates, ketones, and organophosphates. These measurements permitted the determination of response factors with atmospheric pressure chemical ionization and the influence of moisture and temperature on APCI response with correlation to computational models of hydration values. The formation of protonated monomers and proton bound dimers was described by heats of formation for a displacement reaction of water on H+(H2O)n by an analyte vapor and favorably matched results from density functional theory (DFT) with the 6-311 + G(dp) basis set. Response factors worsened with increased moisture and decreased temperature for compounds of medium, and more so, of low proton affinities. Findings here provide a broad measure and understanding for quantitative response in ion mobility spectrometers for substances for combinations of moisture and temperature.

Reactive Tandem Ion Mobility Spectrometry with Electric Field Fragmentation of Alcohols at Ambient Pressure.

A tandem ion mobility spectrometer at ambient pressure with a reactive stage produced fragment ions by water elimination from protonated monomers of alcohols with carbon numbers three to nine. Protonated monomers of individual alcohols were mobility isolated in a first drift region and were fragmented to carbocations at 64 to 128 Td and 45 to 89°C. Precursor and fragment ions were mobility characterized in a second drift region. Enthalpies for fragmentation of ROH2+ to primary carbocations were calculated as 76 to 97 kJ/mol and enthalpies for subsequent charge migration to 2° carbocations were -49 to -58 kJ/mol. Plots of drift times for pairs of protonated monomer and fragment ions from alcohols, esters, alkanes, and aldehydes produced distinctive trend lines attributed to fragmentation paths characteristic of chemical class. Specific combinations of drift times for fragments and precursor ions provide additional chemical information for spectral interpretation in ion mobility spectrometry.

Tandem ion mobility spectrometry at ambient pressure and field decomposition of mobility selected ions of explosives and interferences.

A tandem ion mobility spectrometer at ambient pressure included a thermal desorption inlet, two drift regions, dual ion shutters, and a wire grid assembly in the second drift region. An ion swarm could be mobility isolated in the first drift region using synchronized dual ion shutters and decomposed in a wire grid assembly using electric fields of 1.80 × 104 V cm-1 (118 Td) from a 1.8 MHz sinusoidal waveform. Mobility selected ions that underwent field induced decomposition were NO3-, from PETN·Cl- and NG·Cl-, and NO2- from RDX·Cl-. The extent of decomposition ranged from 60 to 90%, depending on gas temperature, field strength, and ion identity, introducing additional controls to improve selectivity in trace determination of explosives. Ion transmission through the wire grid assembly ranged from 80 to >95% with losses increasing for increased field strength. Studies with pairs of explosives and interfering substances demonstrated decisive detection of explosives and portend reduced rates of false positive using tandem ion mobility spectrometers with a reactive stage.

Stability of proton-bound clusters of alkyl alcohols, aldehydes and ketones in Ion Mobility Spectrometry.

Significant substances in emerging applications of ion mobility spectrometry such as breath analysis for clinical diagnostics and headspace analysis for food purity include low molar mass alcohols, ketones, aldehydes and esters which produce mobility spectra containing protonated monomers and proton-bound dimers. Spectra for all n- alcohols, aldehydes and ketones from carbon number three to eight exhibited protonated monomers and proton-bound dimers with ion drift times of 6.5-13.3 ms at ambient pressure and from 35° to 80 °C in nitrogen. Only n-alcohols from 1-pentanol to 1-octanol produced proton-bound trimers which were sufficiently stable to be observed at these temperatures and drift times of 12.8-16.3 ms. Polar functional groups were protected in compact structures in ab initio models for proton-bound dimers of alcohols, ketones and aldehydes. Only alcohols formed a V-shaped arrangement for proton-bound trimers strengthening ion stability and lifetime. In contrast, models for proton-bound trimers of aldehydes and ketones showed association of the third neutral through weak, non-specific, long-range interactions consistent with ion dissociation in the ion mobility drift tube before arriving at the detector. Collision cross sections derived from reduced mobility coefficients in nitrogen gas atmosphere support the predicted ion structures and approximate degrees of hydration.

Ion Mobility Spectrometer-Fragmenter-Ion Mobility Spectrometer Analogue of a Triple Quadrupole for High-Resolution Ion Analysis at Atmospheric Pressure.

Two differential mobility analyzers (DMAs) acting as narrow band mobility filters are coupled in series, with a thermal fragmentation cell placed in between, such that parent ions selected in DMA1 are fragmented in the cell at atmospheric pressure, and their product ions are analyzed on DMA2. Additional mass spectrometer analysis is performed for ion identification purposes. A key feature of the tandem DMA is the short residence time (∼0.2 ms) of ions in the analyzer, compared to tens of milliseconds in drift tube ion mobility spectrometers (IMS). Ion fragmentation within the analyzer and associated mobility tails are therefore negligible for a DMA but not necessarily so in conventional IMS. This advantage of the DMA is demonstrated here by sharply defined product ion mobility peaks. Ambient pressure ion fragmentation has been previously demonstrated by both purely thermal means as well as rapidly oscillating intense electric fields. Our purely thermal fragmentation cell here achieves temperatures up to 700 °C measured inside the heating coil of a cylindrical ceramic heater, through whose somewhat colder axis we direct a beam of mobility-selected ions. We investigate tandem separation of chloride adducts from the explosives EGDN, nitroglycerine (NG), PETN, and RDX and from deprotonated TNT. Atmospheric pressure fragmentation of the first three ions yields one or several previously reported fragments, providing highly distinctive tandem DMA channels for explosive identification at 1 atm. RDX ions had not been previously fragmented at ambient pressure, yet [RDX + Cl]- converts up to 7% (at 300 °C) into a 166 m/ z product. The known high thermal resilience of TNT is confirmed here by its rather modest conversion, even when the ceramic is heated to 700 °C. At this temperature some previously reported fragments are found, but their mobilities are fairly close to each other and to the one of the far more abundant parent ion, making their identification by mobility alone problematic. We anticipate that moderately higher fragmenter temperatures will produce smaller fragments with mobilities readily separated from that of [TNT - H]-.

Classification of biodiesel and fuel blends using gas chromatography - differential mobility spectrometry with cluster analysis and isolation of C18:3 me by dual ion filtering.

Fatty acid alkyl esters (FAAEs) were determined at 10-100mg/L in biodiesel and blends with petrodiesel without sample pre-treatment using gas chromatography with a tandem differential mobility detector. Selectivity was provided through chromatographic separations and atmospheric pressure chemical ionization reactions in the detector with mobility characterization of gas ions. Limits of detection were ~0.5ng with an average of 2.98% RSD for peak area precision, ≤1.3% RSD for retention time precision, and ≤9.2% RSD for compensation voltage precision. Biodiesel blends were classified using principal component analysis (PCA) and hierarchical cluster analysis (HCA). Unsupervised cluster analysis captured 52.72% of variance in a single PC while supervised analysis captured 71.64% of variance using Fisher ratio feature selection. Test set predictions showed successful clustering according to source or feedstock when regressed onto the training set model. Detection of the regulated substance methyl linolenate (C18:3 me) was achieved in 6-10s with a 1m long capillary column using dual ion filtering in the tandem differential mobility detector.

Analysis of Supramolecular Complexes of 3-Methylxanthine with Field Asymmetric Waveform Ion Mobility Spectrometry Combined with Mass Spectrometry.

Miniaturised field asymmetric waveform ion mobility spectrometry (FAIMS), combined with mass spectrometry (MS), has been applied to the study of self-assembling, noncovalent supramolecular complexes of 3-methylxanthine (3-MX) in the gas phase. 3-MX forms stable tetrameric complexes around an alkali metal (Na(+), K(+)) or ammonium cation, to generate a diverse array of complexes with single and multiple charge states. Complexes of (3-MX)n observed include: singly charged complexes where n = 1-8 and 12 and doubly charged complexes where n = 12-24. The most intense ions are those associated with multiples of tetrameric units, where n = 4, 8, 12, 16, 20, 24. The effect of dispersion field on the ion intensities of the self-assembled complexes indicates some fragmentation of higher order complexes within the FAIMS electrodes (in-FAIMS dissociation), as well as in-source collision induced dissociation within the mass spectrometer. FAIMS-MS enables charge state separation of supramolecular complexes of 3-MX and is shown to be capable of separating species with overlapping mass-to-charge ratios. FAIMS selected transmission also results in an improvement in signal-to-noise ratio for low intensity complexes and enables the visualization of species undetectable without FAIMS.

Dissociation Enthalpies of Chloride Adducts of Nitrate and Nitrite Explosives Determined by Ion Mobility Spectrometry.

The kinetics for thermal dissociations of the chloride adducts of the nitrate explosives 1,3-dinitroglycerin (1,3-NG), 1,2-dinitroglycerin (1,2-NG), the nitrite explosive 3,4-dinitrotoluene (3,4-DNT), and the explosive taggant 2,3-dimethyl-2,3-dinitrobutane (DMNB) have been studied by atmospheric pressure ion mobility spectrometry. Both 1,3-NG·Cl(-) and1,2-NG·Cl(-) decompose in a gas-phase SN2 reaction in which Cl(-) displaces NO3(-) while 3,4-DNT·Cl(-) and DMNB·Cl(-) decompose by loss of Cl(-). The determined activation energy (kJ mol(-1)) and pre-exponential factor (s(-1)) values for the dissociations respectively are 1,3-NG·Cl(-), 86 ± 2 and 2.2 × 10(12); 1,2-NG·Cl(-), 97 ± 2 and 3.5 × 10(12); 3,4-DNT·Cl(-), 81 ± 2 and 4.8 × 10(13); and DMNB·Cl(-), 68 ± 2 and 9.7 × 10(11). Calculations by density functional theory show the structures of the nitrate ester adducts involve three hydrogen bonds: one from the hydroxyl group and the other two from the two nitrated carbons. The relative Cl(-) dissociation energies of the nitrates together with the previously reported smaller value for glycerol trinitrate and the calculated highest value for glycerol 1-mononitrate are explicable in terms of the number of hydroxyl hydrogen bond participants. The theoretical enthalpy changes for the nitrate ester displacement reactions are in agreement with those derived from the experimental activation energies but considerably higher for the nitro compounds.

Decomposition kinetics of nitroglycerine·Cl(-)(g) in air at ambient pressure with a tandem ion mobility spectrometer.

A dual-shutter ion mobility spectrometer operating at atmospheric pressure and interfaced to a gas chromatograph for sample introduction has been used to study the reaction of Cl(-) with explosives. Of particular interest was an investigation of the formation of NO3(-) from the reaction of the Cl(-) with nitroglycerin (NG). The adduct NG·Cl(-) together with NO3(-) and NG·NO3(-) compose the mobility spectrum. Over the temperature range 111 to 122 °C, NG·NO3(-) is stable, but NG·Cl(-) decomposes to NO3(-) and 1,2-dinitro-3-chloropropane (DNClP). The activation energy and pre-exponential factor for this first order decomposition are 80 ± 3 kJ mol(-1) and 1.3 × 10(12) s(-1), respectively. Ab initio calculation shows that the reaction is a substitution reaction occurring over a two well potential energy profile with stable ion-molecule complexes NG·Cl(-) and DNClP·NO3(-).

Tandem differential mobility spectrometry in purified air for high-speed selective vapor detection.

A tandem ion mobility instrument based on differential mobility spectrometry (DMS) was used to demonstrate selectivity in response through differences in field dependence of mobility for ions in purified air at ambient pressure. The concept of chemical selectivity solely from characteristic dispersion curves or from field dependence of ion mobility was experimentally demonstrated in three steps with mixtures of increasing complexity. In a mixture of four alcohols with carbon numbers four and below, distinct pairs of separation voltage and compensation voltage, applied to the first and second DMS stages, permitted isolation of ions from individual substances without detectable levels of other substances. In a three-component mixture of a ketone, alcohol, and organophosphorus compound, the same level of ion isolation was observed using specific and characteristic separation and compensation voltages on each DMS stage. In the last experiment, the isolation of product ions of individual substances from a mixture of 23 volatile organic compounds from four chemical groups was incomplete though the improvement in the ratio of analyte signal to chemical noise was calculated as 31 for DMMP and 106 for 1-hexanol. These findings demonstrate that chemical information available in dispersion curves can be accessed in response times below 100 ms through a tandem DMS measurement.

Low-mobility-pass filter between atmospheric pressure chemical ionization and electrospray ionization sources and a single quadrupole mass spectrometer: computational models and measurements.

RATIONALE: Mixtures of ions produced in sources at atmospheric pressure, including chemical ionization (APCI) and electrospray ionization (ESI) can be simplified at or near ambient pressure using ion mobility based filters. METHODS: A low-mobility-pass filter (LMPF) based on a simple mechanical design and simple electronic control was designed, modeled and tested with vapors of 2-hexadecanone in an APCI source and with spray of peptide solutions in an ESI source. The LMPF geometry was planar and small (4 mm wide × 13 mm long) and electric control was through a symmetric waveform in low kHz with amplitude between 0 and 10 V. RESULTS: Computational models established idealized performance for transmission efficiency of ions of several reduced mobility coefficients over the range of amplitudes and were matched by computed values from ion abundances in mass spectra. The filter exhibited a broad response function, equivalent to a Bode Plot in electronic filters, suggesting that ion filtering could be done in blocks ~50 m/z units wide. CONCLUSIONS: The benefit of this concept is that discrimination against ions of high mobility is controlled by only a single parameter: waveform amplitude at fixed frequency. The effective removal of high mobility ions, those of low mass-to-charge, can be beneficial for applications with ion-trap-based mass spectrometers to remove excessive levels of solvent or matrix ions.

Dissociation of proton bound ketone dimers in asymmetric electric fields with differential mobility spectrometry and in uniform electric fields with linear ion mobility spectrometry.

The kinetics for the decomposition of the symmetrical proton-bound dimers of a series of 2-ketones (M) from acetone to 2-nonanone have been determined at ambient pressure by linear ion mobility spectrometry (IMS) and by differential mobility spectrometry (DMS). Decomposition, M2H(+) →MH(+) + M, in the IMS instrument, observed under thermal conditions over the temperature range 147 to 172 °C, yielded almost identical Arrhenius parameters Ea = 122 kJ mol(-1) and ln A = 38.8 for the dimers of 2-pentanone, 2-heptanone, and 2-nonanone. Ion decomposition in the DMS instrument was due to a combination of thermal and electric field energies at an effective ion internal temperature whose value was estimated by reference to the IMS kinetic parameters. Decomposition was observed with radio frequency (RF) fields with maximum intensities in the range 10 kV cm(-1) to 30 kV cm(-1) and gas temperatures from 30 to 110 °C, which yielded effective temperatures that were higher than the gas temperature by 260° at 30 °C and 100° at 110 °C. There was a mass dependence of the field for the onset of decomposition: the higher the ion mass, the higher the required field at a given gas temperature, which is ascribed to the associated increasing heat capacity with the increasing carbon number, but similar, internal vibrations and rotations.

Ion profiling in an ambient drift tube-ion mobility spectrometer using a high pixel density linear array detector IonCCD.

A linear pixel-based detector array, the IonCCD, is characterized for use under ambient conditions with thermal (<1 eV) positive ions derived from purified air and a 10 mCi (63)Ni foil. The IonCCD combined with a drift tube-ion mobility spectrometer permitted the direct detection of gas phase ions at atmospheric pressure and confirmed a limit of detection of 3000 ions/pixel/frame established previously in both the keV (1-2 keV) and the hyper-thermal (10-40 eV) regimes. Results demonstrate the "broad-band" application of the IonCCD over 10(5) orders in ion energy and over 10(10) in operating pressure. The Faraday detector of a drift tube for an ion mobility spectrometer was replaced with the IonCCD providing images of ion profiles over the cross-section of the drift tube. Patterns in the ion profiles were developed in the drift tube cross-section by control of electric fields between wires of Bradbury Nielson and Tyndall Powell shutter designs at distances of 1-8 cm from the detector. Results showed that ion beams formed in wire sets, retained their shape with limited mixing by diffusion and Coulombic repulsion. Beam broadening determined as 95 µm/cm for hydrated protons in air with moisture of ~10 ppmv. These findings suggest a value of the IonCCD in further studies of ion motion and diffusion of thermalized ions, enhancing computational results from simulation programs, and in the design or operation of ion mobility spectrometers.

A study of the performance of an ion shutter for drift tubes in atmospheric pressure ion mobility spectrometry: computer models and experimental findings.

Ion mobility spectra are initiated when ions, derived from a sample, are pulsed or injected through ion shutters into a drift region. The effect on signal intensity from electric fields arising from the shutter grids (E(s)) and a superimposed electric field of the drift tube (E(d)) was determined experimentally and simulated computationally for ion motion at ambient pressure. The combination of these two fields influenced shutter performance in three ways: (1) intensity of an ion peak was suppressed by increased current in the baseline due to continuous leakage of ions into the drift region from insufficient E(s) to block ion motion when needed, at a given value of E(d); (2) the ion shutter provided maximum peak intensity with some optimal ratio of E(s)/E(d) when ions were fully blocked except using the injection time; (c) the signal intensity was reduced when the blocking voltage of the ion shutter exceeded this optimal E(s)/E(d) ratio from ion depletion at the shutter grids. The optimal ratio from the computer models was equal to 1.50, whereas a value of 2.50 was obtained from the experimental findings. This difference was attributed to nonideal geometry with the grids of the shutter and the conducting elements in the drift tube establishing both E(s) and E(d). As both the experimental and modeling results demonstrated, a mobility dependence of ion yield from the ionization source was found to cause a mobility dependent ion signal at the collector electrode.

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.

Analysis of bacteria by pyrolysis gas chromatography-differential mobility spectrometry and isolation of chemical components with a dependence on growth temperature.

Pyrolysis gas chromatography-differential mobility spectrometry (py-GC-DMS) analysis of E. coli, P. aeruginosa, S. warneri and M. luteus, grown at temperatures of 23, 30, and 37 degrees C, provided data sets of ion intensity, retention time, and compensation voltage for principal component analysis. Misaligned chromatographic axes were treated using piecewise alignment, the impact on the degree of class separation (DCS) of clusters was minor. The DCS, however, was improved between 21 to 527% by analysis of variance with Fisher ratios to remove chemical components independent of growth temperature. The temperature dependent components comprised 84% of all peaks in the py-GC-DMS analysis of E. coli and were attributed to the pyrolytic decomposition of proteins rather than lipids, as anticipated. Components were also isolated in other bacteria at differing amounts: 41% for M. luteus, 14% for P. aeruginosa, and 4% for S. warneri, and differing patterns suggested characteristic dependence on temperature of growth for these bacteria. These components are anticipated to have masses from 100 to 200 Da by inference from differential mobility spectra.