Electrospray ionization-voltage sweep-Ion mobility spectrometry for biomolecules and complex samples

Voltage Sweep Ion Mobility Spectrometry (VSIMS) has been applied to complex samples using electrospray ionization (ESI). The usable range of VSIMS has been extended from that obtained in previous studies where only volatile compounds were investigated. Using ESI, VSIMS was evaluated with compounds with reduced mobility values as low as 0.3 V²cm^?1 s^?1. The primary advantage of VSIMS is to enable a drift time ion mobility spectrometer (DTIMS) to detect both fast and slow moving ions at optimal resolving power, thus improving the peak capacity. In this work ESI-VSIMS was applied to a series of small peptides and drugs spanning a large range of reduced mobility values in order to demonstrate ESI-VSIMS to separation. To demonstrate improved peak capacity of IMS with voltage scan operation, oligomers of silicone oil provided a series of evenly-spaced peaks, ranging in reduced mobility values from 0.85 to 0.3 V²cm^?1 s^?1. The peak capacity of 61 for a standard IMS was improved to 102 when voltage sweep operation was employed. In addition, VSIMS increased the average resolving power of the DTIMS from 66 to 106 for silicone oil.     

Paper spray ionization with ion mobility spectrometry at ambient pressure

A paper spray ion source was combined with a drift tube operating at ambient pressure for mobility measurements of ions derived from pharmaceutical solutions. Paper spray ionization with solvent alone resulted in a mixture of ions convolved to a single peak with a reduced mobility of 2.19 cm²/Vs in the mobility spectrum. These were mass-identified principally as m/z 157, (MeOH)₂(HCOOH)₂H⁺ and m/z 129, (MeOH)₄(H₂O)H⁺ while pharmaceuticals with nitrogen bases formed MH⁺ product ions. The duration of response was governed by the volume of liquid added to the paper source and was limited by evaporation of solvent in gas at 58 °C venting the drift tube. Quantitative variation was attributed in part to morphologic changes in the tip of the paper spray source. This was associated with mass flow in the electrical discharge and not due alone to cycles of wetting and drying of the paper. Mobility spectra of chlorpromazine in urine, exhibited a single product ion peak and linear response was 30 to 500 ng with an estimated limit of detection of 1.5 ng. Ion flux could be prolonged by continuous addition of liquid and findings portend a combination of paper spray ionization IMS with paper chromatography.     

Liquid chromatography/electrospray ionization/ion mobility spectrometry of chlorophenols with full flow from large bore LC columns

Chlorophenols (CPs) as a mixture of fourteen congeners from mono- to pentachlorophenol were determined using liquid chromatography/electrospray ionization/ion mobility spectrometry (LC/ESI/IMS) to describe the response and analytical performance of a mobility spectrometer as a detector for liquid chromatography. The mobility spectrometer was equipped with an interface so that flows from a large bore column could be electrosprayed directly into the drift tube at flow rates up to 500 μL/min without splitting of flow. A linear gradient of the mobile phase from 40% to 90% methanol and 60% to 10% acetic acid (AcOH)–ammonium acetate buffer solution over 40 min with a C18 column provided baseline separations though mobility spectra for CPs were influenced by mobile phase composition. Product ions formed from CPs with ESI included phenoxide anions CPO^?, AcOH·CPO^?, CPOH·CPO^?, and Na⁺·(CPO^?)₂ and were found to be governed by the drift gas temperature. Ions were identified using LC/ESI/mass spectrometry (MS) and supported by results from computational modeling. Quantitative response was affected by congener structure through the acidities of the OH moiety and by the composition of the mobile phase. Limits of detection ranged from 0.135 mg/L for 2,3,5-trichlorophenol and pentachlorophenol to 2.23 mg/L for 2-chlorophenol; corresponding linear ranges were 20 and 70.     

Electrical and optical properties of high-purity p-type single crystals of GeFe2O4

Single crystals of the spinel GeFe₂O₄, grown by the chemical vapor transport technique, are p-type semiconductors with an acceptor ionization energy of 0.39 eV. The material is a heavily compensated band-type semiconductor, with a typical hole concentration of 10¹⁴ cm^?3 near room temperature, and a temperature-independent Hall mobility of 2 cm²/V·sec. Optical absorption measurements show the optical band gap to be ?2.3 eV; the octahedral field splitting of the Fe²⁺d-levels is 10 200 cm^?1. Magnetic measurements show that n_eff is 5.26, from which a trigonal field splitting of 950 cm^?1 is derived.     

Coupling electrospray corona discharge, charge reduction and ion mobility mass spectrometry: From peptides to large macromolecular protein complexes

We present the design and implementation of a home-built point-to-plane corona discharge probe, which rapidly and efficiently charge reduces biological ions generated by electrospray ionization (ESI). The molecules analysed ranged from small peptides such as Glu-fibrinopeptide B (1.5 kDa), small proteins such as myoglobin (16.9 kDa), polymers such as polyethylene glycol (PEG 10 k) which all showed intense singly charged ions; to large native multiprotein complexes such as GroEL (802 kDa) which show a broad range of charge-reduced species. The corona discharge probe operates at atmospheric pressure and was directly interfaced with a standard-ESI or nanoflow-ESI source of quadrupole ion mobility time-of-flight mass spectrometer. The corona discharge probe is completely modular and could potentially be mounted to any commercial or research grade mass spectrometer with an ESI source. The level of charge reduction is precisely controlled by the applied voltage and/or probe gas flow rate and when in operation, results in approximately a 50 % reduction in total ion current. We also present the combination of corona discharge and travelling wave ion mobility and assign helium collision cross-section values (Ω_He) to the charge reduced species of the native protein complex pyruvate kinase. It would appear that the Ω_He of the +20 charge state for pyruvate kinase is approximately 20 % smaller than the +35 charge state. Finally, we discuss the potential benefits and concerns of utilising charge reduced protein species as a means of extending the travelling wave collision cross-section calibration range over that which is already published.     

Corona discharge ion mobility spectrometry for the determination of theophylline and guaifenesin in human serum

This paper describes the determination of theophylline and guaifenesin in human serum using ion mobility spectrometry with positive corona discharge as source ionization. The optimization of parameters that could influence ion mobility spectrometry was investigated. Under optimum conditions (Temperature; injection: 220 and oven: 175 °C, Flow rate; carrier: 300 and drift: 600 mL min^?1, Voltage; corona: 2300 and drift: 7000 V, pulse width: 100 μs), calibration curves were linear in the ranges of 2 to120 and 6 to 120 ng for theophylline and guaifenesin, respectively. The relative standard deviation (n?=?10) was below 12 %. The detection limits were found to be 0.1 ng for theophylline and 0.5 ng for guaifenesin. The recovery results for the theophylline and guaifenesin determination in human serum was about 80 % that indicate the proposed method can be applied for the two drugs analysis in real sample. Furthermore, the proposed method has been evaluated in the simultaneous determination of the two drugs.     

An NO+ reactant ion source for ion mobility spectrometry

The major reactant ion in conventional ion mobility spectrometry (IMS) is the hydronium ion, H₃O⁺ which is produced in the usual ionization sources such as corona discharge or radioactive sources. Using the hydronium reactant ion, mostly the analytes with proton affinity higher than that of water are ionized. A broader range of compounds can be detected by IMS if other alternative ionization channels, such as charge transfer from NO⁺, are employed. In this work we introduce a simple and novel method for producing NO⁺ as the major reactant ion in IMS. This was achieved by adding neutral NO to the corona discharge ionization source. The neutral NO was prepared via an additional discharge in an air stream, flowing into the corona discharge source. A curtain plate was mounted in front of the corona discharge to prevent the influence of the analyte on the production of NO⁺. Using this technique, the reactant ion could easily and quickly switch between the H₃O⁺ and NO⁺. The performance of the new source was evaluated by recording ion mobility spectra of test compounds with both H₃O⁺ and NO⁺ reactant ions.     

Mechanisms for negative reactant ion formation in an atmospheric pressure corona discharge

In an effort to better understand the formation of negative reactant ions in air produced by an atmospheric pressure corona discharge source, the neutral vapors generated by the corona were introduced in varying amounts into the ionization region of an ion mobility spectrometer/mass spectrometer containing a ⁶³Ni ionization source. With no discharge gas the predominant ions were O₂ ⁻, however, upon the introduction of low levels of discharge gas the NO₂ ⁻ ion quickly became the dominant species. As the amount of discharge gas increased the appearance of CO₃ ⁻ was observed followed by the appearance of NO₃ ⁻. At very high levels, NO₃ ⁻ species became effectively the only ion present and appeared as two peaks in the IMS spectrum, NO₃ ⁻ and the NO₃ ⁻·HNO₃ adduct, with separate mobilities. Since explosive compounds typically ionize in the presence of negative reactant ions, the ionization of an explosive, RDX, was examined in order to investigate the ionization properties with these three primary ions. It was found that RDX forms a strong adduct with both NO₂ ⁻ and NO₃ ⁻ with reduced mobility values of 1.49 and 1.44 cm²V⁻¹ s⁻¹, respectively. No adduct was observed for RDX with CO₃ ⁻ although this adduct has been observed with a corona discharge mass spectrometer. It is believed that this adduct, although formed, does not have a sufficiently long lifetime (greater than 10 ms) to be observed in an ion mobility spectrometer.     

Sterically hindered phenols in negative ion mobility spectrometry–mass spectrometry

Negative corona discharge atmospheric pressure chemical ionization (APCI) was used to investigate phenols with varying numbers of tert‐butyl groups using ion mobility spectrometry–mass spectrometry (IMS‐MS). The main characteristic ion observed for all the phenolic compounds was the deprotonated molecule [M–H]⁻. 2‐tert‐Butylphenol showed one main mobility peak in the mass‐selected mobility spectrum of the [M–H]⁻ ion measured under nitrogen atmosphere. When air was used as a nebulizer gas an oxygen addition ion was seen in the mass spectrum and, interestingly, this new species [M–H+O]⁻ had a shorter drift time than the lighter [M–H]⁻ ion. Other phenolic compounds primarily produced two IMS peaks in the mass‐selected mobility spectra measured using the [M–H]⁻ ion. It was also observed that two isomeric compounds, 2,4‐di‐tert‐butylphenol and 2,6‐di‐tert‐butylphenol, could be separated with IMS. In addition, mobilities of various characteristic ions of 2,4,6‐trinitrotoluene were measured, since this compound was previously used as a mobility standard. The possibility of using phenolic compounds as mobility standards is also discussed. Copyright © 2009 John Wiley & Sons, Ltd.     

Improvement in carrier mobility of poly(3,4‐ethylenedioxythiophene) nanowires synthesized in porous alumina templates

Polymeric nanowires of poly(3,4‐ethylenedioxythiophene) (PEDOT) are electrochemically synthesized using porous anodic alumina oxide (AAO) membranes as templates. Four‐point resistivity measurements on more than 100 PEDOT nanowires with different diameters (50–250 nm) reveal a statistically significant size‐dependent phenomenon in which the nanowires with a smaller diameter exhibit higher conductivity. Structural characterization with Raman spectroscopy and doping level estimation with energy‐dispersive X‐ray spectrometry and X‐ray photoelectron spectroscopy indicate that the observed conductivity enhancement can be attributed to improved carrier mobility in PEDOT nanowires having an elongated conjugation structure because of the effect of the AAO template. From the estimated doping levels (～5%) and conductivity data (～100 S/cm), it is found that the carrier mobility reach 2.0 cm²/V s for the nanowire with the smallest diameter, as compared with 4.0 × 10^?4 cm²/V s for a bulk PEDOT film. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

Improving the analytical performance of ion mobility spectrometer using a non-radioactive electron source

For the ionization of gas mixtures, several ionization sources can be coupled to an ion mobility spectrometer. Radioactive sources, e.g. beta radiators like ⁶³Ni and ³H, are the most commonly used ionization sources. However, due to legal restrictions radioactive ionization sources are not applicable in certain applications. Non-radioactive alternatives are corona discharge ionization sources or photoionization sources. However, using an electron gun allows regulation of ion production rate, ionization time and recombination time by simply changing the operating parameters, which can be utilized to enhance the analytical performance of ion mobility spectrometers. In this work, the impact of an ionization source parameter variation on the ion mobility spectrum is demonstrated. Increasing the ion production rate, the amount of the generated ions increases leading to higher signal intensity while the noise remains constant. Thus, the signal to noise ratio can be increased, leading to better limits of detection. In a next step, the ion production rate is kept constant while the influence of ionization time on the ion mobility spectrum is investigated. It is shown, that varying the ionization time allows the determination of the reaction rate constants as additional information to the ion mobility. Furthermore, we show the prevention of discrimination processes by using short ionization times combined with an increased ion production rate. Thus, the limit of detection for benzene in presence of toluene is improved. Additionally, it is shown that using ion-ion recombination leads to the detection of the ion species with the highest proton affinity at higher recombination times while the low proton affine ions already recombined. Thus, the measurement of the ion mobility spectra at a defined recombination time allows a suppression of disturbing low proton affine substances.     

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.     

Spectrophotometric determination of trace amounts of iodide-ions in form of ionic associate with brilliant green using electrochemical oxidation

A combined method involving electrochemical oxidation of iodide to iodate at a platinum electrode followed by extraction in CCl₄ of ionic associates of iodine-iodide complexes with brilliant green, formed in excess of iodide, was developed for the spectrophotometric quantification of iodide. The slope of the calibration curve yields a molar extinction coefficient of ɛ = 3·10⁵ L mol⁻¹cm⁻¹. This method can be used for the quantification of iodide in the concentration range of 3·10⁻⁷ − 3·10⁻⁶ mol L⁻¹ with a detection limit of 5·10⁻⁸ mol L⁻¹. The interfering effect of other ions on the determination of the iodide concentration was also investigated. The method was successfully applied for the determination of iodide in real samples of NaCl and spring water. Relative standard deviation is 1–2%.     

An ion mobility spectrometer sensor system for subsurface use

An ion mobility spectrometer (IMS) probe system for real-time, subsurface soil-gas sampling applications is presented. The system includes an IMS and supporting electronics encased in a 51 mm diameter stainless steel probe housing. The IMS was challenged in the laboratory with 2,6-di-tert-butylpyridine (DtBP) and tetrachloroethylene (PCE) in zero air yielding reduced ion mobility constants (K_o) values of 1.42 cm²/Vs (n = 3) and 1.79 ± 0.01 cm²/Vs (n = 3), respectively. A resolving power of 38 and 31 was obtained for DtBP and PCE, respectively. The system was deployed at a PCE-contaminated site to demonstrate its performance under field conditions. PCE was detected in the vapor samples as evidenced by peaks with a K_o value of 1.80 ± 0.01 cm²/Vs for two measurements that were taken 6 min apart. The presence of PCE at the contaminated site was confirmed by GC-MS analysis of a gas sample at an EPA-certified laboratory, suggesting that this IMS system can be used to detect PCE under field conditions.     

CHCl3电子吸附速率常数的离子迁移谱

The dissociative electron attachment process for CHCl₃ at different electric field have been studied with nitrogen as drift and carrier gas using corona discharge ionization source ion mobility spectrometry (CD-IMS). The corresponding electron attachment rate constants varied from 1.26×10^-8 cm³/(molecules s) to 8.24×10^-9 cm³/(molecules s) as the electric field changed from 200 V/cm to 500 V/cm. At a fixed electric field in the drift region,the attachment rate constants are also detected at different sample concentration. The ion-molecule reaction rate constants for the further reaction between Cl^- and CHCl₃ are also detected, which indicates that the technique maybe becomes a new method to research the rate constants between ions and neural molecules. And the reaction rate constants between Cl^- and CHCl₃ are the first time detected using CD-IMS.     

Evaluation of micro-electrospray ionization with ion mobility spectrometry/mass spectrometry

In recent years, the resolving power of ion mobility instruments has been increased significantly, enabling ion mobility spectrometry (IMS) to be utilized as an analytical separation technique for complex mixtures. In theory, decreasing the drift tube temperature results in increased resolution due to decreased ion diffusion. However, the heat requirements for complete ion desolvation with electrospray ionization (ESI) have limited the reduction of temperatures in atmospheric pressure ion mobility instruments. Micro-electrospray conditions were investigated in this study to enable more efficient droplet formation and ionization with the objective of reducing drift tube temperatures and increasing IMS resolution. For small molecules (peptides), the drift tube temperature was reduced to ambient temperature with good resolution by employing reduced capillary diameters and flow rates. By employing micro-spray conditions, experimental resolution values approaching theoretically predicted resolution were achieved over a wide temperature range (30 to 250 °C). The historical heat requirements of atmospheric pressure IMS due to ESI desolvation were eliminated due to the use of micro-spray conditions and the high-resolution IMS spectra of GLY-HIS-LYS was obtained at ambient temperature. The desolvation of proteins (cytochrome c) was found to achieve optimal resolution at temperatures greater than 125 °C. This is significantly improved from earlier IMS studies that required drift tube temperatures of 250°C for protein desolvation.     

Sprayed liquid-gas extraction in combination with ion mobility spectrometry: a novel approach for the fast determination of semi-volatile compounds in air and from contaminated surfaces

We developed a fast, simple and highly-efficient enrichment procedure for trace levels of semi volatile organic compounds from air and surfaces and combined it with ion mobility spectrometry as field-deployable and rapid analytical technique. Our new technique, the sprayed liquid-gas extraction, was developed and optimized to allow the enrichment of semi volatile organic compounds. The air sample is pumped through a flow blurring nebulizer together with water. The sprayed liquid is collected and the organic compounds are transferred from the water phase to n-hexane via a miniscale liquid-liquid extraction. 50 μL of the n-hexane extract is applied to a fiber tape. After the n-hexane has evaporated, the fiber tape is transferred to the thermodesorber unit of a GDA-X ion mobility spectrometer (Airsense, Schwerin, Germany). The whole sampling and the sample preparation procedure takes no longer than 15 min and only requires 2.5 mL organic solvent. The method was optimized for Malathion, a widely used organophosphate insecticide and an accepted simulant for the nerve-agent, VX. Malathion provides defined ion mobility spectra in both, the positive and negative mode. The positive spectra show one major peak with a reduced mobility of 1.197 cm² Vs^?1 and an additional peak at 1.449 cm² Vs^?1 with lower intensity. A major product ion peak of 1.720 cm² Vs^?1 can be detected in negative mode together with an additional peak of low intensity at 1.403 cm² Vs^?1. The detection limit of the ion mobility spectrometer is approximately 20 ng absolute.     

Diffusion coefficients of tungsten heteropolyacids

Controlled hydrodynamics at rotating platinum and amalgamated copper electrodes were used to measure diffusion coefficients for 12-phosphotungstic and polyphosphotungstic acids in 1 M phosphoric acid, D_112-PTA=2.48 · 10^-6; D_polymer= 2.68 · 10^-7 cm²/sec, assuming only 1 tungsten atom in 12 is reduced at each diffusing entity. The phosphotungstic acids in phosphoric acid probably exist as polymers on initial formation, not greater than tetramers, rearranging to give monomers from calculations based on one reduced tungsten atom to each complex ion. Diffusion parameters of the phosphotungstic acids are compared with diffusion results of tungsten compounds from the literature obtained with dropping mercury electrodes. In all instances, low diffusion values are obtained indicating large diffusing entities.     

Optimisation of piezoelectric injection of dopants and drift gas modifiers in transverse ion mobility spectrometry

Novel experimental methods are described for controlling the levels of dopant or drift gas modifier with piezoelectric actuation. The piezoelectric jetting of 2-butanol, acetone, 4-heptanone and dichloromethane was first optimised by applying a fractional factorial experimental design to the waveform required to actuate the dopants. The concentration of dopant entering a transverse ion mobility cell was dynamically controlled by a series of air flows at the interface between the actuator and the ion source, as well as the droplet injection frequency, as defined by the optimised waveform parameters. The optimisation methodology indicated that dwell time and dwell voltage were the most important factors in controlling the process. The optimised approach was then used to deliver varying levels of candidate dopants; 20.5 to 196.6 μg?m^?3 for 2-butanol, 35.4 to 164.3 μg?m^?3 for acetone, 17.8 to 58.2 μg?m^?3 for 4-heptanone and 27.6 to 270.2 μg?m^?3 for dichloromethane. The method enables reactant ion chemistry to be switched in the order of 3 to 5 sec, indicating the potential for introducing multiple dopants at varying concentrations into ion mobility spectrometers. The most volatile material dichloromethane was more difficult to control and the reproducibility and stability of the instrument responses to this compound was not as good as the other less volatile ones. The concept of extending this approach to mixtures and dual use formulations, doping and modification was proposed.     

Volumetric Studies of 2,2,2-Cryptand in Aqueous and Aqueous KBr Solutions at 298.15 K: An Example Involving Solvent-Induced Hydrophilic and Hydrophobic Interactions

Density measurements of good precision are reported for aqueous and aqueous salt (KBr) solutions containing 2,2,2-cryptand (4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane) (~0.009 to ~0.24 mol·kg^?1) for the binary systems and for the ternary system with ~0.1 mol·kg^?1 2,2,2-cryptand and varying KBr concentrations (~0.06 to ~ 0.16 mol·kg^?1) at 298.15 K. The density data have been used to study the variation of apparent molar volume (\( \varphi_{V} \)) of 2,2,2-cryptand and of KBr as a function of concentration. 2,2,2-Cryptand is a diamine and hence it is hydrolyzed in aqueous solutions and needs an appropriate methodology to obtain meaningful thermodynamic properties. We have adopted a method of hydrolysis correction developed initially by Cabani et al. and later by Kaulgud et al. to analyze our volumetric data for the aqueous solutions. The method is described and we were successful in obtaining the limiting partial molar volume of the bare (free) cryptand in water at 298.15 K. Volumes of ionization as well as volumes of complexation (with KBr) are calculated. Estimations of the apparent molar volume of 2,2,2-cryptand in CCl₄ are also reported. There is a loss in volume for the cryptand on transferring it from CCl₄ to water. The volume changes due to ionization for the cryptand in water are calculated to be –20.5 and –0.6 cm³·mol^?1 for the mono- and di-protonation equilibria respectively, while the volume of complexation for K⁺ is +24.5 cm³·mol^?1. The results are discussed in terms of conformation, protonation equilibria and selective encapsulation of K⁺ ions in cryptand cavities. The solution volume properties seem to depend upon water–solute interaction as well on the solute–solute association because of hydrophobic interactions caused by lowering of the charge density on formation of cryptand-K⁺ species in solution.