Reduced Ion Mobility Research Articles

Breath analysis—performance and potential of ion mobility spectrometry

Ion mobility spectrometry is a fast and sensitive analytical method for the detection of gas phase analytes in the ppbv–pptv range under ambient conditions (pressure and temperature). Ion mobility spectrometers coupled with rapid pre-separation like multi-capillary columns (MCC/IMS) are suitable for the selective characterization of complex and humid mixtures. Recently, MCC/IMS have been applied to analyses of human breath for early diagnosis as well as medication and therapy control. The complete procedure of breath analyses including evaluation and interpretation of the data obtained is demonstrated for the first time on exhaled breath after the consumption of a particular candy as an example. An MCC/IMS equipped with a β-radiation source (63Ni) requires 5 to 10 min for a complete analysis of exhaled breath. Retention time and reduced ion mobility of the detected signals are compared to an analyte database for the identification of the related analytes. These findings were successfully validated by gas-chromatographic mass spectroscopy of the headspace of the candy via solid-phase micro-extraction and of breath samples on Tenax adsorption tubes. Furthermore, signal height of particular analyte signals as a measure for their concentration was used to monitor the concentration development with time. This exemplary investigation demonstrates that MCC/IMS is a powerful and rapid non-invasive tool for human breath analyses. The method can be used for medical applications (diagnosis, therapy control, metabolic profiling) as well as for a general determination of the metabolic state of a subject (medication, nutrition, fasting). The demonstrated procedure is independent of whether the analytes detected in breath are caused by nutrition or medication or whether they are metabolite characteristics for a particular disease. Therefore, it can directly be transferred to any relevant peak pattern.

An implementable approach to obtain reproducible reduced ion mobility

Ion mobility spectrometry is increasingly in demand for medical applications and its potential for implementation in food quality and safety or process control suggest rising use of instruments in this field as well. All those samples are commonly extremely complex and mostly humid mixtures. Therefore, pre-separation techniques have to be applied. As ion mobility spectrometers with gas-chromatographic pre-separation acquire a huge amount of data, effective data processing and automated evaluation by comparison of detected peak pattern with data bases have to be utilised. This requires accurate on-line calibration of the instruments to guarantee reproducible results, in particular with respect to identification of an analyte by determination of its ion mobility and retention time. To reduce environmental and instrumental influence, the reduced ion mobility is used. It is derived from the drift time normalised to electric field, length of the drift region and to temperature and pressure of the drift gas (traditional method). All data required for this normalisation are afflicted with a particular error and thus leading to a deviation of the calculated ion mobility value. Furthermore, this traditional method enables a calculation of the reduced ion mobility only after the measurement. To avoid those errors and to enable on-line calibration of ion mobility, an instrument specific factor is implemented generally representing all relevant variables. This factor can be determined from an initial measurement of few spectra and can thereafter be applied on the following measurement. The application of this approach obtained reproducible reduced ion mobility values for positive and negative ions over a broad drift time range and for common variation of ambient conditions as well for varying instrument conditions such as electric fields respectively drift times and in different drift gases. Moreover, the reduced ion mobility is available already during the measurements with a significantly higher reliability and accuracy which was increased to a factor of 5 compared to the traditional ion mobility determination and enables an on-line identification of analytes for the first time.

Empirical prediction of reduced ion mobilities of secondary alcohols

Ion Mobility Spectrometry is a powerful method for the rapid identification of gas-phase analytes and finds its usage in various fields including the sensitive analysis of extremely complex and humid mixtures such as human breath when additional pre-separation techniques are applied. The output data from an ion mobility spectrometer (IMS), equipped with a Multi-Capillary Column (MCC) for pre-separation, is a chromatogram of the signal intensity versus a particular retention time and a specific reduced ion mobility which are the characteristics of the detected analyte. Hence, it is important to have a database of analytes with both the values for comparison and identification of peaks in any IMS chromatogram. Commonly, such databases are collected by measurements of reference analytes. It is obvious that a prognosis of the values, without the time consuming and costly reference measurements, would be a considerable facilitation for a preliminary identification of unknowns and development of databases. In this study, a correlation between the reduced ion mobilities and the number of carbon atoms was found for secondary alcohols. The correlation was then used to predict the reduced ion mobilities of other analytes in the same homologous series. To verify the accuracy of the prognosis, the analytes were measured individually using a 63Ni-MCC-IMS and compared to the predicted values. The results of the prognosis show an accuracy higher than 99.5%.

Detection of undeclared erectile dysfunction drugs and analogues in dietary supplements by ion mobility spectrometry

An ion mobility spectrometry (IMS) method was developed to screen for the presence of undeclared synthetic erectile dysfunction (ED) drugs or drug analogues in herbal dietary supplements claiming to enhance male sexual performance. Ion mobility spectra of authenticated reference materials including three FDA approved drugs (sildenafil citrate, tadalafil, vardenafil hydrochloride trihydrate) and five previously identified synthetic analogues (methisosildenafil, homosildenafil, piperidenafil, thiosildenafil, thiomethisosildenafil) were measured to determine their reduced ion mobilities (K0). All eight compounds exhibited reduced mobilities between 0.8257 and 1.2876cm2/(Vs). Twenty-six herbal products were then screened for the presence of these compounds, and 15 of the 26 products tested positive for the presence of ED drug or drug analogue adulterants based on their reduced ion mobilities. IMS results were compared against the results obtained from an independent LC/MS reference method for the identical samples. Herbal dietary supplements containing adulterants were classified with 100% accuracy and most of the adulterants were correctly identified by a comparison of the K0 of the adulterant to the K0 of the authenticated reference material. The results demonstrate that IMS is a viable method for screening herbal dietary supplements for the presence of ED drug or drug analogue adulterants.

Prediction of gas-phase reduced ion mobility constants ( K0) based on the multiple linear regression and projection pursuit regression

Multiple linear regression and projection pursuit regression were used to develop the linear and nonlinear models for predicting the gas-phase reduced ion mobility constant ( K 0) of 159 diverse compounds. The six descriptors selected by heuristic method were used as the inputs of the linear and nonlinear models. The linear and nonlinear models gave very satisfactory results; the square of correlation coefficient was 0.9082 and 0.9379, the squared standard error was 0.0043 and 0.0030, respectively for the whole data set. The proposed models can identify and provide some insight into what structural features are related to the K 0 of compounds. They can also help to understand the separation mechanism in ion mobility spectrometry. Additionally, this paper provided two simple, practical and effective methods for analytical chemists to predict the K 0 of compounds in ion mobility spectrometry.

Prediction of gas-phase reduced ion mobility constants (K0).

A method of predicting reduced ion mobility values, K0, for use in ion mobility spectrometry is described. While the method is very similar to a previously reported method based on a neural network, the method described in this paper uses a purely statistical regression approach. Furthermore, it has been applied to a wider class of compounds, including chemical agents. Various molecular parameters were evaluated in the predictive model to determine the qualitative dynamics that have the greatest effect on K0. An R2 value of 80.1% was obtained when calculated K0 values were plotted against measured K0 values for 162 compounds for which experimental K0 values were available. However, when chloroacetophenone and 3-xylyl bromide (3-methylbenzyl bromide) were removed from the set due to their large residual values, the predictability increased to an R2 value of 87.4%. This compares well with the value of 88.7%, which was obtained in a regression step of a previous neural network study for a less diverse set of 168 compounds.

Electrospray Ionization Ion Mobility Spectrometry of Amino Acids: Ion Mobilities and a Mass−Mobility Correlation

As part of an ongoing effort to explore the utility of high-resolution electrospray ionization ion mobility spectrometry (ESI-IMS) for the detection and identification of organic molecules on other planetary bodies, pursuant to NASA objectives, the reduced ion mobilities of 14 amino acids that have been identified in meteoritic material were determined in both N2 and CO2 drift gases. A (12,4) hard core potential model of the ion−neutral interaction was applied to a combined data set of amino acid mobilities from the present work (abiotic) and an earlier investigation of twenty common biotic amino acids (Beegle, L. W.; Kanik, I.; Matz, L.; Hill, H. H. Anal. Chem. 2001, 73, 3028−3034). The model was used to investigate the protonated amino acid mass−mobility correlation to extract details of the ion−neutral interaction and to gain insight into the structural details of these ions.

Effects of drift-gas polarizability on glycine peptides in ion mobility spectrometry

This investigation is a continuation of our previous work on the feasibility of utilizing ultra-high resolution electrospray ionization/ion mobility spectrometry (ESI/IMS) for in situ analysis of biomolecular compounds. The compounds we studied, in this investigation, were glycine, the smallest amino acid and four of its oligomers, namely triglycine, tetraglycine, pentaglycine, and hexaglycine. Experimental effects of drift-gas polarizability on target ions in IMS were explored by utilizing four different drift-gases with differing polarizability values (He, Ar, N 2, and CO 2). The gas-phase ion radii for all five compounds were calculated from the reduced ion mobilities, K 0 m , and the effective drift-gas radii employing a simple hard-sphere model. When ion radii were plotted against the polarizabilities of the drift-gases, linear plots with different slopes were produced. This empirical observation indicated that the polarizing of drift-gas can change the calculated ion radii in a linear fashion over a limited range of polarizability values and does not affect all ions equally. This effect can be exploited in order to alter the separation factors between different ions since all ions that yield different slopes can, theoretically, be separated with IMS using different drift-gases. We demonstrated that the separation factor ( α) is highly dependent on the drift-gas. The maximum separability and, hence, unique identification of target ions was achieved when He and CO 2 were used.

Molecular Dynamics Study of the KcsA Potassium Channel

The structural, dynamical, and thermodynamic properties of a model potassium channel are studied using molecular dynamics simulations. We use the recently unveiled protein structure for the KcsA potassium channel from Streptomyces lividans. Total and free energy profiles of potassium and sodium ions reveal a considerable preference for the larger potassium ions. The selectivity of the channel arises from its ability to completely solvate the potassium ions, but not the smaller sodium ions. Self-diffusion of water within the narrow selectivity filter is found to be reduced by an order of magnitude from bulk levels, whereas the wider hydrophobic section of the pore maintains near-bulk self-diffusion. Simulations examining multiple ion configurations suggest a two-ion channel. Ion diffusion is found to be reduced to ∼1/3 of bulk diffusion within the selectivity filter. The reduced ion mobility does not hinder the passage of ions, as permeation appears to be driven by Coulomb repulsion within this multiple ion channel.

Characterizing Oligosaccharides Using Injected-Ion Mobility/Mass Spectrometry

Injected-ion mobility/mass spectrometry techniques have been used to measure the reduced ion mobilities for negatively charged raffinose, melezitose and α-, β-, and γ-cyclodextrins formed by electrospray ionization. At low injection energies, the mass spectra are dominated by negatively charged (deprotonated) parent ions. At high injection energies, the mass spectra recorded for the cyclodextrins and raffinose display peaks that result from cross-ring cleavage of individual sugar units. Melezitose dissociates by cleavage of the glycosidic bonds. The ion mobility distributions can be used to distinguish between different isomeric forms of parent and fragment ions having the same mass-to-charge ratios.

Detection of methyl isocyanate in air with the use of hand-held ion mobility spectrometers

Methyl isocyanate (MIC), CH3NCO, is a relatively simple molecule, but ion mobility spectra derived from studies of this molecule are complex. MIC is known to polymerize, which would lead one to expect that proton-bound monomer, proton-bound dimer, and even larger proton-bound ions could be observed. Indeed, this is the case, and a number of other species can also be observed. In this case headspace above a relatively fresh (i.e., recently purchased) MIC sample was analyzed, and numerous peaks were observed in a single spectrum. Peak identities and intensities were, of course, concentration dependent. Over a range of concentrations, as many as 16 peaks were observed. IMS systems used for these studies included chemical agent monitors (both water and acetone chemistry), a miniaturized hand-held IMS device (Mini-IMS) and an IMS-MS/MS instrument. Although ion mobility spectra are complex, it has been shown that hand-held IMS devices can be useful for detecting or monitoring airborne concentrations of this toxic and hazardous compound. IMS/MS/MS experimentation yielded some mass identifications, and possible ion compositions are proposed. Reduced ion mobility of H+(CH3NCO)(H2O)n was tentatively determined to be 1.91±0.02 cm2 / V s. © 1997 John Wiley & Sons, Inc. Field Analyt Chem Technol 1: 285–294, 1997

Prediction of Reduced Ion Mobility Constants of Organic Compounds from Molecular Structure

Quantitative structure-property relationships (QSPRs) are used to develop mathematical models that accurately predict the reduced ion mobility constants (K(0)) for a set of 168 organic compounds directly from molecular structure. The K(0) values are taken from an unpublished database collected by G. A. Eiceman, Chemistry Department, New Mexico State University. The data were collected using a Graseby Ionics environmental vapour monitor (EVM) gas chromatography/ion mobility spectrometer. Standardized conditions with controlled temperature, pressure, and humidity were used, and 2,4-lutidine was used as an internal standard. K(0) values were measured for all monomer peaks. The best model was found with a feature selection routine which couples the genetic algorithm with multiple linear regression analysis. The set of six descriptors was also analyzed with a fully connected, feed-forward neural network. The model contains six molecular structure descriptors and has a root-mean-square error of about 0.04 K(0) unit. The descriptors in the model lend insight into some of the important molecular features that influence ion mobility. The model can be utilized for prediction of K(0) values of compounds for which there are no empirical K(0) data.

Prediction of Reduced Ion Mobility Constants from Structural Information Using Multiple Linear Regression Analysis and Computational Neural Networks

Multiple linear regression analysis and computational neural networks are used to develop models that predict reduced ion mobility constants (K 0 ) from quantitative structural information encoded as descriptors. The errors associated with the models are similar to the calculated experimental error of ∼0.040 K 0 units. The best regression model contains five descriptors and has a multiple correlation coefficient (R) value of 0.991 and a standard deviation of 0.0469 K 0 units. The neural network model utilizes the same five descriptors and has a root mean square (RMS) error of 0.0393 K 0 units. The descriptors encode molecular size, weight, functional group, and structural classifications

Dielectric and conductivity relaxation in poly(propylene glycol)–lithium triflate complexes

The electric modulus representation is used to display conductivity and dielectric relaxation occurring in poly(propylene glycol)-4000 (PPG) complexed with LiCF3SO3, as the ether oxygen to lithium (O:Li) ratio is varied from 300:1 to 12:1. The frequency range covered is 10 to 107 Hz. Results are obtained for temperatures above the glass transition temperature appropriate for each PPG–LiCF3SO3 complex. For O:M=300:1, the conductivity peak and the α and α′ relaxation are clearly resolved. As the concentration is increased, there is a coupling between the structural and the conductivity relaxations; the various peaks begin to overlap. The coupling is greatest for an O:Li ratio in the range 30:1 to 12:1, where the highest conductivity is measured. Below room temperature, the 30:1 complex has the highest conductivity, above room temperature the 12:1 complex has the highest. At any particular temperature there is a concentration above which the conductivity drops. This drop is due to reduced ion mobility resulting from a dramatic increase in viscosity to values above ∼100 poise.

Using nonlinear fields in high pressure spectrometry

A technique for enhancing the sensitivity and resolution of commonly used ion mobility spectrometry (IMS) devices is explored experimentally and analytically. In essence, the technique uses linear and nonlinear fields in a timed sequence to control the ions such that the ions will be positioned in the drift region of an IMS device at a particular location at a particular time. By using nonlinear fields, a selected ion of reduced ion mobility ( K 0) can be trapped, controlled ion fracturing performed, and the resultant daughter ions detected (IMS/IMS). Other useful nonlinear field techniques are presented: a field sequence that negates past history of mobility by bringing all ions together, the simultaneous trapping of both positive and negatively charged ions, focusing the ions to the center of the drift region, and the sequentially clocked detection of incremental K 0 values. This presentation describes the art required for the field control and the timing sequences that will achieve the above effects and presents both experimental and computer simulated data. The hardware modifications to an IMS device to achieve optimizing of the above effects are also described.

Ion pairing in polymer electrolytes; A comparative Raman study of NaCF3SO3 complexed in poly(propylene-glycol) and dissolved in acetonitrile

Abstract Raman scattering measurements have been carried out on poly(propylene glycol) (PPG) complexed with NaCF3SO3 salt of monomer unit versus salt concentration in the range O:M=30:1−5:1. Reference spectra were obtained for the same salt dissolved in acetonitrile, CH3CN. As the salt content is increased the internal Raman modes of the salt anion increase in intensity and either increase in frequency or split. The most intense line, i.e. the symmetric SO3 stretch, was analyzed in a three line interpretation corresponding to dissociated ions, ion pairing and multiple ion aggregates. A dramatic increase of the number of anions in pairs or in multiple ion formations was observed with increasing salt content. This occurred at the expense of the number of dissociated ions which increased and later decreased with a maximum close to the concentration reported for the conductivity maximum. The conductivity drop for larger salt concentrations can however not solely be explained by the decrease in the number of available ions. The reduced ion mobility with salt concentration, as reflected in the observed shift of the D-LAM mode from 234 cm−1 of the uncomplexed PPG to ∼266 cm−1 of the complexes, is of major importance.

The mobility of H+(H2O)nions in water vapour

The mobility of positive charge carriers in water vapour has been measured using an ion swarm time-of-flight technique. A pressure range from 40 to 290 Pa and a reduced electric field from 10 to 950 Td have been adopted. The calculated zero-field reduced ion mobility is in good agreement with Langevin's polarisation limit theory and equals 0.69 cm2 V-1 s-1. The quadrupole mass analyser was applied as the ion detector.

Table of reduced mobility values from ambient pressure ion mobility spectrometry

This review presents a list of reduced ion mobilities that have been measured under ambient pressure conditions and reported in the open literature during the 16-year period of 1970-1985. Ions reported are listed in order of increasing reduced

Space charge effects in ionization type particulate detectors

The response to particulates of an ionization chamber with adjacent unipolar and bipolar zones is analyzed. Values of reduced ion mobility from particulate charging in the unipolar zone and the resulting increase in surface recombination in the bipolar zone are determined from experimental data. A solution of the general field equation as a function of distance in parallel plate geometry is plotted. The current–voltage characteristic from the general equation is compared with that from the simpler vacuum field approximation for bipolar volumes. The close agreement warrants general use of the vacuum field in ionization chambers for the small operating current densities employed in these detectors.

Dependence of polyatomic ion mobilities on ionic size

The ion mobilities of 11 negative ions in nitrogen have been measured using a plasma chromatograph. The ions range from small negative ions such as NO2− to large organic ions such as the parent negative ion of 1-naphthaldehyde, (C11H8O)−. The reduced ion mobilities for these negative ions, in addition to previously published ion mobilities of protonated hydrocarbons, were compared with the Langevin theory of ion mobility. The hard sphere average collision cross section between the ion and the neutral carrier gas N2 was estimated using two models: (1) static model where the ion is nonrotating and (2) rotational model where the ion is assumed to be rotating rapidly. Comparison of the calculated reduced ion mobilities with the experimental values reveals that the experimental collision cross sections are intermediate between those calculated using these two models. The experimental and calculated ion mobilities gave the best agreement using the mean collision cross section for the static and rotational models. The average deviation between the experimental and calculated ion mobilities was 4% for a total of 21 positive ions and 14 negative ions. These results suggest (1) the ion size is the dominant parameter affecting the ion mobility of large molecular ions and (2) the rotation of nonspherical ions must be considered.