Correlation analysis on data sets to detect infectious agents in the airways by ion mobility spectrometry of exhaled breath

A correlation analysis of peaks found in IMS-Chromatograms was carried out to show the potential of the method in clinical applications. As an example, the data of exhaled breath of patients suffering infections of Pseudomonas were compared to healthy non-smokers. Using a rank sum calculation and providing a correlation table of all peaks found, delivers the basis for visualisation of highest ranked analytes. In addition, a consideration of positive and negative correlated peaks could support sub-grouping, if present. A set of signals could be found for discriminating the two groups of patients using MCC-IMS. Investigations of exhaled breath using ion mobility spectrometry seems to provide a promising means for the non-invasive identification of patients which are colonized or infected with bacteria such as Pseudomonas aeruginosa.     

Detection of explosives by ion mobility spectrometry

Ion mobility spectrometry is an effective method for detecting mine-explosive devices and explosive charges and for revealing objects and peoples who came into contact with explosives. This is because of the excellent analytical and performance characteristics of the corresponding instruments. In the present work, we described the objects to be detected, formulated the basic terms and definitions, considered the physicochemical basics of the separation of ions by their mobility in a gas under an electric field, and presented experimental data on the main analytical characteristics of spectrometers: their ability to identify analytes, resolution power, time to provide readings, sensitivity, and detection limit.     

Detection of volatile organic compounds (VOCs) in exhaled breath of patients with chronic obstructive pulmonary disease (COPD) by ion mobility spectrometry

COPD is a disease characterised by a chronic inflammation of the airways and a not fully reversible airway obstruction. The spirometry is considered as gold-standard to diagnose the disease and to grade its severity. In this study we used the methodology of Ion Mobility Spectometry in order to detect Volatile Organic Compounds (VOCs) in exhaled breath of patients with COPD. The purpose of this study was to investigate if the VOCs detected in patients with COPD were different from the VOCs detected in exhaled breath of healthy controls. 13 COPD patients and 33 healthy controls were included in the study. Breath samples were collected via a side-steam Teflon tube and directly measured by an ion mobility spectrometer coupled to a multi capillary column (MCC/IMS). One peak was identified only in the patients group compared to the healthy control group. Consequently, the analysis of exhaled breath could be a useful tool to diagnose COPD.     

Selected ion flow tube mass spectrometry of exhaled breath condensate headspace

Collection of exhaled breath condensate (EBC) is a relatively simple noninvasive method of breath analysis; however, no data have been reported that would relate concentration of volatile compounds in EBC to their gaseous concentrations in exhaled air. The aim of the study was to investigate which volatile compounds are present in EBC and how their concentrations relate to results of direct breath analysis. Thus, samples of EBC were collected in a standard way from several subjects and absolute levels of several common volatile breath metabolites (ammonia, acetone, ethanol, methanol, propanol, isoprene, hydrogen cyanide, formaldehyde and acetaldehyde) were then determined in their headspace using selected ion flow tube mass spectrometry (SIFT-MS). Results are compared with those from on-line breath analyses carried out immediately before collecting the EBC samples. It has been demonstrated that SIFT-MS can be used to quantify the concentrations of volatiles in EBC samples and that, for methanol, ammonia, ethanol and acetone, the EBC concentrations correlate with the direct breath levels. However, the EBC concentrations of isoprene, formaldehyde, acetaldehyde, hydrogen cyanide and propanol do not correlate with direct breath measurements. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Detection of perfluorocarbons using ion mobility spectrometry

An ISAS custom-designed ion mobility spectrometer equipped with a ionization source is used for the sensitive detection of traces of perfluorocarbons (PFCs, C₅F₁₂ to C₉F₂₀) in air, a class of substances for which a growing interest for industrial and environmental applications arose within the last years. Mobility spectra of the PFCs are presented, compared and discussed with regard to the possibility of identifying these analytes; detection limits are determined to be in the upper ng l⁻¹ range. Using a specific PFC as an example, a way to prevent unwanted contributions of non-product ions, the difference mobility spectrum, is introduced and described. Advantages and possibilities of this technique are briefly discussed.     

The quantification of carbon dioxide in humid air and exhaled breath by selected ion flow tube mass spectrometry

The reactions of carbon dioxide, CO₂, with the precursor ions used for selected ion flow tube mass spectrometry, SIFT‐MS, analyses, viz. H₃O⁺, NO⁺ and O, are so slow that the presence of CO₂ in exhaled breath has, until recently, not had to be accounted for in SIFT‐MS analyses of breath. This has, however, to be accounted for in the analysis of acetaldehyde in breath, because an overlap occurs of the monohydrate of protonated acetaldehyde and the weakly bound adduct ion, H₃O⁺CO₂, formed by the slow association reaction of the precursor ion H₃O⁺ with CO₂ molecules. The understanding of the kinetics of formation and the loss rates of the relevant ions gained from experimentation using the new generation of more sensitive SIFT‐MS instruments now allows accurate quantification of CO₂ in breath using the level of the H₃O⁺CO₂ adduct ion. However, this is complicated by the rapid reaction of H₃O⁺CO₂ with water vapour molecules, H₂O, that are in abundance in exhaled breath. Thus, a study has been carried out of the formation of this adduct ion by the slow three‐body association reaction of H₃O⁺ with CO₂ and its rapid loss in the two‐body reaction with H₂O molecules. It is seen that the signal level of the H₃O⁺CO₂ adduct ion is sensitively dependent on the humidity (H₂O concentration) of the sample to be analysed and a functional form of this dependence has been obtained. This has resulted in an appropriate extension of the SIFT‐MS software and kinetics library that allows accurate measurement of CO₂ levels in air samples, ranging from very low percentage levels (0.03% typical of tropospheric air) to the 6% level that is about the upper limit in exhaled breath. Thus, the level of CO₂ can be traced through single time exhalation cycles along with that of water vapour, also close to the 6% level, and of trace gas metabolites that are present at only a few parts‐per‐billion. This has added a further dimension to the analysis of major and trace compounds in breath using SIFT‐MS. Copyright © 2009 John Wiley & Sons, Ltd.     

Quantification of methane in humid air and exhaled breath using selected ion flow tube mass spectrometry

In selected ion flow tube mass spectrometry, SIFT‐MS, analyses of humid air and breath, it is essential to consider and account for the influence of water vapour in the media, which can be profound for the analysis of some compounds, including H₂CO, H₂S and notably CO₂. To date, the analysis of methane has not been considered, since it is known to be unreactive with H₃O⁺ and NO⁺, the most important precursor ions for SIFT‐MS analyses, and it reacts only slowly with the other available precursor ion, O. However, we have now experimentally investigated methane analysis and report that it can be quantified in both air and exhaled breath by exploiting the slow O/CH₄ reaction that produces CH₃O ions. We show that the ion chemistry is significantly influenced by the presence of water vapour in the sample, which must be quantified if accurate analyses are to be performed. Thus, we have carried out a study of the loss rate of the CH₃O analytical ion as a function of sample humidity and deduced an appropriate kinetics library entry that provides an accurate analysis of methane in air and breath by SIFT‐MS. However, the associated limit of detection is rather high, at 0.2 parts‐per‐million, ppm. We then measured the methane levels, together with acetone levels, in the exhaled breath of 75 volunteers, all within a period of 3 h, which shows the remarkable sample throughput rate possible with SIFT‐MS. The mean methane level in ambient air is seen to be 2 ppm with little spread and that in exhaled breath is 6 ppm, ranging from near‐ambient levels to 30 ppm, with no significant variation with age and gender. Methane can now be included in the wide ranging analyses of exhaled breath that are currently being carried out using SIFT‐MS. Copyright © 2010 John Wiley & Sons, Ltd.     

Detection of emissions from surfaces using ion mobility spectrometry

Emissions from surfaces (from furniture, wall paintings or floor coverings for instance) significantly influence indoor air quality and therefore the wellbeing or even the health of the occupants. Together with metabolites from mold they are responsible for the well-known “sick building syndrome”. Therefore, it is in the interest of the manufacturer as well as of the occupants to have a fast and accurate method for the detection of substances relevant to this syndrome in order to be able to monitor and control product quality and indoor air quality. The use of small and easy-to-transport ion mobility spectrometers that use UV light as the ionization source enables rapid in situ detection of such substances with high selectivity and sensitivity (detection limits in the lower ppb range). If a multicapillary column is used for preseparation as well, the selectivity is increased and the unwanted influence of humidity on the spectra can be eliminated, thus enabling the use of the instruments under normal ambient conditions. Furthermore, the use of air as carrier gas avoids the need for other sources of high-purity gas. An emission cell with a homogeneous and constant air flow over the surface to be investigated was developed in order to ensure reproducible results. Investigations of emissions from wooden surfaces with and without additional contamination as well as from complex mixtures are presented. The results demonstrate that relevant emissions can be identified and quantified with high sensitivity and selectivity in under five minutes. Therefore, the method is useful for indoor air quality monitoring, especially when miniaturized instruments are applied. Figure     

Detection of acrylamide vapors by ion mobility increment spectrometry at reduced pressures

A possibility of the detection of acrylamide from aqueous solutions at reduced pressures using an ion mobility increment spectrometer-mass spectrometer has been studied. An increase in instrumental resolution for ions containing acrylamide and obtained by coevaporation from an aqueous matrix at reduced pressures from 1 to 0.4 atm has been demonstrated.     

One-year time series of investigations of analytes within human breath using ion mobility spectrometry

Ion mobility Spectrometry is used to detect volatile analytes within human breath directly. Many volatile organic compounds (VOC) show significant day-to-day variation in the signal height related to the concentration of the analyte, although the breath collection had been performed under the same conditions with respect to similar sampling procedure, similar dead volume, similar measurement time, and measurement conditions. Variations of 8 different analytes are investigated over a time period of 11 months in the exhaled breath of the same person in the same room environment. The individual variability is reported for Benzothiazole; D-Limonene; Eucalyptol; Decamethylcyclopentasiloxane; Decanal; 1-Hexanol, 2-ethyl-; Cyclohexanone, 5-methyl-2-(1-methylethyl) and Nonanal. The paper shows, that the individual variability must be taken into consideration to relate the findings to medical questions. Therefore, the room air concentration of VOCs must be taken into account, so that the difference between exhaled and inhaled air has to be used as indicator. Finally, starting with individual variabilities, the normal variation related to the specific analyte should be considered in addition.     

An exploratory comparative study of volatile compounds in exhaled breath and emitted by skin using selected ion flow tube mass spectrometry

Selected ion flow tube mass spectrometry (SIFT-MS) has been used to carry out a pilot parallel study on five volunteers to determine changes occurring in several trace compounds present in exhaled breath and emitted from skin into a collection bag surrounding part of the arm, before and after ingesting 75 g of glucose in the fasting state. SIFT-MS enabled real-time quantification of ammonia, methanol, ethanol, propanol, formaldehyde, acetaldehyde, isoprene and acetone. Following glucose ingestion, blood glucose and trace compound levels were measured every 30 min for 2 h. All the above compounds, except formaldehyde, were detected at the expected levels in exhaled breath of all volunteers; all the above compounds, except isoprene, were detected in the collection bag. Ammonia, methanol and ethanol were present at lower levels in the bag than in the breath. The aldehydes were present at higher levels in the bag than in breath. The blood glucose increased to a peak about 1 h post-ingestion, but this change was not obviously correlated with temporal changes in any of the compounds in breath or emitted by skin, except for acetone. The decrease in breath acetone was closely mirrored by skin-emitted acetone in three volunteers. Breath and skin acetone also clearly change with blood glucose and further work may ultimately enable inferences to be drawn of the blood glucose concentration from skin or breath measurements in type 1 diabetes.     

Separation of amino acids by ion mobility spectrometry

The mobilities of the 20 common amino acids were determined by electrospray ionization ion mobility spectrometry. It was found that each amino acid had a different drift time and hence a different reduced mobility constant K0. This difference in drift time was less than 0.1 ms in many cases. With the instrument used in this study it would not be possible to resolve mixtures of some of the amino acids. It would however be possible to determine any single amino acid. In addition, the detection limits were determined for the 20 amino acids. They ranged from 50 to 700 pg. This indicates that the detection limits were less than 3 pmol for all of the amino acids and that many amino acids had detection limits less than 1 pmol.     

Chemical standards in ion mobility spectrometry

Positive ion mobility spectra for three compounds (2,4-dimethylpyridine (2,4-DMP, commonly called 2,4-lutidine), dimethyl methylphosphonate (DMMP) and 2,6-di-t-butyl pyridine (2,6-DtBP)) have been studied in air at ambient pressure over the temperature range 37-250 °C with (H₂O)_nH⁺ as the reactant ion. All three compounds yield a protonated molecule but only 2,4-dimethylpyridine and dimethyl methylphosphonate produced proton-bound dimers. The reduced mobilities (K₀) of protonated molecules for 2,4-dimethylpyridine and DMMP increase significantly with increasing temperature over the whole temperature range indicating changes in ion composition or interactions; however, K₀ for the protonated molecule of 2,6-di-t-butyl pyridine was almost invariant with temperature. The K₀ values for the proton-bound dimers of 2,4-dimethylpyridine and DMMP also showed little dependence on temperature, but could be obtained only over an experimentally smaller and lower temperature range and at elevated concentrations. Chemical standards will be helpful as mobility spectra from laboratories worldwide are compared with increased precision and 2,6-di-t-butyl pyridine may be a suitable compound for use in standardizing reduced mobilities. The effect of thermal expansion of the drift tube length on the calculation of reduced mobilities is emphasized.     

Orthogonal extraction ion mobility spectrometry

Ion Mobility Spectrometry is a powerful tool for the study of molecular conformations, separation of mass isomers, and analysis of complex mixtures and suppression of chemical background. The factors that limit the capabilities of the technique include its relatively low resolving power and duty cycle. New principle of gas-phase ion separation, based on ion focusing under the influence of electrostatic field and stationary in time gas flow, is proposed. Both analytical calculations and a numerical simulation show that a diffusion-limited resolution of several hundred can be achieved. The new type of ion mobility analyzer is called orthogonal extraction IMS. The proposed ortho-IMS can be interfaced with commercial mass spectrometers and offers the theoretical resolution of several hundred and ion transmission close to 100%.     

Liquid phase ion mobility spectrometry

A novel analytical method, called Liquid Phase Ion Mobility Spectrometry (LiPIMS) was demonstrated, where aqueous phase analytes were ionized and introduced into non-aqueous liquids, transported by an external electric field from the point of generation to a collection electrode. Ions were produced from a unique liquid phase ionization process, called Electrodispersion Ionization. Spectra of analyte ions illustrated the potential of LiPIMS as a new separation technique. Experimental data showed that electrodispersion ionization was effective in generating nanoampere level of ion current in hexane and benzene from aqueous samples. By controlling the ionization voltage in relation to the sample flow rate, it was possible to operate the electrodispersion ionization source in both continuous and pulsed ionization modes. Unique LiPIMS spectra of aqueous samples of tetramethylammonium bromide, tetrabutylammonium bromide and bradykinin were presented and their respected liquid phase ion mobility values were determined.     

Shapes of supramolecular cages by ion mobility mass spectrometry

Mass spectrometry and drift tube ion mobility mass spectrometry have been used to analyse several isobaric, multicomponent cages yielding information on three dimensional structure, interactions and dynamics of assembly in the gas phase.