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Differential mobility spectrometry (DMS) is currently being used for environmental monitoring of space craft atmospheres and has been proposed for the rapid assessment of patients at accident and emergency receptions. Three studies investigated hitherto undescribed complexity in the DMS spectra of methanol, ethanol, propan-1-ol and butan-1-ol product ions formed from a 63Ni ionisation source. 54 000 DMS spectra obtained over a concentration range of 0.01 mg m−3(g) to 1.80 g m−3(g) revealed the phenomenon of auto-modification of the product ions. This occurred when the neutral vapour concentration exceeded the level required to induce a neutral-ion collision during the low field portion of the dispersion field waveform. Further, post-ionisation cluster-ion formation or protonated monomer/proton bound dimer inter-conversion within the ion-filter was indicated by apparent shifts in the values of the protonated monomer compensation field maximum; indicative of post-ionisation conversion of the protonated monomer to a proton-bound dimer. APCI-DMS-quadrupole mass spectrometry studies enabled the ion dissociation products from dispersion-field heating to be monitored and product ion fragmentation relationships to be proposed. Methanol was not observed to dissociate, while propan-1-ol and butan-1-ol underwent dissociation reactions consistent with dehydration processes that led ultimately to the generation of what is tentatively assigned as a cyclo-C3H3+ ion (m/z 39) and hydrated protons. Studies of the interaction of ion filter temperature with dispersion-field heating of product ions isolated dissociation/fragmentation product ions that have not been previously described in DMS. The implications of these combined findings with regard to data sharing and data interpretation were highlighted. [ABSTRACT FROM AUTHOR]

The non-invasive nature of volatile organic compound (VOC) sampling from skin makes this a priority in the development of new screening and diagnostic assays. Evaluation of recent literature highlights the tension between the analytical utility of ambient ionisation approaches for skin profiling and the practicality of undertaking larger campaigns (higher statistical power), or undertaking research in remote locations. This study describes how VOC may be sampled from skin and recovered from a polydimethylsilicone sampling coupon and analysed by thermal desorption (TD) interfaced to secondary electrospray ionisation (SESI) time-of-flight mass spectrometry (MS) for the high throughput screening of volatile fatty acids (VFAs) from human skin. Analysis times were reduced by 79% compared to gas chromatography-mass spectrometry methods (GC-MS) and limits of detection in the range 300 to 900 pg cm−2 for VFA skin concentrations were obtained. Using body odour as a surrogate model for clinical testing 10 Filipino participants, 5 high and 5 low odour, were sampled in Manilla and the samples returned to the UK and screened by TD-SESI-MS and TD-GC-MS for malodour precursors with greater than >95% agreement between the two analytical techniques. Eight additional VFAs were also identified by both techniques with chains 4 to 15 carbons long being observed. TD-SESI-MS appears to have significant potential for the high throughput targeted screening of volatile biomarkers in human skin. [ABSTRACT FROM AUTHOR]

An electrospray ionisation triple quadrupole mass spectrometer (Varian 1200 L) was modified to accept nitrogen samples containing low concentrations of volatile organic compounds. Six candidate probe compounds, methyl decanoate, octan-3-one, 2-ethylhexanoic acid, 1,4-diaminobutane, dimethyl methylphosphonate, and 2,3-butanediol, at concentrations below 50 ppb(v) were generated with permeation tubes in a test atmosphere generator. The concept of using a set of molecular probes to evaluate gas-phase electrospray ionisation of volatile analytes was assessed and the feasibility of adopting a unified ionisation approach for gas and liquid contamination of exobiotic environments established. 450 experiments were run in a five-replicate, fifteen-level, three-factor, central-composite-design with exponential dilution for each of the six probe compounds studied. The three factors studied were ionisation voltage, drying-gas flow and nebulising-gas flow. Parametric modelling by regression analysis enabled the differences in the ionisation behaviours of the probe compounds to be described by the optimisation models. Regression coefficients were in the range 0.91 to 0.99, indicating satisfactory levels of precision in the optimisation models. A wide range in ionisation efficiency was observed, with different optimised conditions required for the probe compounds. It was evident that no one factor appeared to dominate the response and the different factors produced different effects on the responses for the different molecules. 1,4-Butanediamine and dimethyl methylphosphonate required significantly lower ionisation voltages (1.2 kV) than the other four, which achieved optimised sensitivity towards the maximum voltage used in this design (5 to 6 kV). Drying-gas flow rates were found to be more important than nebulising-gas flow rates. However, variations in the constant term B0in the optimisation models indicated that other factors, not included in this study, were also likely to be involved in the ionisation process. Electrolyte-flow rate and ionisation temperature were proposed for follow up studies. Exponential dilution data indicated sensitive and analytically useful responses in the target range of 5 to 50 ppb(v) for all six compounds. Significantly, responses were seen at concentrations significantly below 5 ppb(v), with sub ppt(v) responses observed for 1,4-butanediamine, 2-ethylhexanoic acid, dimethylmethylphosphonate, and 1,3-butanediol. Responses in the ppt(v) to ppb(v) range were observed for the remaining two compounds. The observations from this study demonstrated the utility of adopting a set of probe compounds to evaluate electrospray ionisation performance for volatile organic compound based assays; indicated the existence of multiple ionisation mechanisms; and revealed potential sensitivity at the parts per quadrillion level ppq(v). [ABSTRACT FROM AUTHOR]

The rapid, accurate and non-invasive diagnosis of respiratory disease represents a challenge to clinicians, and the development of new treatments can be confounded by insufficient knowledge of lung disease phenotypes. Exhaled breath contains a complex mixture of volatile organic compounds (VOCs), some of which could potentially represent biomarkers for lung diseases. We have developed an adaptive sampling methodology for collecting concentrated samples of exhaled air from participants with impaired respiratory function, against which we employed two-stage thermal desorption gas chromatography-differential mobility spectrometry (GC-DMS) analysis, and showed that it was possible to discriminate between participants with and without chronic obstructive pulmonary disease (COPD). A 2.5 dm3volume of end tidal breath was collected onto adsorbent traps (Tenax TA/Carbotrap), from participants with severe COPD and healthy volunteers. Samples were thermally desorbed and analysed by GC-DMS, and the chromatograms analysed by univariate and multivariate analyses. Kruskal–Wallis ANOVA indicated several discriminatory (p< 0.01) signals, with good classification performance (receiver operator characteristic area up to 0.82). Partial least squares discriminant analysis using the full DMS chromatograms also gave excellent discrimination between groups (α= 19% and β= 12.4%). [ABSTRACT FROM AUTHOR]

Evaluation of published methods reveals that existing methods for saliva sampling do not address the physical-chemical attributes of volatile organic compounds (VOCs). This study describes and presents evidence for adopting in situ sampling of salivary VOCs directly from the oral cavity using a polydimethylsiloxane (PDMS) based sampler. In vitro studies indicated that the vapour pressure of analytes was a factor in both the recovery of analytes and the precision of the recovery. The highest recoveries were observed for VOCs with the lowest vapour pressures, for example 5-nonanol (vapour pressure (P(v)) = 14 Pa) recoveries were approximately 20 times greater than those observed for octane (P(v) = 1726 Pa). Similarly, relative standard deviations reduced with vapour pressure, with the RSD for 5-nonanol responses observed to be 2.7% when compared to RSD = 26% for octane. Evaluation of VOCs recovered from 6 in vivo samples indicated that VOC concentrations in saliva may follow log-normal distributions; log-normal RSDs falling between 4.4% and 18.2% across the range of volatilities encountered. Increasing sampling time from 1 to 30 minutes indicated that the recovery of VOC into the sampler was affected by interaction between different physical-chemical properties and biogenic flux. A sampling time of 10 min was found to offer an acceptable compromise that enabled a representative sample to be acquired for the widest range of observed VOC behaviours with the sampler. The potential to 'tune' the sampling protocol for targeted analysis based on these factors was also noted. Comparison with passive drool saliva collection revealed up to 10(5) enhancement with reduced variability compared to drooled samples. This approach to in situ saliva sampling appears to have significant analytical utility for studying volatile signatures in humans.

A piezoelectric injector has been interfaced to a differential mobility spectrometer to enable fast and reversible control of dopant/transport-gas modifier levels within the reaction region of the instrument. Operating at 1 Hz with optimised bipolar waveforms for the piezoelectric injector and gas flows within the injector, steady-state 2-butanol mass fluxes of 21 to 1230 ng min(-1) and 1-bromohexane mass fluxes of 149 to 2644 ng min(-1) were delivered to the differential mobility cell. Control of split-flow and transport-gas flow rates enabled rapid and flexible control of the dopant concentrations. The system was consistently reproducible with a relative standard deviation (RSD) of 7.9% at every mass- flux level studied. Stable responses were achieved between 3 to 5 s following a change in the control levels and no significant hysteresis effects were observed. In the positive mode it was possible to control the extent of formation protonated monomer and proton bound cluster ions, tentatively assigned to{C(4)H(9)OH(H(2)O)(n)H}(+) and {(C(4)H(9)OH)(2)(H(2)O)(n)H}(+) and similar control was possible in the negative mode where the concentration relationship for the formation of bromide clusters indicated the presence of multiple ionisation mechanisms. A dopant formulation for the simultaneous control of ions in both the positive and negative modes was demonstrated by the injection of a 50%/50% v/v solution of 2-butanol/1-bromohexane with mass fluxes of 2-butanol in the mixture of between 11 and 1161 ng min(-1) and between 13 and 1325 ng min(-1) for 1-bromohexane.

Discrimination of bacteria was investigated using pyrolysis-gas chromatography-differential mobility spectrometry (Py-GC-DMS). Three strains belonging to the genus Bacillus were investigated and these included two strains of Bacillus subtilis and a single Bacillus megaterium. These were chosen so as to evaluate the possibility of bacterial strain discrimination using Py-GC-DMS. The instrument was constructed in-house and the long-term reproducibility of the instrument was evaluated over a period of 60 days using a Scotch whisky quality control. To assess the reproducibility further each bacterium was cultured six times and each culture was analysed in replicate to give three analytical replicates. The DMS data were generated in both positive and negative modes, and the data in each mode were analysed independently of each other. The Py-GC-DMS data were pre-processed via correlation optimised warping (COW) and asymmetric least square (ALS) to align the DMS chromatograms and to remove any unavoidable baseline shifts, prior to normalisation. Processed chromatograms were analysed using principal component analysis (PCA) followed by supervised learning methodology using partial least squares for discriminant analysis (PLS-DA). It was found that the separations between B. subtilis and B. megaterium can be readily observed by PCA; however, strain discrimination within the two B. subtilis was only possible using supervised learning. As multiple biological replicates were analysed an exhaustive splitting of the training and test sets was undertaken and this allowed correct classification rates (CCRs) to be assessed for the 3375 test sets. It was found that with PLS-DA the negative ion mode DMS data were more discriminatory than the positive mode data.

A thermally-desorbed polydimethylsilicone (PDMS) membrane approach with analysis by gas chromatography-mass spectrometry has been developed and characterised, to enable the VOC arising in, and on skin, from glandular secretions, exogenous materials, products of perfusion from blood, and microbiological metabolites to be sampled in a single procedure. In-vitro studies using a series of volatile fatty acid standards indicated that the recovery efficiency of the technique increased with decreasing volatility; for example, the recovery of hexanoic acid was 3.3 times greater than that for 2-methylpropanoic acid. The relative standard deviation of the methodology decreased with decreasing volatility; RSD = 19% for 2-methylpropanoic acid and RSD = 7% for hexanoic acid. Sampled-mass vs. response relationships were modelled satisfactorily using linear regression analysis with regression coefficients in the range 0.95 to 0.998. In-vivo reproducibility was assessed though the analysis of the responses of 1-dodecane, 3,7-dimethyloct-1-ene, 2-propenoic acid, 2-ethylhexyl ester, 2-ethylhexan-1-ol, butanoic, 2-ethylhexylester, and junipen (1,4-methanoazulene, decahydro-4,8,8-trimethyl-9-methylene-); six compounds selected at random retention times from a GC-MS chromatographic VOC profile of human skin containing several hundred resolved and partially resolved compounds. Five samples were obtained simultaneously from the forearm of a healthy male participant. The in-vivo sample masses were estimated to be in the range 50 pg to 100 ng per sample with observed RSD falling between 15% and 32%; in line with a Horwitz trend. Increasing the sample time from 5 min to 120 min generally resulted in an enrichment of the VOC recovered, and for many VOC substantial increases in sensitivity (x7) were observed over this time range as the PDMS sampling-patch approached equilibrium with the underlying skin. Nevertheless, more volatile components, 2,4,6-trimethylcarbazole for instance, were observed to be lost from the analysis with increasing sample time, in a manner analogous with breakthrough behaviour in adsorbent traps. Finally, a 10 day storage study at 4 degrees C suggested that micro-biological factors were significant in their effect on sample stability. Significant changes (up to x8) were observed in the masses of compounds recovered post storage. These studies confirmed that polydimethylsilicone membrane sampling patches of human skin provide rich and analytical useful data. It is important to note that care in experimental design is needed to avoid sampling artefacts being introduced through sampling selectivity, and/or, sample instability where samples are stored for longer than 24 h at 4 degrees C or higher.

An adaptive sampler for collecting 2.5 dm(3) samples of exhaled air from human subjects with an impaired respiratory function is described. Pressure in the upper respiratory tract is continuously monitored and the data used to control an automated system to collect select portions of the expired breathing cycle onto a mixed bed Tenax(trade mark) and Carbotrap(trade mark) adsorbent trap for analysis by GC-MS. The sampling approach is intended for use in metabolomic profiling of volatiles in human breath at concentrations greater than microg m(-3). The importance of experimental reproducibility in metabolomic data is emphasised and consequently a high purity air supply is used to maintain a stable exogenous volatile organic compound profile at concentrations in the range 5 to 30 microg m(-3). The results of a 90 day stability study showed that exogenous VOCs were maintained at significantly lower levels (40 times lower for isopropyl alcohol) and with significantly higher reproducibility (80 times lower standard deviation for isopropyl alcohol) than would have been be the case if ambient air had been used. The sampling system was evaluated with healthy controls alongside subjects with chronic obstructive pulmonary disease. Subjects were able to breathe normally with control subjects observed to breathe at a rate of 9 to 17 breaths per minute, compared to 16 to 30 breaths per minute for subjects with COPD. This study presents, for the first time, observations and estimates of intra-subject breath sample reproducibility from human subjects. These reproducibility studies indicated that VOCs in exhaled breath exhibit a variety of dynamic behaviours, with some species recovered with a RSD <30%, while other species were observed to have significantly more variable concentrations, 30 to 130% RSD. The approach was also demonstrated to reliably differentiate the differences in the VOC profiles between alveolar and dead space air.

The development of high-throughput environmental screening assays are needed to meet high-specification data quality objectives (DQOs) that require large numbers of samples to be taken and analysed rapidly. The acquisition and stabilisation of the sample is a key technical and operational challenge in analytical sequences associated with the determination of volatile organic compound (VOC) contamination of soils. Further the development of miniaturised and embedded analytical systems for environmental conditioning monitoring requires the development of new sampling techniques. A proof-of-concept study is described that shows how pressurised gas, in this case carbon dioxide, may be used to recover reversibly-bound VOCs from soil into an adsorbent sampler, and then analysed by thermal desorption-gas chromatography. The effects of the volume of the pressurised gas, the gas flow rate and the mass of the soil sample on the recovery efficiency and breakthrough from the adsorbent trap were investigated in a preliminary characterisation study. Two distinct approaches were identified. The first involved ventilation of the voids within the soil matrix to displace the soil-gas headspace, a rapid screening approach. The second involved a more prolonged purge of the matrix to strip reversibly bound species into the gas phase and hence pass them into the adsorbent trap, a purge and trap approach. The shortest possible sample processing time required to yield analytically useful responses was 5 s with the use of the headspace approach. In this case n-octane, benzene and toluene were recovered from conditioned spiked soil samples at concentrations in the range 42 to 1690 mg kg(-1). The limit of detection for the system was estimated to be no greater than 1.2 mg kg(-1). Using the purge and trap variant enabled recovery efficiencies greater than 93% to be achieved with liquid spikes of n-octane onto soil samples. These preliminary studies showed that a system based on this approach would need to balance recovery efficiency, time and analyte breakthrough from the adsorbent trap.

A pulsed corona discharge ionisation source, a candidate replacement for 63Ni ionisation sources for ion mobility spectrometry, is described along with a new design of ion mobility spectrometer-mass spectrometer. Preliminary research on the characterisation of the reactant ion peaks associated with the use of this ionisation source was undertaken by assembling a pulsed corona discharge ionisation switchable high-resolution ion mobility spectrometer-mass spectrometer to enable the mobility spectra, atmospheric chemical ionisation mass spectra and selected-mass mobility spectra to be obtained. With ammonia doping at 2.39 mg m(-3) in air and a water content of approximately 80 mg m(-3) in the positive mode the observed response was attributable to the formation of 1(H2O)(n)NH4]+ and [(H2O)n(NH3)NH4]+ in the reaction region. The observed responses in the negative mode were more complex with evidence for the formation [(H2O)(n)O2]-, [(H2O)(n)CO3]-, [(H2O)(n)HCO3]-, [(H2O)(n)CO4]- and [(H2O)(n)NO3]-. The responses due to these species were clearly discernible in the resultant mobility spectra, with enough oxygen-based species formed to support analytically useful responses.

A membrane inlet 63Ni ion mobility spectrometer interfaced to a quadrupole mass spectrometer with permeation, exponential dilution approaches and syringe-based systems were used to characterise the ion mobility spectrometry (IMS) response to phosgene in dry air (water concentration less than 16.5 mg m(-3)). Phosgene produced a principle product ion in the negative mode with a reduced mobility of 2.16 cm2 V(-1) s(-1), with an unresolved artefact at higher concentrations having a reduced mobility of 2.32 cm2 V(-1) s(-1). The limit of detection of the system with a membrane inlet fitted was estimated to be less than 1 mg m(-3), with an upper limit to the dynamic range of 32 mg m(-3). Mass spectrometric data indicated the existence of [(H2O)nCl]-, [(H2O)nCl2]-; [(H2O)n(O2)Cl]-; [(H2O)n(O)Cl]-; and, [(H2O)n(CO2)Cl]-. The existence of two possible mechanisms for product ion formation is proposed: dissociative electron capture, as well as hydrolysis followed by electron capture. The effect of water contamination of the drying media within the ion mobility spectrometer was also investigated, and the effects were similar to those observed previously with studies on chlorine. Reduced mobility of the product ions was observed to decrease with increasing water contamination of the drying media used within the instrument, while limits of detection increased slightly to less than 2.4 mg m(-3), with no significant effect on dynamic ranges of response or resolution. Preliminary results also indicated a positive mode response for phosgene, albeit at significantly higher concentrations to those observed in the negative mode.