The secret life of small alcohols: the discovery and exploitation of fragmentation, adduct formation and auto-modification phenomena in differential ion mobility spectrometry leading to next-generation toxicity screening

The research presented in this thesis started with the idea to study alcohols as modifiers and dopants in differential ion mobility spectrometry (d-IMS) to produce complicated chemical signatures to explore a concept of chemical labels for product security application. D-IMS is a gas phase atmospheric pressure separation and detection technique which distinguishes compounds based on differences in their ions mobility as their travel under a low and high electric field. The hypothesis was that alcohols will form typical d-IMS products such as protonated monomers and proton bound cluster ions. However, the very first experiments revealed unexpected phenomena which included changes in the mobility of ions over a narrow range of concentrations that could not be explained by existing theory. Another observation was the apparent regeneration of reactant ions. It became evident that the observed phenomena had not been described in the open literature and that addressing the research-questions that were being raised would be essential for the determination of alcohols by d-IMS and its use in medical applications for toxicity screening and monitoring of alcohols. The above discovery shifted the research objective towards a fundamental and comprehensive study on the behaviour of alcohols in d-IMS. This thesis describes designed experiments and constructed systems allowing the efficient study of effect of concentration, electric field and temperature on the d-IMS responses of alcohols. The results of those studies demonstate: extensive fragmentation of alcohols, including previously undescribed fragmentation patterns with regeneration of the hydrated proton; new phenomena of adduct ion formation within the d-IMS drift tube, observed in the case of methanol within a narrow range of concentration; and self-modification of the alpha function of alcohols. This knowledge was exploited by developing an non-invasive analytical method for recovery, separation and detection of toxins from human saliva (including alcohols, diols and GHB) using TD-GC-d-IMS (thermal desorption - gas chromatography d-IMS) within a full range of toxicological concentration levels

Control of dopants / modifiers in differential mobility spectrometry using a piezoelectric injector

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 seconds 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 {C4H9OH(H2O)n}+ and {2C4H9OH(H2O)n}+ 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

A benchmarking protocol for breath analysis: the peppermint experiment

Contains fulltext : 224878.pdf (publisher's version ) (Open Access

Real-time monitoring of exhaled volatiles using atmospheric pressure chemical ionization on a compact mass spectrometer

AIM: Breath analyses have potential to detect early signs of disease onset. Ambient ionization allows direct combination of breath gases with MS for fast, on-line analysis. Portable MS systems would facilitate field/clinic-based breath analyses. Results & methodology: Volunteers ingested peppermint oil capsules and exhaled volatile compounds were monitored over 10 h using a compact mass spectrometer. A rise and fall in exhaled menthone was observed, peaking at 60-120 min. Real-time analysis showed a gradual rise in exhaled menthone postingestion. Sensitivity was comparable to established methods, with detection in the parts per trillion range. CONCLUSION: Breath volatiles were readily analyzed on a portable mass spectrometer through a simple inlet modification. Induced changes in exhaled profiles were detectable with high sensitivity and measurable in real-time

The variability of volatile organic compounds in the indoor air of clinical environments

The development of clinical breath-analysis is confounded by the variability of background volatile organic compounds (VOC). Reliable interpretation of clinical breath-analysis at individual, and cohort levels requires characterisation of clinical-VOC levels and exposures. Active-sampling with thermal-desorption/gas chromatography-mass spectrometry recorded and evaluated VOC concentrations in 245 samples of indoor air from three sites in a large NHS provider trust in the UK over 27 months. Data deconvolution, alignment and clustering isolated 7344 features attributable to VOC and described the variability (composition and concentration) of respirable clinical VOC. 328 VOC were observed in more than 5% of the samples and 68 VOC appeared in more than 30% of samples. Common VOC were associated with exogenous and endogenous sources and 17 VOC were identified as seasonal differentiators. The presence of metabolites from the anaesthetic sevoflurane, and putative-disease biomarkers in room air, indicated that exhaled VOC were a source of background-pollution in clinical breath-testing activity. With the exception of solvents, and PPE waxes, exhaled VOC concentrations above 3 µg m-3 are unlikely to arise from room air contamination, and in the absence of extensive survey-data, this level could be applied as a threshold for inclusion in studies, removing a potential environmental confounding-factor in developing breath-based diagnostics

A benchmarking protocol for breath analysis: The peppermint experiment

International audienceSampling of volatile organic compounds (VOCs) has shown promise for detection of a range of diseases but results have proved hard to replicate due to a lack of standardization. In this work we introduce the 'Peppermint Initiative'. The initiative seeks to disseminate a standardized experiment that allows comparison of breath sampling and data analysis methods. Further, it seeks to share a set of benchmark values for the measurement of VOCs in breath. Pilot data are presented to illustrate the standardized approach to the interpretation of results obtained from the Peppermint experiment. This pilot study was conducted to determine the washout profile of peppermint compounds in breath, identify appropriate sampling time points, and formalise the data analysis. Five and ten participants were recruited to undertake a standardized intervention by ingesting a peppermint oil capsule that engenders a predictable and controlled change in the VOC profile in exhaled breath. After collecting a pre-ingestion breath sample, five further samples are taken at 2, 4, 6, 8, and 10 h after ingestion. Samples were analysed using ion mobility spectrometry coupled to multi-capillary column and thermal desorption gas chromatography mass spectrometry. A regression analysis of the washout data was used to determine sampling times for the final peppermint protocol, and the time for the compound measurement to return to baseline levels was selected as a benchmark value. A measure of the quality of the data generated from a given technique is proposed by comparing data fidelity. This study protocol has been used for all subsequent measurements by the Peppermint Consortium (16 partners from seven countries). So far 1200 breath samples from 200 participants using a range of sampling and analytical techniques have been collected. The data from the consortium will be disseminated in subsequent technical notes focussing on results from individual platforms