Ion mobility spectrometry (IMS), using standalone instrumentation and hyphenated with mass spectrometry (IM-MS), has recently undergone significant expansion in the numbers of users and applications, particularly in sectors outside its established user base; predominantly military and security applications. Although several IMS reference standards have been proposed, there are no currently universally recognised reference standards for the calibration and evaluation of mobility spectrometers. This review describes current practices and the literature on chemical standards for validating IMS systems in positive and negative ion modes. The key qualities and requirements an 'ideal' reference standard must possess are defined, together with the instrumental and environmental factors such as temperature, electric field, humidity and drift gas composition that may need to be considered. Important challenges that have yet to be resolved are also identified and proposals for future development presented.

Lung cancer, chronic obstructive pulmonary disease (COPD) and asthma are inflammatory diseases that have risen worldwide, posing a major public health issue, encompassing not only physical and psychological morbidity and mortality, but also incurring significant societal costs. The leading cause of death worldwide by cancer is that of the lung, which, in large part, is a result of the disease often not being detected until a late stage. Although COPD and asthma are conditions with considerably lower mortality, they are extremely distressful to people and involve high healthcare overheads. Moreover, for these diseases, diagnostic methods are not only costly but are also invasive, thereby adding to people’s stress. It has been appreciated for many decades that the analysis of trace volatile organic compounds (VOCs) in exhaled breath could potentially provide cheaper, rapid, and non-invasive screening procedures to diagnose and monitor the above diseases of the lung. However, after decades of research associated with breath biomarker discovery, no breath VOC tests are clinically available. Reasons for this include the little consensus as to which breath volatiles (or pattern of volatiles) can be used to discriminate people with lung diseases, and our limited understanding of the biological origin of the identified VOCs. Lung disease diagnosis using breath VOCs is challenging. Nevertheless, the numerous studies of breath volatiles and lung disease provide guidance as to what volatiles need further investigation for use in differential diagnosis, highlight the urgent need for non-invasive clinical breath tests, illustrate the way forward for future studies, and provide significant guidance to achieve the goal of developing non-invasive diagnostic tests for lung disease. This review provides an overview of these issues from evaluating key studies that have been undertaken in the years 2010–2019, in order to present objective and comprehensive updated information that presents the progress that has been made in this field. The potential of this approach is highlighted, while strengths, weaknesses, opportunities, and threats are discussed. This review will be of interest to chemists, biologists, medical doctors and researchers involved in the development of analytical instruments for breath diagnosis.

This experiment observed the evolution of metabolite plumes from a human trapped in a simulation of a collapsed building. Ten participants took it in turns over five days to lie in a simulation of a collapsed building and eight of them completed the 6 h protocol while their breath, sweat and skin metabolites were passed through a simulation of a collapsed glass-clad reinforced-concrete building. Safety, welfare and environmental parameters were monitored continuously, and active adsorbent sampling for thermal desorption GC-MS, on-line and embedded CO, CO(2) and O(2) monitoring, aspirating ion mobility spectrometry with integrated semiconductor gas sensors, direct injection GC-ion mobility spectrometry, active sampling thermal desorption GC-differential mobility spectrometry and a prototype remote early detection system for survivor location were used to monitor the evolution of the metabolite plumes that were generated. Oxygen levels within the void simulator were allowed to fall no lower than 19.1% (v). Concurrent levels of carbon dioxide built up to an average level of 1.6% (v) in the breathing zone of the participants. Temperature, humidity, carbon dioxide levels and the physiological measurements were consistent with a reproducible methodology that enabled the metabolite plumes to be sampled and characterized from the different parts of the experiment. Welfare and safety data were satisfactory with pulse rates, blood pressures and oxygenation, all within levels consistent with healthy adults. Up to 12 in-test welfare assessments per participant and a six-week follow-up Stanford Acute Stress Response Questionnaire indicated that the researchers and participants did not experience any adverse effects from their involvement in the study. Preliminary observations confirmed that CO(2), NH(3) and acetone were effective markers for trapped humans, although interactions with water absorbed in building debris needed further study. An unexpected observation from the NH(3) channel was the suppression of NH(3) during those periods when the participants slept, and this will be the subject of further study, as will be the detailed analysis of the casualty detection data obtained from the seven instruments used.

A thermal desorption unit has been interfaced to an electrospray ionization-ion mobilitytime-of-flight mass spectrometer. The interface was evaluated using a mixture of six model volatile organic compounds which showed detection limits of <1 ng sample loaded onto a thermal desorption tube packed with Tenax, equivalent to sampled concentrations of 4 μg L-1. Thermal desorption profiles were observed for all of the compounds, and ion mobility-mass spectrometry separations were used to resolve the probe compound responses from each other. The combination of temperature programmed thermal desorption and ion mobility improved the response of selected species against background ions. Analysis of breath samples resulted in the identification of breath metabolites, based on ion mobility and accurate mass measurement using siloxane peaks identified during the analysis as internal lockmasses. IntroductionThe development of electrospray ionization (ESI) by Fenn and co-workers in 19841enabled the routine analysis of macromolecules and revolutionized the role mass spectrometry plays in the analysis of biological samples. It was suggested as early as 19862 that volatile organic compounds (VOCs) could also be ionized and detected with a high degree of sensitivity using ESI. However the first effective demonstration of the application of ESI to VOC analysis was not reported until 1994,3 when an ESI source was interfaced to an ion mobility spectrometer. Hill and co-workers further developed this approach, termed, secondary electrospray ionization (SESI),4 in conjunction with a hybrid ion mobility-quadrupole mass spectrometer, which they used to study a number of illicit 2 drugs. The charged droplets from the electrospray were reacted with the VOCs in a reaction cell placed immediately before the ion mobility drift cell. This work demonstrated that SESI could be used as an effective ionization method for both gas chromatography (GC) and liquid chromatography-mass spectrometry (LC-MS) experiments and that it was also more sensitive than standard electrospray for the analysis of VOCs. SESI was also later used to analyze vapors from explosives with detection limits at the sub-parts per trillion level, further demonstrating the high sensitivity of the approach.5 Recent work has shown that VOCs may be detected down to parts per quadrillion levels using electrospray ionization and that the ESI source parameters can be optimized to give selectivity toward specific ion species.6 Cooks et al. proposed an alternative approach, showed that EESI could be used to follow the concentration of an exhaled breath metabolite (urea) from breath to breath.12 In the same year, Zenobi and co-workers used EESI to look directly at exhaled breath and were able to detect involatile species such as carbohydrates which were present after eating a meal.13 The analysis of breath samples using gas chromatography/ mass spectrometry (GC/MS) has shown that a large number of VOCs may be detected and that VOC profiles in human breath are characterized by a huge degre...

Bacteria are the main cause of many human diseases. Typical bacterial identification methods, for example culture-based, serological and genetic methods, are time-consuming, delaying the potential for an early and accurate diagnosis and the appropriate subsequent treatment. Nevertheless, there is a stringent need for in situ tests that are rapid, noninvasive and sensitive, which will greatly facilitate timely treatment of the patients. This review article presents volatile organic metabolites emitted from various micro-organism strains responsible for common bacterial infections in humans. Additionally, the manuscript shows the application of different analytical techniques for fast bacterial identification. Details of these techniques are given, which focuses on their advantages and drawbacks in using for volatile organic components analysis.