This method was found to be acceptable for children, and healthy and asthmatic individuals were distinguished on the basis of eight VOCs at elevated levels in the breath of asthmatic children.

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...

This approach facilitated more efficient data modeling and a case study from a 22-participant (10 male, 12 female) stress-intervention experiment. Principal component analysis of data registered by retention indexing did not classify successfully stressed from unstressed states. By contrast, adoption of a breath matrix approach enabled 95% separation.

A two-stage thermal desorption/secondary electrospray ionization/time-of-flight mass spectrometry for faster targeted breath profiling has been studied. A new secondary electrospray ionization (SESI) source was devised to constrain the thermal desorption plume and promote efficient mixing in the ionization region. Further, a chromatographic pre-separation stage was introduced to suppress interferences from siloxanes associated with thermal desorption profiles of exhaled breath samples. In vitro tests with 5-nonanone indicated an increased sensitivity and a lowered limit-of-detection, both by a factor of ~4, the latter to an on-trap mass of 14.3 ng, equivalent to a sampled breath concentration of 967 pptv. Analysis of the mass spectrometric responses from 20 breath samples acquired sequentially from a single participant indicated enhanced reproducibility (reduced relative standard deviations (RSD) for 5-nonanone, benzaldehyde and 2-butanone were 28 %, 16% and 14% respectively. The corresponding values for an open SESI source were that 5-nonanone was not detected, with %RSD of 39% for benzaldehyde and 31% for 2-butanone). The constrained source with chromatographic pre-separation resulted in an increase in the number of detectable volatile organic compounds (VOCs) from 260 mass spectral peaks with an open SESI source to 541 peaks with the constrained source with pre-separation. Most of the observed VOCs were present at trace levels, at less than 2.5% of the intensity of the base peak. Seventeen 2.5 dm3 distal breath samples were collected from asthma patients and healthy controls respectively, and subjected to comparative high-throughput screening using thermal desorption/SESI/time-of-flight mass spectrometry (TD-SESI-ToFMS). Breath metabolites were detected by using a background siloxane ion (hexamethylcyclotrisiloxane m/z 223.0642) as an internal lockmass. Eleven breath metabolites were selected from the breath research literature and successfully targeted. These data reinforce the proposition that TD-SESI-MS has potential for development as a rapid screening method for disease stratification and targeted metabolism profiling.