•Quantification of volatiles emitted by human skin by SPME-GCMS.•Determination of emission rates of 64 skin-borne species.•Selection of potential skin-borne markers of human presence for rescue ...applications.
Gas chromatography with mass spectrometric detection (GC–MS) coupled with solid phase micro-extraction as pre-concentration method (SPME) was applied to identify and quantify volatile organic compounds (VOCs) emitted by human skin. A total of 64 C4-C10 compounds were quantified in skin emanation of 31 healthy volunteers. Amongst them aldehydes and hydrocarbons were the predominant chemical families with eighteen and seventeen species, respectively. Apart from these, there were eight ketones, six heterocyclic compounds, six terpenes, four esters, two alcohols, two volatile sulphur compounds, and one nitrile. The observed median emission rates ranged from 0.55 to 4790fmolcm−2min−1. Within this set of analytes three volatiles; acetone, 6-methyl-5-hepten-2-one, and acetaldehyde exhibited especially high emission rates exceeding 100fmolcm−2min−1. Thirty-three volatiles were highly present in skin emanation with incidence rates over 80%. These species can be considered as potential markers of human presence, which could be used for early location of entrapped victims during Urban Search and Rescue Operations (USaR).
The stability of 41 selected breath constituents in three types of polymer sampling bags, Tedlar, Kynar, and Flexfilm, was investigated using solid phase microextraction and gas chromatography mass ...spectrometry. The tested molecular species belong to different chemical classes (hydrocarbons, ketones, aldehydes, aromatics, sulphurs, esters, terpenes, etc.) and exhibit close-to-breath low ppb levels (3-12 ppb) with the exception of isoprene, acetone and acetonitrile (106 ppb, 760 ppb, 42 ppb respectively). Stability tests comprised the background emission of contaminants, recovery from dry samples, recovery from humid samples (RH 80% at 37 °C), influence of the bag's filling degree, and reusability. Findings yield evidence of the superiority of Tedlar bags over remaining polymers in terms of background emission, species stability (up to 7 days for dry samples), and reusability. Recoveries of species under study suffered from the presence of high amounts of water (losses up to 10%). However, only heavier volatiles, with molecular masses higher than 90, exhibited more pronounced losses (20-40%). The sample size (the degree of bag filling) was found to be one of the most important factors affecting the sample integrity. To sum up, it is recommended to store breath samples in pre-conditioned Tedlar bags up to 6 hours at the maximum possible filling volume. Among the remaining films, Kynar can be considered as an alternative to Tedlar; however, higher losses of compounds should be expected even within the first hours of storage. Due to the high background emission Flexfilm is not suitable for sampling and storage of samples for analyses aiming at volatiles at a low ppb level.
Gas chromatography with mass spectrometric detection (GC-MS) was used to identify and quantify volatile organic compounds in the blood and breath of healthy individuals. Blood and breath volatiles ...were pre-concentrated using headspace solid phase micro-extraction (HS-SPME) and needle trap devices (NTDs), respectively. The study involved a group of 28 healthy test subjects and resulted in the quantification of a total of 74 compounds in both types of samples. The concentrations of the species under study varied between 0.01 and 6700 nmol L(-1) in blood and between 0.02 and 2500 ppb in exhaled air. Limits of detection (LOD) ranged from 0.01 to 270 nmol L(-1) for blood compounds and from 0.01 to 0.7 ppb for breath species. Relative standard deviations for both measurement regimes varied from 1.5 to 14%. The predominant chemical classes among the compounds quantified were hydrocarbons (24), ketones (10), terpenes (8), heterocyclic compounds (7) and aromatic compounds (7). Twelve analytes were found to be highly present in both blood and exhaled air (with incidence rates higher than 80%) and for 32 species significant differences (Wilcoxon signed-rank test) between room air and exhaled breath were observed. By comparing blood, room air and breath levels in parallel, a tentative classification of volatiles into endogenous and exogenous compounds can be achieved.
•The potential of the human volatilome for urban search and rescue operations.•We create a library of potential biomarkers of human presence using literature data.•We predict tentative levels of ...volatile organic compounds in void spaces in ruins.•We assess detecting volatile organic compounds in the urban environment.
Volatile organic compounds (VOCs) emitted by a human body form a chemical signature capable of providing invaluable information on the physiological status of an individual and, thereby, serving as signs of life for detecting victims after natural or man-made disasters. For this review, we created a database of potential biomarkers of human presence based on literature reports on VOCs in human breath, skin emanations, blood and urine. We estimated approximate fluxes of these VOCs from the human body, and used them to predict concentrations in the vicinity of victims. We classified proposed markers in groups by potential for victim detection. The major classification discriminants were the capability of detection by portable, real-time analytical instruments and background levels of VOCs in the urban environment. We intend data summarized in this review to assist studies on the detection of humans via chemical analysis and to accelerate investigations in this area of knowledge.
Researchers looking for biomarkers from different sources, such as breath, urine, or blood, frequently search for specific patterns of volatile organic compounds (VOCs), often using pattern ...recognition or machine learning techniques. However, they are not generally aware that these patterns change depending on the source they use. Therefore, we have created a simple model to demonstrate that the distribution patterns of VOCs in fat, mixed venous blood, alveolar air, and end-tidal breath are different. Our approach follows well-established models for the description of dynamic real-time breath concentration profiles. We start with a uniform distribution of end-tidal concentrations of selected VOCs and calculate the corresponding target concentrations. For this, we only need partition coefficients, mass balance, and the assumption of an equilibrium state, which avoids the need to know the volatiles' metabolic rates and production rates within the different compartments.
Human breath contains a myriad of endogenous volatile organic compounds (VOCs) which are reflective of ongoing metabolic or physiological processes. While research into the diagnostic potential and ...general medical relevance of these trace gases is conducted on a considerable scale, little focus has been given so far to a sound analysis of the
quantitative relationships between breath levels and the underlying systemic concentrations. This paper is devoted to a thorough modeling study of the
end-tidal breath dynamics associated with isoprene, which serves as a paradigmatic example for the class of low-soluble, blood-borne VOCs.
Real-time measurements of exhaled breath under an ergometer challenge reveal characteristic changes of isoprene output in response to variations in ventilation and perfusion. Here, a valid compartmental description of these profiles is developed. By comparison with experimental data it is inferred that the major part of breath isoprene variability during exercise conditions can be attributed to an increased fractional perfusion of potential storage and production sites, leading to higher levels of
mixed venous blood concentrations at the onset of physical activity. In this context, various lines of supportive evidence for an extrahepatic tissue source of isoprene are presented.
Our model is a first step towards new guidelines for the breath gas analysis of isoprene and is expected to aid further investigations regarding the exhalation, storage, transport and biotransformation processes associated with this important compound.
Volatile organic compounds (VOCs) offer unique insights into ongoing biochemical processes in healthy and diseased humans. Yet, their diagnostic use is hampered by the limited understanding of their ...biochemical or cellular origin and their frequently unclear link to the underlying diseases. Major advancements are expected from the analyses of human primary cells, cell lines and cultures of microorganisms. In this review, a database of 125 reliably identified VOCs previously reported for human healthy and diseased cells was assembled and their potential origin is discussed. The majority of them have also been observed in studies with other human matrices (breath, urine, saliva, feces, blood, skin emanations). Moreover, continuing improvements of qualitative and quantitative analyses, based on the recommendations of the ISO-11843 guidelines, are suggested for the necessary standardization of analytical procedures and better comparability of results. The data provided contribute to arriving at a more complete human volatilome and suggest potential volatile biomarkers for future validation. Dedication:This review is dedicated to the memory of Prof. Dr. Anton Amann, who sadly passed away on January 6, 2015. He was motivator and motor for the field of breath research.
Isoprene has received widespread attention in breath research because of its potential to serve as a sensitive and non-invasive biomarker for the detection and monitoring of several metabolic ...effects. To date, research activity on breath isoprene focused on mass spectrometry-based measurement techniques, which are not portable and require skilled operators. Here, we show, for the first time to our knowledge, selective isoprene monitoring in exhaled breath (148 breath samples, 60–1250 parts-per-billion, ppb) with an inexpensive, user-friendly and compact filter–sensor device. This detector is based on a previously developed concept comprising a sorption filter of activated alumina that removes hydrophilic volatiles ahead of a micro gas sensor consisting of chemoresistive Si-doped WO3 nanoparticles to quantify the isoprene down to few ppb concentrations. When tested on humans during exercise and at rest, the detector accurately followed breath isoprene dynamics in linear (Pearson’s coefficient 0.89) correlation to proton transfer reaction mass spectrometry measurements. Most importantly, the output from the device is not interfered by high and variable concentrations of other breath volatile compounds, specifically acetone, ethanol and methanol. This isoprene detector can be readily applied for online monitoring of physical activity.
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•Portable isoprene detector validated on 148 breath samples.•Detector uses a replaceable sorption filter and a chemoresistive, nanostructured gas sensor.•Selective isoprene detection at ppb-levels validated by mass spectrometry.•Accurate tracking of breath isoprene dynamics during physical activity and at rest.
Volatile organic compounds (VOCs) emitted by human body offer a unique insight into biochemical processes ongoing in healthy and diseased human organisms. Unfortunately, in many cases their origin ...and metabolic fate have not been yet elucidated in sufficient depth, thus limiting their clinical application. The primary goal of this work was to identify and quantify volatile organic compounds being released or metabolized by HepG2 hepatocellular carcinoma cells.
The hepatocellular carcinoma cells were incubated in specially designed head-space 1-L glass bottles sealed for 24 hours prior to measurements. Identification and quantification of volatiles released and consumed by cells under study were performed by gas chromatography with mass spectrometric detection (GC-MS) coupled with head-space needle trap device extraction (HS-NTD) as the pre-concentration technique. Most of the compounds were identified both by spectral library match as well as retention time comparison based on standards.
A total of nine compounds were found to be metabolised and further twelve released by the cells under study (Wilcoxon signed-rank test, p<0.05). The former group comprised 6 aldehydes (2-methyl 2-propenal, 2-methyl propanal, 2-ethylacrolein, 3-methyl butanal, n-hexanal and benzaldehyde), n-propyl propionate, n-butyl acetate, and isoprene. Amongst the released species there were five ketones (2-pentanone, 3-heptanone, 2-heptanone, 3-octanone, 2-nonanone), five volatile sulphur compounds (dimethyl sulfide, ethyl methyl sulfide, 3-methyl thiophene, 2-methyl-1-(methylthio)- propane and 2-methyl-5-(methylthio) furan), n-propyl acetate, and 2-heptene.
The emission and uptake of the aforementioned VOCs may reflect the activity of abundant liver enzymes and support the potential of VOC analysis for the assessment of enzymes function.
Adult muscle carnitine palmitoyltransferase (CPT) II deficiency is a rare autosomal recessive disorder of long-chain fatty acid metabolism. It is typically associated with recurrent episodes of ...exercise-induced rhabdomyolysis and myoglobinuria, in most cases caused by a c.338C > T mutation in the
gene. Here we present the pedigree of one of the largest family studies of CPT II deficiency caused by the c.338C > T mutation, documented so far. The pedigree comprises 24 blood relatives of the index patient, a 32 year old female with genetically proven CPT II deficiency. In total, the mutation was detected in 20 family members, among them five homozygotes and 15 heterozygotes. Among all homozygotes, first symptoms of CPT II deficiency occurred during childhood. Additionally, two already deceased relatives of the index patient were carriers of at least one copy of the genetic variant, revealing a remarkably high prevalence of the c.338C > T mutation within the tested family. Beside the index patient, only one individual had been diagnosed with CPT II deficiency prior to this study and three cases of CPT II deficiency were newly detected by this family study, pointing to a general underdiagnosis of the disease. Therefore, this study emphasizes the need to raise awareness of CPT II deficiency for correct diagnosis and accurate management of the disease.
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