Paweł Mochalski

Assessment of the exhalation kinetics of volatile cancer biomarkers based on their physicochemical properties

The current review provides an assessment of the exhalation kinetics of volatile organic compounds (VOCs) that have been linked with cancer. Towards this end, we evaluate various physicochemical properties, such as breath:air and blood:fat partition coefficients, of 112 VOCs that have been suggested over the past decade as potential markers of cancer. With these data, we show that the cancer VOC concentrations in the blood and in the fat span over 12 and 8 orders of magnitude, respectively, in order to provide a specific counterpart concentration in the exhaled breath (e.g., 1 ppb). This finding suggests that these 112 different compounds have different storage compartments in the body and that their exhalation kinetics depends on one or a combination of the following factors: (i) the VOC concentrations in different parts of the body; (ii) the VOC synthesis and metabolism rates; (iii) the partition coefficients between tissue(s), blood and air; and (iv) the VOCs diffusion constants. Based on this analysis, we discuss how this knowledge allows modeling and simulating the behavior of a specific VOC under different sampling protocols (with and without exertion of effort). We end this review by a brief discussion on the potential role of these scenarios in screening and therapeutic monitoring of cancer.

Hybrid Volatolomics and Disease Detection

This Review presents a concise, but not exhaustive, didactic overview of some of the main concepts and approaches related to volatolomics-an emerging frontier for fast, risk-free, and potentially inexpensive diagnostics. It attempts to review the source and characteristics of volatolomics through the so-called volatile organic compounds (VOCs) emanating from cells and their microenvironment. It also reviews the existence of VOCs in several bodily fluids, including the cellular environment, blood, breath, skin, feces, urine, and saliva. Finally, the usefulness of volatolomics for diagnosis from a single bodily fluid, as well as ways to improve these diagnostic aspects by hybrid approaches that combine VOC profiles collected from two or more bodily fluids, will be discussed. The perspectives of this approach in developing the field of diagnostics to a new level are highlighted.

Emission rates of selected volatile organic compounds from skin of healthy volunteers

Highlights • 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.

Temporal profiling of human urine VOCs and its potential role under the ruins of collapsed buildings

Context: The scent profile of human urine was investigated as potential source of chemical markers of human presence in collapsed buildings after natural or man-made disasters. Objective: The main goals of this study were to build a library of potential biomarkers of human urine to be used for the detection of entrapped victims and to further examine their evolution profile in time. Materials and methods: Headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) was used to detect and identify the volatile organic compounds (VOCs) spontaneously released from urine of 20 healthy volunteers. Additionally, the evolution of human urine headspace during four days storage at room temperature was investigated. Results: 33 omnipresent species with incidence higher than 80% were selected as potential urine markers. The most represented chemical classes were ketones with 10 representatives, aldehydes (7 species) and sulfur compounds (7 species). The monitoring of the evolution of the urine scent demonstrated an increase in the emission of 26 omnipresent urinary volatiles (rise from 36% to 526%). The highest increase was noted for dimethyldisulfide and dimethyltrisulfide (fivefold increase) and 3-methyl-2-butanone, 4-methyl-2-pentanone and 3-hexanone (fourfold rise). Only three compounds exhibited decreasing trend; dimethylsulfone, octanal and propanal. Conclusion: The ubiquitous urine VOCs identified within this study create a library of potential markers of human urine to be verified in further field studies, involving portable and sensitive instruments, directly applied in the field.

Blood and breath profiles of volatile organic compounds in patients with end-stage renal disease

BackgroundMonitoring of volatile organic compounds (VOCs) in exhaled breath shows great potential as a non-invasive method for assessing hemodialysis efficiency. In this work we aim at identifying and quantifying of a wide range of VOCs characterizing uremic breath and blood, with a particular focus on species responding to the dialysis treatment.MethodsGas chromatography with mass spectrometric detection coupled with solid-phase microextraction as pre-concentration method.ResultsA total of 60 VOCs were reliably identified and quantified in blood and breath of CKD patients. Excluding contaminants, six compounds (isoprene, dimethyl sulfide, methyl propyl sulfide, allyl methyl sulfide, thiophene and benzene) changed their blood and breath levels during the hemodialysis treatment.ConclusionsUremic breath and blood patterns were found to be notably affected by the contaminants from the extracorporeal circuits and hospital room air. Consequently, patient exposure to a wide spectrum of volatile species (hydrocarbons, aldehydes, ketones, aromatics, heterocyclic compounds) is expected during hemodialysis. Whereas highly volatile pollutants were relatively quickly removed from blood by exhalation, more soluble ones were retained and contributed to the uremic syndrome. At least two of the species observed (cyclohexanone and 2-propenal) are uremic toxins. Perhaps other volatile substances reported within this study may be toxic and have negative impact on human body functions. Further studies are required to investigate if VOCs responding to HD treatment could be used as markers for monitoring hemodialysis efficiency.

A compendium of volatile organic compounds (VOCs) released by human cell lines

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.

Analysis of Volatile Organic Compounds Liberated and Metabolised by Human Umbilical Vein Endothelial Cells (HUVEC) In Vitro

Gas chromatography with mass spectrometric detection combined with head-space needle trap extraction as the pre-concentration technique was applied to identify and quantify volatile organic compounds released or metabolised by human umbilical vein endothelial cells. Amongst the consumed species there were eight aldehydes (2-methyl 2-propenal, 2-methyl propanal, 2-methyl butanal, 3-methyl butanal, n-hexanal, benzaldehyde, n-octanal and n-nonanal) and n-butyl acetate. Further eight compounds (ethyl acetate, ethyl propanoate, ethyl butyrate, 3-heptanone, 2-octanone, 2-nonanone, 2-methyl-5-(methylthio)-furan and toluene) were found to be emitted by the cells under study. Possible metabolic pathways leading to the uptake and release of these compounds by HUVEC are proposed and discussed. The uptake of aldehydes by endothelial cells questions the reliability of species from this chemical class as breath or blood markers of disease processes in human organism. The analysis of volatiles released or emitted by cell lines is shown to have a potential for the identification and assessment of enzymes activities and expression.

Product ion distributions for the reactions of NO(+) with some physiologically significant volatile organosulfur and organoselenium compounds obtained using a selective reagent ionization time-of-flight mass spectrometer.

RATIONALE The reactions of NO+ with volatile organic compounds (VOCs) in Selective Reagent Ionization Time-of-Flight Mass Spectrometry (SRI-TOF-MS) reactors are relatively poorly known, inhibiting their use for trace gas analysis. The rationale for this product ion distribution study was to identify the major product ions of the reactions of NO+ ions with 13 organosulfur compounds and 2 organoselenium compounds in an SRI-TOF-MS instrument and thus to prepare the way for their analysis in exhaled breath, in skin emanations and in the headspace of urine, blood and cell and bacterial cultures. METHODS Product ion distributions have been investigated by a SRI-TOF-MS instrument at an E/N in the drift tube reactor of 130 Td for both dry air and humid air (4.9% absolute humidity) used as the matrix gas. The investigated species were five monosulfides (dimethyl sulfide, ethyl methyl sulfide, methyl propyl sulfide, allyl methyl sulfide and methyl 5-methyl-2-furyl sulfide), dimethyl disulfide, dimethyl trisulfide, thiophene, 2-methylthiophene, 3-methylthiophene, methanethiol, allyl isothiocyanate, dimethyl sulfoxide, and two selenium compounds – dimethyl selenide and dimethyl diselenide. RESULTS Charge transfer was seen to be the dominant reaction mechanism in all reactions under study forming the M+ cations. For methanethiol and allyl isothiocyanate significant fractions were also observed of the stable adduct ions NO+M, formed by ion-molecule association, and [M–H]+ ions, formed by hydride ion transfer. Several other minor product channels are seen for most reactions indicating that the nascent excited intermediate (NOM)+* adduct ions partially fragment along other channels, most commonly by the elimination of neutral CH3, CH4 and/or C2H4 species that are probably bound to an NO molecule. Humidity had little effect on the product ion distributions. CONCLUSIONS The findings of this study are of particular importance for data interpretation in studies of volatile organosulfur and volatile organoselenium compounds employing SRI-TOF-MS in the NO+ mode.

Potential of volatile organic compounds as markers of entrapped humans for use in urban search-and-rescue operations

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.

Quantitative analysis of volatile organic compounds released and consumed by rat L6 skeletal muscle cells in vitro

Knowledge of the release of volatile organic compounds (VOCs) by cells provides important information on the origin of VOCs in exhaled breath. Muscle cells are particularly important, since their release of volatiles during the exertion of an effort contributes considerably to breath concentration profiles. Presently, the cultivation of human skeletal muscle cells is encountering a number of obstacles, necessitating the use of animal muscle cells in in vitro studies. Rat L6 skeletal muscle cells are therefore commonly used as a model for studying the molecular mechanisms of human skeletal muscle differentiation and functions, and facilitate the study of the origin and metabolic fate of the endogenously produced compounds observed in breath and skin emanations. Within this study the production and uptake of VOCs by rat L6 skeletal muscle cells were investigated using gas chromatography with mass spectrometric detection, combined with head-space needle trap extraction as the pre-concentration technique (HS-NTE-GC-MS). Seven compounds were found to be produced, whereas sixteen species were consumed (Wilcoxon signed-rank test, p < 0.05) by the cells being studied. The set of released volatiles included two ketones (2-pentanone and 2-nonanone), two volatile sulphur compounds (dimethyl sulfide and methyl 5-methyl-2-furyl sulphide), and three hydrocarbons (2-methyl 1-propene, n-pentane and isoprene). Of the metabolized species there were thirteen aldehydes (2-propenal, 2-methyl 2-propenal, 2-methyl propanal, 2-butenal, 2-methyl butanal, 3-methyl butanal, n-pentanal, 2-methyl 2-butenal, n-hexanal, benzaldehyde, n-octanal, n-nonanal and n-decanal), two esters (n-propyl propionate and n-butyl acetate), and one volatile sulphur compound (dimethyl disulfide). The possible metabolic pathways leading to the uptake and release of these compounds by L6 cells are proposed and discussed. An analysis of the VOCs showed them to have huge potential for the identification and monitoring of some molecular mechanism and conditions.