Andriy Pysanenko

Analysis of breath, exhaled via the mouth and nose, and the air in the oral cavity

Analyses have been performed, using on-line selected ion flow tube mass spectrometry (SIFT-MS), of the breath of three healthy volunteers, as exhaled via the mouth and the nose and also of the air in the oral cavity during breath hold, each morning over a period of one month. Nine trace compounds have been quantified and concentration distributions have been constructed. Of these compounds, the levels of acetone, methanol and isoprene are the same in the mouth-exhaled and the nose-exhaled breath; hence, we deduce that these compounds are totally systemic. The levels of ammonia, ethanol and hydrogen cyanide are much lower in the nose-exhaled breath than in the mouth-exhaled breath and highest in the oral cavity, indicating that these compounds are largely generated in the mouth with little being released at the alveolar interface. Using the same ideas, both the low levels of propanol and acetaldehyde in mouth-exhaled breath appear to have both oral and systemic components. Formaldehyde is at levels in mouth- and nose-exhaled breath and the oral cavity that are lower than that of the ambient air and so its origin is difficult to ascertain, but it appears to be partially systemic. These results indicate that serious contamination of alveolar breath exhaled via the mouth can occur and if breath analysis is to be used to diagnose metabolic disease then analyses should be carried out of both mouth- and nose-exhaled breath to identify the major sources of particular trace compounds.

A selected ion flow tube mass spectrometry study of ammonia in mouth-and nose-exhaled breath and in the oral cavity

A study has been carried out, involving three healthy volunteers, of the ammonia levels in breath exhaled via the mouth and via the nose and in the static oral cavity using on-line, selected ion flow tube mass spectrometry (SIFT-MS), obviating the problems associated with sample collection of ammonia. The unequivocal conclusion drawn is that the ammonia appearing in the mouth-exhaled breath of the three volunteers is largely generated in the oral cavity and that the ammonia originating at the alveolar interface in the lungs is typically at levels less than about 100 parts-per-billion, which is a small fraction of the total breath ammonia. This leads to the recommendation that exhaled breath analyses should focus on nose-exhaled breath if the objective is to use breath analysis to investigate systemic, metabolic disease.

Acetone, butanone, pentanone, hexanone and heptanone in the headspace of aqueous solution and urine studied by selected ion flow tube mass spectrometry

Urine is commonly analysed in clinical practice by a variety of liquid-phase techniques to check for excessive ketone bodies, proteins and salts to name just a few compounds. However, little work has been carried out to measure the volatile compounds emitted by urine since these do not yet have an established role in clinical diagnosis. There is, however, a growing body of evidence that these volatile compounds can be indicators of adverse physiological conditions and disease and with the advent of sensitive gas-phase analytical methods they can be quickly quantified in urine headspace and potentially provide valuable support for clinical diagnosis. Thus, we are developing selected ion flow tube mass spectrometry, SIFT-MS, for the real-time analysis of urine headspace, ultimately to support rapid diagnosis in the clinical environment. In this paper we focus on volatile ketones in the headspace of aqueous solutions and urine donated by three healthy volunteers. Using SIFT-MS, we have unambiguously quantified in urine headspace acetone, by far the most abundant ketone, butanone, pentanone, hexanone and heptanone using NO(+) precursor ions. Further to this, we have determined the Henrys Law coefficients, HLC, for these ketones in aqueous solution to allow the liquid-phase concentrations in urine to be estimated from headspace levels of their vapours. In addition, the influence of the addition of physiological amounts of dissolved urea, sodium chloride and hydrochloric acid on the partitioning of these ketones between the aqueous phase and gas phase has been investigated and found to be small, which gives greater credence to the use of the HLC obtained using aqueous solutions for the estimation of ketone concentrations in urine. Finally, parallel measurements of the levels of acetone in exhaled breath and urine headspace have been obtained and shown to be very similar, which gives support to the previous deduction from breath analysis that acetone is a truly systemic compound.

Uptake of atmospheric molecules by ice nanoparticles: Pickup cross sections

Uptake of several atmospheric molecules on free ice nanoparticles was investigated. Typical examples were chosen: water, methane, NO(x) species (NO, NO(2)), hydrogen halides (HCl, HBr), and volatile organic compounds (CH(3)OH, CH(3)CH(2)OH). The cross sections for pickup of these molecules on ice nanoparticles (H(2)O)(N) with the mean size of N≈260 (diameter ~2.3 nm) were measured in a molecular beam experiment. These cross sections were determined from the cluster beam velocity decrease due to the momentum transfer during the pickup process. For water molecules molecular dynamics simulations were performed to learn the details of the pickup process. The experimental results for water are in good agreement with the simulations. The pickup cross sections of ice particles of several nanometers in diameter can be more than 3 times larger than the geometrical cross sections of these particles. This can have significant consequences in modelling of atmospheric ice nanoparticles, e.g., their growth.

Microhydration Prevents Fragmentation of Uracil and Thymine by Low-Energy Electrons

When ionizing radiation passes biological matter, a large number of secondary electrons with very low energies (<3 eV) is produced. It is known that such electrons cause an efficient fragmentation of isolated nucleobases via dissociative electron attachment. We present an experimental study of the electron attachment to microhydrated nucleobases. Our novel approach allows significant control over the hydration of molecules studied in the molecular beam. We directly show for the first time that the presence of a few water molecules suppresses the dissociative channel and leads exclusively to formation of intact molecular and hydrated anions. The suppression of fragmentation is ascribed to caging-like effects and fast energy transfer to the solvent. This is in contrast with theoretical prediction that microhydration strongly enhances the fragmentation of nucleobases. The current observation impacts mechanisms of reductive DNA strand breaks proposed to date on the basis of gas-phase experiments.

Nucleation of Mixed Nitric Acid–Water Ice Nanoparticles in Molecular Beams that Starts with a HNO3 Molecule

Mixed (HNO3)m(H2O)n clusters generated in supersonic expansion of nitric acid vapor are investigated in two different experiments, (1) time-of-flight mass spectrometry after electron ionization and (2) Na doping and photoionization. This combination of complementary methods reveals that only clusters containing at least one acid molecule are generated, that is, the acid molecule serves as the nucleation center in the expansion. The experiments also suggest that at least four water molecules are needed for HNO3 acidic dissociation. The clusters are undoubtedly generated, as proved by electron ionization; however, they are not detected by the Na doping due to a fast charge-transfer reaction between the Na atom and HNO3. This points to limitations of the Na doping recently advocated as a general method for atmospheric aerosol detection. On the other hand, the combination of the two methods introduces a tool for detecting molecules with sizable electron affinity in clusters.

The quantification of carbon dioxide in humid air and exhaled breath by selected ion flow tube mass spectrometry.

The reactions of carbon dioxide, CO(2), with the precursor ions used for selected ion flow tube mass spectrometry, SIFT-MS, analyses, viz. H(3)O(+), NO(+) and O(2) (+), are so slow that the presence of CO(2) in exhaled breath has, until recently, not had to be accounted for in SIFT-MS analyses of breath. This has, however, to be accounted for in the analysis of acetaldehyde in breath, because an overlap occurs of the monohydrate of protonated acetaldehyde and the weakly bound adduct ion, H(3)O(+)CO(2), formed by the slow association reaction of the precursor ion H(3)O(+) with CO(2) molecules. The understanding of the kinetics of formation and the loss rates of the relevant ions gained from experimentation using the new generation of more sensitive SIFT-MS instruments now allows accurate quantification of CO(2) in breath using the level of the H(3)O(+)CO(2) adduct ion. However, this is complicated by the rapid reaction of H(3)O(+)CO(2) with water vapour molecules, H(2)O, that are in abundance in exhaled breath. Thus, a study has been carried out of the formation of this adduct ion by the slow three-body association reaction of H(3)O(+) with CO(2) and its rapid loss in the two-body reaction with H(2)O molecules. It is seen that the signal level of the H(3)O(+)CO(2) adduct ion is sensitively dependent on the humidity (H(2)O concentration) of the sample to be analysed and a functional form of this dependence has been obtained. This has resulted in an appropriate extension of the SIFT-MS software and kinetics library that allows accurate measurement of CO(2) levels in air samples, ranging from very low percentage levels (0.03% typical of tropospheric air) to the 6% level that is about the upper limit in exhaled breath. Thus, the level of CO(2) can be traced through single time exhalation cycles along with that of water vapour, also close to the 6% level, and of trace gas metabolites that are present at only a few parts-per-billion. This has added a further dimension to the analysis of major and trace compounds in breath using SIFT-MS.

Cluster cross sections from pickup measurements: Are the established methods consistent?

Pickup of several molecules, H(2)O, HBr, and CH(3)OH, and Ar atoms on free Ar(N) clusters has been investigated in a molecular beam experiment. The pickup cross sections of the clusters with known mean sizes, Ñ≈ 150 and 260 were measured by two independent methods: (i) the cluster beam velocity decrease due to the momentum transfer of the picked up molecules to the clusters, and (ii) Poisson distribution of a selected cluster fragment ion as a function of the pickup pressure. In addition, the pickup cross sections were calculated using molecular dynamics and Monte Carlo simulations. The simulations support the results of the velocity measurements. On the other hand, the Poisson distributions yield significantly smaller cross sections, inconsistent with the known Ar(N) cluster sizes. These results are discussed in terms of: (i) an incomplete coagulation of guest molecules on the argon clusters when two or more molecules are picked up; and (ii) the fragmentation pattern of the embedded molecules and their clusters upon ionization on the Ar cluster. We conclude that the Poisson distribution method has to be cautiously examined, if conclusions should be drawn about the cluster cross section, or the mean cluster size Ñ, and the number of picked up molecules.

Kinetics of ethanol decay in mouth‐ and nose‐exhaled breath measured on‐line by selected ion flow tube mass spectrometry following varying doses of alcohol

A study has been carried out of the decay of ethanol in mouth-exhaled and nose-exhaled breath of two healthy volunteers following the ingestion of various doses of alcohol at different dilutions in water. Concurrent analyses of sequential single breath exhalations from the two volunteers were carried out using selected ion flow tube mass spectrometry, SIFT-MS, on-line and in real time continuously over some 200 min following each alcohol dose by simply switching sampling between the two volunteers. Thus, the time interval between breath exhalations was only a few minutes, and this results in well-defined decay curves. Inspection of the mouth-exhaled and nose-exhaled breath data shows that mouth contamination of ethanol diminished to insignificant levels after a few minutes. The detailed results of the analyses of nose-exhaled breath show that the peak levels and the decay rates of breath ethanol are dependent on the ethanol dose and the volume of ethanol/water mixture ingested. From these data, both the efficiency of the first-pass metabolism of ethanol and the indications of gastric emptying rates at the various doses and ingested volumes have been obtained for the two volunteers. Additionally and simultaneously, acetaldehyde, acetic acid and acetone were measured in each single breath exhalation. Acetaldehyde, the primary product of ethanol metabolism, is seen to track the breath ethanol. Acetic acid, a possible secondary product of this metabolism, was detected in the exhaled breath, but was shown to largely originate in the oral cavity. Breath acetone was seen to increase over the long period of measurement due to the depletion of nutrients.

Clustering and Photochemistry of Freon CF2Cl2 on Argon and Ice Nanoparticles

The photochemistry of CF2Cl2 molecules deposited on argon and ice nanoparticles was investigated. The clusters were characterized via electron ionization mass spectrometry, and the photochemistry was revealed by the Cl fragment velocity map imaging after the CF2Cl2 photodissociation at 193 nm. The complex molecular beam experiment was complemented by ab initio calculations. The (CF2Cl2)n clusters were generated in a coexpansion with Ar buffer gas. The photodissociation of molecules in the (CF2Cl2)n clusters yields predominantly Cl fragments with zero kinetic energy: caging. The CF2Cl2 molecules deposited on large argon clusters in a pickup experiment are highly mobile and coagulate to form the (CF2Cl2)n clusters on ArN. The photodissociation of the CF2Cl2 molecules and clusters on ArN leads to the caging of the Cl fragment. On the other hand, the CF2Cl2 molecules adsorbed on the (H2O)N ice nanoparticles do not form clusters, and no Cl fragments are observed from their photodissociation. Since the CF2Cl2 molecule was clearly adsorbed on (H2O)N, the missing Cl signal is interpreted in terms of surface orientation, possibly via the so-called halogen bond and/or embedding of the CF2Cl2 molecule on the disordered surface of the ice nanoparticles.