Direct-injection mass spectrometry adds the time dimension to (B)VOC analysis

In the past decade, we have witnessed rapid development of direct-injection mass spectrometric (DIMS) technologies that combine ever-improving mass and time resolution with high sensitivity and robustness. Here, we review some of the most significant DIMS technologies, which have been applied to rapid monitoring and quantification of volatile organic compounds (VOCs) and biogenic VOCS (BVOCs). They include MS-e-noses, atmospheric-pressure chemical ionization (APCI), proton-transfer-reaction mass spectrometry (PTR-MS), and selected ion-flow-tube mass spectrometry (SIFT-MS). DIMS-based MS-e-noses provide the possibility to screen large sample sets and may yield rich analytical information. APCI is a widespread ionization method and pioneered DIMS in environmental and flavor-release applications. SIFT-MS and PTR-MS allow better control of precursor-ion generation and hence of the ionization process. SIFT-MS puts the focus on control of the ionization process, while PTR-MS does so on sensitivity. Most (B)VOCs of interest can be efficiently detected and often identified by DIMS, thanks also to the possibility of switching between different precursor ions and the recent realization of time-of-flight-based equipments. Finally, we give selected examples of applications for each of the key technologies, including research in food-quality control (MS-e-nose), flavor release (APCI), environmental sciences (PTR-MS) and health sciences (SIFT-MS).     

On-line measurement of the absolute humidity of air, breath and liquid headspace samples by selected ion flow tube mass spectrometry

We describe how selected ion flow tube mass spectrometry (SIFT-MS) can be used to determine the absolute humidity of air, breath and liquid headspace samples. This involves the determination of the relative count rates of the H3O+ ions and those H3O+.(H2O)(1,2,3) hydrate ions that inevitably form in the helium carrier gas when humid samples are being analysed by SIFT-MS using H3O+ precursor ions. This requires an understanding of the kinetics of hydrated hydronium ion formation, the involvement of mass discrimination in the analytical quadrupole mass spectrometer and the decreased diffusive loss of the heavier hydrates along the flow tube. Thus, we show that the humidity of breath and liquid headspace samples, typically at the few percent level, can be directly obtained on-line to the SIFT-MS instrument along with the concentrations of trace gases, which are present at much lower levels. We emphasise the value of parallel humidity measurements in ensuring good real-time sampling of breath and liquid headspace and the value of such measurements to trace gas analysis using SIFT-MS.     

Ambient analysis of trace compounds in gaseous media by SIFT-MS

The topic of ambient gas analysis has been rapidly developed in the last few years with the evolution of the exciting new techniques such as DESI, DART and EESI. The essential feature of all is that analysis of trace gases can be accomplished either in the gas phase or those released from surfaces, crucially avoiding sample collection or modification. In this regard, selected ion flow tube mass spectrometry, SIFT-MS, also performs ambient analyses both accurately and rapidly. In this focused review we describe the underlying ion chemistry underpinning SIFT-MS through a discourse on the reactions of different classes of organic and inorganic molecules with H(3)O(+), NO(+) and O(2)(+)˙ studied using the SIFT technique. Rate coefficients and ion products of these reactions facilitate absolute SIFT-MS analyses and can also be useful for the interpretation of data obtained by the other ambient analysis methods mentioned above. The essential physics and flow dynamics of SIFT-MS are described that, together with the reaction kinetics, allow SIFT-MS to perform absolute ambient analyses of trace compounds in humid atmospheric air, exhaled breath and the headspace of aqueous liquids. Several areas of research that, through pilot experiments, are seen to benefit from ambient gas analysis using SIFT-MS are briefly reviewed. Special attention is given to exhaled breath and urine headspace analysis directed towards clinical diagnosis and therapeutic monitoring, and some other areas researched using SIFT-MS are summarised. Finally, extensions to current areas of application and indications of other directions in which SIFT-MS can be exploited for ambient analysis are alluded to.     

Selected ion flow tube mass spectrometry for on-line trace gas analysis in biology and medicine

Selected ion flow tube mass spectrometry, (SIFT-MS), is a technique for simultaneous real-time quantification of several trace gases in air and exhaled breath. It relies on chemical ionization of the trace gas molecules in air/breath samples introduced into helium carrier gas, using H(3)O(+), NO(+) and O(2)(+) reagent (precursor ions). Reactions between the precursor ions and the trace gas molecules proceed for an accurately defined time, the precursor and product ions being detected and counted by a downstream mass spectrometer. Absolute concentrations of trace gases in single breath exhalation can be determined by SIFT-MS down to parts-per-billion (ppb) levels, obviating sample collection into bags or onto traps. Calibration using chemical standards is not required, as the concentrations are calculated using the known reaction rate constants and measured flow rates and pressures. SIFT-MS has been used for many pilot investigations in several areas of research, especially as a non-invasive breath analysis tool to investigate physiological processes in humans and animals, for clinical diagnosis and for therapeutic monitoring. Examples of the results obtained from several such studies are outlined to demonstrate the potential of SIFT-MS for trace gas analysis of air, exhaled breath and the headspace above liquids.     

选择离子流动管质谱及其在痕量气体分析中的应用

选择离子流动管质谱(SIFT-MS)结合流动管技术、化学电离和质谱,有选择地使用F13O^ 、NO^ 和O2^ 初始离子,可在几秒之内对空气、呼吸气体和液表蒸气中的痕量气(如乙醇、乙醛、丙酮、氨和2-甲基丁二烯等,行多组分实时在线分析。介绍了选择离子流动管(SIFT)技术、SIFT-MS的分析方法及其物理和离子化学基础、SIFT-MS在不同领域的痕量气体分析中的应用。     

The challenge of breath analysis for clinical diagnosis and therapeutic monitoring

The potential of breath analysis for clinical diagnosis and the strengths and weaknesses of the analytical methods used are discussed. Special attention is given to selected ion flow tube mass spectrometry, SIFT-MS, using which on-line real-time analyses of single breath exhalations can be carried out. Illustrative data on the concentration distributions of several breath metabolites amongst the healthy population are presented and their relations to disease when elevated above the normal are alluded to.     

Quantification of volatile compounds in the headspace of aqueous liquids using selected ion flow tube mass spectrometry

We describe a method by which the concentrations of volatile compounds in the headspace of their dilute aqueous solutions in sealed containers can be determined using on-line selected ion flow tube mass spectrometry (SIFT-MS). Thus, the changing number density of the molecules of the volatile compound in the carrier gas of the SIFT-MS instrument is described in terms of its changing flow rate as the pressure in the sealed container decreases during the sampling procedure. It is shown that the best analytical procedure is to determine the mean concentration of the trace gas in the liquid headspace over a given sampling time and relate this to the required concentration, which is the initial equilibrium concentration established before the pressure in the sealed container reduces significantly. To test the validity of this analytical approach, the headspace concentrations of acetaldehyde, ethanol and acetone above aqueous solutions of known concentrations have been determined. Hence, the Henry's Law constants for these compounds have been determined and found to agree with the published values. The confirmation of the quality of this sampling methodology combined with SIFT-MS for the analysis of volatile compounds in liquid headspace paves the way for the rapid analyses of biological liquids such as urine and serum for clinical diagnosis and physiological monitoring.     

An online ultra-high sensitivity Proton-transfer-reaction mass-spectrometer combined with switchable reagent ion capability (PTR + SRI − MS)

Proton-transfer-reaction mass-spectrometry (PTR-MS) developed in the 1990s is used today in a wide range of scientific and technical fields. PTR-MS allows for real-time, online determination of absolute concentrations of volatile (organic) compounds (VOCs) in air with high sensitivity (into the low pptv range) and a fast response time (in the 40–100 ms time regime). Most PTR-MS instruments employed so far use an ion source consisting of a hollow cathode (HC) discharge in water vapour which provides an intense source of proton donor H₃O⁺ ions. As the use of other ions, e.g. NO⁺ and O₂⁺, can be useful for the identification of VOCs and for the detection of VOCs with proton affinities (PA) below that of H₂O, selected ion flow tube mass spectrometry (SIFT-MS) with mass selected ions has been applied in these instances. SIFT-MS suffers, however, from at least two orders lower reagent ion counts rates and therefore SIFT-MS suffers from lower sensitivity than PTR-MS.Here we report the development of a PTR-MS instrument using a modified HC ion source and drift tube design, which allows for the easy and fast switching between H₃O⁺, NO⁺ and O₂⁺ ions produced in high purity and in large quantities in this source. This instrument is capable of measuring low concentrations (with detection limits approaching the ppqv regime) of VOCs using any of the three reagent ions investigated in this study. Therefore this instrument combines the advantages of the PTR-MS technology (the superior sensitivity) with those of SIFT-MS (detection of VOCs with PAs smaller than that of the water molecule and the capability to distinguish between isomeric compounds).We will first discuss the setup of this new PTR+SRI-MS mass spectrometer instrument, its performance for aromates, aldehydes and ketones (with a sensitivity of up to nearly 1000 cps/ppbv and a detection limit of about several 100 ppqv) and finally give some examples concerning the ability to distinguish structural isomeric compounds.     

Alcohol in breath and blood: a selected ion flow tube mass spectrometric study

In this paper we compare the amounts of ethanol in breath and in blood after ingestion of whisky using analysis by selected ion flow tube mass spectrometry (SIFT-MS). Blood ethanol concentrations were also obtained using standard hospital forensic procedures for blood alcohol analyses. We demonstrate the quantitative nature of SIFT-MS analysis by correlating the observed alcohol content of the headspace above 5-mL amounts of venous blood and aqueous solution to which known trace amounts of alcohol have been added. This procedure provides a Henry's Law coefficient for ethanol in aqueous solution at 298 +/- 3 K of 209 +/- 7 mol/kg*bar. We also demonstrate that measurement of the ethanol concentration in the alveolar portion of a single breath using the SIFT-MS technique gives an accurate measure of blood alcohol and could obviate the need for blood samples in forensic processing. The storage performance of breath samples in Mylar bags with a volume greater than 1 L has been shown to maintain the mixture integrity for ethanol but not for some other species.     

Quantification of hydrogen cyanide in humid air by selected ion flow tube mass spectrometry

Following our recent observation that Pseudomonas bacteria in vitro emit hydrogen cyanide, we have found it necessary to investigate the ion chemistry of this compound and to extend the kinetics database for selected ion flow tube mass spectrometry (SIFT-MS) to allow the accurate quantification of HCN in moist air samples, including exhaled breath. Because of the proximity of the proton affinities of HCN and H2O molecules, the presence of water vapour can significantly distort HCN analysis in the presence of water vapour and a more sophisticated analytical procedure has to be developed. Thus, the reactions of H3O+(H2O)0,1,2,3 ions with HCN molecules have been studied in the presence of varying concentrations of water vapour, reactions on which SIFT-MS analysis of HCN relies. The results of these experiments have allowed an analytical procedure to be developed which has extended the kinetics database of SIFT-MS, such that HCN can now be quantified in humid air and in exhaled breath.     

Selected ion flow tube mass spectrometry of exhaled breath condensate headspace

Collection of exhaled breath condensate (EBC) is a relatively simple noninvasive method of breath analysis; however, no data have been reported that would relate concentration of volatile compounds in EBC to their gaseous concentrations in exhaled air. The aim of the study was to investigate which volatile compounds are present in EBC and how their concentrations relate to results of direct breath analysis. Thus, samples of EBC were collected in a standard way from several subjects and absolute levels of several common volatile breath metabolites (ammonia, acetone, ethanol, methanol, propanol, isoprene, hydrogen cyanide, formaldehyde and acetaldehyde) were then determined in their headspace using selected ion flow tube mass spectrometry (SIFT-MS). Results are compared with those from on-line breath analyses carried out immediately before collecting the EBC samples. It has been demonstrated that SIFT-MS can be used to quantify the concentrations of volatiles in EBC samples and that, for methanol, ammonia, ethanol and acetone, the EBC concentrations correlate with the direct breath levels. However, the EBC concentrations of isoprene, formaldehyde, acetaldehyde, hydrogen cyanide and propanol do not correlate with direct breath measurements. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Combined use of gas chromatography and selected ion flow tube mass spectrometry for absolute trace gas quantification

The value of the gas chromatography (GC) and selected ion flow tube mass spectrometry (SIFT-MS) combination for the analysis of trace gases is demonstrated by the quantification of acetone in air samples using the three precursor ions available to SIFT-MS, viz. H3O+, NO+ and O2+, and by the separation of the isomers 1-propanol and 2-propanol, and their analysis using H3O+ precursor ions. It is shown that the GC/SIFT-MS combination allows for accurate trace gas quantification obviating the regular, time-consuming calibrations that are usually required for the more commonly used detectors of GC systems, and the positive identification of isomers in mixtures that is often challenging using SIFT-MS alone. Thus, the GC/SIFT-MS combination paves the way to more confident analyses of complex mixtures such as exhaled breath.     

Influence of water vapour on selected ion flow tube mass spectrometric analyses of trace gases in humid air and breath

Selected ion flow tube mass spectrometry (SIFT-MS) detects and quantifies in real time the trace gases, M, in air/breath samples introduced directly into a flow tube. Inevitably, relatively large partial pressures of water vapour are introduced with the sample and the water molecules become involved in the ion chemistry on which this analytical technique depends. When H(3)O(+) ions are used as the precursors for chemical ionisation and SIFT mass spectrometric analyses of M, they generally result in the formation of MH(+) ions. Also, when water vapour is present the H(3)O(+) ions are partially converted to hydrated hydronium ions, H(3)O(+).(H(2)O)(1,2,3). The latter may act as precursor ions and produce new product ions like MH(+).(H(2)O)(1,2,3) via ligand switching and association reactions. This ion chemistry and the product ions that result from it must be accounted for in accurate analyses by SIFT-MS. In this paper we describe the results of a detailed SIFT study of the reactions involved in the quantification of acetone, ethyl acetate, diethyl ether, methanol, ethanol, ammonia and methyl cyanide by SIFT-MS in the presence of water vapour. This study was undertaken to provide the essential data that allows more accurate analyses of moist air and breath by SIFT-MS to be achieved. It is shown using our standard analysis procedure that the error of SIFT-MS quantification caused by the presence of water vapour is typically 15%. An improved analysis procedure is then presented that is shown to reduce this error to typically 2%. Additionally, some fundamental data have been obtained on the association reactions of protonated organic molecules, MH(+) ions, with water molecules forming MH(+).H(2)O monohydrate ions. For some types of M, reaction sequences occur that lead to the formation of dihydrate and trihydrate ions.     

Quantification of character-impacting compounds in Ocimum basilicum and 'Pesto alla Genovese' with selected ion flow tube mass spectrometry

Basil (Ocimum basilicum) is an important flavourant plant which constitutes the major ingredient of the pasta sauce 'Pesto alla Genovese'. The characteristic smell of basil stems mainly from a handful of terpenoids (methyl cinnamate, eucalyptol, linalool and estragole), the concentration of which varies according to basil cultivars. The simple and rapid analysis of the terpenoid constituents of basil would be useful as a means to optimise harvesting times and to act as a quality control process for basil-containing foodstuffs. Classical analytical techniques such as gas chromatography/mass spectrometry (GC/MS) are, however, slow, technically demanding and therefore less suitable for routine analysis. A new chemical ionisation technique which allows real-time quantification of traces gases, Selected Ion Flow Tube Mass Spectrometry (SIFT-MS), was therefore utilised to determine its usefulness for the assay of terpenoid concentrations in basil and pesto sauce headspace. Trace gas analysis was performed using the NO(+) precursor ion which minimised interference from other compounds. Character-impacting compound concentration was measured in basil headspace with good reproducibility and statistically significant differences were observed between cultivars. Quantification of linalool in pesto sauce headspace proved more difficult due to the presence of interfering compounds. This was resolved by careful selection of reaction product ions which allowed us to detect differences between various commercial brands of pesto. We conclude that SIFT-MS may be a valid tool for the fast and reproducible analysis of flavourant terpenoids in basil and basil-derived foodstuffs.     

Microfluidics with MALDI analysis for proteomics—A review

Various microfluidic devices have been developed for proteomic analyses and many of these have been designed specifically for mass spectrometry detection. In this review, we present an overview of chip fabrication, microfluidic components, and the interfacing of these devices to matrix-assisted laser desorption ionization (MALDI) mass spectrometry. These devices can be directly coupled to the mass spectrometer for on-line analysis in real-time, or samples can be analyzed on-chip or deposited onto targets for off-line readout. Several approaches for combining microfluidic devices with analytical functions such as sample cleanup, digestion, and separations with MALDI mass spectrometry are discussed.     

Quantification of acetaldehyde released by lung cancer cells in vitro using selected ion flow tube mass spectrometry

The production of volatile compounds from cancer cell lines in vitro has been investigated using selected ion flow tube mass spectrometry (SIFT-MS). This technique enables on-line quantitative analyses of the headspace above cell/medium cultures. This paper reports the discovery that acetaldehyde is released by the lung cancer cell lines SK-MES and CALU-1. The concentration of acetaldehyde in the headspace of the medium/cell culture was measured after 16 h incubation at 37 degrees C and found to be proportional to the number of cancer cells in the medium (typically 10(8)). From these data, the acetaldehyde production rates of the SK-MES cells and the CALU-1 cells in vitro are determined to be 1 x 10(6) and 1.5-3 x 10(6) molecules/cell/min, respectively. The potential value of this new technique in cell biology and in industrial cell biotechnology is discussed.     

Application of a Self-developed Proton Transfer Reaction-Mass Spectrometer to On-line Monitoring Trace Volatile Organic Compounds in Ambient Air

Real-time and on-line monitoring volatile organic compounds(VOCs) are valuable for real-time evalua- ting air quality and monitoring the key source of pollution. A self-developed proton transfer reaction-mass spectrometer(PTR-MS) was constructed and applied to on-line monitoring trace VOCs in ambient air in Hefei, China. With the help of a self-developed catalytic converter, the background signal of the instrument was detected and the stability of the instrument was evaluated. The relative standard deviation of signal at m/z 21 was only 0.74% and the detection limit of PTR-MS was 97 part per trillion(97×10^-12, volume ratio). As a case of the air monitoring in Hefei, the ambient air at Dongpu reservoir spot was on-line monitored for 13 d with our self-developed PTR-MS. Meanwhile, a solid-phase micro-extraction(SPME) technique coupled to gas chromatography-mass spectrometry/mass spectrometry (GC-MS/MS) was also used for the off-line detection of the air. The results show that our self-developed PTR-MS can be used for the on-line and long-term monitoring of VOCs in air at part per trillion level, and the change trend of VOCs concentration monitored with PTR-MS was consistent with that detected with the conventional SPME-GC-MS. This self-developed PTR-MS can fully satisfy the requirements of air quality monitoring and real-time monitoring of the key pollution sources.     

Determination of trihalomethanes in water samples: a review

This article reviews the most recent literature addressing the analytical methods applied for trihalomethanes (THMs) determination in water samples. This analysis is usually performed with gas chromatography (GC) combined with a preconcentration step. The detectors most widely used in this type of analyses are mass spectrometers (MS) and electron capture detectors (ECD). Here, we review the analytical characteristics, the time required for analysis, and the simplicity of the optimised methods. The main difference between these methods lies in the sample pretreatment step; therefore, special emphasis is placed on this aspect. The techniques covered are direct aqueous injection (DAI), liquid-liquid extraction (LLE), headspace (HS), and membrane-based techniques. We also review the main chromatographic columns employed and consider novel aspects of chromatographic analysis, such as the use of fast gas chromatography (FGC). Concerning the detection step, besides the common techniques, the use of uncommon detectors such as fluorescence detector, pulsed discharge photoionization detector (PDPID), dry electrolytic conductivity detector (DELCD), atomic emission detector (AED) and inductively coupled plasma-mass spectrometry (ICP-MS) for this type of analysis is described.     

Rapid white truffle headspace analysis by proton transfer reaction mass spectrometry and comparison with solid-phase microextraction coupled with gas chromatography/mass spectrometry

The gastronomic relevance and high price of white truffle are related mainly to its unique aroma. Here we evaluate, for the first time, the possibility of characterizing in a rapid and non-destructive way the aroma of white truffles based on proton transfer reaction mass spectrometry (PTR-MS). We indicate that anonymous PTR-MS fingerprinting allows sample classification and we also compare qualitatively and quantitatively PTR-MS data with measurements made by solid-phase microextraction gas chromatography (SPME-GC) of the same samples under the same conditions. PTR-MS fragmentation data of truffle-relevant compounds are also published here for the first time. Most of the sulfur-containing compounds detected by GC and relevant for white truffle aroma have a high positive correlation with single PTR-MS peaks. Our work indicates that, after preliminary comparison with GC data, PTR-MS is a new tool for the rapid, quantitative and non-invasive characterization of white truffle by direct headspace injection without any pre-concentration.