Ion–molecule reactions (IMR) are at the very core of trace gas analyses in modern chemical ionization (CI) mass spectrometer instruments, which are increasingly being used in diverse areas of ...research and industry. The focus of this Perspective is on the ion chemistry that underpins gas-phase analytical CI methods. Special attention is given to the soft chemical ionization method known as selected ion flow tube-mass spectrometry (SIFT-MS). The processes involved in the ion chemistry of the reagent cations, H3O+, NO+, and O2 +•, and the anions, O–•, O2 –•, OH–, and NO2 –, are discussed in some detail. Stressed throughout is that an understanding of these processes is mandatory to obtain reliable analyses of humid gaseous media such as ambient air and exhaled breath. It is indicated that further research is needed to understand the consequences of replacing helium in some situations by the more readily available nitrogen as the carrier gas in SIFT-MS.
Rationale
In soft chemical ionization mass spectrometry, analyte ions are produced via ion–molecule reactions in the reactor. When an electric field E is imposed, the ion drift velocity vd determines ...the reaction time and the effective ion temperature. Agreement between experimental ion mobilities and theoretical predictions confirms the accuracy of the ion residence time measurement procedure.
Methods
A selected ion flow‐drift tube (SIFDT), an instrument with a chemical ionization source, was used to produce protonated aldehydes and selectively inject them into the resistive glass drift tube filled with He. Arrival‐time distributions of ions were obtained using the Hadamard modulation. Reduced ion mobilities were then obtained at a pressure of 2 hPa in the E/N range of 5–15 Td. Theoretical ion mobility values were calculated using two methods: hard‐sphere approximation and trajectory modelling.
Results
The measured mobilities of three saturated and three unsaturated protonated aldehydes do not show substantial variation across the studied E/N range. Effective temperatures calculated using the Wannier formula from measured gas temperatures ranged from 300 to 315 K. Experimentally obtained values of the near‐zero‐ E/N‐reduced ion mobilities agree with both methods of calculations typically within ±3% standard deviation (maximum ±5%).
Conclusions
The experimental SIFDT values of reduced mobilities in He of protonated aldehyde molecules generated from a chemical ionization source are in close agreement with two different theoretical methods based on the density functional theory calculations of ion geometries and partial atomic charges. Besides its fundamental importance, the ion mobility results validate the correct operation of the drift tube reactor and the ion residence time measurement procedure. Diffusion losses can also be determined from these results.
Exhaled breath analysis of volatile organic compounds (VOCs) has great potential in terms of disease diagnosis and measuring physiological response to treatment. In this study, selected ion flow tube ...mass spectrometry (SIFT-MS) has been applied for the quantification of VOCs in the exhaled breath from 3 groups of patients, viz., those with esophago-gastric cancer, noncancer diseases of the upper gastro-intestinal tract, and a healthy upper gastrointestinal tract cohort. A total of 17 VOCs have been investigated in this study. The concentrations of 4 VOCs, hexanoic acid, phenol, methyl phenol, and ethyl phenol, were found to be significantly different between cancer and positive control groups using the Mann–Whitney U test. Receiver operating characteristics (ROC) analysis was applied for a combination of 4 VOCs (hexanoic acid, phenol, methyl phenol, and ethyl phenol) to discriminate the esophago-gastric cancer cohort from positive controls. The integrated area under the ROC curve (AUC) is 0.91. The results highlight the potential of VOC profiling as a noninvasive test to identify those with esophago-gastric cancer.
The purpose of this short review is to describe the origins and the principles of operation of selected-ion flow-tube mass spectrometry (SIFT-MS) and proton-transfer-reaction mass spectrometry ...(PTR-MS), and their application to the analysis of biogenic volatile organic compounds (BVOCs) in ambient air, the humid air (headspace) above biological samples, and other samples. We briefly review the ion chemistry that underpins these analytical methods, which allows accurate analyses. We pay attention to the inherently uncomplicated sampling methodologies that allow on-line, real-time analyses, obviating sample collection into bags or onto traps, which can compromise samples.
Whilst these techniques have been applied successfully to the analysis of a wide variety of media, we give just a few examples of data, including for the analysis of BVOCs that are present in tropospheric air and those emitted by plants, in exhaled breath and in the headspace above cell and bacterial cultures (which assist clinical diagnosis and therapeutic monitoring), and the products of combustion. The very wide dynamic ranges of real-time analyses of BVOCs in air achieved by SIFT-MS and PTR-MS – from sub-ppbv to tens of ppmv – ensure that these analytical methods will be applied to many other media, especially when combined with gas-chromatography methods, as recently trialed.
Selected ion flow tube mass spectrometry (SIFT-MS) instruments have significantly developed since this technique was introduced more than 20 years ago. Most studies of the ion–molecule reaction ...kinetics that are essential for accurate analyses of trace gases and vapors in air and breath were conducted in He carrier gas at 300 K, while the new SIFT-MS instruments (optimized to quantify concentrations down to parts per trillion by volume) operate with N2 carrier gas at 393 K. Thus, we pose the question of how to reuse the data from the extensive body of previous literature using He at room temperature in the new instruments operating with N2 carrier gas at elevated temperatures. Experimentally, we found the product ions to be qualitatively similar, although there were differences in the branching ratios, and some reaction rate coefficients were lower in the heated N2 carrier gas. The differences in the reaction kinetics may be attributed to temperature, an electric field in the current flow tubes, and the change from He to N2 carrier gas. These results highlight the importance of adopting an updated reaction kinetics library that accounts for the new instruments’ specific conditions. In conclusion, almost all previous rate coefficients may be used after adjustment for higher temperatures, while some product ion branching ratios need to be updated.
Rationale
Secondary electrospray ionization (SESI) in a water spray environment at atmospheric pressure involves the reactions of hydrated hydronium reagent ions, H3O+(H2O)n, with trace analyte ...compounds in air samples. Understanding the formation and dehydration of reagent and analyte ions is the foundation for meaningful quantification of trace compounds by SESI‐mass spectrometry (MS).
Methods
A numerical model based on gas‐phase ion thermochemistry is developed that describes equilibria in H3O+(H2O)n reagent cluster ion distributions and ligand switching reactions with polar NH3 molecules leading to equilibrated hydrated ammonium ions NH4+(H2O)m. The model predictions are compared with experimental results obtained using a cylindrical SESI source coupled to an ion‐trap mass spectrometer via a heated ion transfer capillary. Non‐polar isoprene, C5H8, was used to further probe the nature of the reagent ions.
Results
Equilibrium distributions of H3O+(H2O)n ions and their reactions with NH3 molecules have been characterized by the model in the near‐atmospheric pressure SESI source. NH3 analyte molecules displace H2O ligands from the H3O+(H2O)n ions at the collisional rate forming NH4+(H2O)m ions, which travel through the heated ion transfer capillary losing H2O molecules. The data for variable NH3 concentrations match the model predictions and the C5H8 test substantiates the notion of dehydration in the heated capillary.
Conclusions
Large cluster ions formed in the SESI region are dehydrated to H3O+(H2O)1,2,3 and NH4+(H2O)1,2 while passing through the heated capillary, and considerable diffusion losses also occur. This phenomenon is also predicted for other polar analyte molecules, A, that can undergo similar switching reactions, thus forming AH+ and AH+(H2O)m analyte ions.
A study was performed of the reactions of protonated acetic acid hydrates, CH3COOHH+(H2O) n , with acetone molecules, CH3COCH3, using a selected ion flow-drift tube (SIFDT). The rationale for this ...study is that hydrated protonated organic molecules are major product ions in secondary electrospray ionization mass spectrometry (SESI-MS) and ion mobility spectrometry (IMS). Yet the formation and reactivity of these hydrates are only poorly understood, and kinetics data are only sparse. The existing SIFDT instrument in our laboratory was upgraded to include an octupole ion guide and a separate drift tube by which hydrated protonated ions can be selectively injected into the drift tube reactor and their reactions with molecules studied under controlled conditions. This case study shows that, in these hydrated ion reactions with acetone molecules, the dominant reaction process is ligand switching producing mostly proton-bound dimer ions (CH3COCH3)H+(CH3COOH), with minor branching into (CH3COCH3)H+(H2O). This switching reaction was observed to proceed at the collisional rate, while other studied hydrated ions reacted more slowly. An attempt is made to understand the reaction mechanisms and the structures of the reaction intermediate ions at the molecular level. Secondary switching reactions of the asymmetric proton-bound dimer ions lead to a formation of strongly bound symmetrical dimers (CH3COCH3)2H+, the terminating ion in this ion chemistry. These results strongly suggest that, in SESI-MS and IMS, the presence of a polar compound, like acetone in exhaled breath, can suppress the analyte ions of low concentration compounds like acetic acid thus compromising their quantification.
Urine is considered an ideal biofluid for clinical investigation because it is obtained noninvasively and relatively large volumes are easily acquired. In this study, selected ion flow tube mass ...spectrometry (SIFT-MS) has been applied for the quantification of volatile organic compounds (VOCs) in the headspace vapor of urine samples, which were retrieved from three groups of patients with gastro-esophageal cancer, noncancer diseases of the upper gastro-intestinal tract, and a healthy cohort. Eleven VOCs have been investigated in this study. The concentrations of seven VOCs–acetaldehyde, acetone, acetic acid, hexanoic acid, hydrogen sulfide, methanol, and phenol–were found to be significantly different between cancer, positive control, and healthy groups using the Kruskal–Wallis test. The concentrations of acetaldehyde, acetone, acetic acid, hexanoic acid, hydrogen sulfide, and methanol were increased in the cancer cohort compared with healthy controls while the concentration of phenol decreased. The differences in the concentrations of ethanol, propanol, methyl phenol, and ethyl phenol were not significant between cancer and control groups. Receiver operating characteristics (ROC) analysis was applied for a combination of six VOCs (acetaldehyde, acetone, acetic acid, hexanoic acid, hydrogen sulfide, and methanol) to discriminate cancer patients from noncancer controls. The integrated area under ROC curve is 0.904. This result indicates that VOC profiling may be suitable in identifying those at high risk of gastro-esophageal cancer. Therefore, further investigations should be undertaken to assess the potential for VOC profiling as a new screening test in gastro-esophageal cancer.
Rationale
The major objective of this exploratory study was to implement selected ion flow tube mass spectrometry, SIFT‐MS, as a method for the on‐line quantification of the volatile organic ...compounds, VOCs, in the headspace of the ground roasted coffee.
Methods
The optimal precursor ions and characteristic analyte ions were selected for real‐time SIFT‐MS quantification of those VOCs that are the most abundant in the headspace or known to contribute to aroma. NO+ reagent ion reactions were exploited for most of the VOC analyses. VOC identifications were confirmed using gas chromatography/mass spectrometry, GC/MS, coupled with solid‐phase microextraction, SPME.
Results
Thirty‐one VOCs were quantified, including several alcohols, aldehydes, ketones, carboxylic acids, esters and some heterocyclic compounds. Variations in the concentrations of each VOC in the seven regional coffees were typically less than a factor of 2, yet concentrations patterns characteristic of the different regional coffees were revealed by heat map and principal component analyses. The coefficient of variation in the concentrations across the seven coffees was typically below 24% except for furfural, furan, methylfuran and guaiacol.
Conclusions
The SIFT‐MS analytical method can be used to quantify in real time the most important odoriferous VOCs in ground coffee headspace to sufficient precision to reveal some differences in concentration patterns for coffee produced in different countries.
Glyoxal (C2H2O2) is a highly reactive molecule present at trace levels in specific gaseous environments. For analyses by chemical ionization mass spectrometry, it is important to understand the ...gas-phase chemistry initiated by reactions of H3O+ ions with C2H2O2 molecules in the presence of water vapour. This chemistry was studied at variable humidity using a selected ion flow tube, SIFT. The initial step is a proton transfer reaction forming protonated glyoxal C2H3O2+. The second step, in the presence of water vapour, is the association forming C2H3O2+(H2O) and interestingly also protonated formaldehyde CH2OH+. Hydrated protonated formaldehyde CH2OH+(H2O) was also observed. Relative signals of these four ionic products were studied at the end of the flow tube where the reactions took place during 0.3 ms in helium carrier gas (1.5 mbar, 300 K) as the water vapour number density varied up to 1014 cm−3. The data were interpreted using numerical kinetics modelling of the reaction sequences and the mechanisms and kinetics of the reaction steps were characterised. The results thus facilitate SIFT-MS analyses of glyoxal in humid air whilst drawing attention to ion overlaps with formaldehyde products.
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