SESI scientific resources
This is a compilation of scientific publications based on Secondary Electro-Spray Ionization (SESI). The purpose of this library is to promote SESI technology as a whole, to help researchers, and to show the broad scope of the applications of SESI. This compilation also includes some Extractive Electro-Spray Ionization (EESI) publications, originally developed by Zenobi and colleagues because, in the early days of these developments, the terms EESI and SESI were used indistinctly. Nowadays the term SESI is used when the ionization occurs mainly via vapor-ion interaction.
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Breath analysis, featured publications,
T. Zivkovic Semren*, S. Majeed, M. Fatarova, C. Laszlo, C. Pak, S. Steiner, G. Vidal, A. Kuczaj, A. Mazurov, M. C. Peitsch, N. V. Ivanov, J. Hoeng, P. A. Guy
Inhalation as a route for administering drugs and dietary supplements has garnered significant attention over the last decade. We performed real-time analysis of aerosols using secondary electrospray ionization (SESI) technology interfaced with high-resolution mass spectrometry (HRMS)
B. Streckenbach, M. Osswald, S. Malesevic, R. Zenobi, and M. Kohler
Chemical analysis of exhaled breath have suggested the existence of an OSA-specific metabolic signature. Here, we validated this diagnostic approach and the proposed marker compounds, as well as their potential to reliably diagnose OSA.
Kapil Dev Singh, Martin Osswald, Victoria C. Ziesenitz, Mo Awchi, Jakob Usemann, Lukas L. Imbach, Malcolm Kohler, Diego García-Gómez, Johannes van den Anker, Urs Frey, Alexandre N. Datta & Pablo Sinues
Therapeutic management of epilepsy remains a challenge, since optimal systemic antiseizure medication (ASM) concentrations do not always correlate with improved clinical outcome and minimal side effects. We tested the feasibility of noninvasive real-time breath metabolomics as an extension of traditional therapeutic drug monitoring for patient stratification by simultaneously monitoring drug-related and drug-modulated metabolites.
Jiayi Lan, Jérôme Kaeslin, Giorgia Greter, Renato Zenobi
Here, we show that besides ion suppression, ion competition in the C-trap of Orbitrap instruments is another important factor that influences sensitivity and reproducibility of SESI-MS. Instead of acquiring the full mass-to-charge ratio (m/z) range, acquisition of consecutive m/z windows to minimize the ion competition effect allows the detection of more features.
K.Dev Singh, G. Tancev, F. Decrue, J. Usemann, R. Appenzeller, P.Barreiro, G. Jaumà, M. Macia Santiago, G. Vidal de Miguel, U.Frey, P. Sinues
Despite the attractiveness of breath analysis as a non-invasive means to retrieve relevant metabolic information, its introduction into routine clinical practice remains a challenge.
Biology & microbiology, featured publications, :
Hendrik G. Mengers, Christina Schier, Martin Zimmermann, Martin C. H. Gruhlke, Eric Block, Lars M. Blank*, Alan J. Slusarenko
Using SESI-Orbitrap MS, we measured gas phase concentrations of allicin evaporating from a pure solution. The SESI-Orbitrap MS was used to follow the known chemistry of alliin, isoallin and methiin conversion in garlic, onion and ramsons. Allicin and its metabolites were also measured in human breath after garlic consumption. These results demonstrate the utility of SESI-Orbitrap MS for analysis of sulfur-containing volatiles from plants and for capturing volatilomes of foodstuffs in general.
Hendrik G. Mengers, Martin Zimmermann & Lars M. Blank
We use secondary electrospray ionisation high-resolution Orbitrap mass spectrometry (SESI-Orbitrap MS) to monitor the complete yeast volatilome every 2.3 s. Over 200 metabolites were identified during growth in shake flasks and bioreactor cultivations, all with their unique intensity profile. Special attention was paid to ethanol as biotech largest product and to acetaldehyde as an example of a low-abundance but highly volatile metabolite. Volatilome shifts are visible, e.g. after glucose depletion, fatty acids are converted to ethyl esters in a detoxification mechanism after stopped fatty acid biosynthesis. This work showcases the SESI-Orbitrap MS system for tracking microbial physiology without the need for sampling and for time-resolved discoveries during metabolic transitions.
Jiayi Lan, Giorgia Greter, Bettina Streckenbach, Markus Arnoldini, Renato Zenobi & Emma Slack
We demonstrate that secondary electrospray ionization mass spectrometry can be used to non-invasively monitor metabolic activity of the intestinal microbiome of a live, awake mouse. This was achieved via analysis of the headspace volatile and semi-volatile metabolome of individual gut microbiota bacterial species growing in pure culture, as well as from live gnotobiotic mice specifically colonized with these microbes. The microbial origin of these compounds was confirmed by feeding of heavy-isotope labeled microbiota-accessible sugars. This reveals that the microbiota is a major contributor to the released metabolites of a whole live mouse, and that it is possible to capture the catabolism of sugars and cross-feeding within the gut microbiota of a living animal using volatile/semi-volatile metabolite monitoring.
Fouad Choueirya, Jiangjiang Zhu
Lung cancer is one of the leading causes of cancer related deaths in the United States. A novel volatile analysis platform is needed to complement current diagnostic techniques and better elucidate chemical signatures of lung cancer and subsequent treatments. A systems biology bottom-up approach using cell culture volatilomics was employed to identify pathological volatile fingerprints of lung cancer in real time. An advanced secondary electrospray ionization (SESI) source, named SuperSESI was used in this study and directly attached to a Thermo Q-Exactive high-resolution mass spectrometer (HRMS).
Jisun H. J. Lee and Jiangjiang Zhu
Gut microbiota plays essential roles in maintaining gut homeostasis. The composition of gut microbes and their metabolites are altered in response to diet and remedial agents such as antibiotics. However, little is known about the effect of antibiotics on the gut microbiota and their volatile metabolites. In this study, we evaluated the impact of a moderate level of ampicillin treatment on volatile fatty acids (VFAs) of gut microbial cultures using an optimized real-time secondary electrospray ionization coupled with high-resolution mass spectrometry (SESI-HRMS).
All publications by year
2023
Fouad Choueiry, Rui Xu, Kelly Meyrath, Jiangjiang Zhu.
Secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS) is an innovative analytical technique for the rapid and non-invasive analysis of volatile organic compounds (VOCs). However, compound annotation and ion suppression in the SESI source has hindered feature detection, stability and reproducibility of SESI-HRMS in untargeted volatilomics.
Fouad Choueiry, Andrew Gold, Rui Xu, Shiqi Zhang and Jiangjiang Zhu.
The symbiotic relationship between the gut microbial population is capable of regulating numerous aspects of host physiology, including metabolism. Bacteria can modulate the metabolic processes of the host by feeding on nutritional components within the lumen and releasing bioactive components into circulation. Endogenous volatile organic compound (VOC) synthesis is dependent on the availability of precursors found in mammalian metabolism
Mo Awchi, Kapil Dev Singh, Patricia E Dill, Urs Frey, Alexandre N Datta, and Pablo Sinues.
Therapeutic drug monitoring (TDM) of medications with a narrow therapeutic window is a common clinical practice to minimize toxic effects and maximize clinical outcomes. Routine analyses rely on the quantification of systemic blood concentrations of drugs. Alternative matrices such as exhaled breath are appealing because of their inherent non-invasive nature. This is especially the case for pediatric patients. We have recently
M.Z. Islam, S. Giannoukos, Räisänen, K. Wang, X. Ma, F. Wahl, R. Zenobi, M. Niu.
To date, the commonly used methods to assess rumen fermentation are invasive. Exhaled breath contains hundreds of volatile organic compounds (VOC) that can reflect animal physiological processes. In the present study, for the first time, we aimed to use a non-invasive metabolomics approach based on high-resolution mass spectrometry to identify rumen fermentation parameters in dairy cows
Ronja Weber, Bettina Streckenbach, Lara Welti, Demet Inci, Malcolm Kohler, Nathan Perkins, Renato Zenobi, Srdjan Micic , and Alexander Moeller.
There is a need to improve the diagnosis and management of pediatric asthma. Breath analysis aims to address this by non-invasively assessing altered metabolism and disease-associated processes.
Patrik Španěl, Kseniya Dryahina, Maroua Omezzine Gnioua, David Smith
The detection sensitivity of secondary electrospray ionisation mass spectrometry (SESI-MS) is much lower for saturated aldehydes than for unsaturated aldehydes. This needs to be understood in terms of gas phase ion-molecule reaction kinetics and energetics to make SESI-MS analytically more quantitative.
Kim Arnold, Philippe Dehio, Jonas Lötscher, Kapil Dev Singh, Diego García-Gómez, Christoph Hess, Pablo Sinues, and Maria L. Balmer
Dendritic cells (DCs) actively sample and present antigen to cells of the adaptive immune system and are thus vital for successful immune control and memory formation. Immune cell metabolism and function are tightly interlinked, and a better understanding of this interaction offers potential to develop immunomodulatory strategies. However, current approaches for assessing the immune cell metabolome are often limited by endpoint measurements, may involve laborious sample preparation, and may lack unbiased, temporal resolution of the metabolome. In this study, we present a novel setup coupled to a secondary electrospray ionization-high resolution mass spectrometric (SESI-HRMS) platform allowing headspace analysis of immature andactivated DCs in real-time with minimal sample preparation and intervention, with high technical reproducibility and potential for automation.
Mo Awchi, Pablo Sinues, Alexandre N. Datta, Diego García-Gómez, and Kapil Dev Singh
Real-time breath analysis using secondary electrospray ionization coupled with high-resolution mass spectrometry is a fast and noninvasive method to access the metabolic state of a person. However, it lacks the ability to unequivocally assign mass spectral features to compounds due to the absence of chromatographic separation. This can be overcomed by using exhaled breath condensate and conventional liquid chromatography–mass spectrometry (LC–MS) systems.
2022:
Bettina Streckenbach, Justinas Sakas, Nathan Perkins, Malcolm Kohler, Alexander Moeller and Renato Zenobi.
Applications for direct breath analysis by mass spectrometry (MS) are rapidly expanding. One of the more recent mass spectrometry-based approaches is secondary electrospray ionization coupled to high-resolution mass spectrometry (SESI-HRMS). Despite increasing usage, the SESI methodology still lacks standardization procedures for quality control and absolute quantification.
Cedric Wüthrich, Zhiyuan Fan, Guy Vergères, Fabian Wahl, Renato Zenobi and Stamatios Giannoukos.s
Quantification of metabolites present within exhaled breath is a major challenge for on-line breath analysis. It is also important for gauging the analytical performance, accuracy, reproducibility, reliability, and stability of the measuring technology. Short-chain fatty acids (SCFAs) are of high interest for nutrition and health.
Amanda Gisler, Kapil Dev Singh, Jiafa Zeng, Martin Osswald, Mo Awchi, Fabienne Decrue, Felix Schmidt, Noriane A. Sievi, Xing Chen, Jakob Usemann, Urs Frey, Malcolm Kohler, Xue Li, Pablo Sinues
Exhaled breath contains valuable information at the molecular level and offers promising potential for precision medicine. However, few breath tests transition to routine clinical practice, partly because of the missing validation in multicenter trials. Therefore, we developed and applied an interoperability framework for standardized multicenter data acquisition and processing for breath analysis with secondary electrospray ionization-high resolution mass spectrometry.
Ronja Weber, Jérôme Kaeslin, Sophia Moeller, Nathan Perkins, Srdjan Micic, and Alexander Moeller.
Environmental volatile organic compounds (VOCs) from the ambient air potentially influence on-line breath analysis measurements by secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS). The aim of this study was to investigate how inhaling through a VOC filter affects the detected breath profiles and whether it is feasible to integrate such filters into routine measurements..
T. Zivkovic Semren*, S. Majeed, M. Fatarova, C. Laszlo, C. Pak, S. Steiner, G. Vidal, A. Kuczaj, A. Mazurov, M. C. Peitsch, N. V. Ivanov, J. Hoeng, P. A. Guy
Inhalation as a route for administering drugs and dietary supplements has garnered significant attention over the last decade. We performed real-time analysis of aerosols using secondary electrospray ionization (SESI) technology interfaced with high-resolution mass spectrometry (HRMS)
R Weber, B Streckenbach, J Kaeslin, L Welti, D Inci, N Perkins, R Zenobi, S Micic, A Möller.
We hypothesized that the breath of children with allergic asthma contains a unique signature of disease specific metabolites. Using secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS), we aimed to identify relevant VOCs to assess underlying interconnections between biomarkers belonging to common metabolic pathways in the pathophysiology of asthma.
Felix Schmidt, Nora Nowak, Patrick Baumgartner, Thomas Gaisl, Stefan Malesevic, Bettina Streckenbach, Noriane A. Sievi, Esther I. Schwarz, Renato Zenobi, Steven A. Brown, and Malcolm Kohler.
The direct pathophysiological effects of obstructive sleep apnea (OSA) have been well described. However, the systemic and metabolic consequences of OSA are less well understood.
A. Gómez-Mejia, K. Arnold, J. Bär, K. Dev Singh, T. C. Scheier, S. D. Brugger, A. S. Zinkernagel, P. Sinues
Early detection of pathogenic bacteria is needed for rapid diagnostics allowing adequate and timely treatment of infections.
Ronja Weber, Nathan Perkins, Tobias Bruderer, Srdjan Micic and Alexander Moeller.
The early detection of inflammation and infection is important to prevent irreversible lung damage in cystic fibrosis. Novel and non-invasive monitoring tools would be of high benefit for the quality of life of patients.
F. Schmidt ; M. Osswald ; R. Zenobi ; M. Kohler
Monitoring of drug pharmacokinetics is used in personalized therapy, therapeutic drug monitoring (TDM), toxicology assessments, doping controls and clinical drug development. Drugs are predominantly measured in plasma, serum or urine. Monitoring of volatile organic compounds (VOCs) in breath has so far not received much attention, but nevertheless it has many advantages over conventional approaches
B. Streckenbach, M. Osswald, S. Malesevic, R. Zenobi, and M. Kohler
Chemical analysis of exhaled breath have suggested the existence of an OSA-specific metabolic signature. Here, we validated this diagnostic approach and the proposed marker compounds, as well as their potential to reliably diagnose OSA.
Jérôme Kaeslin, Cedric Wüthrich, Stamatios Giannoukos, and Renato Zenobi
Secondary electrospray ionization (SESI) is a soft ionization method, which is important to avoid interference from in-source fragments and to simplify compound annotation. In this work, it is shown that SESI is softer than electrospray ionization (ESI), and therefore, SESI indeed qualifies as a soft ionization technique. However…
A. Gómez-Mejia, K. Arnold, J. Bär, K. Dev Singh, T. C. Scheier, S. D. Brugger, A. S. Zinkernagel, P. Sinues
Early detection of pathogenic bacteria is needed for rapid diagnostics allowing adequate and timely treatment of infections.
C. Wüthrich, M.de Figueiredo, K. J. Burton-Pimentel, G. Vergères, F. Wahl, R. Zenobi and S. Giannoukos
For the first time, this study demonstrates the application of SESI-HRMS in the field of nutritional science using a standardized nutritional intervention, consisting of a high-energy shake. Tentative compounds include fatty acids, amino acids, and amino acid derivatives, some of them likely derived from nutrients by the gut microbiome, as well as organic acids from the Krebs cycle. Time-series clustering showed an overlap of observed kinetic trends with those reported previously in blood plasma.
Kim Arnold, Xing Chen, Hui Zhang, Kapil Dev Singh, Zhihong Yin, Yao Yao, Tiangang Luan, Pablo Sinues, and Xue Li
Secondary electrospray ionization-high resolution mass spectrometry allows monitoring in vivo 2H-incorporation of metabolites in a non-invasive and real-time setup and opens new opportunities to use 2H tracing to extend current metabolic studies, especially those with a focus on anaerobic glycolysis, lysine methylation and gut microbiome via monitoring of short-chain fatty acids.
Charles D.Smith, Ashley C.Fulton, Mark Romanczyk, Braden C. Giordano, Christopher J. Katilie, Lauryn E. DeGreeffe
Determination of fentanyl vapor signature enables the identification of target analytes for the indirect detection of the parent opioid without direct sample handling.
Hendrik G. Mengers, Christina Schier, Martin Zimmermann, Martin C. H. Gruhlke, Eric Block, Lars M. Blank*, Alan J. Slusarenko
Using SESI-Orbitrap MS, we measured gas phase concentrations of allicin evaporating from a pure solution. The SESI-Orbitrap MS was used to follow the known chemistry of alliin, isoallin and methiin conversion in garlic, onion and ramsons. Allicin and its metabolites were also measured in human breath after garlic consumption. These results demonstrate the utility of SESI-Orbitrap MS for analysis of sulfur-containing volatiles from plants and for capturing volatilomes of foodstuffs in general.
Hendrik G. Mengers, Martin Zimmermann & Lars M. Blank
We use secondary electrospray ionisation high-resolution Orbitrap mass spectrometry (SESI-Orbitrap MS) to monitor the complete yeast volatilome every 2.3 s. Over 200 metabolites were identified during growth in shake flasks and bioreactor cultivations, all with their unique intensity profile. Special attention was paid to ethanol as biotech largest product and to acetaldehyde as an example of a low-abundance but highly volatile metabolite. Volatilome shifts are visible, e.g. after glucose depletion, fatty acids are converted to ethyl esters in a detoxification mechanism after stopped fatty acid biosynthesis. This work showcases the SESI-Orbitrap MS system for tracking microbial physiology without the need for sampling and for time-resolved discoveries during metabolic transitions.
Wetter Slack, Emma (ETH Zurich)
Dataset used in Non-invasive monitoring of microbiota and host metabolism using secondary electrospray ionization.
Jiayi Lan, Giorgia Greter, Bettina Streckenbach, Markus Arnoldini, Renato Zenobi & Emma Slack
We demonstrate that secondary electrospray ionization mass spectrometry can be used to non-invasively monitor metabolic activity of the intestinal microbiome of a live, awake mouse. This was achieved via analysis of the headspace volatile and semi-volatile metabolome of individual gut microbiota bacterial species growing in pure culture, as well as from live gnotobiotic mice specifically colonized with these microbes. The microbial origin of these compounds was confirmed by feeding of heavy-isotope labeled microbiota-accessible sugars. This reveals that the microbiota is a major contributor to the released metabolites of a whole live mouse, and that it is possible to capture the catabolism of sugars and cross-feeding within the gut microbiota of a living animal using volatile/semi-volatile metabolite monitoring.
R. Weber, B. Streckenbach, L. Welti, D. Inci, M. Kohler, N. Perkins, R. Zenobi, S. Micic⋆, A. Moeller
Breath analysis was performed via a SESI source linked to a high-resolution mass spectrometer. 48 allergic asthmatics and 56 healthy controls were included in the study. We found several pathways that are well-represented by the significant metabolites, for example lysine degradation elevated in the asthmatic group and two arginine pathways in the healthy group. For the first time, a large number of breath-derived volatile organic compounds (VOCs) that discriminate children with allergic asthma from healthy controls were identified. Many are linked to well-described metabolic pathways and chemical families involved in pathophysiological processes of asthma. Furthermore, a subset of these VOCs showed high potential for clinical diagnostic applications.
Chiara Veronese Francesco Segrado Riccardo Caldarella Roberto Boffi Rosaria Orlandi
Breath analysis for the identification of volatile organic compounds by mass spectrometry is a very innovative and non-invasive technology, which represents a great opportunity for an early and personalised diagnosis. In this pilot study we recruited a series of volunteers, smokers and non-smokers, characterized from the respiratory point of view, and profiled their exhaled breath through SESI- HRMS technology. The aim of the study is to identify a volatile molecular signature associated with tobacco use. The supervised analysis highlighted 32 features that discriminate the breath of smokers and non-smoker subjects, at the baseline. We therefore identified a volatile molecular signature closely related to tobacco smoke, which will be characterized in subsequent studies
Fouad Choueiry, Addison Barham, Jiangjiang Zhu
Lung cancer is one of the leading causes of cancer incidence and cancer-related deaths in the world. Early diagnosis of pulmonary tumors results in improved survival compared to diagnosis with more advanced disease, yet early disease is not reliably indicated by symptoms. Despite of the improved testing and monitoring techniques for lung cancer in the past decades, most diagnostic tests, such as sputum cytology or tissue biopsies, are invasive and risky, rendering them unfeasible for large population screening. The non-invasive analysis of exhaled breath has gained attentions as an innovative screening method to measure chemical alterations within the human volatilome profile as a result of oncogenesis. More importantly, volatile organic compounds (VOCs) have been correlated to the pathophysiology of disease since the source of volatile compounds relies mostly on endogenous metabolic processes that are altered as a result of disease onset.
Bettina Streckenbach
Exhaled breath can reveal insights about the metabolic state of the human body through the endo- and exogenous compounds it contains. The extent of detectable compounds, however, was revolutionized by the application of mass spectrometry. More specifically, secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS) enables the detection of a broad range of breath-derived compounds simultaneously and with high sensitivity. Together with its rapid and non-invasive nature, direct breath analysis by SESI-HRMS raised particular interest for clinical applications. Over the past years, various clinical trials successfully demonstrated the technology´s capability for biomarker discovery in exhaled breath in adults and more recently in children. Current challenges lie within the potential translation of SESI-HRMS into clinical settings and the requirements therein, such as biomarker identification and validation, which became a focus of more recent studies..
Jiafa Zeng, Alexandra Christen, Kapil Dev Singh, Urs Frey, and Pablo Sinues
Real-time breath analysis by high-resolution mass spectrometry (HRMS) is a promising method to non-invasively retrieve relevant biochemical information. In this work, we conducted a head-to-head comparison of two ionization techniques: Secondary electrospray ionization (SESI) and plasma ionization (PI), for the analysis of exhaled breath. Two commercially available SESI and PI sources were coupled to the same HRMS device to analyze breath of two healthy individuals in a longitudinal study. We analyzed 58 breath specimens in both platforms, leading to 2,209 and 2,296 features detected by SESI-HRMS and by PI-HRMS, respectively. 60% of all the mass spectral features were detected in both platforms. However, remarkable differences were noted in terms of the signal-to-noise ratio (S/N), whereby the median (interquartile range, IQR) S/N ratio for SESI-HRMS was 115 (IQR = 408), whereas for PI-HRMS it was 5 (IQR = 5). Differences in the mass spectral profiles for the same samples make the inter-comparability of both techniques problematic. Overall, we conclude that both techniques are excellent for real-time breath analysis because of the very rich mass spectral fingerprints. However, further work is needed to fully understand the exact metabolic insights one can gather using each of these platforms.
Kolli, A.R., Semren, T.Z., Bovard, D. et al.
In vitro screening for pharmacological activity of existing drugs showed chloroquine and hydroxychloroquine to be effective against severe acute respiratory syndrome coronavirus 2. Oral administration of these compounds to obtain desired pulmonary exposures resulted in dose-limiting systemic toxicity in humans. However, pulmonary drug delivery enables direct and rapid administration to obtain higher local tissue concentrations in target tissue. In this work, inhalable formulations for thermal aerosolization of chloroquine and hydroxychloroquine were developed, and their physicochemical properties were characterized. Thermal aerosolization of 40 mg/mL chloroquine and 100 mg/mL hydroxychloroquine formulations delivered respirable aerosol particle sizes with 0.15 and 0.33 mg per 55 mL puff, respectively. In vitro toxicity was evaluated by exposing primary human bronchial epithelial cells to aerosol generated from Vitrocell. An in vitro exposure to 7.24 μg of chloroquine or 7.99 μg hydroxychloroquine showed no significant changes in cilia beating, transepithelial electrical resistance, and cell viability. The pharmacokinetics of inhaled aerosols was predicted by developing a physiologically based pharmacokinetic model that included a detailed species-specific respiratory tract physiology and lysosomal trapping.
2021:
Jérôme Kaeslin, Srdjan Micic, Ronja Weber, Simona Müller, Nathan Perkins, Christoph Berger, Renato Zenobi, Tobias Bruderer, and Alexander Moeller
Continuous monitoring of metabolites in exhaled breath has recently been introduced as an advanced method to allow non-invasive real-time monitoring of metabolite shifts during rest and acute exercise bouts. The purpose of this study was to continuously measure metabolites in exhaled breath samples during a graded cycle ergometry cardiopulmonary exercise test (CPET), using secondary electrospray high resolution mass spectrometry (SESI-HRMS).We also sought to advance the research area of exercise metabolomics by comparing metabolite shifts in exhaled breath samples with recently published data on plasma metabolite shifts during CPET.
Jérôme Kaeslin, Srdjan Micic, Ronja Weber, Simona Müller, Nathan Perkins, Christoph Berger, Renato Zenobi, Tobias Bruderer, and Alexander Moeller
Identifying and differentiating bacteria based on their emitted volatile organic compounds (VOCs) opens vast opportunities for rapid diagnostics. Secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS) is an ideal technique for VOC-biomarker discovery because of its speed, sensitivity towards polar molecules and compound characterization possibilities. Here, an in vitro SESI-HRMS workflow to find biomarkers for cystic fibrosis (CF)-related pathogens P. aeruginosa, S. pneumoniae, S. aureus, H. influenzae, E. coli and S. maltophilia is described.
Fouad Choueirya, Jiangjiang Zhu
Lung cancer is one of the leading causes of cancer related deaths in the United States. A novel volatile analysis platform is needed to complement current diagnostic techniques and better elucidate chemical signatures of lung cancer and subsequent treatments. A systems biology bottom-up approach using cell culture volatilomics was employed to identify pathological volatile fingerprints of lung cancer in real time. An advanced secondary electrospray ionization (SESI) source, named SuperSESI was used in this study and directly attached to a Thermo Q-Exactive high-resolution mass spectrometer (HRMS).
Fabienne Decrue, Kapil Dev Singh, Amanda Gisler, Mo Awchi, Jiafa Zeng, Jakob Usemann, Urs Frey and Pablo Sinues
Breath analysis by secondary electrospray ionization-high resolution mass spectrometry (SESI-HRMS) offers the possibility to measure comprehensive metabolic profiles. The technology is currently being deployed in several clinical settings in Switzerland and China. However, patients are required to exhale directly into the device located in a dedicated room. Consequently, clinical implementation in patients incapable of performing necessary exhalation maneuvers (e.g., infants) or immobile (e.g., too weak, elderly, or in intensive care) remains a challenge. The aim of this study was to develop a method to extend such breath analysis capabilities to this subpopulation of patients by collecting breath samples remotely (offline) and promptly (within 10 min) transfer them to SESI-HRMS for chemical analysis.
N.Nowak, T. Gaisl, D. Miladinovic, R. Marcinkevics, M. Osswald, S. Bauer, J. Buhmann, R. Zenobi, P. Sinues, S. A. Brown, M. Kohler
Using exhaled breath analysis by secondary high-resolution mass spectrometry, we measured the human exhaled metabolome at 10-s resolution across a night of sleep in combination with conventional polysomnography. Our subsequent analysis of almost 2,000 metabolite features demonstrates rapid, reversible control of major metabolic pathways by the individual vigilance states. A switch to wake reduces fatty acid oxidation, a switch to slow-wave sleep increases it, and the transition to rapid eye movement sleep results in elevation of tricarboxylic acid (TCA) cycle intermediates. Thus, in addition to daily regulation of metabolism, there exists a surprising and complex underlying orchestration across sleep and wake. Both likely play an important role in optimizing metabolic circuits for human performance and health.
Francisco G. Blanco and Guillermo Vidal-de-Miguel
Here, we review the SESI technology development, the different SESI configurations developed, and the standardization procedures described to translate SESI into the clinical environment. Finally, SESI main applications described in the literature with prompt translation into the clinical environment, namely, biomarker discovery or pharmacokinetics and drug monitoring are revised.
Kseniya Dryahina, Miroslav Polášek, David Smith, Patrik Španěl
Secondary electrospray ionization (SESI) is currently only semi-quantitative. In the Zspray™ arrangement of SESI-MS, the transfer of ions from near atmospheric pressure to a triple quadrupole is achieved by guiding E-fields that partially desolvate both reagent and analyte ions which must be understood.
Kapil Dev Singh, Martin Osswald, Victoria C. Ziesenitz, Mo Awchi, Jakob Usemann, Lukas L. Imbach, Malcolm Kohler, Diego García-Gómez, Johannes van den Anker, Urs Frey, Alexandre N. Datta & Pablo Sinues
Therapeutic management of epilepsy remains a challenge, since optimal systemic antiseizure medication (ASM) concentrations do not always correlate with improved clinical outcome and minimal side effects. We tested the feasibility of noninvasive real-time breath metabolomics as an extension of traditional therapeutic drug monitoring for patient stratification by simultaneously monitoring drug-related and drug-modulated metabolites.
Chao Liu, Jiafa Zeng, Pablo Sinues, Mingliang Fang, Zhen Zhou, Xue Li.
SESI-HRMS has been successfully applied in multiple applications, including breath analysis, animals and plants VOCs emissions, analysis of headspace of cell cultures and indoor and outdoor air. In this study we aim to develop a quantitative method for eight representative VOCs, including ketones (acetone, 2-butanone and 2-pentanone), alkenes (isoprene and α-terpinene) and aromatics (toluene, styrene and mesitylene).
T. Živković Semren, S. Majeed, M. Fatarova, C. Laszlo, C. Pak, S. Steiner, A. Kuczaj, A. Mazurov, M. Peitsch, N. Ivanov, J. Hoeng, and P. A. Guy
We used a programmable dual syringe pump (PDSP) connected to a super secondary electrospray ionisation (SESI) system interfaced with a Q Exactive HF mass spectrometer (MS) to detect the main constituents of thermally generated aerosols in real time. The benefits of Super SESI–HRMS for detecting drug aerosolisation from variably prepared in-house formulations with anatabine, azithromycin, chloroquine, favipiravir, and hydroxychloroquine were evaluated.
Zhihong Yin, Wenbo Huang, Kapil Dev Singh, Zhaoming Chen, Xing Chen, Zhen Zhou, Zifeng Yang, Pablo Sinues and Xue Li
We report that influenza A virus infection induces changes in odor traits that could be captured by real-time high-resolution mass spectrometry in a living mouse model. The most striking changes in the volatile metabolites may be associated mostly to glyoxylate/dicarboxylate metabolism.
Nora Nowak, Anna Engler, Sira Thiel, Anna S. Stöberl, Pablo Sinues, Renato Zenobi, Malcolm Kohler
Here, we could confirm significant differences between metabolic patterns in exhaled breath from OSA patients compared to control subjects without OSA as well as the association of breath biomarker levels with disease severity. Our prediction of the diagnosis for the patients from this completely independent validation study using a classification model trained on the data from the previous study resulted in an area under the receiver operating characteristic curve of 0.66, which is comparable to questionnaire-based OSA screenings.
Xing Chen, Keda Zhang, Zhihong Yin, Mingliang Fang, Weidan Pu, Zhening Liu, Lei Li, Pablo Sinues, Robert Dallmann, Zhen Zhou and Xue Li
This study advances our knowledge on the mechanism by which nonvolatile drugs are transferred from blood into exhaled breath, providing guidance for breath test-based therapeutic drug monitoring.
Jiayi Lan, Jérôme Kaeslin, Giorgia Greter, Renato Zenobi
Here, we show that besides ion suppression, ion competition in the C-trap of Orbitrap instruments is another important factor that influences sensitivity and reproducibility of SESI-MS. Instead of acquiring the full mass-to-charge ratio (m/z) range, acquisition of consecutive m/z windows to minimize the ion competition effect allows the detection of more features.
Xin Xu, · Jia Fa Zeng, · Dan Dan Jin,· Zheng Xu Huang, · Lei Li,·Anthony S. Wexler, · Man Nin Chan, ·Zhen Zhou, · Yong Jie Li and Xue Li
we demonstrated the working principles of secondary nanoelectrospray ionization (Sec-nESI) for real-time measurement of laboratory-generated organic aerosols using l-tartaric acid (TA) as a model compound. Factors affecting the detection of TA particles using a homemade Sec-nESI source coupled with a high-resolution mass spectrometer are systematically investigated.
2020:
Jisun HJ Lee, Jiangjiang Zhu
The analysis of exhaled breath (breathomics) has gained attention as a useful technique to measure the human VOC profile altered as a result of dietary interventions. In this mini-review, we examined recent clinical trials that performed promising dietary interventions, SCFAs analysis in plasma/feces, and VOC profile analysis in exhaling breath to understand the relationship between dietary intervention and metabolic health.
Steven A. Brown, Pablo Sinues
Metabolites like melatonin are essential in determining circadian phase. In the recent years, comprehensive metabolome analyses have unveiled entire panels of small biomolecules fluctuating in a circadian fashion, thus enabling a more precise determination of inner time and understanding of how circadian clock operates at the molecular level. Emerging analytical techniques allowing for the determination of exhaled metabolites in breath show promise to gain further insights noninvasively and in vivo into circadian metabolism.
Ronja Weber, Naemi Haas, Astghik Baghdasaryan, Tobias Bruderer, Demet Inci, Srdjan Micic, Nathan Perkins, Renate Spinas, Renato Zenobi, Alexander Moeller
Early pulmonary infection and inflammation result in irreversible lung damage and are major contributors to cystic fibrosis (CF)-related morbidity. An easy to apply and noninvasive assessment for the timely detection of disease-associated complications would be of high value. We aimed to detect volatile organic compound (VOC) breath signatures of children with CF by real-time secondary electrospray ionisation high-resolution mass spectrometry (SESI-HRMS).
A total of 101 children, aged 4–18 years (CF=52; healthy controls=49) and comparable for sex, body mass index and lung function were included in this prospective cross-sectional study. Exhaled air was analysed by a SESI-source linked to a high-resolution time-of-flight mass spectrometer. Mass spectra ranging from m/z 50 to 500 were recorded.
Out of 3468 m/z features, 171 were significantly different in children with CF (false discovery rate adjusted p-value of 0.05). The predictive ability (CF versus healthy) was assessed by using a support-vector machine classifier and showed an average accuracy (repeated cross-validation) of 72.1% (sensitivity of 77.2% and specificity of 67.7%).
This is the first study to assess entire breath profiles of children with SESI-HRMS and to extract sets of VOCs that are associated with CF. We have detected a large set of exhaled molecules that are potentially related to CF, indicating that the molecular breath of children with CF is diverse and informative.
Ronja Weber, Srdjan Micic, Bettina Streckenbach, Lara Welti, Tobias Bruderer, Nathan Perkins, Demet Inci, Jakob Usemann, Alexander Möller
The diagnosis of asthma in children is still a clinical challenge. Breath-analysis has the potential to overcome this challenge. Our goal is to show that secondary electrospray ionization high-resolution mass-spectrometry (SESI-HRMS) can be used to detect asthma-specific metabolites in exhaled breath.
We are conducting an exploratory observational study comparing the molecular composition of exhaled breath from school children (5-18 years) with allergic asthma (confirmed by objective tests) to healthy controls. Patients are taken off their asthma medication two weeks prior to breath measurements. Breath analysis is performed on an AB SCIEX TripleTOF 5600+ HRMS coupled to a Super SESI ion source, detecting m/z features between 50 and 500 Da (mass accuracy <1ppm). A combination of data extraction and machine learning models is used to isolate the most discriminative features and assess the predictive power of breath profiles.
We acquired data from 47 children (21 with allergic asthma, 26 healthy controls). In our preliminary data analysis, we identified 193 m/z features which differed significantly between the two groups (adjusted p value < 0.05), which showed an average predictive power (asthma vs. healthy) of 78.7% (leave-one-out cross-validation with Random Forests algorithm). We could allocate molecular formulas to most significant m/z peaks. Compound identification is currently ongoing but some of the compounds have previously been reported in a biological context.
For the first time we identified exhaled molecules that differ between children with allergic asthma and healthy controls by real-time SESI-HRMS. Such a discovery has the potential to improve the early diagnosis of asthma.
Jisun H. J. Lee and Jiangjiang Zhu
Gut microbiota plays essential roles in maintaining gut homeostasis. The composition of gut microbes and their metabolites are altered in response to diet and remedial agents such as antibiotics. However, little is known about the effect of antibiotics on the gut microbiota and their volatile metabolites. In this study, we evaluated the impact of a moderate level of ampicillin treatment on volatile fatty acids (VFAs) of gut microbial cultures using an optimized real-time secondary electrospray ionization coupled with high-resolution mass spectrometry (SESI-HRMS).
Li Chen, Fanyi Zhong and Jiangjiang Zhu
This mini-review aims to discuss the development and applications of mass spectrometry (MS)-based hybrid approaches in metabolomics.
Tobias Bruderer, Martin Thomas Gaugg, Luca Cappellin, Felipe Lopez-Hilfiker, Manuel A. Hutterli, Nathan Perkins, Renato Zenobi, and Alexander Moeller.
The analysis of volatiles is of high relevance for a wide range of applications from environmental air sampling, security screening to potential medical applications.
Amanda Gisler, Jiayi Lan, Kapil Dev Singh Jakob Usemann, Urs Frey, Renato Zenobi and Pablo Sinues.
Breath analysis by secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS) has potential for clinical diagnosis and drug monitoring…
Mr Ben Henderson, Dr Dorota M Ruszkiewicz, Mr Maxim Wilkinson, Dr Jonathan D Beauchamp, Dr Simona M Cristescu, Dr Stephen J Fowler, Dr Dahlia Salman, Dr Fabio Di Francesco, Dr Gudrun Koppen, Dr Jens Langejuergen, Dr Olaf Holz, Miss Andria Hadjithekli, Mr Sergi Moreno, Dr Michele Pedrotti, Professor Dr Pablo Sinues, Miss Gitte Slingers, Dr Michael Wilde, Dr Tommaso Lomonaco, Miss Delphine Zanella, Professor Renato Zenobi, Mr Joan Francis Focant, Dr Stanislas Grassin-Delyle, Dr Flavio Antonio Antonio Franchina, Miss Michaela Malásková, Dr Pierre-Hugues Stefanuto, Mr Giovanni Pugliese, Professor Dr Chris A Mayhew and Professor C. L. Paul Thomas.
Jiayi Lan, Amanda Gisler, Tobias Bruderer, Pablo Sinues, Renato Zenobi.
In this study, a secondary electrospray ionization-high resolution mass spectrometer (SESI-HRMS) system was employed to profile the real-time exhaled metabolome of ten subjects who had ingested a peppermint oil capsule.
Breathborne biomarkers carry information on the state of human health, and their role in aiding clinical diagnosis or in therapeutic monitoring has become increasingly important as advances in the field are made. Breathborne Biomarkers and the Human Volatilome, Second Edition, provides a comprehensive update and reworking of the 2013 book Volatile Biomarkers, by Anton Amann and David Smith. The new editing team has expanded this edition beyond volatile organic compounds to cover the broad field of breath analysis, including the many exciting developments that have occurred since the first edition was published. This thoroughly revised volume includes the latest discoveries and applications in breath research from the world's foremost scientists, and offers insights into related future developments. It is an ideal resource for researchers, scientists, and clinicians with an interest in breath analysis.
Jiafa Zeng, Zhujun Yu, Majda Mekic, Jiangping Liu, Sheng Li, Gwendal Loisel, Wei Gao, Adrien Gandolfo, Zhen Zhou, Xinming Wang, Hartmut Herrmann, Sasho Gligorovski, and Xue Li.
Cooking emissions represent a major source of air pollution in the indoor environment and exhibit adverse health effects caused by particulate matter together with volatile organic compounds (VOCs).
2019:
Tobias Bruderer; Thomas Gaisl; Martin T. Gaugg; Nora Nowak; Bettina Streckenbach; Simona Müller; Alexander Moeller; Malcolm Kohler; Renato Zenobi*
On-line analysis of exhaled breath offers insight into a person’s metabolism without the need for sample preparation or sample collection. Due to its noninvasive nature and the possibility to sample continuously, the analysis of breath has great clinical potential
K.Dev Singh, G. Tancev, F. Decrue, J. Usemann, R. Appenzeller, P.Barreiro, G. Jaumà, M. Macia Santiago, G. Vidal de Miguel, U.Frey, P. Sinues
Despite the attractiveness of breath analysis as a non-invasive means to retrieve relevant metabolic information, its introduction into routine clinical practice remains a challenge.
Martin Thomas Gaugg, Anna Engler, Lukas Bregy, Yvonne Nussbaumer-Ochsner, Lara Eiffert, Tobias Bruderer, Renato Zenobi, Pablo ML Sinues and Malcolm Kohler.
BackgroundCollagen-related amino acids are significantly increased in exhaled breath of idiopathic pulmonary fibrosis (IPF) patients compared with healthy controls. The detection of these amino acids using real-time breath analysis results in a good discrimination between the groups, indicating the possibility for a rapid, non-invasive screening for IPF.
Lukas Bregy, Constanze Hirsigerb, Stefanie Gartenmann, Tobias Bruderer, Renato Zenobi, Patrick R.Schmidlinb
It has been shown that bacteria in periodontally diseased patients can be recognized by the detection of volatile metabolites in the headspace of saliva by real-time ambient mass spectrometry. The aim of this study was to use this detection method to analyze the oral metabolome in diseased periodontitis patients before and after therapy to monitor disease evolution and healing events.
Martin Thomas Gaugg, Yvonne Nussbaumer-Ochsner, Lukas Bregy, Anna Engler, Nina Stebler, Thomas Gaisl, Tobias Bruderer, Nora Nowak, Pablo ML Sinues, Renato Zenobi and Malcolm Kohler.
BackgroundExacerbations of chronic obstructive pulmonary disease (COPD) are defined by acute worsening of respiratory symptoms leading to a change in therapy.
2018:
Haorong Li, Mengyang Xu, and Jiangjiang Zhu
This study aimed to sensitively detect volatile metabolites from the headspace of in vitro gut microbial culture in a human colonic model (HCM). Two SESI-tandem mass spectrometry panels with a comparable number of targeted metabolites/features were established.
Haorong Li and Jiangjiang Zhu
SESIMS/MS was applied to examine the VOC metabolome of a pair of isogenic methicillin-susceptible and resistant Staphylococcus aureus (MSSA and MRSA) strains. Our results indicated that MSSA and MRSA strains can be clearly differentiated Furthermore, we studied the stress response of MSSA and MRSA to antibiotics treatment.
Katharina Heschl, Naemi Haas-Baumann, Ronja Weber, Astghik Baghdasaryan, Srdjan J. Micic, Florian Singer, Renato Zenobi, Tobias Bruderer, Alexander Möller
We present data of 41 children, 4-16yrs (23 CF and 17 healthy controls) from an ongoing cross-sectional study. Children were breathing via a mouthpiece into a heated sampling tube connected to the SESI-HRMS-analyser. Carefully pre-processed MS data was used for biomarker detection and classification. Mann-Whitney U tests together with FDR adjusted p-values were applied to isolate mass-to-charge ratios (m/z: representing potential biomarkers) Subsequent variable reduction through principal component analysis was used to perform binary logistic regression.
CF and HC had comparable BMI (17.7±3.0 vs 16.9±2.3; p=0.17) and FEV1 (z-scores -0.45±1.18 vs -0.27±1.13; p=0.37). 4 children were P.aeruginosa positive. We were able to isolate 43 m/z peaks with elevated intensity signals in CF vs HC below an FDR control level of q = 0.15. Classification applied to first principal components resulted in significant outcomes (CF vs. HC) with an average accuracy of 81.3% and a Cohen’s Kappa value of 0.61.
We could annotate the detected m/z peaks with molecular formula and identify different sets of related molecules. Structure elucidation is ongoing based on comparison of fragment spectra with reference chemicals for unequivocal confirmation of the involved molecular markers.
Non-invasive breath analysis with SESI-HRMS identifies CF specific compounds in children. This will allow further phenotyping of CF lung disease with the potential for early detection of airway infection.
Astghik Baghdasaryan, Tobias Bruderer, Simona Mueller, Ronja Weber, Naemi Haas-Baumann, Srdjan J. Micic, Christoph Berger, Renato Zenobi, Alexander Möller
Microbial infection entails recruitment of inflammatory cells and release of proteases and contributes to morbidity in CF. The non-invasive early detection of airway colonization and infection would be a great step forward in the management of children with CF. The Zurich Exhalomics program aims to describe disease state specific breath-prints to assess airway inflammation and infection in children with CF.
We used headspace secondary electrospray Ionisation high-resolution mass spectrometry (SESI-HRMS) to analyze three biological replicates in randomized order for strain specific volatile metabolites of the following CF pathogens: S. aureus, S. maltophilia, H. influenzae, S. pneumoniae, E. coli, B. cepacia, P. aeruginosa and growth medium.
We found good repeatability between measurements and minimal variation between biological replicates. We performed ANOVA on 130 m/z features with intensities over 1000 cps. 61 showed significant difference in signal intensity between strains (under the FDR adjusted significance level of 5%). This resulted in unique sets of 4-12 volatile markers for P. aeruginosa, H. influenzae, S. pneumoniae, S. aureus and E. coli. Several markers for P. aeruginoas, B. cepacia and S. maltophilia were closely related. Compound identification has started by comparison of headspace fragment spectra for cultures with proposed reference compounds. So far, we could identify molecules from the following compound classes: heterocyclic organic compounds, aromatic aldehydes and aromatic heterocyclic organic compounds.
We report unique sets of volatile markers for CF relevant bacteria detected with SESI-HRMS.
aorong Li, Jiangjiang Zhu, Jane E. Hill
Spurred by recent events, there is an ever-growing interest in the detection of volatile metabolites through human breath. Breath analysis, which is entirely noninvasive, can be applied to clinical diagnosis and therapeutic monitoring, where frequent sampling is required.
Ana María Casas-Ferreira, Miguel del Nogal-Sanchez*, Jose Luis Perez-Pavon, Bernardo Moreno-Cordero
In this review, an assessment of non-separative methods based on mass spectrometry used to analyse volatile organic compounds in the field of bioanalysis is performed. The use of non-separative methods based on mass spectrometry has been established as an attractive option for analysing compounds.
A.Tejero Rioseras, K.D. Singh, N. Nowak, M. T. Gaugg, T. Bruderer, R. Zenobi, P. M-L Sinues
The tricarboxylic acid (TCA) cycle is one of the most important metabolic pathway for cellular respiration in aerobic organisms. It provides and collects intermediates for many other interconnecting pathways and acts as a hub connecting metabolism of carbohydrates, fatty acids, and amino acids.
T. Gaisl, L. Bregy, N. Stebler, M. T. Gaugg, T. Bruderer, D. García-Gómez, A, Moeller, F. Singer, E. I. Schwarz, C. Benden, P. M-L Sinues, R. Zenobi, M. Kohler
We aimed at defining profiles of volatile organic compounds in exhaled breath from patients with cystic fibrosis (CF) using a novel real-time mass spectrometry technique. In this prospective matched case-control study, 30 patients with CF, and 30 healthy control 4 subjects were matched one-to-one according to age, gender, and smoking state.
Xue Li, Dan D. Huang, Rui Du, Zhi J. Zhang, Chak K. Chan, Zheng X. Huang, Zhen Zhou
Exhaled volatile organic compounds (VOCs) have aroused considerable interest, since they can serve as biomarkers for disease diagnosis and environmental exposure in a non-invasive manner. In this work, we present a protocol to characterize the exhaled VOCs in real time by using secondary nanoelectrospray ionization coupled to high resolution mass spectrometry (Sec-nanoESI-HRMS).
K. D. Singh, G. Vidal-de-Miguel, M. T.s Gaugg, A. J. Ibañez, R. Zenobi, M. Kohler, U. Frey and P. M-L Sinues
While there has been progress in making use of breath tests to guide clinical decision making, the full potential of exhaled breath analysis still remains to be exploited. Here we summarize some of the reasons why this is the case, what we have done so far to overcome some of the existing obstacles, and our vision of how we think breath analysis will play a more prominent role …
L. Bregy, Y Nussbaumer-Ochsnerb, P. M-L Sinues, D. García-Gómez, Y. Suter, T. Gaisl, N. Stebler, M. T. Gaugg, M. Kohler, R. Zenobi
New mass spectrometry (MS) techniques analysing exhaled breath have the potential to better define airway diseases. Here, we present our work to profile the volatile organic compounds (VOCs) in exhaled breath from patients with chronic obstructive pulmonary disease (COPD), using real-time MS, and relate this disease-specific breath profile to functional disease markers …
L. Bregy, D. García-Gómez, M. Kohler, Y Nussbaumer-Ochsnerb, P. M-L Sinues, Y. Suter, R. Zenobi, J. Schmitz
The present invention provides a method for determining whether a patient suffers from COPD, said method comprising the step of: a. providing at a sample comprising, or consisting of, exhaled breath of said patient to an ionization chamber of a mass spectrometer; b. simultaneously determining the presence, absence or relative concentration of at least two metabolites in said sample using …
2017:
M. Mansurova; Birgitta E. Ebert; Lars M. Blank & Alfredo J. Ibáñez
Here, we introduce the reader to these diverse applications associated with the monitoring and analysis of VOC emissions. We also present our vision of real-time VOC analysis enabled by newly developed analytical techniques, which will further broaden the use of VOCs in even wider applications.
A. Tejero-Rioseras, D. Garcia-Gomez, B. E. Ebert, L. M. Blank, A. J. Ibanez and P. M-L Sinues
While yeast is one of the most studied organisms, its intricate biology remains to be fully mapped and understood. This is especially the case when it comes to capture rapid, in vivo fluctuations of metabolite levels. According to the authors, the results suggest that a large number of metabolites produced by yeast from glucose neither are reported in the literature nor are their biochemical origins deciphered.
M. T. Gaugg, A. Engler, Y. Nussbaumer-Ochsner, L. Bregy, A. S Stöberl, T. Gaisl, T. Bruderer, R. Zenobi, M. Kohler and P. M-L Sinues
The authors explore whether real-time breath research & analysis by SESI-HRMS is suitable to monitor changes at the metabolic level due to inhaling bronchodilator medication. The experimental results strengthen the notion that certain biochemical processes can be monitored.
M. T. Gaugg, T. Bruderer, N. Nowak, L. Eiffert, P. M-L Sinues, M. Kohler, R. Zenobi
Omega-oxidation is a fatty acid degradation pathway that can occur alternatively to the dominant b-oxidation. The dysregulation of fatty acid oxidation has been related with a variety of diseases, termed fatty acid oxidation disorders. This work shows evidence for real-time detection in exhaled breath of the complete series of saturated linear w-hydroxyalkanoic acids, w-oxoalkanoic acids and alkanedioic acids with carbon chain lengths of 5-15.
I. A. Ratiu, T. Ligor, Victor B.-Bintintan, B. Buszewski
Bacteria are the main cause of many human diseases. Typical bacterial identification methods, for example culture-based, serological and genetic methods, are time-consuming, delaying the potential for an early and accurate diagnosis and the appropriate subsequent treatment.
A. T. Rioseras, M. T. Gaugg and P. M-L Sinues
Our main goal was to gain further insights into the mechanism by which gas-phase analytes are ionized by interaction with plumes of electrospray solvents. We exposed target vapors to electrosprays of either water or deuterated water and mass analyzed them …
Ta-Hsuan Ong*, Ted Mendum, Geoff Geurtsen, Jude Kelley, Alla Ostrinskaya, Roderick Kunz
Canines remain the gold standard for explosives detection in many situations, and there is an ongoing desire for them to perform at the highest level. This goal requires canine training to be approached similarly to scientific sensor design. A sensitive, real-time (∼1 s) vapor analysis mass spectrometer was developed to provide tools, techniques, and knowledge to better understand, train, and utilize canines.
P. M-L Sinues, Y. Nussbaumer Ochsner, M.T. Gaugg, L. Bregy, A. Engler, R. Zenobi, M. Kohler.
Idiopathic pulmonary fibrosis (IPF) is recognized as a distinct clinical disorder, however, the diagnosis method remains elusive. Metabolic profiling of biopsied tissue specimens has shown promise to gain insights into IPF pathogenesis. In view of this, the authors hypothesized that the analysis of exhaled metabolites may also provide further insights.
Y. Nussbaumer-Ochsner, M.T. Gaugg, L. Bregy, A. Engler, S. A. Sophie, T. Gaisl, P. M-L Sinues, M. Kohler, R. Zenobi
Recently we found markers in exhaled breath discriminating patients with chronic obstructive pulmonary disease (COPD) from healthy controls using real-time mass spectrometry. The aim of this study was to validate the previously found disease specific metabolic profile of COPD in an independent cohort of patients suffering from chronic obstructive lung disease …
T. Bruderer, A. Baghdasaryan, J. Wyler, M. Kohler, R. Zenobi, A. Möller
Early and often subclinical pulmonary infection and pronounced neutrophilic inflammation are major contributors to CF-related morbidity. There is a causal relationship between high airway neutrophil elastase activity and the development of bronchiectasis. Early detection of disease and disease-associated .
M. T. Gaugg, Y. Nussbaumer-Ochsner, L. Bregy, A. Engler, N. Stebler, T. Bruderer, P. M-L Sinues, R. Zenobi, M. Kohler
The authors successfully identified metabolic patterns in exhaled breath, which discriminate COPD patients with and without frequent exacerbations. They propose that their findings correlate with the increased oxidative stress caused by elevated nitric oxide production in response to the pulmonary inflammation.
HUANG Lei, LI Xue, XU Meng, HUANG Zhengxu, ZHOU Zhen
Human breath contains thousands of volatile organic compounds (VOCs), which would be potentially helpful for studying disease diagnosis and environmental exposure. However, owing to limitations in current analytical methods, only the compounds with molecular weights <300 have been widely reported in exhaled human breath.
黄 磊， 李 雪， 徐 萌， 黄正旭， 周 振
二次电喷雾电离源耦合超高分辨质谱（ＳＥＳＩ⁃ＵＨＲＭＳ）有望检出人体呼出气中分子量大于３００ 的相对 高分子量化合物， 这些化合物的发现将有助于更准确地理解呼出气中挥发性有机化合物（ＶＯＣｓ）的来源、产 生机制以及ＳＥＳＩ 源电离机理， 更好地实现ＳＥＳＩ⁃ＵＨＲＭＳ 的转化应用． 本研究自组装ｎａｎｏＳＥＳＩ 源（尚无商业产 品）耦合四极杆⁃静电场轨道阱质谱（最高质量分辨率１.２×1０<sup>５</sup> ）， 考察了该装置对健康人体呼出气中分子量 为３００～５００ 化合物的检出情况． 结果表明， 所搭建的ｎａｎｏＳＥＳＩ⁃ＵＨＲＭＳ 装置检测人体呼出气的重现性好、灵 敏度高， 可检出数十种分子量为３００～５００ 的化合物．
R. R. Farrell, J. Fahrentrapp, D. Garcia Gomez, P. M-L Sinues, and R. Zenobi
Even though sugar and acidity measurements are the most common indices of grape maturity, it is well recognized that they provide only basic information related to wine quality. In this preliminary study te authors use SESI-MS to analyze VOCs directly from intact grapes without sample concentration.
P. M-L Sinues, M. Kohler, S. A. Brown, R. Zenobi and R. Dallmann
The time-of-day of drug application is an important factor in maximizing efficacy and minimizing toxicity. Real-time in vivo mass spectrometric breath analysis and research of mice was deployed to investigate time-of-day variation in ketamine metabolism. Different production rates of ketamine metabolites were found in opposite circadian phases.
2016:
Xue Li, Lei Huang, Hui Zhu and Zhen Zhou.
RATIONALE: Direct mass spectrometry (MS)-based methods make it possible to monitor the molecular compositions of hundreds of volatile organic compounds (VOCs) in exhaled human breath in real time. Mass resolution and mass accuracy play important roles for direct MS analysis, especially for the low-concentration isobaric compounds in non-target research.
D. García-Gómez, T. Gaisl, L. Bregy, A. Cremonesi, P. M-L Sinues, M. Kohler, and R. Zenobi
Amino acids are frequently determined in clinical chemistry. However, current analysis methods are time-consuming, invasive, and require sample preparation. The authors hypothesized that plasma concentrations of amino acids can be estimated by measuring their concentrations in exhaled breath.
D. García-Gómez, T. Gaisl, L. Bregy, P. M-L Sinues, M. Kohler and R. Zenobi
Disorders in tryptophan metabolism result in diseases such as vitamin B6 responsive xanthurenic aciduria, hydroxy-kynureninuria, tryptophanuria and Hartnup disease. The authors hypotesized that breath analysis may reveal compounds that are metabolically linked to tryptophan. The mass range of detected metabolites reached up to 265 u, which is beyond the mass range limit (150–200 u) of competing breath research techniques such as PTR or SIFT-MS.
G. Trecate, P. M-L Sinues & R. Orlandi
Breast cancer screening and presurgical diagnosis are currently based on mammography, ultrasound and more sensitive imaging technologies; however, noninvasive biomarkers represent both a challenge and an opportunity for early detection of cancer …
M. T. Gaugg, D. Garcia Gomez, C. Barrios-Collado, G. Vidal-de-Miguel, M. Kohler, R. Zenobi and P. M-L Sinues
Coupling a SESI source and a HRMS (Orbitrap), the authors were able to identify exogenous compounds associated to smoking, as well as endogenous metabolites suggesting increased oxidative stress in smokers. According to the authors, most of these compounds correlated significantly with smoking frequency and allowed accurate discrimination of smokers and non-smokers.
D. Garcia-Gomez, T. Gaisl, C. Barrios-Collado, Guillermo Vidal-de-Miguel, M. Kohler and R. Zenobi
Chemical analysis of aerosols collected from electronic cigarettes (ECs) has shown that these devices produce vapors that contain harmful and potentially harmful compounds. Conventional analytical methods used for the analysis of electronic cigarettes do not reflect the actual composition of the aerosols generated because they usually neglect the changes in the chemical composition that occur during the aerosol generation process and after collection.
C. Barrios-Collado, D. Garcia-Gomez, R. Zenobi, G. Vidal-de-Miguel, Alfredo J. Ibanez, and P. M-L Sinues
The authors document how hundreds of species can be tracked with an unparalleled time resolution of 2 min during day−night cycles. To further illustrate the capabilities of SESI-MS for volatile organic compounds (VOCs) analysis, they subjected the plant to mechanical damage and monitored its response.
2015:
E. I Schwarz, P. M-L Sinues, L. Bregy, T. Gaisl, D. Garcia-Gomez, M. T. Gaugg, Y. Suter, N. Stebler, Y. Nussbaumer-Ochsner, K. E. Bloch, J. R. Stradling, R. Zenobi, M. Kohler
Patients with OSA effectively treated with CPAP were randomised to either withdraw treatment or continue CPAP for 2 weeks. Exhaled breath analysis and research by untargeted SESI-MS was performed at baseline and 2 weeks after randomisation. CPAP withdrawal led to a recurrence of OSA, which was accompanied by a significant change in 16 identified metabolites.
Matthew J. Aernecke, Ted Mendum, Geoff Geurtsen, Alla Ostrinskaya, Roderick R. Kunz*
A rapid method for vapor pressure measurement was developed and used to derive the vapor pressure curve of the thermally labile peroxide-based explosive.
L. Bregy, A. R. Müggler, P. M-L Sinues, D. García-Gómez, Y. Suter, G. N. Belibasakis, M. Kohler, P. R. Schmidlin, Renato Zenobi
The detection of bacterial-specific volatile metabolites may be a valuable tool to predict infection. Here we applied a real-time mass spectrometric technique to investigate differences in volatile metabolic profiles of oral bacteria that cause periodontitis. We coupled a secondary electrospray ionization (SESI) source to a commercial high-resolution mass spectrometer …
P. M-L Sinues, Elena Landoni, Rosalba Miceli, Vincenza F. Dibari, Matteo Dugo, Roberto Agresti, Elda Tagliabue, Simone Cristoni, Rosaria Orlandi.
SESI–MS produces high-dimensional data of quality comparable to gene expression analysis output. This prompted the authors to use methods originally developed for gene expression data in analyzing SESI–MS breathprints.
D. García-Gómez, L. Bregy, Y. Nussbaumer-Ochsner, T. Gaisl, M. Kohler, and R. Zenobi
2-Subtituted benzothiazoles are widely used industrial chemicals whose occurrence in environmental samples has been shown to be ubiquitous. However, knowledge about human exposure to these compounds and their excretion route is still scarce. Here, we demonstrate for the first time the detection of benzothiazole derivatives in exhaled breath.
C. Barrios-Collado, G. Vidal-de-Miguel, P. M-L Sinues
The process by which ambient vapors are ionized upon interaction with electrosprays is not fully under-stood, compromising its optimization and widespread use. In this work we evaluated the different scales associated with the processes involved in secondary electrospray ionization (SESI) and developed a new numerical method …
D. García-Gómez, L. Bregy, C. Barrios-Collado, G. Vidal-de-Miguel and R. Zenobi
The identification of chemical compounds in exhaled human breath is promising in the search for new biomakers of diseases. However, the analytical techniques used nowadays are not capable of achieving a robust identification, especially in real-time analysis.
Alex R. Hill, Mark Edgar, Maria Chatzigeorgiou, James C. Reynolds, Paul F. Kelly* and Colin S. Creaser*
The complexation of triacetone triperoxide (TATP) with a range of alkali metals has been studied by electrospray ionisation mass spectrometry to yield [M + Cat]+ ions for all of the alkali metals. The formation of [2TATP + Li + LiX]+ (X = Br, Cl) sandwich complexes was also observed. Collision cross-sections for the lithium-containing complexes of TATP were measured by travelling wave ion mobility spectrometry mass spectrometry and compared well with computationally determined structures. Extractive electrospray ionisation (EESI) using a lithium-doped electrospray is demonstrated for the detection of TATP vapours desorbed from a metal surface. The limit of detection for EESI was shown to be 20 ng using the [TATP + Li]+ ion.
Xue Li, P. M-L Sinues, R. Dallmann, L. Bregy, M.Hollmén, S. Proulx, S. A. Brown, M. Detmar, M. Kohler, and R. Zenobi
Noninvasive, real-time pharmacokinetic (PK) monitoring of ketamine, propofol, and valproic acid, and their metabolites was achieved in mice, using secondary electrospray ionization and high-resolution mass spectrometry. The PK profile of a drug influences its efficacy and toxicity because it determines exposure time and levels …
H. D. Bean, T. R. Mellors, J. Zhu and J. E. Hill
A number of direct injection mass spectrometry methods that can sample foods nondestructively and without sample preparation are being developed with applications ranging from the rapid assessment of food safety to the verification of protected designations of origin. In this pilot study, SESI-MS in positive and negative-ion modes was used to …
D. García-Gómez, P. M.-L. Sinues, C. Barrios-Collado, G. Vidal-de Miguel, M. Gaugg, and R. Zenobi
In recent years, breath analysis in real time has become a noninvasive alternative for the diagnosis of diseases and for molecular fingerprinting of exhaled breath. However, the techniques used lack the capabilities for proper identification of the compounds found in the exhalome.
2014:
P. M-L Sinues, L. Tarokh, Xue Li, M. Kohler, S. A. Brown, R. Zenobi, R. Dallmann
Circadian clocks play a significant role in the correct timing of physiological metabolism, and clock disruption might lead to pathological changes of metabolism. One interesting method to assess the current state of metabolism is metabolomics. Metabolomics tries to capture the entirety of small molecules, i.e. the building blocks of metabolism, in a given matrix …
J-C Wolf, M. Schaer, P. Siegenthaler, R. Zenobi
A novel active capillary dielectric barrier discharge plasma ionization (DBDI) technique for mass spectrometry is applied to the direct detection of thirteen chemical warfare related compounds, including sarin, and compared to secondary electrospray ionization (SESI) in terms of selectivity and sensitivity.
J-C Wolf, M. Schaer, P. Siegenthaler, R. Zenobi
A novel active capillary dielectric barrier discharge plasma ionization (DBDI) technique for mass spectrometry is applied to the direct detection of thirteen chemical warfare related compounds, including sarin, and compared to secondary electrospray ionization (SESI) in terms of selectivity and sensitivity. The investigated compounds include an intact chemical warfare agent and structurally related molecules, hydrolysis products and/or precursors of highly toxic nerve (G-series, V-series and "new" nerve agents), blistering and incapacitating warfare agents. …
James C Reynolds, Modupe A Jimoh, Cristina Guallar-Hoyas, Colin S Creaser, Salman Siddiqui and C L Paul Thomas
A two-stage thermal desorption/secondary electrospray ionization/time-of-flight mass spectrometry for faster targeted breath profiling has been studied. A new secondary electrospray ionization (SESI) source was devised to constrain the thermal desorption plume and promote efficient mixing in the ionization region. Further, a chromatographic preseparation stage was introduced to suppress interferences from siloxanes associated with thermal desorption profiles of exhaled breath samples…
Jingjing He, P. M-L Sinues, M. Hollmén, Xue Li, M. Detmar & R. Zenobi
There is increasing interest in the development of noninvasive diagnostic methods for early cancer detection, to improve the survival rate and quality of life of cancer patients. Identification of volatile metabolic compounds may provide an approach for noninvasive early diagnosis of malignant diseases.
Helen J. Martin,a James C. Reynolds,a Svetlana Riazanskaiab and C. L. Paul Thomas*a
The non-invasive nature of volatile organic compound (VOC) sampling from skin makes this a priority in the development of new screening and diagnostic assays. Evaluation of recent literature highlights the tension between the analytical utility of ambient ionisation approaches for skin profiling and the practicality of undertaking larger campaigns (higher statistical power), or undertaking research in remote locations. This study describes how VOC may be sampled from skin and recovered from a polydimethylsilicone sampling coupon and analysed by thermal desorption (TD) interfaced to secondary electrospray ionisation (SESI) time-of-flight mass spectrometry (MS) for the high throughput screening of volatile fatty acids (VFAs) from human skin…
C. Ballabio, S. Cristoni, G. Puccio, M. Kohler, M. R. Sala, P. Brambilla, P. M-L Sinues
Blood cultures are routine tests to determine whether micro-organisms have entered the patient’s bloodstream. Automated systems, based on the detection of CO2 increase in the culture media, have considerably improved the screening efficiency for the detection of bacteria. However, further identification of bacteria still requires time consuming culturing procedures.
P. M-L Sinues, L. Meier, C. Berchtold, M.Ivanov, N. Sievi, G. Camen, M. Kohler, R. Zenobi
Background: It has been suggested that exhaled breath contains relevant information on health status. Objectives: We hypothesized that a novel mass spectrometry (MS) technique to analyze breath in real time could be useful to differentiate breathprints from chronic obstructive pulmonary disease (COPD) patients and controls (smokers and nonsmokers) …
Neil A. Devenport, Daniel J. Blenkhorn, Daniel J. Weston, James C. Reynolds, and Colin S. Creaser
A direct, ambient ionization method has been developed for the determination of creatinine in urine that combines derivatization and thermal desorption with extractive electrospray ionization and ion mobility-mass spectrometry. The volatility of creatinine was enhanced by a rapid on-probe aqueous acylation reaction, using a custom-made thermal desorption probe, allowing thermal desorption and ionization of the monoacylated derivative..
2013:
P. M-L Sinues, R. Zenobi, M. Kohler
Investigations on breath analysis have provided preliminary data on its potential in the noninvasive diagnosis of lung diseases. Although the conventional comparisons of exhaled breath in study populations (ie, diseased vs healthy) may help to identify patients with various lung diseases, we believe that the analysis of exhaled breath holds promise beyond this scenario …
J. Zhu, J. Jimenez-Díaz, H. D. Bean, N. A. Daphtary, M. I. Aliyeva, L. K. A. Lundblad and J. E. Hill
Before breath-based diagnostics for lung infections can be implemented in the clinic, it is necessary to understand how the breath volatiles change during the course of infection, and ideally, to identify a core set of breath markers that can be used to diagnose the pathogen at any point during the infection …
C. Berchtold, L. Meier, R. Steinhoff, R. Zenobi
Breath is considered to be an easily accessible matrix, whose chemical composition relates to compounds present in blood. Therefore many metabolites are expected in exhaled breath, which may be used in the future for the development of diagnostic methods. In this article, a new strategy to discriminate between exhaled endogenous metabolites and exhaled exogenous contaminants by direct high-resolution mass spectrometry is introduced.
Neil A. Devenport, Laura C. Sealey, Faisal H. Alruways, Daniel J. Weston, James C. Reynolds, and Colin S. Creaser.
A direct, ambient ionization method has been developed using atmospheric pressure thermal desorption–extractive electrospray–mass spectrometry (AP/TD-EESI-MS) for the detection of the genotoxic impurity (GTI) methyl p-toluenesulfonate (MTS) in a surrogate pharmaceutical matrix. A custom-made thermal desorption probe was used to the desorb and vaporize MTS from the solid state, by rapid heating to 200 °C then cooling to ambient temperature, with a cycle time of 6 min…
P. M.-L. Sinues, M. Kohler, R. Zenobi
The metabolic phenotype varies widely due to external factors such as diet and gut microbiome composition, among others. Urine metabolite profiling studies have suggested that there are highly individual phenotypes that persist over extended periods of time. This hypothesis was tested by analyzing the exhaled breath of a group of subjects during nine days by mass spectrometry.
J. Zhu, H. D. Bean, J. Jiménez-Díaz, and J. E. Hill
Bacterial pneumonia is one of the leading causes of disease-related morbidity and mortality in the world, in part because the diagnostic tools for pneumonia are slow and ineffective. To improve the diagnosis success rates and treatment outcomes for bacterial lung infections, we are exploring the use of SESI-MS breath analysis as a rapid, noninvasive method for determining …
Christian Berchtold; Stefan Schmid; Lukas Meiera and Renato Zenobi.
γ-Hydroxybutyrate (GHB) and γ-butyrolactone (GBL) are used as “date rape drugs” since they cause catalepsy and memory loss. A new application of secondary electrospray ionization (SESI) mass spectrometry for in situ detection of GHB and GBL in drinks and body fluids is introduced.
J. Zhu, J. E. Hill
Escherichia coli O157:H7 (EC O157:H7), as well as its recently emerging non-O157 relatives, are a notorious group of pathogenic bacteria associated with foodborne outbreaks. In this study, we demonstrated that secondary electrospray ionization mass spectrometry (SESI-MS) could be a rapid and accurate detection technology for foodborne pathogens …
2012:
P. M-L Sinues, M. Kohler and R. Zenobi
The development of noninvasive analytical techniques is of interest to the field of chronobiology, in order to reveal the human metabolome that seems to show temporal patterns and to predict internal body time. We report on the real-time mass spectrometric analysis of human breath as a potential method to be used in this field.
L. Meier, C. Berchtold, S. Schmid and R. Zenobi
In this study, we used secondary electrospray ionization mass spectrometry assisted by an ion funnel (IF) operating at ambient pressure to find compounds in the mass range of 100–500 m/z in online breath fingerprinting experiments. In low-resolution experiments conducted on an ion trap instrument, we found that pyridin is present in breath of individuals long after drinking coffee …
G. Vidal-de-Miguel, M. Macía, P. Pinacho, and J. Blanco
In secondary electrospray ionization (SESI) systems, gaseous analytes exposed to an elecrospray plume become ionized after charge is transferred from the charging electrosprayed particles to the sample species. Current SESI systems have shown a certain potential. However, their ionization efficiency is limited by …
G. Vidal-de-Miguel, A. Herrero
In secondary electrospray ionization (SESI) systems, gaseous analytes exposed to an electrospray plume become ionized after charge is transferred from the charging electrosprayed particles (the charging agent) to the vapor species. Currently available SESI models are valid for simplified systems having only one type of electrosprayed species …
L. Meier, C. Berchtold, S. Schmid and R. Zenobi
In this study, we use an ion funnel (IF) at ambient pressure to enhance the sensitivity of secondary electrospray ionization (SESI). Atenolol, salbutamol and cocaine as test compounds are delivered to the SESI interface in the gas phase and are charged with three nano electrosprays …
2011:
P. M-L Sinues, E. Criado, G. Vidal-de-Miguel
The fact that electrosprays of pure solvents can efficiently ionize gas-phase analytes has been known for decades, although this method has not been widely exploited. With the advent of ambient mass spectrometry, this approach is becoming increasingly popular. However, the mechanism by which vapors become ionized remains largely unknown …
L. Meier, S. Schmid, C. Berchtold and R. Zenobi
In this study, we investigated how binary mixtures of compounds influence each other's signal intensity in electrospray ionization (ESI), extractive electrospray ionization (EESI) and secondary electrospray ionization (SESI) experiments. The experiments were conducted using a series of homologous primary amines (from 1-butyl to 1- decylamine) …
H. D. Bean, J. Zhu, J. E. Hill
Secondary electrospray ionization mass spectrometry (SESI-MS) is a method developed for the rapid detection of volatile compounds, without the need for sample pretreatment. The method was first described by Fenn and colleagues and has been applied to the detection of illicit drugs and explosives, the characterization of skin volatiles, and the analysis of breath.
Gerardo Gamez, Liang Zhu, Andreas Disko, Huanwen Chen, Vladimir Azov, Konstantin Chingin, Gunter Kramerb and Renato Zenobi
Valproic acid pharmacokinetics and ingestion in humans can be monitored through a novel biomarker in exhaled breath.
P. M-L Sinues, L. Zingaro, A. Finiguerra and S. Cristoni
A series of fatty acids among other compounds have recently been detected in breath in real time by secondary electrospray ionization mass spectrometry (SESI-MS). Our main aim in this work was to quantify their abundance in breath calibrating the system with standard vapors and extend the study to a control group for several days, both under fasting conditions and after sucrose intake.
2010:
C. Berchtold, L. Meier, R. Zenobi
Diagnosis by online breath analysis using mass spectrometry is challenging because of the low concentrations of pertinent compounds in breath. Here we investigate extractive electrospray ionization and atmospheric pressure chemical ionization for the detection of narcotics in breath.
J. Zhu, H. D. Bean, Y-M Kuo, and J. E. Hill
We propose a novel application of secondary electrospray ionization-mass spectrometry (SESI-MS) as a real-time clinical diagnostic tool for bacterial infection. It is known that volatile organic compounds (VOCs), produced in different combinations and quantities by bacteria as metabolites, generate characteristic odors for certain bacteria.
Liang Zhu, Zhong Hu, G. Gamez, Wai Siang Law, Huan Wen Chen, ShuiPing Yang, Konstantin Chingin, Roman M. Balabin, Rui Wang, TingTing Zhang, R. Zenobi
By gently bubbling nitrogen gas through beer, an effervescent beverage, both volatile and non-volatile compounds can be simultaneously sampled in the form of aerosol. This allows for fast (within seconds) fingerprinting by extractive electrospray ionization mass spectrometry (EESI-MS) in both negative and positive ion mode, without the need for any sample pre-treatment …
Leonard A. Dillon, Victoria N. Stone, Laura A. Croasdell, Peter R. Fielden, Nicholas J. Goddard and C. L. Paul Thomas
An electrospray ionisation triple quadrupole mass spectrometer (Varian 1200 L) was modified to accept nitrogen samples containing low concentrations of volatile organic compounds. Six candidate probe compounds, methyl decanoate, octan-3-one, 2-ethylhexanoic acid, 1,4-diaminobutane, dimethyl methylphosphonate, and 2,3-butanediol, at concentrations below 50 ppb(v) were generated with permeation tubes in a test atmosphere generator.
Zhongchen Wu, Konstantin Chingin, Huanwen Chen, Liang Zhu, Bin Jia, R. Zenobi
The development of analytical techniques suitable for sensitive, high-throughput, and nondestructive food analysis has been of increasing interest in recent years. In this study, mass-spectral fingerprints of various cheese products were rapidly recorded in the mass range of m/z 50-300 Da without any sample pretreatment, using ND-EESI-MS in negative ion mode.
J. C. Reynolds,* G. J. Blackburn, C. Guallar-Hoyas, V. H. Moll, V. Bocos-Bintintan, G. Kaur-Atwal, M. D. Howdle, E. L. Harry, L. J. Brown, C. S. Creaser, and C. L. P. Thomas
A thermal desorption unit has been interfaced to an electrospray ionization-ion mobility-time-of-flight mass spectrometer. The interface was evaluated using a mixture of six model volatile organic compounds which showed detection limits of <1 ng sample loaded onto a thermal desorption tube packed with Tenax, equivalent to sampled concentrations of 4 μg L−1. Thermal desorption profiles were observed for all of the compounds, and ion mobility-mass spectrometry separations were used to resolve the probe compound responses from each other…
2009:
P. M-L Sinues
We investigated the volatile organic compounds emanated from the hand of two individuals, on-line by secondary electrospray ionization-mass spectrometry in positive ionization mode. The background ambient air is continuously sampled, ionized and readily mass analyzed. When the probe samples above the headspace of the hand of two subjects, several peaks …
P. M-L Sinues, J. F. de la Mora
Vapors released by the skin in the hand of one human subject are detected in real time by sampling them directly from the ambient gas surrounding the hand, ionizing them by secondary electrospray ionization (SESI, via contact with the charged cloud from an electrospray source), and analyzing them in a mass spectrometer with an atmospheric pressure source (API-MS).
2008:
P. M-L Sinues, J. Rus, G. F. de la Mora, M. Hernández, and J. F. de la Mora
We determine the sensitivity of several commercial atmospheric pressure ionization mass spectrometers towards ambient vapors, ionized by contact with an electrospray of acidified or ammoniated solvent, a technique often referred to as secondary electrospray ionization (SESI).
H. Chen, R. Zenobi
Extractive electrospray ionization mass spectrometry (EESI-MS) allows the real-time, direct analysis of complex gaseous and liquid samples without any sample pretreatment under ambient conditions. By using a neutral desorption (ND) sampling gas beam to gently impact a surface, the analyte present on a surface can be efficiently sampled and then transported …
P. M-L Sinues, J. F. de la Mora
Real time analysis of human breath is achieved in an atmospheric pressure ionization mass spectrometer (API-MS) by negatively charging exhaled vapors via contact with an electrospray cloud. The spectrum observed is dominated by a wide range of deprotonated fatty acids, including saturated chains up to C14. Above C14, the background from cutaneous sources becomes dominant.
L. Zhu, G. Gamez, H. W. Chen, H. X. Huang, K. Chingin and Renato Zenobi
Extractive electrospray ionization mass spectrometry (EESI-MS) for real-time monitoring of organic chemical reactions was demonstrated for a well-established pharmaceutical process reaction and a widely used acetylation reaction in the presence of a nucleophilic catalyst, 4-dimethylaminopyridine (4-DMAP) …
L. Zhu, G. Gamez, H. W. Chen, H. X. Huang, K. Chingin and Renato Zenobi
Extractive electrospray ionization mass spectrometry (EESI-MS) for real-time monitoring of organic chemical reactions was demonstrated for a well-established pharmaceutical process reaction and a widely used acetylation reaction in the presence of a nucleophilic catalyst, 4-dimethylaminopyridine (4-DMAP) …
2007:
H. Chen and R. Zenobi
Spinach contaminated with E. coli leaves 200 people sick in the USA – rapid screening needed for suspected food! Epidemic − thousands of patients need to be rapidly screened in emergencies… What do these and similar headlines have in common? They all challenge modern analytical science in terms of sensitivity, specificity, speed, and especially throughput. It appears that …
H. Chen, S. Yang, A. Wortmann, and R. Zenobi
Mass spectrometry is increasingly used for research purposes and routine measurements in biology, life science, the pharmaceutical industry, and in clinic diagnosis to characterize complex samples. Usually, biological samples are mixtures supported by a biological structure such as skin, tissue, muscle, or vessels and are commonly accompanied by microorganisms …
H. Chen, A. Wortmann, Renato Zenobi
It is of increasing interest and practical importance to develop convenient methods based on mass spectrometry for high-throughput analyses of biological samples. This is usually difficult because of the complex matrix and ion suppression effects. Generation of ions at ambient conditions is a promising solution to these problems …
H. Chen, Y. Sun, A. Wortmann, H. Gu, R. Zenobi
Maturity is an essential factor that determines storage life and final quality of most fruits and vegetables. Maturity monitoring is thus of paramount importance for postharvest handling and fruit quality regulation. Ideal analytical procedures for maturity investigation require high sensitivity, specificity, and high throughput and should be noninvasive.
P. M-L Sinues, J. F. de la Mora
Recent work by Zenobi and colleagues reports that human breath charged by contact with an electrospray (ES) cloud yields many mass peaks of species such as urea, glucose, and other ions, some with molecular weights above 1000Da.
H. Chen, D. Touboul,M. C. Jecklin, J. Zheng, M. Luoa, Renato Zenobid
A home-made extractive electrospray ionization source is coupled to a linear quadrupole ion trap mass spectrometer to investigate ion/molecule reactions of biopolymers at ambient pressure. Multiply charged biopolymers such as peptides and proteins generated in an electrospray are easily reduced to a low charge state by …
H. Chen, A. Wortmann, W. Zhang, and R. Zenobi
Quantitative analysis of trace constituents in exhaled gas can provide useful insights into biochemical processes in the body, thus revealing information about metabolic dynamics and providing, theoretically, a scientific base for biomarker research or clinical diagnoses. Breath, however, is rarely used practically for diagnostic purposes in clinical medicine …
2004:
M. Tam and H. H. Hill, Jr.
The unique capability of secondary electrospray ionization (SESI) as a nonradioactive ionization source to detect analytes in both liquid and gaseous samples was evaluated using aqueous solutions of three common military explosives: cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX), nitroglycerin (NG) and pentaerythritol tetranitrate (PETN).
2003:
W. E. Steiner, B. H. Clowers, P. E. Haigh, and H. H. Hill
For the first time, the use of a traditional ionization source for ion mobility spectrometry (radioactive nickel (63Ni) beta emission ionization) and three alternative ionization sources (electrospray ionization (ESI), secondary electrospray ionization (SESI), and electrical discharge (corona) ionization (CI)) were employed with …
2000:
C. Wu, W. F. Siems, and H. H. Hill, Jr.
A secondary electrospray ionization (SESI) method was developed as a nonradioactive ionization source for ion mobility spectrometry (IMS). This SESI method relied on the gas-phase interaction between charged particles created by electrospray ionization (ESI) and neutral gaseous sample molecules. Mass spectrometry (MS) was used as …