M. Z. Islam, S. E. Räisänen, A. Schudel, K. Wang, T. He, C. Kunz, Y. Li, X. Ma, A. M. Serviento, Z. Zeng, F. Wahl, R. Zenobi, S. Giannoukos, and M. Niu.

Previously, we used secondary electrospray ionization-mass spectrometry (SESI-MS) to investigate the diurnal patterns and signal intensities of exhaled (EX) volatile fatty acids (VFA) of dairy cows. The current study aimed to validate the potential of an exhalomics approach for evaluating rumen fermentation. The experiment was conducted in a switchback design, with 3 periods of 9 d each, including 7 d for adaptation and 2 d for sampling. Four rumen-cannulated original Swiss Brown (Braunvieh) cows were randomly assigned to 1 of 2 diet sequences (ABA or BAB): (A) low starch (LS; 6.31% starch on a dry matter basis) and (B) high starch (HS; 16.2% starch on a dry matter basis). Feeding was once per day at 0830 h. Exhalome (with the GreenFeed System), and rumen samples were collected 8 times to represent every 3 h of a day, and EX-VFA and ruminal (RM)-VFA were analyzed using SESI-MS and HPLC, respectively. Furthermore, the VFA concentration in the gas phase (HR-VFA) was predicted based on RMVFA and Henry’s Law (HR) constants….

Mo Awchi, Kapil Dev Singh, Sara Bachmann Brenner, Marie-Anne Burckhardt, Melanie Hess, Jiafa Zeng, Alexandre N Datta, Urs Frey, Urs Zumsteg, Gabor Szinnai, Pablo Sinues

Purpose: This feasibility study aimed to investigate the use of exhaled breath analysis to capture and quantify relative changes of metabolites during resolution of acute diabetic ketoacidosis under insulin and rehydration therapy…

Cedric Wüthrich, Renato Zenobi, Stamatios Giannoukos

Rationale

Secondary-electrospray ionization (SESI) coupled with high-resolution mass spectrometry is a powerful tool for the discovery of biomarkers in exhaled breath. A primary electrospray consisting of aqueous formic acid (FA) is currently used to charge the volatile organic compounds in breath. To investigate whether alternate electrospray compositions could enable different metabolite coverage and sensitivities, the electrospray dopants NaI and AgNO3 were tested….

Cedric Wüthrich, Renato Zenobi, Stamatios Giannoukos

The mass spectrometer used in this study was an Orbitrap Q-Exactive Plus (Thermo Scientific) operated with the manufacturer’s standard control software (ExactiveTune, version 2.9, Thermo Scientific) and Xcalibur (version 4.1. 31.9, Thermo Scientific). Mass calibration was done according to the instrument manual and was always more recent than seven days according to specifications…

Stamatios Giannoukos, Cedric Wüthrich

The measurement of volatile organic compounds (VOCs) originating from organisms allows continuous monitoring and a unique insight into the metabolism. One method offering the sensitivity to detect these VOCs is secondary electrospray ionization coupled to high-resolution mass spectrometry (SESI-HRMS). SESI was derived from electrospray ionization (ESI) and has found widespread application in clinical research and monitoring of animals. This review discusses the technical aspects behind SESI, the advancements, and the technical hurdles faced. Additionally, the recent advances in the applications of SESI in human and animal-centered research are presented.

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

Bettina Streckenbach

Metabolomics, or the comprehensive study of metabolites and involved processes, provides insights into the current physiological state of humans. In the clinical setting, the detection and quantification of specific metabolites has proven to be invaluable in diagnostic testing. Herein, body samples that are non-invasively accessible are of particular interest…

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

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.

Nora Kristina Nowak

Most physiological processes in humans are synchronized with their environment by socalled circadian clocks. These molecular time-keeping machineries are present in almost every cell. While light is the most important external stimulus to reset the circadian clocks, they can also be entrained by other stimuli, such as feeding or rest/activity cycles. Sleep is both, one of the major outputs of circadian clocks and also an independently regulated recuperative neurobiological process.

Martin Thomas Gaugg

Respiratory diseases are among the leading causes of death worldwide and pose a great financial burden on the health care system. During the last decades the medical community has started to recognize that a patient’s individual set of genes, along with environmental factors, are immensely important for the diagnosis and treatment of diseases. This has led to a strong drive towards further developments in personalized and evidencebased medicine. Understanding the underlying metabolic fundamentals of diseases is crucial to provide the appropriate patient care.One of the fastest methods to obtain new insights in this regard is to analyze metabolites in exhaled breath, which offers a non-invasive window into human metabolism, and which can be monitored in real time.

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…

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..

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…

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…