Pablo Sinues

University Children's Hospital Basel, University of Basel · Department of Biomedical Engineering

While evidence exists for metabolic changes after exercise, little is known about metabolic alterations during exercise. Therefore, we aimed to assess real-time changes of metabolism during exercise tests via exhaled breath. We measured exhaled metabolites using real-time secondary electrospray ionization high-resolution mass spectrometry (SESI-HRM...

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 dedica...

The advantages that on-line breath analysis has shown in different fields have already made it stand as an interesting tool for pharmacokinetic studies. This review summarizes recent progress in the field, diving into the different analytical methods and the different advantages and hurdles encountered. We conclude that there is a wealth of limitat...

Sleep is crucial to restore body functions and metabolism across nearly all tissues and cells, and sleep restriction is linked to various metabolic dysfunctions in humans. Using exhaled breath analysis by secondary electrospray ionization high-resolution mass spectrometry, we measured the human exhaled metabolome at 10-s resolution across a night o...

Rationale Infants born prematurely have impaired capacity to deal with oxidative stress shortly after birth. Objectives We hypothesize that the relative impact of exposure to air pollution on lung function is higher in preterm than in term infants. Methods In the prospective BILD-birth-cohort of 254 preterm and 517 term infants, we investigated ass...

Background 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 p...

Background and objectives Obstructive sleep apnea (OSA) is an underdiagnosed respiratory disease with negative metabolic and cardiovascular effects. The current gold standard for diagnosing OSA is in-hospital polysomnography, a time-consuming and costly procedure, often inconvenient for the patient. Recent studies revealed evidence for the potentia...

Secondary electrospray ionization coupled with high resolution mass spectrometry (SESI-HRMS) is a direct mass spectrometry technique, which can identify trace volatile organic compounds (VOCs) in real time without sample pretreatment and chromatographic separation. SESI-HRMS has been successfully applied in multiple applications, including breath a...

Rapid and accurate diagnosis of infectious diseases is crucial to control outbreaks. Here we report that influenza A virus infection induces changes in odor traits that could be captured by...

Background and objectives: Obstructive sleep apnea (OSA) is an underdiagnosed respiratory disease with negative metabolic and cardiovascular effects. The current gold standard for diagnosing OSA is in-hospital polysomnography, a time-consuming and costly procedure, often inconvenient for the patient. Recent studies revealed evidence for the potenti...

We used online secondary electrospray ionization mass spectrometry to measure venlafaxine (VEN), a nonvolatile drug, in the exhaled air of mice intraperitoneally treated with VEN. The breath pharmacokinetic (PK) profile of VEN was recorded, which was in good agreement with that of the blood. Combined with online collection of exhaled breath particl...

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. Emerg...

Breath analysis by secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS) has potential for clinical diagnosis and drug monitoring. However, there is still a lack of benchmarking data that shows the capability of this technique and allows comparability with other breath analysis techniques. In this regard, the goal of this...

Sampling of volatile organic compounds (VOCs) has shown promise for detection of a range of diseases but results have proved hard to replicate due to a lack of standardization. In this work we introduce the ‘Peppermint Initiative’. The initiative seeks to disseminate a standardized experiment that allows comparison of breath sampling and data analy...

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. In total, six time points were sampled during the experiment. Using an untargeted way of profiling breath metabolome, 2333 m/z uni...

Background: Exacerbations of COPD are defined by acute worsening of respiratory symptoms leading to a change in therapy. Identifying altered metabolic processes in patients at risk for future exacerbations is desirable for treatment optimization, the development of new therapeutic strategies, and perhaps diagnostic value. We aimed to identify affe...

Background Therapeutic Drug Monitoring (TDM) is essential aspect for the clinical management of patients. However, despite the clear advantages of TDM, it faces several challenges to being more widely used in the clinic. Specially challenging is the case of TDM in children, as they experience rapid physiologic developments, leading to great pharmac...

Background In the field of medicine, serum concentrations of drugs with a narrow therapeutic window, used to treat seizures, are measured to assure the most efficacious and safe way of treating every individual patient. This form of personalised medicine is called therapeutic drug monitoring (TDM). We have explored the possibility to measure and mo...

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. Among all the different analytical techniques available to interrogate exhaled breath, secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS)...

Background and objective Diagnosis of idiopathic pulmonary fibrosis (IPF) is complex and its pathogenesis is poorly understood. Recent findings indicate elevated levels of proline and other amino acids in lung tissue of IPF patients which may also be of diagnostic value. Following these findings, we hypothesized that such altered metabolic profiles...

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. Alteration in intracellular levels of its intermediate...

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 subjects were matched one-to-one according to age, gender, and smoking state. We perfor...

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 wi...

Background 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 profi...

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. Secondary electrospray ionization-high resolution mass spectrometry SESI-HRMS is introduced here as a sensitive and noninvasive anal...

We explore whether real-time breath analysis by high resolution mass spectrometry is suitable to monitor changes at the metabolic level due to inhaling bronchodilator medication. We compared the breath levels of metabolites in a group of patients (n = 50) at baseline and 10 and 30 min after inhalation of 200 μg salbutamol. The same procedure was pe...

Omega-oxidation is a fatty acid degradation pathway that can occur alternatively to the dominant β 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 ω hy...

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. Regardless of the solvent used, the analytes were detected in protonated form. In contrast, w...

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 of mice was deployed to investigate time-of-day variation in ketamine metabolism. Different production rates of ketamine metabolites, including the recently described anti-depressant hydroxy...

Amino acids studies are a cornerstone in clinical medicine. However, current analysis methods are time-consuming, invasive, and suffer from pre-analytic pitfalls. We hypothesized that blood levels of amino acids can be accurately estimated in real-time via breath analysis, and thus may facilitate more efficient diagnostics and give insights into th...

Background: Amino acids are frequently determined in clinical chemistry. However, current analysis methods are time-consuming, invasive, and suffer from artifacts during sampling, sample handling, and sample preparation. We hypothesized in this proof-of-principle study that plasma concentrations of amino acids can be estimated by measuring their c...

Many studies and personalized medicine in general require frequent measurements and/or rapid results of biomarker levels. Here we show that 20 low volatility metabolites of the tryptophan pathway can be detected in exhaled human breath. This real-time and non-invasive method offers an attractive alternative to blood analysis.

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. An extensive number of potential breast cancer biomarkers have been discovered by microarray hybridizat...

Online breath analysis is an attractive approach to track exhaled compounds without sample preparation. Current commercially available real-time breath analysis platforms require the purchase of a full mass spectrometer. Here we present an ion source compatible with virtually any preexisting atmospheric pressure ionization mass spectrometer that al...

The process by which ambient vapors are ionized upon interaction with electrosprays is not fully understood , 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 that merges the analyt...

We have deployed an efficient secondary electrospray ionization source coupled to an Orbitrap mass analyzer (SESI-MS) to investigate the emissions of a Begonia Semperflorens. We 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 this system...

Background Obstructive sleep apnoea (OSA) is highly prevalent and associated with cardiovascular and metabolic changes. OSA is usually diagnosed by polysomnography which is time-consuming and provides little information on the patient's phenotype thus limiting a personalised treatment approach. Exhaled breath contains information on metabolism whic...

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-resoluti...

Breath analysis represents a new frontier in medical diagnosis and a powerful tool for cancer biomarker discovery due to the recent development of analytical platforms for the detection and identification of human exhaled volatile compounds. Statistical and bioinformatic tools may represent an effective complement to the technical and instrumental...

Aims: Obstructive sleep aponea (OSA) is associated with metabolic changes. OSA can effectively be treated with continuous positive airway pressure (CPAP) which is presumed to reverse its pathophysiological consequences. Exhaled breath contains biochemical information on the pathophysiological state. We aimed to answer the questions whether a diseas...

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. The antidepressant a...

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. The antidepressant a...

Mittels sekundärer Elektrosprayionisation und hochauflösender Massenspektrometrie wurde eine nichtinvasive Bestimmung der Pharmakokinetik (PK) von Ketamin, Propofol und Valproinsäure sowie deren Metaboliten in der Atemluft von Mäusen erzielt. Das PK-Profil eines Medikaments beeinflusst dessen Wirksamkeit und Toxizität, weil es die Exposition und ef...

Introduction: Obstructive sleep apnea (OSA) is associated with cardiovascular and metabolic changes. OSA can effectively be treated with continuous positive airway pressure (CPAP) therapy which is presumed to reverse its pathophysiological consequences. Exhaled breath contains biochemical information on metabolism and the pathophysiological state....

In recent years, breath analysis in real time has become a non-invasive 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. Here, we report the use of UHPLC-HRMS as a tool for the identificat...

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...

We report on an improved design of a differential ion mobility analyzer (DMA) coupled to laser-induced fluorescence (LIF) for the simultaneous retrieval of two-dimensional information on the electric mobility and fluorescence spectroscopy of gas-phase ions. This enhanced design includes an ion funnel inter-face at the input orifice of the DMA and a...

A novel analytical technique to detect chemical warfare agent (CWA) simulants in forensic samples is presented. Three G-agent type simulants that closely mimic real CWAs, namely dimethyl methylphosphonate (DMMP), diethyl ethylphosphonate (DEEP), and diethyl phosphoramidate (DEPA) and in addition a hydrolysis product, pinacolyl methylphosphonate (PM...

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. Here we analyzed the volatile metabolic signa...

Supplemental Information

Suppl. Fig. 3

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.1 However, further identification of bacteria still requires time-consuming cu...

On-line analysis of exhaled human breath is a growing area in analytical science, for applications such as fast and non-invasive medical diagnosis and monitoring. In this work, we present a novel approach based on ambient ionization of compounds in breath and subsequent real-time mass spectrometric analysis. We introduce a plasma ionization source...

This contribution covers the most important activities of the Zenobi research group at the Organic Chemistry Laboratory, ETH Zurich. We work in a number of interrelated areas that encompass fundamental/mechanistic research, instrument and methods development, and applications. This is illustrated with examples from the mass spectrometric study of n...

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)....

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...