Biomarker Discovery,
pharmaco-kinetics, &
Real-time metabolomics

Every living organism breathes in one way or another. We do it between 17,000 and 30,000 times every day.
Each exhalation carries several thousand molecular species that reflect our metabolism in that particular moment.
Breath research via SUPER SESI is non invasive, and can be continuously monitored, offering an excellent window to the metabolism.

 

 

selected scientific literature:
- Breath Biomarker Discovery -


Method of detecting COPD by mass spectrometry

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L. Bregy, D. Garcia-Gomez, M. Kohler, Y. Nussbaumer-Ochsner, P. M-L Sinues, Y. Suter, R. Zenobi.

Successful biomarker identification of COPD with SESI-MS, by ETH-Zurich & Zurich University Hospital: Method of detecing COPD by mass spectrometry (WIPO, January 2018)

This patent provides a method for the medical diagnosis of COPD patients and Acute Exacerbation COPD patients. The biomarkers described in this patent were identified with SESI-MS.


Exhaled breath analysis by real-time MS in patients with pulmonary fibrosis

Levels of  fulvine (C16H23NO5) in the exhaled breath of a control group (black) and in IPF patients (red).

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.


SESI-MS and a novel statistical bioinformatic approach identifies a cancer-related profile in exhaled breath of breast cancer patients: a pilot study

Heatmap showing color coded ion abundance values of the 8 features of the final classifier.

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.


Effects of CPAP therapy withdrawal on exhaled breath pattern in obstructive sleep apnoea (OSA)

Real-time breath analysis showing time traces of the signal intensity of one exemplary breath metabolite (pentenal) in a subject from the CPAP-withdrawal group at baseline and at follow-up two weeks later.

M.T. Gaugg, Y. Nussbaumer-Ochsner, L. Bregy, A. Engler, N. Stebler, T. Bruderer, P. M-L Sinues, 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.


On-line breath analysis with SESI discriminates between COPD patients with and without frequent exacerbations

ROC-AUC curve of 0.89 (95% c.i 0.75 - 0.96) with an accuracy of 86.5% at the optimal operating point (circle).

M. T. Gaugg, Y. Nussbaumer-Ochsner, L. Bregy, A. Engler, N. Stebler, T. BrudererP. 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.

 
 
 

- Breath Pharmacokinetics -


Metabolic effects of inhaled salbutamol determined by exhaled breath analysis

 Time traces for C14H26O4, for two subjects before and after inhaling salbutamol & placebo

Time traces for C14H26O4, for two subjects before and after inhaling salbutamol & placebo

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.


Expanding metabolite coverage of real-time breath analysis by coupling a universal SESI source and a HRMS. A pilot study on tobacco smokers

 Box plot and linear regression  of  trimethyl-silylacetonitrile vs No. of cigarrettes.

Box plot and linear regression  of trimethyl-silylacetonitrile vs No. of cigarrettes.

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.


Real-Time Quantification of Amino Acids in the Exhalome by SESI-MS: A Proof-of-Principle Study

 Longitudinal amino acid profiles in 3 subjects over 12 h. Individual and grouped amino acids showed similar results, starting with high concentrations in fasting conditions that decreased after meals.

Longitudinal amino acid profiles in 3 subjects over 12 h. Individual and grouped amino acids showed similar results, starting with high concentrations in fasting conditions that decreased after meals.

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.


SESI-HRMS reveals tryptophan pathway metabolites in exhaled human breath

 Tryptophan metabolites detected in breath by means of  SESI-HRMS  (red). Pink, pathways related to a disease. Blue, reactions related to a drug. Green, other reactions known in Homo sapiens.

Tryptophan metabolites detected in breath by means of SESI-HRMS (red). Pink, pathways related to a disease. Blue, reactions related to a drug. Green, other reactions known in Homo sapiens.

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.

 
 
 

- Real time metabolomics -


Capturing in Vivo Plant Metabolism by Real-Time Analysis of Low to High Molecular Weight Volatiles

 Time traces for β caryophyllene and indole illustrate a typical diurnal and nocturnal pattern.

Time traces for β caryophyllene and indole illustrate a typical diurnal and nocturnal pattern.

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.


Comprehensive Real-Time Analysis of the Yeast Volatilome

 Kinetic profiles of the food-relevant metabolite for different baker's yeast mutations illustrates the potential of SESI-HRMS to monitor industrial processes.

Kinetic profiles of the food-relevant metabolite for different baker's yeast mutations illustrates the potential of SESI-HRMS to monitor industrial processes.

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.


Gauging circadian variation in ketamine metabolism by real-time breath analysis

 Metabolism of norketamine (NK) depending on internal time, two measures in the evening and another two in the opposite circadian phase.

Metabolism of norketamine (NK) depending on internal time, two measures in the evening and another two in the opposite circadian phase.

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.


Rapid fingerprinting of grape volatile composition using SESI orbitrap MS: A preliminary study of grape ripening

 Principal component analysis score plot for first and second components for three grape cultivars

Principal component analysis score plot for first and second components for three grape cultivars

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.