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Integrated system for in operando characterization and development of portable breath analyzers

Applicant Pratsinis Sotiris E.
Number 170729
Funding scheme R'EQUIP
Research institution Institut für Verfahrenstechnik ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Mechanical Engineering
Start/End 01.12.2016 - 30.11.2017
Approved amount 192'081.00
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All Disciplines (5)

Discipline
Mechanical Engineering
Microelectronics. Optoelectronics
Material Sciences
Biomedical Engineering
Chemical Engineering

Keywords (7)

Breath Analysis; Kidney Failure; Lung Cancer; Diabetes; Sensor Characterization; Gas Sensor; Nanostructured Materials

Lay Summary (German)

Lead
Gassensoren können aus der Atemluft Krankheiten wie Lungenkrebs, Diabetes oder Nierenversagen schon in einem frühen Stadium erkennen und deren Therapie überwachen. Sie stellen somit eine nicht-invasive Alternative zu Methoden wie Blutbildanalyse oder Biopsie dar. Besonders gut geeignet sind chemoresistive Sensoren basierend auf Metalloxiden. Diese bieten ein hohes Mass an Miniaturisierung, sehr hohe Sensitivität, tiefe Herstellungskosten und eine einfache Bedienung und sind somit ideal für die Integration in tragbare Geräte für den alltäglichen Gebrauch. Für die Anwendung in der Atemgasanalye verbleiben jedoch zwei grosse Herausforderungen: Erstens müssen die Sensoren am Menschen ausreichend getestet und mit einer verlässlichen Methode validiert werden und zweitens muss der Sensormechanismus besser verstanden werden um eine weitere Sensoroptimierung bezüglich Sensitivität und Selektivität zu ermöglichen.
Lay summary
Diese Herausforderungen können mit dem hier vorgeschlagenen und einzigartigen System zur in operando Charakterisierung von Atemgassensoren bewältigt werden. Hauptbestandteil des Systems ist ein Hochleistungsmassenspektrometer für eine präzise Atemgasanalyse bei Menschen zur Validierung des Sensors. Zusätzliche Messgeräte ermöglichen die Bestimmung der Partikelgrösse, deren Selektion sowie die piezoelektrische Eigenschaften des nanostrukturierten Metalloxidfilms des Sensors für eine gezielte Optimierung auf maximale Sensitivität und Selektivität. Das beschriebene System soll verwendet werden um Atemgassensoren für die Erkennung von Diabetes, Nierenversagen, Lungenkrebs sowie die Überwachung der Blutdialyse und des Blutzuckerspiegels zu entwickeln. Dieses Forschungsprojekt ist Teil von „Zurich Exhalomics“ der Hochschulmedizin Zürich, einem interdisziplinären Zusammenschluss für medizinische Forschung der ETH Zürich, der Universität Zürich, dem Universitätsspital Zürich und dem Kinderspital Zürich.
Direct link to Lay Summary Last update: 21.11.2016

Responsible applicant and co-applicants

Publications

Publication
Zeolite membranes for highly selective formaldehyde sensors
Güntner Andreas, Abegg Sebastian, Wegner Karsten, Pratsinis Sotiris (2018), Zeolite membranes for highly selective formaldehyde sensors, in Sensors and Actuators B: Chemical, 257, 916-923.
Non-invasive body fat burn monitoring from exhaled acetone with Si-doped WO3 sensing nanoparticles
Güntner Andreas, Sievi Noriane, Theodore Jonathan, Gulich Tobias, Kohler Malcolm, Pratsinis Sotiris (2017), Non-invasive body fat burn monitoring from exhaled acetone with Si-doped WO3 sensing nanoparticles, in Analytical Chemistry, 89, 10578-10584.

Collaboration

Group / person Country
Types of collaboration
Prof. A Agapiou, Department of Chemistry, University of Cyprus Cyprus (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Dr. E. Wehrle, Laboratory for Bone Biomechanics Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. M. Kohler, Klinik für Pneumologie, Universitätsspital Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Dr. Schmid, Breath Research Institut, Medizinische Universität Innsbruck Austria (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. J. Buhmann, Information Science and Engineering Group, ETH Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. H. Burtscher, Institut für Aerosol- und Sensortechnik, Fachhochschule Nordwestschweiz Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. C. Hierold, Micro- and Nanosystems, Eth Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. R. Zenobi, Dept. of Chem. and Appl. Biosciences, ETH Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. T. H. Risby, Bloomberg School of Public Health, The John Hopkins University United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
European Aerosol Conference Poster Highly selective formaldehyde detection with microporous membranes for indoor air quality monitoring 27.08.2017 Zürich, Switzerland Pratsinis Sotiris E.;


Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Breath instead of a blood test Eurekalert International 2017
Media relations: print media, online media Den Fettabbau über die Atemluft messen NZZ German-speaking Switzerland International 2017
Media relations: print media, online media Dieses Gerät misst in der Atemluft, wie gut jemand Fett verbrennt Luzerner Zeitung German-speaking Switzerland 2017
Media relations: print media, online media ETH entwickelt günstigen Fettweg-Sensor 20min German-speaking Switzerland 2017
Media relations: print media, online media Fettabbau über Atemluft messen Walliser Bote German-speaking Switzerland 2017
Media relations: radio, television Fettabbau über die Atemluft Radio24 German-speaking Switzerland 2017
Media relations: radio, television Fettabbau über die Atemluft messen Südwestrundfunk International 2017
Media relations: print media, online media New breath test being developed to help weight- watchers shed kilos Malaysian Times International 2017
Media relations: print media, online media Researchers Develop A Sensor To Tell When You're Burning Fat Huffington Post International 2017
Media relations: print media, online media Zürcher ETH-Forscher messen Fettabbau über die Atemluft Blick German-speaking Switzerland 2017

Awards

Title Year
ETH Medal for outstanding PhD Thesis of Dr. Andreas Güntner 2017
European Aerosol Conference, Zürich, Switzerland (27/8-1/9/2017): RSC Advances Poster Prize for Sebastian Abegg 2017
European Aerosol Conference, Zürich, Switzerland (27/8-1/9/2017):Best Poster Award for Instrumentation of Chemical Aerosol Characterization for Sebastian Abegg. 2017

Associated projects

Number Title Start Funding scheme
175754 Flame-made gas sensor arrays: Membrane-enhanced selectivity for breath analysis 01.04.2018 Project funding (Div. I-III)
159763 Nanostructured metal-oxide gas sensors for non-invasive disease detection by breath analysis 01.04.2015 Project funding (Div. I-III)
177037 Versatile Characterization system for novel theranostic nanomaterials 01.12.2017 R'EQUIP

Abstract

The aim of this request is to acquire a unique in operando characterization system to advance our chemoresistive sensors towards real breath analyzers applicable for non-invasive disease detection. Breath analysis offers a simple and rapid alternative to standard techniques such as blood analysis. Especially inexpensive hand-held breath analysis devices that do not require trained personnel bear the potential to drastically reduce medical diagnostic and monitoring costs and they could be applied by wide populations without medical personnel. More specifically, the ability to detect diseases already in an early stage and monitor their progress may improve medical treatment to a point-of-care therapy with higher chance for patient recovery and thus better quality of life. Our group focuses on the development of such portable breath analyzers consisting of compact metal-oxide sensors (funded by SNF grant #159763). We have significantly advanced this field by exploring unique sensing materials that feature unprecedented analyte selectivity, such as Cr/Si-doped e-WO3 (for acetone), Si-doped a-MoO3 (for NH3), Ti-doped ZnO (for isoprene) and a SnO2-based electronic nose (for formaldehyde). These sensors can be incorporated into portable breath analyzers and they are ready for extensive testing with humans for disease detection including diabetes, kidney failure and lung cancer. Despite their potential, two major challenges remain: (a) the validation of the sensors with real human breath and (b) understanding of the sensing mechanism to guide material optimization with respect to analyte sensitivity and selectivity and exploration of novel sensing materials. With the proposed system, both challenges can be addressed by combining well-established high performance mass spectrometry for reference gas analysis with particle structure (mobility analyzer) and electroceramic (piezoelectric) characterization to understand and optimize solid-gas interactions involved in breath sensor devices. We propose a proton transfer reaction time-of-flight mass spectrometer (PTR-TOF-MS), featuring high selectivity for all target analytes, lower limit of detection down to ppt concentrations. Such devices have been applied worldwide becoming increasingly recognized as the golden standard for real-time breath analysis. We had applied exactly such a system before (provided by Medical University of Innsbruck) to validate our breath acetone detector (e-WO3) revealing promising correlations between the sensor signal, breath acetone and blood glucose after overnight fasting. An additional mobility particle size selector and piezometer will be combined with the PTR-TOF-MS to provide better understanding of analyte interaction with the sensing film at the single particle level and enable systematic optimization of the sensors as particle aggregates exhibit stronger sensor response than particle agglomerates. The resulting high performance in operando characterization platform will be applied in projects for the development of breath analyzers for (A) non-invasive diabetes detection and blood glucose monitoring, (B) kidney malfunction assessment and hemodialysis monitoring and (C) lung cancer detection from breath and it will guide the (D) optimization of the sensing films. Most of these projects will involve extensive testing on humans in collaboration with the Department of Pulmonology at the University Hospital of Zurich. For these clinical trials, ethical permission has been granted already by the Kantonale Ethikkomission Zürich (KEK-ZH-Nr. 2015-0675). Our research for the development of portable breath analyzers is part of the flagship project Zurich Exhabolomics of Hochschulmedizin Zürich. This project is an interdisciplinary collaboration of highly motivated experts from both, technical and clinical areas of ETH Zurich, University Hospital Zurich, University of Zurich, University Children’s Hospital Zurich (Kispi) and EMPA. A key goal of this initiative is the development of instrumentation, devices and statistical data analysis to improve state-of-the-art breath analysis. We believe that there exists a unique constellation in Zurich for fundamental and translational research to pioneer the exploitation of exhaled breath analysis for medical diagnostics and patient management. The proposed system will contribute significantly to realize this vision since it will be made available for all collaborators within this network serving as a proven reference technique for breath studies.
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