Breath analysis project
Breath analysis as a diagnostic tool for early disease detection
A EURAMET joint research project funded by the EC’s 7th framework programme, ERA-NET Plus
Objective:
Development of spectroscopic techniques for the identification and accurate quantification of biomarkers in human breath
Project duration:
May 2008-April 2011
Project partners
• VSL, the Netherlands (coordinator)
• Danish institute for Fundamental Metrology (DFM), Denmark
• Portuguese Institute for Quality (IPQ), Portugal
• Institut National de Métrologie (LNE-INM-Cnam), France
• Physikalisch-Technische Bundesanstalt (PTB), Germany
• HC Photonics, Taiwan www.hcphotonics.com
INTRODUCTION
Early disease detection is getting increased attention in the medical sector. In early stages, many diseases know little or no suffering at all, and the prospects of curing are much better. Breath analysis is one of the clinical tests that can be used for early disease detection. It is non-invasive, relatively easy to maintain and handle “on-site”. Recent developments in infrared laser absorption spectroscopy techniques, and in particular cavity ring down spectroscopy and tuneable diode laser absorption spectroscopy, allow developing compact devices for performing these tests. The devices must have a high level of accuracy and reliability with respect to measurement of extremely low levels of trace gas components encountered in human breath.
Although the development of equipment is well underway, progress is hindered because of a lack of accuracy and reliability in measurement results. The project addresses these issues by aiming to make reliable identification of the species present in the exhaled breath, and reduce the uncertainty of measurement of the amount of substance from the current typical 10% down to at most 1-2%.
The project team is supported by an advisory board that is being formed containing experts from equipment manufacturers, medical and clinical research groups, and spectroscopists. The advisory board will also serve as the scientific committee that supports the organisation of the closing symposium.
MAIN TOPICS WITHIN THE PROJECT
Development of instrumentation for breath analysis
-Development and use of infrared sources covering the 1.5-12 µm wavelength range: difference frequency generation, diode lasers, quantum cascade lasers, fibre lasers, and optical parametric oscillators (OPOs)
-Construction of spectrometers based on cavity ringdown spectroscopy and direct absorption spectroscopy (using single/multi-pass cells or hollow-core photonic bandgap fibres)
Validation of spectroscopic methods and determination of spectroscopic parameters
-Determine line strengths of selected molecules and setting-up uncertainty budgets
-Comparative measurements using gas chromatography, mass spectrometry and FTIR
Dealing with interferences
-Use of physical and chemical scrubbers to reduce interferences by water and carbon dioxide.
-Use of advanced analysis software to deal with multi-component gas mixtures.
-Preparation of gas mixtures (amongst others mixtures with high water and carbon dioxide content)
Dissemination, exploitation and knowledge transfer activities
-Reports, publications, presentations and a final symposium
RECENT ACHIEVEMENTS
Instrument development
-construction of two OPO’s with wide tunability in the mid-infrared and high output power
-reduction of losses at the collapsed end of the hollow-core photonic bandgap fiber
-finalizing cavity ringdown set-up for the 2.7-3.4 µm wavelength region
Spectroscopic measurements
-high resolution recordings of methane at 1.5 µm using hollow-core photonic bandgap fibres
-extensive line shape analyses of acetylene and ammonia spectra with fitting routines including almost all known line shapes
-comparison measured infrared spectra with Fourier Transform Infrared (FTIR) spectra from NIST and PNNL database. Data agree within the measurement uncertainty for propane, ethane, formaldehyde, and benzene
Other highlights
-test of chemical and physical techniques to remove moisture from human breath
-preparation of gravimetrically prepared gas mixtures
-documenting technical method for calibration-free amount fraction measurements based on spectroscopic absorption techniques
Activities that have been undertaken in dissemination, exploitation and knowledge transfer include:
-established contacts with equipment manufacturers and medical hospitals in the Netherlands, Germany, and France
-HC Photonics, a Taiwanese manufacturer of periodically poled non-linear crystals, joined the consortium
PRESENTATIONS
1. Stefan Persijn, Annarita Baldan. Dynamic generation of trace levels of formaldehyde standard gas mixtures and measurement by cavity ring down spectroscopy. Oral presentation. Gas 2009, Rotterdam. 9-11 February 2009. Click here for presentation.
2. Stefan Persijn and Adriaan van der Veen. Spectroscopic analysis of biomarkers in breath. Poster presentation at GAS2009, Rotterdam, the Netherlands 9-11 February 2009
3. Olav Werhahn. European metrology project on breath gas analysis (EMRP). Poster presentation at National Gas-Sensor-Workshop, Fraunhofer IPM, Germany March 2009. Click here for presentation.
4. Stefan Persijn and Adriaan van der Veen. Versatile spectrometer for gas detection down to the part per billion level. Poster presentation at Fotonica, Nieuwegein, the Netherlands 2 April 2009
5. Adriaan M.H. van der Veen, Stefan T. Persijn, Jan C. Petersen, Florbela Dias, Fernanda Saraiva, Gonçalo Baptista, Jean-Jacques Zondy, Stephan Briaudeau, Olav Werhahn. Breath analysis as a diagnostic tool for early disease detection. Oral presentation at ICM 2009, Paris, France 22-25 June, 2009. Click here for presentation.
6. Stefan Persijn and Adriaan van der Veen. Gas measurements using a versatile spectrometer and the comparison with HITRAN and PNNL database, Poster presentation at TDLS 2009, Zermatt, Switzerland 13-17 July 2009
7. Jean-Jacques Zondy. A Ti:Sapphire pump-resonant singly-resonant OPO for spectroscopic breath analysis, Oral presentation at FLAIR 2009, Garmisch-Partenkirchen, Germany 7-11 September 2009. Click here for presentation.
8. Stefan Persijn and Adriaan van der Veen. Gas measurements using a versatile spectrometer and the comparison with Hitran and PNNL database. Oral presentation at Cavity enhanced spectroscopy – Recent developments, and new challenges, Leiden, the Netherlands 2-6 November 2009. Click here for presentation.
PUBLICATIONS
1. Stefan Persijn, Frans Harren, and Adriaan van der Veen, Quantitative gas measurements using a versatile OPO-based cavity ring down spectrometer and the comparison with spectroscopic databases, Applied Physics B (accepted)
2. Two manuscripts on the instrumentation developed within the framework of the project have recently been submitted.
RESEARCH AND MANAGEMENT TEAM
Click here