EMRP-HLT02: Metrological Characterisation of Micro-Vesicles from Body Fluids as Noninvasive Diagnostic Biomarkers

• Research unit: METAS
• Project number: F-5111.30013

Key words (English)

Microvesicles, exosome, biomarkers, nanoparticles, body fluids, non-invasive

Short description (English)

In the past years, medical research has developed new diagnostic methods based on microvesicle analysis. Microvesicles are products of metabolism expelled from cells which are often smaller than 100 nm. For a diagnosis, body fluids are searched for microvesicles and their number, size, shape and other parameters are determined. As a simple non-invasive method this could help in future to detect early cancer and to avoid thrombosis. However, in medical studies the methods used so far were hardly traceable and consistent interpretation was not possible up to now.
Within this project, several measurement methods will be refined and standardised. Specific reference particles and synthetic microvesicles will be made available in order to correctly trace back these methods. The improved methods will then finally be validated by means of international comparisons. Based on the experience for nanoparticle calibration, the laboratory for nano- and microtechnology of METAS will adapt scanning probe measurement methods for microvesicles and particularly characterise reference particles and pilot an international comparison.
Efficient early diagnosis will help to reduce health care costs by improved efficacy of medical treatments and will enforce the European health sector. The laboratory for nano- and micro-technology of METAS will be able to offer new, validated calibration services as a result of this project.

This project is part of the European Metrology Research Programme (EMRP, http://www.euramet.org/index.php?id=emrp); it is partly funded by the European Union on the basis of Decision No 912/2009/EC.

Project aims (English)

Reliable microvesicle analysis in order to achieve precise early diagnoses in the health sector. Improved efficacy of medical treatments and thus reduced health care costs. The laboratory for nano- and microtechnology of METAS will offer new, validated calibration services for microvesicle calibrations.

Abstract (English)

The project was very successful and has received a broad international attention. To a large extent the planned goals were achieved. In particular our AFM measurements and the international comparison on synthetic nanoparticles, which was organised by METAS, showed interesting results. For the first time bimodal samples were calibrated in a comparison and at the same time their long term stability was measured. A major difficulty during the project was to find biological reference materials of sufficient quality, i.e. monodisperse and long term stable.
The collaboration of physicists with biologists was also something new for most of the Project partners. The initial problem of a common terminology was quickly overcome and an interesting and fruitful period followed. The project was mostly running according to the plan. There were no major problems with respect to scope, schedule and quality.

Transfer and application (English)

The project has received plenty of interest in the international medical community. The sensibility of this community with respect to the applied measurement methods and the reference materials has increased. Standardised procedures for everyday measurements at hospitals are now initiated. The project was followed and supported by the impressive number of 17 stakeholders from all over the world.
Appropriate internationally validated methods for particle size calibrations of suitable reference materials are now established and can be used for customer services. At METAS a first customer services were delivered towards the end of the project.

Publications / Results (English)

The Project generated 9 scientific publications and 37 conference contributions. See www.metves.eu for an actual list.

Results measurement comparison:

Anaïs Nicolet, Felix Meli, Edwin van der Pol, Yuana Yuana, Christian Gollwitzer, Michael Krumrey, Petr Cizmar, Egbert Buhr, Jasmine Pétry, Noham Sebaihi, Bert de Boeck, Vin-cent Fokkema, Rob Bergmans, Rienk Nieuwland, "Inter-laboratory comparison on the size and stability of monodisperse and bimodal synthetic reference particles for stand-ardization of extracellular vesicle measurements", Meas. Sci. Technol., submitted July 2015.