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Metrological characterisation of micro-vesicles from body fluids as non-invasive diagnostic biomarkers

Short Name: MetVes, Project Number: HLT02
Doctor with test tube

Microvesicle biomarkers: Early diagnosis of diseases

Extracellular vesicles, or EV, are cell fragments present in body fluids, such as blood and urine. They are different in patients and healthy people so can be used as biomarkers for diseases such as cancer, diabetes and cardiovascular disease. Using extracellular vesicles as biomarkers would be less invasive than current techniques and could aid early detection of common diseases and reduce the cost of healthcare. However, detecting EV is difficult because of their small size. Current techniques can only detect around 1–2 % of the total amount present, which is insufficient for disease diagnosis.


The EMRP project HLT02 Metrological characterisation of microvesicles from body fluids as non-invasive diagnostic biomarkers developed reliable sample preparation procedures, a method for isolating EV and comparable and standardised ways of measuring their size and population. These techniques have been disseminated internationally as a route for introducing harmonised clinical practices prior to the creation of documentary standards – a precursor to the introduction of the use of EV as a diagnostic tool.


The project:

  • Developed a light scattering method capable of measuring the refractive index of small particles in biological samples, making it possible to derive the true diameter of EV in suspension for the first time.
  • Developed an EV reference standard suitable for use in the calibration of flow cytometry instruments, routinely used for analysing the EV in biological research samples.
  • Developed reliable, standardised procedures and best practice for the collection, handling and storage of samples; and pioneered the use of an existing size exclusion chromatography technique (SEC) for the concentration of EV in samples prior to analysis.
  • Demonstrated the feasibility of using atomic-force microscopy to identify the specific protein present in a single type of EV.
  • Enabled the comparison of EV measurement results between different instruments and institutions,which will facilitate multi-centre EV trials.


Flow cytometry, a frequently used technique for EV analysis, now benefits from a metrological infrastructurethat ensures the analysis results are sufficiently accurate and robust to be used for disease diagnosis.Widespread adoption of the technique in clinical practice requires formal documentary standards tosupport quality assurance systems in hospitals. Three key international organisations (ISAC, ISEV and ISTH) for EV research have come together to draft a standardised procedure that will incorporate the methodsdeveloped in the project for sample preparation and measurement. This is an important first step towards theintroduction of an ISO / IEC documentary standard.


EMPIR project 18HLT01 METVES II builds on this work.

Project website
Other Participants
Academisch Medisch Centrum bij de Universiteit van Amsterdam (Netherlands)


2012 - 2015
Researcher Grants