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Platform for label-free quantitative detection of single proteins and extracellular vesicles

Periodic Reporting for period 1 - IBIS (Platform for label-free quantitative detection of single proteins and extracellular vesicles)

Reporting period: 2017-09-01 to 2019-02-28

ERC PoC project no. 755196, IBIS
“Platform for label‐free quantitative detection of single proteins and extracellular vesicles”
Principal Investigator: Niek F. van Hulst

The main objective of the IBIS project is the development of an ultrasensitive, compact and low cost platform for the label-free quantitative detection of single proteins, and specifically the characterisation of nanometric extracellular vesicles. Exosomes have moved into the research spotlight, being perceived as potential biomarkers for cancer and neurodegenerative diseases, that can be sampled non-invasively. There is currently a need for reliable label-free quantitative detection and analysis techniques. We have developed a platform that allow such label free detection based on detection of scattering signal. Most importantly, we detect interferometric signal, making the contrast proportional to the volume of the particles (not volume-squared), thus being particularly sensitive for ultra small particles. Moreover implementing a balanced detection we have pushed the sensitivity even deeper, reaching limits of 15kD level. In practice the balanced detection proved to limit the size range, thus we first implemented a multiple balanced mask approach and later moved to back focal plane detection, yielding a contrast response suitable for particles with a range of 30x in volume. At the end of the PoC project the platform has sufficient range to enter into first tests on exosomes. Throughout the project we have developed a compact prototype instrument that should allow transfer of our novel detection scheme from the laboratory to the clinical environment.