Extracellular vesicle detection

Extracellular vesicles (EVs) are the generic term for particles naturally released from the cell that are delimited by a lipid bilayer and cannot replicate. Consequently, EVs are present in fluids contacting cells. As cells and EVs interact continuously, applications of EVs include liquid biopsy biomarkers, therapeutic agents, and quality monitoring of ecosystems and food production. However, realization of EV applications is challenging because (1) the subcellular size of EVs hampers their detection and characterization, and (2) EVs are often outnumbered by non-EV particles.

In the Department of Biomedical Engineering & Physics we develop software as well as novel fluidic and optical technologies to isolate and characterize EVs in health and disease, with the goal to use EVs as clinical biomarkers. Therefore, we have optical benches available with e.g. customized flow cytometers and a home-build Raman micro-spectrometer. New technologies and standardization procedures can be directly applied to clinical research study thanks to our strong collaboration with the Laboratory of Experimental Clinical Chemistry, with which we work together under the name: Amsterdam Vesicle Center.

microparticles_moore
Transmission electron microscopy (TEM) of vesicles from fresh cell-free human urine. From: Optical and non‐optical methods for detection and characterization of microparticles and exosomes
(Van der Pol et al., 2010)
Focus

Count disease-related extracellular vesicles 1000-fold faster (1E3)

EVs are present in all body fluids and regulate pathophysiological processes. As their properties change during disease, EVs offer potential biomarkers for diseases as stroke and cancer. The technical challenge is to identify sufficient disease-related EVs between a multitude of other particles within a clinically relevant time. To address this challenge, project 1E3 aims to increase the detection rate of disease-related EVs by a factor of 1,000 through three innovative steps. This project is financed with a VIDI grant, which is awarded by the Dutch Research Council (NWO) to top researchers who have conducted successful research for at maximum eight years after their PhD.

impression-photo-facscanto-leonie

Photonic integrated OCT-enhanced flow cytometry for cancer and cardiovascular diagnostics enabled by extracellular vesicles discrimination (PHOREVER)

The aim of PHOREVER is to develop a platform wherein sample preparation and characterization of single EVs down to 80 nm take place on a stack of chips. The platform will enable determination of the concentration of EVs with specific proteins on their surface in the blood while data analysis empowered by artificial intelligence will correlate the measurement data to disease specific medical information. The roles of our team are (1) defining the user requirements for the fluidical and optical systems on the chip, (2) validating the detection potential of the developed platform and AI algorithms using reference materials, and (3) demonstrating the use of the platform for the clinical analysis of EVs in blood samples of patients with a suspicion of stroke. The PHOREVER consortium is funded by the European Union and consists of 8 partners originating from 4 countries.

Targeted-fluorescence inspection of extracellular vesicles as liquid biopsy biomarkers for cancer

The aim of this project is to achieve the reliable characterization of the smallest, single EVs at a throughout of at least 1000 Hz. Therefore, two state-of-art technologies for single particle detection in fluids will be evaluated and improved. The first technology, nanoCET, consists of a microfluidic channel (<1 μm) centred in an optical fibre. Illuminated particles in the channel scatter light, which is detected by a dark-field microscope. NanoCET is currently the state-of-art for long duration tracking of single nanoparticles down to 20 nm. The second technology, ARC, is a microfluidic Coulter counter able to detect the electrical resistance and fluorescence emission of EVs as small as 50 nm. This project is part of the “Perspectief” program Photonics Translational Research – Medical Photonics (MEDPHOT) funded by the Dutch Research Council (NWO).

dsc_1193

Circulating Nano Traces to Identify the Cause of Stroke (CINTICS)

In the Western world, stroke is the most frequent cause of major disability and the third cause of death. The causes of stroke can be subdivided into haemorrhagic stroke (ruptured artery) or an ischemic stroke (blocked artery). These different subtypes of stroke need different acute treatment approaches. The ‘Time is brain’ principle is thereby crucial, because 2 million brain cells die per minute in an acute stroke. Currently, a CT-scan in the nearest hospital determines the exact cause of stroke, which is used to decide whether the patient needs further transport to a comprehensive stroke centre, thereby losing precious time. In CINTICS, we aim to develop and apply nanotechnology to detect EVs in the blood containing information about the underlying cause of stroke. We will test the technology in patient blood samples and compare the results to information from CT-scans. Early identification of the underlying cause of stroke results in important time savings, because treatment might start already in the ambulance and patients can be transported directly to the correct hospital for additional treatment. CINTICS is part of the CONTRAST consortium and funded by the Dutch Heart Foundation.

Output

See more…

Internships

See below for examples of internship projects that we offer. The projects may not always be entirely up-to-date, but they give a good impression of the work at our department. In addition, you can find the contact details of supervisors that you can send a message. Also if you have your own project proposal matching our research scope, please don’t hesitate to contact us.