Projects

Circulating nano traces to identify the cause of stroke (CINTICS II)

“CINTICS II” is a research project funded by the Dutch Heart Foundation that works towards pre-hospital triage of stroke patients based on circulating extracellular vesicles (EVs) and short non-coding RNA sequences. Distinguishing between stroke types in the ambulance would enable (1) the start of adequate treatment by emergency services and (2) rapid transportation of the patient to the appropriate stroke center, thereby reducing the stroke onset-to-treatment time and improving long-term patient outcome.

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

“1E3” is a VIDI project funded by the Dutch Research Council aiming to increase the detection rate of single disease-related EVs by a factor of 1,000 (1E3) using flow cytometry, in order to identify sufficient disease-related EVs between a multitude of other particles within a clinically relevant time. The aim will be achieved through three innovative steps. First, we will reduce the concentration of lipoprotein particles 10-fold within 15 minutes using beads with a “romantic surface”. Second, we will reduce the electronic dead time 10-fold by developing “smarter electronics”. Third, we will increase the count rate 10-fold by interferometry, which enables shot-noise limited detection and parallelization.

Exploring early EV-based biomarkers for acute myocardial infarction using a Chandler loop

Troponin is widely used as a blood biomarker to confirm the diagnosis of acute myocardial infarction (AMI). However, troponin lacks specificity for AMI and only increases after arterial occlusion. As a result, there is an ongoing search for new biomarkers capable of diagnosing AMI at earlier stages. Although EVs in the blood of AMI patients have been extensively studied, no EV-based blood biomarkers for AMI have been identified to date.

To address this gap, we adopted a different approach by utilizing an in vitro model, the Chandler loop, which enables the generation of arterial thrombi under high shear stress conditions. This home-built model allows us to investigate EVs released during thrombus formation, with the aim of identifying novel and early EV-based biomarkers for AMI.

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

“PHOREVER” is a research and innovation action funded by the European Union that aims to develop a disruptive multi-sensing platform with a great medical impact. The platform will enable, for the first time, the reliable detection of EVs with size down to 80 nm, the detection of EVs with specific biomarkers (proteins) on their surface, and the calculation of the corresponding EV concentrations in blood while data analysis empowered by artificial intelligence will correlate the measurement data to disease specific medical information.

RNA-top

Cells communicate by exchanging RNA associated with EVs. Analyzing EV-associated RNA (EV-RNA) holds great potential for identifying disease biomarkers. However, current EV-RNA biomarkers have proven to be irreproducible. Traditionally, RNA is believed to reside within EVs, leading most protocols to focus on isolating intra-vesicular RNA. Emerging evidence, however, suggests that EV-RNA may also be present on the EV surface. Are we inadvertently "throwing out the baby with the bathwater"?

Supported by the Marie Skłodowska-Curie Actions programme, the RNA-top project aims to investigate the precise topology of EV-RNA, i.e. its intra- and extra-vesicular localization, to advance the development of robust EV-RNA biomarkers.