In vitro models of the blood-brain and blood-CSF barriers using an integrated microfluidic device
© Manu Friederich / Universität Bern

ESR 2 vision / project

Ana Raquel Santa Maria - Biological Research Centre

ESR 2

In vitro models of the blood-brain and blood-CSF barriers using an integrated microfluidic device

Project Results

Models of brain barriers are important to study physiological functions, transport mechanisms, drug delivery and pathologies. Microfluidic and microelectronic integrated biochips are new tools to monitor several of the crucial parameters of cell-culture-based brain barrier models. We further developed a lab-on-a-chip device designed by our team (Walter et al. 2016) to model blood-brain and blood-cerebrospinal fluid barriers. The device allows co-culture of two or three types of cells, flow of culture medium, visualization of the entire cell layer by microscopy, real-time transcellular electrical resistance monitoring, and permeability measurements. The design of the chip was improved. A chip manufacturing protocol was established together with an individual registry system for each biochip to allow follow up, reproducibility and easy problem solving. Experiments were performed on a human brain endothelial cell line in the biochips to monitor the effect of fluid flow on resistance and other electrical parameters. In cooperation with UART, a stem cell derived human endothelial cell and bovine pericyte co-culture model (Cecchelli et al. 2014) was also tested in the biochip. The barrier tightening effect of fluid flow/shear stress was confirmed on both human cell-based blood-brain barrier models in the new version of the biochip. In addition, we investigated the role of glycocalyx and negative surface charge in blood-brain barrier permeability, and modulated the surface charge of brain endothelial cells with different methods.

Awards

2019 Finalist in the national Famelab in Hungary
2019 Best presentation in the PhD Journal Club course at the University of Szeged
2019 Best presenter in the international conference “International Student Congress of (Bio) Medical Sciences”, Groningen, Netherlands
2019 MCAA Micro grant to attend to “International Student Congress of (Bio) Medical Sciences”, Groningen, Netherlands
2018 Straub Young Scientist Prize, Biological Research Centre, Szeged, Hungary
2018 Special Prize at the 21st International Symposium on Signal Transduction at the BBB
2017 Best poster prize at the Hungarian Biophysics Conference, Szeged, Hungary

Outreach Experience

2019 Project manager, “NativeScientist” project, Hungary

Hosting institution

Biological Research Centre, HAS, Biological Barriers research group, Hungary

Supervisor

Maria Deli

Early Stage Researcher

Ana Raquel Santa Maria