MICROPHYSIOLOGICAL SYSTEMS FOR DRUG SCREENING

Ciprian Iliescu1,2,3

1 eBio-hub Research Center, National University of Science and Technology PolitehnicaBucharest; 2 National Institute for Research and Development in Microtechnologies- IMT Bucharest; 3 Academy of Romanian Scientists

The low probability of a drug candidate’s clinical success, the time consumed and the high cost of bringing a drug from concept to market emphasizes the need for new approaches to drug discovery. Recent development in microfluidic technologies, such as organ-on-a-chip, droplet microfluidics and high-throughput screening are revealing the potential of these platforms to address some of these challenges, due to the small volume of samples used, short processing time, and improved process control. 

The talk is focus on the recent research of the author in the field of microfluidic platforms (so call “microphysiological systems”) for drug screening. A new approach in cell culture model (so called “constrained spheroids”) will be analysed. The perfusion system – “Incubator on a chip” -was further developed for this cell culture model – a microphysiological system that integrate the perfusion of the media with the functions of the classical incubator, offering also the opportunity of real time monitoring of cell culture. The system was tested using rat hepatocyte for acute and chronic repeat dosing drug safety testing using two model-drugs diclofenac and acetaminophen (APAP). The incubator-on a chip system was further develop for a vascular-liver (co-culture) chip for sensitive detection of nutraceutical metabolites from human pluripotent stem cell derivatives. Moreover, preliminary testing was performed for testing rat “tissue on a chip”, in this case tissue slides were inserted in a cage having on top and bottom ultrathin parylene C membranes. A tangential flow over the membranes was assured using a microfluidic structure for metabolites collection and refreshing the culture media. A step forward: “animal-on chip” – drug screening on zebra-fish embryo. The perfusion based microfluidic chip presents a fluidic concentration gradient generator and eight fish tanks of 1.4 mm-diameter (and a depth of 1mm). 

Finally, the opportunities and challenges of microfluidic applications in drug discovery will be presented with examples of the use of microfluidics in translational research.