Infected body on a chip”: Microfluidic impedance platform for antischistosomal drug discovery
Project Abstract
Many new methods in drug discovery originate from the field of microfluidics, which also include innovative methods to monitor the status of cells or tissues by means of electric impedance spectroscopy (EIS). This fact has motivated the Helminth Drug Development Unit (HDDU) at the Swiss Tropical and Public Health Institute and the Bio Engineering Laboratory (BEL) at the ETH Zurich to combine their expertise and innovate on an “infected body-on-a-chip” (iBoC) microfluidic EIS platform for antischistosomal drug discovery. The device will allow, for the first time, to measure continuous, online drug dose-response effects on the larval stage of the worms, rendering the screening process higher throughput, more objective, and richer in quality data. The chip will incorporate spherical myocardial and liver microtissues, which, upon exposure to the drug, will capture two highly relevant toxicity parameters- cardiotoxicity and hepatotoxicity. The liver spheroids, included in the testing procedure with the schistosomes, will also be used to model drug metabolism and enable us to immediately predict, whether a compound will lose its antischistosomal activity in vivo as a result of metabolic processes. By screening compounds directly in the presence of both, newly transformed schistosomula (NTS) and liver spheroids, we may even be able to identify prodrugs. Finally, we will use the chip to analyze, why a set of already tested compounds might have failed in vivo. If we can characterize efficacious in vitro compounds and also the reasons for why they are likely to fail or succeed in vivo, we will not only be able to better predict good candidates for in vivo tests, but also gain a deep understanding of the pivotal aspects in finding effective antischistosomal drugs.
