Development of a fully integrated impedance-based platform for in-vitro antischistosomal pharmacodynamic analysis

Schistosomiasis is a tropical disease caused by a worm of the genus Schistosoma that infects around 230 million people worldwide, predominantly children living in poor rural areas of Sub-Saharan Africa. The demand for improving the identification of promising drugs is particularly high in the field of neglected tropical diseases, where funding and commercial investments are typically low. In addition to drug efficacy, information on pharmacodynamics is becoming tremendously urgent to enable the discovery of fast-acting compounds. Fast pharmacodynamic properties, low toxicity and long-lasting effects represent key parameters for the selection of highly promising compounds among potential leads during the in vitro screening process. A platform for in-vitro continuous dose-response characterization of drug candidates on S. mansoni larvae, using electrical impedance measurements to detect parasite viability, was recently released. As a further development, successively in the screening cascade, a supplementary drug wash-out assay for better in vitro selection prior to in vivo testing would be advantageous. An automated drug wash-out procedure would provide effectiveness insights on candidate compounds while still maintaining an adequate throughput for hit selection. This thesis presents a portable integrated platform for additional pharmacodynamic analysis of drug candidates against S. mansoni larvae. A tube-free microfluidic chip for antischistosomal drug wash-out assays was designed, simulated and fabricated with rapid prototyping techniques, using almost exclusively thermoplastic polymers. The chip was validated and a suitability study for assays on S. mansoni larvae was performed with encouraging results. In parallel, the requirements for a lock-in demodulator block for the impedance-based readout, which could be used for single-frequency impedance analysis at 500 kHz, were determined. The device thus selected performs similarly to the standard instrument and would drastically reduce the costs of the experimental test setups. Finally, the results appear to be encouraging both for the microfluidic chip and for the readout platform. The early development parts were carried out successfully and will be the basis for future improvements in the context of parallelized high throughput screening on S. mansoni.