Electrode Droplet Microarray (eDMA): An Impedance Platform for Label-Free Parallel Monitoring of Cellular Drug Response in Nanoliter Droplets

Label-free real-time monitoring of cellular behavior using impedance spectroscopy is important for drug development and toxicological assessments. Parallelization and miniaturization of such experiments are essential for increasing throughput and enabling experiments with low abundant stem or primary cells. Traditional methods are not miniaturized and require large volumes of reagents and number of cells, limiting their suitability for cost effective high-throughput screening of cells of limited availability. Here, the fabrication, optimization, and application of a bioelectrical signaling monitoring system - electrode droplet microarray (eDMA) are demonstrated. The eDMA platform is based on preparation of a hydrophilic-superhydrophobic patterns covering an array of individually addressable microelectrodes, which confines cells to individual microelectrodes, allowing for parallel, real-time, and label-free detection of cellular responses to drug treatments in nanoliter droplets. The real-time monitoring of cytotoxic effect of an anticancer drug is demonstrated over 48 h with real-time calculation of the half-inhibitory concentration (IC50) values through impedance spectroscopy. This demonstrates eDMA's ability to dynamically assess responses to various drugs in parallel at any given time point, which is crucial for functional personalized oncology. Specifically, the platform can be employed for monitoring anticancer drug toxicity using limited patient samples, where the miniaturization provided by eDMA is essential.