Large-scale in vitro screening techniques have greatly advanced basic research and helped to identify drug candidates for treating human diseases, but current methods are optimized for dividing cells that can be expanded to generate large sample sizes, not for post-mitotic cells such as neurons. As such, the effort and cost of obtaining neurons for large-scale screens have limited drug discovery efforts in neuroscience. The authors used the CellRaft® Technology to generate thousands of neuronal mini-cultures for both mouse neurons and human-induced pluripotent stem cell-derived neurons. Furthermore, they were able to successfully detect disease-related defects in synaptic transmission and identify candidate small molecule therapeutics. CytoSort™ Arrays were seeded to create sufficient neuronal densities for network maturation while maintaining effective numbers of neurons for compound screening. This new approach was shown to have advantages in terms of evaporation issues that plague traditional long-term micro-cultures, and favorable viability was demonstrated when the CytoSort™ Arrays were compared to 384-well plates.