We present preliminary recordings on chip of three-dimensional (3D) electric neuronal activity from cultures of cortical neurons derived from human-induced pluripotent stem cells (hiPSCs). The recordings were obtained through 3D microelectrode arrays (MEAs) composed of truncated, 90 μm-high Si micropyramids endowed with multiple, electrically distinct, and vertically arranged TiN microelectrodes. The unique design and implementation of the 3D microelectrodes, complemented by a 60-electrode readout interface, allow for 3D spatial recording of neuronal activity, as well as single-unit recordings in high throughput, which are currently not possible with commercial MEA platforms. Future work will aim at optimizing extended 3D MEAs over optically transparent substrates for electro-physiological investigation of 3D neuronal tissues and organoids.

Stemming from the convergence of tissue engineering and microfluidics, organ-on-chip (OoC) technology can reproduce in vivo-like dynamic microphysiological environments for tissues in vitro. The possibility afforded by OoC devices of realistic recapitulation of tissue and organ (patho)physiology may hold the key to bridge the current translational gap in drug development, and possibly foster personalized medicine. Here we underline the biotechnological convergence at the root of OoC technology, and outline research tracks under development in our group at TU Delft along two main directions: fabrication of innovative microelectromechanical OoC devices, integrating stimulation and sensing of tissue activity, and their embedding within advanced platforms for pre-clinical research. We conclude with remarks on the role of open technology platforms for the broader establishment of OoC technology in pre-clinical research and drug development.