Insulative Compression of Neuronal Tissues on Microelectrode Arrays by Perfluorodecalin Enhances Electrophysiological Measurements

Abstract Microelectrode array (MEA) techniques provide a powerful method for exploration of neural network dynamics. A critical challenge is to interface 3D neural tissues including neural organoids with the flat MEAs surface, as it is essential to place neurons near to the electrodes for recording weak extracellular signals of neurons. To enhance performance of MEAs, most research have focused on improving their surface treatment, while little attention has been given to improve the tissue‐MEA interactions from the medium side. Here, a strategy is introduced to augment MEA measurements by overlaying perfluorodecalin (PFD), a biocompatible fluorinated solvent, over neural tissues. Laying PFD over cerebral organoids insulates and compresses the tissues on MEA, which significantly enhances electrophysiological recordings. Even subtle signals such as the propagation of action potentials in bundled axons of motor nerve organoids can be detected with the technique. Moreover, PFD stabilizes tissues in acute recordings and its transparency allows optogenetic manipulations. This research highlights the potential of PFD as a tool for refining electrophysiological measurements of in vitro neuronal cultures. This can open new avenues to leverage precision of neuroscientific investigations and expanding the toolkit for in vitro studies of neural function and connectivity.