Micro- nano-electrodes have demonstrated superior performances in measuring attenuated intracellular action potentials from electrogenic cell cultures compared to traditional multi-electrode arrays. Yet, the understanding of the critical electrode features enabling intracellular access are limited by a lack of appropriate tools to characterize the cell/electrode interface. Consequently, the translation of these micro- nano-electrodes from cardiac to neuronal electrophysiology is difficult with only a few technologies successful for the latter so far. This is a common pitfall that supports a mounting consensus in the field that nanostructures need to be pitched to the cell of interest to enable intracellular access.

This thesis, address this limitation by presenting the implementation of an impedance spectroscopy method to resolve the interface of cells with nanostructures in a multi-site, scalable manner while remaining label free and harmless to the cell. This method allows to rationalize the impact of various electrode features (e.g., geometry, chemical functionalization) on the cell/electrode coupling and is implementable for any micro- nano-electrode with moderate impedance.

In a second time, this thesis exploited the knowledge gathered in the field of electrophysiology to adapt a volcano-shaped nanostructure for parallelizable electrochemical measurements. The sensor developed allows the longitudinal study of exocytosis from neuron-like cells within a confined volume and over multiple sites. Interestingly, the kinetics of exocytosis registered at the volcano-shaped structure was faster than expected which suggests a possible role for nanoscale features to regulate exocytosis; a fundamental discovery never reported so far.

On the long term, the device developed for electrochemical study is envisioned to allow scalable, longitudinal intracellular sampling from single cells for in situ detection of neurotransmitter by redox cycling.