Exploring innovative stimulation protocols to promote neuromodulation in brain-on-a-chip models

The aim of my project is to investigate a non-invasive alternative to classical electrical stimulation in the field of neuromodulation techniques, which employ ultrasound (US). Even though ultrasound are collecting enough interest in the scientific community for their several advantages (high spatial resolution, low cost, and non-invasiveness), the mechanisms through which sound waves interact with cells and their activity are still unclear. Under this perspective, I consider a few possible strategies to induce an in vitro electrophysiological response of neuronal assemblies of different sizes to short and low-intensity US pulses; first of all, I had been applied US on neuronal cells treated with piezoelectric barium titanate nanoparticles (BTNPs), in order to exploit their piezoelectric effect to transduce the mechanical stimulus into an electrical one. To make the experimental model closer to the in vivo scenario, I also designed a more complex experimental set-up to investigate the above strategy on heterogeneous (i.e., neurons coming from different brain areas) and three-dimensional (3D) neuronal networks. As it is known, cells in the brain are characterized by a 3D structure and multi-cellular links, so 3D structures are a more powerful model than 2D ones1 in order to emulate the in vivo effects. Moreover, I wanted to merge the two aforementioned strategies to establish an experimental protocol to release a model drug, Doxorubicin, stored in polyelectrolyte microcapsules, fabricated with the layer-by-layer technique, using an ultrasound.