Final Report Summary - NEURO-PLASMONICS (Neuro-Plasmonics) Broadly speaking, neurons communicate to each other by exchanging chemical and electrical signals. The formers are transported by neuro-transmitters and other bio-molecules whereas the latter, the so-called action potentials, travel along connection between neurons (axons and neurites). The aim of this project is to develop a multifunctional in-vitro platform capable of investigating neuronal signaling on different scales, namely from the single cell to the network level. Current methods for investigating action potentials are the well-known patch&clamp and the micro-electrode array. In the first a sharp electrode is pushed against or inside a single neuron thus accessing the intracellular potential that is more intense and informative than the extracellular one. However, by using this method only a limited number of cells can be monitored whereas brain capabilities likely emerge from large ensemble of cells. Micro-electrode arrays (MEA) and CMOS technology partially overcome this limitation by monitoring a large number of neurons. Unfortunately, being realized with planar fabrication technologies, they lie in close contact with the cell membrane but they cannot access the intracellular compartment (hence only the extra-cellular potential is monitored). The pivotal step of the project is to develop 3D nano-electrodes integrated with electronic devices (CMOS and MEA) capable of accessing the intracellular compartments. In order to develop this pioneering neuro-interface two hard challenges have to be faced: the realization of 3D nano-electrodes and the development of a method for inserting the nano-electrodes into the cells with no side effect (intracellular coupling). In the first two years of the project we successfully developed a method for realizing this 3D nano-structured interface and we combined this technology with CMOS technology. We developed a method capable of accessing the intracellular compartment with no side effect. Furthermore, we showed that by using these 3D nano-structures as optical enhancers (plasmonic) is possible to investigate bio-chemical process occurring at the cell membrane by means of enhanced Raman Scattering. Finally we also showed that by using the developed platform is possible to deliver arbitrary molecules inside the intracellular compartment with single cell selectivity. The latter may give access to radically new experiments involving single selected cells within large populations. The possibility of administrating selected molecules to selected cells while monitoring the electrical and biochemical activity represent a fundamental tool for pharmacological screening and drug testing for brain related disease with a clear a direct societal impact.
