Development of neural guidance for neuro-electronic hybrid systems

In the last few decades, significant progress has been made in our knowl edge and understanding of neurophysiology and the development of microel ectronics. Convergeance of both researchfields offers a promising future for the creation of neuron-chip hybrids. These devices can provide new insights into the mechanisms underlying several neurological disorders a nd could be used for fast and efficient screening of active substances f or drug development. In addition, optimalisation of bidirectional commun ication between individual neurons and micro-electronics could lead to t he development of neuroprosthetics equipped with neuro-electronic hybrid s directly coupled to higher brain functions. Despite considerable progress in micro-electronic design, there remain s ome serious challenges to improve the interface between neurons and chip . In particular, current devices suffer from a low signal-to-noise read- out ratio and lack a one-to-one correspondence between neurons and elect rodes. Our objective was to develop a neuron-chip interface which promot es long-term adhesion of neurons on top of sensors and enables to contro l outgrowth of neurites and the formation of synaptic contacts.< br> To guide cell adhesion and neurite outgrowth, we developed a microcontac t printing method to pattern cytophilic molecules on a cytophobic backgr ound. Micro-contact printing is a cost-efficient and relatively simple m ethod enabling the local transfer of molecules to a substrate. By optimi sing this method, we succeeded in establishing neuronal networks with hi gh spatial resolution on a simple PLL pattern. However, after ten days i n vitro, neurite growth and shortening caused neurons to be dislocated f rom their initial adhesion sites. In order to confine neurons to their i nitial adhesion site, we createdTeflon microstructures to complement our PLL pattern. Our results show that these microstructures are effective at long-term confinement of neurons. Immunocytochemical double stainings and viability assays clearly showed that neuronal development on these substrates was unnaffected by the Tef lon micro-structures and comparable to control cultures. Intracellular&n bsp;[Ca2+] measurements demonstrate that neurons grown on these substrat esexhibited normal responses to glutamate application. In addition,we ob served a significant decrease in the number of synaptic connections. In the last part of our work, we aimed at controlling neuronal polarity. Influencing neuronal