Chatting with Neurons: A novel approach to the study of neurophysiologic responses of neuronal tissue in vitro, combining nanotechnology, tissue engineering, microfluidics and neuroelectrophysiology

Laboratory-on-a-Chip technology was introduced in this field. To avoid the complexity of an animal model and to reduce the number of animals for pre-clinical research cell culture models are important. Here, the combination of microfluidics, tissue engineering and neuroelectrophysiology on MEA-chips is suggested. Because neuronal tissue on chip may act differently from the neurons in their natural environment, the first objective is to follow a systems engineering approach to realize a platform technology, which allows us to reliably co-culture cells in a 3D interconnected configuration, providing an artificially vascularized system on a MEA. For on-line monitoring of the culturing conditions, we will implement micro-total analysis systems (TAS) technology proposing microchip capillary electrophoresis, potentially coupled to mass spectrometry, to correlate electrophysiology with neurochemistry. Previously, it has been demonstrated that physical and chemical micro- and nanostructures influence cell guidance, viability and cell differentiation, so far, unfortunately without a unifying theory to explain the involved mechanisms. Therefore, our second objective is to further our understanding with respect to the influence of nanocues, implementing microfluidic programming to activate porous nanostructures on MEA and investigate cellular signaling and pathway reactions related to the cell’s adhesion mechanism. Combining the first and the second objective will allow us to work towards clinical questions of neurodynamic diseases as epilepsy, characterized by intermittent abnormal synchronization of different neuronal populations. We hypothesize that for these disorders, 3D cell co-culture models will resemble the natural neural networks more closely than 2D, which may subsequently serve as a model to study novel therapeutic procedures, for instance selective neurostimulation. Thus, we propose, as our third objective, nanostimulation of neuronal subsystem.