Microfluidic platform for cell culture, in vitro construction of complex neuronal networks and the screening of neuroprotective molecules – Neuroscreen

This proposal is based on interdisciplinary work that combines microfluidic and nanobiophysics technologies developed at Curie Institute (team ofL. Malaquin/JL Viovy) with fundamental neuroscience methods and experimental models developed in the team of B. Brugg/JM Peyrin at Université Pierre et Marie Curie. It is aimed at developing new micro-nanofluidic tools to bridge the gap currently existing between in vivo and in vitro methods for neurosciences studies, and thus to provide tools with an unprecedented accuracy to create well controlled in vitro living neuronal networks. Current experimental models used to study brain physiology range from whole animal models that preserve the anatomical structures but strongly limit the experimentation at the cellular level, to dissociated cell culture systems that allow detailed manipulation of cell phenotype but lack the highly ordered and instructive brain environment. In order to fill in this gap, we proposed in a previous ANR project under the "Neurosciences" programme, the new concept of "axon diodes", allowing for the first time the culture of two neuron populations, with a deterministically imposed connection polarity. A first series of results demonstrated the high efficiency of this concept, but further progress towards the realization of more realistic architecture will require further technological developments, regarding notably the management and deterministic connection of multiple populations, and the deterministic positioning of neurons more accurately down to the single cell level. The present project is aimed at such progress. Specific technological developments, compatible with a future industrial production, will allow the implementation of this new experimental paradigm into a mature, high throughput and high content cell screening assay platform.
Thanks to the participation of Fluigent, the first French microfluidics company, , a platform suitable for rapid future industrialization, using all the resources of industrial-scale microfabrication and instrumentation, will be built from the above fundamental and technological research.. This will allow dissemination of the technology beyond the current very limited number of academic consortia possessing both the soft lithography skills and the cell biology expertise. It will also permit its use in large scale screening projects in the pharmaceutical industry.
As both a guide and validation, these developments will be applied to unraveling the molecular mechanisms underlying neurodegenerative diseases, and to the screening of potential neuroprotective drugs. These progress in the control of the environment and mutual organization of cells, however, will open a more general field of applications, encompassing for instance other neurodegenerative diseases (Huntington, Parkinson) studies of brain development, stem cells research, cognitive neurology, and replacement of animal testing by cell studies in numerous fields of pharmacology , toxicology or cosmetics.