Top-Down approach to nanotechnology for cell-on-chip applications

Standard cell culture techniques have remained basically unchanged for almost a century; today, thanks to advances in micro and nanotechnology related techniques, the toolbox available to biolo- gists is rapidly growing, enabling them to increase their experimental capabilities up to the level of manipulating single cells and controlling cells environment. The transition from macro to microscale gives unprecedented possibilities to generate gradients and patterns that cannot be captured in Petri dishes and well plates. Micro and nanofabrication integrating micropatterning techniques with advanced surface chemistry makes it possible to reproducibly tailor the cell microenvironment at cellular resolution. Nanopatterned surfaces that investigate the extracellular matrix with microfluidic networks for soluble factor signaling delivery have the potential to modulate spatially and temporally differentiated cellular phenotypes. Moreover, properly engineered micro and nanopatterns allow a great enhancement in the detection techniques both from the spatial and spectroscopic point of view. Future perspective will lead to develop platforms for cocolture of different populations on a single chip, in order to mimic cellular communication systems in vivo. In this paper we explore the importance of reducing the observation scale of the cellular environment and provide an essential overview of the micro and nanofabrication potentials and capabilities which are today available.