Out-of-plane graphene materials for enhanced cell-chip coupling

Bioelectronic devices interact directly with biological systems to monitor cellular electrical activity and promote cell reaction to electrical stimulation. The capabilities of such devices, in terms of recording and stimulation, are affected by the effective cell-platform coupling. Therefore, during the last years, the development of engineered 2.5-3D micro and nanostructures has improved the effectiveness of biosensors using protruding structures to achieve a more intimate contact between cells and substrates. The vertical structures, due to their surface curvature, can actively modulate the cell-material interaction and the coupling conditions by regulating peculiar cellular processes at the interface such as membrane bending, ruffling, which ultimately reduce the distance between the electroactive materials and the biological components. In parallel, the rising of carbon-based materials (i.e., graphene) for bioelectronics has gained attention during the last years because of their outstanding chemical properties which allow improved cell-device interfacing. Given this scenario, 3D out-of-the-plane graphene structures has been designed and grown on planar platforms, exploiting the electrical, mechanical and optical features of this promising material. 3D fuzzy graphene (3DFG) and two nanowire-templated arrangements (NT-3DFG collapsed and non-collapsed) were realized to ultimately increase the dimensionality at the interface with cells through nanoscale features and wire-based architectures. Here we report a comprehensive study of the electrogenic cells-material interface by using fluorescence and electron microscopy for characterizing cell-graphene materials interactions at micro and nanoscale. First, we investigated the biocompatibility and the adhesion effect (cell stretching and outgrowth) of the diverse graphene-based pseudo-3D surfaces coupled to cardiomyocytes-like cells and primary cortical neuronal cells. Then, we examined the membrane deformation and the actual cell-device coupling via scanning electron microscopy/focused ion beam sectioning. We found out an enhanced cells adhesion on the substrates, suggesting that out-of-the-plane platform could improve the coupling between cells and sensors not only for electrophysiology application but also to modulate cellular functionalities and outgrowth