Substrate-Mediated Fluorination of Graphene Directs Biointerface Chemistry and Cellular Interactions

Pristine graphene biointerfaces exhibit inert surface chemistry and hydrophobicity that restrict protein adsorption and limit control over cellular interactions. Chemical functionalization provides a route to overcome these constraints by introducing specific covalent bonds and hydrophilic groups that reprogram interfacial chemistry and wettability. Here we demonstrate xenon difluoride fluorination of CVD monolayer graphene as a versatile strategy to engineer interfacial properties and cellular response. The fluorination of graphene is mediated by the supporting substrate: on SiO₂ it remains single-sided, on Si it becomes double-sided via pinhole-assisted substrate etching, and on PET it couples to polymer chemistry, with subsurface acyl fluoride (-COF) species evolving into hydrophilic -COOH groups. These mechanistically distinct routes produce markedly different surface chemistries and wetting behaviors, from hydrophobic SiO₂/FGr (∼88°) to superhydrophilic Si/FGr (∼15°) to tunable PET/FGr (47-78°). Complementary characterization via Raman spectroscopy, XPS, AFM, and electrical measurements reveals that C-F bond formation and the resulting polar functional groups, rather than surface roughness changes, are the primary drivers of the observed wettability changes. These polar groups also directly enhance protein adsorption on fluorinated surfaces, as confirmed by XPS analysis of media-exposed samples. Consequently, breast cancer cell adhesion and proliferation are promoted on fluorinated graphene with respect to pristine graphene on PET, demonstrating that reprogramming of surface chemistry effectively overcomes graphene's inherent bioinertness. This substrate-controlled approach opens versatile pathways for engineering graphene-based biomedical devices.