An innovative novel interface has been designed and developed, in order to be used as a potential active layer in Chem-FET sensor devices for the specific sensing of Cs +. In this study, the synthesis of a specific Cs + probe based calix[4]arene benzocrown ether, its photophysical properties as well as its grafting onto a single lipid monolayer (SLM) recently used as efficient ultrathin organic dielectric in Chem-FETs are reported simultaneously. On the basis of both optical and NMR titration experiments, the probe has shown high selectivity and specificity for Cs + compared to interfering cations, even if an admixture is used. Additionally, ATR-FTIR spectroscopy was successfully used to characterize and prove the efficient grafting of the probe onto a SLM and the formation of the innovative novel sensing layer.