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Localized surface plasmon resonance (LSPR) biosensing based on supported metal nanoparticles offers unparalleled possibilities for high-end miniaturization,multiplexing and high-throughput label-free molecular interaction analysis in real time when integrated within an opto-fluidic environment.However,such LSPR-sensing devices typically contain extremely large regions of dielectric materials that are open to molecular adsorption,which must be carefully blocked to avoid compromising the device readings.To address this issue,we made the support essentially invisible to the LSPR by carefully removing the dielectric material overlapping with the localized plasmonic fields through optimized wet-etching.The resulting LSPR substrate,which consists of gold nanodisks centered on narrow SiO2 pillars,exhibits markedly reduced vulnerability to nonspecific substrate adsorption,thus allowing,in an ideal case,the implementation of thicker and more efficient passivation layers.We demonstrate that this approach is effective and fully compatible with state-of-the-art multiplexed real-time biosensing technology and thus represents the ideal substrate design for high-throughput label-free biosensing systems with minimal sample consumption.