Facile Fabrication of Large‐Area Biofunctionalized Metallic Nanostructures for High Performance Affinity Plasmonic Biosensors

Abstract An approach is presented to the facile preparation of biointerface‐caped periodic arrays of gold nanoparticles (Au NP) with controlled plasmonic and advanced sensing properties. It relies on feedback‐controlled UV‐laser interference lithography combined with a novel ion milling method. These advancements improved preparation reproducibility yielding localized surface plasmon resonance (LSPR) wavelength tuned to near infrared spectrum with standard deviation of 10 nm. Moreover, a novel molecular toolkit of thiols and silatrane linkers with carboxybetaine/sulfobetaine headgroups is employed for orthogonal chemical modification of Au NPs and passivation of the optically non‐active sensor chip regions, to prevent non‐specific sorption of molecules from liquid samples. As part of this toolbox, the use of mercaptopropyl silatrane is reported as an adhesion‐promoting coating for attaching Au NPs to an oxide substrate, replacing the traditionally used strongly absorbing chromium. The developed biofunctional optical nanostructures show LSPR with improved quality factor and enable 2.5‐fold increase in accuracy for tracking of biomolecular binding on their surface via LSPR wavelength variations monitoring. In addition, a strategy is demonstrated to mitigate unspecific biomolecule sorption not only at the plasmonic hotspot on the metal surface, but also on the often‐overlooked oxide substrate, highlighting the importance of the described orthogonal modification.