Interfacial chemicals for metal surface functionalization were developed for applications of high water dispersibility and environmental stability. Metal nanomaterials, i.e., gold nanoparticles (AuNPs), were synthesized by introducing various interfacial chemicals, to improve the hydrophilicity of biosensors, such as those used in fluorescence resonance energy transfer (FRET) and lateral flow assay (LFA), respectively. Previously, thiolated AuNPs (SH-AuNPs) exhibited colloidal instability by forming irreversible aggregates in extreme environmental conditions; this phenomenon led to limitations such as poor sensitivity and reproducibility, in terms of biosensor application fields. Therefore, the development of novel interfacial chemicals remained a challenge for AuNP-based biosensor applications. Here, we first synthesized and demonstrated an ultra-stable AuNP functionalization by introducing N-heterocyclic carbene (NHC) compounds with a polyethylene glycol chain and azide terminal groups (NHC-AuNPs). The high binding energy of NHC-AuNPs compared with SH-AuNPs was demonstrated by density functional theory simulation, with NHC-AuNPs showing an unprecedented stability in extreme environmental conditions with varying ranges of pH, salts, and temperature; in particular, ultra-stability was observed in condition by freezing/thawing over 120 times. NHC-AuNPs were applied FRET and LFA biosensors and showed excellent sensing performances. Based on the results, NHC-AuNPs can be introduced for performance improvement in the development of diagnostic platforms to utilize in extreme environmental conditions.

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