Protein/virus-imprinted self-assembled monolayers for real-time selective detection

The imprinting of proteins and viruses remains among the most formidable challenges. This article reviews protein/virus-imprinted self-assembled monolayers (SAMs) fabricated in aqueous media containing alkanethiols and protein/virus templates on smooth and rough gold surfaces by self-assembly of alkanethiols around protein/virus templates via AuS bonds, without polymerization initiators. Subsequently, complementary cavities that match the shapes of templates were formed in the SAMs with selective binding sites through non-covalent interactions and dynamic covalent bonds, as well as the assistance of niches of rough gold surfaces. The technique of protein/virus-imprinted SAMs offers several great advantages: both organic solvents and polymerization initiators are avoided, preventing denaturation of proteins/viruses; the imprinted cavities reside in the SAMs, allowing rapid ingress and egress of proteins/viruses; the SAMs are constructed directly on the transducer surface, enabling signal transduction and real-time monitoring of binding events. The accuracy of potentiometric imprinted SAM sensors is demonstrated to be comparable to that of enzyme-linked immunosorbent assay. Current challenges in the rational choice of thiols and the precise engineering of surface roughness are also outlined. Collectively, the strategy of tailoring protein/virus-imprinted SAMs on gold surfaces opens a new avenue for creating smart materials and fabricating biomacromolecule sensors.