Ultrasensitive electrochemical biosensor of interferon-gamma based on gold nanoclusters-graphene@zeolitic imidazolate framework-8 and layered-branched hybridization chain reaction

Abstract In this work, a novel electrochemical biosensor was constructed for ultrasensitive interferon-gamma (IFN-γ) detection based on graphene@zeolitic imidazolate framework-8 hybrids anchored gold nanoclusters (AuNCs-GR@ZIF-8) and hemin/G-quadruplex DNAzyme decorated layered-branched hybridization chain reaction (LB-HCR). The two-dimensional GR@ZIF-8 hybrids were utilized as template to anchor AuNCs through a sequential deposition method. On the AuNCs-GR@ZIF-8 platform, an improved and efficient LB-HCR pattern was designed on the strength of traditional HCR with the cascade-like assembly of four hairpins. In which, HP1 and HP2 participated in traditional HCR process to form long double-helix DNA, AD1 and AD2 assembled alternately to facilitate the layerly chain-branching growth of DNA nanostructures. The target-triggered LB-HCR resulted in the generation of dendritic DNA nanostructures integrated with numerous in-situ formed hemin/G quadruplex DNAzyme as amplifying labels, which catalyzed the reduction of H2O2 with thionine acted as the electron mediator to realize amplified signal output. This multiple-amplified strategy exhibited good analytical performance towards IFN-γ with a wide linear range form 1 fM to 50 pM and a low detection limit of 0.6 fM, holding promising application in disease diagnosis and monitoring.