Hybridization chain reaction and target recycling enhanced tumor necrosis factor alpha aptasensor with host-guest interaction for signal probe collection

Abstract In this paper, we have proposed a new hybridization chain reaction (HCR) and target recycling enhanced tumor necrosis factor alpha (TNF-α) aptasensor with host-guest interaction for signal probe collection. HCR induced DNA nanowires can load substantial methylene blue (MB) on electrode surface, in the presence of target TNF-α and RecJf exonuclease, the TNF-α firstly bound with corresponding TNF-α binding aptamer (S2, which used for TNF-α recognition and HCR initiation) and thus resulted in the dissociation of MB intercalated DNA nanowires from electrode into solution, while the RecJf exonuclease further made the recycling of TNF-α to obtain more dissociated DNA nanowires. With the assistant of duplex-specific nuclease (DSN), the dissociated DNA nanowires with substantial intercalated MB in solution released the free MB, which then selectively captured by the cucurbituril 7 (CB)/nano gold@chitosan functionalized electrode via host-guest interaction to produce the electrochemical signal, so the electrochemical signal would be changed by TNF-α. By tracing the electrochemical signal of adsorbed MB, our aptasensor can exhibit high sensitivity for TNF-α detection with a wide linear range from 0.001 ng/mL to 100 ng/mL and an extremely low detection limit of 0.5 pg/mL, which can also easily distinguish TNF-α in the complex samples with high specificity, providing a great potential in clinical applications in the future.