Design of a cost-effective inverted tetrahedral DNA nanostructure-Based interfacial probe for electrochemical biosensing with enhanced performance

DNA nanostructure-based interfacial probes have been an emerging candidate for constructing next-generation biosensors. However, one major limitation of these sensors is the high cost for preparing DNA nanostructure probes caused by the requirement of multiple modification groups (e.g., several thiol groups and other functional tags), which greatly increase synthesis difficulty and hinder their large-scale application. Herein, we demonstrate that an inverted tetrahedral DNA nanostructure (iTDN) can be a cost-effective interfacial probe for electrochemical sensing. Thanks to the symmetric and rigid structure of iTDNs, only one thiol group is needed in the probe, greatly reducing the cost in each assay. The relative freedom of iTDNs makes them consistently keep appropriate orientation for molecular recognition and the involved sensors can tightly capture target molecules, because iTDN has multiple recognition elements, thus resulting in improved performance compared to traditional E-DNA sensors. Moreover, by simply adjusting the recognition elements in the iTDN, different analytes such as microRNA and exosome are detected with high sensitivity and specificity in the complex media, indicating its potential application in the future.