Resettable and enzyme-free molecular logic devices for the intelligent amplification detection of multiple miRNAs via catalyzed hairpin assembly

The integration of multi-level DNA logic gates for biological diagnosis is far from being fully realized. In particular, the simplification of logical analysis to implement advanced logic diagnoses is still a critical challenge for DNA computing and bioelectronics. Here, we developed a magnetic bead/DNA system to construct a library of logic gates, enabling the sensing of multiplex target miRNAs. In this assay, the miRNA-catalyzed hairpin assembly (CHA) was successfully applied to construct two/three-input concatenated logic circuits with excellent specificity extended to design a highly sensitive multiplex detection system. Significantly, the CHA-based multiplex detection system can distinguish individual target miRNAs (such as miR-21, miR-155, and miR let-7a) under a logic function control, which presents great applications in the development of rapid and intelligent detection. Another novel feature is that the multiplex detection system can be reset by heating the output system and the magnetic separation of the computing modules. Overall, the proposed logic diagnostics with high amplification efficiency is simple, fast, low-cost, and resettable, and holds great promise in the development of biocomputing, multiparameter sensing, and intelligent disease diagnostics.