Programmable High‐Speed and Hyper‐Efficiency DNA Signal Magnifier

Herein, a programmable dual‐catalyst hairpin assembly (DCHA) for realizing the synchronous recycle of two catalysts is developed, displaying high reaction rate and outstanding conversion efficiency beyond traditional nucleic acid signal amplifications (NASA). Once catalyst I interacts with the catalyst II, the DCHA can be triggered to realize the simultaneous recycle of catalysts I and II to keep the highly concentrated intermediate product duplex I‐II instead of the steadily decreased one in typical NASA, which can accomplish in about only 16 min and achieves the outstanding conversion efficiency up to 4.54 × 10(8), easily conquering the main predicaments of NASA: time‐consuming and low‐efficiency. As a proof of the concept, the proposed DCHA as a high‐speed and hyper‐efficiency DNA signal magnifier is successfully applied in the rapid and ultrasensitive detection of miRNA‐21 in cancer cell lysates, which exploits the new generation of universal strategy for the applications in biosensing assay, clinic diagnose, and DNA nanobiotechnology.