Anchorhold-Actuated Strand Migration for Implementing High-Efficiency and Orthogonal DNA Logic Circuits

Toehold-mediated strand displacement (TMSD) is essential for dynamic DNA nanotechnology but often suffers from slow kinetics and nonspecific leakage, limiting efficient logic systems. To address this, we propose an anchorhold-actuated strand migration (AASM) strategy that programs a modular duplex with three specific sites to modulate the dynamic exchange, selective recognition, and transient equilibrium. The anchorhold promotes invader docking and forms metastable intermediates for rapid, leak-free separator detachment via an out-of-equilibrium branch migration. With flexible DNA building blocks, we construct basic logic gates and two-layer circuits that perform algorithmic tasks with high efficiency and accuracy. We further update the responsive AASM to realize a square-root circuit for four-bit binary numbers and a two-digit DNA molecular keypad lock for information security using cascaded combinations. These systems exhibit a fast response, simple arithmetic, and correct input–output reporting. This scalable AASM strategy offers great potential for advancing complex yet effective digital biocomputing networks for molecular information processing applications.