Simulation‐Assisted DNA Nanodevice Serve as a General Optical Platform for Multiplexed Analysis of Micrornas

Small frame nucleic acids (FNAs) serve as excellent carrier materials for various functional nucleic acid molecules, showcasing extensive potential applications in biomedicine development. The carrier module and function module combination is crucial for probe design, where an improper combination can significantly impede the functionality of sensing platforms. This study explores the effect of various combinations on the sensing performance of nanodevices through simulations and experimental approaches. Variances in response velocities, sensitivities, and cell uptake efficiencies across different structures are observed. Factors such as the number of functional molecules loaded, loading positions, and intermodular distances affect the rigidity and stability of the nanostructure. The findings reveal that the structures with full loads and moderate distances between modules have the lowest potential energy. Based on these insights, a multisignal detection platform that offers optimal sensitivity and response speed is developed. This research offers valuable insights for designing FNAs‐based probes and presents a streamlined method for the conceptualization and optimization of DNA nanodevices. The impact of the connection mode between functional and carrier modules, including load number, load position, and distance between them, on response speed, sensitivity, and cell uptake efficiency of DNA nanodevices is systematically investigated, which provides guidance for designing DNA nanodevices. A TP‐3CHA probe with significantly improved response speed and sensitivity is constructed to detect multiple microRNAs simultaneously.