A Nanoparticle‐Decorated Biomolecule‐Responsive Polymer Enables Robust Signaling Cascade for Biosensing

To meet the increasing demands for ultrasensitivity in monitoring trace amounts of low‐abundance early biomarkers or environmental toxins, the development of a robust sensing system is urgently needed. Here, a novel signal cascade strategy is reported via an ultrasensitive polymeric sensing system (UPSS) composed of gold nanoparticle (gNP)‐decorated polymer, which enables gNP aggregation in polymeric network and electrical conductance change upon specific aptamer‐based biomolecular recognition. Ultralow concentrations of thrombin (10 −18 m ) as well as a low molecular weight anatoxin (165 Da, 10 −14 m ) are detected selectively and reproducibly. The biomolecular recognition induced polymeric network shrinkage responses as well as dose‐dependent responses of the UPSS are validated using in situ real‐time atomic‐force microscopy, representing the first instance of real‐time detection of biomolecular binding‐induced polymer shrinkage in soft matter. Furthermore, in situ real‐time confocal laser scanning microscopy imaging reveals the dynamic process of gNP aggregation responses upon biomolecular binding.