An immune-inspired intelligent aptasensor with broad detection capability

Biosensors, particularly aptasensors, play a pivotal role in rapid diagnostics, but their practical performance is limited by suboptimal aptamers and conventional aptamer-material combination-based approaches. To overcome the limitations, we drew inspiration from living systems by pioneering an immune-inspired biomimetic strategy that harnesses V(D)J recombination for aptamer engineering. The resulting topology-refactored aptamers demonstrate a 133.3-fold enhancement in binding affinity. Target-aptamer binding precisely regulates the self-assembly of DNA nanosphere-Cu(II) biomimetic nanozymes, establishing the core biosensing mechanism. Integrated with smartphone-based colorimetric analysis, this platform enables high-throughput screening of various trace food contaminants in real-world complex samples, achieving high accuracy and an ultra-low limit of detection [342.1 pM for enrofloxacin, 330.8 pM for ciprofloxacin, 116.3 pM for okadaic acid, and 104.0 pM for cadmium, respectively], demonstrating broad detection capability. By redefining aptamer design, this biomimetic strategy opens new avenues for developing robust, nature-inspired biosensors for real-world use.