Interfacial Electric Locking of the Aptamer Conformation for Accurate Liquid Biopsy Detection

The binding affinity of aptamer, which plays a key role in aptamer-based liquid biopsy, is affected by the unstable aptamer conformation. Existing strategies enhancing the binding affinity are complex, time-consuming, not easily generalizable, and lack universality to different aptamers. Herein, we discovered an interfacial electric locking effect and developed a universal strategy to stabilize aptamer conformations at the semiconductor-liquid interface. A positive liquid gate voltage redistributes the ions, forming a positively charged environment with an increasing cation concentration at the interface. The positive environment and the ionic interaction between the cations and phosphate backbone locks the aptamer conformation, decreasing the dissociation constant down to 10^-10 M with universality to different aptamers. The platform based on this strategy monitors a wide range of analytes in less than 5 min with a lowest limit of detection down to 10^-20 M. With such ultrasensitive detection capability, the platform demonstrates a robust classification accuracy of 98.6% in 51 clinical samples of bladder cancer.