Confined and fluid entropy-driven strand displacement reaction on red blood cell membrane for rapid and efficient detection of MicroRNA

Entropy-driven Strand Displacement Reaction (ESDR) serves as a fundamental tool for designing DNA signal-amplified biosensors, demonstrating significant potential in early disease diagnosis. Unfortunately, most ESDR systems still face problems such as complex design, long reaction time (typically several hours), low efficiency, and poor stability in complex biological environments. Inspired by the natural fluid cell membrane, we employed the simply prepared red blood cell (RBC) membrane as a carrier to design a confined and fluid RBC-ESDR system for rapid and efficient detection of microRNA. RBC-ESDR is convenient and efficient in loading different probes and adjusting the probe ratio. By utilizing its spatial confinement effect and membrane fluidity, the local concentration of the probes and the collision efficiency between the probes are significantly improved, thus greatly accelerating the reaction kinetics. Compared to conventional free-ESDR system relying on free diffusion and random collision, RBC-ESDR system achieves higher reaction speed (increased by 6 times) and higher sensitivity (2 orders of magnitude), allowing rapid and sensitive detection of microRNA in complex biological matrices, exhibiting economic, rapid, and sensitive clinical diagnostic potential.