Phase Separation of DNA‐Encoded Artificial Cells Boosts Signal Amplification for Biosensing

Abstract Life‐like hierarchical architecture shows great potential for advancing intelligent biosensing, but modular expansion of its sensitivity and functionality remains a challenge. Drawing inspiration from intracellular liquid‐liquid phase separation, we discovered that a DNA‐encoded artificial cell with a liquid core (LAC) can enhance peroxidase‐like activity of Hemin and its DNA G‐quadruplex aptamer complex (DGAH) without substrate‐selectivity, unlike its gelled core (GAC) counterpart. The LAC is easily engineered as an ultrasensitive biosensing system, benefiting from DNA′s high programmability and unique signal amplification capability mediated by liquid‐liquid phase separation. As proof of concept, its versatility was successfully demonstrated by coupling with two molecular recognition elements to monitor tumor‐related microRNA and profile cancer cell phenotypes. This scalable design philosophy offers new insights into the design of next generation of artificial cells‐based biosensors.