A reconfigurable DNA memory architecture for hierarchical data management via programmable phase transitions

Abstract DNA has emerged as a promising medium for the post-silicon era of information storage due to its ultrahigh density and longevity. However, current systems are bifurcated, with solid-state systems providing robust cold archival but lacking accessibility, while fluidic molecular computing systems offer dynamic processing but suffer from low density and instability. This mutual exclusivity has hindered the development of hierarchical memory, a standard in modern computing, within molecular storage systems. Here, we bridge this gap by engineering a reconfigurable DNA memory architecture driven by programmable liquid-liquid phase separation (LLPS). Our system leverages sequence-based encoding to achieve an ultrahigh storage density of 7×1010 GB/g, approaching the theoretical limits of DNA accessibility. In its fluidic hot state, DNA droplets enable rapid data loading (∼83.8% in 5 min) and function as an in-memory editing platform supporting versatile, addressable bit-level operations including selective erasure (∼65.1%) and high-efficiency rewriting and replacement (>99%) via programmable strand displacement. Importantly, to resolve the stability trade-off, we engineered a programmable phase transition whereby the triggered assembly of a rigid tetrahedral DNA framework (TDF) armor transforms liquid condensates into robust armored droplets. This cold state confers exceptional resistance to enzymatic and physical degradation, projecting multi-millennial data stability. By enabling reversible transitions between a editable, high-density computing mode and a stabilized archival mode, this work establishes the architectural foundation for scalable molecular information storage capable of hierarchical data management. Competing Interest Statement The authors have declared no competing interest.