Engineered Living Memory Microspheroid‐Based Archival File System for Random Accessible In Vivo DNA Storage

Abstract Given its exceptional durability and high information density, deoxyribonucleic acid (DNA) has the potential to meet the escalating global demand for data storage if it can be stored efficiently and accessed randomly in exabyte‐to‐yottabyte‐scale databases. Here, this work introduces the Engineered Living Memory Microspheroid (ELMM) as a novel material for DNA data storage, retrieval, and management. This work engineers a plasmid library and devises a random access strategy pairing plasmid function with DNA data in a key‐value format. Each DNA segment is integrated with its corresponding plasmid, introduced into bacteria, and encapsulated within matrix material via droplet microfluidics within 5 min. ELMMs can be stored at room temperature following lyophilization and, upon rehydration, each type of ELMM exhibits specific functions expressed by the plasmids, allowing for physical differentiation based on these characteristics. This work demonstrates fluorescent expression as the plasmid function and employs fluorescence‐based sorting access image files in a prototype database. By utilizing N optical channels, to retrieve 2 N file types, each with a minimum of 10 copies. ELMM offers a digital‐to‐biological information solution, ensuring the preservation, access, replication, and management of files within large‐scale DNA databases.