Orchestrating Self‐Replication in Artificial Cells with Digital Microfluidics

Abstract A defining feature of living cells is their ability to self‐replicate; but creating artificial cells with this capability remains challenging, due to the complexity of biological division machinery. Rather than seeking to reconstitute this machinery, direct control of DNA replication and compartment division using digital microfluidics (DMF). This approach allows us to precisely orchestrate these two fundamental processes, providing insight into how they must be coupled for successful self‐replication. The system achieves controlled cycles of replication and division, with daughter compartments inheriting parental DNA and maintaining genetic continuity across multiple generations ‐ a key feature of living systems that has been difficult to achieve in artificial cells. By implementing these processes through direct physical manipulation rather than biochemical complexity, a simple testbed is provided that will help to disentangle the essential requirements for self‐replicating systems.