Microfluidics-Based Engineering of Molecular Self-Assembly and Manufacturing for Artificial Cell Systems

Bottom-up synthetic biology has achieved remarkable success in designing molecular architectures at the nanoscale. However, constructing functional, cell-sized artificial systems at the mesoscale remains a significant challenge due to the stochastic nature of pure molecular self-assembly. Natural cells overcome this thermodynamic limitation by employing active, energy-consuming mechanisms to maintain size, identity, and structural hierarchy. In this Perspective, I argue that, to construct consistent and robust molecular systems that can withstand practical use, we must seek a synergy between intrinsic self-assembly and deterministic engineering. Microfluidics should be viewed not merely as a replacement for biological regulation, but as a platform that provides extrinsic physical boundary conditions to guide and amplify the potential of molecular self-assembly. By categorizing microfluidic platforms into four hierarchical levels─from molecular assembly to multicellular bodies─I illustrate how engineering can recapitulate or replace complex biological regulatory systems. Finally, I discuss the necessary paradigm shift from bespoke laboratory craftsmanship to standardized biofoundries, outlining the applications and manufacturing breakthroughs required to democratize artificial cell technology for industrial and biomedical applications.