[Microfluidics-driven synthetic biology and biomanufacturing: research progress in methods and applications and...

Synthetic biology and biomanufacturing, two cutting-edge directions in biotechnology, are rapidly developing and regarded as the core driving force of the "third biotechnology revolution". They reshape the paradigm of industrial manufacturing through designing life and making useful products and promote the industrial revolution in healthcare, energy, agriculture, and environmental protection. However, the development of synthetic biology and biomanufacturing, especially in terms of designing life for practical applications, still faces challenges such as insufficient screening capabilities, culture heterogeneity, and limited regulation and control over biological processes. Microfluidics, with its micro-scale fluid manipulation capability, offers new solutions to these challenges through single-cell precision, high-throughput screening, and rapid iteration. This study reviews microfluidics regarding the applications in the design-build-test-learn (DBTL) cycle of synthetic biology and the role in intensifying biomanufacturing processes, including upstream stain and culture improvement and downstream processing integration and optimization. Then, some case studies of microfluidics-driven synthetic biology and biomanufacturing in the fields of chemicals & materials, agrifood, and healthcare were summarized. Finally, the bottlenecks of microfluidics in synthetic biology and biomanufacturing, such as micro-scale amplification and chip materials, were analyzed, and the future directions, including its role as an enabling technology, interdisciplinary integration, and AI-driven intelligent systems, were discussed. This review is expected to serve as a valuable reference for further innovation in synthetic biology and biomanufacturing.