Microfluidics-driven high-throughput phenotyping and screening in synthetic biology: from single cells to cell-free systems

The interdisciplinary nature of synthetic biology merges engineering principles with biology and provides innovative solutions for issues in the biomanufacturing industry. To develop industrially applicable biocatalysts and/or microbial cell factories, a design-build-test-learn cycle-based iterative process is necessary, which is often time-consuming and labor-intensive. The integration of microfluidic technologies into synthetic biology can accelerate these processes, particularly for achieving high-throughput phenotyping and screening. In this review, we examine the potential of microfluidic technologies to revolutionize synthetic biology. Although commercial microfluidics demonstrate superior throughput for single-cell assays, their application can be limited, for example, in cases where products are retained inside the cells. Droplet microfluidics, on the other hand, is a rather flexible platform and shows high diversity in single-cell, cell-to-cell interaction-based, and cell-free reaction-based analyses. By examining previous studies, we have summarized the potential of microfluidic technologies to foster sustainable biomanufacturing and advanced biological engineering.