Cell-free extract based optimization of biomolecular circuits with droplet microfluidics

Engineering an efficient biomolecular circuit often requires time-consuming iterations of optimization. Cell-free protein expression systems allow rapid testing of biocircuits in vitro, speeding the design–build–test cycle of synthetic biology. In this paper, we combine this with droplet microfluidics to densely scan a transcription–translation biocircuit space. Our system assays millions of parameter combinations per hour, providing a detailed map of function. The ability to comprehensively map biocircuit parameter spaces allows accurate modeling to predict circuit function and identify optimal circuits and conditions.