Precise, automated control of conditions for high-throughput growth of yeast and bacteria with eVOLVER

Precise control over microbial cell growth conditions could enable detection of minute phenotypic changes, which would improve our understanding of how genotypes are shaped by adaptive selection. Although automated cell-culture systems such as bioreactors offer strict control over liquid culture conditions, they often do not scale to high-throughput or require cumbersome redesign to alter growth conditions. We report the design and validation of eVOLVER, a scalable DIY framework that can be configured to carry out high-throughput growth experiments in molecular evolution, systems biology, and microbiology. We perform high-throughput evolution of yeast across systematically varied population density niches to show how eVOLVER can precisely characterize adaptive niches. We describe growth selection using time-varying temperature programs on a genome-wide yeast knockout library to identify strains with altered sensitivity to changes in temperature magnitude or frequency. Inspired by large-scale integration of electronics and microfluidics, we also demonstrate millifluidic multiplexing modules that enable multiplexed media routing, cleaning, vial-to-vial transfers and automated yeast mating.