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High-throughput phenotyping of cell-to-cell interactions in gel microdroplet pico-cultures.

Microbiomes exert significant influence on our planet's ecology. Elucidating the identities of individual microbes within these communities and how they interact is a vital research imperative. Using traditional plating and culturing methods, it is impractical to assess even a small fraction of the interactions that exist within microbial communities. To address this technology gap, we integrated gel microdroplet technology with microfluidics to generate millions of microdroplet cultures (MDs) that sequester individual cells for phenotyping MDs, facilitating rapid analysis and viable recovery using flow cytometry. Herein, we describe a validated high-throughput phenotyping pipeline that elucidates cell-to-cell interactions for millions of combinations of microorganisms. Through iterative co-culturing of an algae and a pool of environmentally sourced microbes, we successfully isolated bacteria that improved algal growth.