Robotic Printed Combinatorial Droplet (RoboDrop) for Antibiotic Combination Screening

Antibiotic resistance has become a critical public health issue. Combination therapies have become a promising solution that leverages the existing antibiotics to combat drug-resistance bacteria. To widely adopt combination therapies, it is important to develop efficient screening platforms to investigate the combination effects among different antibiotics and find the rational combination choices. In response, we have developed a Robotic Printed Combinatorial Droplet (RoboDrop) platform that can programmatically control the droplet compositions and automatically print thousands of droplets onto petri dishes. In RoboDrop, the upstream is a valve-based droplet microfluidic device that can generate droplets with desired composition on demand. The droplets are subsequently transported via a PTFE tubing, which is mounted on a robotic arm. As the robotic arm moves, the droplets are orderly ejected from the tubing and printed as an array onto a petri dish. We have demonstrated to print around 2,700 droplets onto a single petri dish using RoboDrop, indicating its high scalability. For demonstration of the feasibility and robustness of RoboDrop, we integrated a resazurin-based cell viability assay with RoboDrop and verified two known pairwise antibiotic combinations and further found a new synergistic three-drug combination for treating a model Escherichia coli (E. coll) strain