Automated and miniaturized screening of antibiotic combinations via robotic-printed combinatorial droplet platform

Antimicrobial resistance (AMR) has become a global health crisis in need of novel solutions. To this end, antibiotic combination therapies, which combine multiple antibiotics for treatment, have attracted significant attention as a potential approach for combating AMR. To facilitate advances in anti...

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Bibliographic Details
Published in:Acta pharmaceutica Sinica. B 2024-04, Vol.14 (4), p.1801-1813
Main Authors: Shao, Fangchi, Li, Hui, Hsieh, Kuangwen, Zhang, Pengfei, Li, Sixuan, Wang, Tza-Huei
Format: Article
Language:English
Subjects:
Antibiotic combinatorial screening
Antibiotic interactions
Antimicrobial resistance
Contact printing
Droplet microfluidics
High-throughput
Original
Pharmaceutical analysis
Robotics
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Summary:Antimicrobial resistance (AMR) has become a global health crisis in need of novel solutions. To this end, antibiotic combination therapies, which combine multiple antibiotics for treatment, have attracted significant attention as a potential approach for combating AMR. To facilitate advances in antibiotic combination therapies, most notably in investigating antibiotic interactions and identifying synergistic antibiotic combinations however, there remains a need for automated high-throughput platforms that can create and examine antibiotic combinations on-demand, at scale, and with minimal reagent consumption. To address these challenges, we have developed a Robotic-Printed Combinatorial Droplet (RoboDrop) platform by integrating a programmable droplet microfluidic device that generates antibiotic combinations in nanoliter droplets in automation, a robotic arm that arranges the droplets in an array, and a camera that images the array of thousands of droplets in parallel. We further implement a resazurin-based bacterial viability assay to accelerate our antibiotic combination testing. As a demonstration, we use RoboDrop to corroborate two pairs of antibiotics with known interactions and subsequently identify a new synergistic combination of cefsulodin, penicillin, and oxacillin against a model E. coli strain. We therefore envision RoboDrop becoming a useful tool to efficiently identify new synergistic antibiotic combinations toward combating AMR. We report the robotic-printed combinatorial droplet platform as a potential solution to automate and miniaturize the screening of antibiotic combinations to identify synergistic combinations for combating antimicrobial resistance. [Display omitted]
ISSN:2211-3835
2211-3843
DOI:10.1016/j.apsb.2023.11.027