High-Throughput Process for the Discovery of Antimicrobial Polymers and Their Upscaled Production via Flow Polymerization

Abstract

The combination of high-throughput (HTP) processes and flow-mediated synthesis allows large data sets to be generated quickly while also permitting large quantities of materials to be prepared in a continuous fashion. In this work, the benefits of well-plate-based HTP polymerization and flow-mediated chemistry are used to streamline the screening and upscaling of value-added biomedical materials through a robust photopolymerization strategy, namely, photoinduced electron/energy transfer-reversible addition–fragmentation chain transfer (PET-RAFT) polymerization. A library of potential antimicrobial polymers was generated from an initial pool of monomers and tested for their activity against Pseudomonas aeruginosa (PA). The antimicrobial activity of the most promising candidates was then elucidated through structure–property analyses performed via both plate and flow polymerization processes; interestingly, terpolymerization of mixtures of acrylate and acrylamide monomers produced terpolymers with gradient architectures due to their reactivity ratios, which ultimately dictated the resulting antimicrobial activity. Finally, the polymers found to have the highest antimicrobial activity were upscaled in a flow reactor. This workflow provides a general and highly accessible methodology for the discovery and synthetic scaling of optimized polymer structures for biomedical applications such as new antimicrobial agents.