Ultra-High-Throughput Discovery of Multifunctional Polyphenolic Coatings on Droplet Microarrays

The rapid discovery of functional coatings is vital for advancing technologies in healthcare, energy, and environmental protection, yet it remains limited by the lack of scalable high-throughput (HT) methods. Here, an ultra-high-throughput (UHT) combinatorial strategy is introduced for the miniaturized synthesis and screening of polyamine-polyphenolic (PaPp) coatings (formed in Tris buffer) using droplet microarrays (DMA). Approximately 30 000 coatings were generated from binary and ternary combinations of 51 polyphenols (Pp) and 12 polyamines (Pa), each produced in 160 nL volumes (<5 mL total reagent use), enabling the rapid identification of hundreds of previously unknown functional materials, including over 225 fluorescent coatings and more than 100 redox-active, metal-reducing surfaces. Antibacterial screening uncovered seven coatings with reproducible activity against Pseudomonas aeruginosa, and subsequent validation on macroscale substrates confirmed up to <1-log colony-forming unit (CFU) reduction against P. aeruginosa and E. coli. Importantly, five coatings exhibited multiple functionalities, combining surface stability, intrinsic fluorescence, metal-reducing activity, antibacterial effects, and compatibility with adherent human cells. This UHT approach yields the first comprehensive functionality map of PaPp coatings, revealing previously inaccessible multifunctional materials and demonstrating a scalable strategy for the discovery of surface chemistries with tailored optical, redox, and biological properties.