PhD Candidate: John Burdick
DNA-encoded library (DEL) technology is rapidly emerging as a cornerstone of early-stage drug discovery, with ongoing innovations in screening strategies expanding its applicability across diverse target classes. One-bead-one-compound (OBOC)-DELs enable the synthesis and activity-based high-throughput screening of highly diverse and customizable compound libraries. However, traditional implementations rely on complex microfluidic systems for screening and require manual, labor-intensive bead handling during synthesis—factors that present significant barriers to adoption by academic and smaller research institutions. In this work, we overcome these limitations by executing fully automated DEL synthesis on 2.8-μm magnetic beads using a commercially available KingFisher magnetic bead handler, significantly improving efficiency. DEL beads are encapsulated within a functionalized polyacrylamide hydrogel matrix that supports in-gel biological activity assays and are screened in water-in-oil emulsion droplets generated without microfluidic devices. This ultra-miniaturized activity-based screening technology uses only commercially available automation for streamlined synthesis and flow cytometry for screening. Altogether, this platform offers a streamlined, scalable, and broadly adoptable strategy for OBOC-DEL-based ligand discovery.
