Chapter 3: Solid-phase DNA-encoded Library Technology

Solid-phase DNA-encoded library (DEL) technology introduces advanced activity-based screening capabilities by virtue of its “one-bead-one-compound” (OBOC) format. In this review, we first describe the design and construction of so-called “OBOC-DELs.” We then explore the engineering of a microfluidic screening platform that integrates and automates high-throughput bead-based screening, highlighting examples of fluorescence-based functional assay development and miniaturization to microfluidic droplets. Additionally, we detail the statistical framework of OBOC-DEL screening experimental design and data interpretation. Finally, we summarize the numerous applications that have spawned since OBOC-DEL technology’s inception, including screening by biochemical activity, dose-response, cellular activity, competition binding affinity, and pharmacokinetic properties. Looking forward, there are likely further opportunities to employ bead-based synthesis and screening strategies to other encoded library modalities.