PROJECT SUMMARY/ABSTRACT Antibodies (immunoglobulins) are among the most widely used biologics for life science research and have been the major driving force for disease diagnosis and therapeutics. Despite enormous efforts in the past, high-quality research antibodies remain sparse, which have led to the poor reproducibility of numerous scientific research papers and the immense costs associated with misleading literature. Major challenges include poor quality of antibodies (e.g., low affinity and specificity), batch-to-batch variations, and difficulties in production, bioengineering, manufacturing and storage. There is a pressing need to develop new technological platforms to address these challenges and to provide new applications in biomedical research and drug therapeutics. Camelid single-chain VHH antibodies or Nanobodies (Nbs) are a compelling new class of antibodies characterized by exceptionally high solubility and thermostability. We have recently developed a robust pipeline for the discovery and characterization of high-quality antigen-specific Nb repertoires. This pipeline has been extensively tested and optimized for a dozen of antigens with different structures and immune responses. With this approach, a large cohort of high-quality conformational Nb binders can be identified. Here we propose to developing innovative integrative technologies to revolutionize Nb discovery and characterization. In parallel, we are keen to apply these methods and reagents to enable new biomedical discoveries and therapeutics. Development of the next generation Nb platform technologies will offer numerous exciting new possibilities in biomedical research, disease diagnosis and therapeutics.