Monoclonal antibodies are increasingly used to prevent and treat viral infections and are pivotal in pandemic response efforts. Antibody-secreting cells (ASCs; plasma cells and plasmablasts) are an excellent source of high-affinity antibodies with therapeutic potential. Current methods to study antigen-specific ASCs either have low throughput, require expensive and labor-intensive screening or are technically demanding and therefore not widely accessible. Here we present a straightforward technology for the rapid discovery of monoclonal antibodies from ASCs. Our approach combines microfluidic encapsulation of single cells into an antibody capture hydrogel with antigen bait sorting by conventional flow cytometry. With our technology, we screened millions of mouse and human ASCs and obtained monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 with high affinity (<1 pM) and neutralizing capacity (<100 ng ml⁻¹) in 2 weeks with a high hit rate (>85% of characterized antibodies bound the target). By facilitating access to the underexplored ASC compartment, the approach enables efficient antibody discovery and immunological studies into the generation of protective antibodies.

单克隆抗体越来越多地用于预防和治疗病毒感染，并且在大流行应对工作中发挥着关键作用。抗体分泌细胞（ASC；浆细胞和浆母细胞）是具有治疗潜力的高亲和力抗体的极好来源。目前研究抗原特异性 ASC 的方法要么通量低，需要昂贵且劳动密集型的筛选，要么技术要求高，因此无法广泛使用。在这里，我们提出了一种从 ASC 中快速发现单克隆抗体的简单技术。我们的方法将单细胞的微流体封装到抗体捕获水凝胶中与通过传统流式细胞术进行抗原诱饵分选相结合。利用我们的技术，我们筛选了数百万只小鼠和人类ASC，并在两周内以高命中率获得了具有高亲和力（<1 pM）和中和能力（<100 ng ml ^-1 ）的针对严重急性呼吸综合征冠状病毒2的单克隆抗体（>85% 的特征抗体与靶标结合）。通过促进进入未充分探索的 ASC 区室，该方法能够实现有效的抗体发现和保护性抗体生成的免疫学研究。