英国剑桥大学Florian Hollfelder等研究人员合作发现，通过微流控辅助的FACS对单个病原体特异性抗体分泌细胞的筛选实现快速发现单克隆抗体。2024年8月14日，国际知名学术期刊《自然—生物技术》在线发表了这一成果。

研究人员提出了一种简便的技术，用于从抗体分泌细胞（ASC）中快速发现单克隆抗体。该方法将单细胞微流控封装在抗体捕获水凝胶中，并通过传统流式细胞术对抗原进行诱饵筛选。

利用该技术，研究人员筛选了数百万个小鼠和人类ASC，并在两周内获得了针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的高亲和力（<1 pM）和中和能力（<100 ng/ml）的单克隆抗体，且命中率高（>85%的鉴定抗体结合了目标抗原）。通过便捷地获取未充分研究的ASC库，该方法使抗体发现和保护性抗体生成的免疫学研究更加高效。

据悉，单克隆抗体在预防和治疗病毒感染以及应对疫情方面的作用日益重要。ASC（如浆细胞和浆母细胞）是具有治疗潜力的高亲和力抗体的重要来源。目前研究抗原特异性ASC的方法要么通量低，要么需要昂贵且劳动密集型的筛选过程，或者技术要求高，因而难以广泛应用。

附：英文原文

Title: Rapid discovery of monoclonal antibodies by microfluidics-enabled FACS of single pathogen-specific antibody-secreting cells

Author: Fischer, Katrin, Lulla, Aleksei, So, Tsz Y., Pereyra-Gerber, Pehun, Raybould, Matthew I. J., Kohler, Timo N., Yam-Puc, Juan Carlos, Kaminski, Tomasz S., Hughes, Robert, Pyeatt, Gwendolyn L., Leiss-Maier, Florian, Brear, Paul, Matheson, Nicholas J., Deane, Charlotte M., Hyvnen, Marko, Thaventhiran, James E. D., Hollfelder, Florian

Issue&Volume: 2024-08-14

Abstract: 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 (<1pM) and neutralizing capacity (<100ngml1) in 2weeks 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.

DOI: 10.1038/s41587-024-02346-5

Source: https://www.nature.com/articles/s41587-024-02346-5