单克隆抗体药物是制药行业全球增长速度最快的市场。针对当前单抗药物制备中蛋白A（SpA）色谱的技术"瓶颈"，本项目提出了基于多尺度认知的SpA色谱过程高效化的创新研究思路。围绕抗体－SpA结合作用和色谱介质"结构－性能"关系两个科学问题，开展了固液界面抗体与SpA结合作用的研究，全面地认知了材料在结合过程中作用；观测了SpA色谱介质结构对抗体吸附性能的影响，完善了色谱介质"结构－性能"关系的阐述。基于上述认知，研究了材料、间隔臂以及固定化方法对SpA配基利用率的影响，建立SpA配基高效固定化技术；制备孔道结构可控的快速色谱基质，合成高容量SpA色谱介质，进而开发高效SpA色谱技术；同时，建立并完善SpA色谱过程理论；最终实现SpA色谱技术高效化。本研究对深化抗体－SpA结合作用及介质"结构－性能"关系的认知具有重要的科学意义，将为完善SpA色谱技术，推动单抗药物发展奠定强有力的技术基础。

Monoclonal-antibody based drugs are a large and growing segment of pharmaceuticals worldwide. In order to mitigate the bottleneck in downstream process, the research devotes to develop novel high-throughput protein A (SpA) chromatography based on multi-scale approaches to understanding of antibody-SpA interaction and structure-performance relationship of chromatographic materials. In this research, antibody-SpA interaction on solid interface is investigated to acquire scientific understanding of materials contribution to the antibody interaction; the influence between the structure of the adsorbent for SpA chromatography and performance of antibody adsorption are measured and monitored to reveal the structure-performance relationship in depth during antibody adsorption. On a basis of above understanding, the role of materials, linkers and immobilization strategies are evaluated to improve the utilization of SpA, and thus the optimized strategy for immobilization of SpA is proposed. Then chromatographic materials with controlled pore architecture are fabricated and the high-capacity SpA adsorbent for antibody adsorption is synthesized. Then, the novel high-throughput SpA chromatography is developed and the corresponding theoretical model is proposed to describe the uptake kinetics in adsorbents. Finally, SpA chromatography developed herein is applied to purify antibody from various feedstock to demonstrate the applicability of the multi-scale approaches. The research provides insight into the understanding to antibody-SpA interaction and structure-performance relationship of chromatographic material, and establishes a powerful underpinning in reshaping SpA chromatographic technique and growing monoclonal-antibody based drugs.