Development of Predictive Modeling for Immuno-Affinity Chromatography Using Distributed Parameter System: For Purification of Therapeutic Blood Protein

目前正在进行一项全面的基础生化工程研究，以开发分布参数系统工作模型，该模型考虑了分布平衡系数作为系统和操作变量的函数，用于免疫亲和纯化。将对生化和免疫化学反应系统以及提纯过程进行系统研究，以开发实用的系统模型。为了建立这个模型，将使用的系统是：(1)人血浆蛋白C的免疫亲和纯化，和(2)用蛋白A亲和层析纯化单抗。预期的研究成果的好处和影响将是：(1)用于血液蛋白质纯化的大规模免疫亲和过程设计和优化的开发的知识库将被拓宽和先进，(2)将形成一种合理的策略，通过该策略可以基于预测建模和系统性能模拟来设计和优化大规模的免疫亲和纯化过程。这项研究将对大规模免疫亲和纯化系统的微观现象和与优化设计和操作策略相关的宏观现象有更好的了解。将进行实验和理论研究，以建立知识库，并通过数学建模和实验验证来制定最优设计和运行策略。蛋白C是一种蛋白质，其在血液中的功能包括阻断动物体内的凝血途径和溶解凝块，从而维持人体的止血。缺乏这种蛋白质会导致复杂的血液凝结相关症状，如血栓栓塞症、中风，甚至猝死。

A comprehensive fundamental biochemical engineering study is being undertaken to develop a distributed parameter system working model, which takes into consideration distributed equilibrium coefficients as a function of system's and operational variables, for immuno-affinity purification. The biochemical and immuno-chemical reaction system as well as the purification process will be studied systematically to develop a practical systems model. For the development of this model the systems to be used are: (1) immuno-affinity purification of human plasma Protein C, and (2) purification of monoclonal antibodies using Protein A affinity chromatography. The benefits and impact of the anticipated research results will be: (1) The knowledge base for the development of large-scale immuno-affinity process design and optimization for the purification of blood proteins will be broadened and advanced, (2) A rational strategy will evolve by which large-scale immuno-affinity purification processes can be designed and optimized based on predictive modeling and the simulation of system performance. This study should provide a greater insight into the microscopic phenomena and also a better understanding of macroscopic phenomena related to the optimal design and operational strategy for large scale immuno-affinity purification systems. Both experimental and theoretical studies will be carried out to establish a knowledge base and to develope an optimal design and operational strategy through mathematical modeling and experimental verification. Protein C is a protein whose functions in blood include both blocking the blood coagulation pathways and dissolution of clots in animal, thus maintaining hemostasis in the human body. Lack of this protein causes complicated blood clotting related symptoms, such as thromboembolism, stroke, or even sudden death.