An Intercalcated-Spiral Dual Circuit Hollow Fiber Bioreactorfor the Culture of Human Hybridomas

本工作的目的是开发一种中空纤维生物反应器 其利用了插入螺旋缠绕的双回路， 建设 中空纤维系统用于生产人体 特异于肿瘤相关抗原的单克隆抗体。 人类 单克隆抗体应该优于单克隆抗体， 体内诊断和治疗试剂。 许多人类杂交瘤 分泌单克隆抗体的速率远低于鼠 杂交瘤 因此，开发能够 有效地生产人单克隆抗体。 问题 研究了连续生产。 数据和系统分析是 由结合流体动力学的数学模型补充， 膜运输和细胞动力学。 该项目将生物反应器工程的原理应用于大规模 细胞培养 由于哺乳动物细胞培养对生化物质的需求 增加，有相应的需要发展先进的 生物反应器技术不仅可以大量生产， 有效地，生物化合物。 一个重要的例子是 制造单克隆抗体。 单克隆抗体非常纯净 并具有特定的生化反应性。 其已被证明 在许多诊断和治疗应用中非常有用。 抗体是大而复杂的蛋白质分子， 由（融合）哺乳动物细胞在先进的中空培养合成 纤维生物反应器，其模仿人工器官， 生物反应器具有非常均匀的动脉和静脉分布 毛细血管网 这是一个试图了解 流体力学、营养物质运输和细胞 physiology. 有必要合并来自这些不同的 解决一般问题的领域。

The objective of this work is to develop a hollow fiber bioreactor which makes use of an intercalated-spiral wound dual circuit construction. The hollow fiber system is used to produce human monoclonal antibodies specific to tumor-associated antigens. Human monoclonal antibodies should be superior to monoclonal antibodies as in vivo diagnostic and therapeutic reagents. Many human hybridomas secrete monoclonal antibodies at a much lower rate than murine hybridomas. Hence it is crucial to develop processes which can produce human monoclonal antibodies effectively. Problems in continuous production are investigated. Data and system analyses are complemented by mathematical models which incorporate hydrodynamics, membrane transport and cellular kinetics. This project applies the principles of bioreactor engineering to mass cell culture. As demand for biochemicals from mammalian cell cultures increases, there is a corresponding need to develop advanced bioreactor technology to produce not only in large quantitie, but also effectively, biological compounds. One important example is the making of monoclonal antibodies. Monoclonal antibodies are very pure and have specific biochemical reactivities. They have proven to be very useful in many diagnostic and therapeutic applications. Antibodies are big and complex protein molecules which can best be synthesized by (fusion) mammalian cells cultured in an advanced hollow fiber bioreactor which mimics an artificial organ in the sense that the bioreactor has a very uniform distribution of arterial and venous capillary networks. This is an attempt to understand the fundamental aspects of fluid mechanics, nutrient transport, and cell physiology. It is necessary to merge information from these different areas to solve the general problem.