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.
