Membrane-Based Process for the Removal of Toxic Ammonia Produced During Mammalian-Cell Culture

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Mammalian cells grown in culture excrete a toxic byproduct, ammonia, that accumulates in quantities that limit cell growth and reduce product synthesis. The usual tactics for limiting the effects of ammonia accumulation are uneconomical, requiring large amounts of media and high capital costs. In Phase I of this project, a novel membrane process was demonstrated that rapidly and irreversibly removes ammonia to well below inhibitory levels. It was further demonstrated that media treated via this membrane process can be reused in the culturing of mammalian cells. The savings in capital and operating costs offered by the membrane process are substantial, and the estimated payback period for the process is less than 30 days. In Phase II, work will be concentrated on determining the performance of the membrane process under long-term use and on integrating the membrane with a cell-culture reactor. It is also proposed to investigate coating small particles with the membrane developed in Phase I for use in removing ammonia from cell-culture media in small-scale applications. In pursuit of the Phase II goals, a collaboration has been arranged with a major pharmaceutical company, which will test the membrane system on an operating cell-culture reactor. The information gained in this test will provide information vital to the commercialization of the process in Phase III.