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

培养的哺乳动物细胞会分泌一种有毒的副产品， 氨，它积累的数量限制了细胞 生长和减少产物合成。 通常的策略是 限制氨积累的影响是 不经济，需要大量的媒体和高 资本成本。 在该项目的第一阶段， 证明了快速和不可逆地去除氨 远低于抑制水平。 据进一步 证明了通过这种膜过程处理的介质 可重复用于哺乳动物细胞的培养。 的 节省资本和运营成本 膜过程是巨大的，估计投资回报 该过程的时间不超过30天。 在第二阶段，工作将集中于确定 长期使用下的膜工艺性能， 将膜与细胞培养反应器结合起来。 还建议研究包覆小颗粒 在第一阶段开发的膜用于去除 在小规模应用中从细胞培养基中去除氨。 为了实现第二阶段的目标， 与一家大型制药公司达成协议， 在操作细胞培养物上测试膜系统 反应器 本测试中获得的信息将提供 对工艺商业化至关重要的信息 在第三阶段。

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.