HIGH-DENSITY CULTURE OF FM-3A CELLS USING A BIOREACTOR WITH AN EXTERNAL TANGENTIAL-FLOW FILTRATION DEVICE

A novel bioreactor system developed for high-density cultures of suspe nded mammalian cells is described using a tangential-flow filtration d evice outside the culture vessel to separate viable cells from spent m edium. The filtration device is based on thin porous microfiltration m embranes with a pore size of 0.20-0.65 mu m. Because cells have a diam eter of about 10-20 mu m, they cannot permeate these membranes with th e spent medium. So, allowing a perfusion culture to be created using t his system. In most membrane filtration systems, clogging of the membr anes has made long-term operation difficult. In this system, however, high pressure is not applied directly to the membrane, thus minimizing clogging. Also, clogging of the membrane was prevented by washing the membrane surface once a day, and increasing the membrane surface area . With this system, FM-3A cells were cultured and maintained at a high density of 3.0 x 10(7) cells/ml for two weeks, and a continuous cultu re was supported for as long as 34 days.