A novel perfusion system for animal cell cultures by two step sequential sedimentation

A novel perfusion system was developed for high density culture of animal c ells. The system consists of an airlift bioreactor, a setting tank and a fl at settler. Both the settling tank and flat settler have two connecting pip es for transporting the cells from and back to the reactor, respectively. T hus, the cell flow in the settlers can be controlled in uni-direction, avoi ding the countercurrent Row of the cells. During perfusion cultures, the ce lls firstly settled in the settling tank, then, unsettled cells in the tank were transferred to the flat settler for re-settling. With the application of the system to hybridoma cell cultures, it was found that the maximum vi able cell density, monoclonal antibody concentration and average productivi ty were 1.31 x 10(7) cells ml(-1), 400 mg 1(-1) and 461 mg 1(-1) d(-1), res pectively, which were much higher than those of a batch culture. Both theor etical analysis and experimental results showed a much higher separation ef ficiency in such a two-step sedimentation system than that in a conventiona l one-step sedimentation system. In addition, the Volumetric ratio of the s edimentation devices to the culture volume in our developed system is much lower, which may be potentially useful on an industrial-scale. (C) 2000 Els evier Science B.V. All rights reserved.