Acoustic cell filter for high density perfusion culture of hybridoma cells

Abstract

We have developed a flow-through device which uses high frequency, low energy ultrasonic resonance fields to transiently aggregate hybridoma cells and return them by sedimentation to a perfusion bioreactor. The system retained up to 99 percent of the inflowing viable cells with no measurable effect on viability. Viable cells were selectively retained at up to 3 percent higher efficiency than nonviable cells. A stirred tank bioreactor was operated for 700 hours with acoustic cell recycle. Concentrations greater than 5×107 cells/ml were attained with a 5-fold increase in antibody concentration and a 70-fold increase in volumetric productivity compared with batch culture. © 1994 Nature Publishing Group.