Selective recycle of viable animal cells by coupling of airlift reactor and cell settler

Abstract

A new system for the perfusion culture of animal cells in suspension is described. It consists of an airlift loop reactor and a settling tank for cell retention. Insufficient nutrient and oxygen supply of the cells in the settling tank was prevented by cooling the cell suspension before entering the settler. As a result, the catabolic activity of the cells in the settler was reversibly reduced. Furthermore, the density gradient induced by cooling caused a liquid motion through the settler. Thus, it was not necessary to pump medium containing shear, sensitive cells. With this simple system, it was possible to prduce 2 to 5 g of antibodies in a 5.4-L reactor in continuous runs of 400 to 600 h. The productivity was increased by a factor of 17 and the cell density was 4 times higher in comparison with the corresponding batch system. The cell retention system was found to have the property of separating viable and nonviable cells. With the increasing perfusion rate, dead cells and debris were preferably washed out. For perfusion rates up to 1.3 d(-1), the retention efficiency of the settler was nearly 100% for viable cells; hence, this system may show advantages at the industrial scale.