Effects of ammonium ion removal on growth and MAb production of hybridoma cells

Production of monoclonal antibody against hepatitis B surface antigen was carried out by perfusion culture coupled with a selective removal system for ammonium ion. The removal system is composed of three sub-systems namely, cell separation by cross-flow ceramic filter, dialysis by hollow fiber module and ion-exchange by zeolite A-3 packed bed column. The ammonium ion concentration in the culture broth was effectively maintained below the inhibitory level, and the viable cell density reached 2.5 x 10(7) cells ml(-1) which was three times that of conventional perfusion cultures. The monoclonal antibody accumulated to a concentration as high as 26.3 x 10(5) mIU(-1). This is already almost half of the amount produced in vivo. The numerical investigation of the ammonium ion removal system showed the possibility to improve much more the performance of this perfusion cultivation system.