Production of monoclonal antibodies in the miniPERM™ bioreactor:: comparison with other hybridoma culture methods

The miniPERM(TM) bioreactor is a novel and easy to handle reusable minifermenter for high-density culture of hybridoma and other cells. The culture apparatus is composed of two modules: a 40-ml disposable cell culture and antibody production chamber (the "production module") and a 550-ml medium reservoir (the "supply module"). The two modules are separated from each other by a dialysis membrane allowing passage of low molecular mass nutrients and metabolites. The monoclonal antibodies are produced and enriched in the production module. The outer part of this module is made from a thin gas-permeable silicone rubber membrane allowing exchange of gases (oxygen and carbon dioxide). Depending on the individual properties of the hybridoma cells cultured, cell densities of more than 10 million (in some cases up to 35 million cells per mi) and monoclonal antibody concentrations of several mg per mi can be obtained in the miniPERM(TM). On average, 61 mg (range: 9-159 mg) could be produced within 1-4 weeks. In terms of their properties, the monoclonal antibodies produced in the miniPERM(TM) were indistinguishable from antibodies prepared from ascitic fluid or from the supernatant of conventional stationary culture. Monoclonal antibody production in the miniPERM(TM) is a useful alternative to the in vivo production method in mice. In addition, the miniPERM(TM) represents a completely new, inexpensive and easy to handle general solution to the problem of culturing cells in high densities and obtaining cellular products at high concentrations.