Small-scale bioreactor system for process development and optimization

An agitated 12-well microtiter place system with a working volume of 2 ml w as investigated for cell culture process development. Agitation assures hom ogeneity in wells and enhances mass transfer between the gas and the liquid phase, thus improving maximum cell density and pH stability. The pH of the NaHCO3-buffered system can be adjusted by altering the carbon dioxide cont ent of the gas phase. The non-toxic, visual pH indicator phenol red was use d in combination with a spectrophotometric plate reader for rapid and preci se pH measurements. For high throughputs, cell growth was assessed non-inva sively using stable green fluorescent protein (GFP) expressing cells and a fluorescence plate reader. The setup is simple and inexpensive. The system can be automated and allows several hundred small-scale bioreactor experime nts to be run in parallel. (C) 2001 Elsevier Science B.V. All rights reserv ed.