Apparent volumetric oxygen mass transfer coefficient (kLa) values ranged between 3-22 h鈭? and 4-53 h鈭? for headspace aeration and direct gas sparging respectively. The higher kLa values with direct gas sparging correlated directly with the increase in gas-liquid interfacial area per unit volume. Mixing times (tm) over a range of conditions were generally in the range 1-13 s and decreased with increasing shaking frequency (500-800 rpm). Direct gas sparging also served to reduce tm values by a factor of up to 19 fold.
The impact of aeration strategies on cell culture kinetics of a model CHO cell line was also determined. Cultures performed with head space aeration alone showed the highest viable cell density (VCD) (15.2 脳 106 cells mL鈭?), viability retention and antibody titre (1.58 g L鈭?). These were greater than in conventional shake flask cultures due to the improved control of the 渭24 bioreactor system. In all cases the miniature bioreactor managed good control of process parameters such as pH 6.95 卤 0.4, temperature T掳C 37 卤 0.4 and DO% 57 卤 32. Cultures performed with direct gas sparging showed a 25-45% reduction in VCD (depending on the aeration strategy used) and a similar reduction in antibody titre. Overall this work shows the successful application of the miniature bioreactor system for industrially relevant fed-batch cultures and highlights the impact of the dispersed gas phase on cell culture performance at the small scale.