Axial impeller selection for anchorage dependent animal cell culture in stirred bioreactors: Methodology based on the impeller comparison at just-suspended speed of rotation

Animal cells, which are nowadays essential for the industrial production of proteinic compounds, are commonly cultivated inside stirred tank bioreactors. In case of anchorage dependent cells, they are usually fixed on microcarriers. The choice of agitation conditions (impeller type, rotational speed ... ) in this type of process is not an easy task as it has to fulfil three potentially conflicting goals: (1) maintaining microcarriers in complete suspension,(2) homogenizing the culture medium, and (3) limiting mechanical constraints generated by the hydrodynamics on the cells. The aim of this study is to present an original methodology to select the most appropriate axial impeller for this specific application. Seven propellers are preselected on basis of their characteristics available in the literature. Instead of comparing impellers at a given rotational speed or a given power input, they are compared at their respective minimum impeller rotational speed that leads to a complete microcarrier suspension, i.e. at their respective just-suspended speed N-js. They are then compared at higher rotational speeds N, expressed as multiples of N-js. The impeller classification is based on the intensity of mechanical constraints they produced, evaluated from: (1) the macro-shear rate quantified by the spatial derivative of time average velocity fields measured by P.I.V., (2) the micro-shear rate characterized by the ratio between the microcarrier diameter to the average Kolmogorov scale computed from power input measurements, and (3) the impact of microcarrier collisions on cells described via the turbulent collision severity index also computed from power input measurements. Results show that the 125 mm diameter TTP impeller (Mixel) and the 150 mm diameter Elephant Ear impeller (Applikon) produce the smallest mechanical constraints at their just-suspended speed (50 and 20 rpm, respectively). Moreover, the mechanical constraints they produce increase more slowly with the N/N-js ratio than the mechanical constraints produced by other impellers. These propellers are thus even more advantageous if rotational speeds higher than the just-suspended speed have to be used. (C) 2010 Elsevier Ltd. All rights reserved.