The fluid dynamics of hollow fibre bioreactors was studied using residence
time distribution (RTD) and protein polarisation experiments. Small differe
nces in the densities of tracer protein solution and carrier liquid resulte
d in broad RTDs with long tails due to settling of tracer solution near the
upstream extracapillary space (ECS) port. Moreover, module orientation and
ECS flow direction had a significant influence on the observed RTDs. After
matching the densities of the tracer and the carrier fluid, the tracer mov
ed through the ECS as a dispersed plug. The reactor orientation and flow di
rection did not influence RTDs in these density-matched experiments. The re
actor orientation had a dramatic effect on protein polarisation in the ECS.