Solid-liquid suspension of microcarriers in stirred tank bioreactor – Experimental and numerical analysis

Abstract

Solid-liquid suspensions in stirred tank reactors are common operations in many processes, including bioprocesses such as animal or stem cell cultures. These cells are often anchorage-dependent, i.e. they need to adhere to a surface to grow. Typically, they are cultivated on the surface of small spherical microbeads, the so-called microcarriers, suspended in stirred-tank bioreactors.As far as we know, no extensive experimental characterization, and thus no validated simulation approach, of microcarrier suspensions in stirred-tank reactor exists in the literature. Therefore, the first aim of this work is to develop an experimental technique based on light attenuation to characterize the spatial distribution of particle concentration for various particle suspension states. The second aim is to determine the validity of Euler-Euler CFD simulations to predict the spatial distribution of low density particles, such as microcarriers, in a stirred tank bioreactor.Experiments and simulations were performed in a small hemispherical bottom bioreactor stirred with a down-pumping axial impeller. The particles used were Cytodex-1 microcarriers (dP=162μm and ρS=1020 kg m−3) at a solid concentration of 10% in volume.The light attenuation technique enabled the characterization of the spatial distribution of the solid phase in the whole bioreactor, even for very dense suspensions by advantageously using the optical properties of the Cytodex-1 microcarriers. The analysis of the solid spatial distribution shows that the bioreactor volume can be divided in three distinct zones: a clear layer below the free surface where αS,layer tends to 0, a bulk zone where the solid phase is homogeneously distributed (αS,bulk⩽αS) and a packed bed of motionless particles at the bottom (αS,bed=αS,max). One very interesting finding is that the evolution of the bulk solid concentration is directly proportional to the agitation rate and its value equals the averaged volume fraction αS,bulk=αS at N=Njs.Concerning the simulation results, the modeling approach presented in this work enables a reasonable estimation of the just-suspended agitation rate Njs. Nevertheless, the solid spatial distributions are not well predicted for agitation rates below or above Njs. The solid concentration at the vessel bottom is underestimated for N<Njs but overestimated for N⩾Njs.