Modeling flocculation of biological cells

Abstract: Biotechnological manufacturing processes often include a bioreactor harvesting step which involves separation of cells, cell debris and other particulate matter from the suspending medium which frequently contains the product of interest. Tangential flow microfiltration is used to separate the particulate matter from the suspending medium. The efficiency of this microfiltration step is often improved by increasing the particle size through flocculation prior to microfiltration. Here flocculation of yeast suspensions using a cationic polyelectrolyte has been investigated. A self-similar steady state floc size distribution is obtained experimentally. The experimental results may be modeled using a population balance approach. The dimensionless floc size distribution is found to be independent of the particulate volume fraction, initial particle size and shear rate during flocculation for the ranges of these variables considered. However, the actual floc size distribution does depend upon these parameters. In addition, the approach to the self-similar steady state floc size distribution depends upon the particulate volume fraction. At higher particulate volume fractions, the volume average floc size is found to increase during flocculation, pass through a maximum and then decrease to the final steady state value. However, at lower particle volume fractions, a maximum in the volume average floc size is not observed. Flocculation of cells leads to an increase in the volume average particle diameter. However, it also leads to a broadening of the particle size distribution. Consequently, when determining the improvement in permeate flux for tangential flow microfiltration, it is essential to include the effects of an increased average particle diameter and a broadened particle size distribution. [Copyright &y& Elsevier]