Micro-scale definition of the engineering properties of complex biological materials

• Main Author: Papantoniou, Ioannis
• Published: University College London (University of London) 2008
• Subjects: 660.63
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.498386

Shear is present in almost all bioprocesses and high shear is associated with processes involving agitation, pumping and separation. The capability of predicting parameters such as the effect of shear on the processed material, from a small scale experiment to large scale processes is of importance in the successful development of bioprocesses especially in cases were the process material is scarce. The target of this work was to conduct experiments at the ultra scale-down level using a rotating disc device requiring quantities of processed material in the range of a few tens of millilitres and then moving down to even smaller volumes using an alternative capillary based design. For the experiments two ultra scale-down devices were designed, capable of producing high levels of shear rate ( > 105s 1). The flow field within the two devices was mapped and a profile of shear rate was established using computational fluid dynamic simulations (CFD). The effect of shear on two aggregate biological systems was examined. Microbial protein precipitate was chosen to be studied as a material which could be prepared reproducibly and was of relevance to the bio-processing area where the final scale of operation can be many thousands of litres. Mouse embryoid bodies (EBs) are representative of another class of aggregated biological material where the final scale of operation volume will be small due to its limited availability. The translation between rotating disc and capillary devices was studied using the larger quantities of the protein precipitate available. The break-up of protein precipitates was demonstrated to be a function of the exposure time to high shear fields whereas the final size was related to the extent of shear in the capillary. It was possible to correlate between the results of the rotating disc and the capillary by using the energy dissipation rate as a connecting parameter. The capillary system was further used for the controlled processing of the embryoid bodies since only small quantities were available for experimentation. It was of interest not only to study the break-up of the embryoid bodies and their final size distribution, but also the viability of the released cells. It was seen that the break-up was a function of both the amount of shear as well as of the exposure time of the particle in high shear regions. Total breakage of the embryoid bodies was observed when material was exposed to sufficiently high flow intensities.