Weheliye, WH; (2013) Mixing, Velocity and Turbulence Characteristics of Shaken Bioreactors (Weheliye, WE, Trans.). Doctoral thesis , UCL (University College London).

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Abstract

The thesis describes an experimental investigation of the flow in a shaken bioreactor of cylindrical geometry with a flat bottom. Several reactor designs can be distinguished that attain mixing in different ways: oscillatory flow mixers (OFM), static mixers, stirred vessels and shaken bioreactors. Shaken bioreactors are often small-scale mixers (microwells) employed in the early stage of bioprocess development (i.e. microbial fermentation, bioconversion and product recovery techniques), before the developed process is implemented in a large-scale industrial stirred tank. However, despite their wide use, little is known about the fluid mechanics of these systems. In the present study Particle Image Velocimetry (PIV) measurements are carried out to determine the variation of the flow dynamics in a cylindrical shaken geometry for different operating conditions such as medium height, shaking frequency, orbital shaking diameter, cylinder inner diameter and fluid viscosity. In the first part phase-resolved measurements are carried out with PIV to provide a thorough characterisation of the flow and mixing dynamics occurring in a cylindrical shaken bioreactor for a fluid of low viscosity (i.e. water). From this analysis a flow scaling law based on the Froude number, Fr, is identified, which correlates the shape and inclination of the free surface to the occurrence of a flow transition. More specifically it was found that at low Fr the mean flow ischaracterised by a toroidal vortex with its axis aligned along the azimuthal direction, while after flow transition the free surface exhibits a phase lag and a vortical structure with a vertical axis that precesses around the cylinder axis is present. In the second part of the thesis flow characteristics, such as the interfacial area, circulation time, vortex size and location, kinetic energy and viscous dissipation rate of kinetic energy for a fluid of low viscosity are analysed in depth. The free surface interfacial area was directly measured by image analysis to assess oxygen transfer potential and was compared to an analytical solution valid for low Fr. The non-dimensional time and length scales of the vortical structures occurring in the cylindrical bioreactor were determined to provide an insight into the mixing dynamics, while a Reynolds decomposition analysis of the kinetic energy was carried out to assess the onset of a laminar-turbulent flow transition with increasing Fr. Direct measurements of the viscous dissipation rate of the kinetic energy, ǫ, were obtained across the tank to help assess micro-mixing and identify regions in the bioreactor experiencing higher levels of viscous stresses that can potentially affect cell growth. In the third part of the thesis the flow obtained with Newtonian fluids of higher viscosity is investigated and the flow scaling law determined for water is extended to a broader range of viscosity. A flow transition map based on Fr and Re is identified and four main regions characterised by different mean flow dynamics are shown. The turbulent kinetic energy levels and shear rate magnitudes are assessed for different combinations of Fr and Re. The results offer valuable new information for the design of mixing processes and crucial data to validate computational fluid dynamics simulations of cylindrical shaken bioreactors.

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