Dynamics of polymeric solutions in complex kinematics bulk and free surface flows: Multiscale/Continuum simulations and experimental studies

While rheological and microstructural complexities have posed tremendous challenges to researchers in developing first principles models and simulation techniques that can accurately and robustly predict the dynamical behaviour of polymeric flows, the past two decades have offered several significant advances towards accomplishing this goal. These accomplishments include: (1). Stable and accurate formulation of continuum-level viscoelastic constitutive models and their efficient implementation using operator splitting methods to explore steady and transient flows in complex geometries, (2). Prediction of rheology of polymer solutions and melts based on micromechanical models as well as highly parallel self-consistent multiscale simulations of non-homogeneous flows. The main objective of this study is to leverage and build upon the aforementioned advances to develop a quantitative understanding of the flow-micro-structure coupling mechanisms in viscoelastic polymeric fluids and in turn predict, consistent with experiments, their essential macroscopic flow properties e.g. frictional drag, interface shape, etc. To this end, we have performed extensive continuum and multiscale flow simulations in several industrially relevant bulk and free surface flows. The primary motivation for the selection of the specific flow problems is based on their ability to represent different deformation types, and the ability to experimentally verify the simulation results as well as their scientific and industrial significance

Development and qualification of a scale-down model of a commercial mammalian cell culture bioreactor using Computational Fluid Dynamics

The use of computational fluid dynamics (CFD) techniques can be used to develop and/or optimize a scale-down model to investigate mixing, oxygen mass transfer characteristics and turbulence, strain rate, and bubble size distribution in laboratory-scale stirred-tank bioreactors. In this work, CFD was used to test and modify a laboratory-scale bioreactor model of a manufacturing-scale bioreactor. The laboratory-scale model was originally established based on power per volume (P/V) and volume of gas per bioreactor volume per minute (vvm). CFD simulations of mixing time, power input, and gas volume hold-up were performed to demonstrate comparability between the laboratory-scale model and the manufacturing-scale bioreactor. These simulations were verified with experimental measurement of mixing time and gas hold-up. The results were used to propose sparge rate and impeller agitation as factors in a Design of Experiments (DoE) study in laboratory-scale bioreactors. The impact of sparge rate and impeller agitation on cell growth, productivity, and product quality attributes were evaluated in the DOE study. The laboratory-scale production bioreactor model was compared to the manufacturing-scale production bioreactor. The results confirmed that CFD techniques could be used to establish sparge rate and impeller agitation to improve a scale-down model

Computational Fluid Dynamics (CFD) modelling and experimental confirmation of hollow fiber tangential flow filtration (HFTFF) and alternating tangential flow filtration (ATF) In a perfusion bioreactor

Hollow fiber tangential flow filtration (HFTFF) and Alternating tangential flow filtration (HFATF) are technologies of choice in continuous (perfusion) bioreactor operations. A major drawback of these technologies is membrane fouling and associated reduction in membrane permeability. Membrane fouling leads to a gradual decline in trans-membrane flux and the sieving of the protein product. Additionally, experimental data suggests that under otherwise similar conditions protein sieving may be different in TFF vs. ATF, indicating that flow behavior patterns in the two technologies may be different. Many models of fouling and protein sieving have been reported in the literature for HFTFF. In comparison, however, there is limited research work on HFATF, making it hard to compare mechanisms of fouling and product sieving between HFTFF and HFATF. Additionally, almost all mechanisms of fouling and predictive models make sweeping assumptions with regards to the complex flow patterns prevailing in HFTFF and HFATF. In this study, we provide experimental data and computational fluid dynamics (CFD) information to gain insight into factors that impact fouling and product sieving. Specifically, first we present the confirmation of CFD model outputs by comparing experimentally measured trans-membrane flux and pressure with model predictions. Next, we compare the CFD model predictions of pressure drop, shear rate profile and axial and radial fluid velocity distributions between HFTFF and HFATF. Subsequently, we investigate the shear effect on cell damage, using the concept of constant Camp number, defined as Gt = constant, where G is the prevailing shear rate and t is the exposure time. Our CFD model predicts that shear rate (G) and hence the resulting stress experienced by cells in HFATF has a distribution that is determined by the operation of the diaphragm pump. Finally, we use CFD to compare Gt profile generated by imposing different pump condition