Flow Induced by Dual-Turbine of Different Diameters in a Gas-Liquid Agitation System: the Agitation and Turbulence Indices

Flow induced by a dual turbine stirred tank was characterized measuring local velocities with a LDV and drawing the main velocity fields and the maps of turbulence intensities. The hydrodynamic regime studied in all the experiments was the so-called merging flow regime. Two impeller configurations were studied. In the first one, two disk style turbine of the same dimensions (configuration A) were used, while in the second one, the dimensions of the upper turbine were 20 % proportionally smaller than those of the lower turbine (configuration B). The agitation and turbulence indices were used to evaluate, as a first order approximation, the power consumption distribution between convective and turbulent flows. The comparison of the two-phase agitation systems studied showed that configuration B seems to be more efficient than configuration A, since both induce a similar global convective flow, but the first one assures a significant reduction of power consumption. The distribution of power consumption between convective and turbulent flows was evaluated using the agitation index and a new global parameter: turbulence ind

Two-dimensional Stokes flow driven by elliptical paddles

A fast and accurate numerical technique is developed for solving the biharmonic equation in a multiply connected domain, in two dimensions. We apply the technique to the computation of slow viscous flow (Stokes flow) driven by multiple stirring rods. Previously, the technique has been restricted to stirring rods of circular cross section; we show here how the prior method fails for noncircular rods and how it may be adapted to accommodate general rod cross sections, provided only that for each there exists a conformal mapping to a circle. Corresponding simulations of the flow are described, and their stirring properties and energy requirements are discussed briefly. In particular the method allows an accurate calculation of the flow when flat paddles are used to stir a fluid chaotically

Design and characterization of a novel perfusion reactor for biopharmaceuticals production

The demand for commercially valuable biopharmaceuticals able to treat different immunopathological diseases has accelerated in the last few decades. In recent years the industry has shifted the preferred mode of operation towards continuous strategies and has favoured the adoption of perfusion approaches for the cell culture step. In this mode successful perfusion process examples have reached up to 10-fold higher cell densities and product titres than fed-batch, while maintaining product quality at reduced costs. Perfusion processes are operated at high cell densities where cells are retained, while product and waste are continuously removed. This leads to different requirements in flow and mixing in comparison to lower cell density operations, potentially influencing the cellular production performance and therefore product quality. As the pharmaceutical industry is highly regulated, ensuring homogeneity in the bulk throughout the process is critical, while oxygen and mixing requirements of high cell density cultures must be continuously met. This paper presents the design and characterization of a novel 250 mL stirred tank reactor (STR) developed to work in perfusion mode. The results presented include the experimental measurement of the power consumption, the mixing analysis of the flow within the bioreactor which informs design consideration and scaling efforts and the biological data of the perfusion stage with an industrially relevant cell line producing an IgG monoclonal antibody. The characterization allows the operating window of the reactor to be established, resulting in increased productivity of intensified cultures

Gas-liquid mass transfer : a comparison of down-and up-pumping axial flow impellers with radial impellers

The performance of a down- and up-pumping pitched blade turbine and A315 for gas-liquid dispersion and mass transfer was evaluated and then compared with that of Rushton and Scaba turbines in a small laboratory scale vessel. The results show that when the axial flow impellers are operated in the up-pumping mode, the overall performance is largely improved compared with the down-pumping configuration. Compared with the radial turbines, the up-pumping A315 has a high gas handling capacity, equivalent to the Scaba turbine and is economically much more efficient in terms of mass transfer than both turbines. On the other hand, the uppumping pitched blade turbine is not as well adapted to such applications. Finally, the axial flow impellers in the down-pumping mode have the lowest performance of all the impellers studied, although the A315 is preferred of the pitched blade turbine

The circulation of liquid in the mixing vessel equipped with different dual impellers

The circulation of liquid in the mixing vessel equipped with different dual impeller

Gas-liquid mass transfer performance of dual impeller system employing rushtons, concave-bladed disc (CD-6) turbines and their combination in stirred tank bioreactor

The degree of oxygenation in stirred tank bioreactor is normally described and characterized L by the volumetric gas-liquid mass transfer coefficient (kL a). Throughout this study, the gas liquid mass transfer performance of dual impeller stirring system employing either two Rushton turbines (RT), two Concave-bladed disc (CD-6) turbines or the combination of both was comparatively investigated in Newtonian and non-Newtonian fluid systems. Static gassing-out technique was applied in all experimental kLa determinations and subsequent modeling of mass transfer correlations for all configurations were developed by incorporating the effects of power number (N3D2) and superficial velocity (Vg) on kLa. Ultimately, the use of dual CD-6 stirrers on a mixing shaft improved the oxygen transfer rate (OTR) by about 5-50 % and 18-65 % higher than the conventional RT-RT system in Newtonian and non-Newtonian systems, respectively

Gas maldistribution in a fermenter stirred with multiple turbines

The study is focused on modeling of gas maldistribution of aerated liquid systems in a multiple impeller bioreactor. The phenomenon may or may not depend on column design. The latter case is dependent merely on bed fluid dynamics and could be treated by using the methodology of the residence time distribution (RTD) theory. Accordingly, a specific methodology is proposed, as follows: the fermenter has been modelled as a reactor network involving a combination of zones representing basic ideal flow patterns. The methodology is based on the wide-spread experimental gas tracer technique extended by a new systemic identification approach. The approach is based on a Mellinmodification of the Laplace transform over the relevant equations. The method allows zero-time solutions for identification analysis. Unlike the diffusion model approximation, the technique considered allows exact approximation of the RTD curves with circulation. The proposed transfer function represents adequately the bioreactor gas maldistribution thus allowing fast overview of the studied reaction and prompt feed back control on the physical situation

Scale-down Technologies for Perfusion Culture for Rapid Biopharmaceutical Process Development

Perfusion culture is becoming an increasingly popular choice for the production of therapeutic proteins, however few scale-down devices capable of small scale and/or high throughput optimisation of high cell density perfusion cultures have been published. To address this technology gap, this thesis describes the development, implementation, and engineering characterisation of two scale-down technologies; (i) a quasi-perfusion method at mL-scale in microwell plates (MWPs) and (ii) a purposely designed novel bioreactor (BR) at 250mL scale. Quasi-perfusion in MWP was developed at mL-scale and is capable of achieving many of the specific characteristics of perfusion culture, namely elevated cell density, cell retention and good productivity. The quasi-perfusion methodology was implemented to screen a range of process conditions, exchanging at a constant vessel volume per day (VVD) between 0.5-1.8, or at constant cell specific perfusion rate (CSPR) with a range of media, with cell retention achieved via sedimentation or centrifugation. Viable cell densities (VCDs) of 42 × 10^{6} cells mL-1and volumetric productivities up to 2 fold greater than fed-batch were achieved. Design and engineering characterisation of the novel 250mL BR ensured favourable hydrodynamics, with a dual impeller system selected to maximise mass transfer. Cell retention was achieved via a tangential flow filter (TFF) at perfusion rates between 0.5- 1.8 VVD, maintaining maximum VCDs of 92 × 10^{6} cells mL-1 at >95% viability. Good scalability was demonstrated for a range of performance metrics, including µmax, qAb and biomass production, between each system when compared to a bench scale 5L BR, while scaling was based on constant volumetric power input. The combined use of quasi-perfusion methodologies, shown to be sensitive to changes in perfusion rate and media composition, for high throughput screening studies, followed by the 250mL BR for in-depth study of a small range of conditions, is shown to be a powerful tool for the development and optimisation of perfusion processes