Mixing performance of viscoelastic fluids in a kenics km in-line static mixer

AbstractThe mixing of ideal viscoelastic (Boger) fluids within a Kenics KM static mixer has been assessed by the analysis of images obtained by Planar Laser Induced Fluorescence (PLIF). The effect of fluid elasticity and fluid superficial velocity has been investigated, with mixing performance quantified using the traditional measure of coefficient of variance CoV alongside the areal method developed by Alberini et al. (2013). As previously reported for non-Newtonian shear thinning fluids, trends in the coefficient of variance follow no set pattern, whilst areal analysis has shown that the >90% mixed fraction (i.e. portion of the flow that is within ±10% of the perfectly mixed concentration) decreases as fluid elasticity increases. Further, the >90% mixed fraction does not collapse onto a single curve with traditional dimensionless parameters such as Reynolds number Re and Weissenberg number Wi, and thus a generalised Reynolds number Reg=Re/(1+2Wi) has been implemented with data showing a good correlation to this parameter

Fluid flow and mixing in a novel intermittently rotating bioreactor for CAR-T cell therapy manufacturing

This work explores the mixing and fluid dynamics in a novel bioreactor currently used for the automated manufacturing of CAR-T cell therapy, which offers a single-dose cure for several forms of advanced blood cancer. The cylindrical bioreactor has a low aspect ratio and a free surface. Agitation is achieved by intermittent rotation of the entire vessel around its central axis. No engineering characterisation has been conducted to date for this system in a bioprocessing context. The study examines the fluid dynamics problems of spin-up from rest and spin-down to rest. Novel Particle Image Velocimetry and Planar Laser-Induced Fluorescence data is presented alongside reflective flakes results, shedding light on the different transient flow regions inside the intermittently rotating bioreactor, and determining the timescales of macro- and micromixing. The results presented can be used to design a custom rotation pattern of the bioreactor for improved mixing performance during the cell expansion step

Micromixing in chemical reactors : test reactions

Tese de doutoramento. Engenharia Química. Faculdade de Engenharia. Universidade do Porto. 200

Image Analysis and Multiphase Bioreactors

The applications of visualisation and image analysis to bioreactors can be found in two main areas: the characterisation of biomass (fungi, bacteria, yeasts, animal and plant cells, etc), in terms of size, morphology and physiology, that is the far most developed, and the characterisation of the multiphase behaviour of the reactors (flow patterns, velocity fields, bubble size and shape distribution, foaming), that may require sophisticated visualisation techniques

Experimental and computational investigation of turbulent mixing in microscale reactors

Flash Nanoprecipitation (FNP) is a promising technique for mass production of nanoparticles for use in various areas. Mixing time is such a crucial factor that it affects the particle size distribution as well as the particle morphology. Turbulent mixing in microscale nanoprecipitation reactors, i.e., the planar conned impinging-jet reactor (CIJR) and the multi-inlet vortex reactor (MIVR), is therefore investigated by means of numerical simulations as well as experimental flow visualization methods. In the process of studying, the computational fluid dynamics (CFD) models are validated by comparing simulation results with experimental data. One of the experimental visualization techniques developed in this work uses the phenolphthalein as the tracer that characterizes the acid-base neutralization reaction. Mixing is qualitatively and, by applying a special image processing technique, also quantitatively evaluated. Coherent flow structures are also analyzed through spatial correlation and POD. For the MIVR, the microscopic particle velocimetry (micro-PIV or microPIV) is first employed to measure the velocity field. Results from Reynolds-averaged Navier-Stokes (RANS) simulations and large eddy simulations (LES) are compared to the micro-PIV results. Comparisons show LES is more suitable for simulating flow field in these reactors. In addition, another experimental method developed in this work is also applied to the MIVR, which couples the confocal laser scanning microscopy (CLSM) and the microscopic laser induced fluorescence (micro-LIF). More detailed and quantitatively accurate data are obtained for the CFD model validation. Passive scalar mixing and reactive mixing experiments are both accomplished to quantify the mixing at the maroscale and microscale respectively

Investigation of turbulence modulation in solid-liquid suspensions using FPIV and micromixing experiments

The focus of this thesis is the study of turbulent solid-liquid stirred suspensions, which are involved in many common unit operations in the chemical, pharmaceutical and food industries. The studies of two-phase flows present a big challenge to researchers due to the complexity of experiments; hence there is a lack of quantitative solid and liquid hydrodynamic measurements. Therefore, an investigation of turbulence modulation by dispersed particles on the surrounding fluid in stirred vessels has been carried out, via two-phase fluorescent Particle Image Velocimetry (FPIV) and micromixing experiments. The main property of interest has been the local dissipation rate, as well as root-mean-square (rms) velocities and turbulent kinetic energy (TKE) of the fluid. Initially a single-phase PIV study was conducted to investigate the flow field generated by a sawtooth (EkatoMizer) impeller. The purpose of this study was to gain insight into various PIV techniques before moving on to more complex two-phase flows. Subsequently stereo-, highspeed and angle-resolved measurements were obtained. The EkatoMizer formed a good case study as information regarding its hydrodynamics is not readily available in literature, hence knowledge has been extended in this area. An analysis of the mean flow field elucidated the general structure of fluid drawn into the impeller region axially and discharged radially; the latter characterised the impeller stream. The radial rms velocity was considered to represent best the system turbulence, even though the tangential rms velocity was greater close to the blade; however the radial component was more prevalent in the discharge stream. Due to differences in rms velocities, TKE estimates obtained from two and three velocity components deviated, being greater in the latter case. Integral (1-D and 2-D) length scales were overestimated by the quantity W / 2 in the impeller region. Ratios of longitudinal-to-lateral length scales also indicated flow anisotropy (as they deviated from 2:1). The anisotropy tensor showed that the flow was anisotropic close to the blade, and returned to isotropy further away from the impeller. Instantaneous vector plots revealed vortices in the discharge stream, but these were not associated with flow periodicity. Alternatively, the vortex structures were interpreted as low frequency phenomena between 0-200 Hz; macro-instabilities were found to have a high probability of occurrence in the discharge stream. Dissipation is the turbulent property of most interest as it directly influences micromixing processes, and its calculation is also the most difficult to achieve. Its direct determination from definition requires highly resolved data. Alternative methods have been proposed in the literature, namely dimensional analysis, large eddy simulation (LES) analogy and deduction from the TKE balance. All methods were employed using 2-D and 3-D approximations from stereo-PIV data. The LES analogy was deemed to provide the best estimate, since it accounts for three-dimensionality of the flow and models turbulence at the smallest scales using a subgrid scale model. (Continues...)

Mixing processes in anti-solvent crystallisation

Mass transfer phenomena play an important role in many chemical and physical processes, such as crystallisation, and, therefore, it is essential to develop a better fundamental understanding of mass transfer effects in order to design more efficient crystallisation processes. It is aimed to investigate mixing within the context of anti-solvent crystallisation. Two mixing scales are studied, micro-mixing and macro-mixing. The first part of this thesis focuses on diffusive mixing in anti-solvent process and how it relates to turbulent mixing. This is subsequently followed by the characterisation of mixing times in one litre vessels. Through using a combined experimental and CFD approach insight into macroscopic mixing process will be gained for common anti-solvent solvent pairs. At the micro-scale local concentration profiles at interfaces between segregated fluid elements are controlled through diffusion. Consequently diffusion is a significant step of the mixing process. This is particularly true for anti-solvent crystallisation in which nucleation outcomes are strongly influenced by localised concentration profiles. Previous work on modelling relied on a Fickian framework where concentration gradients are the driving force for diffusion. This predicts large overshoots in the supersaturation at interfaces between solution and anti-solvent, as is often intuitively expected. In this work, a thermodynamically consistent diffusion model was developed and applied to anti-solvent systems. In this model chemical potential gradients provide a more physically realistic driving force for diffusion. "Non-intuitive” behaviour was predicted for diffusion in highly non-ideal liquid systems. In particular, as solute diffusion towards anti-solvent is severely hindered, it can diffuse against its concentration gradient away from anti-solvent. Furthermore large supersaturation overshoots above that at the final mixture composition are not found when thermodynamically consistent approach is used, demonstrating that these overshoots are modelling artefacts and are not expected to be present in physical systems. In addition, for certain conditions, localised liquid-liquid spinodal demixing is predicted to occur during the diffusive mixing process, even when the final mixture composition is outside the liquid-liquid phase separation region. Intermittent spinodal demixing driven by diffusive mixing may provide a novel explanation for differences of nucleation behaviours among various anti-solvents. Further investigation of this phenomenon found that higher anti-solvent content within the system increased the likelihood for LLPS. On the macro-scale, mixing occurs predominately through turbulent mechanisms in which velocity fields act to spatially rearrange fluid elements within the system. Turbulent dissipation leads to the reduction of these elements to the Batchelor length scale, in which diffusion becomes the prevalent mass transfer mechanism. Periodic boundary conditions were used to approximate the case of multiple solution-anti-solvent layers in parallel to give a better representation of diffusive mixing in turbulent systems. A qualitative discussion is offered on the relation of the developed model to other micro-mixing models reported in literature. Macroscopic mixing was investigated through characterising mixing times for a 1litre optimax reactor using a combined experimental and computational fluid dynamics (CFD) approach. Mixing times were then calculated from the resulting conductivity profiles in three ways; the 95% homogenisation method, and through fitting exponential and first order plus dead-time models. The geometry of the system was modelled and simulated on Mstar CFD to predict mixing times. Local and global mixing times were calculated by using a simulated probe, and the tracer concentration relative standard deviation throughout the vessel respectively. Firstly, The predicted variability of mixing from the Mstar simulations for the addition of a tracer to water, including the effects of tracer repeats and addition location is explored. Following this, the experimental results are discussed, with a comparison of mixing time determination methods shown. Subsequently, the predicted and experimental results are compared. Effects of initial solvent composition on mixing times are then investigated. Lastly, we present the mixing times for the addition of ethanol to water, once more utilising both CFD and experimental conductivity method. Across all mixing time measurements, a wide variance was found to be present, highlighting the inherent variability associated with mixing processes.Mass transfer phenomena play an important role in many chemical and physical processes, such as crystallisation, and, therefore, it is essential to develop a better fundamental understanding of mass transfer effects in order to design more efficient crystallisation processes. It is aimed to investigate mixing within the context of anti-solvent crystallisation. Two mixing scales are studied, micro-mixing and macro-mixing. The first part of this thesis focuses on diffusive mixing in anti-solvent process and how it relates to turbulent mixing. This is subsequently followed by the characterisation of mixing times in one litre vessels. Through using a combined experimental and CFD approach insight into macroscopic mixing process will be gained for common anti-solvent solvent pairs. At the micro-scale local concentration profiles at interfaces between segregated fluid elements are controlled through diffusion. Consequently diffusion is a significant step of the mixing process. This is particularly true for anti-solvent crystallisation in which nucleation outcomes are strongly influenced by localised concentration profiles. Previous work on modelling relied on a Fickian framework where concentration gradients are the driving force for diffusion. This predicts large overshoots in the supersaturation at interfaces between solution and anti-solvent, as is often intuitively expected. In this work, a thermodynamically consistent diffusion model was developed and applied to anti-solvent systems. In this model chemical potential gradients provide a more physically realistic driving force for diffusion. "Non-intuitive” behaviour was predicted for diffusion in highly non-ideal liquid systems. In particular, as solute diffusion towards anti-solvent is severely hindered, it can diffuse against its concentration gradient away from anti-solvent. Furthermore large supersaturation overshoots above that at the final mixture composition are not found when thermodynamically consistent approach is used, demonstrating that these overshoots are modelling artefacts and are not expected to be present in physical systems. In addition, for certain conditions, localised liquid-liquid spinodal demixing is predicted to occur during the diffusive mixing process, even when the final mixture composition is outside the liquid-liquid phase separation region. Intermittent spinodal demixing driven by diffusive mixing may provide a novel explanation for differences of nucleation behaviours among various anti-solvents. Further investigation of this phenomenon found that higher anti-solvent content within the system increased the likelihood for LLPS. On the macro-scale, mixing occurs predominately through turbulent mechanisms in which velocity fields act to spatially rearrange fluid elements within the system. Turbulent dissipation leads to the reduction of these elements to the Batchelor length scale, in which diffusion becomes the prevalent mass transfer mechanism. Periodic boundary conditions were used to approximate the case of multiple solution-anti-solvent layers in parallel to give a better representation of diffusive mixing in turbulent systems. A qualitative discussion is offered on the relation of the developed model to other micro-mixing models reported in literature. Macroscopic mixing was investigated through characterising mixing times for a 1litre optimax reactor using a combined experimental and computational fluid dynamics (CFD) approach. Mixing times were then calculated from the resulting conductivity profiles in three ways; the 95% homogenisation method, and through fitting exponential and first order plus dead-time models. The geometry of the system was modelled and simulated on Mstar CFD to predict mixing times. Local and global mixing times were calculated by using a simulated probe, and the tracer concentration relative standard deviation throughout the vessel respectively. Firstly, The predicted variability of mixing from the Mstar simulations for the addition of a tracer to water, including the effects of tracer repeats and addition location is explored. Following this, the experimental results are discussed, with a comparison of mixing time determination methods shown. Subsequently, the predicted and experimental results are compared. Effects of initial solvent composition on mixing times are then investigated. Lastly, we present the mixing times for the addition of ethanol to water, once more utilising both CFD and experimental conductivity method. Across all mixing time measurements, a wide variance was found to be present, highlighting the inherent variability associated with mixing processes

Visualisieren des Mikro- und Makromischens mit Hilfe zweier fluoreszierender und chemisch reagierender Farbstoffe

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Non-Newtonian fluid mixing in agitated vessels in the transitional flow regime

This thesis provides an original contribution to knowledge of fluid mixing in agitated vessels. This flow application has a critical importance in the manufacture of a wide range of intermediates and products in Johnson Matthey. The novelty of the research undertaken is twofold. Firstly, it presents quantitative investigations of the agitation of Newtonian and non-Newtonian fluids under transitional flow conditions. Despite the fact that transitional mixing is very common in industry, particularly for formulated products showing non-Newtonian rheology, most studies in the literature focus on fully laminar or fully turbulent mixing. Secondly, with the development of a methodology for 3D Particle Tracking Velocimetry measurements in laboratory scale vessels, this thesis has taken a step towards more accessible flow visualisation capabilities in industry. Numerical simulations have also been carried out to cross-validate the 3D-PTV data and provide additional information that could not be obtained experimentally. Experiments and simulations have been conducted for many combinations of fluid rheology and impeller speed and at two vessel sizes. The hydrodynamics of transitional flows have been shown to depend significantly on the Reynolds number and fluid rheological behaviour. Non-Newtonian fluids showed smaller values of shear rate, Lagrangian acceleration and flow numbers, compared to the Newtonian ones. For Newtonian fluids, the local energy dissipation rate scaled differently depending on the position relative to the impeller. Non-Newtonian fluids did not follow the same scaling. The information obtained in this thesis will help the design, optimisation and scale-up of mixing operations within Johnson Matthey