The impact of baffles and probes on flow and power consumption in single- use bioreactors

In upstream processing single-use bioreactors (SUBs) are used in for the production of 66% of biopharmaceutical products due to high flexibility and reduction of time to market1. Even though SUBs offer economic feasibility for cell culture, there are limitations on the selection of optimal scale-up criteria which ensure that the cultivation process is adequately translated to larger scales. Therefore, rigorous hydrodynamic analysis is essential in novel SUBs, for the understanding of flow dynamics and energy consumption characteristics and secures that the equivalency of critical quality attributes (CQAs) across different scales is met2. To date scaling procedures have been mainly limited to pilot and larger scale systems but this must be extended and tested to smaller scales, where probes and baffle dimensions relative to the reactor size can greatly affect the overall flow and mixing performance. In this framework, a systematic characterisation of engineering features in small-scale SUBs is particularly important for the development of valid scale-down models (SDMs) and a thorough understanding of the flow field at that scale is essential to evaluate the way critical design parameters affect the fluid dynamics, assisting in the optimisation of mixing and cell growth3. The aim of this work is to assess the flow patterns and power consumption in different stirred tank bioreactor geometries, with working volumes ranging between 200 mL - 1L, actively used in mammalian and stem-cell cultures, in fed-batch and perfusion modes. The bioreactors are equipped with different baffle and probe sizes focusing on the optimisation of probe design. For fluid flow experiments the Reynolds number ranges from Re=2500-7000 with mixtures of water and glycerol being the working fluids. Flow hydrodynamics and power consumption have been characterised via computational fluid dynamics (CFD) and validated experimentally via Particle Image Velocimetry (PIV). The impact of design parameters is assessed with particular focus on baffle and probe number and size in order to evaluate the dependency of bioreactor hydrodynamics and power consumption on key geometrical features. Preliminary results indicate that the presence of probes highly impact the flow dynamics and impeller power number with the latter acting equivalently to baffles. The computational and experimental analysis of the flow dynamics in the current work, verifies the accuracy of CFD simulations and emphasises that the investigation of small-scale reactors is essential, highlighting the sensitivity of mixing features on bioreactor design parameters

Controls on modern tributary-junction alluvial fan occurrence and morphology: High Atlas Mountains, Morocco

Modern tributary-junction alluvial fans (cone-shaped depositional landforms formed in confined valley settings) were analysed from a 20-km-long reach of the Dades River in the distal part of the fold-thrust belt region in the south-central High Atlas Mountains of Morocco. Here, a deeply dissected network of ephemeral tributary streams and a perennial trunk drainage characterised by an arid mountain desert climate are configured onto a folded and thrust faulted Mesozoic sedimentary sequence. Out of 186 tributary streams, only 29 (16%) generated alluvial fans at their tributary junctions. The fan-generating catchments possess higher relief, longer lengths, lower gradients, and larger areas than nonfan-generating catchments. Whilst geologically, fan-generating catchments are underlain by folded / steeply dipping weak bedrock conducive to high sediment yield. Tributary-junction fans are built from debris flow or fluvial processes into open or confined canyon trunk valley settings. The proximity of the perennial trunk drainage combined with the valley morphology produces lobate or foreshortened trimmed fan forms. Analysis of fan (area, gradient, process), catchment (area, relief, length, gradient), and tributary valley (width) variables reveals weak morphometric relationships, highlighted by residual plots that show dominance of smaller and lower gradient than expected fan forms. These morphometric relationships can be explained by interplay between the catchment and trunk drainage geology, morphology, climate, and flood regime that are combined into a conceptual ‘build and reset’ model. Ephemeral tributary-junction fans develop progressively during annual localised winter-spring storm events, attempting to build toward a morphological equilibrium. However, the fans never reach an equilibrium morphological form as they are reset by rare (>10 year) large floods along the River Dades that are linked to regional incursions of Atlantic low pressure troughs. The model highlights the spatial and temporal variability of tributary-junction fan building and illustrates the connectivity / coupling importance of such features in dryland mountainous terrains

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on fourteen research projects.National Institutes of Health Grant RO1 DC00117National Institutes of Health Grant RO1 DC02032National Institutes of Health/National Institute on Deafness and Other Communication Disorders Grant R01 DC00126National Institutes of Health Grant R01 DC00270National Institutes of Health Contract N01 DC52107U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-95-K-0014U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-96-K-0003U.S. Navy - Office of Naval Research Grant N00014-96-1-0379U.S. Air Force - Office of Scientific Research Grant F49620-95-1-0176U.S. Air Force - Office of Scientific Research Grant F49620-96-1-0202U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-96-K-0002National Institutes of Health Grant R01-NS33778U.S. Navy - Office of Naval Research Grant N00014-92-J-184

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on twelve research projects.National Institutes of Health Grant R01 DC00117National Institutes of Health Grant R01 DC02032National Institutes of Health/National Institute of Deafness and Other Communication Disorders Grant 2 R01 DC00126National Institutes of Health Grant 2 R01 DC00270National Institutes of Health Contract N01 DC-5-2107National Institutes of Health Grant 2 R01 DC00100U.S. Navy - Office of Naval Research Grant N61339-96-K-0002U.S. Navy - Office of Naval Research Grant N61339-96-K-0003U.S. Navy - Office of Naval Research Grant N00014-97-1-0635U.S. Navy - Office of Naval Research Grant N00014-97-1-0655U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research Grant N00014-96-1-0379U.S. Air Force - Office of Scientific Research Grant F49620-96-1-0202National Institutes of Health Grant RO1 NS33778Massachusetts General Hospital, Center for Innovative Minimally Invasive Therapy Research Fellowship Gran

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on fifteen research projects.National Institutes of Health Grant RO1 DC00117National Institutes of Health Grant RO1 DC02032National Institutes of Health Contract P01-DC00361National Institutes of Health Contract N01-DC22402National Institutes of Health/National Institute on Deafness and Other Communication Disorders Grant 2 R01 DC00126National Institutes of Health Grant 2 R01 DC00270National Institutes of Health Contract N01 DC-5-2107National Institutes of Health Grant 2 R01 DC00100U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-94-C-0087U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-95-K-0014U.S. Navy - Office of Naval Research/Naval Air Warfare Center Grant N00014-93-1-1399U.S. Navy - Office of Naval Research/Naval Air Warfare Center Grant N00014-94-1-1079U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research Grant N00014-92-J-1814National Institutes of Health Grant R01-NS33778U.S. Navy - Office of Naval Research Grant N00014-88-K-0604National Aeronautics and Space Administration Grant NCC 2-771U.S. Air Force - Office of Scientific Research Grant F49620-94-1-0236U.S. Air Force - Office of Scientific Research Agreement with Brandeis Universit

Multiscale study of hydrodynamics, mixing and gas-liquid mass transfer in a stirred-tank bioreactor

The growth of industrial biotechnology has created a pull for advancing bioreactor design. The requirements of the culture system have led to a variety of technical issues that generally involve transfer of mass and energy. Predicting bioreactor performance has proved to be complex as it requires not only a deep knowledge of all the biological aspects, but also a proper characterization of transport and transfer phenomena within the bioreactor which are equipment design and scale dependent. In stirred-tank bioreactors, hydrodynamics governs bulk fluid mixing and gas-liquid mass transfer. The understanding and quantification of these three physical key aspects and of their interactions are required within the framework of scale-up or scale-down. Due to their simplicity, traditional scaling criteria based on global quantities are obviously not able to account for the intricacy of the local hydrodynamics, mixing and mass transfer properties. This dissertation is part of a project aiming at a better mastering of phenomena linked to gas-liquid transfer that govern the performance of biochemical processes. It studies the influence of mixing and circulation imposed by hydrodynamics, within a baffled stirred-tank reactor, on the gas-liquid transfer through the liquid free surface and on the spatiotemporal distribution of the dissolved gas concentration. The major thrust of this work is to improve the description of fluid dynamics, mixing and gas-liquid mass transfer in stirred-tank bioreactors. The main input is the development and validation of a characterization experimental and computational approach that allows understanding, quantifying and modeling these multiscale transport and transfer phenomena during bioreactor implementation, in particular the selection of agitation configuration and operating conditions

Study of fixed-biomass photobioreactor for the production of high added-value metabolites

This master thesis is part of the FOTOBIOMAT research project financed by the Walloon Region, the aim of which is the development of a photobioreactor (PBR) using hybrid materials in the shape of beads within which photosynthetic microalgae producing high added-value metabolites are encapsulated. The most important limiting factor for the design of a PBR is the illumination of the culture medium. Externally illuminated rectangular reactors with a small thickness and with a high surface to volume ration allows optimising the supply of light. Nevertheless, due to the strong absorption by the cells, the recirculation of encapsulated microalgae is necessary to insure their access to the light provided at the PBR walls. To avoid any risk of deleterious shock or attrition, the beads recirculation is performed by fluidisation (hydraulic mixing) in a reclining reactor. The present work aims at describing the influence of the illumination distribution and of the fluid and particle flows on the levels and on the fluctuation of light intensity encountered by microalgae encapsulated in solid beads. Several experimental techniques were used to quantitatively characterise the illumination distribution and the liquid phase hydrodynamics. The motion of the solid particles was analysed more qualitatively. All these information on light distribution, liquid phase hydrodynamics and displacement of encapsulated microalgae in beads will have to be integrated and coupled to kinetic data on photosynthesis reactions to build a complete model of the PBR performance.Ce travail de fin d’études prend place dans le projet de recherche FOTOBIOMAT financé par la Région Wallonne dont le but est le développement d’un photobioréacteur (PBR) mettant en œuvre des matériaux hybrides sous forme de billes, dans lesquelles sont encapsulées des microalgues photosynthétiques, afin de produire des métabolites à haute valeur ajoutée. Le facteur limitant le plus important lors de la conception d’un PBR est l’illumination du milieu de culture. Des réacteurs rectangulaires éclairés par des sources externes, caractérisés par une faible épaisseur et un rapport hauteur sur volume élevé, permettent un apport lumineux optimisé. Cependant, à cause de la forte absorption des cellules, une recirculation des microalgues encapsulées s’avère nécessaire pour promouvoir leur accès à la lumière pénétrant par les parois transparentes du PBR. Dès lors, ce déplacement des billes est réalisé par agitation hydraulique dans un réacteur inclinable afin d’éviter tout risque de choc néfaste et attrition. Le présent travail tente de décrire l’influence de la distribution de l’éclairement ainsi que celles des écoulements liquide et particulaire sur les niveaux et les fluctuations de l’intensité lumineuse qui serait perçue par des microalgues encapsulées dans des billes. Les résultats ont été obtenus au moyen de différentes mesures et observations permettant de caractériser l’atténuation et la répartition de l’éclairement et l’hydrodynamique ainsi que la fluidisation du lit de particules. Toutes ces informations sur la distribution de lumière, l’écoulement de la phase liquide et le déplacement des microalgues encapsulées dans des billes devront être par la suite intégrées et couplées à des données cinétiques des réactions photosynthétiques afin d’établir un modèle complet des performances du PBR