Multiphase Stirred Tank Bioreactors – New Geometrical Concepts and Scale‐up Approaches

Mainly with respect to biotechnological cases, current developments in the field of impeller geometries and findings for multistage configurations with a specific view on aerated stirred tanks are reviewed. Although often the first choice, in the given case the 6‐straight blade disc turbine is usually not the best option. Furthermore, quantities usable for scale‐up, specifically applicable in this field are discussed. Only quantities taking local conditions into account appear to be able to actually compare different stirrer types and scales.DFG, 56091768, TRR 63: Integrierte chemische Prozesse in flüssigen MehrphasensystemenDFG, 315464571, Interaktion der mechanischen Beanspruchung und der Produktivität von biologischen Agglomeraten in RührfermenternDFG, 256647858, Stoffübergang von aufsteigenden Blasen in reagierenden FlüssigphasenTU Berlin, Open-Access-Mittel - 201

Growth behavior of human adipose tissue-derived stromal/stem cells at small scale : numerical and experimental investigations

Human adipose tissue-derived stromal/stem cells (hASCs) are a valuable source of cells for clinical applications, especially in the field of regenerative medicine. Therefore, it comes as no surprise that the interest in hASCs has greatly increased over the last decade. However, in order to use hASCs in clinically relevant numbers, in vitro expansion is required. Single-use stirred bioreactors in combination with microcarriers (MCs) have shown themselves to be suitable systems for this task. However, hASCs tend to be less robust, and thus, more shear sensitive than conventional production cell lines for therapeutic antibodies and vaccines (e.g., Chinese Hamster Ovary cells CHO, Baby Hamster Kidney cells BHK), for which these bioreactors were originally designed. Hence, the goal of this study was to investigate the influence of different shear stress levels on the growth of humane telomerase reversed transcriptase immortalized hASCs (hTERT-ASC) and aggregate formation in stirred single-use systems at the mL scale: the 125 mL (= SP100) and the 500 mL (= SP300) disposable Corning® spinner flask. Computational fluid dynamics (CFD) simulations based on an Euler⁻Euler and Euler⁻Lagrange approach were performed to predict the hydrodynamic stresses (0.06⁻0.87 Pa), the residence times (0.4⁻7.3 s), and the circulation times (1.6⁻16.6 s) of the MCs in different shear zones for different impeller speeds and the suspension criteria (Ns1u, Ns1). The numerical findings were linked to experimental data from cultivations studies to develop, for the first time, an unstructured, segregated mathematical growth model for hTERT-ASCs. While the 125 mL spinner flask with 100 mL working volume (SP100) provided up to 1.68.10⁵ hTERT-ASC/cm² (= 0.63 × 10⁶ living hTERT-ASCs/mL, EF 56) within eight days, the peak living cell density of the 500 mL spinner flask with 300 mL working volume (SP300) was 2.46 × 10⁵ hTERT-ASC/cm² (= 0.88 × 10⁶ hTERT-ASCs/mL, EF 81) and was achieved on day eight. Optimal cultivation conditions were found for Ns1u < N < Ns1, which corresponded to specific power inputs of 0.3⁻1.1 W/m³. The established growth model delivered reliable predictions for cell growth on the MCs with an accuracy of 76⁻96% for both investigated spinner flask types

From single drop coalescence to droplet swarms - Scale-up considering the influence of collision velocity and drop size on coalescence probability

Coalescence modelling in liquid/liquid dispersions is a challenging task and field of investigations up to now, which becomes apparent when comparing the various existent models with their different and partly even contradictive implementation of influencing factors. In this work, systematic investigations of single drop coalescence were used to compare and validate different coalescence efficiency models regarding the important influencing parameters relative collision velocity and drop size. The impact of these parameters could be analysed independently from each other for the first time and used to identify the best modelling approach. Moreover, the numerical parameter of the coalescence efficiency model could be obtained based on single drop experiments. Using this determined parameter the simulation of drop size distributions within a lab scale stirred vessel was possible. The presented method offers the possibility of independent parameter estimation for population balance equation simulations based on single drop experiments. The application of this systematic approach allows the separate validation of submodels and reliable parameter determination by small scale investigations. On this basis a sound scale-up is possible using population balance equation simulations. (C) 2016 Elsevier Ltd. All rights reserved

Coalescence efficiency model including electrostatic interactions in liquid/liquid dispersions

The drop size distribution is an essential process variable in liquid/liquid systems and relevant in many technical applications. It can be described by population balance equations. A coalescence efficiency model was developed to be able to describe the well-known coalescence inhibition due to changing pH value or salt concentration. The model includes the attractive van der Waals and repulsive electrostatic force according to the DLVO theory into the population balance equation framework. This DLVO model can extend existing simulations in a straightforward manner due to a conceptual implementation. Moreover, zeta potential measurements were performed and the model was applied to simulate experiments in a stirred Lank. Hence, the drop size distribution could be predicted well with changing pH value. The results are discussed in comparison to simulations with existing models in literature. (C) 2014 Elsevier Ltd. All rights reserved

Influence of drop size and superimposed mass transfer on coalescence in liquid/liquid dispersions - Test cell design for single drop investigations

The detailed understanding of droplet coalescence is important for the accurate description of liquid/liquid dispersions. A test cell is designed which enables serial examinations of the random coalescence process with high repetition rate, good observability and accuracy of experimental parameters. Within this rectangular test cell a rising droplet collides with a pendant one, while recorded by a high speed camera. The gained experimental data allows a validation and further development of appropriate models. The investigated parameters in this work are the drop size and the superimposed mass transfer influencing the coalescence probability. These examinations were carried out in the EFCE standard test system toluene/acetone/water. The effect of varying the drop size seems to be interfered by the different rising velocities due to buoyancy. Introducing a transferring component has a significant impact on the coalescence process. A transfer direction from disperse to continuous phase results in a coalescence probability of almost 100%, whereas the reverse mass transfer direction induces a repulsion of nearly all droplets. (C) 2013 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved

Influence of different silica nanoparticles on drop size distributions in agitated liquid‐liquid systems

The impact of different silica nanoparticles on rheology, interfacial tension and drop size distributions in liquid‐liquid systems is determined experimentally. The particles vary in wettability and specific surface area. In contrast to commonly used high‐energy devices for Pickering emulsion preparation, low energy input by stirring allows to quantify drop breakage and coalescence in steady state and dynamic conditions. The experiments can provide essential information for drop size model development in nanoparticle‐stabilized emulsions.DFG, 56091768, TRR 63: Integrierte chemische Prozesse in flüssigen MehrphasensystemenTU Berlin, Open-Access-Mittel - 201

Drop coalescence in technical liquid/liquid applications : a review on experimental techniques and modeling approaches

The coalescence phenomenon of drops in liquid/liquid systems is reviewed with particular focus on its technical relevance and application. Due to the complexity of coalescence, a comprehensive survey of the coalescence process and the numerous influencing factors is given. Subsequently, available experimental techniques with different levels of detail are summarized and compared. These techniques can be divided in simple settling tests for qualitative coalescence behavior investigations and gravity settler design, single-drop coalescence studies at flat interfaces as well as between droplets, and detailed film drainage analysis. To model the coalescence rate in liquid/liquid systems on a technical scale, the generic population balance framework is introduced. Additionally, different coalescence modeling approaches are reviewed with ascending level of detail from empirical correlations to comprehensive film drainage models and detailed computational fluid and particle dynamics

Growth Behavior of Human Adipose Tissue-Derived Stromal/Stem Cells at Small Scale: Numerical and Experimental Investigations

Human adipose tissue-derived stromal/stem cells (hASCs) are a valuable source of cells for clinical applications, especially in the field of regenerative medicine. Therefore, it comes as no surprise that the interest in hASCs has greatly increased over the last decade. However, in order to use hASCs in clinically relevant numbers, in vitro expansion is required. Single-use stirred bioreactors in combination with microcarriers (MCs) have shown themselves to be suitable systems for this task. However, hASCs tend to be less robust, and thus, more shear sensitive than conventional production cell lines for therapeutic antibodies and vaccines (e.g., Chinese Hamster Ovary cells CHO, Baby Hamster Kidney cells BHK), for which these bioreactors were originally designed. Hence, the goal of this study was to investigate the influence of different shear stress levels on the growth of humane telomerase reversed transcriptase immortalized hASCs (hTERT-ASC) and aggregate formation in stirred single-use systems at the mL scale: the 125 mL (=SP100) and the 500 mL (=SP300) disposable Corning® spinner flask. Computational fluid dynamics (CFD) simulations based on an Euler–Euler and Euler–Lagrange approach were performed to predict the hydrodynamic stresses (0.06–0.87 Pa), the residence times (0.4–7.3 s), and the circulation times (1.6–16.6 s) of the MCs in different shear zones for different impeller speeds and the suspension criteria (Ns1u, Ns1). The numerical findings were linked to experimental data from cultivations studies to develop, for the first time, an unstructured, segregated mathematical growth model for hTERT-ASCs. While the 125 mL spinner flask with 100 mL working volume (SP100) provided up to 1.68 × 105 hTERT-ASC/cm2 (=0.63 × 106 living hTERT-ASCs/mL, EF 56) within eight days, the peak living cell density of the 500 mL spinner flask with 300 mL working volume (SP300) was 2.46 × 105 hTERT-ASC/cm2 (=0.88 × 106 hTERT-ASCs/mL, EF 81) and was achieved on day eight. Optimal cultivation conditions were found for Ns1u < N < Ns1, which corresponded to specific power inputs of 0.3–1.1 W/m3. The established growth model delivered reliable predictions for cell growth on the MCs with an accuracy of 76–96% for both investigated spinner flask types

Europes, errances : la littérature européenne et ses projets d’unification du continent

L’Europe ? C’est une invention des écrivains, écrit Heinrich Mann. Sa phrase renvoie à une relation qui persiste depuis des siècles : celle entre la littérature européenne et l’Europe comme son sujet. Cet article se propose d’examiner de plus près cette relation. Qu’est-ce qui a poussé les auteurs européens à la recherche acharnée d’un projet d’unification utopique pendant des siècles ? Y a-t-il une connexion entre, d’un côté, les expériences d’exil et d’errance que la plupart d’entre ces auteurs ont vécues, et de l’autre, leurs projets européens ? Finalement, comment cette connexion se manifeste-elle sur le plan littéraire ? En s’appuyant sur le concept des « bons européens » apatrides de Friedrich Nietzsche, l’article construit l’image d’une Europe littéraire dont les frontières ne peuvent être celles d’une identité ou une géographie statiques.Europe? That is an invention of poets, Heinrich Mann said, referring to a relationship that has existed for centuries: the relationship between European literature and the theme of Europe in this literature. Empire, civilization, United States, regulatory force or peace project – especially in the 19th and 20th centuries the most diverse ideas of Europe were formulated and discussed in literary works. This article tries to get to the bottom of this relationship: What is it that incited European writers to strive to find a project of unification which was to remain purely utopian for centuries? Is there a relationship between exile and migration that most of these writers experienced on the one hand and their European projects on the other? And finally: How is this relationship expressed in their literary works? This article uses Nietzsche’s concept of the homeless « good Europeans » to outline a representation of a literary Europe whose boundaries cannot be fixed in terms of identity and geography

Langzeituntersuchungen von 52 behandelten Patienten mit Gastrointestinalen Stromatumoren (GIST)

Tumor location of GIST was gastric in 32, small bowel in 14, rectum in 3 and extraintestinal in 3 patients. Median tumor size was 46 mm. Median mitotic index was 4 per 50 hpf. Resection was achieved R0 in 46 patients, R1 in 4 patients and R2 in 2 patients. Mean overall survival was 58.9 months (range, 46– 73 months). Mean recurrence free survival was 45.6 months (range, 36–57 months). Mean overall survival was 58.9 months (range, 46–73 months). Risk factors for recurrence were tumor location and high mitotic index Ki-67