1,720,955 research outputs found
Microbial lifelines in bioprocesses: From concept to application
No full textBlöbaum L, Haringa C, Grünberger A. Microbial lifelines in bioprocesses: From concept to application. Biotechnology Advances. 2022;62.Bioprocesses are scaled up for the production of large product quantities. With larger fermenter volumes, mixing becomes increasingly inefficient and environmental gradients get more prominent than in smaller scales. Environmental gradients have an impact on the microorganism's metabolism, which makes the prediction of large-scale performance difficult and can lead to scale-up failure. A promising approach for improved understanding and estimation of dynamics of microbial populations in large-scale bioprocesses is the analysis of microbial lifelines. The lifeline of a microbe in a bioprocess is the experience of environmental gradients from a cell's perspective, which can be described as a time series of position, environment and intracellular condition. Currently, lifelines are predominantly determined using models with computational fluid dynamics, but new technical developments in flow-following sensor particles and microfluidic single-cell cultivation open the door to a more interdisciplinary concept. We critically review the current concepts and challenges in lifeline determination and application of lifeline analysis, as well as strategies for the integration of these techniques into bioprocess development. Lifelines can contribute to a successful scale-up by guiding scale-down experiments and identifying strain engineering targets or bioreactor optimisations. Copyright © 2022. Published by Elsevier Inc
Through the Organism’s eyes: The interaction between hydrodynamics and metabolic dynamics in industrial-scale fermentation processes
No full textThe broth in industrial scale fermentors may contain significant gradients in, for example, substrate concentration, dissolved oxygen and shear rates. From the perspective of microbes in this fermentor, these gradients translate to temporal variations in their environment that may affect their metabolic response. As a result, there may be differences in process yield between laboratory scale fermentations and their industrial counterpart. Rather than scaling-up bioprocesses based on equivalence, it is recommended to scale-down: mimic the large-scale environment in lab scale setups, to account for hydrodynamic-metabolic interaction from the start. In this thesis, the use of Euler-Lagrange computational fluid dynamics to capture the large-scale fermentation environment is explored. Lagrangian simulations offer to study processes from the microbial perspective (so-called “lifelines”), and enable coupling of metabolic models describing the response to external variations. With this, it is possible to take the history of the trajectory of the microbe into account, as organisms may not adapt to their surroundings instantaneously. Guidelines for the setup of fermentor simulations are presented, and several means for processing the lifelines are discussed. The obtained information is used to design lab-scale fermentations that mimic large-scale conditions. It is furthermore shown how coupled hydrodynamic-metabolic simulations can be used to predict yield-loss, assess process improvements, and study the onset of population heterogeneity in large-scale fermentors. Additionally, a more fundamental towards the role of the turbulent Schmidt number in multi-impeller mixing is included.ChemE/Transport Phenomen
Inter-compartment interaction in multi-impeller mixing: Part I. Experiments and multiple reference frame CFD
No full textCFD simulations of mixing in single-phase multi-Rushton stirred tanks based on the RANS methodology frequently show an over-prediction of the mixing time. This hints at an under-prediction of the mass exchange between the compartments formed around the individual impellers. Some studies recommend tuning the turbulent Schmidt number to address this issue, but this appears to be an ad-hoc correction rather than physical adjustment, thereby compromising the predictive value of the method. In this work, we study the flow profile in between two Rushton impellers in stirred tank. The data hints at the presence of macro-instabilities, and a peak in turbulent kinetic energy in the region of convergent flow, which both may promote inter-compartment mass exchange. CFD studies using the steady-state multiple reference frame model (unsteady simulations are treated in part II) inherently fail to include the macro-instability, and underestimate the turbulent kinetic energy, thereby strongly over-estimating mixing time. Furthermore, the results are highly mesh-sensitive, with increasing mesh density leading to a poorer prediction of the mixing time. Despite proper results for 1-impeller studies, we do not deem MRF-RANS models suitable for mixing studies in multi-impeller geometries.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.ChemE/Transport Phenomen
From industrial fermentor to CFD-guided downscaling: what have we learned?
No full textEuler–Lagrange computational fluid dynamics simulations offer great potential for the integration of transport dynamics and metabolic dynamics in fermentation systems. Since the seminal work of Lapin et al. [1,2], progress has been made, mainly in the analysis of CFD data and translation to laboratory setup designs. Different large-scale processes require different analysis methods; in this paper we discuss which analysis methods are best suited for given reactor types, by reviewing prior simulation cases as well as introducing new test cases. Furthermore, we address challenges in the translation from Euler–Lagrange simulations to laboratory scale systems, and propose methods to work around these shortcomings. Based on the current state of the art, we propose guidelines for the selection of data analysis methods, and we discuss the design of rational scale-down simulators. We conclude with a brief discussion regarding the requirements and possibilities of next-generation scale-down simulators, such as microfluidic single-cell analysis, and possible ways to approximate cellular lifelines from invasive intra-cellular measurements.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.ChemE/Transport PhenomenaImPhys/Imaging PhysicsExecutive boardBT/Bioprocess Engineerin
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
An analysis of organism lifelines in an industrial bioreactor using Lattice-Boltzmann CFD
No full textEuler-Lagrange CFD simulations, where the biotic phase is represented by computational particles (parcels), provide information on environmental gradients inside bioreactors from the microbial perspective. Such information is highly relevant for reactor scale-down and process optimization. One of the major challenges is the computational intensity of CFD simulations, especially when resolution of dynamics in the flowfield is required. Lattice-Boltzmann large-eddy simulations (LB-LES) form a very promising approach for simulating accurate, dynamic flowfields in stirred reactors, at strongly reduced computation times compared to finite volume approaches. In this work, the performance of LB-LES in resolving substrate gradients in large-scale bioreactors is explored, combined with the inclusion of a Lagrangian biotic phase to provide the microbial perspective. In addition, the hydrodynamic performance of the simulations is confirmed by verification of hydrodynamic characteristics (radial velocity, turbulent kinetic energy, energy dissipation) in the impeller discharge stream of a 29 cm diameter stirred tank. The results are compared with prior finite volume simulation results, both in terms of hydrodynamic and biokinetic observations, and time requirements.BT/Bioprocess Engineerin
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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