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Item type:Publication, Access status: with files , Novel sparging strategies to enhance dissolved carbon dioxide stripping in industrial scale stirred tank reactors(Frontiers Media S.A., 2024-11-15); ; ; ; Schulz, Torsten W.Aerated stirred tank reactors are widely used in bio-process engineering and pharmaceutical industries. To supply the organisms with oxygen and control the pH value, oxygen is transferred from air bubbles into the liquid phase, and, at the same time, carbon dioxide is stripped from the liquid phase with the same gas bubbles. The volumetric mass transfer coefficients for oxygen and carbon dioxide are, therefore, of crucial importance for the design and scale-up of aerated stirred tank reactors. In this experimental work, the volumetric mass transfer coefficients for oxygen and carbon dioxide are investigated simultaneously to study their mutual influence. The mass transfer performance for oxygen and carbon dioxide is conducted in stirred tank reactors on the 3 L laboratory scale, 30 L pilot scale, and 15,000 L production scale. First, the influence of dissolved carbon dioxide on the oxygen mass transfer performance is investigated in a 30 L pilot scale stirred tank reactor. The results show that the volumetric mass transfer coefficient of oxygen is not affected by the concentration of dissolved carbon dioxide, but the total mass flux of oxygen decreases with increasing carbon dioxide concentration due to the decreasing partial pressure difference. With rising gassing rate and volumetric power input, both mass transfer coefficients for oxygen and carbon dioxide show the same increasing trend. Although this trend can also be observed when scaling down to the 3 L laboratory scale reactor, a significantly different effect must be considered for the scale-up to the 15,000 L industrial scale reactor. The limited absorption capacity for carbon dioxide of the gas bubbles during the long residence time in the industrial scale reactor is noticeable here, which is why the specific interfacial area is of negligible importance. This effect is used to develop a method for independent control of oxygen and carbon dioxide mass transfer performance on an industrial scale and to increase the mass transfer performance for carbon dioxide by up to 25%.Publicationtype: Journal Article35 21 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Experimental analysis of lifelines in a 15,000 L bioreactor by means of Lagrangian Sensor Particles(Elsevier, 2024-05-01); ; ; ; This study employs Lagrangian Sensor Particles (LSPs) with a diameter of 40 mm equipped with a pressure sensor to investigate cell lifelines in a 15,000 L stirred tank reactor (STR) with three Elephant Ear impellers. The Stokes number of the LSPs is approx. 0.004 on a macro-scale. The vertical probability of presence, axial velocity profiles, circulation time distributions, and residence time distributions are quantified to analyze single-phase mixing heterogeneities, detect hydrodynamic compartments and conduct a Lagrangian regime analysis. Results reveal a similarly distributed probability of presence in the vertical reactor center but emphasize the LSP's sensitivity to fluctuating densities. Axial velocity distributions illustrate characteristic impeller-induced flow patterns, and circulation time distributions identify three compartments with comparatively shorter times in the axial center. Residence time distributions exhibit a similar compartmentalized profile. Moreover, the study estimates a potential oxygen deprivation zone for CHO cells in the upper compartment and demonstrates the LSP's efficacy in characterizing impeller systems. Contrary to literature, the ratio of examined global mixing times to circulation times is 1.0, highlighting macro-scale mixing. The research underscores that LSPs offer crucial insights into industrial-scale STRs, specifically for determining hydrodynamic compartments without having optical access.Publicationtype: Journal Article27 128 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Advances in Characterization of Industrial Bioreactors for Cell Culture Process(Springer, 2023); ; ; ; Aerated stirred tank reactors are widely used in the biopharmaceutical industry for cell culture applications due to their flexibility and broad range of uses. This book chapter provides an overview of the main characterization methods for aerated stirred tank reactors in the context of cell culture processes. The methods described include mechanical power input, volumetric mass transfer, flow field, and mixing characterization. Examples are given using stirred tank reactors of different scales, ranging from a 3 L laboratory scale to a 15,000 L industrial scale. The chapter also discusses recent developments in the use of mobile, encapsulated sensors known as Lagrangian Sensor Particles (LSP) for continuous data collection and transmission throughout the entire reactor volume, providing insights from the perspective of cells during a cell culture process. Additionally, the state-of-the-art in numerical flow simulation is discussed, using aerated stirred tank reactors as an example to illustrate the challenges and opportunities offered by numerical flow simulation. It is highlighted that the methods described are specifically focused on cell culture applications, which have lower specific power inputs and aeration rates compared to other types of applications such as microbial fermentations or chemical reactions. The chapter also provides a brief overview of the fundamentals of aerated stirred tank reactors, including their design and components, and emphasizes the importance of equipment characterization for successful process transfer and scale-up in cell culture processes.Publicationtype: Book part56