20 results
Now showing1 - 10 of 20
- Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Modeling and validating of oxygen transport in wave bioreactors: optimized experimental mass transfer method and novel Lattice-Boltzmann CFD approach(Frontiers Media S.A., 2026-01-21); ; ; Wave bioreactors are commonly used in biopharmaceutical upstream processes as an intermediate stage between shake flasks and stirred tanks within the seed train. They offer a controlled environment for cell cultivation while minimizing shear stress. Accurate characterization of these systems is essential for optimizing cell culture performance, particularly as state of the art cell lines require higher volumetric mass transfer coefficients k<inf>L</inf>a. This study aims to determine the volumetric mass transfer coefficient through experiments and computational fluid dynamics (CFD) simulations. An improved experimental method for the measurements of the volumetric mass transfer is presented, with results correlated to key process parameters: rocking angle, rocking rate, and filling volume. In addition, CFD simulations were caried out using M-Star CFD by means of a Lattice-Boltzmann Method-based solver. The mass transfer was calculated using Higbie’s penetration theory, incorporating the Kolmogorov scale to define contact time. The analysis also integrates concepts from Friedl and the surface renewal model, introducing the surface normal velocity as an additional parameter in the mass transfer coefficient k<inf>L</inf> calculation. Analyzes were carried out for 10 and 50 L wave bioreactors, with one degree of freedom movement. Optimized process parameters were identified and validated in biological cultivations, resulting in increased dissolved oxygen levels in the medium. These findings contribute to improved characterization and control of wave bioreactors, enabling more accurate prediction of process parameter effects.Publicationtype: Journal Article28 14 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Lagrangian sensor particles for detecting hydrodynamic heterogeneities in industrial bioreactors: experimental analysis and Lattice-Boltzmann simulations(Elsevier, 2025-04-19); ; ; ; This study analyzes trajectories of three particle types in an industrial-scale bioreactor, equipped with a Rushton turbine and a pitched blade turbine, to characterize hydrodynamic compartments. The trajectories obtained from measurements with Lagrangian Sensor Particles (LSP,exp) are compared to those generated by Lattice-Boltzmann large eddy simulations (LB LES). The latter method is used to reproduce analogous simulated LSPs (LSP,sim) as resolved particles. Additionally, for benchmarking purposes, massless tracer particles (tracer,sim) are incorporated to accurately represent fluid flow dynamics. Discrepancies in the axial probability of presence and velocity between LSP,exp and LSP,sim likely stem from differences in mass distribution, density, number of particles, and ratio of particle size to grid. A necessarily high LSP,sim volume fraction in LB LES leads to increased collisions and clustering, negatively impacting flow dynamics, and reducing turbulent kinetic energy by at least 3%. Circulation and residence time distributions for the three types of particles identify three hydrodynamic compartments within the bioreactor, validated by local mixing time distributions. The ratio of overall average circulation time to global mixing time is Θglob,95≈3.0⋅t¯circ for LSP,exp, which largely corresponds to literature results. A theoretical LSP size of dp,th≈1mm is estimated to be flow following on micro-scale in the bulk phase, if a Stokes number of St=0.1 is assumed. However, Stokes number estimations confirm that LSP,exp are capable to follow flow patterns on the meso-scale and macro-scale with St≈0.2 and St≈0.002, respectively. Hence, hydrodynamic structures at length scales greater than or equal to the size of the impeller can be investigated by current state-of-the-art LSPs, which proves their technological readiness for industrial bioreactors.Publicationtype: Journal Article53 26 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Gas-Liquid Flow, Oxygen Mass Transfer, and Mixing Characterization of a Transparent Single-Use Bioreactor Model (Biostat STR® 200)(Sartorius, 2025); ; ; ; In recent years, the biopharmaceutical industry has had to become more flexible and increase upstream yields, driving the uptake of process intensification strategies such as perfusion. This requires production equipment to support high cell density cell cultures requesting an oxygen uptake rate of 20 mmol O2 L-1 h-1 and above. Testing equipment capabilities typically involves characterization approaches such as determining oxygen mass transfer, energy input, and mixing performance. A broad measurement database and an appropriate mass transfer model CFD can be applied to better predict culture impact. However, cell activity sometimes deviates from expectations, and empirical validation of the used model is often lacking. In this research, a transparent version of the Biostat STR® 200, made of acrylic glass, was erected at the Institute of Multiphase Flows at Hamburg University of Technology to gain deeper insights into the two-phase flow pattern. The gas distribution and mixing behavior were investigated using high-resolution pictures and videos. In these assessments, two different stirrer combinations have been investigated for varied aeration rates and stirrer frequencies. With regards to oxygen mass transfer rate, the acrylic reactor replica behaves similarly to the industrial single-use bioreactor system, with deviations lying within the predefined ranges determined by the Sartorius Biostat STR product characterization approach. The volumetric mass transfer coefficient kLa is also comparable for both reactors. Consequently, it can be assumed that the visual recordings from the transparent model reflect dynamics from industrialized single-use cultivation chambers. Furthermore, high-resolution imaging of the acrylic replica of the Biostat STR® 200 enabled the systematic characterization of the mixing and mass transfer performance, helping us to understand the influence of stirrer speeds and gassing rates in combination with different sparger and impeller types as well as their interaction.Publicationtype: Learning Object73 301 - Some of the metrics are blocked by yourconsent settings
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: without files , Study of hydrodynamic stress in cell culture bioreactors via lattice-Boltzmann CFD simulations supported by micro-probe shear stress method(Elsevier, 2024-08-01); ; ; Mammalian cell cultivation in pharmaceutical industry can last up to units of weeks and requires proper transport of nutrients and oxygen for cell growth and production. Given the long time period, cells experience flow fields from all bioreactor's zones, where the energy dissipation rate (ε) varies substantially. Shear sensitive micro-probes with size comparable to cells and Kolmogorov eddies are used for the determination of the maximum hydrodynamic stress (τmax) in bioreactors. For the very first time, the micro-probe method is applied successfully not only to laboratory (3 L) and pilot scale (80 L and 200 L), but also to industrial production scale bioreactor (12,500 L) with Rushton turbine and pitched-blade (RT-PB) impeller configuration. Experimentally obtained data are used for the validation of comprehensive CFD scale-up study, using the Lattice-Boltzmann large eddy simulation (LB-LES) method. Besides τmax, this work also focuses on the study of mixing time and flow field attributes.Publicationtype: Journal Article28 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Characterization data for the establishment of scale-up and process transfer strategies between stainless steel and single-use bioreactors(Multidisciplinary Digital Publishing Institute (MDPI), 2024-05-16); ; ; 38 99 - 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: with files , Introduction of novel characteristic time quantities to describe chemical reactors(Elsevier, 2023-11-15); ; ; ; The Mean Residence Time is a quantity which is used very often to characterise chemical reactors. This quantity can be calculated using the Residence Time Distribution of a specific, continuous reactor and assuming closed-closed boundary conditions. Many reactors in the industry though, are discontinuous ones and the direct application of these methods is in general not possible. This work presents a new distribution, the Local Residence Time Distribution, which observes each position in a specific reactor. Furthermore, two new, local quantities, the Mean Distribution Time and the Mean Dead Time, are introduced, which can be applied as characteristic times to evaluate the internal behaviour of chemical reactors used for discontinuous processes such as fermentations.Publicationtype: Journal ArticleScopus© Citations 1 29 100 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Experimental investigation of circulation times with lagrangian sensor particles in a 15,000 L acrylic glass bioreactor(Curran Associates, Inc., 2023-07); ; ; ; Publicationtype: Conference Paper11 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Computational study of three-dimensional Lagrangian transport and mixing in a stirred tank reactor(Elsevier, 2023-01-13); ; ; ; The detection of compartments and dead zones as well as the estimation of the mixing efficiency in stirred tanks are of vital interest for a variety of biochemical and chemical processes. Here, numerically derived time-dependent 3D fluid velocity fields of a stirred tank reactor are computed using the Lattice Boltzmann Method. Mixing in the stirred tank reactor is analysed by means of Lagrangian Coherent Structures which allow to unravel the mixing states of complex flows. This Lagrangian analysis is achieved by computing Finite Time Lyapunov Exponents and applying recent trajectory-based network methods on the three-dimensional flow. The results reveal a zone of low interaction in the upper region of the stirred tank reactor and five additional transient compartments. The trajectory-based network analysis detects low cross-mixing of fluid parcels between different compartments but a very high mixing of fluid parcels inside of each compartment. This high interaction is also found in an analysis of the Finite Time Lyapunov Mixing Intensity. Time-averaging of the fluid velocity field prior to the Lagrangian analysis is considered to extract the most influential Lagrangian Coherent Structures.Publicationtype: Journal ArticleScopus© Citations 5 79 354