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The reliable transfer of bioprocesses from single-use bioreactors (SUBs) of different scales to conventional stainless steel stirred-tank bioreactors is of steadily growing interest. In this publication, a scale-up study for SUBs with volumes of 200 L and 2000 L and the transfer to an industrial-scale conventional stainless steel stirred-tank bioreactor with a volume of 15,000 L is presented. The scale-up and transfer are based on a comparison of mixing times and the modeling of volumetric mass transfer coefficients kLa, measured in all three reactors in aqueous PBS/Kolliphor solution. The mass transfer coefficients are compared with the widely used correlation of van’t Riet at constant stirrer tip speeds. It can be shown that a van’t Riet correlation enables a robust and reliable prediction of mass transfer coefficients on each scale for a wide range of stirrer tip speeds and aeration rates. The process transfer from single-use bioreactors to conventional stainless steel stirred-tank bioreactors is proven to be uncritical concerning mass transfer performance. This provides higher flexibility with respect to bioreactor equipment considered for specific processes., Boehringer Ingelheim Pharma GmbH & Co. KG, Sartorius Stedim Biotech

The Villermaux-Dushman protocol with UV-Vis analytics is an established tool to characterize the global micro mixing performance in process equipment. The local mixing process is described by a micro mixing model (incorporation model), originally designed for turbulent flows. The novel imaging UV-Vis spectroscopy used in this work uncovers locally resolved micro mixing phenomena in a laminar split-and-recombine (SAR) mixer unit manufactured from selective laser-induced etching (SLE). The local absorbance is recorded with a high spatial resolution camera through a telecentric lens and post-processed into local concentration fields of components. The method unveils discrepancies of the micro mixing time determined from the conventional incorporation model in laminar flow and the locally recorded mixing process. The micro mixing time rather needs to be seen as a mean micro mixing time instead. Furthermore, the spatial information obtained by the imaging UV-Vis spectroscopy gives insight into local micro mixing and selectivity, yielding new approaches to equipment optimization.

Breakthroughs in computing have led to development of new generations of Earth Systems Models providing detailed information on how our planet may locally respond to the ongoing global warming. Access to such climate information systems presents an unprecedented opportunity for engineers to make tangible contributions to climate adaptation through integration of climate information in their products, designs, and services. We introduce the concept of “Climate Informed Engineering” (CIE) as an emerging interdisciplinary field integrating climatic considerations in engineering products and services. The concept behind CIE is to enable engineers to build infrastructure, devices, sensors or develop new materials and processes that are informed by climate and climate change information. We believe CIE will be an increasingly important dimension of Engineering Science resonating with engineers and scientists with different backgrounds.

During the scale-up of biopharmaceutical production processes, insufficiently predictable performance losses may occur alongside gradients and heterogeneities. To overcome such performance losses, tools are required to explain, predict, and ultimately prohibit inconsistencies between laboratory and commercial scale. In this work, we performed CHO fed-batch cultivations in the single multicompartment bioreactor (SMCB), a new scale-down reactor system that offers new access to study large-scale heterogeneities in mammalian cell cultures. At volumetric power inputs of 20.4–1.5 W m−3, large-scale characteristics like long mixing times and dissolved oxygen (DO) heterogeneities were mimicked in the SMCB. Compared to a reference bioreactor (REFB) set-up, the conditions in the SMCB provoked an increase in lactate accumulation of up to 87%, an increased glucose uptake, and reduced viable cell concentrations in the stationary phase. All are characteristic for large-scale performance. The unique possibility to distinguish between the effects of changing power inputs and observed heterogeneities provided new insights into the potential reasons for altered product quality attributes. Apparently, the degree of galactosylation in the evaluated glycan patterns changed primarily due to the different power inputs rather than the provoked heterogeneities. The SMCB system could serve as a potent tool to provide new insights into scale-up behavior and to predict cell line-specific drawbacks at an early stage of process development.

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.