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Item type:Publication, Access status: without files , Bioprocess monitoring: How much do we need to know for successful scale-up?To address the challenges posed by climate change and the demand for sustainable production, robust and efficient bioprocesses are alternatives to conventional chemical processes. However, many promising bioprocesses that perform well at laboratory scale fail upon scale-up to industrial scale. This discrepancy among other arises from environmental gradients in large scale bioreactors causing phenotypic population heterogeneity, metabolic burden, and genetic instability. Traditional assumptions of homogeneous cell behavior under well-mixed conditions are challenged by complex intracellular networks and spatial-temporal environmental variations, necessitating a multi-level bioprocess monitoring approach. This chapter reviews bioprocess monitoring strategies across hierarchical cell-physiological levels and discusses physical, chemical, and biological parameters critical for bioprocess understanding and control. It highlights measurement techniques, from in-line sensors enabling real-time control to off-line comprehensive analyses, and contrasts laboratory-scale flexible, multi-level monitoring with industrial-scale demands for robust, cost-effective, and regulative-compliant systems. Bridging the monitoring gap between scales involves applying “beginning-with-the-end-in-mind” in bioprocess design, integrating advanced monitoring such as single-cell analysis, scalable in-line sensors, and multi-level bioprocess modeling. Combining experimental data with computational models predicts scale-dependent cellular behavior, guides bioprocess optimization, and enables soft sensor development for real-time, automated closed-loop industrial bioprocess control. This integrated framework promises improved scale-up and enhanced robustness in industrial-scale bioprocesses.Publicationtype: Book Part10 - 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 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , 83