•Current state of the art of hPSC large scale expansion.•2D and 3D culture systems for hPSC expansion.•hPSC processing in suspension culture.•hPSC production control by hPSC aggregation, operation ...modes and process parameters.•Challenges for cGMP-compliant hPSC processing.
The constant supply of high cell numbers generated by defined, robust, and economically viable culture processes is indispensable for the envisioned application of human pluripotent stem cells (hPSCs) and their progenies for drug discovery and regenerative medicine. To achieve required cell numbers and to reduce process-related risks such as cell transformation, relative short batch-like production processes at industry- and clinically-relevant scale(s) must be developed and optimized. Here, we will review recent progress in the large-scale expansion of hPSCs with particular focus on suspension culture, which represents a universal strategy for controlled mass cell production. Another focus of the paper relates to bioreactor-based approaches, including technical aspects of bioreactor technologies and operation modes. Lastly, we will discuss current challenges of hPSC process engineering for enabling the transition from early stage process development to fully optimized hPSC production scale operation, a mandatory step for hPSCs’ industrial and clinical translation.
In aerobic process oxygen must be continuously supplied in order to achieve acceptable productivities, Since the role of oxygen in microorganism growth and its metabolism is of vital importance, both ...the oxygen consumption by the cell and the oxygen transfer rate (OTR) into the system have to be understood.
The main function of a properly designed bioreactor is to provide a controlled environment and a concentration of nutrients (dissolved oxygen, mainly) sufficient to achieve optimal growth and/or optimal product formation in a particular bioprocess. Dissolved oxygen in the broths is the result of a balance of its consumption rate in the cells, and the rate of oxygen transfer from the gas to the liquid phase. Monitoring dissolved oxygen in the broth is mandatory because often oxygen becomes the factor governing the metabolic pathways in microbial cells.
In this work the oxygen uptake rate (OUR) in different fermentation broths is examined. Experimental techniques have been compiled from the literature and their applicability to microbial processes reviewed. The reciprocal influence of OUR and OTR is presented and an analysis of rate-limiting variables is carried out.
Mathematical models are a fundamental tool in bioprocess design, optimisation, scale-up, operation and control at large-scale fermentation. Kinetic models describing aerobic bioprocesses have to include an oxygen balance taking into account OTR and OUR. Many different specific rate expressions for cell growth, substrate consumption, product formation and oxygen uptake have been developed and incorporated in the models, and simulations of different bioprocess have been carried out. Some of them are presented here.
This open access book explores the multifaceted interplay of technology, knowledge, and place. While digital technology is increasingly influencing our way of knowing, conversely it is itself the ...consequence of human creativity and local social interaction. Part I analyzes how digital technologies transform markets through artificial intelligence and decentralized blockchain models. Its contributions discuss novel governance mechanisms, including the responsible use and analysis of big data. Part II illustrates various ways in which technology supports humanity, be it algorithms supporting complex decision-making processes or the use of robotics in care services. The chapters highlight that technology's efficiency and potential rely on social norms and human capital. Finally, Part III shows that digitization is generating vibrant entrepreneurship, reflected in geographically clustered urban scale-up economies, as well as opening up new ways for people to connect with one another, organize civic engagement and enable new forms of labor. The book offers theoretical reflections as well as empirical cases from the United States, Canada, Japan, South Africa, and Europe. This volume provides a valuable read for scholars, students and professionals in the fields of knowledge creation, technology and governance.
This open access book goes into the details of the characteristics of scale-ups, touching upon various theoretical perspectives (stages of growth models, the role of intangible capital, the tradeoffs ...between fixed costs and marginal costs) relating to firm growth, to provide a clear definition of this emerging concept. Given the disproportionately large economic contribution of a small number of fast-growing firms, there has been growing interest in a category of dynamic ventures called "scale-ups". The term was popularized by Silicon Valley Venture Capitalists before receiving attention from academics and public policy makers. However, there remains considerable confusion regarding what a scale-up actually is. This is an open access book.
Abstract
Der Scale‐up strukturierter Packungskolonnen ist ein zeit‐ und kostenintensiver Prozess. Um den Aufwand zur Ermittlung packungsspezifischer Kennzahlen zu reduzieren, wurde eine Messzelle für ...strukturierte Packungen entwickelt. Diese ermöglicht es charakteristische Bestandteile einer Packungskolonne im Labor‐Maßstab abzubilden. Im Rahmen dieses Beitrages wird der Einfluss der bei Packungskolonnen üblichen Randabweiser und des Abstands zwischen Wand und Packung auf die Fluiddynamik in der Messzelle untersucht.
Abstract
The scale‐up of columns equipped with structured packings is a time and cost intensive process. In order to improve scale‐up efficiency, a measurement cell for structured packings has been developed. This makes it possible to investigate characteristic sections of packed columns, such as bulk and wall area on a small scale. The study shows the influence of commonly installed wall wipers and the distance between wall and packing on the fluid dynamics in the measuring cell.
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