Predictive macroscopic modeling of Chinese hamster ovary cells in fed-batch processes

This thesis focuses on developing a systematic modeling method that can capture the essential features for prediction of cell metabolism, growth and monoclonal antibody (mAb) production in Chinese Hamster Ovary (CHO) cells. In a first step all specific consumption rates are calculated based on time courses of extracellular metabolites, viable cell density and mAb. Then the metabolic phases within which the metabolic pseudo-steady state approximation is verified are identified. In a third step, all metabolic rates are expressed as a function of the specific growth rate within each metabolic phase. We have applied this method to a set of small bioreactor data and have shown that the model obtained can predict specific conversion rates both small and also at large scale. In the second part of this thesis, a kinetic model of the cell growth has been developed. Together with previously described methodology, this kinetic model results in a predictive metabolic model for each experimental cell growth data are not required. The kinetic model is based on Monod kinetics with a few modifications such as a varying the maximum specific growth rate as a function of the integral viable cell density. The full kinetic model can be used off line to design optimal feeding profiles. The results of this thesis demonstrate that rich knowledge can be derived from macroscopic data that can then be used to predict new production conditions in an industrial environment at small and large scale.Der Schwerpunkt dieser Dissertation liegt auf der systematischen Entwicklung Modellen für die Vorhersage des zellulären Stoffwechsels, des Wachstums und der Produktion von monoklonalen Antikörpern (mAb) in Kulturen von Chinesischen Hamster-Ovarzellen (CHO). Zunächst wurden mit segmentierter linearer Regression metabolischer Phasen identifiziert. Diese Identifizierung beruht auf der Annahme eines pseudo-stationären Zustands und somit, dass in einer Phase alle Raten linear miteinander korreliert waren. Die spezifischen Raten wurden aus den Zeitverläufen der Konzentrationen der Metabolite und des mAb sowie der Lebendzellzahl bestimmt. Durch die Korrelation konnten alle Raten über die Wachstumsrate im 2 L und im 2000 L Maßstab berechnet werden. Danach wurde ein kinetisches Modell des Wachstums der Zellen etabliert, was die Vorhersage aller Raten auch in fed-batch Kulturen erlaubt. Die Kinetik basiert auf der Monod-Kinetik modifiziert mit einer variablen maximalen spezifischen Wachstumsrate. Das kinetische Modell erlaubt eine rechnerische Optimierung der Substratzuführung für eine maximale Produktion. Damit wurde gezeigt, dass aus makroskopischen Daten, d.h. ohne intrazelluläre Messungen, wesentliche Informationen erhalten werden können, mit denen neue Experimente in einem industriellen Umfeld vorhergesagt werden können. Diese innovative und systematische Vorgangsweise eröffnet neue Perspektiven für die Reduzierung von Kosten und für eine Beschleunigung der Prozessentwicklung

Environmental Impact Assessment by Green Processes

Primary energy consumption around the world has been increasing steadily since the Industrial Revolution and shows no signals of slowing down in the coming years. This trend is accompanied by the increasing pollutant concentration on the Earth’s biosystems and the general concerns over the health and environmental impacts that will ensue. Air quality, water purity, atmospheric CO2 concentration, etc., are some examples of environmental parameters that are degrading due to human activities. These ecosystems can be safeguarded without renouncing industrial development, urban and economic development through the use of low environmental impact technologies instead of equivalent pollutant ones or through the use of technologies to mitigate the negative impact of high emissions technologies. Pollutant abatement systems, carbon capture technologies, biobased products, etc. need to be established in order to make environmental parameters more and more similar to the pre-industrialization values of the planet Earth. In 15 papers international scientists addressed such topics, especially combining a high academic standard coupled with a practical focus on green processes and a quantitative approach to environmental impacts

Bioprocess Systems Engineering Applications in Pharmaceutical Manufacturing

Biopharmaceutical and pharmaceutical manufacturing are strongly influenced by the process analytical technology initiative (PAT) and quality by design (QbD) methodologies, which are designed to enhance the understanding of more integrated processes. The major aim of this effort can be summarized as developing a mechanistic understanding of a wide range of process steps, including the development of technologies to perform online measurements and real-time control and optimization. Furthermore, minimization of the number of empirical experiments and the model-assisted exploration of the process design space are targeted. Even if tremendous progress has been achieved so far, there is still work to be carried out in order to realize the full potential of the process systems engineering toolbox. Within this reprint, an overview of cutting-edge developments of process systems engineering for biopharmaceutical and pharmaceutical manufacturing processes is given, including model-based process design, Digital Twins, computer-aided process understanding, process development and optimization, and monitoring and control of bioprocesses. The biopharmaceutical processes addressed focus on the manufacturing of biopharmaceuticals, mainly by Chinese hamster ovary (CHO) cells, as well as adeno-associated virus production and generation of cell spheroids for cell therapies

Advances in Phytochemistry, Textile and Renewable Energy Research for Industrial Growth

The International Conference on Phytochemistry, Textile, & Renewable Energy Technologies for Sustainable Development (ICPTRE 2020) was hosted by the World bank funded Africa Centre of Excellence in Phytochemicals, Textile and Renewable Energy (ACEII-PTRE) based at Moi University in conjunction with Donghua University, China and the Sino–Africa International Symposium on Textiles and Apparel (SAISTA). The theme of the conference was Advancing Science, Technology and Innovation for Industrial Growth. The research relationships between universities and industry have enabled the two entities to flourish and, in the past, have been credited for accelerated sustainable development and uplifting of millions out poverty. ICPTRE 2020 therefore provided a platform for academic researchers drawn from across the world to meet key industry professionals and actively share knowledge while advancing the role of research in industrial development, particularly, in the developing nations. The conference also provided exhibitors with an opportunity to interact with professionals and showcase their business, products, technologies and equipment. During the course of the conference, industrial exhibitions, research papers and presentations in the fields of phytochemistry, textiles, renewable energy, industry, science, technology, innovations and much more were presented

Methods in Computational Biology

Modern biology is rapidly becoming a study of large sets of data. Understanding these data sets is a major challenge for most life sciences, including the medical, environmental, and bioprocess fields. Computational biology approaches are essential for leveraging this ongoing revolution in omics data. A primary goal of this Special Issue, entitled “Methods in Computational Biology”, is the communication of computational biology methods, which can extract biological design principles from complex data sets, described in enough detail to permit the reproduction of the results. This issue integrates interdisciplinary researchers such as biologists, computer scientists, engineers, and mathematicians to advance biological systems analysis. The Special Issue contains the following sections:•Reviews of Computational Methods•Computational Analysis of Biological Dynamics: From Molecular to Cellular to Tissue/Consortia Levels•The Interface of Biotic and Abiotic Processes•Processing of Large Data Sets for Enhanced Analysis•Parameter Optimization and Measuremen

Advances in Phytochemistry, Textile and Renewable Energy Research for Industrial Growth

The International Conference on Phytochemistry, Textile, & Renewable Energy Technologies for Sustainable Development (ICPTRE 2020) was hosted by the World bank funded Africa Centre of Excellence in Phytochemicals, Textile and Renewable Energy (ACEII-PTRE) based at Moi University in conjunction with Donghua University, China and the Sino–Africa International Symposium on Textiles and Apparel (SAISTA). The theme of the conference was Advancing Science, Technology and Innovation for Industrial Growth. The research relationships between universities and industry have enabled the two entities to flourish and, in the past, have been credited for accelerated sustainable development and uplifting of millions out poverty. ICPTRE 2020 therefore provided a platform for academic researchers drawn from across the world to meet key industry professionals and actively share knowledge while advancing the role of research in industrial development, particularly, in the developing nations. The conference also provided exhibitors with an opportunity to interact with professionals and showcase their business, products, technologies and equipment. During the course of the conference, industrial exhibitions, research papers and presentations in the fields of phytochemistry, textiles, renewable energy, industry, science, technology, innovations and much more were presented

A Sustainable Revolution

The parties of the United Nations Framework Convention on Climate Change (UNFCCC) attained the Paris Agreement to tackle climate change and to strengthen the actions required for a sustainable transition towards an environmentally friendly future. This transition will involve holistic approaches and multifaceted societal shifts, requiring answers and collaboration between private, public, and academic sectors. This book gathers together contributions which study the transition towards a more sustainable future, involving and identifying the development and implications of more sustainable alternatives, in collaboration with all relevant stakeholders (e.g. communities, firms, policy makers, researchers, etc.), to achieve this transition. The approaches proposed are all concerned with a common perspective: imaging our globe with a greener picture, built upon a transversal sustainable revolution to clean up the Earth

Energy Supply within Sustainable Agricultural Production: Challenges, Policies and Mechanisms

Providing the security of a broad-based energy and slowing the speed of climate change are the main challenges today of the basic of legal framework to stimulate the development of alternative energy sources. Energy from renewable sources is one part of the system, which not only enables to provide energy self-sufficiency, but also contributes to the reduction heating of the Earth’s atmosphere. International climate agreements indicate the need to intensify the prevention of global warming and accelerate the reduction in CO2 emissions. The implementation of such challenging plans as outlined in the European Green Deal or "Fit for 55," among others, entails the almost complete elimination of GHG emissions in the energy sector, which can be very challenging for some member states. In the EU, the preferred direction of development of RES use is distributed generation and increasing the share of the use of by-products and organic waste for the production biofuels. This creates great opportunities for rural areas, which until the last century were identified with agriculture and the production of food or raw materials. While the role of agriculture will not diminish, as incomes are rising in relatively poor countries with a high elasticity of demand for food, these areas will increasingly perform a number of other important functions as well. The production of energy raw materials and energy, which is no longer a mere idea, but is becoming, thanks to the development of new technologies, a mainstream energy sector that can make contribution to improving energy security and achieving climate neutrality