Development of soft sensors for monitoring and control of bioprocesses


Book Description

In the manufacture of bio-therapeutics the importance of a well-known process is key for a high product titer and low batch to batch variations. Soft sensors are based on the concept that online sensor signals can be used as inputs to mathematical models to derive new valuable process information. This information could then be used for better monitoring and control of the bioprocess. The aim of the present thesis has been to develop soft sensor solutions for upstream bioprocessing and demonstrate their usefulness in improving robustness and increase the batch-to-batch reproducibility in bioprocesses. The thesis reviews the potential and possibilities with soft sensors for use in production of bio-therapeutics to realize FDA´s process analytical technology (PAT) initiative. Modelling and hardware sensor alternatives which could be used in a soft sensor setup are described and critically analyzed. Different soft sensor approaches to control glucose feeding in fed-batch cultures of Escherichia coli are described. Measurements of metabolic fluxes and specific carbon dioxide production was used as control parameters to increase product yield and decrease the variability of produced recombinant proteins. Metabolic heat signals were used in uninduced cultures to estimate and control the specific growth rate at a desired level and thereby also estimate the biomass concentration online. The introduction of sequential filtering of the signal enabled this method to be used in a down-scaled system. The risk and high impact of contaminations in cell cultures are also described. An in situ microscope (ISM) was used as an online tool to estimate cell concentration and also to determine cell diameter size which enabled the detection of contaminant cells at an early stage. The work presented in this thesis supports the idea that soft sensors can be a useful tool in the strive towards robust and reliable bioprocesses, to ensure high product quality and increased economic profit.




Soft Sensors for Monitoring and Control of Industrial Processes


Book Description

This book reviews current design paths for soft sensors, and guides readers in evaluating different choices. The book presents case studies resulting from collaborations between the authors and industrial partners. The solutions presented, some of which are implemented on-line in industrial plants, are designed to cope with a wide range of applications from measuring system backup and what-if analysis through real-time prediction for plant control to sensor diagnosis and validation.




Computational Intelligence Techniques for Bioprocess Modelling, Supervision and Control


Book Description

Computational Intelligence (CI) and Bioprocess are well-established research areas which have much to offer each other. Under the perspective of the CI area, Biop- cess can be considered a vast application area with a growing number of complex and challenging tasks to be dealt with, whose solutions can contribute to boosting the development of new intelligent techniques as well as to help the refinement and s- cialization of many of the already existing techniques. Under the perspective of the Bioprocess area, CI can be considered a useful repertoire of theories, methods and techniques that can contribute and offer interesting alternative approaches for solving many of its problems, particularly those hard to solve using conventional techniques. Although throughout the past years CI and Bioprocess areas have accumulated substantial specific knowledge and progress has been quick and with a high degree of success, we believe there is still a long way to go in order to use the potentialities of the available CI techniques and knowledge at their full extent, as tools for supporting problem solving in bioprocesses. One of the reasons is the fact that both areas have progressed steadily and have been continuously accumulating and refining specific knowledge; another reason is the high level of technical expertise demanded by each of them. The acquisition of technical skills, experience and good insights in either of the two areas is very demanding and a hard task to be accomplished by any professional.




Bioprocessing Technology for Production of Biopharmaceuticals and Bioproducts


Book Description

Written for industrial and academic researchers and development scientists in the life sciences industry, Bioprocessing Technology for Production of Biopharmaceuticals and Bioproducts is a guide to the tools, approaches, and useful developments in bioprocessing. This important guide: • Summarizes state-of-the-art bioprocessing methods and reviews applications in life science industries • Includes illustrative case studies that review six milestone bio-products • Discuses a wide selection of host strain types and disruptive bioprocess technologies




Bioprocess Monitoring and Control


Book Description

Process monitoring and control are fundamental to all processes; this holds especially for bioprocesses, due to their complex nature. Usually, bioprocesses deal with living cells, which have their own regulatory systems. It helps to adjust the cell to its environmental condition. This must not be the optimal condition that the cell needs to produce whatever is desired. Therefore, a close monitoring of the cell and its environment is essential to provide optimal conditions for production. Without measurement, no information of the current process state is obtained. In this book, methods and techniques are provided for the monitoring and control of bioprocesses. From new developments for sensors, the application of spectroscopy and modelling approaches, the estimation and observer implementation for ethanol production and the development and scale-up of various bioprocesses and their closed loop control information are presented. The processes discussed here are very diverse. The major applications are cultivation processes, where microorganisms were grown, but also an incubation process of bird's eggs, as well as an indoor climate control for humans, will be discussed. Altogether, in 12 chapters, nine original research papers and three reviews are presented.




Process Control, Intensification, and Digitalisation in Continuous Biomanufacturing


Book Description

Process Control, Intensification, and Digitalisation in Continuous Biomanufacturing Explore new trends in continuous biomanufacturing with contributions from leading practitioners in the field With the increasingly widespread acceptance and investment in the ??technology, the last decade has demonstrated the utility of continuous ??processing in the pharmaceutical industry. In Process Control, Intensification, and Digitalisation in Continuous Biomanufacturing, distinguished biotechnologist Dr. Ganapathy Subramanian delivers a comprehensive exploration of the potential of the continuous processing of biological products and discussions of future directions in advancing continuous processing to meet new challenges and demands in the manufacture of therapeutic products. A stand-alone follow-up to the editor’s Continuous Biomanufacturing: Innovative Technologies and Methods published in 2017, this new edited volume focuses on critical aspects of process intensification, process control, and the digital transformation of biopharmaceutical processes. In addition to topics like the use of multivariant data analysis, regulatory concerns, and automation processes, the book also includes: Thorough introductions to capacitance sensors to control feeding strategies and the continuous production of viral vaccines Comprehensive explorations of strategies for the continuous upstream processing of induced microbial systems Practical discussions of preparative hydrophobic interaction chromatography and the design of modern protein-A-resins for continuous biomanufacturing In-depth examinations of bioprocess intensification approaches and the benefits of single use for process intensification Perfect for biotechnologists, bioengineers, pharmaceutical engineers, and process engineers, Process Control, Intensification, and Digitalisation in Continuous Biomanufacturing is also an indispensable resource for chemical engineers seeking a one-stop reference on continuous biomanufacturing.




Industrial Scale Suspension Culture of Living Cells


Book Description

The submersed cultivation of organisms in sterile containments or fermenters has become the standard manufacturing procedure, and will remain the gold standard for some time to come. This book thus addresses submersed cell culture and fermentation and its importance for the manufacturing industry. It goes beyond expression systems and integrally investigates all those factors relevant for manufacturing using suspension cultures. In so doing, the contributions cover all industrial cultivation methods in a comprehensive and comparative manner, with most of the authors coming from the industry itself. Depending on the maturity of the technology, the chapters address in turn the expression system, basic process design, key factors affecting process economics, plant and bioreactor design, and regulatory aspects.




Current Developments in Biotechnology and Bioengineering


Book Description

Current Developments in Biotechnology and Bioengineering: Bioprocesses, Bioreactors and Controls provides extensive coverage of new developments, state-of-the-art technologies, and potential future trends, reviewing industrial biotechnology and bioengineering practices that facilitate and enhance the transition of processes from lab to plant scale, which is becoming increasingly important as such transitions continue to grow in frequency. Focusing on industrial bioprocesses, bioreactors for bioprocesses, and controls for bioprocesses, this title reviews industrial practice to identify bottlenecks and propose solutions, highlighting that the optimal control of a bioprocess involves not only maximization of product yield, but also taking into account parameters such as quality assurance and environmental aspects. - Describes industrial bioprocesses based on the reaction media - Lists the type of bioreactors used for a specific bioprocess/application - Outlines the principles of control systems in various bioprocesses




Control in Bioprocessing


Book Description

Closes the gap between bioscience and mathematics-based process engineering This book presents the most commonly employed approaches in the control of bioprocesses. It discusses the role that control theory plays in understanding the mechanisms of cellular and metabolic processes, and presents key results in various fields such as dynamic modeling, dynamic properties of bioprocess models, software sensors designed for the online estimation of parameters and state variables, and control and supervision of bioprocesses Control in Bioengineering and Bioprocessing: Modeling, Estimation and the Use of Sensors is divided into three sections. Part I, Mathematical preliminaries and overview of the control and monitoring of bioprocess, provides a general overview of the control and monitoring of bioprocesses, and introduces the mathematical framework necessary for the analysis and characterization of bioprocess dynamics. Part II, Observability and control concepts, presents the observability concepts which form the basis of design online estimation algorithms (software sensor) for bioprocesses, and reviews controllability of these concepts, including automatic feedback control systems. Part III, Software sensors and observer-based control schemes for bioprocesses, features six application cases including dynamic behavior of 3-dimensional continuous bioreactors; observability analysis applied to 2D and 3D bioreactors with inhibitory and non-inhibitory models; and regulation of a continuously stirred bioreactor via modeling error compensation. Applicable across all areas of bioprocess engineering, including food and beverages, biofuels and renewable energy, pharmaceuticals and nutraceuticals, fermentation systems, product separation technologies, wastewater and solid-waste treatment technology, and bioremediation Provides a clear explanation of the mass-balance–based mathematical modelling of bioprocesses and the main tools for its dynamic analysis Offers industry-based applications on: myco-diesel for implementing "quality" of observability; developing a virtual sensor based on the Just-In-Time Model to monitor biological control systems; and virtual sensor design for state estimation in a photocatalytic bioreactor for hydrogen production Control in Bioengineering and Bioprocessing is intended as a foundational text for graduate level students in bioengineering, as well as a reference text for researchers, engineers, and other practitioners interested in the field of estimation and control of bioprocesses.




Towards Green Hydrogen Generation


Book Description

Readers will find a multidisciplinary approach elucidating all the important features of green hydrogen so that science researchers and energy engineers as well as those in economics, political science and international relations, will also find value. Energy sources and generation is the foremost concern of all governments, NGOs, and activist groups. With Green New Deals and reduced or net zero emission goals being implemented on a global scale, the quest for economic, scalable, efficient, and sustainable energy systems has reached a fever pitch. No one energy source ticks all the boxes and new energy technologies are being developed all the time as potential disruptors. Enter green hydrogen with zero emissions. Hydrogen is a rare gas in nature and is often found together with natural gas. While hydrogen is the most abundant element in the known universe, molecular hydrogen is very rare in nature and needs to be produced—and produced in large quantities, if we are serious about the Green Deal. This book has been organized into three parts to introduce and discuss these crucial topics. Part I discusses the Green Deal and the current state and challenges encountered in the industrialization of green hydrogen production, as well as related politics. Chapters in this section include how to decarbonize the energy industry with green hydrogen, and one that describes a gradual shift in the approach of hydrogen production technologies from non-renewable to renewable. Part II is devoted to carbon capturing and hydrogen. Chapters on biomass mass waste-to-hydrogen conversion and related efficient and sustainable hydrogen storage pathways, life cycle assessment for eco-design of biohydrogen factory by microalgae, and metal oxide-based carbon capture technologies are all addressed in this section. The third and final part of the book was designed to present all features of green hydrogen generation. Chapters include PEM water electrolysis and other electrolyzers, wind-driven hydrogen production, and bifunctional electrocatalysts-driven hybrid water splitting, are introduced and thoroughly discussed. Audience This book is directed to researchers and industry professionals in energy engineering, chemistry, physics, materials science, and chemical engineering, as well as energy policymakers, energy economists, and others in the social sciences.




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