Development Of Soft Sensors For Monitoring And Control Of Bioprocesses
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Development of soft sensors for monitoring and control of bioprocesses
Author: Robert Gustavsson
language: en
Publisher: Linköping University Electronic Press
Release Date: 2018-10-31
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.
Bioprocess Monitoring and Control
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.
Computational Intelligence Techniques for Bioprocess Modelling, Supervision and Control
Author: Maria Carmo Nicoletti
language: en
Publisher: Springer Science & Business Media
Release Date: 2009-06-29
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.