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Operator training in recombinant protein production using a structured simulator model
Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology. University of Applied Sciences, Bremen, Germany.
University of Applied Sciences, Bremen, Germany .
Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
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2014 (English)In: Journal of Biotechnology, ISSN 0168-1656, E-ISSN 1873-4863, Vol. 177, 53-59 p.Article in journal (Refereed) Published
Abstract [en]

Model-based operator training simulators ( OTS) could be powerful tools for virtual training of operational procedures and skills of production personnel in recombinant protein processes. The applied model should describe critical events in the bioprocess so accurately that the operators ability to observe and alertly act upon these events is trained with a high degree of efficiency. In this work is shown how this is accomplished in a structured multi-compartment model for the production of a recombinant protein in an Escherichia coli fed-batch process where in particular the induction procedure, the stress effects and overflow metabolism were highlighted. The structured model was applied on the OTS platform that virtually simulated the operational bioreactor procedures in real or accelerated time. Evaluation of training using the model-based OTS showed that trained groups of operators exhibited improved capability compared with the untrained groups when subsequently performing real laboratory scale cultivations. The results suggest that this model-based OTS may provide a valuable resource for enhancing operator skills in large scale recombinant protein manufacturing.

Place, publisher, year, edition, pages
Elsevier , 2014. Vol. 177, 53-59 p.
Keyword [en]
Training simulator; Recombinant protein production; Cultivation; Modelling
National Category
Bioprocess Technology
URN: urn:nbn:se:liu:diva-106511DOI: 10.1016/j.jbiotec.2014.02.022ISI: 000333811200007ScopusID: 2-s2.0-84896536648OAI: diva2:716652
Available from: 2014-05-12 Created: 2014-05-09 Last updated: 2015-09-21Bibliographically approved
In thesis
1. Operator Training Simulators towards Industrial Biotechnology
Open this publication in new window or tab >>Operator Training Simulators towards Industrial Biotechnology
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Biotechnological processes are carried out by applying advanced and demanding process strategies. Thus, fundamental understanding and knowledge about the applied microorganism is required to achieve high productivity and profitability. Therefore, computer-based simulation has been integrated into training methodologies for supplementing and expanding academic education and industrial operator training, in order to provide more effective as well as cost- and time-efficient training.

Operator training simulators (OTS) are computer-based training tools that represent the real laboratory or plant within an interactive, virtual environment. Trainees can learn about cause-and-effect relationships during the virtual process to improve process understanding. Also, trainees and operators get the opportunity to develop, maintain and improve their operational skills. The virtual environment allows delayed operational actions and operational faults, as they are not interfering with the real process. Acceleration of the simulation speed makes training more effective. For instance, different procedures such as start-up and shut-down can be trained in a limited period of training time. Incident and trouble-shooting training can be realized in a safe, virtual environment without exposing the operator to potential risks. So far, OTS are mainly used in military, aviation, medicine and chemical industries. However, there are only a few examples where OTS are applied in biotechnological process applications.

The aim of this thesis is to expose the benefits of using OTS for biotechnological process applications in academic education and industrial operator training. For this purpose, the feasibility of developing and applying OTS was investigated and discussed. Three OTS for the production of bio-ethanol and recombinant protein production were developed in order to investigate the benefits and their requirements as well as to assess the training effectiveness of these. To visualize the technical system including equipment and distributed control system (DCS), graphical user interfaces (GUIs) were designed, allowing the user to interact with the simulator. Mathematical models were developed and implemented in the OTS to ensure dynamic simulation of the process, where cause-and-effect relationships are realistically described. The essential part of an OTS for biotechnological process applications is the embedded sub-model which describes the biological production system. It is important that the cell growth behaviour within a bioreactor can be  simulated with sufficient accuracy in order to ensure high training effectiveness.

In the assessment of the training effectiveness in academic education, it was observed that the students’ capability of understanding and controlling complex biotechnological processes improved after OTS training. Students showed better performance in laboratory experiments after participating in OTS pre-training. Moreover, the development of an OTS for an industrial, large-scale bio-ethanol plant illuminates the needs of OTS in biotechnological process industries. It was shown how the conceptual design methodology can be applied in designing an OTS, based on training needs from the industrial user perspective. Also, construction of the OTS including the formulation of mathematical models, the model structure which is embedded in the OTS and the design of the GUIs is covered in this thesis. Whether the use of the OTS will become cost-effective and assure maximum transfer of training depends on long term evaluation. However, application and evaluation of the developed OTS reveal the benefits and training effectiveness of these systems. The findings of the thesis might considerably facilitate the introduction of OTS into academic education and industrial operator training for biotechnological process applications.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. 43 p.
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1683
National Category
Bioprocess Technology
urn:nbn:se:liu:diva-121476 (URN)978-91-7519-031-0 (print) (ISBN)
Public defence
2015-10-15, Planck, Fysikhuset, Campus Valla, Linköping, 14:00 (English)
Available from: 2015-09-21 Created: 2015-09-21 Last updated: 2015-10-13Bibliographically approved

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