This course brings together contributions from different disciplines, i.e. bioprocess technology, applied physics, transport phenomena, molecular biology and biomedical sciences. They all address different elements on the coupling between several time and length scales in the simulation of different bioprocesses (e.g. bioreactor and bioprocess operation, microbial strain improvement, tissue and organ cultivation, plant design and integration). Computational methods will deepen the understanding of the connecting principles between different scales. The industrial relevance is underlined by the venue being the Biotech Campus Delft.
The idea of this course is to move from large-scale industrial bioprocesses (hectometers/days) down to the intracellular level (nanometers/microseconds), through several intermediate scales. These intermediate scales describe details inside the bioreactor (meters/hours) and in multicellular aggregates, as e.g. appearing in biofilms or tissues (millimeters/seconds). Top-down approaches allow answering particular questions in a natural way: a quantitative understanding at a higher level will – due to progressing insight or new requirements – be enhanced by details revealed by smaller scales approaches. A higher resolution description of the system will require a greater experimental effort to identify mechanisms and parameter values, together with considerably larger computational expenses. With the material presented in the course, the participants will better grasp the complexity of multileveled systems based on the underlying mechanisms. The increasing power of computational methods and hardware drastically reduces the need for simplification and thereby enhances the predictive capabilities of numerical models and our level of process understanding. This trend is expected to further develop at high pace in the coming years.
Advanced Course Multiscale Computational Methods in Bioprocesses
This intensive one-week course aims at active participation by those attending. A combination of theoretical (lectures) and practical (exercises, case study) work is offered. The course is build up around a few currently relevant biotechnological systems (e.g., lactic acid fermentations, antibiotic production, aerobic/anaerobic processes). Applications will be demonstrated with numerical models at all relevant scales, from factory and bioreactor to cell aggregate and intracellular processes, Particular emphasis will be on the identification of mechanisms and parameters, as well as on integration of scales to maximize complete system insight.
The lectures are mainly scheduled in the mornings and late afternoons and will focus on the following themes:
• Industrial bioprocess design, integration and flowsheeting
• Gradients (concentration, shear rate, temperature) in bioreactors coupled to dynamic microbial response and compartmented kinetic models
• Industrial fermentation models with computational fluid dynamics and reaction dynamics by Euler-Lagrange approach and cell lifelines
• Micro-gradients in multicellular aggregates (biofilms, granules, tissues)
• Single-cell models including membrane transport, metabolic variation, intracellular dynamics and genetic diversity
Exercises and case study
The theory presented in lectures will be applied in exercises in the afternoon sessions. The participants will receive hands-on experience with state-of-the-art computational tools implemented in Ansys/Fluent, Comsol Multiphysics and MATLAB.
Who should attend?
The course is primarily aimed at academic and industrial specialists (MSc, PhD or equivalent experience) who seek broadening their knowledge and practical skills in multiscale modelling. Educational background in transport phenomena, basic reaction engineering and biotechnology is strongly advised. Affinity with biological systems is recommended.
Preparatory materials will be provided to help participants reaching the basic prerequisite knowledge for this course.
Please register clicking the tab Register to attend the course. Deadline for application is 29 October 2019. Applicants will be handled in order of the date of receipt. There is a maximum of participants for this course. We will inform you within two weeks if participation is possible.
Programme for 2019:
|Monday, 18 November 2019
Theme: Process scale (homogeneous)
|08.45||Introductions and welcome||Caroline Villa-Sanin and Vincent Renken|
|09.15||Course introduction||Henk Noorman|
|09.30||Black box model of microbes||Sef Heijnen|
|10:30||Flow sheeting using black box models||Adrie Straathof|
|13.00||Exercise: plant/full process simulation using SuperPro Designer||Adrie Straathof|
|16.30||Overview of modeling techniques in biotechnology||Peter Verheijen|
|17.30||Social drink and buffet|
|Tuesday, 19 November 2019
Theme: Fermentor – industrial scale
|09.00||Time and length scales in the fermentor||Sef Heijnen|
|10.00||Characteristics of large scale bioreactors (gradients)||Henk Noorman|
|11.00||Structured kinetic models||Sef Heijnen|
|13.00||Exercise on Time & Length scales||Cees Haringa|
|13.30||Flow and reaction modeling/computation||Cees Haringa|
|14.00||Exercise: fermentor computation using Fluent||Cees Haringa|
|17.00||A tale about the history of large bioreactor modeling||Matthias Reuss|
|18.00||End of day|
|Wednesday, 20 November 2019
Theme: Fermentor scale-down – lab scale
|09.00||Use of computational models to design scale-down simulators||Cees Haringa|
|11.00||Observability of in vivo kinetic models||Sef Heijnen|
|13.00||Exercise: scale-down design using Fluent||Cees Haringa|
|17.00||Scale-down in practice||Ralf Takors|
|18.00||End of day|
|Thursday, 21 November 2019
Theme: Aggregate scale
|09.00||Multiscale modeling of tumour growth linking subcellular, cellular, tissue and organ level||Matthias Reuss|
|10.00||Models for cell aggregates||Cristian Picioreanu|
|13.00||Exercises: modelling gradients and microbial growth using COMSOL Multiphysics||Cristian Picioreanu|
|17.00||Tissue modeling||Roeland Merks|
|Friday, 22 November 2019
Theme: Single cell/molecule scale
|09.00||Molecular Systems Biology: cell dimensions, molecule numbers, time scales, diffusion issues||Frank Bruggeman|
|10.00||Defining and solving the master equation||Frank Bruggeman|
|10.30||Exercise: the Gillespie algorithm using Matlab||Frank Bruggeman|
|11.30||Euler-Lagrange/Agent-based cell population modeling||Cees Haringa|
|12.30||The impact of stochastics on cellular production systems||Frank Bruggeman|
|13.45||Exercise: stochastic processes in cell biology||Frank Bruggeman|
|14.15||Moddels, software, methods and outlook (plenary discussion)||Henk Noorman|
|15.00||Understanding and directing microbial cell populations||Frank Delvinge|
|16.00||Closing of the course||Henk Noorman|
The course will be held at:
DSM Biotechnology Center (part of Biotech Campus Delft)
Alexander Fleminglaan 1
2613 AX Delft
Contact course organisation:
Deadline for registration is 4 Noverber 2019.
The course fee is:
*To be eligible for the reduced early bird fee you need to register before 9th of September 2019. If this date is exceeded, the regular fee applies.
**A limited number of fellowships is available for PhD students. To apply, please include a copy of your registration as a PhD student from your university.
The fee includes course materials, lunches and the buffets and the course dinners as indicated on the program. The fee does not cover other meals or lodging. Hotel accommodation can be arranged at your request.
The course fee is preferably paid by bank transfer. Payment by PayPal is possible. TU Delft employees can use their internal (project) code.
Preparatory texts will be sent one month before start of the course and after receipt of the course fee. The complete set of course books will be supplied at the start of the course.
In the event of your cancellation before 23 September 2019, a full refund will be granted. After this date, a 25% fee charge can be made.
Delay of payment past the final deadline as indicated on the invoice may result in cancellation of entry to the course. Re-entry is only possible in case of vacancies and the regular fee will be applied. Payment terms and deadlines will be indicated on the invoice and/or provided in an e-mail after registration, but the course fee should always be paid before the start of the course.
When the number of participants is too low to have a fruitful course, the Institute BioTech Delft will cancel the event no later than six weeks before the start of the course. The course fee will be reimbursed within three weeks after cancellation. In case a speaker will not be able to present his/her lecture, due to unforeseen circumstances, BioTech Delft will arrange an equivalent replacement.
Henk Noorman was trained as Chemical Engineer from Groningen University (NL). He obtained a PhD in Bioprocess Technology from Delft University of Technology (NL, 1991), on microbal systems modeling. He became a post-doc fellow in a Nordic research consortium, and co-ordinated a fermentation scale-up project among academic groups in Sweden, Denmark and Norway. He then joined Gist-brocades and DSM in Delft (NL) and worked on fermentation development and implementation projects, mainly in the area of antibiotics and bio-based products. He also has been project manager for innovation projects, and received the DSM R&D Award 2010. Henk Noorman is currently working as Senior Science Fellow Bioprocess Technology in the DSM Biotechnology Center and involved in numerous projects in Industrial Biotechnology, Food Specialties, Anti-Infectives, and the Corporate Research Program. In addition he is honorary professor at Technical University Delft working on Bioprocess Design and Integration. Teaching activities include courses in Delft, Wageningen (NL), Brac (Croatia) and Shanghai (China).
Environmental Biotechnology, Delft University of Technology, Delft, the Netherlands
Bioprocess Engineering, Delft University of Technology, Delft, the Netherlands
Systems Bioinformatics, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
Gembloux Agro-Bio Tech, University of Liège, Luik, Belgium
Senior Associate Scientist, DSM Biotechnology Center, Delft, the Netherlands
After his MSc studies in Chemical Engineering, Sef Heijnen worked at DSM (then: Gist Brocades) for 15 years and in this period he also completed his PhD thesis in bioprocess technology at Delft University of Technology. In 1988, he became full professor and group leader in Cell Systems Engineering within the Department of Biotechnology of Delft University of Technology. He has an impressive track record: he is (co-) author of over 400 scientific publications, has supervised nearly 60 PhD students and is a member of the Royal Netherlands Academy of Arts and Sciences (KNAW). He is recipient of several science and education awards. His research interests are (1) metabolic engineering and systems biology applied to industrial microbial processes using Saccharomyces cerevisiae, Penicillium chrysogenum and Escherichia coli, (2) metabolome measurement and 13C-tracer analysis in steady state and dynamic conditions, and (3) thermodynamic and kinetic modelling of metabolism, fermentation design and scale-up and scale down of industrial processes. Prof. Heijnen teaches a wide variety of courses, and was elected at TU Delft’s 2003 ‘Leermeester’ (best lecturer).
Mathematical Institute (MI), Leiden University, Leiden, the Netherlands
Centrum Wiskunde & Informatica (CWI), Amsterdam, the Netherlands
Stuttgart Center Sytems Biology, Stuttgart, Germany
Institut für Bioverfahrenstechnik, University of Stuttgart, Germany
Department of Biotechnology, Delft University of Technology, Delft, The Netherlands