Advanced Course

Multiscale Computational Methods in Bioprocesses

Course description

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.

19-23 November 2018 (Delft, the Netherlands)

Delft University of Technology, the Netherlands

A limited number of fellowships is available for PhD students (reduced fee).

THE COURSE

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.

Lectures
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.

Course registration

Please register clicking the tab Register to attend the course. Deadline for application is 29 October 2018. 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

Programme for 2018:

Monday, 19 November 2018
Theme: Process scale (homogeneous)
08.45 Registration
09.00 Course introduction Henk Noorman
09.30 Black box model of microbes Sef Heijnen
10:30 Flow sheeting using black box models Adrie Straathof
12.00 Lunch
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, 20 November 2018
Theme: Fermentor – industrial scale
09.00 Time and length scales in the fermentor Sef Heijnen
10.oo Characteristics of large scale bioreactors (gradients) Henk Noorman
11.00 Structured kinetic models Sef Heijnen
12.00 Lunch
13.00 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, 21 November 2018
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
12.00 Lunch
13.00 Exercise: scale-down design using Fluent Cees Haringa
17.00 Scale-down in practice Ralf Takors
18.00 End of day
 
Thursday, 22 November 2018
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
12.00 Lunch
13.00 Exercises: modelling gradients and microbial growth using COMSOL Multiphysics Cristian Picioreanu
17.00 Tissue modeling Roeland Merks
19.00 Course dinner
 
Friday, 23 November 2018
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
12.00 Lunch
13.00 The impact of stochastics on cellular production systems Frank Bruggeman
14.00 Exercise: stochastic processes in cell biology Frank Bruggeman
15.00 Understanding and directing microbial cell populations Frank Delvinge
16.00 Closing of the course Henk Noorman
LOCATION

The course will be held at:

DSM Biotechnology Center  (part of Biotech Campus Delft)
Alexander Fleminglaan 1
2613 AX Delft
The Netherlands

Contact course organisation:

Department of Biotechnology
Delft University of Technology
Van der Maasweg 9
2629 HZ Delft
The Netherlands
P +31 (0)15 278 1922 / 8311
E BiotechDelft@tudelft.nl
W http://www.biotechnologycourses.nl/


FEE

The course fee is:

The course fee is € 2.500 in case of registration before 10 September 2018 or € 2.750 in case of registration after this date. In the event of cancellation before 24 September 2018, a full refund will be granted. After this date, a 25% fee charge will be made. To facilitate enrollment of young PhD-students from universities, a limited number of fellowships is available. The course fee with fellowship is € 1250. To apply, please include a copy of your registration as a PhD-student from your university.

The fee includes course materials, lunches, the buffet on Monday and the course dinner on Thursday. The fee does not cover other meals and lodging.

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.

Hotel accommodation can be arranged at your request addressed to BiotechDelft@tudelft.nl

The complete course book will be supplied at the start of the course.

Course fees can be paid by bank transfer or credit card (we are required to charge extra costs for this option; please contact us). TU Delft employees can use their internal (project) code. Customers are requested to pay the course fee within 30 days after the invoice date, but at the latest six weeks before the course starts. In case of payment before this date, the reduced course fee applies. After this date, we charge the full course fee. The course fees need to be on our bank account before the course starts.

DOWNLOADS
LECTURERS

Course board

Prof. Henk Noorman

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).

Robert Mudde

Multi-phase Flow, Delft University of Technology, Delft, the Netherlands

Cristian Picioreanu

Environmental Biotechnology, Delft University of Technology, Delft, the Netherlands

Adrie Straathof

Bioprocess Engineering, Delft University of Technology, Delft, the Netherlands

Guest lecturers

Frank Bruggeman

Systems Bioinformatics, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands

Frank Delvigne

Gembloux Agro-Bio Tech, University of Liège, Luik, Belgium

Cees Haringa

Senior Associate Scientist, DSM Biotechnology Center, Delft, the Netherlands

Sef Heijnen

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).

Roeland Merks

Mathematical Institute (MI), Leiden University, Leiden, the Netherlands
Centrum Wiskunde & Informatica (CWI), Amsterdam, the Netherlands

Matthias Reuss

Stuttgart Center Sytems Biology, Stuttgart, Germany

Ralf Takors

Institut für Bioverfahrenstechnik, University of Stuttgart, Germany

Peter J.T. Verheijen

Department of Biotechnology, Delft University of Technology, Delft, The Netherlands

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