Advanced Course

Downstream Processing

Course description

The challenge for biochemical engineers is to design compact and clean processes to efficiently separate instable products, such as recombinant proteins, from dilute complex fermentation broths to the required pharmaceutical degree of purity. Therefore, the quantitative systematic design of integrated downstream processes is the general theme of this Advanced Course. The aim of the course is to provide the tools for the participants to be able to quantitatively and systematically design an integrated downstream process. This course was held for the 27th time in 2016.

2-6 July 2018

Delft University of Technology, the Netherlands

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


Advanced Course Downstream Processing

This intensive course consists of theoretical and applied lectures, exercises, case studies and computer simulations. The course will be given in English. A laptop and pocket calculator is required.

The course presents the state of the art in downstream processing of biotechnological products. It provides knowledge of different techniques for solid-liquid separation, product release, refolding, concentration and purification of precious biotechnology products with a focus on the total integrated process. An international group of experts from both industry and academia will lecture to assure an optimal balance of practical knowledge and theoretical insight, which subsequently will be trained by exercises, into the quantitative engineering aspects of bioseparations. At the end of the course, the participants should be able to estimate main equipment dimensions, know qualitative constraints to the integrated bioprocess and have a quantitative insight in process streams, structure and economics.

The course starts with an overview of possibilities and problems typically associated with the recovery of bioproducts. Physico-chemical characteristics of the products, as well as the fermentation broth with its multiple contaminants, are discussed in relation to possibilities for selective separation. Using this information, the general structure of large scale industrial processes will be outlined.

The thermodynamical basics and biochemical engineering principles will be introduced and developed during the course related to bio-separations. Special attention will be paid to the unit operations typically used in this field of industry. Firstly, various solid-liquid separation techniques and cell disruption will be treated. Particular consideration will be given to the application of major concentration techniques such as extraction, adsorption and membrane separation. Furthermore, the scientific and industrial aspects of purification by means of precipitation and chromatography will be discussed. In addition, the release of intracellular products as well as protein folding in industrial protein processes will be discussed.

Process integration is the binding element in the course. During the course, a case study on the design of an integrated purification process for a recombinant protein will offer the participants the opportunity to practice on the individual unit operations as well as on the integrated process. Finally, possibilities of computer-aided, rational design of integrated separation processes will be demonstrated.

Who should attend?

This Advanced Course is aimed at professionals (MSc or PhD level is required) in (bio)chemical engineering, or in microbiology or biochemistry with a basic knowledge in chemical engineering. The course is primarily aimed at those already employed in industry and who are interested in the separation of biotechnological products. In addition, this Advanced Course is an option in the two-year postgraduate programs of Delft University of Technology.


Monday 3 July 2017
Theme: Today’s bioseparation processes.
Mechanical separations: solid-liquid separation

08:45   Registration
09:00   Introduction to the separation processes
Pitfalls and challenges in bioseparation processes
            Luuk van der Wielen
10:00   Engineering fundamentals
Mass balances: from batch to continuous counter current processes
            Luuk van der Wielen
11:15   Case study: industrial protein production (I)
Marcel Ottens and Exercise Assistances
12.30   Lunch
13:30   Solid-liquid separation: filtration and centrifugation
            Marcel Ottens
14:15   Assignment: design of filtration equipment
15:15   Predicting molecular properties. Molecular properties and selection of separation conditions:    Equilibrium calculations
            Luuk van der Wielen
16:15   Case study: industrial protein production (II)
18:00   Social drink and buffet

Tuesday 4 July 2017
Theme: Mechanical separations: solid liquid separation. Concentration and design

09:00   Centrifugation in the biopharmaceutical industry
Design considerations of sedimentation and centrifugation processes: from biomass removal to centrifugal extraction
            Joe Shultz
10:30   Assignment: centrifugation
11:30   Extractive separation: Solvent selection and equipment design in extraction processes
            Marcel Ottens
12.30   Lunch
13:30   Assignment: extraction
14:30   Membrane technology: theory, design & industrial application
            Reinoud Noordman
13:30   Assignment: membrane separation
14:30   Case study: industrial protein production (III)
18:00   End of the day

Wednesday 5 July 2017
Theme: Purification processes

09:00   Design of chromatographic separations. Equilibrium theory and column design: Non-linear and mass transfer effects
            Marcel Ottens
10:15   Chromatography in industrial practice
            Jan-Christer Janson
11:45   Industrial cases and applications of chromatography
Column design and operation from theory and practice
            Jeroen den Hollander 
12.30   Lunch
14:00   Assignment: chromatography
15:15   Quality by Design
            Danielle Horneman
16:30   Case study: industrial protein production (IV)
17:45   End of the day
18:00  Lab tour: High Throughput facilities (optional)

Thursday 6 July 2017
Theme: Purification & formulation processes

9:00     Continuous chromatography and Simulated Moving Bed (SMB) Technology: Practical aspects and implementation for large scale chromatography in industry
            Marc Bisschops
10:15   Bulk crystallization: Unit operation design for the crystallization of small and large biomolecules
            Geert-Jan Witkamp
11:30   Assignment: crystallization
12.15   Lunch
13:15   Industrial crystallization: Real life examples
            Rob Geertman
14:45   The use of continuous operations to enable next generation production economics
            Joe Shultz 
16:00   Design of an industrial process for purification of biologicals
            Michel Eppink
17:15   Case study: industrial protein production (V)
18:15   End of the day
19:00   Course dinner

Friday 7 July 2017
Theme: Process development & process integration

9:00     Rational methodology for protein purification
            Beckley Nfor
10:15   High Throughput techniques in downstream process
            Jürgen Hubbuch
11:30   Process integration in industry
            Matthias Wiendahl
12.15   Lunch
14:15   Case study: industrial protein production (VI)
Presentations of the three winning teams: the strategy DSP award ceremony
14:45   Evaluation of the course
15:00   Farewell drinks


The course will be held at:

Faculty of Applied Sciences (building 58)
Department of Biotechnology
Delft University of Technology
Van der Maasweg 9
2629 HZ Delft
The Netherlands
P +31 (0)15 278 1922
F +31 (0)15 278 2355


The course fee is:

Early bird fee: € 2750 in case of payment received before 22 May 2017 or
Regular fee: € 3000 in case of payment received on or after this date.

To facilitate enrolment of PhD-students, a limited number of fellowships are available. The course fee with fellowship is € 1375. To apply, please include a copy of your registration as a PhD-student at your university. The course fee includes course materials, lunches, the buffet on Monday and the course dinner on Thursday. The fee does not cover other meals and lodging.

In the event of your cancellation before 22 May 2017, a full refund will be granted, after this date, a 25% fee charge will be made. When the number of participants is too low to have a fruitful course, 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 directly at

Preparatory texts will be sent after receipt of the course fee. 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.


Course board

Luuk van der Wielen – Full professor

Luuk van der Wielen is distinguished Professor for Biobased Economy as well as full professor and group leader Bioprocess Engineering at the Department of Biotechnology of TU Delft. The activities of the section resulted in several spin-off companies. His research interests include thermodynamics for bioprocesses, bioseparation/-conversion technologies, multifunctional bioreactors and miniaturized (‘on-chip’), high throughput technology for rapid process development, as well as analysis and development of large scale and distributed, low carbon biorenewables production systems, and their societal impacts. Since 2004 he is director of BE-BASIC (, the globally operating private-public research organisation for Biobased Sustainable Industrial Chemistry & Energy, which is based in The Netherlands with hubs in South East Asia and Brazil. He was and is coordinator of several leading (inter)national programs on biobased innovation and member of many committees in this field, including on green technology investments. He is one of the initiators of the successful academic program on Life Science & Technology of Leiden University and TU Delft, and director of the postgraduate program Bioprocess Design.

Marcel Ottens

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


Marc Bisschops

Pall Europe, Medemblik, the Netherlands

Michel Eppink

Synthon BV, Nijmegen, the Netherlands

Rob Geertman

DSM Fibre Intermediates BV, Geleen, the Netherlands

Jeroen den Hollander

DSM Biotechnology Center, Delft, the Netherlands

Danielle Horneman

Bataviabiosciences, Leiden, the Netherlands

Jürgen Hubbuch

Karlsruhe Universität (TH), Karlsruhe, Germany

Jan-Christer Janson

Uppsala Biomedical Centre, Department of Surface Biotechnology, Uppsala, Sweden

Beckley Kungah Nfor

Beckley Kungah Nfor finished his BSc in Biochemistry at the University of Buea (Cameroon). After that, he moved to Delft University of Technology, where he completed his MSc, PDEng and PhD degrees, and subsequently did a postdoc. Dr. Kungah Nfor has published several peer-reviewed journal papers and a book chapter on protein purification process development. In his current role as Scientist at Crucell Holland B.V., he focuses on a variety of activities including Early Stage Vaccine Process Development, Technology Transfer and Process Characterization. His main research interests are biopharmaceutical process development, downstream processing, process modeling, quality by design.

Reinoud Noordman

Pentiar X-Flow, Enschede, the Netherlands

Joe Shultz

Novartis, Basel, Switzerland

Matthias Wiendahl

NOVO Nordisk A/S, Gentofte, Denmark

Geert-Jan Witkamp

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

Exercises Assistance

Silvia Pirrung, MSc

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

Marcelo Silva, MSc

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

Debora Gernat, MSc

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

Victor Koppejan, MSc

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


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