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 (FULLY BOOKED)

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.

Study load

The course (including preparatory materials) is valued 41 hours of work.

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 2 july 2018
Theme: Today’s bioseparation processes. Mechanical separations: solid-liquid separation
08:30 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 Assistants
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 3 july 2018
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
Alex Hanke
10:30 Assignment: centrifugation
Marcel Ottens and Exercise Assistants
11:30 Extractive separation: Solvent selection and equipment design in extraction processes
Marcel Ottens
12.30 Lunch
13:30 Assignment: extraction
Marcel Ottens and Exercise Assistants
14:30 Membrane technology: theory, design & industrial application
Reinoud Noordman
16:00 Case study: industrial protein production (III)
Marcel Ottens and Exercise Assistants
18:00 Lab tour: High Throughput Facilities
18:30 End of day

Wednesday 4 july 2018
Theme: Purification processes
09:00 Design of chromatographic separations. Equilibrium theory and column design: Non- linear and mass transfer effects
Marcel Ottens
10:15 Assignment: ultrafiltration
Marcel Ottens and Exercise Assistants
11:15 Large-scale Continuous Chromatography and
Simulated Moving Bed (SMB) technology for biotechnological products Assistants
Marc Bisschops
12.30 Lunch
13:30 Industrial cases and applications of chromatography
Column design and operation from theory and practice
Jeroen den Hollander
14.15 Assignment: chromatography
Marcel Ottens and Exercise Assistants
15:45 Quality by Design
Danielle Horneman
17:00 Case study: industrial protein production (IV)
Marcel Ottens and Exercise Assistants
18:00 End of the day

Thursday 5 july 2018
Theme: Purification & formulation processes
9:00 Bulk crystallization: Unit operation design for the crystallization of small and large biomolecules
Geert-Jan Witkamp
10:15 Assignment: crystallization
Marcel Ottens and Exercise Assistants
11:30 Industrial crystallization: Real life examples
Rob Geertman
12.15 Lunch
13:15 Inclusion Body processing
Michel Eppink
14:45 Design of an industrial process for purification of biologicals
Michel Eppink
16:00 Case study: industrial protein production (V)
Process design: sequencing and interfacing of unit operations
Marcel Ottens and Exercise Assistants
18:00 End of the day
19:00 Course dinner

Friday 6 july 2018
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
12.30 Lunch
13:30 Case study: industrial protein production (VI)
Presentations of the three winning teams:
the strategy DSP award ceremony
Marcel Ottens and Exercise Assistants
14:00 Evaluation of the course
14:30 Farewell drink


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


Deadline for registration is 10 June 2019

The course fee is:

Early Bird €2.750,-*
Regular Fee €3.000,-
PhD Students €1.375,-**

*To be eligible for the reduced early bird fee you need to register before 22th of April 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 6 May 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.


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

Alex Hanke

Novartis Pharma AG, Basel, Switzerland

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

Matthias Wiendahl

NOVO Nordisk A/S, Gentofte, Denmark

Geert-Jan Witkamp

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

Exercises Assistance

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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(2018 is FULLY BOOKED)

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