Downstream Process Design

By choosing from a series of unit operations, students try to design a DSP chain with an optimal cost / benefit ratio.

Learning objectives

The module focuses on:
  • Design of a flow sheet for a typical biotechnological product.
  • Recognise the most common unit operations.
  • Describe the function of the unit operations.
  • Describe how they work.
  • Order unit operations in a flow sheet.


A background to this module has been published as:
  • H. van der Schaaf, M.H. Vermuë, J. Tramper, & R.J.M. Hartog (2003). A design environment for downstream processes for Bioprocess-Engineering students. Eur.J.Eng.Edu. 28: 507 - 521 (click for an Abstract, or download from the menu on the right for a full pdf).


Below is a description for the DownStream Processing module. When started, the module will open in a new window, but it might be convenient to print this page.

The demo requires a recent browser (Mozilla, Opera, or Internet Explorer) with the Flash plugin.

Start the DSP module

Tour description

The story: You are a junior consultant for the Wageningen Virtual Consultancy firm and you are being placed at the biotechnological company FMT to design a downstream process for a new product.

  • Click the first 'example' link.

This is the production process scheme for the Kikkoman soy sauce.

  • Click introduction and the second 'example' link. This is an example downstream process for the purification of an enzyme.
  • Click 'Practice design'.

Here you can practice with the designer. At the start of the design, only a reactor and a storage vessel (called 'endpoint') are shown. The reactor contains 'protein5' and 'Target'. Because you haven't made any changes to the design yet, the storage vessel also contains 'protein5' and 'Target'.

The assignment in this exercise is to separate 'protein 5' from 'Target'.

  • In the dropdown between the reactor and the vessel, select filter and click the icon right of the dropdown .

You have now added a Filtration unit between the ractor and the endpoint. Currently, the filter does not separate the two components. Both components are in the 'Output' stream. The 'waste' stream only contains water. In the table next to the reactor, we can see that protein5 has a diameter of 15nm and target has a diameter of 5nm.

  • In the textbox of the filter labeled Pore Size, change the 1 to a 14 and click the Submit new settings button .

You now see the concentrations of the output of the filter change. In the 'output' there is now more protein5 then Target, and in the 'Waste' there is more Target then protein5.

Because you want the target in the output stream and not in the waste stream, you need to change the 'use' dropdown from 'retentate' to 'permeate' and click Submit.

In the listings of the endpoint, you can see that the purity of the contents are about 86%, and that 96% of 'Target' is recovered, at a cost of € 527316.

  • Click the trashcan icon of the filter to remove it from the design and add an ion-exchange unit. Change pH On to 6.5 and pH Off to 8 and click Submit.

Now you see in the listing of the endpoint that the purity is 93.6% with a recovery of 96% with a cost of only €1133. An Ion exchange unit is a lot more efficient when separating these two proteins then a filter unit!

  • Click continue.

Here you see an overview of the design you just made.

  • Click go on here.

You find a note from the management of FMT on your desk. Read the note and

  • Click Go to the first question.

A question about the definition of Purity.

  • Give the last answer (5 minutes have passed and I have still no clue. Help!) and read the feedback.
  • Give the second answer and click continue here.

A question about the definition of Recovery.

  • Give the third answer and click continue here.

You now have to make your first design. As you can see, there are a lot more unwanted substances in this reactor then in the practice design. First get rid of the E. coli 913 cells.

  • Add a filter, Use the permeate, Pore size of 80 nm.

Next, add two ion-exchange units below the filter:

    Type: Kation; eluent: 0.05m3; pH On: 6.7 ; pH Off: 7.5
    Type: Anion; eluent: 0.05m3; pH On: 7.5; pH Off: 6.7
  • Click 'Your Result' and then 'Continue'.

A new note from the management! The research department changed to a new E. coli strain... you will have to adapt your design. Go to the process designer.

The difference with the previous design is that the target enzyme is now inside the cells. The easiest way to change your design is to add a centrifuge as the first unit to your design.

  • Add a centrifuge, Use: pellet, S (size): 200, resuspend in 3 m3

Between the centrifuge and the filter:

  • Add a disruptor to destroy the cells: N: 6 m2 , DP: 65 MPa

After these changes, you can see that the last ion-exchange unit doesn't have very much effect anymore. So, remove the last ion-exchange unit. In it's place:

  • Add a gelfiltration unit:

    Column V: 0.002 m3, Geltype: fine, flow 0.001 m3/hr; collect fractions between 62 and 67 min.

  • Click Your Result at the bottom

Here you can see an overview of your second design.

  • Click Continue

These are the top scoring designs of other students, you can compare your results with those. Can you do better?