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Development of a dynamic bioreactor for cancer metastasis research

Metastatic cancer cells travel with the blood stream to reach remote locations in the body. They squeeze through the endothelial cell lining of blood vessels, enter the surrounding tissue and form new tumors (Figure 2). The cancer cell passage (extravasation) occurs in a complex interplay with monocytes (a type of white blood cells) and various signaling molecules.

The aim of this project is to design and build a dynamic bioreactor to study the interaction of cancer, endothelial and white blood cells in a controlled environment. This in vitro system needs to reproduce both the biochemical and mechanical conditions that are encountered in vivo. In particular, the transient and pulsatile blood flow and the therewith associated shear stresses at the vessel wall have to be replicated.

During the current semester, an initial reactor design has been validated and implemented in Simulink. A working prototype including all the components in (Figure 1) is being completed. This project will now focus on the inclusion of additional environmental control inputs in order to regulate temperature, atmospheric gas concentration and the pH of the cell culture medium as well as on the expansion of the existing controller to allow for bidirectional flow control. If time allows, the completed bioreactor will be used to conduct a number of initial experiments with live cells.

At the end of this project a completed bioreactor has been implemented and tested. It was decided to remove the gas valves and peristaltic pump and implement the controller based on a sterilizable magnetic bearing rotary pump instead. The system includes a complete heated enclosure and is ready for experimental use. It includes control of flow rate, pressure and temperature and is able to reproduce frequencies up to 5 Hz. There was no time left for experimental validation with live cells but the system has been shown able to reproduce the desired flow profiles with a noise in the order of 10% which is a large improvement in comparison with a peristaltic pump based system.

Information

(position closed)
Student: Martina Grab, ETH Zürich
Project type: Master thesis (2014)

For further information, please contact
Prof. Vartan Kurtcuoglu
Dr. Marianne Schmid Daners
Dr. Anastasios Marmaras

  • Figure 1

  • Figure 2