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PhD defense ceremony Hossein Eslami Amirabadi: A novel Microfluidic Platform to study Cancer Cell Invasion

Mon, 11 June 2018, 13:30 - 16:00, TU/e (Auditorium, Senaatzaal)

Hossein Eslami Amirabadi

Most cancers start with a primary tumor which is a mass within an organ consisting mainly of cancer cells. Cancer becomes dangerous when these cells leave the tumor and enter the blood stream. They can then spread throughout the body and make new tumors in other organs. This process, called metastasis, is responsible for 90% of cancer associated deaths. To prevent metastasis, scientists use different models to understand what drives the cells to move. On the one hand, they use animals to study the process. In addition to the ethical issues and high expenses associated with sacrificing the animals, they often poorly represent the human body. On the other hand, many scientists take advantage of human cells but in simple "dishes", such as a petri dish, to understand cancer cell behavior, but this approach is often a very simple representation of what really happens in the human body. Therefore, the field of cancer suffers from a large gap between the complex animal models and simple dish models.

The current thesis tackles this problem by using "microfluidic devices". These are small chips normally a few centimeters in width and length, and a few millimeters thick. These chips contain very small microchannels with hundreds of micrometers in height and width. Fluids like water flow very smoothly in these tiny channels, and therefore they can be easily controlled. Also, we can create mini tissues in these chips that can show different functions of the tissue in the human body. In this thesis, we have developed a microfluidic chip to study how cancer cells move when they leave the tumor. We were able to make an artificial network consisting of fibers, representing the direct environment of the tumor, and integrate them in a microfluidic device. We also made use of the smooth flow in the microchannels to create a gradient of nutrients around the cells. Using this chip, we studied how breast cancer cells behave in fibrous networks with different fiber diameters. In addition, we could also capture different movement patterns of three different breast cancers. Finally, we extended the application of this technology to other diseases such as Osteoarthritis.

This new microfluidic device enables us to use more network materials, natural or artificial, in a controlled microfluidic environment, and study the motion of cells in these materials. It allows biologists and doctors to advance their disease models, simpler and more realistic than animal models, yet more complex and more representative than a petri dish. This technology is now being further developed and used in three different projects in collaboration with medical centers.

The microfluidic chip developed in this thesis. Two pieces of electrospun matrices with different properties are sandwiched between two microfluidic layers using a novel microfabrication method called "selective curing". The top layer has a straight microfluidic channel and the bottom layer has two connected microchannels for two pieces of the matrix layers. The right image shows a schematic cross-section of the invasion assay. The cells are seeded in the top microchannel and attracted to the bottom using a chemo-attractant.
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