Two-chamber Microfluidic System Used as Artificial Blood Vessel for the Investigation of the Entire Migration Steps of Metastatic Intravascular Cancer Cells

We present the design and the fabrication process of an artificial blood vessel system for the in vitro examination of the entire migration steps of metastasticintravascular cancer cells under continuous laminar flow conditions at distinct tunable shear rates using live cell fluorescence microscopy. The microfluidic system iscomposed of two layers: An upper layer with two sets of microstructured channels simulating the bloodvasculature, and the lower layer, which consists of twolarge channels filled with components of human vascular surrounding tissue. Both layers are separatedby a porous membrane with a specific pore density distribution. Prior to the experiments the membrane is coated with a homogeneous monolayer of endothelialcells (EC) to mimic the blood vessel wall. The whole system consists of the polymer polycarbonate due to its excellent biocompatibility andoptical transparency. The two layers of the microfluidic system are fabricated by hot embossing and finallyassembled using a thermal bonding process.The work was accompanied by numerical simulations of the flow behavior of the cancer cells considering celldiameter and viscosity of the blood. It could be shown that a predictable number of the cancer cells remains in the blood vessel system, where they can interact withthe monolayer of endothelial cells. Our experiments have shown that a small number of those cancer cellspenetrate the EC monolayer and the porous membraneentering the matrix of the lower channel. Thus it was possible to observe the process of cancer cell extravasation under laminar flow conditions.

کلیدواژه ها:

microfluidic system ، hot embossing ، thermal bonding ، artificial blood vessel ، cancer cell