Microfluidic System for the Study of Cancer Invasion and Intravasation
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Cancer cells in solid tumors often experience low oxygen and nutrition concentrations due to underdeveloped vasculature. Many studies have indicated that the altered oxygen and nutrition levels have profound effects on cancer metastasis, although the exact mechanism is still elusive. Improved understanding of the specific roles of oxygen and nutrition levels on metastasis could lead to the discovery of new therapeutic targets and better treatment methods. In this project, we aim to develop a microfluidic system to simulate the tumor microenvironment and tumor-vascular interface. We hope to use the system to study the effects of hypoxia and low nutrition concentrations on cancer local invasion and intravasation, two critical steps in early metastasis. Such in vitro models allow quantitative analysis of cell behaviors under precisely controlled cellular environment, which could generate valuable information for the study of specific microenvironmental factors. The design of the microfluidic device includes two main compartments: a cancer compartment connected with an endothelial channel, which mimics a blood vessel. In the cancer compartment, cancer cells were encapsulated in collagen hydrogel, which provided a more physiological relevant environment for cell culture and migration. The main objective of the design was to independently control the chemical concentrations in the two compartments, in particular, the oxygen tension. To accomplish the goal, our design employs two separate flow circuits to supply cell culture media for the two compartments. In order to achieve a better control of the oxygen concentration, the device was made of oxygen impermeable poly (methyl methacrylate). One device was built and tested. Oxygen reading in the two compartments and fluorescent dye diffusion test indicate that we could independently control the concentrations of oxygen and other soluble molecules in the two compartments. Cancer cell and endothelial seeding were attempted. Due to time constraints, co-culture experiments were not performed in this project. In summary, we successfully developed and tested a microfluidic system that is suitable for the study of cancer metastasis under different oxygen and nutrition concentrations.