FABRICATION OF A MICROFLUIDIC TUMOR-ON-A-CHIP MODEL FOR PERSONALIZED CANCER THERAPY
by Shailesh Senthil Kumar
Abstract – Cancer has had a defining impact on medicine for the past few decades, and its effects can be felt worldwide, with 91 out of 172 countries listing it as their first or second cause of mortality before the age of 70. However, cancer has shown a significantly low turnout for clinical use of anti-cancer drugs, with less than 10 percent of these drugs entering the market. Current models are not sufficient and fail to reproduce the human body’s environment in two key ways. First, three-dimensional human tumors’ biophysical and biochemical aspects drastically change tumor susceptibility due to shear stress and extracellular matrix production. Cancer drug screening has a second hurdle: each person’s tumor is different, caused by DNA mutations, RNA regulation, and the proteins expressed. Cancer cells have demonstrated intratumoral heterogeneity within tumors, allowing cell subtypes to be artificially selected against therapeutics. Therefore, tumors require a personalized and precise form of medicine suited for the new age of personalized patient therapy. A microfluidic 3D model is required to replicate a three-dimensional tumor microenvironment, incorporating model blood vessels and embedded tumor spheroids to allow 3D tumoroids to form. The project hopes to pair this highly replicable and reusable microfluidic device with microscopy to characterize phenotypic heterogeneity spatially and temporally. Specific factors cell cycle patterns, necrosis, cell size, and motility will be analyzed to evaluate tumor aggressiveness and identify tumor subtypes for personalized therapy.