Date of Award

12-2021

Degree Name

MS in Biomedical Engineering

Department/Program

Biomedical and General Engineering

College

College of Engineering

Advisor

Christopher Heylman

Advisor Department

Biomedical and General Engineering

Advisor College

College of Engineering

Abstract

Colorectal cancer is the third most common cancer in the United States with a 5-year late-stage survival rate of only 14%. Due to the lack of translation between animal models and clinical trials as well as the inefficacy of many chemotherapeutics in initial clinical trials, researchers are turning to in vitro drug screening models in an effort to mimic the conditions in vivo. This research project aimed to validate an in vitro tumor culture model within a microfluidic device using a clinically relevant chemotherapy drug. The first experiment consisted of a cell density and drug concentration study to determine the correct cell density and oxaliplatin concentration combinations that would result in a spectrum of quantifiable effects on the tumor cells. This experiment was then converted from a monolayer cell culture on glass into a 2D culture on top of a fibrin extracellular matrix (ECM) to ensure that the cells would respond in a similar way to the drug in the presence of an ECM as they did in the first experiment. The third experiment involved SW620 cells cultured within the fibrin hydrogel to create a 3D tumor model that better mimics the growing conditions in vivo. The goal of this experiment was again to ensure that the cells would respond in the same way to the oxaliplatin treatments as the previous experiments when adding complexity to the model. The final experiment was then to convert this 3D experiment performed in chamber slides into a 3D culture within a microfluidic device with media and oxaliplatin treatments perfused through the chamber using a syringe pump. The purpose of this experiment was to assess whether tumor cells could grow and survive within a microfluidic device with interstitial flow as well as determining if they responded as expected to the oxaliplatin treatment. The first three experiments performed within chamber slides showed that tumor count and average tumor size decreased with increasing oxaliplatin concentrations as expected, which is comparable to the in vivo tumor response to the drug. The fourth experiment demonstrated that, although cells are able to grow within the microfluidic device, this model did not accurately replicate the in vivo condition and future work needs to be aimed at improving the design of the device as well as optimizing parameters within the experiment.

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