Microfluidic Platform to Quantify Intra-tumoral Stress

Student’s name: Erica Rios Hernandez Home Institution: San Jose State University NNCI Site: KY Multiscale @ University of Louisville REU Principal Investigator: Kevin Walsh REU Mentor: Joseph Chen Abstract: Glioblastoma has a short life expectancy, a potential avenue for new therapeutics is through understanding tumor development and growth within its microenvironment. As a tumor grows in a confined space, it generates intra-tumoral stress. Current research shows compressive stress intratumorally has direct impacts on cancer progression. These forces assist the cancer cells in escaping tumors, highlighting an emergent mechanobiological driver of cancer progression. However, with current in-vitro tools this driver is poorly understood. To better understand this phenomenon, we have developed a microfluidic device that generates alginate microbeads that allows us to quantify intra-tumoral stress. The fabrication of the device was done using PDMS molds plasma bonded to glass slides, with inlets for alginate and oil, and a collection outlet. To generate beads, the alginate and oil went through channels ranging from 10-40um into an alginate-in-oil emulsion. Beads were then soaked in a Calcium Chloride solution where they underwent a chemical cross-linked via the outlet channel to then further be collected. Characterization of the beads involves using the ImageJ to calculate average radius range and atomic force microscopy (AFM) to get the elastic moduli, allowing for quantification of the force required for deformation. The beads were embedded into a glioblastoma stem-cell spheroid using the hanging drop method and subsequently embedded into a methacrylate hyaluronic acid gel, a biomimetic matrix. As the spheroid progresses, stress is exerted on the bead, causing it to deform. Deformation of the beads was studied using z-stack images of bead, images were taken using confocal microscopy.