| Summary: | The ability to separate cells based on biomechanical properties such as size and deformability is emerging as a potential alternative to biochemical methods for cell separation, particularly in cases where biochemical markers are unknown or expressed at low levels. The separation of circulating tumor cells (CTCs) is an example problem where this type of technology is important because the cell surface markers currently used to capture these cells are known to be unreliable. The performance of existing biomechanical cell separation techniques is currently hindered by clogging, which reduces specificity of the separation process. We previously demonstrated a microfluidic ratchet mechanism that overcomes the reversible nature of low Reynolds number flow. In this thesis, we leverage this mechanism to prevent clogging while preserving high selectivity by periodically clearing the filter microstructure to create an automated microfluidic platform that demonstrates the size and deformability-based separation of cultured human bladder UC13 cancer cells from white blood cells (WBCs). This platform has two components: the first is a size-based hydrodynamic concentrator, which performs an initial sample preparation step to reduce the sample volume while removing a fraction of the contaminant WBCs. The second is an automated cell separation device where cells are transported through a 2D array of ratcheting funnel constrictions and sorted using an oscillatory flow. We evaluate the ability of this platform for separating rare cancer cells doped into WBCs at low concentration to assess the potential of this technology for biomechanical separation of CTCs. Specifically, using a sample where cancer cells are doped into WBCs at a ratio of 1:1000, the combined system achieved a cancer cell yield of 96.0±0.1%; the outlet had a purity of 75±3%; and the population of cancer cells in the mixture was enriched by a factor 3000 (+643, -278). === Applied Science, Faculty of === Mechanical Engineering, Department of === Graduate
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