Biomedical Engineering - Theses

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    Surface Acoustic Wave Microfluidic Platform for Cell Mechanical Measurement
    Wu, Yanqi ( 2021)
    Cells are dynamic, living structures that remodel themselves in response to stimuli from environment or in relation to cellular processes such as cell growth, proliferation, differentiation, migration and death. The change of cell mechanical property can be a biophysical indicator in response to the abnormal alteration in cell functionality under pathological conditions. The advances in tool development for cell mechanical measurement have facilitated in-depth discussion of cell mechanics, but heavily limited by low throughput and high cost. The emerging lab-on-a-chip microfluidic methods provide a promising solution due to the miniaturisation, among which the acoustofluidic method (the fusion of acoustics and microfluidics) appears to be advantageous due to its tunability, biocompatibility and acousto-mechanical nature. In this dissertation, I explored the application of surface acoustic wave (SAW) microfluidics in the area of cell mechanics, including establishing SAW devices for cell mechanical measurement, comparing SAW-based measurement with the benchmark from a conventional method, investigating the impacts on cell mechanical characteristic, and extending the concept to a high-throughput cytometry comparable to the real-world need. The results show that the SAW microfluidic method can provide an effective measurement on cell mechanical characteristics and probe the impact of cellular interior structure or cellular phenotype. It is consistent with the conventional benchmark and can be a complement for some cellular structures of interest. At last, it can operate as a continuous-flow high-throughput cytometry, which could be exploited in future studies related to cell mechanics.
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    Red Blood Cell Passage through Narrow Capillaries: Sensitivity to Stiffness and Shape
    Namvar, Arman ( 2020)
    Red blood cells (RBCs) squeeze through narrow capillaries as they transport oxygen to tissues and carbon dioxide to the lungs. The deformability of RBCs has been shown to depend on the viscoelasticity of the cell membrane and cytoplasm as well as the surface area to volume ratio (SA:V ratio) of the cell. In certain pathological diseases such as malaria, RBCs undergo restructuring of the membrane structure and modifications to the cell shape, which significantly reduce their deformability. Nonetheless, it is still unclear which factor has the greatest impact on the passage of RBCs through small capillaries. Here, we present a systematic analysis designed to identify the individual contributions of cell stiffness and SA:V ratio to the ability of RBCs to traverse narrow capillaries in a microfluidic device. We modified cellular rigidity using glutaraldehyde fixation, changed SA:V ratio by altering the buffer osmolarity and probed RBCs passage through microchannels. Our results showed that dramatic stiffening (~8 fold) had little effect (~6% retardation) on the ability of RBCs of the same geometry to traverse the channels. On the other hand, a moderate decrease (~13%) in the SA:V ratio affected the traversal of RBCs of similar stiffness more markedly (~19% decrease). We further studied RBCs infected by two different species of malaria parasites known to affect humans, Plasmodium falciparum and knowlesi. We found that P. falciparum rigidified the host RBC, but infected RBCs penetrated into microchannels with similar efficiency to uninfected RBCs. By contrast, P. knowlesi reduced the SA:V ratio of the host RBC resulting in restricted passage. We found that the earliest stage immature RBCs (reticulocytes) exhibited a similar SA:V ratio to mature RBCs and, despite being 30% larger, travelled into microchannels as efficiently as mature cells. Our finite element (FE) model provides a coherent rationale for our experimental observations, indicating that cell stiffness changes do not significantly affect RBC traversal in small capillaries due to the highly nonlinear mechanical behaviour of the cell membrane. Our numerical simulations predict that RBCs with low SA:V ratios are more prone to trapping in small capillaries (within the physiological size range) than RBCs with high membrane stiffness. Therefore, therapies targetting surface area to volume ratio of RBCs may be more effective than those that target cell stiffness.