Biomedical Engineering - Theses
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ItemAcoustic metasurfaces for micromanipulation( 2023-07)Acoustic methods are ideal tools for micromanipulation due to their biocompatibility and ability to generate acoustic fields with micro/nano-scale resolution. These methods utilize the force generated by acoustic waves to pattern, manipulate, and sort cells and microparticles without physical contact. These approaches have several advantages including the ability to handle fragile or sensitive cells without damaging them, and the potential for high-throughput manipulation of multiple cells/micro-particles simultaneously. While acoustic methods have shown great potential in micromanipulation, several challenges need to be addressed. One of the primary challenges is to generate flexible and complex acoustic fields to achieve desired manipulations, such as the trapping of cells or particles with complex patterns. Another challenge is the ability to generate programmable acoustic fields to generate instantly reconfigurable acoustic fields. Acoustic methods for micromanipulation also face challenges related to planarization and integration with other techniques. Therefore, this work introduces the following acoustic approaches based on metasurfaces for micromanipulation: (1) sawtooth acoustic metasurfaces for generating flexible acoustic fields in microfluidic channels using only a single travelling acoustic wave, (2) micropillar-based acoustic metasurfaces for applications in generating complex acoustic holographic patterns, (3) the creation of reconfigurable acoustic holograms through the modification of the sound velocity of the medium, and (4) the integration of acoustic holography with microfluidic systems to generate complex acoustic fields in microfluidic channels, where acoustic metasurfaces with subwavelength structures can achieve unique acoustic properties that do not normally exist in nature. These metasurface methods can generate flexible, complex, and programmable acoustic fields through subwavelength structures, holding great significance for various applications including acoustic tweezers, microfluidics, and biomedical sensing.
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ItemOptimizing Acoustic Systems for Biomedical Applications with Numerical Modeling( 2023-06)This thesis explores the development and optimization of acoustic and acoustofluidic devices. Acoustofluidic devices, which combine principles of acoustics and microfluidics, have emerged as a promising platform for biological micro-object micromanipulation due to their non-invasive, accurate, rapid, and label-free qualities. Acoustofluidic devices have found utility in various biomedical applications including single-cell studies, point-of-care testing, lab-on-a-chip studies, and tissue engineering. The objective of this thesis is to develop key components of these devices and explore new device configurations employing computational modeling and optimization techniques. As a result, novel device configurations are developed enabling complex and high-resolution micromanipulation of suspended micro-objects. In the studies presented here, computational analysis is utilized to optimize (1) traveling surface acoustic wave device dimensions, (2) the configuration of a planar acoustic resonator that integrates a structured surface, (3) the thickness of the coupling layer and superstrate materials for bulk-wave transmission, (4) the shape of acoustically-actuated 3D microstructures, and (5) waveguide topology in reusable face masks. In doing so, this work demonstrates that computational analysis is an integral part of the development of acoustofluidic devices for advanced micromanipulation and sound-transmitting structures, which have extensive potential in biomedical applications.
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ItemSurface Acoustic Wave Microfluidic Platform for Cell Mechanical Measurement( 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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ItemRed Blood Cell Passage through Narrow Capillaries: Sensitivity to Stiffness and Shape( 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.