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Award-winning Theses and Dissertations

Permanent URI for this collection

https://hdl.handle.net/10919/71751
Every year, the Virginia Tech Graduate School honors several outstanding theses and dissertations, and some theses and dissertations have won external awards. Browse these works here. Read about applying for thesis and dissertation awards at graduateschool.vt.edu/academics/awards/.

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Browsing Award-winning Theses and Dissertations by Author "Agah, Masoud"

Now showing 1 - 3 of 3
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    The AFM Study of Ovarian Cell Structural Mechanics in the Progression of Cancer
    Ketene, Alperen Nurullah (Virginia Tech, 2011-05-06)
    According to the American Cancer Society, Cancer is the second most common cause of death in the United States, only exceeded by heart disease. Over the past decade, deciphering the complex structure of individual cells and understanding the symptoms of cancer disease has been a highly emphasized research area. The exact cause of Cancer and the genetic heterogeneity that determines the severity of the disease and its response to treatment has been a great challenge. Researchers from the engineering discipline have increasingly made use of recent technological innovations, namely the Atomic Force Microscope (AFM), to better understand cell physics and provide a means for cell biomechanical profiling. The presented work's research objective is to establish a fundamental framework for the development of novel biosensors for cell separation and disease diagnosis. By using AFM nanoindentation, several studies were conducted to identify key distinctions in the trends of cell viscoelasticity between healthy, nontumorigenic cells and their malignant, highly tumorigenic counterparts. The possibility of identifying useful 'biomarkers' was also investigated. Due to the lack of an available human ovarian cell line, experiments were done on a recently developed mouse ovarian surface epithelial (MOSE) cell line, which resembles to human cell characteristics and represents early, intermediate, and late stages of the ovarian cancer. Material properties were extracted via Hertz model contact theory. The experimental results illustrate that the elasticity of late stage MOSE cells were 50% less than that of the early stage. Cell viscosity also decreased by 65% from early to late stage, indicating that the increase in cell deformability directly correlates with increasing levels of malignancy. Various cancer treatment and component-specific drugs were used to identify the causes for the changes in cell biomechanical behavior, depicting that the decrease in the concentration levels of cell structural components, predominantly the actin filament framework, is directly associated with the changes in cell biomechanical property. The investigation of MOSE cells being subject to multiple mechanical loads illustrated that healthy cells react to shear forces by stiffening up to 25% of their original state. On the other hand, cancerous cells are void of such response and at times show signs of decreasing rigidity. Finally, deformation studies on MOSE cancer stem cells have shown that these cells carry a unique elasticity profile among other cell stage phenotypes that could allow for their detection. The results herein carry great potential into contributing to cell separation methods and analysis, furthering the understanding of cell mechanism dynamics. While prior literature emphasizes on the elastic modulus of cells, the study of cell viscosity and other key material properties holds a critical place in the realistic modeling of these complex microstructures. A comprehensive study of individual cells holds a great amount of promise in the development of effective clinical research in the fight against cancer.
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    Identification of Cell Biomechanical Signatures Using Three Dimensional Isotropic Microstructures
    Nikkhah, Mehdi (Virginia Tech, 2010-12-03)
    Micro and nanofabrication technologies have been used extensively in many biomedical and biological applications. Integration of MEMS technology and biology (BioMEMS) enables precise control of the cellular microenvironments and offers high throughput systems. The focus of this research was to develop three dimensional (3-D) isotropic microstructures for comprehensive analysis on cell-substrate interactions. The aim was to investigate whether the normal and cancerous cells differentially respond to their underlying substrate and whether the differential response of the cells leads to a novel label-free technique to distinguish between normal and cancerous cells. Three different generations of 3-D isotropic microstructures comprised of curved surfaces were developed using a single-mask, single-etch step process. Our experimental model included HS68 normal human fibroblasts, MCF10A normal human breast epithelial cells and MDA-MB-231 metastatic human breast cancer cells. Primary findings on the first generation of silicon substrates demonstrated a distinct adhesion and growth behavior in HS68 and MDA-MB-231 cells. MDA-MB-231 cells deformed while the fibroblasts stretched and elongated their cytoskeleton on the curved surfaces. Unlike fibroblasts, MDA-MB-231 cells mainly trapped and localized inside the deep microchambers. Detailed investigations on cytoskeletal organization, adhesion pattern and morphology of the cells on the second generation of the silicon substrates demonstrated that cytoskeletal prestress and microtubules organization in HS68 cells, cell-cell junction and cell-substrate adhesion strength in MCF10A cells, and deformability of MDA-MB-231 cells (obtained by using AFM technique) affect their behavior inside the etched cavities. Treatment of MDA-MB-231 cells with experimental breast cancer drug, SAHA, on the second generation of substrates, significantly altered the cells morphology, cytoarchitecture and adhesion pattern inside the 3-D microstructures. Third generation of silicon substrates was developed for comprehensive analysis on behavior of MDA-MB-231 and MCF10A cells in a co-culture system in response to SAHA drug. Formation of colonies of both cell types was evident inside the cavities within a few hours after seeding the cells on the chips. SAHA selectively altered the morphology and cytoarchitecture in MDA-MB-231 cells. Most importantly, the majority of MDA-MB-231 cells stretched inside the etched cavities, while the adhesion pattern of MCF10A cells remained unaltered. In the last part of this dissertation, using AFM analysis, we showed that the growth medium composition has a pronounced effect on cell elasticity. Our findings demonstrated that the proposed isotropic silicon microstructures have potential applications in development of biosensor platforms for cell segregation as well as conducting fundamental biological studies.
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    MEMS-Based Micro Gas Chromatography: Design, Fabrication and Characterization
    Zareian-Jahromi, Mohammad Amin (Virginia Tech, 2009-05-22)
    This work is focused on the design, fabrication and characterization of high performance MEMS-based micro gas chromatography columns having wide range of applications in the pharmaceutical industry, environmental monitoring, petroleum distillation, clinical chemistry, and food processing. The first part of this work describes different approaches to achieve high-performance microfabricated silicon-glass separation columns for micro gas chromatographic (µgC) systems. The capillary width effect on the separation performance has been studied by characterization of 250 µm-, 125 µm-, 50 µm-, and 25 µm-wide single-capillary columns (SCCs) fabricated on a 10à 8 mm2 die. The plate number of 12500/m has been achieved by 25 µm-wide columns coated by a thin layer of polydimethylsiloxane stationary phase using static coating technique. To address the low sample capacity of these narrow columns, this work presents the first generation of MEMS-based "multicapillary" columns (MCCs) consisting of a bundle of narrow-width rectangular capillaries working in parallel. The second contribution of this work is the first MEMS-based stationary phase coating technique called monolayer protected gold (MPG) for ultra-narrow single capillary (SCC) and multicapillary (MCC) microfabricated gas chromatography (μGC) columns yielding the highest separation performance reported to date. This new μGC stationary phase has been achieved by electrodepositing a uniform functionalized gold layer with an adjustable thickness (250nm-2µm) in 25μm-wide single columns as well as in four-capillary MCCs. The separation performance, stability, reproducibility and bleeding of the stationary phase have been evaluated over time by separating n-alkanes as non-polar and alcohols as polar gas mixtures.