Thesis (Ph. D.)--University of Missouri-Columbia, 2003. / Typescript. Vita. Includes bibliographical references (leaves 107-109). Also available on the Internet.

Two technologies, immersion and imprint lithography, represent important stepping stones for the development of the next generation of lithography tools. However, although the two approaches offer important advantages, both pose many significant technological challenges that must be overcome before they can be successfully implemented. For imprint lithography, special care must be taken when choosing an etch barrier because studies have indicated that some physical material properties may be size dependent. Additionally, regarding immersion lithography, proper image focus requires that the optical path length between the lens and substrate be maintained during the entire writing process. The work described in this document was undertaken to address the two challenges described above. A new mathematical model was developed and used in conjunction with AFM nano-indentation techniques to measure the elastic modulus of adhesive, thin polymer films as a function of the film thickness. It was found that the elastic modulus of the polymer tested did not change appreciably from the value determined using bulk measurement techniques in the thickness range probed. Additionally, a method for monitoring and controlling the optical path length within the gap of a nearly index-matching cavity based on coherent broadband interference was developed. In this method, the spectrum reflected for a cavity illuminated with a modelocked Ti:Sapphire laser was collected and analyzed using Fourier techniques. It was found that this method could determine the optical path length of the cavity, quickly and accurately enough to control a servo-based feedback system to correct deviations in the optical path length in real time when coupled with special computation techniques that minimized unnecessary operations. / text

Carbon nanotubes (CNTs) have extraordinary electrical and mechanical properties, and many potential applications have been proposed, ranging from nanoscale devices to reinforcement of macroscopic structures. However, due to their small sizes, characterization of their mechanical properties and deformation behaviours are major challenges. Theoretical modelling of deformation behaviours has shown that multi-walled carbon nanotubes (MWCNTs) can develop ripples in the walls on the contracted side when bent above a critical curvature. The rippling is reversible and accompanied by a reduction in the bending stiffness of the tubes. This behaviour will have implications for future nanoelectromechanical systems (NEMS). Although rippling has been thoroughly modelled there has been a lack of experimental data thus far. In this study, force measurements have been performed on individual MWCNTs and vertically aligned carbon nanofibers (VACNFs). This was accomplished by using a custom-made atomic force microscope (AFM) inside a scanning electron microscope (SEM). The measurements were done by bending free-standing MWCNTs/VACNFs with the AFM sensor in a cantilever-to-cantilever fashion, providing force-displacement curves. From such curves and the MWCNT/VACNF dimensions, measured from SEM-images, the critical strain for the very onset of rippling and the Young’s modulus, E, could be obtained. To enable accurate estimations of the nanotube diameter, we have developed a model of the SEM-image formation, such that intrinsic diameters can be retrieved. We have found an increase in the critical strain for smaller diameter tubes, a behaviour that compares well with previous theoretical modelling. VACNFs behaved very differently, as they did not display any rippling and had low bending stiffnesses due to inter-wall shear. We believe that our findings will have implications for the design of future NEMS devices that employ MWCNTs and VACNFs. / <p>Artikel 2 Image formation mechanisms tidigare som manuskript, nu publicerad: urn:nbn:se:kau:diva-16425 (MÅ 150924)</p>

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The cellular mechanical environment, including the elasticity of the extracellular matrix, profoundly affects cellular mechanical and biological responses. This responsiveness depends on and may influence the inherent mechanical properties of the cell and the nucleus. In this thesis, the local and global elastic moduli of valve interstitial cells (VICs) cultured on substrates of varying stiffness were characterized using atomic force microscopy (AFM). A novel AFM technique used to directly determine nuclear elastic moduli in situ was also tested and preliminary results for VIC nuclear elasticity and isolated VIC nuclei elasticity were presented. This study confirmed that both local and global elasticity of VICs were sensitive to substrate compliance, and demonstrated that the nucleus was consistently two to four times stiffer than the cytoplasm and that isolated VIC nuclei were significantly softer than the intact nuclei in situ. It also provides practical guidelines for efficient AFM-based measurement of cell mechanical properties.

This thesis describes the development of a high-throughput approach towards the encapsulation of cancer cells in biopolymer microgels with tunable mechanical properties. In particular, this thesis is focused on: i) the high-throughput generation of biopolymer microgels with tunable mechanical properties ii) the measurement of the mechanical properties of the microgels, and iii) the high-throughput encapsulation of a cancer cell line within biopolymer gels. The microgels will be generated by (i) introducing in a microfluidic device two distinct streams of biopolymer solutions; (ii) mixing the streams; (iii) emulsifying the biopolymer and (iv) using thermosetting to transform the droplets in situ into microgels. By applying a compression force to the hydrogel microbead and measuring its deformation, the Young’s modulus and relaxation time of the microgel can be examined. The properties of cells were examined within the gels using various spectroscopic techniques such as absorption (UV-Vis) and fluorescence microscopy (fluorescent microscopy, confocal microscopy).

This thesis describes the development of a high-throughput approach towards the encapsulation of cancer cells in biopolymer microgels with tunable mechanical properties. In particular, this thesis is focused on: i) the high-throughput generation of biopolymer microgels with tunable mechanical properties ii) the measurement of the mechanical properties of the microgels, and iii) the high-throughput encapsulation of a cancer cell line within biopolymer gels. The microgels will be generated by (i) introducing in a microfluidic device two distinct streams of biopolymer solutions; (ii) mixing the streams; (iii) emulsifying the biopolymer and (iv) using thermosetting to transform the droplets in situ into microgels. By applying a compression force to the hydrogel microbead and measuring its deformation, the Young’s modulus and relaxation time of the microgel can be examined. The properties of cells were examined within the gels using various spectroscopic techniques such as absorption (UV-Vis) and fluorescence microscopy (fluorescent microscopy, confocal microscopy).

The cellular mechanical environment, including the elasticity of the extracellular matrix, profoundly affects cellular mechanical and biological responses. This responsiveness depends on and may influence the inherent mechanical properties of the cell and the nucleus. In this thesis, the local and global elastic moduli of valve interstitial cells (VICs) cultured on substrates of varying stiffness were characterized using atomic force microscopy (AFM). A novel AFM technique used to directly determine nuclear elastic moduli in situ was also tested and preliminary results for VIC nuclear elasticity and isolated VIC nuclei elasticity were presented. This study confirmed that both local and global elasticity of VICs were sensitive to substrate compliance, and demonstrated that the nucleus was consistently two to four times stiffer than the cytoplasm and that isolated VIC nuclei were significantly softer than the intact nuclei in situ. It also provides practical guidelines for efficient AFM-based measurement of cell mechanical properties.

This thesis is an investigation of methods to remediate methicillin-resistant Staphylococcus pseudintermedius (MRSP) biofilms through conventional and microfluidic-based in vitro assays. MRSP biofilm related infections are a major concern for veterinary clinicians as they may complicate remediation by the immune system or antimicrobials. Novel antimicrobials that have been found to reduce biofilm growth in other staphylococci were assessed in both mono- and combination therapy against MRSP biofilm. Quantitative assay results (p < 0.05) suggest fosfomycin alone and in combination with clarithromycin can significantly reduce biofilm formation. Morphological examination using scanning electron microscopy and atomic force microscopy further demonstrated the effectiveness of fosfomycin alone on biofilm formation on orthopaedic screws and mica sheets. Fabricated microfluidic assays were utilized to assess multiple concentrations of antimicrobial therapy against pre-formed biofilm under physiologically relevant conditions in a quick and repeatable manner. Results demonstrated the usefulness of microfluidic platforms in determining minimum biofilm eradication concentrations.

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