ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
Filtering by
- All Subjects: Biomedical Engineering
- Creators: Goryll, Michael
The flexible x-ray detector technology was then extended to demonstrate the viability of a new technique to seamlessly combine multiple smaller flexible x-ray detectors into a single very large, ultimately human sized, composite x-ray detector for new medical imaging applications such as single-exposure, low-dose, full-body digital radiography. Also explored, is a new approach to increase the sensitivity of digital x-ray detectors by selectively disabling rows in the active matrix array that are not part of the imaged region. It was then shown how high-resolution, flexible, organic light-emitting diode display (OLED) technology can be used to selectively stimulate and/or silence small groups of neurons on the cortical surface or within the deep brain as a potential new tool to diagnose and treat, as well as understand, neurological diseases and conditions. This work also explored the viability of a new miniaturized high sensitivity fluorescence measurement-based lab-on-a-chip optical biosensor using OLED display and a-Si:H PiN photodiode active matrix array technology for point-of-care diagnosis of multiple disease or pathogen biomarkers in a low cost disposable configuration.
Nanoscale confinement biogenetic silica template-based electrical biosensor assay offers the user the ability to detect and quantify the biomolecules. Diatoms have been demonstrated as part of a sensor. The sensor works on the principle of electrochemical impedance spectroscopy. When specific protein biomarkers from a test sample bind to corresponding antibodies conjugated to the surface of the gold surface at the base of each nanowell, a perturbation of electrical double layer occurs resulting in a change in the impedance.
Diatoms are also a new source of inspiration for the design and fabrication of nanostructured materials. Template-directed deposition within cylindrical nanopores of a porous membrane represents an attractive and reproducible approach for preparing metal nanopatterns or nanorods of a variety of aspect ratios. The nanopatterns fabricated from diatom have the potential of the metal-enhanced fluorescence to detect dye-conjugated molecules.
Another approach presents a platform integrating biogenic silica nanostructures with micromachined silicon substrates in a micro
ano hybrid device. In this study, one can take advantages of the unique properties of a marine diatom that exhibits nanopores on the order of 40 nm in diameter and a hierarchical structure. This device can be used to several applications, such as nano particles separation and detection. This platform is also a good substrate to study cell growth that one can observe the reaction of cell growing on the nanostructure of frustule.
First, a simple detection paradigm based on reflectance interferometry is developed. This method is simple, low cost and can be easily applied for protein array detection.
Second, a label-free charge sensitive optical detection (CSOD) technique is developed for detecting of both large and small molecules. The technique is based on that most molecules relevant to biomedical research and applications are charged or partially charged. An optical fiber is dipped into the well of a microplate. It detects the surface charge of the fiber, which does not decrease with the size (mass) of the molecule, making it particularly attractive for studying small molecules.
Third, a method for mechanically amplification detection of molecular interactions (MADMI) is developed. It provides quantitative analysis of small molecules interaction with membrane proteins in intact cells. The interactions are monitored by detecting a mechanical deformation in the membrane induced by the molecular interactions. With this novel method small molecules and membrane proteins interaction in the intact cells can be detected. This new paradigm provides mechanical amplification of small interaction signals, allowing us to measure the binding kinetics of both large and small molecules with membrane proteins, and to analyze heterogeneous nature of the binding kinetics between different cells, and different regions of a single cell.
Last, by tracking the cell membrane edge deformation, binding caused downstream event – granule secretory has been measured. This method focuses on the plasma membrane change when granules fuse with the cell. The fusion of granules increases the plasma membrane area and thus the cell edge expands. The expansion is localized at the vesicle release location. Granule size was calculated based on measured edge expansion. The membrane deformation due to the granule release is real-time monitored by this method.
Methods of fluid actuation were explored to allow delayed delivery of fluidic reagents in multistep detection lateral flow assays (LFAs). Certain hydrophobic materials such as wax were successfully implemented in the LFA with the use of precision dispensed valves. Sublimating materials such as naphthalene were also characterized along with the implementation of a heating system for precision printing of the valves.
Various techniques of blood fractionation were also investigated and this work demonstrates successful blood fractionation in an LFA. The fluid flow of reagents was also characterized and validated with the use of mathematical models and multiphysics modeling software. Lastly intuitive, user-friendly mobile and desktop applications were developed to interface the underlying Arduino software. The work advances the development of a system which successfully integrates all components of fluid separation and delivery along with highly sensitive detection and a user-friendly interface; the system will ultimately provide clinically significant diagnostics in a of point-of-care device.
This effort grew out of the need to develop a highly sensitive, field-deployable platform to be used as a primary screening and early detection tool for serologic biomarkers for the high-risk human papillomavirus (hrHPV) infection. A hrHPV infection is a precursor for developing high-grade cervical intraepithelial neoplasia (CIN 2/3+). Early detection requires high sensitivity and a low limit-of-detection (LOD). To this end, the developed platform (DxArray) takes advantage of the specificity of immunoassays and the selectivity of fluorescence for early disease detection. The long term goal is to improve the quality of life for several hundred million women globally, at risk of being infected with hrHPV.
The developed platform uses fluorescent labels over the gold-standard colorimetric labels in a compact, high-sensitivity lateral flow assay configuration. It is also compatible with POC settings as it substitutes expensive and bulky light sources for LEDs, low-light CMOS cameras, and photomultiplier tubes for photodiodes, in a transillumination architecture, and eliminates the need for expensive focusing/transfer optics. The platform uses high-quality interference filters at less than $1 each, enabling a rugged and robust design suitable for field use.
The limit of detection (LOD) of the developed platform is within an order of magnitude of centralized laboratory diagnostic instruments. It enhances the LOD of absorbance or reflectometric and visual readout lateral flow assays by 2 - 3 orders of magnitude. This system could be applied toward any chemical or bioanalytical procedure that requires a high performance at low-cost.
The knowledge and techniques developed in this effort is relevant to the community of researchers and industry developers looking to deploy inexpensive, quantitative, and highly sensitive diagnostic devices to resource-limited settings.
This dissertation presents a work to develop optical methods for studying cell mechanics which encompasses four applications. Surface plasmon resonance microscopy based optical method has been applied to image intracellular motions and cell mechanical motion. This label-free technique enables ultrafast imaging with extremely high sensitivity in detecting cell deformation. The technique was first applied to study intracellular transportation. Organelle transportation process and displacement steps of motor protein can be tracked using this method. The second application is to study heterogeneous subcellular membrane displacement induced by membrane potential (de)polarization. The application can map the amplitude and direction of cell deformation. The electromechanical coupling of mammalian cells was also observed. The third application is for imaging electrical activity in single cells with sub-millisecond resolution. This technique can fast record actions potentials and also resolve the fast initiation and propagation of electromechanical signals within single neurons. Bright-field optical imaging approach has been applied to the mechanical wave visualization that associated with action potential in the fourth application. Neuron-to-neuron viability of membrane displacement was revealed and heterogeneous subcellular response was observed.
All these works shed light on the possibility of using optical approaches to study millisecond-scale and sub-nanometer-scale mechanical motions. These studies revealed ultrafast and ultra-small mechanical motions at the cellular level, including motor protein-driven motions and electromechanical coupled motions. The observations will help understand cell mechanics and its biological functions. These optical approaches will also become powerful tools for elucidating the interplay between biological and physical functions.
This dissertation presents the development of a laser lysis chip combined with a two-photon laser system to perform single-cell lysis of single cells in situ from three-dimensional (3D) cell spheroids followed by analysis of the cell lysate with two-step reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The 3D spheroids were trapped in a well in the custom-designed laser lysis chip. Next, each single cell of interest in the 3D spheroid was identified and lysed one at a time utilizing a two-photon excited laser. After each cell lysis, the contents inside the target cell were released to the surrounding media and carried out to the lysate collector. Finally, the gene expression of each individual cell was measured by two-step RT-qPCR then spatially mapped back to its original location in the spheroids to construct a 3D gene expression map.
This novel technology and approach enables multiple gene expression measurements in single cells of multicellular organisms as well as cell-to-cell heterogeneous responses to the environment with spatial recognition. Furthermore, this method can be applied to study precancerous tissues for a better understanding of cancer progression and for identifying early tumor development.