Theses and Dissertations
This collection includes both ASU Theses and Dissertations, submitted by graduate students, and the Barrett, Honors College theses submitted by undergraduate students.
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- All Subjects: Biomedical Engineering
Description
Continuous monitoring in the adequate temporal and spatial scale is necessary for a better understanding of environmental variations. But field deployments of molecular biological analysis platforms in that scale are currently hindered because of issues with power, throughput and automation. Currently, such analysis is performed by the collection of large sample volumes from over a wide area and transporting them to laboratory testing facilities, which fail to provide any real-time information. This dissertation evaluates the systems currently utilized for in-situ field analyses and the issues hampering the successful deployment of such bioanalytial instruments for environmental applications. The design and development of high throughput, low power, and autonomous Polymerase Chain Reaction (PCR) instruments, amenable for portable field operations capable of providing quantitative results is presented here as part of this dissertation. A number of novel innovations have been reported here as part of this work in microfluidic design, PCR thermocycler design, optical design and systems integration. Emulsion microfluidics in conjunction with fluorinated oils and Teflon tubing have been used for the fluidic module that reduces cross-contamination eliminating the need for disposable components or constant cleaning. A cylindrical heater has been designed with the tubing wrapped around fixed temperature zones enabling continuous operation. Fluorescence excitation and detection have been achieved by using a light emitting diode (LED) as the excitation source and a photomultiplier tube (PMT) as the detector. Real-time quantitative PCR results were obtained by using multi-channel fluorescence excitation and detection using LED, optical fibers and a 64-channel multi-anode PMT for measuring continuous real-time fluorescence. The instrument was evaluated by comparing the results obtained with those obtained from a commercial instrument and found to be comparable. To further improve the design and enhance its field portability, this dissertation also presents a framework for the instrumentation necessary for a portable digital PCR platform to achieve higher throughputs with lower power. Both systems were designed such that it can easily couple with any upstream platform capable of providing nucleic acid for analysis using standard fluidic connections. Consequently, these instruments can be used not only in environmental applications, but portable diagnostics applications as well.
ContributorsRay, Tathagata (Author) / Youngbull, Cody (Thesis advisor) / Goryll, Michael (Thesis advisor) / Blain Christen, Jennifer (Committee member) / Yu, Hongyu (Committee member) / Arizona State University (Publisher)
Created2013
Description
Human papillomavirus (HPV) infection has a large burden on society. It is a causal agent of 99.7% of all cervical cancer cases. The prevalence of HPV infection worldwide is high, but the burden of HPV infections lies on less developed regions. Cervical cancer is not associated with immediate symptoms, screening methods are needed to detect HPV disease presence before lesions progress to cervical cancer. Protein biomarkers are a growing area of diagnostic medicine and facilitate the detection of disease at an early and treatable stage. Technologies for healthcare diagnostics often require laboratory space or expensive instrumentation, which are not feasible for point of care applications. In order for clinical diagnostics to advance in developing countries, low cost, rapid, portable, and easy to use point of care diagnostic tests are needed. The project adapts the Enzyme Linked Immunosorbent Assays (ELISA) and Nucleic Acid-Programmable Protein Array (NAPPA) to a proof of concept assay for use in magnetic bead based microfluidics. The biomarker used for analyte detection was E7, as a strong correlation has been found between presence of E7 antibodies and development of advanced cervical cancer. It is demonstrated that magnetic microfluidic assay design for rapid detection of antibodies is amenable to fluorescence detection in point of care settings. The data demonstrates that the microfluidic assay is rapid, low-cost, specific, and relevant to serology detection. The assay detects antibody responses to analytes with the point of care reader system and is realized in an on chip capacity. With the integration of anti-GST capture antibodies conjugated to the magnetic beads in the microfluidic system, many analytes can be detected without large changes to the existing assay structure, which gives the ability to adapt the system to analytes of interest rapidly.
ContributorsSnow, Kylie (Author) / Anderson, Karen (Thesis advisor) / Blain Christen, Jennifer (Committee member) / Lake, Douglas (Committee member) / Arizona State University (Publisher)
Created2022
Description
Optical Fibers coupled to laser light sources, and Light Emitting Diodes are the two classes of technologies used for optogenetic experiments. Arizona State University's Flexible Display Center fabricates novel flexible Organic Light Emitting Diodes(OLEDs). These OLEDs have the capability of being monolithically fabricated over flexible, transparent plastic substrates and having power efficient ways of addressing high density arrays of LEDs. This thesis critically evaluates the technology by identifying the key advantages, current limitations and experimentally assessing the technology in in-vivo and in-vitro animal models. For in-vivo testing, the emitted light from a flat OLED panel was directly used to stimulate the neo-cortex in the M1 region of transgenic mice expressing ChR2 (B6.Cg-Tg (Thy1-ChR2/EYFP) 9Gfng/J). An alternative stimulation paradigm using a collimating optical system coupled with an optical fiber was used for stimulating neurons in layer 5 of the motor cortex in the same transgenic mice. EMG activity was recorded from the contralateral vastus lateralis muscles. In vitro testing of the OLEDs was done in primary cortical neurons in culture transfected with blue light sensitive ChR2. The neurons were cultured on a microelectrode array for taking neuronal recordings.
ContributorsShah, Ankur (Author) / Muthuswamy, Jitendran (Thesis advisor) / Greger, Bradley (Committee member) / Blain Christen, Jennifer (Committee member) / Arizona State University (Publisher)
Created2015
Description
This work explores how flexible electronics and display technology can be applied to develop new biomedical devices for medical, biological, and life science applications. It demonstrates how new biomedical devices can be manufactured by only modifying or personalizing the upper layers of a conventional thin film transistor (TFT) display process. This personalization was applied first to develop and demonstrate the world's largest flexible digital x-ray detector for medical and industrial imaging, and the world's first flexible ISFET pH biosensor using TFT technology. These new, flexible, digital x-ray detectors are more durable than conventional glass substrate x-ray detectors, and also can conform to the surface of the object being imaged. The new flexible ISFET pH biosensors are >10X less expensive to manufacture than comparable CMOS-based ISFETs and provide a sensing area that is orders of magnitude larger than CMOS-based ISFETs. This allows for easier integration with area intensive chemical and biological recognition material as well as allow for a larger number of unique recognition sites for low cost multiple disease and pathogen detection.
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.
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.
ContributorsSmith, Joseph T. (Author) / Allee, David (Thesis advisor) / Goryll, Michael (Committee member) / Kozicki, Michael (Committee member) / Blain Christen, Jennifer (Committee member) / Couture, Aaron (Committee member) / Arizona State University (Publisher)
Created2014
Description
Cellular assays are the backbone of biological studies - be it for tissue modeling, drug discovery, therapeutics, or diagnostics. Two-dimensional (2D) cell culture has been deployed for several decades to garner physiologically relevant information and predict data before the cost-intensive animal testing. Although 2D techniques have been valuable for cellular assays, they have a colossal limitation - they do not adequately consider the natural three-dimensional (3D) microenvironment of the cells. As a result, they sometimes provide misleading statistics. Therefore, it is important to develop a 3D model that predicts cellular behaviors and their interaction with neighboring cells and extracellular matrix (ECM) in a more realistic manner. In recent biomedical research, various platforms have been modeled to generate 3D prototypes of tissues, spheroids, in vitro that could allow the study of cellular responses resembling in vivo environments, such as matrices, scaffolds, and devices. But most of these platforms have drawbacks such as lack of spheroid size control, low yield, or high cost associated with them. On the other hand, Amikagel is a low cost, high-fidelity platform that can facilitate the convenient generation of tumor and stem cell spheroids. Furthermore, Amikabeads are aminoglycoside-derived hydrogel microbeads derived from the same monomers as Amikagel. They are a versatile platform with several chemical groups that can be exploited for encapsulating the spheroids and investigating the delivery of bioactive compounds to the cells. This thesis is focused on engineering novel 3D tumor and stem cell models generated on Amikagel and encapsulated in Amikabeads for proximal delivery of bioactive compounds and applications in regenerative medicine.
ContributorsNanda, Tanya (Author) / Rege, Kaushal (Thesis advisor) / Blain Christen, Jennifer (Committee member) / Weaver, Jessica (Committee member) / Arizona State University (Publisher)
Created2020