Theses and Dissertations from UMD
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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
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Item Lab-on-CMOS Sensors and Real-time Imaging for Biological Cell Monitoring(2019) Senevirathna, Bathiya; Abshire, Pamela; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Monitoring biological cell growth and viability is essential for in vivo biomedical diagnosis and therapy, and in vitro studies of pharmaceutical efficacy and material toxicity. Conventional monitoring techniques involve the use of dyes and markers that can potentially introduce side effects into the cell culture and often function as end-point assays. This eliminates the opportunity to track fast changes and to determine temporal correlation between measurements. Particularly in drug screening applications, high-temporal resolution cell viability data could inform decisions on drug application protocols that could lead to better treatment outcomes. This work presents development of a lab-on-chip (LoC) sensor for real-time monitoring of biological cell viability and proliferation, to provide a comprehensive picture of the changes cells undergo during their lifecycle. The LoC sensor consists of a complementary metal-oxide-semiconductor (CMOS) chip that measures the cell-to-substrate coupling of adherent cells that are cultured directly on top. This technique is non-invasive, does not require biochemical labeling, and allows for automated and unsupervised cell monitoring. The CMOS capacitance sensor was designed to addresses the ubiquitous challenges of sensitivity, noise coupling, and dynamic range that affect existing sensors. The design includes on-chip digitization, serial data output, and programmable control logic in order to facilitate packaging requirements for biological experiments. Only a microcontroller is required for readout, making it suitable for applications outside the traditional laboratory setting. An imaging platform was developed to provide time-lapse images of the sensor surface, which allowed for concurrent visual and capacitance observation of the cells. Results showed the ability of the LoC sensor to detect single cell binding events and changes in cell morphology. The sensor was used in in vitro experiments to monitor chemotherapeutic agent potency on drug-resistant and drug-sensitive cancer cell lines. Concentrations higher than 5 μM elicited cytotoxic effects on both cell lines, while a dose of 1 μM allowed discrimination of the two cell types. The system demonstrates the use of real-time capacitance measurements as a proof-of-concept tool that has potential to hasten the drug development process.Item Surface enhanced Raman spectroscopy technologies and techniques for on-site quantification of chemical and biological analytes(2017) Restaino, Stephen Mario; White, Ian M; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The rapid advancement in mobile devices has illustrated the widening technological gap in health and environmental sensing. Unfortunately, the time and financial burdens imposed by the current central lab model prohibit regular sensing of crucial biological and ecological elements, which can lead to delayed responses and exacerbated conditions. Current portable diagnostic solutions lack the necessary sensitivity or multiplexing potential to address the ever-expanding library of biomarkers. An emerging solution known as surface enhanced Raman spectroscopy (SERS) can provide the sensitivity of current techniques, but with drastically improved multiplexing density. Many existing SERS applications however, require multiple processing steps to introduce samples to the enhancement surface. Practical application of SERS to diagnostics and environmental samples requires more convenient materials and methods to support the broad array of conditions in on-site sensing. In this work, three new methods to apply SERS to portable sensing systems are developed. Specifically, a new SERS diagnostic is presented that details the first implementation of SERS for real-time PCR; we accomplished multiplexed detection of MRSA genes to specifically identify species and drug resistance. Second, we developed a new flexible SERS sponge based on PDMS that provides unprecedented control over sample handling and can readily concentration organic analytes. Finally, we present a novel raster scanning protocol to address the persistent reproducibility issues that has slowed commercialization of new SERS devices. Together, these three techniques advance the development SERS as a practical and portable solution for on-site diagnostics and environmental sensing.Item Bridging the biology-electronics communication gap with redox signaling(2015) Gordonov, Tanya; Bentley, William E; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Electronic and biological systems both have the ability to sense, respond to, and communicate relevant data. This dissertation aims to facilitate communication between the two and create bio-hybrid devices that can process the breadths of both electronic and biological information. We describe the development of novel methods that bridge this bi-directional communication gap through the use of electronically and biologically relevant redox molecules for controlled and quantitative information transfer. Additionally, we demonstrate that the incorporation of biological components onto microelectronic systems can open doors for improved capabilities in a variety of fields. First, we describe the original use of redox molecules to electronically control the activity of an enzyme on a chip. Using biofabrication techniques, we assembled HLPT, a fusion protein which generates the quorum sensing molecule autoinducer-2, on an electrodeposited chitosan film on top of an electrode. This allows the electrode to controllably oxidize the enzyme in situ through a redox mediator, acetosyringone. We successfully showed that activity decrease and bacterial quorum sensing response are proportional to the input charge. To engineer bio-electronic communication with cells, we first aimed for better characterizing an electronic method for measuring cell response. We engineered Escherichia coli (E.coli) cells to respond to autoinducer-2 by producing the β-galactosidase enzyme. We then investigated an existing electrochemical method for detecting β-galactosidase activity by measuring a redox-active product of the cleavage of the added substrate molecule PAPG. In our novel findings, the product, PAP, was found to be produced at a rate that correlated with the standard spectrophotometric method for measuring β-galactosidase, the Miller assay, in both whole live and lysed cells. Conversely, to translate electronic signals to something cells can understand, we used pyocyanin, a redox drug which oxidizes the E.coli SoxR protein and allows transcription from the soxS promoter. We utilized electronic control of ferricyanide, an electron acceptor, to amplify the production of a reporter from soxS. With this novel method, we show that production of reporter depends on the frequency and amplitude of electronic signals, and investigate the method’s metabolic effects. Overall, the work in this dissertation makes strides towards the greater goal of creating multi-functional bio-hybrid devices.Item Bio-templated Substrates for Biosensor Applications(2013) Fu, Angela Li-Hui; Kofinas, Peter; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Nanopatterning of materials is of particular interest for applications in biosensors, microfluidics, and drug delivery devices. In biosensor applications there is a need for rapid, low cost, and durable system for detection. This dissertation aims to investigate methods to pattern nanostructured surfaces using virus particles as templates. The virus species used in these experiments is a cysteine modified tobacco mosaic virus. The first project utilized the lamellar microphase separation of a block copolymer to pattern the virus particles. Although microphase separation of the poly(styrene-b-2-vinylpyridine) (PS-P2VP) into lamellae was confirmed, specificity of the viruses to the gold doped block of the polymer could not be achieved. Single virus particles lay across multiple lamellae and aggregated in side-to-side and head-to-tail arrangements. The second project studied the effect of a surfactant on virus assembly onto a gold chip. The experiments included placing a gold chip in virus solutions with varying triton concentrations (0-0.15%), then plating the virus particles with a metal. Results showed that as the triton concentration in the virus solution increases, the virus density on the surface decreases. The gold coated virus particles were applied to Surface Enhanced Raman Spectroscopy (SERS) detection in the final project. SERS is of interest for biosensor applications due to its rapid detection, low cost, portability, and label-free characteristics. In recent years, it has shown signal enhancement using gold, silver, and copper nanoparticles in solutions and on roughened surfaces. The gold plated virus surfaces were tested as SERS substrates using R6G dye as the analyte. An enhancement factor (EF) of 10^4 was seen in these samples versus the non-SERS substrate. This corresponded to the sample with 0.05% triton in the virus solution which showed the most intersection points between the virus particles and the most uniform coverage of the viruses on the surface. This value is lower than that of previous studies; however, future work may be performed to optimize conditions to achieve the highest signal possible.Item SPECTROSCOPIC ENHANCEMENT FROM NOBLE METALLIC NANOPARTICLES(2011) Tsai, Shu-Ju; Phaneuf, Raymond J.; Material Science and Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Resonant coupling of localized surface plasmon resonances (LSPRs) in noble metallic nanostructures to incident radiation and the related subject of localized behavior of electromagnetic waves are currently of great interest due to their potential application to sensors, biochemical assays, optical transmission, and photovoltaic devices. My thesis research is made up of two related parts. In part one I examined enhanced fluorescence in dye molecules in proximity to Ag nanostructures. In part two I studied the effect of Au nanostructure arrays on the performance of poly(3-hexylthiophene-2,5-diyl) : [6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCBM) bulk heterojunction (BHJ) organic solar cells (OSCs). Nanostructures were fabricated by two different methods: e-beam lithography (top down) and spray pyrolysis (bottom up). Using e-beam lithography, we produced arrays of nanostructures with well defined shapes, sizes, and spacings. By systematically varying these topographical parameters, we measured their effect on nanometer-sized metallic structure-enhanced fluorescence (nMEF) and on absorption and external quantum efficiency (EQE) in OSC devices as a function of optical wavelength. In analyzing experimental results, we carried out numerical simulations of the local electric field under incident light, across plasmonic resonances. The comparison between the calculated local field squared and measured fluorescence/EQE provides physical insight on the configuration- dependence of these two processes. Our results indicate that local field enhancement near nanostructures is dominant in nMEF, and that the local field is strongly affected by the substrate and device architectures. For the OSCs, both measurements and calculations show that absorbance within the active layer is enhanced only in a narrow band of wavelengths (~640-720 nm) where the active layer is not very absorbing for our prototype nanopillar-patterned devices. The peak enhancement for 180 nm wide Au nanopillars was approximately 60% at 675nm. The corresponding resonance involves both localized surface plasmon excitation and multiple reflections/diffraction within the cavity formed by the electrodes. Finally, we explore the role of the size of the nanostructures in such a device on the optical absorption in the OSC active layer. We find that small Au nanopillars produce strong internal absorption resulting in Joule heating, and suppressing the desired enhancement in EQE in OSC devices.Item Development of Carbon Nanotube Field-Effect Transistor Arrays for Detection of HER2 Overexpression in Breast Cancer(2011) Aschenbach, Konrad Hsu; Gomez, Romel D; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)We developed a carbon nanotube biosensor platform that was deployed at the National Cancer Institute and successfully detected the HER2 oncogene in real cancer cells at clinically relevant levels. HER2 is a receptor protein that resides on the surface of certain cancer cells and is associated with higher aggressiveness in breast cancers. Overabundance of HER2 at the chromosomal, cell surface, and intermediate gene expression levels can all indicate a dangerous HER2 status. At the present, testing for HER2 status requires labor-intensive laboratory procedures using expensive reagents. Cost remains the major barrier to widespread screening. We propose an integrated electronic testing platform based on direct label-free gene detection. The system would integrate the various labor-intensive processes that are usually performed by skilled laboratory technicians. The heart of the system is an array of carbon nanotube field-effect transistors that can detect unlabelled nucleic acids via their intrinsic electric charges. We developed a scalable fabrication technique for carbon nanotube biosensor arrays, hardware and software for data acquisition and analysis, theoretical models for detection mechanism, and protocols for immobilization of peptide nucleic acid probes and hybridization of nucleic acids extracted from cells. We demonstrated detection of HER2 from real cell lines which express cancer genes, thereby lowering the technological barrier towards commercialization of a low-cost gene expression biosensor. The system is suitable for lab-on-a-chip integration, which could bring rapid, low-cost cancer diagnoses into the clinical setting.Item Highly Sensitive Fiber Bragg Grating Biosensors(2008) Stanford, Christopher John; Dagenais, Mario; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Fiber Bragg grating sensors are highly sensitive, cost-effective solutions in chemical and biological sensing. By reducing the resolution of the optical interrogation set-up and enhancing the fiber's evanescent field, etched fiber Bragg gratings (FBG) can detect minimal refractive index shifts. Etched FBG Fabry Perot sensors decrease detectable index shifts (~2x10-9 riu) by introducing extremely narrow spectral resonances to single FBG spectra. Furthermore, we describe the fabrication of ultrahigh finesse fiber cavities and a temperature-compensated mount that will be implemented in future chemical testing. With highly sensitive refractive index sensors, we developed procedures for investigating complex surface chemistry. Chemical species are immobilized on the sensor's silica surface in order to study protein conjugation with Concanavalin A, 21-mer DNA hybridization, monolayer adsorption, and silanization. Sensor results with homogeneous or multilayer environments demonstrate good agreement with theoretical Bragg shifts calculated using the beam propagation method of determining the effective modal index.Item STUDIES OF THE OPTICAL PROPERTIES OF PLASMONIC NANOSTRUCTURES(2007-11-28) Hung, Yu-Ju; Davis, Christopher C; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Various properties of Surface Plasmon Polaritons (SPPs) at the interface between a layer of PMMA (polymethyl methacrylate) gratings and a 50 nm thick gold film have been studied. Gold has a negative dielectric constant at visible wavelength range which results in negative refraction phenomenon without medium of both permittivity () and permeability () constants negative. A direct observation of negative refraction has been demonstrated. It verifies our assumption that in the 1-D stripe PMMA gratings on top of a gold film, SPPs experience negative group velocity and positive phase velocity. With this criterion, negative refraction is the natural choice in Snell's Law. Correspondingly, it was previously claimed that with a highly anisotropic layered structure (metal/dielectric stack), the high spatial frequency k vectors scattered from an object can be preserved in an imaging system and the conventional diffraction limit is defeated. In this thesis, this kind of layered structure, a so-called "hyperlens" or "superlens", has been experimentally demonstrated and the results verify theoretical predictions. A proof of concept on corner resonators has also been demonstrated. Four squares with PMMA/Au and Air/Au are arranged so that SPPs are trapped in the corner. It shows the possibility of making a tiny resonator with zero phase paths in the cavity. An experiment utilizing the field enhancement of SPPs is designed. A surface field is excited on R6G(Rhodamine 6G, fluorophore)/PMMA gratings/Au substrate. The enhanced pumping light pushes up the emission intensity 10-fold or higher compared to a sample with a R6G/PMMA gratings/Glass platform, a transparent substrate. This device with a R6G/PMMA gratings/Au platform has the advantage that the emission light is converted to the normal direction; the collection efficiency is high and the directivity makes the examination easy under a commercial fluorescence optical microscope. This device shows the potential of R6G/PMMA/Au platforms in gene chip industry.Item Analog System-on-a-Chip with Application to Biosensors(2005-04-28) Hodge, Angela Marie; Newcomb, Robert W.; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This dissertation facilitates the design and fabrication of analog systems-on-a-chip (SoCs). In this work an analog SoC is developed with application to organic fluid analysis. The device contains a built-in self-test method for performing on-chip analysis of analog macros. The analog system-on-a-chip developed in this dissertation can be used to evaluate the properties of fluids for medical diagnoses. The research herein described covers the development of: analog SoC models, an improved set of chemical sensor arrays, a self-contained system-on-a-chip for the determination of fluid properties, and a method of performing on-chip testing of analog SoC sub-blocks.