Electrical & Computer Engineering Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/2765
Browse
5 results
Search Results
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 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.