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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

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
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Description
Surface plasmon resonance (SPR) has emerged as a popular technique for elucidating subtle signals from biological events in a label-free, high throughput environment. The efficacy of conventional SPR sensors, whose signals are mass-sensitive, diminishes rapidly with the size of the observed target molecules. The following work advances the current SPR

Surface plasmon resonance (SPR) has emerged as a popular technique for elucidating subtle signals from biological events in a label-free, high throughput environment. The efficacy of conventional SPR sensors, whose signals are mass-sensitive, diminishes rapidly with the size of the observed target molecules. The following work advances the current SPR sensor paradigm for the purpose of small molecule detection. The detection limits of two orthogonal components of SPR measurement are targeted: speed and sensitivity. In the context of this report, speed refers to the dynamic range of measured kinetic rate constants, while sensitivity refers to the target molecule mass limitation of conventional SPR measurement. A simple device for high-speed microfluidic delivery of liquid samples to a sensor surface is presented to address the temporal limitations of conventional SPR measurement. The time scale of buffer/sample switching is on the order of milliseconds, thereby minimizing the opportunity for sample plug dispersion. The high rates of mass transport to and from the central microfluidic sensing region allow for SPR-based kinetic analysis of binding events with dissociation rate constants (kd) up to 130 s-1. The required sample volume is only 1 μL, allowing for minimal sample consumption during high-speed kinetic binding measurement. Charge-based detection of small molecules is demonstrated by plasmonic-based electrochemical impedance microscopy (P-EIM). The dependence of surface plasmon resonance (SPR) on surface charge density is used to detect small molecules (60-120 Da) printed on a dextran-modified sensor surface. The SPR response to an applied ac potential is a function of the surface charge density. This optical signal is comprised of a dc and an ac component, and is measured with high spatial resolution. The amplitude and phase of local surface impedance is provided by the ac component. The phase signal of the small molecules is a function of their charge status, which is manipulated by the pH of a solution. This technique is used to detect and distinguish small molecules based on their charge status, thereby circumventing the mass limitation (~100 Da) of conventional SPR measurement.
ContributorsMacGriff, Christopher Assiff (Author) / Tao, Nongjian (Thesis advisor) / Wang, Shaopeng (Committee member) / LaBaer, Joshua (Committee member) / Chae, Junseok (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Distributed inference has applications in a wide range of fields such as source localization, target detection, environment monitoring, and healthcare. In this dissertation, distributed inference schemes which use bounded transmit power are considered. The performance of the proposed schemes are studied for a variety of inference problems. In the first

Distributed inference has applications in a wide range of fields such as source localization, target detection, environment monitoring, and healthcare. In this dissertation, distributed inference schemes which use bounded transmit power are considered. The performance of the proposed schemes are studied for a variety of inference problems. In the first part of the dissertation, a distributed detection scheme where the sensors transmit with constant modulus signals over a Gaussian multiple access channel is considered. The deflection coefficient of the proposed scheme is shown to depend on the characteristic function of the sensing noise, and the error exponent for the system is derived using large deviation theory. Optimization of the deflection coefficient and error exponent are considered with respect to a transmission phase parameter for a variety of sensing noise distributions including impulsive ones. The proposed scheme is also favorably compared with existing amplify-and-forward (AF) and detect-and-forward (DF) schemes. The effect of fading is shown to be detrimental to the detection performance and simulations are provided to corroborate the analytical results. The second part of the dissertation studies a distributed inference scheme which uses bounded transmission functions over a Gaussian multiple access channel. The conditions on the transmission functions under which consistent estimation and reliable detection are possible is characterized. For the distributed estimation problem, an estimation scheme that uses bounded transmission functions is proved to be strongly consistent provided that the variance of the noise samples are bounded and that the transmission function is one-to-one. The proposed estimation scheme is compared with the amplify and forward technique and its robustness to impulsive sensing noise distributions is highlighted. It is also shown that bounded transmissions suffer from inconsistent estimates if the sensing noise variance goes to infinity. For the distributed detection problem, similar results are obtained by studying the deflection coefficient. Simulations corroborate our analytical results. In the third part of this dissertation, the problem of estimating the average of samples distributed at the nodes of a sensor network is considered. A distributed average consensus algorithm in which every sensor transmits with bounded peak power is proposed. In the presence of communication noise, it is shown that the nodes reach consensus asymptotically to a finite random variable whose expectation is the desired sample average of the initial observations with a variance that depends on the step size of the algorithm and the variance of the communication noise. The asymptotic performance is characterized by deriving the asymptotic covariance matrix using results from stochastic approximation theory. It is shown that using bounded transmissions results in slower convergence compared to the linear consensus algorithm based on the Laplacian heuristic. Simulations corroborate our analytical findings. Finally, a robust distributed average consensus algorithm in which every sensor performs a nonlinear processing at the receiver is proposed. It is shown that non-linearity at the receiver nodes makes the algorithm robust to a wide range of channel noise distributions including the impulsive ones. It is shown that the nodes reach consensus asymptotically and similar results are obtained as in the case of transmit non-linearity. Simulations corroborate our analytical findings and highlight the robustness of the proposed algorithm.
ContributorsDasarathan, Sivaraman (Author) / Tepedelenlioğlu, Cihan (Thesis advisor) / Papandreou-Suppappola, Antonia (Committee member) / Reisslein, Martin (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2013
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Description
This research emphasizes the use of low energy and low temperature post processing to improve the performance and lifetime of thin films and thin film transistors, by applying the fundamentals of interaction of materials with conductive heating and electromagnetic radiation. Single frequency microwave anneal is used to rapidly recrystallize the

This research emphasizes the use of low energy and low temperature post processing to improve the performance and lifetime of thin films and thin film transistors, by applying the fundamentals of interaction of materials with conductive heating and electromagnetic radiation. Single frequency microwave anneal is used to rapidly recrystallize the damage induced during ion implantation in Si substrates. Volumetric heating of the sample in the presence of the microwave field facilitates quick absorption of radiation to promote recrystallization at the amorphous-crystalline interface, apart from electrical activation of the dopants due to relocation to the substitutional sites. Structural and electrical characterization confirm recrystallization of heavily implanted Si within 40 seconds anneal time with minimum dopant diffusion compared to rapid thermal annealed samples. The use of microwave anneal to improve performance of multilayer thin film devices, e.g. thin film transistors (TFTs) requires extensive study of interaction of individual layers with electromagnetic radiation. This issue has been addressed by developing detail understanding of thin films and interfaces in TFTs by studying reliability and failure mechanisms upon extensive stress test. Electrical and ambient stresses such as illumination, thermal, and mechanical stresses are inflicted on the mixed oxide based thin film transistors, which are explored due to high mobilities of the mixed oxide (indium zinc oxide, indium gallium zinc oxide) channel layer material. Semiconductor parameter analyzer is employed to extract transfer characteristics, useful to derive mobility, subthreshold, and threshold voltage parameters of the transistors. Low temperature post processing anneals compatible with polymer substrates are performed in several ambients (oxygen, forming gas and vacuum) at 150 °C as a preliminary step. The analysis of the results pre and post low temperature anneals using device physics fundamentals assists in categorizing defects leading to failure/degradation as: oxygen vacancies, thermally activated defects within the bandgap, channel-dielectric interface defects, and acceptor-like or donor-like trap states. Microwave anneal has been confirmed to enhance the quality of thin films, however future work entails extending the use of electromagnetic radiation in controlled ambient to facilitate quick post fabrication anneal to improve the functionality and lifetime of these low temperature fabricated TFTs.
ContributorsVemuri, Rajitha (Author) / Alford, Terry L. (Thesis advisor) / Theodore, N David (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Zinc oxide (ZnO), a naturally n-type semiconductor has been identified as a promising candidate to replace indium tin oxide (ITO) as the transparent electrode in solar cells, because of its wide bandgap (3.37 eV), abundant source materials and suitable refractive index (2.0 at 600 nm). Spray deposition is a convenient

Zinc oxide (ZnO), a naturally n-type semiconductor has been identified as a promising candidate to replace indium tin oxide (ITO) as the transparent electrode in solar cells, because of its wide bandgap (3.37 eV), abundant source materials and suitable refractive index (2.0 at 600 nm). Spray deposition is a convenient and low cost technique for large area and uniform deposition of semiconductor thin films. In particular, it provides an easier way to dope the film by simply adding the dopant precursor into the starting solution. In order to reduce the resistivity of undoped ZnO, many works have been done by doping in the ZnO with either group IIIA elements or VIIA elements using spray pyrolysis. However, the resistivity is still too high to meet TCO's resistivity requirement. In the present work, a novel co-spray deposition technique is developed to bypass a fundamental limitation in the conventional spray deposition technique, i.e. the deposition of metal oxides from incompatible precursors in the starting solution. With this technique, ZnO films codoped with one cationic dopant, Al, Cr, or Fe, and an anionic dopant, F, have been successfully synthesized, in which F is incompatible with all these three cationic dopants. Two starting solutions were prepared and co-sprayed through two separate spray heads. One solution contained only the F precursor, NH 4F. The second solution contained the Zn and one cationic dopant precursors, Zn(O 2CCH 3) 2 and AlCl 3, CrCl 3, or FeCl 3. The deposition was carried out at 500 &degC; on soda-lime glass in air. Compared to singly-doped ZnO thin films, codoped ZnO samples showed better electrical properties. Besides, a minimum sheet resistance, 55.4 Ω/sq, was obtained for Al and F codoped ZnO films after vacuum annealing at 400 &degC;, which was lower than singly-doped ZnO with either Al or F. The transmittance for the Al and F codoped ZnO samples was above 90% in the visible range. This co-spray deposition technique provides a simple and cost-effective way to synthesize metal oxides from incompatible precursors with improved properties.
ContributorsZhou, Bin (Author) / Tao, Meng (Thesis advisor) / Goryll, Michael (Committee member) / Vasileska, Dragica (Committee member) / Yu, Hongbin (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Chalcogenide glass (ChG) materials have gained wide attention because of their applications in conductive bridge random access memory (CBRAM), phase change memories (PC-RAM), optical rewritable disks (CD-RW and DVD-RW), microelectromechanical systems (MEMS), microfluidics, and optical communications. One of the significant properties of ChG materials is the change in the resistivity

Chalcogenide glass (ChG) materials have gained wide attention because of their applications in conductive bridge random access memory (CBRAM), phase change memories (PC-RAM), optical rewritable disks (CD-RW and DVD-RW), microelectromechanical systems (MEMS), microfluidics, and optical communications. One of the significant properties of ChG materials is the change in the resistivity of the material when a metal such as Ag or Cu is added to it by diffusion. This study demonstrates the potential radiation-sensing capabilities of two metal/chalcogenide glass device configurations. Lateral and vertical device configurations sense the radiation-induced migration of Ag+ ions in germanium selenide glasses via changes in electrical resistance between electrodes on the ChG. Before irradiation, these devices exhibit a high-resistance `OFF-state' (in the order of 10E12) but following irradiation, with either 60-Co gamma-rays or UV light, their resistance drops to a low-resistance `ON-state' (around 10E3). Lateral devices have exhibited cyclical recovery with room temperature annealing of the Ag doped ChG, which suggests potential uses in reusable radiation sensor applications. The feasibility of producing inexpensive flexible radiation sensors has been demonstrated by studying the effects of mechanical strain and temperature stress on sensors formed on flexible polymer substrate. The mechanisms of radiation-induced Ag/Ag+ transport and reactions in ChG have been modeled using a finite element device simulator, ATLAS. The essential reactions captured by the simulator are radiation-induced carrier generation, combined with reduction/oxidation for Ag species in the chalcogenide film. Metal-doped ChGs are solid electrolytes that have both ionic and electronic conductivity. The ChG based Programmable Metallization Cell (PMC) is a technology platform that offers electric field dependent resistance switching mechanisms by formation and dissolution of nano sized conductive filaments in a ChG solid electrolyte between oxidizable and inert electrodes. This study identifies silver anode agglomeration in PMC devices following large radiation dose exposure and considers device failure mechanisms via electrical and material characterization. The results demonstrate that by changing device structural parameters, silver agglomeration in PMC devices can be suppressed and reliable resistance switching may be maintained for extremely high doses ranging from 4 Mrad(GeSe) to more than 10 Mrad (ChG).
ContributorsDandamudi, Pradeep (Author) / Kozicki, Michael N (Thesis advisor) / Barnaby, Hugh J (Committee member) / Holbert, Keith E. (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2013
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Description
ABSTRACT



Post Translational Modifications (PTMs) are a series of chemical modifications with the capacity to expand the structural and functional repertoire of proteins. PTMs can regulate protein-protein interaction, localization, protein turn-over, the active state of the protein, and much more. This can dramatically affect cell processes as relevant

ABSTRACT



Post Translational Modifications (PTMs) are a series of chemical modifications with the capacity to expand the structural and functional repertoire of proteins. PTMs can regulate protein-protein interaction, localization, protein turn-over, the active state of the protein, and much more. This can dramatically affect cell processes as relevant as gene expression, cell-cell recognition, and cell signaling. Along these lines, this Ph.D. thesis examines the role of two of the most important PTMs: glycosylation and phosphorylation.

In chapters 2, 3 and 4, a 10,000 peptide microarray is used to analyze the glycan variations in a series lipopolysaccharides (LPS) from Gram negative bacteria. This research was the first to demonstrate that using a small subset of random sequence peptides, it was possible to identify a small subset with the capacity to bind to the LPS of bacteria. These peptides bound to LPS not only in the solid surface of the array but also in solution as demonstrated with surface plasmon resonance (SPR), isothermal titration calorimetry (ITC) and flow cytometry. Interestingly, some of the LPS binding peptides also exhibit antimicrobial activity, a property that is also analyzed in this work.

In chapters 5 and 6, the role of protein phosphorylation, another PTM, is analyzed in the context of human cancer. High risk neuroblastoma, a very aggressive pediatric cancer, was studied with emphasis on the phosphorylations of two selected oncoproteins: the transcription factor NMYC and the adaptor protein ShcC. Both proteins were isolated from high risk neuroblastoma cells, and a targeted-directed tandem mass spectrometry (LC-MS/MS) methodology was used to identify the phosphorylation sites in each protein. Using this method dramatically improved the phosphorylation site detection and increased the number of sites detected up to 250% in comparison with previous studies. Several of the novel identified sites were located in functional domain of the proteins and that some of them are homologous to known active sites in other proteins of the same family. The chapter concludes with a computational prediction of the kinases that potentially phosphorylate those sites and a series of assays to show this phosphorylation occurred in vitro.
ContributorsMorales Betanzos, Carlos (Author) / LaBaer, Joshua (Thesis advisor) / Allen, James (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Inductors are fundamental components that do not scale well. Their physical limitations to scalability along with their inherent losses make them the main obstacle in achieving monolithic system-on-chip platform (SoCP). For past decades researchers focused on integrating magnetic materials into on-chip inductors in the quest of achieving high inductance density

Inductors are fundamental components that do not scale well. Their physical limitations to scalability along with their inherent losses make them the main obstacle in achieving monolithic system-on-chip platform (SoCP). For past decades researchers focused on integrating magnetic materials into on-chip inductors in the quest of achieving high inductance density and quality factor (QF). The state of the art on-chip inductor is made of an enclosed magnetic thin-film around the current carrying wire for maximum flux amplification. Though the integration of magnetic materials results in enhanced inductor characteristics, this approach has its own challenges and limitations especially in power applications. The current-induced magnetic field (HDC) drives the magnetic film into its saturation state. At saturation, inductance and QF drop to that of air-core inductors, eliminating the benefits of integrating magnetic materials. Increasing the current carrying capability without substantially sacrificing benefits brought on by the magnetic material is an open challenge in power applications. Researchers continue to address this challenge along with the continuous improvement in inductance and QF for RF and power applications.

In this work on-chip inductors incorporating magnetic Co-4%Zr-4%Ta -8%B thin films were fabricated and their characteristics were examined under the influence of an externally applied DC magnetic field. It is well established that spins in magnetic materials tend to align themselves in the same direction as the applied field. The resistance of the inductor resulting from the ferromagnetic film can be changed by manipulating the orientation of magnetization. A reduction in resistance should lead to decreases in losses and an enhancement in the QF. The effect of externally applied DC magnetic field along the easy and hard axes was thoroughly investigated. Depending on the strength and orientation of the externally applied field significant improvements in QF response were gained at the expense of a relative reduction in inductance. Characteristics of magnetic-based inductors degrade with current-induced stress. It was found that applying an externally low DC magnetic field across the on-chip inductor prevents the degradation in inductance and QF responses. Examining the effect of DC magnetic field on current carrying capability under low temperature is suggested.
ContributorsKhdour, Mahmoud (Author) / Yu, Hongbin (Thesis advisor) / Pan, George (Committee member) / Goryll, Michael (Committee member) / Bearat, Hamdallah (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Semiconductor manufacturing economics necessitate the development of innovative device measurement techniques for quick assessment of products. Several novel electrical measurement techniques will be proposed for screening silicon device parameters. The studied parameters range from oxide reliability, and carrier lifetime in MOS capacitors to the power MOSFET reverse recovery.

It will be

Semiconductor manufacturing economics necessitate the development of innovative device measurement techniques for quick assessment of products. Several novel electrical measurement techniques will be proposed for screening silicon device parameters. The studied parameters range from oxide reliability, and carrier lifetime in MOS capacitors to the power MOSFET reverse recovery.

It will be shown that positive charge trapping is a dominant process when thick oxides are stressed through the ramped voltage test (RVT). Exploiting the physics behind positive charge generation/trapping at high electric fields, a fast I-V measurement technique is proposed that can be used to effectively distinguish the ultra-thick oxides' intrinsic quality at low electric fields.

Next, two novel techniques will be presented for studying the carrier lifetime in MOS Capacitor devices. It will be shown that the deep-level transient spectroscopy (DLTS) can be applied to MOS test structures as a swift mean for screening the generation lifetime. Recombination lifetime will also be addressed by introducing the optically-excited MOS technique as a promising tool.

The last part of this work is devoted to the reverse recovery behavior of the body diode of power MOSFETs. The correct interpretation of the LDMOS reverse recovery is challenging and requires special attention. A simple approach will be presented to extract meaningful lifetime values from the reverse recovery of LDMOS body-diodes exploiting their gate voltage and the magnitude of the reverse bias.
ContributorsElhami Khorasani, Arash (Author) / Alford, Terry L. (Thesis advisor) / Goryll, Michael (Committee member) / Theodore, David (Committee member) / Arizona State University (Publisher)
Created2015
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Description
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by progressive autoimmune destruction of insulin-producing pancreatic β-cells. Genetic, immunological and environmental factors contribute to T1D development. The focus of this dissertation is to track the humoral immune response in T1D by profiling autoantibodies (AAbs) and anti-viral antibodies using an

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by progressive autoimmune destruction of insulin-producing pancreatic β-cells. Genetic, immunological and environmental factors contribute to T1D development. The focus of this dissertation is to track the humoral immune response in T1D by profiling autoantibodies (AAbs) and anti-viral antibodies using an innovative protein array platform called Nucleic Acid Programmable Protein Array (NAPPA).

AAbs provide value in identifying individuals at risk, stratifying patients with different clinical courses, improving our understanding of autoimmune destructions, identifying antigens for cellular immune response and providing candidates for prevention trials in T1D. A two-stage serological AAb screening against 6,000 human proteins was performed. A dual specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) was validated with 36% sensitivity at 98% specificity by an orthogonal immunoassay. This is the first systematic screening for novel AAbs against large number of human proteins by protein arrays in T1D. A more comprehensive search for novel AAbs was performed using a knowledge-based approach by ELISA and a screening-based approach against 10,000 human proteins by NAPPA. Six AAbs were identified and validated with sensitivities ranged from 16% to 27% at 95% specificity. These two studies enriched the T1D “autoantigenome” and provided insights into T1D pathophysiology in an unprecedented breadth and width.

The rapid rise of T1D incidence suggests the potential involvement of environmental factors including viral infections. Sero-reactivity to 646 viral antigens was assessed in new-onset T1D patients. Antibody positive rate of EBV was significantly higher in cases than controls that suggested a potential role of EBV in T1D development. A high density-NAPPA platform was demonstrated with high reproducibility and sensitivity in profiling anti-viral antibodies.

This dissertation shows the power of a protein-array based immunoproteomics approach to characterize humoral immunoprofile against human and viral proteomes. The identification of novel T1D-specific AAbs and T1D-associated viruses will help to connect the nodes in T1D etiology and provide better understanding of T1D pathophysiology.
ContributorsBian, Xiaofang (Author) / LaBaer, Joshua (Thesis advisor) / Mandarino, Lawrence (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2015