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- All Subjects: Biomedical Engineering
- Genre: Doctoral Dissertation
Description
A dual-channel directional digital hearing aid (DHA) front-end using a fully differential difference amplifier (FDDA) based Microphone interface circuit (MIC) for a capacitive Micro Electro Mechanical Systems (MEMS) microphones and an adaptive-power analog font end (AFE) is presented. The Microphone interface circuit based on FDDA converts the capacitance variations into voltage signal, achieves a noise of 32 dB SPL (sound pressure level) and an SNR of 72 dB, additionally it also performs single to differential conversion allowing for fully differential analog signal chain. The analog front-end consists of 40dB VGA and a power scalable continuous time sigma delta ADC, with 68dB SNR dissipating 67u¬W from a 1.2V supply. The ADC implements a self calibrating feedback DAC, for calibrating the 2nd order non-linearity. The VGA and power scalable ADC is fabricated on 0.25 um CMOS TSMC process. The dual channels of the DHA are precisely matched and achieve about 0.5dB gain mismatch, resulting in greater than 5dB directivity index. This will enable a highly integrated and low power DHA
ContributorsNaqvi, Syed Roomi (Author) / Kiaei, Sayfe (Thesis advisor) / Bakkaloglu, Bertan (Committee member) / Chae, Junseok (Committee member) / Barnby, Hugh (Committee member) / Aberle, James T., 1961- (Committee member) / Arizona State University (Publisher)
Created2011
Description
Demand for biosensor research applications is growing steadily. According to a new report by Frost & Sullivan, the biosensor market is expected to reach $14.42 billion by 2016. Clinical diagnostic applications continue to be the largest market for biosensors, and this demand is likely to continue through 2016 and beyond. Biosensor technology for use in clinical diagnostics, however, requires translational research that moves bench science and theoretical knowledge toward marketable products. Despite the high volume of academic research to date, only a handful of biomedical devices have become viable commercial applications. Academic research must increase its focus on practical uses for biosensors. This dissertation is an example of this increased focus, and discusses work to advance microfluidic-based protein biosensor technologies for practical use in clinical diagnostics. Four areas of work are discussed: The first involved work to develop reusable/reconfigurable biosensors that are useful in applications like biochemical science and analytical chemistry that require detailed sensor calibration. This work resulted in a prototype sensor and an in-situ electrochemical surface regeneration technique that can be used to produce microfluidic-based reusable biosensors. The second area of work looked at non-specific adsorption (NSA) of biomolecules, which is a persistent challenge in conventional microfluidic biosensors. The results of this work produced design methods that reduce the NSA. The third area of work involved a novel microfluidic sensing platform that was designed to detect target biomarkers using competitive protein adsorption. This technique uses physical adsorption of proteins to a surface rather than complex and time-consuming immobilization procedures. This method enabled us to selectively detect a thyroid cancer biomarker, thyroglobulin, in a controlled-proteins cocktail and a cardiovascular biomarker, fibrinogen, in undiluted human serum. The fourth area of work involved expanding the technique to produce a unique protein identification method; Pattern-recognition. A sample mixture of proteins generates a distinctive composite pattern upon interaction with a sensing platform consisting of multiple surfaces whereby each surface consists of a distinct type of protein pre-adsorbed on the surface. The utility of the "pattern-recognition" sensing mechanism was then verified via recognition of a particular biomarker, C-reactive protein, in the cocktail sample mixture.
ContributorsChoi, Seokheun (Author) / Chae, Junseok (Thesis advisor) / Tao, Nongjian (Committee member) / Yu, Hongyu (Committee member) / Forzani, Erica (Committee member) / Arizona State University (Publisher)
Created2011
Description
Alzheimer's Disease (AD) is a debilitating neurodegenerative disease. The disease leads to dementia and loss of cognitive functions and affects about 4.5 million people in the United States. It is the 7th leading cause of death and is a huge financial burden on the healthcare industry. There are no means of diagnosing the disease before neurodegeneration is significant and sadly there is no cure that controls its progression. The protein beta-amyloid or Aâ plays an important role in the progression of the disease. It is formed from the cleavage of the Amyloid Precursor Protein by two enzymes - â and ã-secretases and is found in the plaques that are deposits found in Alzheimer brains. This work describes the generation of therapeutics based on inhibition of the cleavage by â-secretase. Using in-vitro recombinant antibody display libraries to screen for single chain variable fragment (scFv) antibodies; this work describes the isolation and characterization of scFv that target the â-secretase cleavage site on APP. This approach is especially relevant since non-specific inhibition of the enzyme may have undesirable effects since the enzyme has been shown to have other important substrates. The scFv iBSEC1 successfully recognized APP, reduced â-secretase cleavage of APP and reduced Aâ levels in a cell model of Alzheimer's Disease. This work then describes the first application of bispecific antibody therapeutics to Alzheimer's Disease. iBSEC1 scFv was combined with a proteolytic scFv that enhances the "good" pathway (á-secretase cleavage) that results in alternative cleavage of APP to generate the bispecific tandem scFv - DIA10D. DIA10D reduced APP cleavage by â-secretase and steered it towards the "good" pathway thus increasing the generation of the fragment sAPPá which is neuroprotective. Finally, treatment with iBSEC1 is evaluated for reduced oxidative stress, which is observed in cells over expressing APP when they are exposed to stress. Recombinant antibody based therapeutics like scFv have several advantages since they retain the high specificity of the antibodies but are safer since they lack the constant region and are smaller, potentially facilitating easier delivery to the brain
ContributorsBoddapati, Shanta (Author) / Sierks, Michael (Thesis advisor) / Arizona State University (Publisher)
Created2011
Description
In this work, a novel method is developed for making nano- and micro- fibrous hydrogels capable of preventing the rejection of implanted materials. This is achieved by either (1) mimicking the native cellular environment, to exert fine control over the cellular response or (2) acting as a protective barrier, to camouflage the foreign nature of a material and evade recognition by the immune system. Comprehensive characterization and in vitro studies described here provide a foundation for developing substrates for use in clinical applications. Hydrogel dextran and poly(acrylic acid) (PAA) fibers are formed via electrospinning, in sizes ranging from nanometers to microns in diameter. While "as-electrospun" fibers are continuous in length, sonication is used to fragment fibers into short fiber "bristles" and generate nano- and micro- fibrous surface coatings over a wide range of topographies. Dex-PAA fibrous surfaces are chemically modified, and then optimized and characterized for non-fouling and ECM-mimetic properties. The non-fouling nature of fibers is verified, and cell culture studies show differential responses dependent upon chemical, topographical and mechanical properties. Dex-PAA fibers are advantageously unique in that (1) a fine degree of control is possible over three significant parameters critical for modifying cellular response: topography, chemistry and mechanical properties, over a range emulating that of native cellular environments, (2) the innate nature of the material is non-fouling, providing an inert background for adding back specific bioactive functionality, and (3) the fibers can be applied as a surface coating or comprise the scaffold itself. This is the first reported work of dex-PAA hydrogel fibers formed via electrospinning and thermal cross-linking, and unique to this method, no toxic solvents or cross-linking agents are needed to create hydrogels or for surface attachment. This is also the first reported work of using sonication to fragment electrospun hydrogel fibers, and in which surface coatings were made via simple electrostatic interaction and dehydration. These versatile features enable fibrous surface coatings to be applied to virtually any material. Results of this research broadly impact the design of biomaterials which contact cells in the body by directing the consequent cell-material interaction.
ContributorsLouie, Katherine BoYook (Author) / Massia, Stephen P (Thesis advisor) / Bennett, Kevin (Committee member) / Garcia, Antonio (Committee member) / Pauken, Christine (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2011
Description
Biological membranes are critical to cell sustainability by selectively permeating polar molecules into the intracellular space and providing protection to the interior organelles. Biomimetic membranes (model cell membranes) are often used to fundamentally study the lipid bilayer backbone structure of the biological membrane. Lipid bilayer membranes are often supported using inorganic materials in an effort to improve membrane stability and for application to novel biosensing platforms. Published literature has shown that a variety of dense inorganic materials with various surface properties have been investigated for the study of biomimetic membranes. However, literature does not adequately address the effect of porous materials or supports with varying macroscopic geometries on lipid bilayer membrane behavior. The objective of this dissertation is to present a fundamental study on the synthesis of lipid bilayer membranes supported by novel inorganic supports in an effort to expand the number of available supports for biosensing technology. There are two fundamental areas covered including: (1) synthesis of lipid bilayer membranes on porous inorganic materials and (2) synthesis and characterization of cylindrically supported lipid bilayer membranes. The lipid bilayer membrane formation behavior on various porous supports was studied via direct mass adsorption using a quartz crystal microbalance. Experimental results demonstrate significantly different membrane formation behaviors on the porous inorganic supports. A lipid bilayer membrane structure was formed only on SiO2 based surfaces (dense SiO2 and silicalite, basic conditions) and gamma-alumina (acidic conditions). Vesicle monolayer adsorption was observed on gamma-alumina (basic conditions), and yttria stabilized zirconia (YSZ) of varying roughness. Parameters such as buffer pH, surface chemistry and surface roughness were found to have a significant impact on the vesicle adsorption kinetics. Experimental and modeling work was conducted to study formation and characterization of cylindrically supported lipid bilayer membranes. A novel sensing technique (long-period fiber grating refractometry) was utilized to measure the formation mechanism of lipid bilayer membranes on an optical fiber. It was found that the membrane formation kinetics on the fiber was similar to its planar SiO2 counterpart. Fluorescence measurements verified membrane transport behavior and found that characterization artifacts affected the measured transport behavior.
ContributorsEggen, Carrie (Author) / Lin, Jerry Y.S. (Thesis advisor) / Dai, Lenore (Committee member) / Rege, Kaushal (Committee member) / Thornton, Trevor (Committee member) / Vogt, Bryan (Committee member) / Arizona State University (Publisher)
Created2011
Description
Computed tomography (CT) is one of the essential imaging modalities for medical diagnosis. Since its introduction in 1972, CT technology has been improved dramatically, especially in terms of its acquisition speed. However, the main principle of CT which consists in acquiring only density information has not changed at all until recently. Different materials may have the same CT number, which may lead to uncertainty or misdiagnosis. Dual-energy CT (DECT) was reintroduced recently to solve this problem by using the additional spectral information of X-ray attenuation and aims for accurate density measurement and material differentiation. However, the spectral information lies in the difference between two low and high energy images or measurements, so that it is difficult to acquire the accurate spectral information due to amplification of high pixel noise in the resulting difference image. In this work, a new model and an image enhancement technique for DECT are proposed, based on the fact that the attenuation of a high density material decreases more rapidly as X-ray energy increases. This fact has been previously ignored in most of DECT image enhancement techniques. The proposed technique consists of offset correction, spectral error correction, and adaptive noise suppression. It reduced noise, improved contrast effectively and showed better material differentiation in real patient images as well as phantom studies.
ContributorsPark, Kyung Kook (Author) / Metin, Akay (Thesis advisor) / Pavlicek, William (Committee member) / Akay, Yasemin (Committee member) / Towe, Bruce (Committee member) / Muthuswamy, Jitendran (Committee member) / Arizona State University (Publisher)
Created2011
Description
Phase contrast magnetic resonance angiography (PCMRA) is a non-invasive imaging modality that is capable of producing quantitative vascular flow velocity information. The encoding of velocity information can significantly increase the imaging acquisition and reconstruction durations associated with this technique. The purpose of this work is to provide mechanisms for reducing the scan time of a 3D phase contrast exam, so that hemodynamic velocity data may be acquired robustly and with a high sensitivity. The methods developed in this work focus on the reduction of scan duration and reconstruction computation of a neurovascular PCMRA exam. The reductions in scan duration are made through a combination of advances in imaging and velocity encoding methods. The imaging improvements are explored using rapid 3D imaging techniques such as spiral projection imaging (SPI), Fermat looped orthogonally encoded trajectories (FLORET), stack of spirals and stack of cones trajectories. Scan durations are also shortened through the use and development of a novel parallel imaging technique called Pretty Easy Parallel Imaging (PEPI). Improvements in the computational efficiency of PEPI and in general MRI reconstruction are made in the area of sample density estimation and correction of 3D trajectories. A new method of velocity encoding is demonstrated to provide more efficient signal to noise ratio (SNR) gains than current state of the art methods. The proposed velocity encoding achieves improved SNR through the use of high gradient moments and by resolving phase aliasing through the use measurement geometry and non-linear constraints.
ContributorsZwart, Nicholas R (Author) / Frakes, David H (Thesis advisor) / Pipe, James G (Thesis advisor) / Bennett, Kevin M (Committee member) / Debbins, Josef P (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2011
Description
An accurate sense of upper limb position is crucial to reaching movements where sensory information about upper limb position and target location is combined to specify critical features of the movement plan. This dissertation was dedicated to studying the mechanisms of how the brain estimates the limb position in space and the consequences of misestimation of limb position on movements. Two independent but related studies were performed. The first involved characterizing the neural mechanisms of limb position estimation in the non-human primate brain. Single unit recordings were obtained in area 5 of the posterior parietal cortex in order to examine the role of this area in estimating limb position based on visual and somatic signals (proprioceptive, efference copy). When examined individually, many area 5 neurons were tuned to the position of the limb in the workspace but very few neurons were modulated by visual feedback. At the population level however decoding of limb position was somewhat more accurate when visual feedback was provided. These findings support a role for area 5 in limb position estimation but also suggest that visual signals regarding limb position are only weakly represented in this area, and only at the population level. The second part of this dissertation focused on the consequences of misestimation of limb position for movement production. It is well known that limb movements are inherently variable. This variability could be the result of noise arising at one or more stages of movement production. Here we used biomechanical modeling and simulation techniques to characterize movement variability resulting from noise in estimating limb position ('sensing noise') and in planning required movement vectors ('planning noise'), and compared that to the variability expected due to noise in movement execution. We found that the effects of sensing and planning related noise on movement variability were dependent upon both the planned movement direction and the initial configuration of the arm and were different in many respects from the effects of execution noise.
ContributorsShi, Ying (Author) / Buneo, Christopher A (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Santello, Marco (Committee member) / He, Jiping (Committee member) / Santos, Veronica (Committee member) / Arizona State University (Publisher)
Created2011
Description
Treatment of cerebral aneurysms using non-invasive methods has existed for decades. Since the advent of modern endovascular techniques, advancements to embolic materials have largely focused on improving platinum coil technology. However, the recent development of Onyx®, a liquid-delivery precipitating polymer system, has opened the door for a new class of embolic materials--liquid-fill systems. These liquid-fill materials have the potential to provide better treatment outcomes than platinum coils. Initial clinical use of Onyx has proven promising, but not without substantial drawbacks, such as co-delivery of angiotoxic compounds and an extremely technical delivery procedure. This work focuses on formulation, characterization and testing of a novel liquid-to-solid gelling polymer system, based on poly(propylene glycol) diacrylate (PPODA) and pentaerythritol tetrakis(3-mercaptopropionate) (QT). The PPODA-QT system bypasses difficulties associated with Onyx embolization, yet still maintains non-invasive liquid delivery--exhibiting the properties of an ideal embolic material for cerebral aneurysm embolization. To allow for material visibility during clinical delivery, an embolic material must be radio-opaque. The PPODA-QT system was formulated with commercially available contrast agents and the gelling kinetics were studied, as a complete understanding of the gelling process is vital for clinical use. These PPODA-QT formulations underwent in vitro characterization of material properties including cytotoxicity, swelling, and degradation behaviors. Formulation and characterization tests led to an optimized PPODA-QT formulation that was used in subsequent in vivo testing. PPODA-QT formulated with the liquid contrast agent ConrayTM was used in the first in vivo studies. These studies employed a swine aneurysm model to assess initial biocompatibility and test different delivery strategies of PPODA-QT. Results showed good biocompatibility and a suitable delivery strategy, providing justification for further in vivo testing. PPODA-QT was then used in a small scale pilot study to gauge long-term effectiveness of the material in a clinically-relevant aneurysm model. Results from the pilot study showed that PPODA-QT has the capability to provide successful, long-term treatment of model aneurysms as well as facilitate aneurysm healing.
ContributorsRiley, Celeste (Author) / Vernon, Brent L (Thesis advisor) / Preul, Mark C (Committee member) / Frakes, David (Committee member) / Pauken, Christine (Committee member) / Massia, Stephen (Committee member) / Arizona State University (Publisher)
Created2011
Description
Gene manipulation techniques, such as RNA interference (RNAi), offer a powerful method for elucidating gene function and discovery of novel therapeutic targets in a high-throughput fashion. In addition, RNAi is rapidly being adopted for treatment of neurological disorders, such as Alzheimer's disease (AD), Parkinson's disease, etc. However, a major challenge in both of the aforementioned applications is the efficient delivery of siRNA molecules, plasmids or transcription factors to primary cells such as neurons. A majority of the current non-viral techniques, including chemical transfection, bulk electroporation and sonoporation fail to deliver with adequate efficiencies and the required spatial and temporal control. In this study, a novel optically transparent biochip is presented that can (a) transfect populations of primary and secondary cells in 2D culture (b) readily scale to realize high-throughput transfections using microscale electroporation and (c) transfect targeted cells in culture with spatial and temporal control. In this study, delivery of genetic payloads of different sizes and molecular characteristics, such as GFP plasmids and siRNA molecules, to precisely targeted locations in primary hippocampal and HeLa cell cultures is demonstrated. In addition to spatio-temporally controlled transfection, the biochip also allowed simultaneous assessment of a) electrical activity of neurons, b) specific proteins using fluorescent immunohistochemistry, and c) sub-cellular structures. Functional silencing of GAPDH in HeLa cells using siRNA demonstrated a 52% reduction in the GAPDH levels. In situ assessment of actin filaments post electroporation indicated a sustained disruption in actin filaments in electroporated cells for up to two hours. Assessment of neural spike activity pre- and post-electroporation indicated a varying response to electroporation. The microarray based nature of the biochip enables multiple independent experiments on the same culture, thereby decreasing culture-to-culture variability, increasing experimental throughput and allowing cell-cell interaction studies. Further development of this technology will provide a cost-effective platform for performing high-throughput genetic screens.
ContributorsPatel, Chetan (Author) / Muthuswamy, Jitendran (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Jain, Tilak (Committee member) / Caplan, Michael (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2012