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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

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
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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

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
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Description
Coronary heart disease (CHD) is the most prevalent cause of death worldwide. Atherosclerosis which is the condition of plaque buildup on the inside of the coronary artery wall is the main cause of CHD. Rupture of unstable atherosclerotic coronary plaque is known to be the cause of acute coronary syndrome.

Coronary heart disease (CHD) is the most prevalent cause of death worldwide. Atherosclerosis which is the condition of plaque buildup on the inside of the coronary artery wall is the main cause of CHD. Rupture of unstable atherosclerotic coronary plaque is known to be the cause of acute coronary syndrome. The composition of plaque is important for detection of plaque vulnerability. Due to prognostic importance of early stage identification, non-invasive assessment of plaque characterization is necessary. Computed tomography (CT) has emerged as a non-invasive alternative to coronary angiography. Recently, dual energy CT (DECT) coronary angiography has been performed clinically. DECT scanners use two different X-ray energies in order to determine the energy dependency of tissue attenuation values for each voxel. They generate virtual monochromatic energy images, as well as material basis pair images. The characterization of plaque components by DECT is still an active research topic since overlap between the CT attenuations measured in plaque components and contrast material shows that the single mean density might not be an appropriate measure for characterization. This dissertation proposes feature extraction, feature selection and learning strategies for supervised characterization of coronary atherosclerotic plaques. In my first study, I proposed an approach for calcium quantification in contrast-enhanced examinations of the coronary arteries, potentially eliminating the need for an extra non-contrast X-ray acquisition. The ambiguity of separation of calcium from contrast material was solved by using virtual non-contrast images. Additional attenuation data provided by DECT provides valuable information for separation of lipid from fibrous plaque since the change of their attenuation as the energy level changes is different. My second study proposed these as the input to supervised learners for a more precise classification of lipid and fibrous plaques. My last study aimed at automatic segmentation of coronary arteries characterizing plaque components and lumen on contrast enhanced monochromatic X-ray images. This required extraction of features from regions of interests. This study proposed feature extraction strategies and selection of important ones. The results show that supervised learning on the proposed features provides promising results for automatic characterization of coronary atherosclerotic plaques by DECT.
ContributorsYamak, Didem (Author) / Akay, Metin (Thesis advisor) / Muthuswamy, Jit (Committee member) / Akay, Yasemin (Committee member) / Pavlicek, William (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Aqueous solutions of temperature-responsive copolymers based on N-isopropylacrylamide (NIPAAm) hold promise for medical applications because they can be delivered as liquids and quickly form gels in the body without organic solvents or chemical reaction. However, their gelation is often followed by phase-separation and shrinking. Gel shrinking and water loss is

Aqueous solutions of temperature-responsive copolymers based on N-isopropylacrylamide (NIPAAm) hold promise for medical applications because they can be delivered as liquids and quickly form gels in the body without organic solvents or chemical reaction. However, their gelation is often followed by phase-separation and shrinking. Gel shrinking and water loss is a major limitation to using NIPAAm-based gels for nearly any biomedical application. In this work, a graft copolymer design was used to synthesize polymers which combine the convenient injectability of poly(NIPAAm) with gel water content controlled by hydrophilic side-chain grafts based on Jeffamine® M-1000 acrylamide (JAAm). The first segment of this work describes the synthesis and characterization of poly(NIPAAm-co-JAAm) copolymers which demonstrates controlled swelling that is nearly independent of LCST. The graft copolymer design was then used to produce a degradable antimicrobial-eluting gel for prevention of prosthetic joint infection. The resorbable graft copolymer gels were shown to have three unique characteristics which demonstrate their suitability for this application. First, antimicrobial release is sustained and complete within 1 week. Second, the gels behave like viscoelastic fluids, enabling complete surface coverage of an implant without disrupting fixation or movement. Finally, the gels degrade rapidly within 1-6 weeks, which may enable their use in interfaces where bone healing takes place. Graft copolymer hydrogels were also developed which undergo Michael addition in situ with poly(ethylene glycol) diacrylate to form elastic gels for endovascular embolization of saccular aneurysms. Inclusion of JAAm grafts led to weaker physical crosslinking and faster, more complete chemical crosslinking. JAAm grafts prolonged the delivery window of the system from 30 seconds to 220 seconds, provided improved gel swelling, and resulted in stronger, more elastic gels within 30 minutes after delivery.
ContributorsOverstreet, Derek (Author) / Caplan, Michael (Thesis advisor) / Massia, Stephen (Committee member) / Mclaren, Alexander (Committee member) / Vernon, Brent (Committee member) / McLemore, Ryan (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Biosensors offer excellent diagnostic methods through precise quantification of bodily fluid biomarkers and could fill an important niche in diagnostic screening. The long term goal of this research is the development of an impedance immunosensor for easy-to-use, rapid, sensitive and selective simultaneously multiplexed quantification of bodily fluid disease biomarkers. To

Biosensors offer excellent diagnostic methods through precise quantification of bodily fluid biomarkers and could fill an important niche in diagnostic screening. The long term goal of this research is the development of an impedance immunosensor for easy-to-use, rapid, sensitive and selective simultaneously multiplexed quantification of bodily fluid disease biomarkers. To test the hypothesis that various cytokines induce empirically determinable response frequencies when captured by printed circuit board (PCB) impedance immunosensor surface, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods were used to test PCB biosensors versus multiple cytokine biomarkers to determine limits of detection, background interaction and response at all sweep frequencies. Results indicated that sensors for cytokine Interleukin-12 (IL-12) detected their target over three decades of concentration and were tolerant to high levels of background protein. Further, the hypothesis that cytokine analytes may be rapidly detected via constant frequency impedance immunosensing without sacrificing undue sensitivity, CV, EIS, impedance-time (Zt) methods and modeling were used to test CHITM gold electrodes versus IL-12 over different lengths of time to determine limits of detection, detection time, frequency of response and consistent cross-platform sensor performance. Modeling and Zt studies indicate interrogation of the electrode with optimum frequency could be used for detection of different target concentrations within 90 seconds of sensor exposure and that interrogating the immunosensor with fixed, optimum frequency could be used for sensing target antigen. This informs usability of fixed-frequency impedance methods for biosensor research and particularly for clinical biosensor use. Finally, a multiplexing impedance immunosensor prototype for quantification of biomarkers in various body fluids was designed for increased automation of sample handling and testing. This enables variability due to exogenous factors and increased rapidity of assay with eased sensor fabrication. Methods were provided for simultaneous multiplexing through multisine perturbation of a sensor, and subsequent data processing. This demonstrated ways to observe multiple types of antibody-antigen affinity binding events in real time, reducing the number of sensors and target sample used in the detection and quantification of multiple biomarkers. These features would also improve the suitability of the sensor for clinical multiplex detection of disease biomarkers.
ContributorsFairchild, Aaron (Author) / La Belle, Jeffrey T (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Nagaraj, Vinay (Committee member) / Pizziconi, Vince (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2012
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Description
The goal of this research study was to empirically study a poster-based messaging campaign in comparison to that of a project-based learning approach in assessing the effectiveness of these methods in conveying the scope of biomedical engineering to upper elementary school students. For the purpose of this honors thesis, this

The goal of this research study was to empirically study a poster-based messaging campaign in comparison to that of a project-based learning approach in assessing the effectiveness of these methods in conveying the scope of biomedical engineering to upper elementary school students. For the purpose of this honors thesis, this research paper specifically reflects and analyzes the first stage of this study, the poster-based messaging campaign. 6th grade students received socially relevant messaging of juniors and seniors at ASU achieving their biomedical aspirations, and received information regarding four crucial themes of biomedical engineering via daily presentations and a website. Their learning was tracked over the course of the weeklong immersion program through a pre/post assessment. This data was then analyzed through the Wilcoxon matched pairs test to determine whether the change in biomedical engineering awareness was statistically significant. It was determined that a poster-based messaging campaign indeed increased awareness of socially relevant themes within biomedical engineering, and provided researchers with tangible ways to revise the study before a second round of implementation. The next stage of the study aims to explain biomedical engineering through engaging activities that stimulate making while emphasizing design-aesthetic appeal and engineering habits of mind such as creativity, teamwork, and communication.
ContributorsSwaminathan, Swetha Anu (Author) / Ganesh, Tirupalavanam (Thesis director) / Shrake, Scott (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
A fetus physiologically relies on blood for nutrients given by the mother. Blood supply is provided to a fetus through an umbilical cord having the structure of two pulsatile arteries with smooth muscle surrounding a thin walled vein. The two arteries transport deoxygenated blood from the fetus in the direction

A fetus physiologically relies on blood for nutrients given by the mother. Blood supply is provided to a fetus through an umbilical cord having the structure of two pulsatile arteries with smooth muscle surrounding a thin walled vein. The two arteries transport deoxygenated blood from the fetus in the direction of the placenta while the one vein transports oxygenated blood in the direction of the fetus. This process of the movement of blood is continuous throughout the gestation cycle. Conventionally, there are two arterial coils for every one coil of the vein. Undercoiling and overcoiling of the arteries leads to fetal distress, resulting in researchers to speculate that there is a relationship between these geometries with altered blood flow patterns that may be deleterious to the fetus. The fluid dynamics of an umbilical cord artery blood flow has not been extensively modeled on a computer, meaning there is an absence of knowledge on the ideal pitch of the coiling of the umbilical cord arteries. In this study, I developed computer models with ANSYS Fluent containing fluid dynamic variables and boundary conditions including: density of blood, viscosity of blood, diameter of each artery, pitch of artery coil, flow rate in each artery, and inlet velocity. Care was taken to investigate the effect of fluid finite element size, through mesh refinement, to improve accuracy of the models. The finalized models illustrate velocity and stress distribution in a coiled artery, showing different patterns in a model representing normal as compared to abnormal pitch. Further study of the fluid mechanics in the coil of the umbilical cord arteries, may elucidate the correlation between ideal pitch and fetal distress.
ContributorsSeaney, Amanda Marie (Author) / VanAuker, Michael (Thesis director) / Lilien, Lawrence (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
The use of saliva sampling as a noninvasive way for drug analysis as well as the monitoring systems within the body has become increasingly important in recent research. Because of the growing interest in saliva, this project proposes a way to analyze sodium ion concentration in a saliva solution based

The use of saliva sampling as a noninvasive way for drug analysis as well as the monitoring systems within the body has become increasingly important in recent research. Because of the growing interest in saliva, this project proposes a way to analyze sodium ion concentration in a saliva solution based on its fluorescence level when in the presence of a sodium indicator dye and recorded with a smartphone camera. The dyed sample was placed in a specially designed housing to exclude all ambient light from the images. A source light of known wavelength was used to excite the fluorescent dye and the smartphone camera images recorded the emission light wavelengths. After analysis of the images using ImageJ, it was possible to create a model to determine the level of fluorescence based on sodium ion concentration. The smartphone camera image model was compared to readings from a standard fluorescence plate recorder to test the accuracy of the model. The study found that the model was accurate within 5 % as compared to the fluorescence plate recorder. Based on the results, it was concluded that the method and resulting model proposed in this study is a valid was to analyze saliva or other solutions for their sodium ion concentration via images recorded by a smartphone camera.
ContributorsSmith, Catherine Julia (Author) / Antonio, Garcia (Thesis director) / Caplan, Michael (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Biofeedback music is the integration of physiological signals with audible sound for aesthetic considerations, which an individual’s mental status corresponds to musical output. This project looks into how sounds can be drawn from the meditative and attentive states of the brain using the MindWave Mobile EEG biosensor from NeuroSky. With

Biofeedback music is the integration of physiological signals with audible sound for aesthetic considerations, which an individual’s mental status corresponds to musical output. This project looks into how sounds can be drawn from the meditative and attentive states of the brain using the MindWave Mobile EEG biosensor from NeuroSky. With the MindWave and an Arduino microcontroller processor, sonic output is attained by inputting the data collected by the MindWave, and in real time, outputting code that deciphers it into user constructed sound output. The input is scaled from values 0 to 100, measuring the ‘attentive’ state of the mind by observing alpha waves, and distributing this information to the microcontroller. The output of sound comes from sourcing this into the Musical Instrument Shield and varying the musical tonality with different chords and delay of the notes. The manipulation of alpha states highlights the control or lack thereof for the performer and touches on the question of how much control over the output there really is, much like the experimentalist Alvin Lucier displayed with his concepts in brainwave music.
ContributorsQuach, Andrew Duc (Author) / Helms Tillery, Stephen (Thesis director) / Feisst, Sabine (Committee member) / Barrett, The Honors College (Contributor) / Herberger Institute for Design and the Arts (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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Description
Motor behavior is prone to variable conditions and deviates further in disorders affecting the nervous system. A combination of environmental and neural factors impacts the amount of uncertainty. Although the influence of these factors on estimating endpoint positions have been examined, the role of limb configuration on endpoint variability has

Motor behavior is prone to variable conditions and deviates further in disorders affecting the nervous system. A combination of environmental and neural factors impacts the amount of uncertainty. Although the influence of these factors on estimating endpoint positions have been examined, the role of limb configuration on endpoint variability has been mostly ignored. Characterizing the influence of arm configuration (i.e. intrinsic factors) would allow greater comprehension of sensorimotor integration and assist in interpreting exaggerated movement variability in patients. In this study, subjects were placed in a 3-D virtual reality environment and were asked to move from a starting position to one of three targets in the frontal plane with and without visual feedback of the moving limb. The alternating of visual feedback during trials increased uncertainty between the planning and execution phases. The starting limb configurations, adducted and abducted, were varied in separate blocks. Arm configurations were setup by rotating along the shoulder-hand axis to maintain endpoint position. The investigation hypothesized: 1) patterns of endpoint variability of movements would be dependent upon the starting arm configuration and 2) any differences observed would be more apparent in conditions that withheld visual feedback. The results indicated that there were differences in endpoint variability between arm configurations in both visual conditions, but differences in variability increased when visual feedback was withheld. Overall this suggests that in the presence of visual feedback, planning of movements in 3D space mostly uses coordinates that are arm configuration independent. On the other hand, without visual feedback, planning of movements in 3D space relies substantially on intrinsic coordinates.
ContributorsRahman, Qasim (Author) / Buneo, Christopher (Thesis director) / Helms Tillery, Stephen (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05