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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
Description
Single cell phenotypic heterogeneity studies reveal more information about the pathogenesis process than conventional bulk methods. Furthermore, investigation of the individual cellular response mechanism during rapid environmental changes can only be achieved at single cell level. By enabling the study of cellular morphology, a single cell three-dimensional (3D) imaging system

Single cell phenotypic heterogeneity studies reveal more information about the pathogenesis process than conventional bulk methods. Furthermore, investigation of the individual cellular response mechanism during rapid environmental changes can only be achieved at single cell level. By enabling the study of cellular morphology, a single cell three-dimensional (3D) imaging system can be used to diagnose fatal diseases, such as cancer, at an early stage. One proven method, CellCT, accomplishes 3D imaging by rotating a single cell around a fixed axis. However, some existing cell rotating mechanisms require either intricate microfabrication, and some fail to provide a suitable environment for living cells. This thesis develops a microvorterx chamber that allows living cells to be rotated by hydrodynamic alone while facilitating imaging access. In this thesis work, 1) the new chamber design was developed through numerical simulation. Simulations revealed that in order to form a microvortex in the side chamber, the ratio of the chamber opening to the channel width must be smaller than one. After comparing different chamber designs, the trapezoidal side chamber was selected because it demonstrated controllable circulation and met the imaging requirements. Microvortex properties were not sensitive to the chambers with interface angles ranging from 0.32 to 0.64. A similar trend was observed when chamber heights were larger than chamber opening. 2) Micro-particle image velocimetry was used to characterize microvortices and validate simulation results. Agreement between experimentation and simulation confirmed that numerical simulation was an effective method for chamber design. 3) Finally, cell rotation experiments were performed in the trapezoidal side chamber. The experimental results demonstrated cell rotational rates ranging from 12 to 29 rpm for regular cells. With a volumetric flow rate of 0.5 µL/s, an irregular cell rotated at a mean rate of 97 ± 3 rpm. Rotational rates can be changed by altering inlet flow rates.
ContributorsZhang, Wenjie (Author) / Frakes, David (Thesis advisor) / Meldrum, Deirdre (Thesis advisor) / Chao, Shih-hui (Committee member) / Wang, Xiao (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Anticipatory planning of digit positions and forces is critical for successful dexterous object manipulation. Anticipatory (feedforward) planning bypasses the inherent delays in reflex responses and sensorimotor integration associated with reactive (feedback) control. It has been suggested that feedforward and feedback strategies can be distinguished based on the profile of gri

Anticipatory planning of digit positions and forces is critical for successful dexterous object manipulation. Anticipatory (feedforward) planning bypasses the inherent delays in reflex responses and sensorimotor integration associated with reactive (feedback) control. It has been suggested that feedforward and feedback strategies can be distinguished based on the profile of grip and load force rates during the period between initial contact with the object and object lift. However, this has not been validated in tasks that do not constrain digit placement. The purposes of this thesis were (1) to validate the hypothesis that force rate profiles are indicative of the control strategy used for object manipulation and (2) to test this hypothesis by comparing manipulation tasks performed with and without digit placement constraints. The first objective comprised two studies. In the first study an additional light or heavy mass was added to the base of the object. In the second study a mass was added, altering the object's center of mass (CM) location. In each experiment digit force rates were calculated between the times of initial digit contact and object lift. Digit force rates were fit to a Gaussian bell curve and the goodness of fit was compared across predictable and unpredictable mass and CM conditions. For both experiments, a predictable object mass and CM elicited bell shaped force rate profiles, indicative of feedforward control. For the second objective, a comparison of performance between subjects who performed the grasp task with either constrained or unconstrained digit contact locations was conducted. When digit location was unconstrained and CM was predictable, force rates were well fit to a bell shaped curve. However, the goodness of fit of the force rate profiles to the bell shaped curve was weaker for the constrained than the unconstrained digit placement condition. These findings seem to indicate that brain can generate an appropriate feedforward control strategy even when digit placement is unconstrained and an infinite combination of digit placement and force solutions exists to lift the object successfully. Future work is needed that investigates the role digit positioning and tactile feedback has on anticipatory control of object manipulation.
ContributorsCooperhouse, Michael A (Author) / Santello, Marco (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Buneo, Christopher (Committee member) / Arizona State University (Publisher)
Created2011
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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

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
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Description
Advancements in mobile technologies have significantly enhanced the capabilities of mobile devices to serve as powerful platforms for sensing, processing, and visualization. Surges in the sensing technology and the abundance of data have enabled the use of these portable devices for real-time data analysis and decision-making in digital signal processing

Advancements in mobile technologies have significantly enhanced the capabilities of mobile devices to serve as powerful platforms for sensing, processing, and visualization. Surges in the sensing technology and the abundance of data have enabled the use of these portable devices for real-time data analysis and decision-making in digital signal processing (DSP) applications. Most of the current efforts in DSP education focus on building tools to facilitate understanding of the mathematical principles. However, there is a disconnect between real-world data processing problems and the material presented in a DSP course. Sophisticated mobile interfaces and apps can potentially play a crucial role in providing a hands-on-experience with modern DSP applications to students. In this work, a new paradigm of DSP learning is explored by building an interactive easy-to-use health monitoring application for use in DSP courses. This is motivated by the increasing commercial interest in employing mobile phones for real-time health monitoring tasks. The idea is to exploit the computational abilities of the Android platform to build m-Health modules with sensor interfaces. In particular, appropriate sensing modalities have been identified, and a suite of software functionalities have been developed. Within the existing framework of the AJDSP app, a graphical programming environment, interfaces to on-board and external sensor hardware have also been developed to acquire and process physiological data. The set of sensor signals that can be monitored include electrocardiogram (ECG), photoplethysmogram (PPG), accelerometer signal, and galvanic skin response (GSR). The proposed m-Health modules can be used to estimate parameters such as heart rate, oxygen saturation, step count, and heart rate variability. A set of laboratory exercises have been designed to demonstrate the use of these modules in DSP courses. The app was evaluated through several workshops involving graduate and undergraduate students in signal processing majors at Arizona State University. The usefulness of the software modules in enhancing student understanding of signals, sensors and DSP systems were analyzed. Student opinions about the app and the proposed m-health modules evidenced the merits of integrating tools for mobile sensing and processing in a DSP curriculum, and familiarizing students with challenges in modern data-driven applications.
ContributorsRajan, Deepta (Author) / Spanias, Andreas (Thesis advisor) / Frakes, David (Committee member) / Turaga, Pavan (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Flow measurement has always been one of the most critical processes in many industrial and clinical applications. The dynamic behavior of flow helps to define the state of a process. An industrial example would be that in an aircraft, where the rate of airflow passing the aircraft is used to

Flow measurement has always been one of the most critical processes in many industrial and clinical applications. The dynamic behavior of flow helps to define the state of a process. An industrial example would be that in an aircraft, where the rate of airflow passing the aircraft is used to determine the speed of the plane. A clinical example would be that the flow of a patient's breath which could help determine the state of the patient's lungs. This project is focused on the flow-meter that are used for airflow measurement in human lungs. In order to do these measurements, resistive-type flow-meters are commonly used in respiratory measurement systems. This method consists of passing the respiratory flow through a fluid resistive component, while measuring the resulting pressure drop, which is linearly related to volumetric flow rate. These types of flow-meters typically have a low frequency response but are adequate for most applications, including spirometry and respiration monitoring. In the case of lung parameter estimation methods, such as the Quick Obstruction Method, it becomes important to have a higher frequency response in the flow-meter so that the high frequency components in the flow are measurable. The following three types of flow-meters were: a. Capillary type b. Screen Pneumotach type c. Square Edge orifice type To measure the frequency response, a sinusoidal flow is generated with a small speaker and passed through the flow-meter that is connected to a large, rigid container. True flow is proportional to the derivative of the pressure inside the container. True flow is then compared with the measured flow, which is proportional to the pressure drop across the flow-meter. In order to do the characterization, two LabVIEW data acquisition programs have been developed, one for transducer calibration, and another one that records flow and pressure data for frequency response testing of the flow-meter. In addition, a model that explains the behavior exhibited by the flow-meter has been proposed and simulated. This model contains a fluid resistor and inductor in series. The final step in this project was to approximate the frequency response data to the developed model expressed as a transfer function.
ContributorsHu, Jianchen (Author) / Macia, Narciso (Thesis advisor) / Pollat, Scott (Committee member) / Rogers, Bradley (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Controlled release formulations for local, in vivo drug delivery are of growing interest to device manufacturers, research scientists, and clinicians; however, most research characterizing controlled release formulations occurs in vitro because the spatial and temporal distribution of drug delivery is difficult to measure in vivo. In this work, in vivo

Controlled release formulations for local, in vivo drug delivery are of growing interest to device manufacturers, research scientists, and clinicians; however, most research characterizing controlled release formulations occurs in vitro because the spatial and temporal distribution of drug delivery is difficult to measure in vivo. In this work, in vivo magnetic resonance imaging (MRI) of local drug delivery is performed to visualize and quantify the time resolved distribution of MRI contrast agents. I find it is possible to visualize contrast agent distributions in near real time from local delivery vehicles using MRI. Three dimensional T1 maps are processed to produce in vivo concentration maps of contrast agent for individual animal models. The method for obtaining concentration maps is analyzed to estimate errors introduced at various steps in the process. The method is used to evaluate different controlled release vehicles, vehicle placement, and type of surgical wound in rabbits as a model for antimicrobial delivery to orthopaedic infection sites. I are able to see differences between all these factors; however, all images show that contrast agent remains fairly local to the wound site and do not distribute to tissues far from the implant in therapeutic concentrations. I also produce a mathematical model that investigates important mechanisms in the transport of antimicrobials in a wound environment. It is determined from both the images and the mathematical model that antimicrobial distribution in an orthopaedic wounds is dependent on both diffusive and convective mechanisms. Furthermore, I began development of MRI visible therapeutic agents to examine active drug distributions. I hypothesize that this work can be developed into a non-invasive, patient specific, clinical tool to evaluate the success of interventional procedures using local drug delivery vehicles.
ContributorsGiers, Morgan (Author) / Caplan, Michael R (Thesis advisor) / Massia, Stephen P (Committee member) / Frakes, David (Committee member) / McLaren, Alex C. (Committee member) / Vernon, Brent L (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Magnetic Resonance Imaging using spiral trajectories has many advantages in speed, efficiency in data-acquistion and robustness to motion and flow related artifacts. The increase in sampling speed, however, requires high performance of the gradient system. Hardware inaccuracies from system delays and eddy currents can cause spatial and temporal distortions in

Magnetic Resonance Imaging using spiral trajectories has many advantages in speed, efficiency in data-acquistion and robustness to motion and flow related artifacts. The increase in sampling speed, however, requires high performance of the gradient system. Hardware inaccuracies from system delays and eddy currents can cause spatial and temporal distortions in the encoding gradient waveforms. This causes sampling discrepancies between the actual and the ideal k-space trajectory. Reconstruction assuming an ideal trajectory can result in shading and blurring artifacts in spiral images. Current methods to estimate such hardware errors require many modifications to the pulse sequence, phantom measurements or specialized hardware. This work presents a new method to estimate time-varying system delays for spiral-based trajectories. It requires a minor modification of a conventional stack-of-spirals sequence and analyzes data collected on three orthogonal cylinders. The method is fast, robust to off-resonance effects, requires no phantom measurements or specialized hardware and estimate variable system delays for the three gradient channels over the data-sampling period. The initial results are presented for acquired phantom and in-vivo data, which show a substantial reduction in the artifacts and improvement in the image quality.
ContributorsBhavsar, Payal (Author) / Pipe, James G (Thesis advisor) / Frakes, David (Committee member) / Kodibagkar, Vikram (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Coronary computed tomography angiography (CTA) has a high negative predictive value for ruling out coronary artery disease with non-invasive evaluation of the coronary arteries. My work has attempted to provide metrics that could increase the positive predictive value of coronary CTA through the use of dual energy CTA imaging. After

Coronary computed tomography angiography (CTA) has a high negative predictive value for ruling out coronary artery disease with non-invasive evaluation of the coronary arteries. My work has attempted to provide metrics that could increase the positive predictive value of coronary CTA through the use of dual energy CTA imaging. After developing an algorithm for obtaining calcium scores from a CTA exam, a dual energy CTA exam was performed on patients at dose levels equivalent to levels for single energy CTA with a calcium scoring exam. Calcium Agatston scores obtained from the dual energy CTA exam were within ±11% of scores obtained with conventional calcium scoring exams. In the presence of highly attenuating coronary calcium plaques, the virtual non-calcium images obtained with dual energy CTA were able to successfully measure percent coronary stenosis within 5% of known stenosis values, which is not possible with single energy CTA images due to the presence of the calcium blooming artifact. After fabricating an anthropomorphic beating heart phantom with coronary plaques, characterization of soft plaque vulnerability to rupture or erosion was demonstrated with measurements of the distance from soft plaque to aortic ostium, percent stenosis, and percent lipid volume in soft plaque. A classification model was developed, with training data from the beating heart phantom and plaques, which utilized support vector machines to classify coronary soft plaque pixels as lipid or fibrous. Lipid versus fibrous classification with single energy CTA images exhibited a 17% error while dual energy CTA images in the classification model developed here only exhibited a 4% error. Combining the calcium blooming correction and the percent lipid volume methods developed in this work will provide physicians with metrics for increasing the positive predictive value of coronary CTA as well as expanding the use of coronary CTA to patients with highly attenuating calcium plaques.
ContributorsBoltz, Thomas (Author) / Frakes, David (Thesis advisor) / Towe, Bruce (Committee member) / Kodibagkar, Vikram (Committee member) / Pavlicek, William (Committee member) / Bouman, Charles (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Over the past fifty years, the development of sensors for biological applications has increased dramatically. This rapid growth can be attributed in part to the reduction in feature size, which the electronics industry has pioneered over the same period. The decrease in feature size has led to the production of

Over the past fifty years, the development of sensors for biological applications has increased dramatically. This rapid growth can be attributed in part to the reduction in feature size, which the electronics industry has pioneered over the same period. The decrease in feature size has led to the production of microscale sensors that are used for sensing applications, ranging from whole-body monitoring down to molecular sensing. Unfortunately, sensors are often developed without regard to how they will be integrated into biological systems. The complexities of integration are underappreciated. Integration involves more than simply making electrical connections. Interfacing microscale sensors with biological environments requires numerous considerations with respect to the creation of compatible packaging, the management of biological reagents, and the act of combining technologies with different dimensions and material properties. Recent advances in microfluidics, especially the proliferation of soft lithography manufacturing methods, have established the groundwork for creating systems that may solve many of the problems inherent to sensor-fluidic interaction. The adaptation of microelectronics manufacturing methods, such as Complementary Metal-Oxide-Semiconductor (CMOS) and Microelectromechanical Systems (MEMS) processes, allows the creation of a complete biological sensing system with integrated sensors and readout circuits. Combining these technologies is an obstacle to forming complete sensor systems. This dissertation presents new approaches for the design, fabrication, and integration of microscale sensors and microelectronics with microfluidics. The work addresses specific challenges, such as combining commercial manufacturing processes into biological systems and developing microscale sensors in these processes. This work is exemplified through a feedback-controlled microfluidic pH system to demonstrate the integration capabilities of microscale sensors for autonomous microenvironment control.
ContributorsWelch, David (Author) / Blain Christen, Jennifer (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Frakes, David (Committee member) / LaBelle, Jeffrey (Committee member) / Goryll, Michael (Committee member) / Arizona State University (Publisher)
Created2012