Theses and Dissertations from UMD
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Item Blueprinting Self-Assembled Soft Matter: An `Easy' Approach to Advanced Material Synthesis in Drug Delivery and Wound Healing(2010) Dowling, Matthew Burke; Raghavan, Srinivasa R; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)From Jello to mayonnaise to silly putty to biological cells, our world is replete with "soft matter" - materials that behave as soft, deformable solids or highly viscoelastic liquids. Living systems, in particular, can be thought of as extremely sophisticated `soft' machines, with each cellular unit representing a touchstone for the functional potential of soft materials built via self-assembly. Drawing inspiration from biology, we blueprint soft biomaterial designs which rely upon self-assembly to achieve enhanced functionality. As opposed to complex synthesis schemes often used to develop improved biomaterials, we take an `easy' approach by allowing relatively simple molecules orchestrate themselves into advanced machines. In this dissertation, we describe four separate "soft" systems, all constructed by self-assembly of amphiphilic molecules under designed and/or triggered conditions in aqueous media. These systems revolve around a common theme: the structural tandem of (1) vesicles and (2) biopolymers, and the resulting interactions between the two. Our blueprints show promise in several important biomedical applications including controlled drug release, tissue engineering, and wound care. In the first part of this study, we blueprint a biopolymer gel that entraps pH-sensitive vesicles. The vesicles are formed by the self-assembly of a single-tailed fatty acid surfactant. We show that the gel has pH-responsive properties imparted upon it via the embedded vesicle nanostructures. Specifically, when the gel is brought in contact with a high pH buffer, the diffusion of buffer into the gel disrupts the vesicles and transforms them into micelles. Accordingly, a vesicle-micelle front moves through the gel, and this can be visually seen by a difference in color. The disruption of vesicles means that their encapsulated solutes are released into the bulk gel, and in turn these solutes can rapidly diffuse out of the gel. Thus, we can use pH to tune the release rate of model drug molecules from these vesicle-loaded gels into the external solution. In the second part, we have blueprinted hybrid biopolymer capsules containing drug-loaded vesicles by means of a one-step self-assembly process. These capsules are called "motherships" as each unit features a larger container, the polymer capsule, carrying a payload of smaller vesicular containers, or "babyships," within its lumen. These motherships are self-assembled via electrostatic interactions between oppositely charged polymers/surfactants at the interface of the droplet. Capsule size is simply dictated by drop size, and capsules of sizes 200-5000 µm are produced here. Lipid vesicles, i.e. the babyships, are retained inside motherships due to the diffusional barrier created by the capsule shell. The added transport barrier provided by the vesicle bilayer in addition to the capsule shell provides sustained drug release from the motherships. Furthermore, this one-step drop method allows for the rapid synthesis of soft materials exhibiting structural features over a hierarchy of length scales, from nano-, to micro- to macro-. Thirdly, we have therapeutically functionalized biopolymer films by simply passing a solution of vesicles over the film surface. We deposit films of an associating biopolymer onto patterned solid substrates. Subsequently, these polymer films are able to spontaneously capture therapeutically-loaded vesicles from solution; this is demonstrated both for surfactant as well as lipid vesicles (liposomes). Importantly, it is verified that the vesicles are intact - this is shown both by direct visualization of captured vesicles (via optical and cryo-transmission electron microscopy) as well as through the capture and subsequent disruption of drug filled vesicles. Such therapeutically-functionalized films may be of use in the treatment of chronic wounds and burns. Lastly, we have demonstrated that the addition of a certain biopolymer transforms a suspension of whole blood into a gel. This blueprint is inspired from previous research in our group on the biopolymer-induced gelation of vesicles, which are structurally similar to cells. Upon mixture with heparinized human whole blood, this amphilic biopolymer rapidly forms into an "artificial clot." These mixtures have highly elastic character, with the mixtures able to hold their own weight upon vial inversion. Moreover, the biopolymer shows significant hemorrhage-controlling efficacy in animal injury models. Such biopolymer-cell gelation processes are shown to be reversed via introduction of an amphiphilic supramolecule, thus introducing the novel concept of the "revesible hemostat." Such a hemostatic functionality may be of large and unprecedented use in clinical the treatment of problematic hemorrhage both in trauma and routine surgeries.Item SCAFFOLD DESIGN PARAMETERS TO STIMULATE THE OSTEOGENIC SIGNAL EXPRESSION FOR BONE TISSUE ENGINEERING APPLICATIONS(2010) KIM, KYOBUM; Fisher, John P; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The fundamental components of bone tissue engineering are (a) progenitor cells which subsequently express tissue matrix, (b) scaffolds which can act as temporary frameworks to support bone growth, and (c) growth factors to induce osteoblast regeneration. A variety of growth factors are involved during the differentiation cascade and these chemical and biological signals dynamically interact with cell populations to facilitate the differentiation. Therefore, enhanced expression of endogenous growth factor genes might facilitate abundant existence of growth factors in the surrounding microenvironment, stimulate the osteogenic differentiation of progenitor cell population, and finally induce bone regeneration. This work is focused on the augmentation of osteogenic signal expressions to stimulate the downstream differentiation of transplanted bone marrow stromal cells (BMSCs) population through the optimization of a variety of properties of three dimensional (3D) biodegradable poly(propylene fumarate) (PPF) scaffold. Changes in the microenvironment of cell population would affect the responses of localized cell population and the manipulated scaffold properties might be associated with induction of endogenous osteogenic signal expressions. First, the effect of cell-to-cell paracrine signaling distance, which can by modulated by initial cell seeding density, on the osteogenic signal expressions and osteoblastic differentiation of BMSCs on 2D PPF disks was investigated. Next, in order to investigate the improvement of the 3D macroporous PPF scaffold by the incorporation with nanoparticle filler materials, PPF/hydroxyapatite (HA) nanocomposite scaffolds were fabricated. The effect of HA content and initial cell seeding density on the osteogenic signal expression in 3D porous system was then determined. Finally, the incorporation of diethyl dumarate (DEF) with PPF was tested based on the photocrosslinking characteristics of PPF/DEF composite material with increased mechanical properties. The effect of two scaffold design parameters including the stiffness by modulating the DEF content as well as the pore size of porous scaffold on the signal expression and downstream osteoblastic differentiation was investigated. In addition, the feasibility of PPPF/DEF materials for stereolithographical fabrication was also tested in this work. Controlling these construction parameters to optimize engineered bone substitutes could affect various cellular functions of attachment, proliferation, signal expression, and differentiation. This research provided the insight of stimulation of the expression of target endogenous genes to induce the osteogenic differentiation and bone regeneration as well as the fabrication of improved bone substitute implant materials which is clinically applicable.Item A MULTISCALE MODEL FOR AN ATOMIC LAYER DEPOSITION PROCESS(2010) Dwivedi, Vivek Hari; Adomaitis, Raymond A; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Atomic layer deposition (ALD) is a deposition technique suitable for the con- trolled growth of thin films. During ALD, precursor gasses are supplied to the reactor in an alternating sequence producing individual atomic layers through self- limiting reactions. Thin films are grown conformally with atomic layer control over surfaces with topographical features. A very promising material system for ALD growth is aluminum oxide. Alu- minum oxide is highly desirable for both its physical and electronic characteristics. Aluminum oxide has a very high band gap (~ 9 ev) and a high dielectric constant (k ~ 9). The choice of precursors for aluminum oxide atomic layer deposition vary from aluminum halide, alkyl, and alkoxides for aluminum-containing molecules; for oxygen-containing molecules choices include oxygen, water, hydrogen peroxide and ozone. For this work a multiscale simulation is presented where aluminum oxide is deposited inside anodic aluminum oxide (AAO) pores for the purposes of tuning the pore diameter. Controlling the pore diameter is an import step in the conversion of AAO into nanostructered catalytic membranes (NCM). Shrinking the pore size to a desired radius allows for the control of the residence time for molecules entering the pore and a method for molecular filtration. Furthermore pore diameter control would allow for the optimization of precursor doses making this a green process. Inherently, the ALD of AAO is characterized by a slow and a faster time scale where film growth is on the order of minutes and hours and surface reactions are near instantaneous. Likewise there are two length scales: film thickness and composition on the order of nanometers and pore length on the order of microns. The surface growth is modeled in terms of a lattice Monte Carlo simulation while the diffusion of the precursor gas along the length of the pore is modeled as a Knudsen diffusion based transport model.Item Computational studies of droplet motion and deformation in a microfluidic channel with a constriction(2010) Lee, Moon Soo; Dimitrakopoulos, Panagiotis; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)In the present thesis, we investigate the interfacial dynamics of a three-dimensional droplet in a viscous fluid flowing through a square microfluidic channel with a rectangular cross-sectional constriction. The effects of various parameters of the two fluids and the sizes of the constriction geometry are considered. The numerical computation for the current problem requires a highly-accurate and efficient method owing to the very small/large deformation of the droplet shape at low/high flow rates, the small droplet-solid gap and the complicated three-dimensional geometries. An efficient fully-implicit three-dimensional Spectral Boundary Element method developed by Dimitrakopoulos is employed. Our results show that the droplet dynamics is significantly influenced by the non-symmetric shape of the rectangular cross-sectional constriction, i.e. owing to the constriction shape the droplet deforms much less in the flow-direction by forming a flat disk shape. As the capillary number is decreased, the droplet deformation in the flow-direction decreases owing to the larger surface tension. The effects of the viscosity ratio are complicated with viscosity ratio near unity showing the largest deformation.Item COMPUTATIONAL STUDIES ON DROPLET DYNAMICS AT INTERSECTING FLOWS IN MICROFLUIDIC JUNCTIONS(2010) Mamidi, Sai Kishore Reddy; Dimitrakopoulos, Panagiotis; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The current thesis involves a computational study of drop dynamics in microfluidic junctions, at the moderate capillary number of Ca = 0.1. We utilize a three-dimensional Spectral Boundary Element algorithm to determine the drop motion in the presence of intersecting lateral flows in microfluidic, T-junctions and cross-junctions, and analyze the effect on drop deformation and motion with varying shear rates in the channels leading to the junctions, and for viscosity ratios of 0.2 and 20.0 between the drop and the surrounding fluid. We find that the presence of intersecting flows, drastically affects the transient behavior at the junctions, and the drop reaches steady state further away, both up- stream and downstream of these junctions. The time taken to reach steady state in the T-junctions was found to be significantly greater than that in the cross-junction, under identical conditions. Drop velocities were found to be a linear function of the effective shear rate in the channel, and length scale fluctuations as high as 30 percent were observed in the junction region for the cases studied in the thesis. We observed that the excess presure drop with respect to the flow of a single phase fluid was strongly related to the length of the droplet at a given spatial coordinate. The peak surface area of the drop in the junction was found to be a slighly non-linear function of the flow rates in the lateral channels, and almost all the surface area increase was occurring at the head of the drop, in the direction of the flow. Velocity was found to be a weak, inverse function of the viscosity ratio, the increase in drop surface area was found to be greater in drops with lower viscosity. It was found that the junction bend radius/smoothness had a more significant effect on the dynamics of the drop in a T-junction, compared to that in a cross-junction.Item Lipid-Hydrogel Nanoparticles: Synthesis Methods and Characterization(2009) Hong, Jennifer S.; Raghavan, Srinivasa R; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This dissertation focuses on the directed self-assembly of nanoscale soft matter particles using methods based on liposome-templating. Nanoscale liposomes, nano-sized hydrogel particles ("nanogels"), and hybrids of the two have enormous potential as carriers in drug delivery and nanotoxicity studies, and as nanovials for enzyme encapsulation and single molecule studies. Our goal is to develop assembly methods that produce stable nanogels or hybrid lipid-polymer nanoparticles, using liposomes as size and shape templates. First we describe a bulk method that employs liposomes to template relatively monodisperse nanogels composed of the biopolymer, alginate, which is a favorable material for nanogel formation because it uses a gentle ionic crosslinking mechanism that is suitable for the encapsulation of cells and biomolecules. Liposomes encapsulating sodium alginate are suspended in aqueous buffer containing calcium chloride, and thermal permeabilization of the lipid membrane facilitates transmembrane diffusion of Ca2+ ions from the surrounding buffer into the intraliposomal space, ionically crosslinking the liposome core. Subsequent lipid removal results in bare calcium alginate nanogels with a size distribution consistent with that of their liposome template. The second part of our study investigates the potential for microfluidic-directed formation of lipid-alginate hybrid nanoparticles by adapting the above bulk self-assembly procedure within a microfluidic device. Specifically we investigated the size control of alginate nanogel self-assembly under different flow conditions and concentrations. Finally, we investigate the microfluidic directed self-assembly of lipid-polymer hybrid nanoparticles, using phospholipids and an N-isopropylacrylamide monomer as the liposome and hydrogel precursors, respectively. Microfluidic hydrodynamic focusing is used to control the convective-diffusive mixing of the two miscible nanoparticle precursor solutions to form nanoscale vesicles with encapsulated hydrogel precursor. The encapsulated hydrogel precursor is polymerized off-chip and the resultant hybrid nanoparticle size distributions are highly monodisperse and precisely controlled across a broad range relevant to the targeted delivery and controlled release of encapsulated therapeutic agents. Given the ability to modify liposome size and surface properties by altering the lipid components and the many polymers of current interest for nanoparticle synthesis, this approach could be adapted for a variety of hybrid nanoparticle systems.Item NANOSTRUCTURED THIN FILM POLYMER ELECTROLYTES FOR FLEXIBLE BATTERY APPLICATIONS(2009) Ghosh, Ayan; Kofinas, Peter; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)In recent years, the interest in polymeric batteries has increased dramatically. With the advent of lithium ion batteries being used in cell phones and laptop computers, the search for an all solid state battery has continued. Current configurations have a liquid or gel electrolyte along with a separator between the anode and cathode. This leads to problems with electrolyte loss and decreased performance over time. The highly reactive nature of these electrolytes necessitates the use of protective enclosures which add to the size and bulk of the battery. Polymer electrolytes are more compliant than conventional inorganic glass or ceramic electrolytes. The goal of this work was to design and investigate novel nanoscale polymer electrolyte flexible thin films based on the self-assembly of block copolymers. Block copolymers were synthesized, consisting of a larger PEO block and a smaller block consisting of random copolymer of methyl methacrylate (MMA) and the lithium salt of methacrylic acid (MAALi). The diblock copolymer [PEO-b-(PMMA-ran-PMAALi)] with added lithium bis(oxalato)borate, LiBC4O8 (LiBOB) salt (in the molar ratio ethylene oxide:LiBOB = 3:1) was used to form flexible translucent films which exhibited nearly two orders of magnitude greater conductivity than that shown by traditional high molecular weight PEO homopolymer electrolytes, in the absence of ceramic fillers and similar additives. The presence of the smaller second block and the plasticizing effect of the bulky lithium salt were shown to effectively reduce the crystallinity of the solid electrolyte, resulting in improved ion transporting behavior. The tailored solid self-assembled diblock copolymer electrolyte matrix also exhibits an exceptionally high lithium-ion transference number of 0.9, compared to a value between 0.2 and 0.5, shown by typical polymer-lithium salt materials. The electrolyte material also has a wide electrochemical stability window and excellent interfacial behavior with lithium metal electrode. The combination of these properties make electrolyte membranes composed of the diblock copolymer PEO-b-(PMMA-ran-PMAALi) and LiBOB salt, viable electrolyte candidates for flexible lithium ion based energy conversion/storage devices.Item Evaluation of the transcription of small RNA SgrS and glucose transporter mRNA ptsG in E. coli B and E. coli K cultures under high glucose conditions(2009) Ng, Weng Ian; Wang, Nam Sun; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Escherichia coli is commonly used as the production system for recombinant proteins. However, acetate accumulation in fermentation affects cell growth and protein yield. Recent studies have showed that the small RNA SgrS regulates the major glucose transporter mRNA ptsG in a post–transcriptional manner when the metabolic intermediate glucose–6–phosphate is accumulated intracellularly in E. coli K. Here, comparative analysis of the transcription of SgrS and ptsG is performed between E. coli B and E. coli K cultures in both shake flasks and bioreactor. Both strains expressed SgrS when grown on the non–metabolizable glucose analog α–methyl–glucoside. However, under high glucose conditions, only E. coli B showed significant expression of SgrS. This behavior is unaffected by oxygen supply and pH control. E. coli B produced less acetate on glucose than E. coli K in the bioreactor settings. This provides evidence of a possible connection between SgrS and acetate production in aerobic fermentation of E. coli.Item MOLECULAR DYNAMICS SIMULATIONS OF LASER INDUCED SHOCK RESPONSE IN REACTIVE Ni/Al NANOLAMINATES(2009) Meissner, Alexander Blacque; Zachariah, Michael; Mechanical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)To characterize the self-propagating, high-temperature exothermic alloying reactions of Ni/Al nanoscaled multilayered films induced by laser pulse shock loading, classical molecular dynamics simulations were performed. In the current work, a novel technique was developed to facilitate the energy input and distribution into nanolaminate thin films. The laser pulse shock loading technique enables the initial shock response of the material to be captured as well as the late-time mass diffusion controlled alloying reaction and Ni3Al formation. Shock compression raises the temperature, pressure, and density of the Ni and Al layers which triggers the Ni to diffuse into the Al and initiate the self-propagating alloying reaction. Thermodynamic states, enthalpy of reaction, and global reaction rates of the laminated films were obtained. It was determined that the series of complex rarefaction and reflection waves play a significant role in altering the thermodynamic state of the laminate. Attributes of the rarefaction and reflection waves are controlled by the geometry and thickness of the alternating layers. The dependence of layer thickness on the temperature, pressure, enthalpy of reaction, and global reaction rate was investigated and characterized.Item Self-Assembled Photoresponsive and Thermoresponsive Nanostructures(2009) Sun, Kunshan; Raghavan, Srinivasa R.; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Responsive complex fluids based on nanostructures (e.g., micelles, vesicles and nanoparticles) have received considerable attention recently. The ability of these materials to be tuned by light or heat can have many potential applications in the areas of drug delivery, coatings, sensors, or microfluidic valves and dampers. However, most current photoresponsive and thermoresponsive formulations require the synthesis of complex organic molecules, and this prevents them from being used widely for commercial applications. In this dissertation, we seek to develop new classes of photoresponsive (PR) and thermoresponsive (TR) nanostructures based on commercially available, inexpensive precursors. In the first part of this study, we report a new PR fluid based on light-activated nanoparticle assembly. Our system consists of disk-like nanoparticles of laponite along with a surfactant stabilizer (Pluronic F127) and the photoacid generator (PAG), diphenyliodonium-2-carboxylate monohydrate. Initially, the nanoparticles are sterically stabilized by the surfactant and the result is a stable, low-viscosity dispersion. Upon UV irradiation, the PAG gets photolyzed, lowering the pH by about 3 units. In turn, the stabilizing surfactant is displaced from the negatively charged faces of the nanoparticle disks while the edges of the disks become positively charged. The particles are thereby induced to assemble into a 3 dimensional "house-of-cards" network that extends through the sample volume. The net result is a light-induced sol to gel transition, i.e., from a low, water-like viscosity to an infinite viscosity and yield stress. The yield stress of the photogel is sufficiently high to support the weight of small objects. The gel can be converted back to a sol by either increasing the pH or the surfactant content. Evidence for the above mechanism is provided from a variety of techniques, including small-angle neutron scattering (SANS). In the second part of this study, we demonstrate that laponite/PF127 mixtures also show thermogelling, i.e., the fluids transform from low viscosity sols to stiff gels upon heating above a critical temperature. This phenomenon is reversible and it requires the presence of sufficient amounts of both components. At room temperature, PF127 adsorbs onto laponite disks and stabilizes them by steric repulsion. Upon heating, the PF127 layer on the disks becomes thicker, and more importantly, PF127 micelles in the bulk solution grow significantly. Evidence for the growth of micelles is presented from SANS modeling and from transmission electron microscopy (TEM). At a distinct temperature, we believe the micelles induce depletion flocculation of the laponite particles into a gel network. Interestingly, if the PF127 concentration is increased further, the thermogelling is eliminated - this is suggested to be due to the micelles providing depletion stabilization of the particles.