Browsing by Subject "Nanoparticles"
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Item Active three-dimensional protein microstructures(2006) Hill, Ryan Toler; Shear, Jason B.Item Apoptotic and antiproliferative effect of nanoencapsulated (-)-Epigallocatechin gallate in human estrogen receptor positive breast cancer cells MCF 7(2011-05) Castillo-Cohen, Rita; Wang, Shu; Boylan, Lee M.; Gao, WeiminConsumption of green tea has been associated with many different health benefits; from weight loss to heart disease and different types of cancer. The chemopreventive actions exerted by green tea are thought to be due to its major polyphenol, (-)-Epigallocatechin-3-gallate (EGCG). Studies in human cancer cell lines and some animal models have demonstrated that EGCG can have chemopreventive activities without affecting their normal healthy cell counterpart. EGCG has a relative low bioavailability and stability, and studies have shown that the concentrations humans are able to absorb are five to fifty times less than the concentrations which seem to be responsible for the chemopreventive actions in past studies. Nanotechnology offers the means by which the bioavailability of EGCG can be improved to a level at which it can be useful in the fight against different diseases, including breast cancer. Breast cancer is considered to be the second most common type of cancer among women in the United States, accounting for more than one in four cancers in women (about 28%). Although current treatments for breast cancer have improved over the past several years, the side effects which accompany current cancer treatments (such as system toxicity stemming from chemotherapy) are still devastating, even potentially life threatening, to the patient. This study studied different nanoparticles and demonstrated that chitosan-coated nanoliposome at a dose of 10µM has a significant effect on decreasing proliferation and some apoptotic effect on MCF 7 breast cancer cells.Item Bayesian Spatial Modeling of Complex and High Dimensional Data(2012-02-14) Konomi, BledarThe main objective of this dissertation is to apply Bayesian modeling to different complex and high-dimensional spatial data sets. I develop Bayesian hierarchical spatial models for both the observed location and the observation variable. Throughout this dissertation I execute the inference of the posterior distributions using Markov chain Monte Carlo by developing computational strategies that can reduce the computational cost. I start with a "high level" image analysis by modeling the pixels with a Gaussian process and the objects with a marked-point process. The proposed method is an automatic image segmentation and classification procedure which simultaneously detects the boundaries and classifies the objects in the image into one of the predetermined shape families. Next, I move my attention to the piecewise non-stationary Gaussian process models and their computational challenges for very large data sets. I simultaneously model the non-stationarity and reduce the computational cost by using the innovative technique of full-scale approximation. I successfully demonstrate the proposed reduction technique to the Total Ozone Matrix Spectrometer (TOMS) data. Furthermore, I extend the reduction method for the non-stationary Gaussian process models to a dynamic partition of the space by using a modified Treed Gaussian Model. This modification is based on the use of a non-stationary function and the full-scale approximation. The proposed model can deal with piecewise non-stationary geostatistical data with unknown partitions. Finally, I apply the method to the TOMS data to explore the non-stationary nature of the data.Item Biomedical photoacoustics beyond thermal expansion : photoacoustic nanoDroplets(2012-05) Wilson, Katheryne Elizabeth; Emelianov, Stanislav Y.; Fowlkes, Brian; Hamilton, Mark; Sokolov, Konstantin; Williams, RobertThe recent increase in survival rates of most cancers is due to early detection greatly aided by medical imaging modalities. Combined ultrasound and photoacoustic imaging provide both morphological and functional/molecular information which can help to detect and diagnose cancer in its earliest stages. However, both modalities can benefit from the use of contrast agents. The objective of this thesis was to design, synthesize, and test a nano-sized, dual contrast agent for combined ultrasound and photoacoustic imaging named Photoacoustic nanoDroplets. This agent consists of liquid perfluorocarbon nanodroplets with encapsulated plasmonic nanoparticles. These dual contrast agents utilize optically triggered vaporization for photoacoustic signal generation, providing significantly higher signal amplitude than that from the traditionally used mechanism, thermal expansion. Upon pulsed laser irradiation, liquid perfluorocarbon undergoes a liquid-to-gas phase transition generating giant photoacoustic transients from these dwarf nanoparticles. Once triggered, the gaseous phase provides ultrasound contrast enhancement. Demonstrated in this work are the design, synthesis, characterization, and testing of Photoacoustic nanoDroplets in phantom and animal studies, and preliminary work into adapting these agents into targeted, drug delivery vehicles for simultaneous detection, diagnosis, and treatment of diseases.Item Characterization of biological hydrogel barriers(2014-12) Kaliki, Srimahitha; Smyth, Hugh D.C.,; Barr, Ronald; Milner, Thomas; Dunn, Andrew; Marek, StephenBiological hydrogel barriers include mucus, bacterial biofilms, fungal biofilms, and others. Biofilms are polysaccharide hydrogels. Biofilms are commonly found in the lungs of cystic fibrosis patients. Cystic fibrosis (CF) patients are susceptible to these types of chronic infections because their mucus barrier is abnormal. A common bacterial infection in these patients is caused by the bacterium Pseudomonas aeruginosa. While it is found that the bacteria can infect CF patients easily, the treatment of such infections by drugs had been found to be quite inefficient due to the structure of the biofilm itself and formidable mucus barrier. Mucus is a hydrogel which protects the gastrointestinal, genitor-urinal and respiratory tracts from pathogens and external environments. In our preliminary studies, topically applied nanoparticles disrupted these hydrogel barriers and resulted in the increase in permeability to solutes. The long term goal of this proposal is to understand and quantify the effects of the interaction between nanoparticles and biological hydrogel barriers. Discovering how nanoparticles disrupt the hydrogel barriers is important for understanding the health risks. The hypothesis of this research is that nanoparticles result in disruption of the hydrogel barrier structure that leads to increased exposures to co-deposited solutes. Quantifying the structural changes and diffusivity of such solutes using different novel techniques is the central object of my thesis. Bulk Rheological studies were performed using mucin samples treated with nanoparticles. It was noticed that the viscosities showed a negative trend with regards to the nanoparticle sizes which seemed to be contradictory to Einstein’s prediction. A possible mechanism of action was explained. Multiple particle tracking was performed to quantify viscosities of nanoparticles in mucin solution. Subsequently, drug diffusion studies were performed on similar samples to provide a relationship between the nanoparticle size and the drug permeability. Atomic force microscopy was performed in liquid cell using force mode on biofilms when treated with different sized nanoparticles. Micro-elasticity of these biofilms was calculated and compared.Item Characterization of Individual Nanoparticles and Applications of Nanoparticles in Mass Spectrometry(2011-08-08) Rajagopal Achary, Sidhartha RajaThe chemical characterization of individual nanoparticles (NPs)Item Coalescence and sintering in metallic nanoparticles : in-situ transmission electron microscopy (TEM) study(2012-05) Asoro, Michael Adewunmi, 1982-; Kovar, Desiderio; Ferreira, Paulo J. (Paulo Jorge); Rabenberg, Llewellyn K.; Meyers, Jeremy P.; Becker, Michael F.Nanoparticles possess unique physical, chemical, optical and electronic properties stemming from their nanoscale dimensions and are currently used in catalysis, microelectronics, drug delivery, as well as other applications. However, due to their large surface area-to-volume ratio, nanoparticles have a strong tendency to coalesce and sinter during processing or usage over short time scales and at low temperatures, which lead to significant changes in behavior and performance. In this work, in-situ transmission electron microscopy (TEM) heating has been used to investigate the effects of particle size, temperature and carbon capping layers on sintering in face-centered cubic (FCC) metallic nanoparticles. For the first time, we make direct and real-time measurements of nanoparticle size, neck growth, dihedral angle and grain boundary motion during sintering, which are then used to calculate fundamental material transport parameters such as surface diffusivity and grain boundary mobility. We observe that carbon surface coatings typically present on most commercial nanoparticles can significantly inhibit sintering in nanoparticles. Also, a new mechanism for coalescence in nanoparticles is shown where small clusters on the support can initiate neck growth by forming a bridge between the nanoparticles consisting of individual atoms or small clusters of atoms. In-situ TEM experiments provide critical and valuable real-time dynamic information for direct investigation of the link between the evolution of sintering and controlling mechanisms, which conventional experiments such as post-mortem TEM observations are not capable of conveying.Item Colloidal nanoparticles : a new class of laser gain media(2009-12) Morgan, Robert Douglas; Ditmire, Todd R.; Keto, John; Downer, Michael; Sitz, Greg; Desidero Kovar, DesideroDevelopment of high average power lasers has historically been limited by the properties of available gain media. As a result it is either too costly or impractical to employ lasers in many applications for which they would otherwise be well suited. We have synthesized a new type of colloidal laser gain material that should possess many of the advantages of solid state media without their primary disadvantage: poor thermal performance. The colloid consisted of an emulsion of 20% Nd+3 doped phosphate glass nanoparticles suspended in nonanoic acid. The spectroscopic properties of the material were found to be consistent with those of bulk Nd+3 doped materials and suitable for laser development.Item Composite nanogels for the triggerable release of chemotherapeutics(2015-12) Peters, Jonathan Thomas; Peppas, Nikolaos A., 1948-; Freeman, Benny; Johnston, Keith; Sanchez, Isaac; Zoldan, JanetaThe development of external stimuli responsive nanoparticles has progressed greatly since its inception in the seventies. However, apart from some clinical success for slow release delivery via liposomes, the technology has stalled for the delivery of chemotherapeutics due to a myriad of problems with cytocompatibility and premature diffusion of drug payload. The solution to cytocompatibility has been the coating of the system with polyethylene glycol. New methods have been developed to attach polyethylene glycol (PEG) tethers to the surface of otherwise unreactive particles. Surface hydrolysis of acrylamide containing polymers can be used to produce carboxylic acid functional groups near the surface of the polymeric nanoparticles. These nanoparticles can then be functionalized with PEG via EDC/NHS chemistry. The use of surface hydrolysis not only allows for reaction with these neutral polymers, but also provides greater control of PEG localization and leads to an unintrusive method to add the much needed stealth coating. In order to address the issue with premature release, new polymer systems have been developed. These systems are based around theory of hydrophobic interaction in order to improve the polymer/drug interaction in order to limit the unwanted diffusional release of drug payload. This interaction was addressed in a number of ways, focusing on both compartmentalization and copolymerization in order to develop nanogels that can entrap and withhold more drug from the surrounding area. An in depth look into the interactions that encourage drug uptake in these systems was performed by altering the copolymer chosen for these systems. This work looks into effects on phase transition, functional groups, hydrophobicity, and any structural changes that occur as a result of the polymerization scheme. After drawing conclusions on the interactions that encourage drug uptake, complex systems were devised to take advantage of these interactions. Core shell systems were designed to take advantage of the convective release of lower critical solution systems while still utilizing the mechanisms that improve drug retention. These systems were synthesized by two methods, emulsion polymerization and micelle crosslinking. These systems have been showed to improve the drug interaction and retention of doxorubicin as a model chemotherapeutic.Item Contrast and sensitivity enhanced molecular imaging using photoacoustic nanoamplifiers(2012-08) Chen, Yun-Sheng, active 2012; Emelianov, Stanislav Y.Molecular imaging is an emerging imaging principle which can visually represent the biological processes both spatially and temporally down to the sub-cellular level in vivo. The outcome of this research is expected to have a profound impact on facilitating the early diagnosis of diseases, accelerating the development of new drugs, and improving the efficacy of therapy. In general, molecular imaging highly relies on probes to sense the occurrence of molecular biological events, and to generate signals which could be picked up by diagnostic imaging modalities. The advances in the design of molecular probes not only have equipped traditional anatomical medical imaging with new capabilities but also, in some cases, stimulated developments of new imaging modalities and renaissance of existing medical imaging modalities. One of these is photoacoustic imaging, which as an emerging medical imaging modality, unites the merits from both optical imaging and ultrasound imaging. It shares with optical imaging, that it uses non-ionizing radiation and provides higher contrast and higher sensitivity than ultrasound imaging. Unlike optical imaging, which requires ballistic photons for imaging, photoacoustic imaging requires only diffusive photons to excite the ultrasound signal from the imaging target; therefore, it is capable of imaging much deeper into the tissue. In combination with molecular probes, photoacoustic molecular imaging has been demonstrated by several research groups using various photoacoustic molecular probes. However, the molecular probes used for most of these studies were contrast agents simply adopted from other optical imaging modalities. Our research on photoacoustic contrast agents indicated that the mechanism of photoacoustic signal generation from nanometer-sized contrast agents is distinct from that of optically homogeneous materials, such as tissue. We have discovered that, the amplitude of the photoacoustic signal generated from nano-contrast agents depends not only on the optical absorption of the particles, but more importantly, on the dynamic process of the heat conduction from the nanoparticles to the ambient, and the thermal properties of the surrounding materials. Based on our finding, we explored and further improved the photoacoustic response of the nanoparticles by exploiting the heat conduction process between the nanoparticle and its surrounding materials and by manipulating the excitations. This research allows to create optimized molecular specific contrast enhanced photothermal stable probes which can aid photoacoustic imaging and image guided photothermal cancer therapy.Item Controlled assembly of biodegradable gold nanoclusters for in vivo imaging(2015-12) Stover, Robert John; Johnston, Keith P., 1955-; Truskett, Thomas M; Fan, Donglei; Korgel, Brian; Sokolov, KonstantinGold nanoparticles are of interest in biomedical imaging applications due to their inert nature and ability to exhibit surface plasmon resonance. These phenomena can result in high near-infrared extinction (NIR) due to asymmetry or close interparticle spacings within gold structures, making these materials ideal for photoacoustic imaging. Using this imaging modality, these materials allow for high contrast compared to the body’s tissues which exhibit a transparent “window” between 700-1100 nm, making them perfect for early cancer detection. However many gold structures designed for this application fail to achieve high NIR-absorbance at the <5 nm sizes which are required for efficient kidney clearance. Therefore, we designed a system which assembles ~4 nm primary gold particles into closely-spaced clusters of controlled size using a biodegradable, weakly adsorbing polymer and balance of colloidal attractive and repulsive forces. Thus, when the polymer degrades in acidic environments – such as within cells – the residual charge on the primary particles leads to dissociation of the clusters back to renal-clearable constituents. Since proteins in the blood and cells can increase the diameter of the primary particles above the 5 nm threshold, nanoparticle surfaces were designed to have a mixture of charged and zwitterionic molecules to limit protein interactions through buried charges and increased particle hydration. Strongly-bound, zwitterionic thiol-containing ligands were also investigated to resist the intracellular exchange of biomolecules which could compromise the clearable nature of the particles. These decorated nanoparticles were then assembled into clusters through one of two methods which varied either gold and polymer concentrations through evaporation, or particle charge via electrolyte addition prior to quenching by dilution in DI water. Once assembled, clusters assembled with polymer showed dissociation behavior after incubation in pH 5 acidic solutions to mimic the cellular pH environment. In other cases, sintering of the gold nanoparticle clusters prevented such dissociation. This thesis demonstrates the ability to not only create biocompatible nanoparticle surfaces, but to establish control size control over nanocluster assemblies which are capable of being used as NIR contrast agents.Item Defects and deformation in nanostructured metals(2009-12) Carlton, Christopher Earl; Ferreira, Paulo J. S. G.A better understanding of how the nanoscale environment affects the mechanical properties of materials, in particular metallic nanoparticles and nanocrystalline metals is vital to the development of next generation materials. Of special interest is obtaining a fundamental understanding of the inverse Hall-Petch Effect in nanocrystalline metals, and nanoindentation in individual nanoparticles. Understanding these subjects is critical to understanding how the mechanical properties of materials are fundamentally affected by nanoscale dimensions. These topics have been addressed by a combination of theoretical modeling and in-situ nanoindentation transmission electron microscopy (TEM) analysis. Specifically, the study of the inverse Hall-Petch effect in nanocrystalline metals will be investigated by a thorough review of the literature followed by a proposed novel theoretical model that better explains the experimentally observed behavior of nanocrystalline metals. On the other hand, the nanoindentation of individual nanoparticles is a very new research topic that has yet to aggregate a large body of experimental data. In this context, in-situ TEM nanoindentation experiments on silver nanoparticles will be first performed to determine the mechanisms of deformation in these nanostructures. A theoretical explanation for the observed deformation mechanisms will be then developed and its implications will be discussed. In addition to nanoparticles, this study will also provide unique and valuable insight into the deformation mechanisms of nanopillars, a growing area of research despite much controversy and speculation about their actual mechanisms of deformation. After studying the novel behavior of both nanocrystalline metals and nanoparticles, useful applications of both classes of materials will be explored. The discussion of applications will focus on utilizing the interesting behaviors explored in the dissertation. Of particular interest will be applications of nanoparticles and nanocrystalline materials to coatings, radiation resistance and super-plastic materials.Item Dendrimer-encapsulated nanoparticles : synthetic methods and characterization including extended X-ray absorption-fine structure(2010-12) Weir, Michael Glen; Crooks, Richard M. (Richard McConnell); Bard, Allen J.; Frenkel, Anatoly I.; Henkelman, Graeme; Johnston, Keith; Willets, KatherineThis work describes the synthesis of dendrimer-encapsulated nanoparticles (DENs) and the expansion of the characterization ability for these materials. The dendrimer-template method for the synthesis of nanoparticles allows precise control over the size, composition and structure of nanoparticles in the 40-250 atom range. In this size regime, the surface structure of the nanoparticles dominates their catalytic properties. The long term goal of this research is to correlate the structure of these nanoparticles to their catalytic activity, improving the ability to predict superior catalysts a priori. As a prerequisite for this analysis, the precise structure of the catalytically active nanoparticle must be determined. Characterization of nanoparticles in the 1-2 nm region is significantly more difficult than more commonly used nanoparticles of 3-5 nm diameter or larger. Typical characterization of these nanoparticles involves UV-vis spectroscopy for Mie absorbance and transmission electron microscopy for size analysis. This work involves the use of extended X-ray absorption-fine structure (EXAFS) to determine the local structure of the nanoparticles. For monometallic Pt DENs, EXAFS was combined with UV-vis, TEM, X-ray photoelectron spectroscopy (XPS) and electrochemistry to determine that the Pt system is not simply nanoparticles but a more complex, bimodal state. EXAFS has also been used to differentiate between different bimetallic structures. For PdAu DENs, there are two synthetic methods used. When both metals are reduced simultaneously, the resulting nanoparticles have a quasi-random alloy structure. These nanoparticles were then extracted from the dendrimer into an organic solvent by use of alkanethiols. The extraction process changed the alloy structure into Au-core/Pd-shell. When Pd and Au were reduced in sequence, the DENs were formed as a Au-core/Pd-shell material, regardless of the order of the reduction of the metals. The Au-core/Pd-shell structure was also present after extraction. In addition to structural analysis to determine the result of different synthetic methods, EXAFS was also used in situ to measure the structure of Pt DENs during the oxidation of absorbed CO. These in situ measurements are important for determining the structure of the actual catalyst rather than the precursor nanoparticle. In this case, the Pt DENs changed from a bimodal distribution into fully reduced nanoparticles by the application of a reducing potential. The binding of CO to the Pt DENs and subsequent oxidation did not cause measurable agglomeration of the nanoparticles. This reduction of the Pt system by electrochemical means was also explored as a synthetic method. The Pt-dendrimer complex was placed on a TEM grid for electrochemical treatment. A potential step was shown to reduce some of the Pt-dendrimer complexes into Pt nanoparticles of the expected size. However, most of the complexes were not reduced. Therefore, only the standard chemical reduction followed by electrochemical treatment is sufficient to fully reduce the nanoparticle samples. This work has explored additional synthetic methods for the synthesis of monometallic and bimetallic DENs. The use of EXAFS, as well as other advanced characterization techniques, has advanced knowledge of the structure of various DENs. Both the characterization toolset and the synthetic methods will provide a basis for investigations of catalytically active materials.Item The Design and Control of Stability and Magnetic Properties of Imaging Nanoparticles(2012-12) Yoon, Ki Youl; Johnston, Keith P., 1955-; Bryant, Steven L; Milner, Thomas E; Huh, Chun; Ruoff, Rodney S; Ferreira, Paulo JThere is significant interest in applying nanoparticle (NP) science to subsurface reservoirs to facilitate oil and gas recovery, image subsurface reservoirs, aid sequestration of CO2 and benefit environmental remediation. Imaging nanoparticles have been designed with long-term dispersion stability in brine and minimal retention in reservoir rock and with preferential adsorption at oil-water interfaces. Polymer-stabilized nanoparticles provide sufficient electrostatic repulsion for high colloidal stability, as characterized by the zeta potential. The small size of the clusters, superparamagnetic properties, and high salt tolerance are highly beneficial in various applications including magnetomotive and electromagnetic imaging and mapping of petroleum reservoirs. Superparamagnetic nanoclusters may be used in imaging in biomedicine and in mapping of petroleum reservoirs, by generating either ultrasonic or acoustic signals with oscillating magnetic motion. For a given magnetization per weight of iron oxide, nanoclusters with sub ~100 nm diameters experience a much larger magnetic force than that of the primary sub- 10 nm primary particles. Aqueous dispersions of 0.1-0.2 wt% superparamagnetic iron oxide nanoclusters were stabilized with citric acid, poly(acrylic acid) (PAA), or poly(styrene sulfonate-alt-maleic acid) (PSS-alt-MA) on the particle surface, with a high loading of ~90% iron oxide. For nanoclusters with only 12% (w/w) PSS-alt-MA electrosteric stabilization was sufficient even in 8 wt% NaCl. Both PAA and PSS-alt-MA were used to stabilize nanoclusters with controlled size during synthesis in aqueous media. To obtain a permanent coating on the surface of clusters cross-linking of the polymer for different cross-linking densities was applied. In this general and highly flexible approach, iron oxide nanoparticles may be formed with an adsorbed polymer stabilizer, which is then permanently bound to the surface via cross-linking. To investigate interfacial activity of nanoparticles, oil-in-water emulsions were stabilized with iron oxide nanoclusters or graphene oxide platelets. In each case, the stabilization was achieved by designing the hydrophilic/hydrophobic nature of surface coating. For oil/water emulsions, the droplet size was as low as ~1 micron diameter, and strongly shear-thinning rheology was observed. A series of sub-100 nm superparamagnetic iron oxide nanoparticles with amphiphilic poly(acrylic acid-b-butylacrylate), (PAA-b-PBA) copolymer shells was synthesized to investigate the effect of the polymer structure on the interfacial tension for nanoparticles adsorbed at the dodecane-water interface. Large reductions in interfacial tension of up to 27.6 mN/m were obtained for a 0.27 wt% nanoparticle concentration indicating significant nanoparticle adsorption and interaction with the oil and water molecules at the interface. The adsorption energy of the polymer-coated nanoparticles at the dodecane/water interface was determined from the interfacial tension and nanoparticle radius, and analyzed in terms of the structure of the polymer stabilizer. Furthermore, oil-in-water emulsions stabilized with graphene oxide nanoplatelets were found to remain stable for several months even at high salinity (up to 5 wt% NaCl, for pH = 2 to 10). The droplet sizes were as small as ~1 μm with a low nanoplatelet concentration of 0.2 wt%.Item Detection of magneto-activated water/oil interfaces containing nanoparticles(2011-12) Ryoo, SeungYup; Huh, Chun; Milner, Thomas E.; Driga, Micea; Becker, Michael; Neikirk, Dean; Johnston, Keith P.Accurate, non-invasive determination of multiphase fluids distribution in reservoir rock can greatly help the evaluation and monitoring of oil reservoirs. This laboratory thesis research, carried but utilizing the biomedical engineering concepts and measurement facilities, is an important step in developing a novel magnetic field-based oil detection method. When paramagnetic nanoparticles are either adsorbed oil/water interface or dispersed in a fluid phase in reservoir rock pores, and exposed to external magnetic field, the resultant particle movements displace the interface. Interfacial tension acts as a restoring force, leading to interfacial fluctuation and a pressure (sound) save. As the first step, the motion of the interface between a suspension of paramagnetic nanoparticles and a non-magnetized fluid (placed in a cylindrical dish) is measured by phase-sensitive optical coherence tomography (PS-OCT). Experiments were carried out with a range of iron-oxide nanoparticles that were synthesized and surface-coated by our Chemical Engineering collaborators. The numerical method was improved to be volume conserving, and extended to 3D, for more quantitative matching. The measurements of interfacial motion by PS-OCT confirm theoretical predictions of the frequency doubling and importance of material properties, such as the particle size, for the interface displacements. The relative densities of the fluid phase(air/aqueous and dodecane/aqueous) strongly affect the interfacial displacement. Next, the acoustic responses to the external magnetic oscillation, from the rock samples into which different aqueous dispersions of nanoparticles were injected, were measured in terms of the magnetic frequency, nanoparticle concentration, and other process parameters. Subsequently, the PS-OCT displacements in response to the external magnetic oscillation, from the rock samples into which different aqueous dispersions of nanoparticles were injected, were also measured in terms of the magnetic frequency, nanoparticle concentration, and other process parameters. Conclusions and the recommendations for further study are then given.Item Development and evaluation of enzymatically-degradable hydrogel microparticles for pulmonary delivery of nanoparticles and biologics(2012-12) Wanakule, Prinda 1985-; Roy, KrishnenduThe emerging class of biologic drugs, including proteins, peptides, and gene therapies, are widely administered by injection, despite potential systemic side effects. Rational design of targeted carriers that can be delivered non-invasively, with reduced side effects, is essential for the success of these therapies, as well as for the improvement of patient compliance and quality of life. One potential approach is to take advantage of specific physiological cues, such as enzymes, which would trigger drug release from a drug carrier. Enzymatic cleavage is highly specific and could be tailored for certain diseased tissues where specific enzymes are up regulated. Enzymatically-degradable hydrogels, which incorporate an enzyme- cleavable peptide into the network structure, have been extensively reported for releasing drugs for tissue engineering applications. These studies showed that a rapid response and corresponding drug release occurs upon enzyme exposure, whereas minimal degradation occurs without enzyme. Recently, Michael addition reactions have been developed for the synthesis of such enzymatically-degradable hydrogels. Michael addition reactions occur under mild physiological conditions, making them ideally suited for polymerizing hydrogels with encapsulated biologic drugs without affecting its bioactivity, as in traditional polymerization and particle synthesis. The focus of my research was to create enzymatically-degradable hydrogel microparticles, using Michael addition chemistry, to evaluate for use as an inhalable, disease-responsive delivery system for biologic drugs and nanoparticles. In this dissertation, I utilize bioconjugation and Michael addition chemistries in the design and development of enzymatically-degradable hydrogels, which may be tailored to a multitude of disease applications. I then introduce a new method of hydrogel microparticle, or microgel, synthesis known as the Michael Addition During Emulsion (MADE) method. These microgel carriers were evaluated in vitro, and found to exhibit triggered release of encapsulated biologic drugs in response to enzyme, no significant cytotoxic effects, and the ability the avoid rapid clearance by macrophages. Lastly, in vivo studies in mice were conducted, and microgels were found to exhibit successful delivery to the deep lung, as well as prolonged pulmonary retention after intratracheal aerosol delivery. In conclusion, a new class of enzymatically-degradable microgels were successfully developed and characterized as a versatile and promising new system for pulmonary, disease-responsive delivery of biologic drugs.Item Development of anode catalysts for direct alcohol fuel cells(2010-08) Lee, Eungje; Manthiram, Arumugam; Goodenough, John B.; Bard, Allen J.; Ferreira, Paulo; Meyers, Jeremy P.Direct alcohol fuel cells (DAFC) are attracting considerable interest to meet a variety of energy needs as they offer higher efficiency with less pollution compared to other conventional energy-conversion devices. However, the sluggish alcohol oxidation reaction kinetics and durability problems of the conventional Pt-Ru anode catalyst hamper the commercialization of the DAFC systems. With an aim to overcome these problems, there have been intensive efforts to alloy Pt-Ru with other metals. Although such strategies have led to some enhancement in activity, the durability problem caused by the instability of Ru could still not be alleviated. In this regard, this dissertation focuses on the development of non-Ru electrocatalysts with high activity and durability for DAFC applications. First, Ru-free, Pt-based bimetallic electrocatalysts for methanol oxidation reaction (MOR) were studied. Particularly, Pt-Sn and Pt-CeO₂ catalysts were synthesized, respectively, by a polyol method and a one-step reverse microemulsion (RME) method. The prepared samples are investigated for phase and morphological evaluations by various material-characterization techniques. Cyclic voltammetry and accelerated durability tests revealed that these alternative catalysts have much higher stability with a catalytic activity for MOR comparable to that of Pt-Ru. In the case of Pt-CeO₂, an improved particle morphology is obtained by the RME synthesis, and the advantage of the RME method is reflected by a higher catalytic activity in comparison to that of Pt-CeO₂ synthesized by the conventional synthesis method. It has been known that Pt-Sn is better than Pt-Ru for ethanol oxidation reaction (EOR), and the direct ethanol fuel cells (DEFC) employing Pt-Sn as the anode catalyst have better durability than the DMFC system employing a Pt-Ru anode catalyst. Therefore, this dissertation then focused on the enhancement of the catalytic activity for EOR by incorporating a third metal M to the Pt-Sn catalyst. Following the synthesis and characterization of the Pt-Sn-M (M = Mo and Pd) alloys, the effect of M on the enhanced catalytic activity of Pt-Sn-M is presented. The activity enhancement of the above catalysts is based on the promoting effect of the second or third elements added to Pt. However, in the final chapter of this dissertation, the activity enhancement of Pt nanoparticle itself through the formation of low energy surfaces is investigated. Carbon-supported Pt nanoparticles are synthesized in mixed water-ethylene glycol solvent, and the positive effect of the mixed solvent on both the morphology and surface structure of the Pt nanoparticles for COad oxidation is discussed.Item Development of Iron Oxide Based Nanoparticles as Dual-Modality Imaging Probes(2008-09-12) Guo, Yi; Sun, XiankaiDual-modality (MR/nuclear) imaging can combine exquisite anatomical resolution with superior molecular sensitivity, and significantly facilitate the accuracy of cancer diagnosis. However, the application of this technique is hampered by the paucity of sensitive dual-modality imaging probes that target tumors specifically. Here we synthesized dual-modality imaging probes by doping positron- or gamma-emitting nuclides to the core of dextran-coated superparamagnetic iron oxide nanoparticles (NUSPIONs). The synthesized nanoparticles were characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), atomic force microscope (AFM), and high performance liquid chromatography (HPLC). The evaluations of these nanoparticles were performed both in vitro and in vivo. Four radioisotopes (111In, 177Lu, 64Cu, and 77As) were successfully incorporated into the core of nanoparticles. The purification of nanoparticles via centricon filter accelerated the separation process effectively without apparent aggregation. These nanoparticles exhibited good in vitro stability in both phosphate buffered saline (> 99% intact) and rat serum (> 92% intact) out to 72 h, and the high r2-to-r1 ratio indicating their potential as MRI T2 contrast agents. Two distinctly sized 177Lu-doped nanoparticles (NUSPION-1 and NUSPION-2 with hydrodynamic radii of 11.8 3 nm and 30.6 5 nm respectively) were used for biodistribution studies in normal mice. NUSPION-1 showed significantly (p < 0.0001) higher uptake and longer retention in blood and less uptake in liver and spleen than NUSPION-2, which is advantageous for both passive and active targeting. Due to its optimal tissue distribution pattern, NUSPION-1 was chosen for further in vivo evaluation in PC-3 tumor-bearing mice. High tumor uptake and contrast ratios of tumor-to-muscle and tumor-to-blood were observed. A proof-of-principle dual-modality imaging study was carried out by a virtually single-dose injection in PC-3 tumor-bearing mice. The tumors were visualized by both MRI and autoradiography. Post-MRI Prussian blue iron staining and post-autoradiographic imaging biodistribution confirmed the accumulation of nanoparticles in tumors. Taken together, we have demonstrated a practical method to develop iron oxide based MRI/nuclear imaging probes.Item Development of nanofiber protective substrates(Texas Tech University, 2004-08) Subbiah, ThandavamoorthyElectrospinning uses high voltage electric field to produce high surface area fibers in the nanometer range. Polymeric nanofibers were prepared by the electrospinning process and were characterized using Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). A study on the relationship between process parameters and fiber characteristics was undertaken. The dependence of fiber morphology on the solvent volatility and collector substrate characteristics was critically analyzed. Results on the self assembling nature of the charged fibers over different collector substrates were obtained and reported in the thesis. Defect free nanofiber webs with high specific surface area and low porosities suitable enough to be used as adsorptive filtration membranes were prepared. Polyurethane nanofibers were used as nano metal oxide catalyst carriers by successfully impregnating the catalyst in a single-step electrospinning process. Aerosol filtration abilities of nanofiber membranes were tested and the results are presented.Item Direct numerical simulation and reaction path analysis of titania formation in flame synthesis(2012-08) Singh, Ravi Ishwar; Ezekoye, Ofodike A.; Raman, VenkatFlame-based synthesis is an attractive industrial process for the large scale generation of nanoparticles. In this aerosol process, a gasifi ed precursor is injected into a high-temperature turbulent flame, where oxidation followed by particle nucleation and other solid phase dynamics create nanoparticles. Precursor oxidation, which ultimately leads to nucleation, is strongly influenced by the turbulent flame dynamics. Here, direct numerical simulation (DNS) of a canonical homogeneous flow is used to understand the interaction between a methane/air flame and titanium tetrachloride oxidation to titania. Detailed chemical kinetics is used to describe the combustion and precursor oxidation processes. Results show that the initial precursor decomposition is heavily influenced by the gas phase temperature field. However, temperature insensitivity of subsequent reactions in the precursor oxidation pathway slow down conversion to the titania. Consequently, titania formation occurs at much longer time scales compared to that of hydrocarbon oxidation. Further, only a fraction of the precursor is converted to titania, and a signi cant amount of partially-oxidized precursor species are formed. Introducing the precursor in the oxidizer stream as opposed to the fuel stream has only a minimal impact on the oxidation dynamics. In order to understand modeling issues, the DNS results are compared with the laminar flamelet model. It is shown that the flamelet assumption qualitatively reproduces the oxidation structure. Further, reduced oxygen concentration in the near-flame location critically a ffects titania formation. The DNS results also show that titania forms on the lean and rich sides of the flame. A reaction path analysis (RPA) is conducted. The results illustrate the di ffering reaction pathways of the detailed chemical mechanism depending on the composition of the mixture. The RPA results corroborate with the DNS results that titania formation is maximized at two mixture fraction values, one on the lean side of the flame, and one on the rich side.