The present research involves two projects: a surface science study of the room-temperature adsorption and thermal evolution of allylamine and ethanolamine on Si(100)2×1, studied by using temperature-dependent X-ray photoelectron spectroscopy (XPS) and thermal desorption spectrometry (TDS), as well as Density Functional Theory (DFT) calculations; and a materials science study on the shape control of copper nanoparticles (Cu NPs) deposited on H-terminated Si(100) substrate with an extended size regime of 5-400 nm, by using a simple, one-step electrochemical method. The Cu NPs of three primary shapes were characterized with scanning-electron microscopy (SEM), glancing-incidence X-ray diffraction (GIXRD) and XPS. In the first surface science study, the presence of broad N 1s XPS features at 398.9-399.1 eV, corresponding to N–Si bonds, indicates N–H dissociative adsorption for both allylamine and ethanolamine on Si(100)2×1. For allylamine, the presence of C 1s features at 284.6 eV and 286.2 eV, corresponding to C=C and C−N, respectively, and the absence of the Si−C feature expected at 283.5 eV show that the reactions involving the ethenyl group such as the [2+2] C=C cycloaddition or those producing the [N, C, C] tridentate adstructures do not occur at room temperature. For ethanolamine, the O 1s feature at 533.1 eV indicates the formation of Si−O bond and O−H dissociation, which confirms an [O, N] bidentate adstructure and excludes the N−H and O−H dissociation unidentate structures. These XPS data are consistent with the N−H unidentate, and N−H and O−H double dissociation [O, N] bidentate adstructures for allylamine and ethanolamine, respectively, as predicted by the DFT calculations. TDS and temperature-dependent XPS data further show the desorption of propene and ethylene at 580 K and of acetylene at 700 K for allylamine and the desorption of ethylene at 615 K for ethanolamine, while the lack of N- or O-containing desorbates suggests that the dissociated N and O species are likely bonded to multiple surface Si atoms or diffused into the bulk at elevated temperatures (as confirmed by the corresponding temperature-dependent XPS spectra). Unlike the multidentate allyl alcohol and allylamine adstructures that have been found to be not favored kinetically, the present [O, N] bidentate ethanolamine adstructure appears to be kinetically favored on Si(100)2×1. In the second materials science study, Cu NPs of three primary shapes have been deposited on H-terminated Si(100) by a simple, one-step electrochemical method. By precisely manipulating the electrolyte concentration [CuSO4.5H2O] below their respective critical values, cubic, cuboctahedral, and octahedral Cu NPs of ranges of average sizes and number densities can be easily obtained by varying the deposition time. Combined GIXRD and depth-profiling XPS studies show that these Cu NPs have a crystalline core-shell structure, with a face-centered cubic metallic Cu core and a simple cubic Cu2O shell with a CuO outerlayer. The shape control of Cu NPs can be understood in terms of a progressive growth model under different kinetic conditions as dictated by different [CuSO4.5H2O] concentration regimes. The two studies in the present work lay the foundation for future investigation of surface biofunctionalization of these fascinating Cu NPs with different shapes and therefore different surface chemistries as controlled by the relative amounts of the (100) and (111) facets, and their boundaries.

With the industry striving for smaller devices, new technologies are developed to further miniaturize electronics devices. To this end, realization of 3D/non-planar interconnects, which aim at miniaturizing the interconnects formed between components on the same device, has attracted many researchers. This thesis focuses on a feasibility analysis for developing non-planar interconnects on various flexible substrates using laser assisted maskless microdeposition (LAMM), which is a pressure-less process. There are two types of flexible substrates that are used: double-sided copper substrates separated by a layer of polyethylene terephthalate (PET) as well as a polyethylene terephthalate flexible substrate with surface-mounted resistors. For both substrates, multiple types of experiments were conducted to discover procedures which result in the highest rate of success for forming conductive interconnects. Optimal process parameters and deposition techniques were determined after multiple experiments. After experiments were completed, the resultant substrates were subject to various characterization methodologies including optical and scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction and profilometery. The results of these methodologies are documented in this thesis. After many types of experiments involving substrate manipulation of the double-sided copper substrates, it was shown that the silver nano-particles were more likely to form a conductive interconnect when a polished slant was fabricated on the substrate. Many deposition patterns were used for the flexible substrates with surface-mounted resistors. Of these patterns, the two patterns, the ‘zigzag’ and ‘dot solder’ patterns, proved to have a much higher success rate for creating conductive interconnects compared to the other patterns. During this study, the results of the experiments using the LAMM process show that this technology has great potential for creating non-planar interconnects on flexible substrates. The experiments however suggest that the process is very sensitive to the material composition and process parameters. As such, with a small change in parameters, the 3D interconnects can fail to be produced. It was also observed that the possibility of silver interconnect fractures is higher where dissimilar materials with different thermal expansion rates are used for the underlying substrates.

The interaction of nanoparticles with biological systems, especially interactions with cell membranes, has been a subject of active research due to its numerous applications in many areas of soft-matter and biological systems. Within only a few relevant physical parameters profound structural properties have been discovered in the context of simple coarse-grained theoretical models. In this Thesis we study the structure of a tubular membrane adhering to two rigid cylindrical particles on a basis of a free-energy model that uses Helfrich energy for the description of the membrane. A numerical procedure is developed to solve the shape equations that determine the state of lowest energy. Several phase transitions exist in the system, arising from the competition between the bending energy of the membrane and the adhesion energy between the membrane and the particles. A continuous adhesion transition between the free and bound states, as well as several discontinuous shape transitions are identified, depending on the physical parameters of the system. The results are then generalized into a single phase diagram separating free, symmetric- and asymmetric-wrapping states in the phase space of the size of the particles and the adhesion energy. We show that for a relatively small size of the membrane tube the interaction between the cylinders becomes attractive in the strong curvature regime, leading to aggregation of the particles in the highly curved area of the tube that is characteristically different from the aggregation in a related three-dimensional system. For a relatively large membrane tube size the cylinders prefer to have a non-zero separation, even in the completely engulfed state. This indicates that, i) the spontaneous curvature of the membrane may play a role in the sign of the interaction of two colloidal particles adhered to a membrane and ii) cylindrical particles can aggregate on membrane tubes and vesicles if the curvature of the membrane around the aggregation region is sufficiently large.

This work attempted to detect chemical warfare agent (CWA) simulants via electrochemistry utilizing two approaches. The first approach consisted of a ferrocene (Fc) amino acid derivative film on Au surfaces. The molecule [(BocHN)Fc(CO)CSA]2 was electrodeposited onto Au microelectrodes through a SAu bond. Once immobilized, the Fc amino acid derivative was Boc deprotected allowing for the amino group to react with the target molecule. Detection of the target simulant was monitored by cyclic voltammetry (CV) while following the formal potential of the Fc molecule, which is influenced by its immediate electronic microenvironment. Reaction with either 1 mM diethyl cyanophosphonate (DECP) or 2 chloroethyl ethyl sulfide (2 CEES), both effectively simulants for the CWAs Tabun nerve agent and blistering sulfur mustard respectively, was not observed. However, detection of 1 mM acetyl chloride was achieved by observing a potential anodic shift from 217 ± 6 mV, for the Boc deprotected form, to 388 ± 7 mV for the reacted state of the molecule. The lack of reactivity with the Fc amino acid system was hypothesized as a kinetic issue.<p> In the second approach, the electrochemistry of gas generated naked Ag nanoparticles (NPs) deposited on indium tin oxide covered glass plates is compared to bulk polycrystalline Ag. The nano specific electrochemistry of Ag NPs has been identified and includes the preferential formation of â oxides. In 100 mM KOH supporting electrolyte, disruption of â oxide formation is exploited to test for the presence of 1 mM DECP resulting in the dissolution of Ag via cyanide complexes leading to a CV signal decrease. While in 8.0 M KOH, â oxide formation is enhanced leading to testing capabilities for 1 mM 2 CEES resulting in the disappearance of the â oxide peak and the appearance of surface oxide peak during CV. Analogous electrochemistry is not observed on polycrystalline bulk Ag.

<p>Traditionally, the goal of nanoparticle-based chemotherapy has been to decrease normal tissue toxicity by improving drug specificity to tumor. Relying on the EPR effect (Enhanced Permeability and Retention), a host of nanoparticles (from micelles and dendrimers to liposomes and lipidic nanoparticles) have been developed and tested for passive accumulation into tumor interstitium. Unfortunately, most nanoparticles achieve only suboptimal drug delivery to tumors, due to heterogeneity of tumor vessel permeability, limited nanoparticle penetration, and relatively slow drug release. However, recent developments in nanoparticle technology have occurred with the design and testing of a fast drug-releasing liposome triggered by local heat. This temperature-sensitive liposome formulation loaded with doxorubicin (Dox-TSL) has already shown substantial anti-tumor efficacy and is currently in clinical trials.</p><p> Previous pre-clinical work to understand the mechanism of efficacy has illustrated increases in overall drug concentration in the tumor, and an anti-vascular effect not observed with heat alone. These initial studies have also suggested that these liposomes may be the most efficacious when they are injected into a pre-heated tumor, with the hypothesis that in this treatment scheme the liposomes may be releasing inside the tumor vasculature. However, whether intravascular release is indeed occurring, and the subsequent implications this paradigm change in drug delivery could have are still unanswered questions. </p><p>The experiments presented herein aimed to investigate two effects: the existence and influence of intravascular drug release on drug delivery and distribution within the tumor, and the effect of drug delivery on subsequent anti-vascular effects. To investigate drug delivery, two mouse models were used. Dorsal window chambers implanted with FaDu human squamous carcinomas were used with real-time intravital confocal microscopy to evaluate time-resolved delivery of doxorubicin and liposome extravasation over the first 20 minutes of treatment. As a complimentary mouse model, flank FaDu tumors were also treated with Dox-TSL or treatment controls (doxorubicin with and without heat and Doxil with heat), and subsequently sectioned and histologicaly imaged to evaluate drug delivery and penetration depth, as well as impact on hypoxia and perfusion parameters. To investigate vascular effects, a GFP-eNos transgenic mouse model was used, also with window chamber confocal microscopy, to evaluate morphological changes occurring in the tumor vasculature following treatment.</p><p> The results presented herein demonstrate that contrary to the traditional liposome paradigm of extravasation and subsequent drug release, thermally sensitive liposomes release drug inside the tumor vasculature, and that the released free drug diffuses into the tumor interstitium. Real-time confocal imaging of doxorubicin delivery to murine tumor window chambers illustrates that intravascular drug release provides a mechanism to increase both the time that tumor cells are exposed to maximum drug levels and the penetration distance achievable by free drug diffusion. Histological analysis further confirms this finding, illustrating that drug delivered with Dox-TSL intravascular release can result in drug penetration levels up to 80 µm from vessels, in comparison with 40 µm achievable with free drug with heat. Further, Dox-TSL delivers drug to a higher percentage of a tumor's hypoxic area than possible with free drug with or without heat. Endothelial cells display marked morphological changes apparent immediately following treatment, with significant vascular destruction at 6 hours. However, heat had a similar influence on vascular morphology, underscoring the complexity of the anti-vascular effect, particularly in the more sensitive vasculature of a mouse model compared with reported human vascular heat tolerances. This work establishes intravascular release as a new paradigm in drug delivery to solid tumors, resulting in improved drug bioavailability, penetration depth, and enhanced delivery of drug to hypoxic regions of tumors.</p> / Dissertation

<p>Background: Silver nanoparticles (AgNPs) act as antimicrobials by releasing monovalent silver (Ag+) and are increasingly used in consumer products, thus elevating exposures in human and environmental populations. Materials and Methods: We evaluated Ag+ in a standard model of neuronal cell replication and differentiation, and then determined whether there were similar effects of the ion in vivo using zebrafish. Next, we compared Ag+ and AgNP exposures in the same two models and incorporated the effects of particle coating, size and composition. Conclusions: This work is the first to show that both Ag+ and AgNPs are developmental neurotoxicants in vitro and in vivo. Moreover, although both the soluble ion and the particles impair measures of neurodevelopment, the outcomes and underlying mechanisms of each toxicant are often wholly distinct. Superimposed on the dichotomies between Ag+ and AgNP exposures are clear effects of particle coating, size and composition that will necessitate evaluation of individual AgNP types when considering potential environmental and human health effects. The results presented here provide hazard identification that can help isolate the models and endpoints necessary for developing a risk assessment framework for the growing use of AgNPs.</p> / Dissertation

Surface Biological Modification and Cellular Interactions of Magnetic Spinel Nanoparticles Eva Liang-Huang Heintz 191 Pages Directed by Dr. Z. John Zhang The interest in magnetic nanoparticles is multi-dimensional. Fundamentally, it is important to be able to control their magnetic properties and to correlate to specific applications. In biology, magnetic nanoparticles offer promising potential as magnetic carriers or chaperones for magnetic localization and manipulation of therapeutic reagents. The synthesis of superparamagnetic CoFe2-xSmxO4 nanoparticles and the tunability of their magnetic properties by size and composition variations are discussed. An increase in size of CoSm0.19Fe1.81O4 nanoparticles produced an increase in blocking temperature and saturation magnetization, but a non-linear coercitivity response was observed with change in size. By varying the composition, the saturation magnetization of CoFe2-xSmxO4 decreased dramatically while the coercitivity increased when compared to native cobalt spinel ferrite (CoFe2O4) nanoparticles. These results demonstrate how the magnetic properties of cobalt spinel ferrite nanoparticles can be tailored to specific applications. Surface modifications of cobalt spinel ferrite nanoparticles facilitated the conjugation of oligonucleotides. Using a transfection reagent, CoFe2O4 ??igonucleotide conjugates were delivered into mammalian cells. Post transfection, synchronized movement of cells in response to an external magnetic field was observed. This demonstrated the possibility of magnetic manipulation and localization of therapeutic reagents coupled to CoFe2O4 magnetic nanoparticles. Results from this thesis demonstrate the potential role of magnetic spinel nanoparticles in cell biology and will facilitate the progress towards in vivo testing.

The synthesis of precipitated calcium carbonate nanoparticles with the use of double water in oil emulsion has been developed. Restricting the mass of calcium ions present in the system makes it possible to predict particle size precipitated. A model was developed to calculate the concentration required to synthesize a desired particle size. This model took into account a coalescence factor. The coalescence factor is described at the probability of two emulsion droplets, with separate nucleation processes within them, colliding and forming one nucleation process. The Ca2+ ions diffused through the oil membrane into the emulsion droplets with (CaCO3)2- ions by concentration gradients and facilitated transport. The size and shape of precipitated calcium carbonate synthesized was confirmed using scanning electron microscope and light scattering. Particles ranging from 100 nm to 1200 nm have been synthesized using mass restriction. The effect of temperature on the crystalline structure of precipitated calcium carbonate was studied. This was done by x-ray diffraction, where it was found that calcite was the dominating crystalline structure.

This dissertation focuses on utilization of poly(N-isopropylacylamide) (pNIPAm) based mirogels for regulated macromolecule drug delivery applications. There is particular emphasis on incorporation of stimuli responsive materials into multi-layer thin film constructs with the main goal being fabrication of highly functional materials with tunable release characteristics. Chapter 1 gives a broad overview of hydrogel and microgel materials focusing on fundamental properties of pNIPAm derived materials. Chapter 2 illustrates the progression of controlled macromolecule release from hydrogel and microgel materials and sets up the scope of this thesis work. Chapter 3 details studies on thermally modulated insulin release from microgel thin films where extended pulsatile release capabilities are shown. Chapters 4 and 5 focus on more fundamental synthesis and characterization studies of PEG and acrylic acid modified pNIPAm microgels that could ultimately lead to the design of protein loaded microgel films with tunable release characteristics. Chapter 6 illustrates fundamental macromolecule loading strategies, which could also prove useful in future protein drug delivery design using stimuli responsive networks. Chapter 7 concentrates on direct insulin release studies that probe the interaction between entrapped and freely diffusing protein and microgels. These model experiments could prove useful in design of tunable macromolecule drug release from functionally modified microgels and could aid in the tailored design of peptide-loaded microgel thin films. Chapter 8 discusses the future outlook of controlled macromolecule release from microgel based materials.

The objective of this research was to develop efficient, non-invasive separation systems for various biological and non-biological substances. One of the major technological pushes in modern bioanalysis instrumentation development is the realization of efficient, miniaturized bioanalysis systems. In this work, three sizes of micromachined electrical field-flow fractionation (m-ElFFF) systems, with complementary on-column electrical and optical detection modalities were fabricated to achieve this objective. Field-flow fractionation (FFF) technology is capable of fractionating (or separating) a wide variety of materials and is capable of hundreds of consecutive analysis runs using a single system. A highly promising sub-technique, particularly for the analysis of biological / biochemical materials, is electrical field-flow fractionation (ElFFF). In this work, microfabrication technologies were used to fabricate m-ElFFF systems that have smaller system volumes, require smaller sample volumes and have shorter run times than their macro-scale counterparts. Direct, on-column detection within the miniaturized separation device improved the resolution, decreased the band broadening, lowered the plate height, and shortened the overall analysis time. Also, the information obtained from these detection systems can be used to elucidate information on the electrical and physical characteristics of a sample. Therefore, complimentary on-column detection systems, were designed, fabricated and characterized. Additionally, the data from the two detection systems was compared and a quantitative correlation was performed, enabling the independent use of each detection system.