An important goal of nanoscience is the self-assembly of nanoscale building blocks into complex nanostructures. DNA is an important and versatile building block for nanostructures because of its small size, predictable base pairing, and numerous sequence possibilities. I use DNA origami to design and fold DNA into predesigned shapes, to assemble thin, branched DNA nanostructures as templates for nanoscale metal features. Using a PCR-based scaffold strand generation procedure, several wire-like nanostructures with varying scaffold lengths were assembled. In addition, more complex prototype circuit element structures were designed and assembled, demonstrating the utility of this technique in creating complex templates. My fabrication method for DNA-templated nanodevices involves a combination of techniques, including: solution assembly of the DNA templates, surface orientation and placement, and selective nanoparticle attachment to form nanowires with designed gaps for the integration of semiconducting elements to incorporate transistor functionality. To demonstrate selective surface placement of DNA templates, DNA origami structures have been attached between gold nanospheres assembled into surface arrays. The DNA structures attached with high selectivity and density on the surfaces. In a similar base-pairing technique, 5 nm gold nanoparticles were aligned and attached to specific locations along DNA templates and then plated to form continuous metallic wires. The nanoparticles packed closely, through the use of a high density of short nucleotide attachment sequences (8 nucleotides), enabling a median gap size of 4.1 nm between neighboring nanoparticles. Several conditions, including hybridization time, magnesium ion concentration, ratio of nanoparticles to DNA origami, and age of the nanoparticle solution were explored to optimize the nanoparticle attachment process to enable thinner wires. These small, branched nanowires, along with the future addition of semiconducting elements, such as carbon nanotubes, could enable the formation of high-density self-assembled nanoscale electronic circuits.

Philosophiae Doctor - PhD / The field of nanotechnology continues to offer solutions for biotechnologists whose target is to improve the quality of life by finding new therapies to combat diseases. Gold nanoparticles (AuNPs) have been showing great potentials in many biomedical applications. The antibacterial activity of the AuNPs presents a therapeutic option for conditions caused by bacterial infections such as chronic wounds. Also, these versatile particles can offer solutions in the treatments of infectious diseases and can also be exploited as “smart” vehicles to carry drugs, such as antibiotics, for improved efficiency. Moreover, the anti-inflammatory activity of AuNPs makes them useful in the management of prolonged inflammation caused by bacterial infections. The synthesis of AuNPs can be achieved by variety of physical and chemical methods that have been successfully applied in labs and industry. Nonetheless, the drawbacks of these “conventional” methods in terms of high cost, adverse health side effects and incompatibility with the ecosystem cannot be overlooked. Thus, new safer and more cost-effective protocols have been reported for the synthesis of AuNPs. Plants have provided alternate synthesis methods in which the reducing capabilities of the phytochemicals, found in the aqueous plant extracts, can be used to chemically synthesize AuNPs from gold precursors. The biosynthesis and characterization of AuNPs from the phytochemicals of several South African plants is investigated in this study. The study also reports the optimization of the AuNPs biosynthesis by varying reaction conditions such as temperature and plant extracts’ concentrations. Furthermore, the study highlights the wound healing activity of the AuNPs synthesized from selected plants by investigating their antibacterial activity on bacterial strains known to cause chronic wounds. The ability of these AuNPs to carry ampicillin in order to enhance the antibacterial activity is also described herein. The cytotoxicity of the biosynthesized AuNPs was evaluated on human normal fibroblasts cells (KMST-6). Additionally, the immunomodulatory effect of the biosynthesized AuNPs on the cytokines production from macrophages and Natural Killer (NK) cells was examined. The study was successful to produce biocompatible and safe AuNPs synthesized from the tested aqueous plant extracts. The resulted AuNPs showed different physicochemical properties by varying the reaction conditions. The AuNPs exhibited antibacterial activity against several Gram-positive and Gram-negative bacteria. Also, ampicillin was successfully loaded on the biosynthesized AuNPs, which led to the formation of more antibacterial active conjugated AuNPs compared to the free AuNPs. The green synthesized AuNPs were also found to have anti-inflammatory responses as shown by the reduction of pro-inflammatory cytokines from immune cells. In vitro assays showed that the biogenic AuNPs were not toxic to KMST-6 cells. Overall, the data suggest that plant extracts produce biologically safe AuNPs with antibacterial and anti-inflammatory activities that can be exploited in the treatment of chronic wounds and in the management of chronic inflammation.

Thesis (Ph. D.)--University of Oregon, 2006. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 173-182). Also available for download via the World Wide Web; free to University of Oregon users.

In the first part of the study, power conversion efficiency enhancement of organic solar cells by addition of gold nanorods and gold nanostars into PEDOT: PSS (Poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate)) layer was investigated. Efficiency of each sample set has been characterized by measuring current density-voltage characteristics. The best efficiencies obtained during this study are 2.88 % and 2.54 % by addition of gold nanostars and nanorods, respectively. The increase in PCEs is notable when these values are compared with the ones (1.67 %) obtained with a reference device which is prepared without adding any gold nanoparticles under the same conditions. In the second part of the study, branched gold nanoparticles were succesfully grown directly on different types of surfaces such as glass, silicon wafer, and indium-tin-oxide (ITO) coated glass with a simple solution-based method in order to utilize them for further applications.

Metallic nanoparticles (NPs) with various elemental composition, size, shape and physical or chemical properties has become active field of research. Among all the metal NPs noble metal ones are receiving much attention due to their special optical properties which make them useful for different applications. Noble metal NPs have bright colors resulting from strong surface plasmon resonance absorption usually in the visible region. The colors are size and shape dependent and provide the tuning of optical properties. The optical properties of NPs are also strongly depending on the nature of the NPs surface which plays a crucial role on chemical sensing. Therefore, surface modification of NPs has become increasingly important. In this study, gold NPs were prepared in aqueous phase by seed-mediated growth method. To enhance the optical properties, surface functionalization was performed by coating NPs with silver. The coating process was achieved by chemical reduction of silver ions on NPs surface. Thickness of silver layer on the NPs were attempted to be controlled by the amount of silver salt added into NPs solution. Coating process of different types of gold NPs (rod, octahedral, star) was done by the same procedure. Moreover, this attempt yielded control over silver layer thickness on sphere, rod and octahedral shaped gold NPs, but not on branched NPs. The structure, composition and spectroscopic properties of Au-Ag core shell NPs were characterized by UV-Vis spectroscopy, Field Emission Transmission Electron Microscope (FE-TEM) and Energy-dispersive X-ray (EDX) studies, Scanning Electron Microscope (SEM), and X-Ray Photoelectron Spectroscopy (XPS). The analysis showed that all NPs studied were successfully coated with silver and promising for further explorations in sensing and imaging applications.

Alloying is an old trick used to produce new materials by synergistically combining at least two components. New developments in nanoscience have enabled new degrees of freedom, such as size, solubility and concentration of the alloying element to be utilized in the design of the physical properties of alloy nanoparticles (ANPs). ANPs as multi-functional materials have applications in catalysis, biomedical technologies and electronics. Phase diagrams of ANPs are very little known and may not represent that of bulk picture, furthermore, ANPs with different crystallite orientation and compositions could remain far from equilibrium. Here, we studied the synthesis and stability of Au-Sn and Ag-Ni ANPs with chemical reduction method at room temperature. Due to the large difference in the redox potentials of Au and Sn, co-reduction is not a reproducible method. However, two step successive reductions was found to be more reliable to generate Au-Sn ANPs which consists of forming clusters in the first step (either without capping agent or with weakly coordinated surfactant molecules) and then undergoing a second reduction step in the presence of another metal salt. Our observation also showed that capping agents (Cetrimonium bromide or (CTAB)) and Polyacrylic acid (PAA)) play a key role in the alloying process and shorter length capping agent (PAA) may facilitate the diffusion of individual components and thus enabling better alloying. Different molar ratios of Sn and Au precursors were used to study the effect of alloying elements on the melting point and the crystalline structures and melting points were determined by various microscopy and spectroscopy techniques and differential scanning calorimetry (DSC). A significant depression (up to150°C) in the melting transition was observed for the Au-Sn ANPs compared to the bulk eutectic point (T m 280°C) due to the size and shape effect. Au-Sn ANPs offer a unique set of advantages as lead-free solder material which can reflow at lower temperatures leading to lower thermal stresses in adjacent electronic components during the manufacturing process, offering better thermal and mechanical properties suitable for high temperature electronic applications. The second system studied here is Ag-Ni ANPs and electron microscopy and spectroscopy confirm the formation of Ag 0.5 Ni 0.5 ANPs with cubic structure, stable up to125°C. Atomic size and crystalline structure have less effect on the alloy formation process at the nanoscale; therefore, metals with limited solubility in bulk could form solid solutions at the nanoscale. Ag and Ni are immiscible in both solid and liquid states due to the large lattice mismatch and thermodynamically, the formation of core-shell structures is favoured. The effect of capping agents on the alloying was also studied here. Polyvinyl alcohol (PVA) with shorter length shows Ag-Ni ANPs with higher content of Ni compared to sodium citrate; the systems lead to the formation of Ag, Ag 2 O 2 and Ag 0.5 Ni 0.5 ANPs. The study of multi-component nanoparticle systems could shed light into the various parameters that affect stability of structure and phases, which could be quite distinct from their bulk counterparts.

The ability to produce monomolecular coatings with well-defined structural and functional properties is of key importance in biosensing, drug delivery, and many recently developed applications of nanotechnology. Organic chemistry has proven to be a powerful tool to achieve this in many research areas. Herein, we present the synthesis of three oligo(lactosides) glycosylated in a (1 → 3) manner, and which are further functionalized with amide-linked short alkanethiol spacers. The oligosaccharides (di-, tetra-, and hexasaccharide) originate from the inexpensive and readily available lactose disaccharide. These thiolated derivatives were immobilized onto gold surfaces, and the thus formed self-assembled monolayers (SAMs) on planar gold were characterized by wettability, ellipsometry and infrared reflection–absorption spectroscopy. Further, the ability of these SAMs to stabilize gold nanoparticles in saline solutions was also demonstrated, indicating that the oligosaccharides may be used as stabilizing agents in gold nanoparticle-based assays.

There is an increased interest in understanding the toxicity and rational design of gold nanoparticles (GNPs) for biomedical applications in recent years. Such efforts warrant reliable, viable, and biofriendly synthetic methodology for GNPs with homogeneous sizes and shapes, particularly sizes above 30 nm, which is currently challenging. In the present study, an environmentally benign, biofriendly, singlestep/ single-phase synthetic method using dextrose as a reducing and capping agent in a buffered aqueous solution at moderate temperature is introduced. The resulting GNPs are near-spherical, stable, catalytically active, place exchangeable, and water-soluble within the size range of 10-120 nm. The added advantage of the biologically friendly reaction medium employed in this new synthetic approach provides a method for the direct embedment/integration of GNPs into biological systems such as the E. coli bacterium without additional capping ligand or surface modification processes.

En una primera parte de esta tesis fue desarrollado un nuevo electrodo a base de pasta de grafito-epoxi composite (GECE) conteniendo nitrato de bismuto [Bi(NO3)3] como precursor de bismuto incorporado [Bi(NO3)3-GECE)], como una posible alternativa para el análisis electroquímico por redisolución de metales pesados en cantidades traza. Los resultados claramente muestran las ventajas del Bi(NO3)3-GECE en combinación con la técnica de voltamperometría de redisolución anódica de onda cuadrada (SWASV) para la detección de metales pesados. Se llevaron a cabo medidas individuales y simultáneas de Pb y Cd y los resultados mostraron claramente las ventajas del Bi(NO3)3-GECE en combinación con la técnica SWASV para la detección de metales pesados. Con el uso del Bi(NO3)3-GECE construido se pueden realizar análisis rápidos y eficaces de iones de metal en cantidades traza como Pb y Cd entre otros en muestras ambientales de suelo, aguas naturales y aguas residuales. La ventaja inherente de la no necesidad de mercurio elimina muchas de las objeciones para el uso de métodos electroquímicos en la detección de tales especies en estos medios. Comparando el Bi(NO3)3-GECE con el electrodo de película de mercurio comúnmente usado y electrodo de película de bismuto desarrollado antes por nuestro grupo, el nuevo electrodo propuesto ofrece un notable funcionamiento en el análisis de metales pesados en cantidades traza, que puede ser de gran ventaja en electroquímica, contribuyendo a una aplicabilidad más amplia de técnicas electroquímicas por redisolución relacionadas con electrodos "sin mercurio". Además de aplicaciones ambientales el electrodo desarrollado basado en bismuto tendría interés especial para la aplicación en la detección de puntos cuánticos (QDs) basados en metales pesados. Tales aplicaciones están actualmente en proceso de estudio en nuestro grupo de investigación para la detección de ADN.Las otras partes de la tesis se dedican al desarrollo de nuevos sensores de ADN y proteínas basados en la misma técnica electroquímica de redisolución y el uso de nanopartículas de oro como marcas. Actualmente la detección electroquímica de secuencias de ADN específicas vía el evento de hibridación es una cuestión importante por lo cual diversas estrategias han sido propuestas.Genosensores electroquímicos de afinidad basados en el marcaje con nanopartículas de oro (AuNPs) y el uso de partículas paramagnéticas (MB) como plataforma para la inmovilización de la sonda de ADN de captura también han sido desarrollados en esta tesis a fin de demostrar la inducción magnética eficaz de un nuevo electrodo de grafito-epoxi composite-magnético (M-GECE) el cual fue construido también con pasta de grafito-epoxi composite con un pequeño imán de neodimio integrado.Todos los ensayos para la detección electroquímica de la hibridación del ADN desarrollados en esta tesis fueron basados en la detección directa de las marcas de AuNPs por medio de la técnica de voltametría de pulso diferencial (DPV) usando el M-GECE donde la intensidad de la corriente de la señal generada es directamente proporcional a la cantidad de ADN en la muestra. Como también ha sido demostrado, con el sensor de ADN asistido magnéticamente, el ADN analito condujo a una muy bien definida señal mientras que esencialmente ninguna señal fue observada para el ADN no complementario.Un nuevo inmunoensayo electroquímico sensible ha sido desarrollado, también basado en AuNPs como marca y MB como plataforma. El método fue evaluado para un inmunoensayo heterogéneo no competitivo de una IgG humana como proteína modelo. La detección electroquímica fue llevada a cabo en la misma forma que lo fue para ADN.La detección electroquímica de marcas de AuNPs en biosensores de afinidad usando métodos de redisolución permite el estudio detallado de la hibridación de ADN así como también inmuno-reacciones con interés en aplicaciones relacionadas con genosensores o inmunosensores. Los métodos electroquímicos usados para la detección de AuNPs como marca pueden ser muy prometedores tomando en cuenta su sensibilidad alta, límite de detección bajo, selectividad, simplicidad, bajo coste, y disponibilidad de instrumentos portátiles.Como conclusión final, las estrategias de análisis electroquímico de ADN y proteínas fueron demostradas con éxito y debido a los resultados prometedores su uso en muestras reales es viable. Tales biosensores de ADN e inmunosensores dan lugar a un enorme potencial de aplicación principalmente para diagnóstico clínico y monitoreo ambiental entre otros campos. / In the first part of this thesis a new graphite-epoxy composite electrode containing bismuth nitrate [Bi(NO3)3-GECE)], as built-in bismuth precursor as a possible alternative for electrochemical stripping analysis of trace heavy metals has been developed. Individual and simultaneous measurements of Pb and Cd were carried out and the results clearly showed the advantages of the Bi(NO3)3-GECE in combination with square wave anodic stripping voltammetry (SWASV) technique for heavy metals detection. Fast and effective analyses of trace metal ions such as Pb and Cd among others in environmental samples of soil, natural waters and effluents can be carried out by using the new Bi(NO3)3-GECE constructed. The inherent advantage of no necessity of mercury removes many of the objections for the use of the developed sensor. When comparing the Bi(NO3)3-GECE with the commonly used mercury film electrode and previously developed bismuth film electrode, the newly proposed electrode offers a remarkable performance in analysis of trace heavy metals, which can be advantageous in electrochemical, hence contributing to the wider applicability of electrochemical stripping techniques in connection with "mercury-free" electrodes. Beside environmental applications the developed bismuth based electrode would have special interest for application to heavy metal based quantum dots. Such applications are currently in the studying process at our research group for DNA detection.The other parts of the thesis are dedicated to the application of electrochemical stripping analysis in connection to gold nanoparticles for DNA and protein detection. Currently the electrochemical detection of specific DNA sequences via hybridization event is an important issue by which diverse strategies have been proposed. Affinity electrochemical genosensors based on labelling with gold nanoparticles (AuNPs) and the use of paramagnetic beads (MB) as platform for the immobilization of capture DNA probe have been also developed in this thesis in order to demonstrate the effective magnetic triggering of a new magnetic-graphite epoxy composite electrode (M-GECE) which was constructed with graphite-epoxy composite paste, with a small neodymium magnet integrated.All the assays for the DNA hybridization electrochemical detection developed in this thesis were based on the direct detection of AuNPs labels (anchored onto the M-GECE) by means of differential pulse voltammetry (DPV). The intensity of the generated current is directly proportional to the amount of DNA at the sample. As also has been demonstrated, with this magnetically assisted DNA sensor, target DNA leaded to very well defined signal whereas essentially no signal was observed for non-complementary DNA. By the other side a novel, sensitive electrochemical immunoassay has been also developed based in AuNPs as label and MB as platform. The method was studied and evaluated for a noncompetitive heterogeneous immunoassay of a human IgG as a model protein. The electrochemical detection was carried out in the same way that as for DNA.The electrochemical detection of AuNPs labels in affinity biosensors using stripping methods allows the detailed study of DNA hybridization as well as immunoreactions with interest in genosensor or immunosensor applications. The developed detection methodologies may be very promising taking into account their high sensitivity, low detection limit, selectivity, simplicity, low cost, and availability of portable instruments.As final conclusion, the DNA and protein electrochemical analysis strategies were successfully demonstrated and according to the promising results obtained its use for real samples is viable. Such DNA biosensors and immunosensors hold an enormous application potential principally for clinical diagnostic and environmental monitoring among other fields.

This study presents studies on camptothecin (CPT), a potent antitumor agent in order to improve its stability and solubility without reducing its activity. The work describes the modification of camptothecin at 20-OH position a new strategy to overcome the stability and solubility problems of the free drug. Camptothecin is conneted to linker that could be processed to a terminal thiol group and this thiol group was connected to gold surface, to obtain CPT-gold nanoparticles. In the first part of the study / undecenol was chosen as the starting material and reacted with azobisisobutylonitrile to obtain S-11-hydroxyundecyl ethanethioate. 11-hydroxyundecyl ethanethioate was reacted with NaOMe to synthesize the target linker 11, 11&rsquo / -disulfanediyldiundecan. After synthesis of the target linker, the 20- OH functional group of CPT was replaced with this linker to obtain 20- (11, 11&rsquo / -disulfanediyldiundecan) - captothecin. The second part of the study, gold nanoparticles were synthesized by using HAuCl4 solution and the camptothecin derivative containing thiol group at 20-OH position was connected to the gold surface.