It was hypothesized that superparamagnetic nanoparticles encapsulated in a silica shell with a fluorescent dye could be functionalized with axonal tracers and could be used for serial, non-invasive imaging with magnetic resonance imaging (MRI) for axon tract tracing. Nanoparticles functionalized with amine, octadecyl, silica, and biotinylated dextran amine were manufactured and characterized with MRI, scanning electron microscopy, and UV-visible, infrared, and fluorescence spectroscopy. Nanoparticle concentrations of 10 mM were not toxic to adult rat neural progenitor cells (NPCs) and labeled approximately 90% of cells. Nanoparticles were assessed for anterograde and retrograde tract tracing in adult rat models. With MRI and microscopy, the nanoparticles did not appear to trace axons but did provide an MRI signal for up to 3 weeks post implantation. While functionalized nanoparticles did not appear to trace axons, they are not toxic to NPCs and may be used as a MRI contrast agent in the neural axis.

<p>The study and application of materials possessing size dimensions in the nano scale range and, as a result, unique properties have led to the birth of a new field; nanotechnology. Scientists and engineers have discovered and are exploiting the novel physicochemical characteristics of nanoparticles (NPs) to enhance consumer products and technologies in ways superior to their bulk counterparts. Escalating production and use of NPs will unavoidably lead to release and exposure to environmental systems. This introduction of emerging potential contaminant NPs will provide new and interesting challenges for exposure and risk forecasting as well as environmental endurance.</p><p>The ultimate goal of this research is to develop a framework that incorporates experimental and computational efforts to assess and better understand the exposure of metal and metal-oxide NPs released to wastewater treatment plants (WWTPs) and further implications on land application units (LAUs) where biosolids can be applied. The foundation of the computational effort is comprised of Monte Carlo mass balance models that account for the unique processes affecting NP fate and transport through the different technical compartments of a WWTP and LAU. Functional assay and bioreactor experiments in environmental media were used to determine parameters capable of describing the critical processes that impact the fate of NPs in wastewater. </p><p>The results of this research indicate that a simplified, but still environmentally relevant nano-specific exposure assessment is possible through experimentation to parameterize adapted models. Black box modeling efforts, which have been shown in previous studies, show no disadvantage relative to discretization of technical compartments as long as all key transport and fate mechanisms are considered. The distribution coefficient (_), an experimentally determined, time-dependent parameter, can be used to predict the distribution of NPs between the liquid and solid phase in WWTPs. In addition, this parameter can be utilized a step further for the estimation of the more fundamental, time independent attachment efficiency between the NPs and the solids in wastewater. The NP core, size, and surface coating will influence the value of these parameters in addition to the background particle characteristics as the parameters are specific to the environmental system of study. For the metal and metal-oxide NPs studied, preferential overall association of approximately 90% or greater with the solid phase of wastewater was observed and predicted. </p><p>Furthermore, NP transformations including dissolution, redox reactions, and adsorption can potentially impact exposure. For example, experimental results showed that nano-CeO2 is reduced from Ce(IV) to Ce(III) when in contact with wastewater bacteria where Ce2S3 will likely govern the Ce(III) phase in biosolids. From the literature, similar transformations have been observed with Ag and ZnO NPs to Ag2S and ZnS. With respect to TiO2 NPs, studies indicated that due to high insolubility, these NPs would not undergo transformation in WWTPs. The distribution and transformation rate coefficients can then be used in fate models to predict the NP species exposed to aquatic and terrestrial systems and environmentally relevant concentrations released from WWTPs. </p><p>Upon completion of the WWTP model, the predicted concentrations of NPs and NP transformation byproducts released in effluent and biosolids were attainable. A simple mass balance model for NP fate in LAUs was then developed to use this output. Results indicate that NP loading on LAUs would be very low but that build up over time to steady state could result in mass concentrations on the order of the typical level for the background metal in soil. Transport processes of plant uptake and leaching were expected to greatly impact the solid phase concentration of the NPs remaining in the LAU, while rainfall did not impart a significant influence upon variation between low and high annual amounts. The significance of this research is the introduction of a method for NP exposure assessment in WWTPs and subsequently in LAUs. This work describes and quantifies the key processes that will impact Ag, TiO2, CeO2 and ZnO NP fate and transport, which can inform future studies, the modeling community and regulatory agencies.</p> / Dissertation

Nanoscale protein arrays have shown promise for biological and biomedical applications. Compared to traditional protein arrays, nanoarrays have the potential for higher throughput, better sensitivity, and require less sample volumes. In this thesis, protein nanoarrays were fabricated using a simple and inexpensive "natural lithography" approach. This method allows the fabrication of large-area ordered nanoparticle arrays consisting of metallic dots with tunable diameters down to 10 nm or less. The nanoparticle arrays are formed by depositing metal through the openings of colloidal monolayer polystyrene sphere masks. After removing the masks, nanoarrays remain and are exposed to further processing. COOH-terminated self-assembled monolayers (SAM) and N-hydroxysuccinimide (NHS) chemistry is used for surface functionalization. These surface modifications covalently attach proteins onto the nanoparticles. A single monolayer of immunoglobulin G (IgG) molecules is successfully attached on the functionalized surfaces and the bioactivity of the protein arrays is tested by attaching anti-IgG molecules, as a standard immunological assay. Results of fabrication trials and efforts to control nanoparticle size, spacing, and surface adhesion are described. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) images of hexagonal gold nanoarrays consisting of approximately 150 nm particles and 3.5x108-1.5x109 per cm2 array density is shown, depending on the size of colloidal spheres. An increased height of approximately 6 nm characterized via scanning probe methods shows the attachment of a single monolayer of protein molecules to the nanoparticles. This was confirmed with SEM. A similar height increase was detected via AFM showing the attachment of anti-IgG molecules onto IgG functionalized particles. Potential applications of the protein nanoarrays and future work are discussed.

There has been an increasing focus on using nanoscale devices for various applications ranging from computer components to biomechanical sensors. In order to effectively design devices of this size, it is important to understand the properties of materials at this length scale and their relevant transport equations. At everyday length scales, heat transport is governed by Fourier’s law, but at the nanoscale, it becomes increasingly inaccurate. Phonon kinetic theory can be used to develop more accurate governing equations. We present the moment method, which takes integral moments of the phonon Boltzmann kinetic equation to develop a set of equations based on macroscopic properties such as energy and heat flux. The advantage of using this method is that transport properties in nanodevices can be approximated analytically and efficiently. A number of simplifying assumptions are used in order to linearize the equations. Boundary conditions for the moment method are derived based on a microscopic model of phonons interacting with a surface by scattering, reflection or thermalization. Several simple, one dimensional problems are solved using the moment method equation. The results show the effects of phonon surface interactions and how they affect overal properties of a nanoscale device. Some of these effects were observed in a recent experiment and are replicated by other modeling techniques. Although the moment method has described some effects of nanoscale heat transfer, the model is limited by some of its simplifying assumptions. Several of these simplifying assumptions could be removed for greater accuracy, but it would introduce non-linearity into the moment method. / Graduate

<p> Supercapacitors have occupy an indispensable role in today's energy storage systems due to their high power density and long life. The introduction of car- bon nanotube (CNT) forests as electrode offers the possibility of nano-scale design and high capacitance. We have performed molecular dynamics simulations on a CNT forest-based electrochemical double-layer capacitor (EDLC) and a widely used electrolyte solution (tetra-ethylammonium tetra-fluoroborate in propylene carbonate, TEABF₄ /PC) </p><p> We compare corresponding primitive model and atomically detailed model of TEABF₄ /P, emphasizing the significance of ion clustering in electrolytes. The molecular dynamic simulation results suggests that the arrangement of closest neigh- bors leads to the formation of cation-anion chains or rings. Fuoss's discussion of ion-pairing model provides the approximation for a primitive model of 1-1 electrolyte is not broadly satisfactory for both primitive and atomically detailed cases. A more general Poisson statistical assumption is shown to be satisfactory when coordina- tion numbers are low, as is likely to be the case when ion-pairing initiates. We examined the Poisson-based model over a range of concentrations for both models of TEABF₄ /P, and the atomically detailed model results identified solvent-separated nearest-neighbor ion-pairs. </p><p> Large surface areas plays an essential role in nanomaterial properties, which calls for an accurate description of interfaces through modeling. We studied propylene carbonate, a widely used solvent in EDLC systems. PC wets graphite with a contact angle of 31&deg;. The MD simulation model reproduced this contact angle after reduction 40% of the strength of graphite-C atom Lennard-Jones interactions with the solvent. The critical temperature of PC was accurately evaluated by extrapolating the PC liquid-vapor surface tensions. PC molecules tend to lie flat on the PC liquid-vapor surface, and project the propyl carbon toward the vapor phase. Liquid PC simulations also provide basic data for construction of accurate information to assist in device- level modeling of EDLCs. </p><p> The most serious uncertainty with previous simulations of CNT based EDLCs was definition of the actual composition of the pores. Therefore, direct simulations of filling of CNT forest based electrochemical double-layer capacitors with TEABF₄ /P solution was performed. Those calculation characterize the charging and discharg- ing process, including rates of charging responses, the possibility of bubble forma- tion, and kinetic properties with confinement. The mobilities of ions and solvent was investigated through mean square displacement (MSD) and velocity autocorrela- tion functions (VACF). The memory kernel was extracted from VACF by discretized linear-equation solving and a specialized Fourier transform method, results implies the existence of dielectric friction. </p><p> With the interest in chemical features of EDLCs, a multi-scale theory was de- veloped to embed high resolution ab <i>initio</i> molecular dynamics (AIMD) methods into studies of EDLCs. This theory was based on McMillan-Mayer theory, potential dis- tribution approach, and quasi-chemical theory. The quasi-chemical theory allow us to break-up the free energies into <i> packing, outer-shell</i> and <i>chemical</i> contributions, where the last part can be done by AIMD directly. For the primitive model of TEABF₄ /P, Gaussian statistical models are effective for these <i> outer-shell</i> contributions. And the Gaussian approximation is more efficient than the Bennett method in achieving an accurate mean activity coefficient. </p>

<p> There has been much interest in colloidal noble metal nanoparticles due to their fascinating plasmonic and catalytic properties. These properties make noble metal nanoparticles potentially useful for applications such as targeted drug delivery agents and hydrogen storage devices. Historically, shape-controlled noble metal nanoparticles have been predominantly monometallic. Recent synthetic advances provide access to bimetallic noble metal nanoparticles wherein their inherent multifunctionality and ability to fine tune or expand their surface chemistry and light scattering properties of metal nanoparticles make them popular candidates for many applications. Even so, there are currently few synthetic strategies to rationally design shape-controlled bimetallic nanocrystals; for this reason, few architectures are accessible. For example, the "seed-mediated method" is a popular means of achieving monodisperse shape-controlled bimetallic nanocrystals. In this process, small metal seeds are used as platforms for additional metal addition, allowing for conformal core@shell nanostructures. However, this method has only been applied to single metal core/single metal shell structures; therefore, the surface compositions and architectures achievable are limited. This thesis expands upon the seed-mediated method by coupling it with co-reduction. In short, two metal precursors are simultaneously reduced to deposit metal onto pre-formed seeds in hopes that the interplay between two metal species facilitates bimetallic shell nanocrystals. Au/Pd was used as a test system due to favorable reduction potentials of metal precursors and good lattice match between Au and Pd. Alloyed shelled Au@Au/Pd nanocrystals were achieved using this "seed-mediated co-reduction" approach. Symmetric eight-branched Au/Pd nanocrystals (octopods) are also prepared using this method. This thesis investigates many synthetic parameters that determine the shape outcome in Au/Pd nanocrystals during seed-mediated co-reduction. Plasmonic, catalytic, and assembly properties are also investigated in relation to nanocrystal shape and architecture. This work provides a foundation for the rational design of architecturally defined bimetallic nanostructures. </p>

This thesis presents the development and optimization of a high-throughput fluorescence microbead based approach for multiplexed, large scale medical diagnostics of biological fluids. Specifically, different sizes of semiconductor nanocrystals, called quantum dots, are infused into polystyrene microspheres, yielding a set of spectrally unique optical barcodes. The surface of these barcodes are then used for sandwich assays with target molecules and fluorophore-conjugated detection antibodies, changing the optical spectra of beads that have associated with (or captured) biomolecular targets. These assayed microbeads are analyzed at a single bead level in a high-throughput manner using an electrokinetic microfluidic system and laser induced fluorescence. Optical signals collected by solid state photodetectors are then processed using novel signal processing algorithms. This document will discuss developments made in each area of the platform as well as optimization of the platform for improved future performance.

The objectives of this thesis were to optimize the synthesis and surface coating of metallic and semiconductor nanoparticles, to understand how these materials interact with cells and physiological systems and to investigate how they can be used to deliver thermal therapy for medical applications. Reproducible high-yield synthesis of gold nanorods and surface coating with a variety of polymers and silica was optimized. Using gold nanorods as a model system, the relationship between particle surface chemistry, surface charge and cellular uptake was studied, as well as the toxicity of nanoparticles of different surface chemistry. Low toxicity in vitro was encouraging and was confirmed in vivo by intravenously injecting Sprague-Dawley rats with semiconductor quantum dots of various surface coatings. Low toxicity was found during biochemical, haematological and pathological assessment, and these results indicate that applications of nanoparticles should be further investigated. One such application is the use of near infrared absorbing gold nanorods in remotely activated hyperthermia. It was shown that gold nanorods act synergistically with the chemotherapeutic cisplatin to improve cytotoxicity, and reduce the required cytotoxic drug dose to 33% of the unheated amount. Due to the success of hyperthermia treatment in vitro, continuing and future work involves the use of gold nanorods ex vivo on excised human corneas in a novel application to weld corneal tissue for improved wound closure following cataract surgery.

The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non-transport permissive and intact BBB, we also assessed the role of magnetic resonance imaging (MRI) guided focused ultrasound (MRgFUS) disruption of the BBB in enhancing permeation of AuNPs across the intact BBB and tumor BBB in vivo. MRgFUS is a novel technique that can transiently increase BBB permeability thereby allowing delivery of therapeutics into the CNS. We demonstrated enhanced delivery of AuNPs with therapeutic potential into the CNS via MRgFUS. Our study was the first to establish a definitive role for MRgFUS in delivering AuNPs into the CNS. In summary, this thesis describes results from a series of research projects that have contributed to our understanding of the influence of design features on AuNP permeation through the BBB and also the potential role of MRgFUS in AuNP permeation across the BBB.

Studies various nanostructured materials have gained considerable interest within the past several decades. This novel class of materials has opened up a new realm of possibilities, both for the fundamental comprehension of matter, but also for innovative applications. The size-dependent effect observed for these systems often lies in their interaction with the surrounding environment and understanding such interactions is the pivotal point for the investigations undertaken in this thesis. Three families of nanoparticles are analyzed: semiconductor quantum dots, metallic silver nanoparticles and rare-earth oxide nanomaterials. The radical scavenging ability of cerium oxide nanoparticles (CeO2) is quite controversial since they have been labeled as both oxidizing and antioxidant species for biological systems. Here, both aqueous and organic stabilized nanoparticles are examined in straightforward systems containing only one reactive oxygen species to ensure a controlled release. The apparent absence of their direct radical scavenging ability is demonstrated despite the ease at which CeO2 nanoparticles generate stable surface Ce3+ clusters, which is used to explain the redox activity of these nanomaterials. On the contrary, CeO2 nanoparticles are shown to have an indirect scavenging effect in Fenton reactions by annihilating the reactivity of Fe2+ salts. Cadmium selenide quantum dots (CdSe QD) constitute another highly appealing family of nanocolloids in part due to their tunable, size-dependent luminescence across the visible spectrum. The effect of elemental sulfur treatment is investigated to overcome one of the main drawbacks of CdSe QD: low fluorescence quantum yield. Herein, we report a constant and reproducible quantum yield of 15%. The effect of sulfur surface treatment is also assessed following the growth of a silica shell, as well as the response towards a solution quencher (4-amino-TEMPO). The sulfur treated QD is also tested for interaction with pyronin Y, a xanthene dye that offers potential energy and electron transfer applications with the QD. Interaction with the dye molecule is compared to results obtained with untreated quantum dots, as well as CdSe/ZnS core shell examples. In another chapter of this thesis, the catalytic potential of silver nanoparticles is addressed for the grafting of polyhydrosiloxane polymer chains with various alkoxy groups. A simple one-pot synthesis is presented with silver salts and the polymer. the latter serves as a mild reducing agent and a stabilizing ligand, once silver nanoparticles are formed in-situ. We evaluate the conversion of silane into silyl ethers groups with the addition of several alcohols, whether primary, secondary or tertiary, and report the yields of grafting under the mildest conditions: room temperature, under air and atmospheric pressure.