Modeling molecular structures is critical for understanding the principles that govern the behavior of molecules and for facilitating the exploration of potential pharmaceutical drugs and nanoscale designs. Biological molecules are flexible bodies that can adopt many different shapes (or conformations) until they reach a stable molecular state that is usually described by the minimum internal energy. A major challenge in modeling flexible molecules is the exponential explosion in computational complexity as the molecular size increases and many degrees of freedom are considered to represent the molecules’ flexibility. This research work proposes a novel generic computational geometric approach called enhanced BioGeoFilter (g.eBGF) that geometrically interprets inter-atomic interactions to impose geometric constraints during molecular conformational search to reduce the time for identifying chemically-feasible conformations. Two new methods called Kinematics-Based Differential Evolution ( kDE) and Biological Differential Evolution ( BioDE) are also introduced to direct the molecular conformational search towards low energy (stable) conformations. The proposed kDE method kinematically describes a molecule’s deformation mechanism while it uses differential evolution to minimize the intra-molecular energy. On the other hand, the proposed BioDE utilizes our developed g.eBGF data structure as a surrogate approximation model to reduce the number of exact evaluations and to speed the molecular conformational search. This research work will be extremely useful in enabling the modeling of flexible molecules and in facilitating the exploration of nanoscale designs through the virtual assembly of molecules. Our research work can also be used in areas such as molecular docking, protein folding, and nanoscale computer-aided design where rapid collision detection scheme for highly deformable objects is essential.

The use of beta-sheets as building blocks for biomaterials is already firmly established. In particular, self-assembled beta-sheet peptides are promising for engineering new fibrous nanostructures and hydrogels. Peptide-synthetic polymer hybrids are especially attractive since they combine the advantages of biomolecular recognition and functional properties of peptides with the low cost and easy fabrication of polymers. Significant developments in the area have included beta-sheet fibrillar networks, and self-assembled hybrid hydrogels, which add further control and utility to these systems. The studies described in this dissertation dealt with the design and evaluation of novel nanofibrous and hydrogel materials based on poly(HPMA)-beta-sheet copolymers and their application as scaffolds for bone tissue engineering. In the first part of this research, the effect of conjugating poly(HPMA) to a beta-sheet peptide via thiol-maleimide chemistry was estimated. The ability of the peptide to adopt a beta-sheet conformation could be imposed in the hybrid at basic pH, through electrostatic interactions between the oppositely charged amino acid residues in the sequence. Hierarchically organized structures, such as micrometer long fibrils, were obtained. In the second part, formation of fibril-like nanostructures was demonstrated for beta-sheet peptides conjugated as grafts to poly(HPMA). The polymer had a shielding effect, decreasing the peptide grafts sensitivity to temperature and pH variations. The tendency of beta-sheets to form hydrogels was preserved in the copolymer depending on the concentration, graft density, and incubation time. Finally, the last part of this research attempted to explore the ability of a hybrid hydrogel self-assembled from copolymers of poly(HPMA) and complementary beta-sheet grafts to act as scaffolds for bone tissue engineering. The hydrogel displayed anisotropic porosity, thus, it provided surfaces characterized by epitaxy that favored template-driven mineralization of hydroxyapatite, and support for preosteoblast cells. Although attachment did not occur, long-term viability of cells and proliferation indicated that the hybrid hydrogel is not cytotoxic, therefore, once optimized, could be used as a bone scaffold. In summary, we have presented novel beta-sheet-based hybrid nanostructures and hydrogels that could be applied successfully in regenerative medicine. Such an approach may lead to the development of new materials for drug delivery, wound healing or other tissue engineering applications.

Tip Enhanced Near-field Optical Microscopy (TENOM) is a method for optically imaging at resolutions far below the diffraction limit. This technique requires optical nano-probes with very specialized geometries, in order to obtain large, localized enhancements of the electromagnetic field, which is the driver behind this imaging method. Traditional methods for the fabrication of these nano-probes involve electrochemical etching and subsequent FIB milling. However, this milling process is non-trivial, requiring multiple cuts on each probe. This requires multiple rotations of the probe within the FIB system, which may not be possible in all systems, meaning the sample must be removed from vacuum, rotated by hand and placed back under vacuum. This is time consuming and costly and presents a problem with reproducibility. The method presented here is to replace multiple cuts from a side profile with a small number of cuts from a top down profile. This method uses the inherent imaging characteristics of the FIB, by assigning beam dwell times to specific locations on the sample, through the use of bitmap images. These bitmaps are placed over the sample while imaging and provide a lookup table for the beam while milling. These images are grayscale with the color of each pixel representing the dwell time at that pixel. This technique, combined with grayscale gradients, can provide probes with a symmetric geometry, making the system polarization independent.

This thesis focuses on the development and application of gold nanoparticle based detection systems and biomimetic structures. Each class of modified nanoparticle has properties that are defined by its chemical moieties that interface with solution and the gold nanoparticle core. In Chapter 2, a comparison of the biomolecular composition and binding properties of various preparations of antibody oligonucleotide gold nanoparticle conjugates is presented. These constructs differed significantly in terms of their structure and binding properties. Chapter 3 reports the use of electroless gold deposition as a light scattering signal enhancer in a multiplexed, microarray-based scanometric immunoassay using the gold nanoparticle probes evaluated in Chapter 2. The use of gold development results in greater signal enhancement than the typical silver development, and multiple rounds of metal development were found to increase the resulting signal compared to one development. Chapter 4 describes an amplified scanometric detection method for human telomerase activity. Gold nanoparticles functionalized with specific oligonucleotide sequences can efficiently capture telomerase enzymes and subsequently be elongated. Both the elongated and unmodified oligonucleotide sequences are simultaneously measured. At low telomerase concentrations, elongated strands cannot be detected, but the unmodified sequences, which come from the same probe particles, can be detected because their concentration is higher, providing a novel form of amplification. Chapter 5 reports the development of a novel colorimetric nitrite and nitrate ion assay based upon gold nanoparticle probes functionalized with Griess reaction reagents. This assay takes advantage of the distance-dependent plasmonic properties of the gold nanoparticles and the ability of nitrite ion to facilitate the cross coupling of novel nanoparticle probes. The assay works on the concept of a kinetic end point and can be triggered at the EPA limit for this ion in drinking water. Finally, Chapter 6 describes the synthesis of high density lipoprotein biomimetic nanoparticles capable of binding cholesterol. These structures use a gold nanoparticle core to template the assembly of a mixed phospholipid layer and the adsorption of apolipoprotein A-I. These synthesized structures have the general size and surface composition of natural HDL and bind free cholesterol with a Kd of 4 nM.

Measuring the heat released when gas phase species adsorb onto surfaces provides essential information about the energies of surface species and the reactions they undergo. Here, heats of adsorption of technologically-interesting surface species were measured using a unique microcalorimetric technique in ultrahigh vacuum. Specifically, systems were studied which are relevant to understanding and improving transition metal catalysts and organic electronics. Metal adsorption energies were measured which elucidate metal-to-oxide and metal-to-polymer interfacial binding, and molecule adsorption energies were measured to understand how catalyst structure influences the energies of adsorbed reaction intermediates. Oxide-supported metal nanoparticles form the basis for many industrial catalysts. Nanoparticle activity, selectivity and resistance to sintering can depend strongly on particle size, oxide support, and defects on the oxide. To investigate the dependence of catalytic properties on oxide surface defects, defects were introduced on MgO100) and CeO2111), and their affect on the adsorption energy of metal atoms and the energy of supported nanoparticles was measured. These measurements help to explain why transition metal catalysts sinter more slowly and maintain smaller particles when supported on CeO 2 compared to other oxides, and how surface defects influence nanoparticle formation and film growth on oxides. The effect of nanoparticle size on the adsorption energy of CO on different-sized Pd nanoparticles on Fe3O 4111) was measured, providing the first direct evidence that the heat of adsorption of CO decreases with decreasing Pd nanoparticle size. Knowledge of the direction and magnitude of particle size effects is necessary for improving existing catalysts and designing new ones. The metal/polymer interface is important because it impacts charge injection, extraction, and transport in organic electronics. Large-scale energy production using polymer photovoltaics is currently unfeasible due in part to their low efficiency and short lifetimes. Polymer degradation at the interface with the metal electrode is believed to impact device efficiency and lifetime. Calcium adsorption on poly3-hexylthiophene) was investigated because it is one of the most efficient electrode/polymer combinations. The results were striking: calcium diffused nanometers into the polymer and reacted with the polymer backbone. A method to suppress diffusion was demonstrated, which may lead to improved devices.

Self-assembled monolayers SAMs) of alkanethiolates on Au111) represent promising platforms to study the molecular surfaces and interfaces for applications ranging from molecular electronics, nanophotonics to biology. Understanding the effect of growth conditions on SAMs particularly on their structural features is important from both fundamental and applied points of view. Knowledge of SAM structural features and structural phase transitions provides important insights into molecular packing for the control of the molecular self-assembly. We compared SAMs grown from different media, from 1 mM C10 solution in decalin, hexadecane and triethylene glycol and from C10 vapor. We present a molecularly-resolved scanning tunneling microscopy study showing the dependence of the SAM structure on the growth conditions. We have established conditions for making samples almost vacancy islands VI) free with very large SAM domains of 2 3 x 3)rect. superstructure and 3 x 4 3)R30&deg； striped-phase and investigated the orientation of low-index step edges of Au111) for normal and striped-phase SAMs. We showed that the striped phase is stable to converting to 2 3 x 3)rect. below 40&deg；C. We demonstrate that flat gold nanoparticles FGNPs) supported on indium tin oxide glass ITO) are excellent substrates for molecularly-resolved STM imaging of alkanethiol SAMs. Nanoparticles were characterized using STM, TEM, and SEM techniques. Surface treatment techniques, Ar/O2 and H 2 plasma treatments, dry thermal annealing and exposures to UV/O 3, were used to prepare the surfaces of FGNPs supported on ITO and Au/mica substrates for high-resolution STM imaging of alkanethiol SAMs. We developed a convergent approach to functionalize SAM surfaces. Ordered mixed monolayers comprised of alkanethiols and azidoalkanethiols islands are formed and subsequent IMesCuIBr catalyzed [3＋2] “click” cycloaddition reaction with substituted alkyne introduced dilute substituent onto the ordered surface. Mechanical stress is one of the major factors in current design and manufacture of very large scale integrated VLSI) devices. Mechanical stress in deep sub-micron silicon technologies can drastically alter carrier mobility e.g., approximately 25% dependent on device geometry). This affects the device performance. Current in-line production stress metrology is conducted only at a wafer monitor level. The available stress measurement techniques such as micro-Raman spectroscopy, nano beam diffraction NBD), converging electron beam diffraction CEBD) either do not have required resolution or they require complex data interpretation. We present a method for measuring mechanical stress in deep submicron silicon devices with high spatial resolution using scanning Kelvin probe force microscopy and scanning surface photovoltage SSPVM) techniques.

Through polarization-dependent magneto-optical absorption spectroscopy, the magnetic susceptibility anisotropy for metallic single-walled carbon nanotubes has been extracted and found to be up to 4x greater than values for semiconducting single- walled carbon nanotubes. Consistent with theoretical predictions, this is the first experimental evidence of the paramagnetic nature arising from the Aharonov-Bohm-phase-induced gap opening in metallic nanotubes. We also compare our values with previous work for semiconducting nanotubes, which confirm a break from the prediction that the magnetic susceptibility anisotropy increases linearly with the diameter.

Magnetic nanoparticles have recently attracted much attention for potential biomedical applications such as targeted drug delivery, magnetic resonance imaging contrast agents and hyperthermia treatment of cancerous cells. Future research on biomedical applications also includes use of magnetic nanoparticles for cell and DNA separation. By functionalizing magnetic nanoparticles with cells or DNA selective biomolecules, the particles attach to the target and are removed from the sample upon passing through magnetic field gradients. The field gradients apply a force that attracts the particles given by the equation F ＝ &nabla；m &middot； B), where m is the magnetization of the MNP, and B is the applied magnetic field. This type of magnetic manipulation is potential for in vivo applications such as targeted drug delivery, magnetic resonance imaging contrast enhancement and hyperthermia treatment of cancer. The magnitude of the field gradients of magnetic nanoparticles are significantly reduced due to the inverse square law dependence of magnetic field strength and subsequently the forces set up are reduced. Although the research in this field has focused primarily on iron oxide nanoparticles, these oxide nanoparticles have a low magnetization that renders them ineffective, at the distances required for in vivo applications, due to the reduced forces felt by the nanoparticles. Successful implementation of such magnetic nanoparticles based system in vivo may require higher magnetization. The aim of this proposal is to synthesize high magnetization Fe-based MNPs functionalized with artificial proteins. The research described in this dissertation focuses on synthesis, size control, structural and magnetic characterization and associated experimental studies to characterize their properties for application in magnetic fluid hyperthermia and magnetic resonance imaging applications. The method used for the synthesis of the Fe-based nanoparticles is the conventional borohydride reduction of the metal salt solution. Since our intention is to synthesize iron based nanoparticles we used iron salts such as FeCl3. A polymer such as polyethylene glycol is coated onto the oxide shell to make it biocompatible. Parameters such as length of the tube, diameter of the Y-tube junction and concentration of the reactants were varied to study the effect on particle size, structure and morphology of the magnetic nanoparticles. X-ray diffraction measurements revealed that the particles typically contain three iron based phases such as a crystalline alpha-Fe), nanocrystalline/amorphous a-FeB/n-Fe) and Fe-oxide. By controlling the synthesis parameters such as length of the reaction tube, inner diameter of the Y-tube and concentration of the reagents the volume percentage of the three phases of the nanoparticles, viz. crystalline phase, amorphous phase and Fe-Oxide phases can be controlled effectively. The Fe-Oxide phase could not be determined whether is magnetite and maghemite phase because of the very broad nature of the peak. Transmission electron microscopy was used to study the particle size and the microstructural property of the samples. Samples with particle size in the range of 3 nm to 30 nm were fabricated. The magnetic properties of the nanoparticles studied were measured with a vibrating sample magnetometer with a maximum field of 1 Tesla. The particles magnetic properties such as magnetization and coercivity were typical of a soft ferromagnetic material with a high magnetization in emu/g) and the coercivity was in range of 50 to 450 Oe. The nanoparticles synthesized were used to study their performance in magnetic fluid hyperthermia and magnetic resonance imaging applications. In the hyperthermia, the power loss due to an alternating magnetic field had a direct correlation with the magnetization and the particle size of the nanoparticle. The power loss in magnetic fluid hyperthermia is an outcome from four loss mechanism, they are Brownian rotational loss, Neels relaxational loss, hysteresis loss and eddy current loss. The Brownian rotation loss is the major contributor in monodispersed particle size while Neels relaxational loss exist only in particle below 5 nm. The hysteresis loss is very small in superparamagnetic nanoparticles and increases with the particle size and predominantly exist in particles of all sizes； the eddy current loss in sub-nanometer particle very negligible when compared to the other major loss mechanism. In magnetic resonance imaging contrast enhancement by estimating the spinlattice relaxation time T1), spin-spin relaxation time T 2) and spin-spin relaxation due to field inhomogeneity T*2) the enhancement can be related to the particle size and magnetization. The contrast enhancement of the magnetic nanoparticle suspension in water, was responsible for shortening of the relaxation time of the proton in water. The contrast enhancement depends on the magnetization and the particle size of the magnetic nanoparticles.

The controlled etching of micro/nano structures is essential for a variety of technological applications, including microelectromechanical systems (MEMS) fabrication. XeF2 is an isotropic and highly selective etching gas used to remove semiconductors and metals in the fabrication of MEMS and other devices. While the kinetics of XeF2 etching Si has been widely documented, XeF2 etching of metals is not widely understood. For better process control and device quality, it is important to understand the etching mechanism at the molecular level. In this work, we explore the surface and gas phase chemistry of XeF2 etching Mo films. Studies on the general characteristics of etching Mo blanket films were carried out on 1000AMo/475ASiO2/100ANi/glass samples at different sample temperatures and etchant pressures in a standalone etching chamber. They were analyzed ex-situ by atomic force microscopy (AFM) and x-ray photoelectron spectroscopy (XPS) for investigating morphology and chemical composition of the surfaces after etchings, respectively. Rutherford back scattering (RBS) was used to measure the thickness of the films and the depth profile of near-surface species after etching. Downstream mass spectrometry was used to identify the volatile products of the etching process. The composition and chemical state of the etched surface (reaction layer) is further investigated by in-vacuo etching and XPS analysis experiments using 3750AMo/quartz samples in an integrated etching/analysis system. The XPS studies have clarified issues on: (i) the thickness and chemical composition of the reaction layer during etching, (ii) the effects of the surface native oxides and adventitious hydrocarbons on the initiation and progress of etching, (iii) the re-deposition of etched products. Post-etching thermal processing and XPS analysis studies were performed to investigate the chemical composition of residues left after etching. Kinetics of etching blanket Mo films was investigated using total pressure change and a quartz crystal micro balance (QCM). The rates of etching blanket films were determined to be 60-75 nm/sec at 25-90&deg；C. The rate of undercut etching, measured on patterned samples, changes significantly (0.5-2.5 mu/min) under different conditions, depending on the etching method, temperature, and pattern size. Different gas delivery methods were tested and their efficiency is discussed.

Among recent proposals for next-generation, non-charge-based logic is the notion that a single electron can be trapped and spin of the electron can be manipulated through the application of gate potentials. In the thesis, there are two major contributions of the manipulation of electron spin. In regard to the first contribution, we present numerical simulations of such a spin in single electron devices for realistic asymmetric potentials in electrostatically confined quantum dot. Using analytical and numerical techniques we show that breaking in-plane rotational symmetry of the confining potential by applied gate voltage leads to a significant effect on the tuning of the electron g-factor. In particular, we find that anisotropy extends the tunability to larger quantum dots in the GaAs case. Although the same extension of tunability exists in the InAs quantum dot case, we find a new effect in the InAs case. The new discovery is that broken in-plane rotational symmetry due to the Rashba spin-orbit coupling in an asymmetric potential results in a significant reverse effect in the tuning of the electron g-factor. This effect can not be observed in symmetric case. The derivative of the g-factor with respect to the electric field has the opposite sign in the above two potentials. The manipulation of Berry phases of spin in nano-scale devices is a topic that has received recent attention as a promising candidate for solid state quantum computation and non-charge-based logic devices. A single electron in an electrostatically defined quantum dot located in a 2 dimensional electron gas 2DEG), for example, can be trapped and the spin can be manipulated by simply moving the center of mass of the quantum dot adiabatically along a closed loop in the 2D plane via the application of gate potentials. In relation to the second contribution, we present numerical simulations and analytical expressions for the spin-dependent electron propagator a matrix-valued function of position) for an electron trapped in a quantum dot, while the center of mass of the quantum dot is adiabatically moved in the 2D plane in the presence of the Rashba and Dresselhaus spin-orbit interactions. We apply the Feynman disentangling technique to determine the non-abelian matrix Berry phase, we find exact analytical expression for the propagator in three cases: a) pure Rashba coupling； b) pure Dresselhaus coupling； and c) a combination of equally strong Rashba and Dresselhaus couplings. For other cases of interest where the solution of the propagator can not be found analytically, we present results obtained by numerically solving the Riccati equation resulting from the disentangling procedure. We also find that the presence of both spin-orbit couplings leads to a larger spin-flip probability than what would result from either mechanism considered separately.