Molecular nanotechnology has matured in the last thirty-nine years from the germ of an idea by a Nobel Laureate physicist to a rapidly growing international research site with more than $1 billion dollars in annual investment. Although only recently accepted as "mainstream" by the R&D community, nanotechnology research is now populated by eminent researchers in such fields as physics, chemistry, molecular biology, and computer science. Refereed journal articles appear with increasing frequency. The National Academy of Sciences, the RAND Corporation, the Department of Defense, and the National Science Foundation have recently issued reports calling for more structure and organization in nanotechnology research to improve synergy and research efficiency. Others insist that centralization would restrict independent approaches, one of which might be the best path to follow. This thesis addresses the following issues for the emerging field of molecular nanotechnology: • The field is extensive, growing, and in need of policy review. • The parties responsible for strategic science and technology policy in the United States as well as the current infrastructure for R&D funding are identified. • External evaluators have appraised our current policy and found it lacking in some key respects. • There are substantive issues that might be considered by American policymakers in assessing nanotechnology policy strategies. • We need to find a way to reconcile the sometimes conflicting aims of peer review and interdisciplinarity. • A workable framework for a national nanotechnology program is identified. / Master of Science

Yes / Bimetallic nanoparticles are of immense scientific and technological interest given the synergistic properties observed when two different metallic species are mixed at the nanoscale. This is particularly prevalent in catalysis, where bimetallic nanoparticles often exhibit improved catalytic activity and durability over their monometallic counterparts. Yet despite intense research efforts, little is understood regarding how to optimize bimetallic surface composition and structure synthetically using rational design principles. Recently, it has been demonstrated that peptide-enabled routes for nanoparticle synthesis result in materials with sequence-dependent catalytic properties, providing an opportunity for rational design through sequence manipulation. In this study, bimetallic PdAu nanoparticles are synthesized with a small set of peptides containing known Pd and Au binding motifs. The resulting nanoparticles were extensively characterized using high-resolution scanning transmission electron microscopy, X-ray absorption spectroscopy, and high-energy X-ray diffraction coupled to atomic pair distribution function analysis. Structural information obtained from synchrotron radiation methods was then used to generate model nanoparticle configurations using reverse Monte Carlo simulations, which illustrate sequence dependence in both surface structure and surface composition. Replica exchange with solute tempering molecular dynamics simulations were also used to predict the modes of peptide binding on monometallic surfaces, indicating that different sequences bind to the metal interfaces via different mechanisms. As a testbed reaction, electrocatalytic methanol oxidation experiments were performed, wherein differences in catalytic activity are clearly observed in materials with identical bimetallic composition. Taken together, this study indicates that peptides could be used to arrive at bimetallic surfaces with enhanced catalytic properties, which could be leveraged for rational bimetallic nanoparticle design using peptide-enabled approaches. / Air Force Office for Scientific Research (T.R.W., Grant No. FA9550-12-620 1-0226). S.P.E. and E.B.C. gratefully acknowledge financial support from the Army Research Office through a MURI award, W911NF-10-1-0520

Yes / Investigation of the non-covalent interaction of biomolecules with aqueous graphene interfaces is a rapidly expanding area. However, reliable exploitation of these interfaces in many applications requires that the links between the sequence and binding of the adsorbed peptide structures be clearly established. Molecular dynamics (MD) simulations can play a key role in elucidating the conformational ensemble of peptides adsorbed at graphene interfaces, helping to elucidate these rules in partnership with experimental characterisation. We apply our recently-developed polarisable force-field for biomolecule–graphene interfaces, GRAPPA, in partnership with advanced simulation approaches, to probe the adsorption behaviour of peptides at aqueous graphene. First we determine the free energy of adsorption of all twenty naturally occurring amino acids (AAs) via metadynamics simulations, providing a benchmark for interpreting peptide–graphene adsorption studies. From these free energies, we find that strong-binding amino acids have flat and/or compact side chain groups, and we relate this behaviour to the interfacial solvent structuring. Second, we apply replica exchange with solute tempering simulations to efficiently and widely sample the conformational ensemble of two experimentally-characterised peptide sequences, P1 and its alanine mutant P1A3, in solution and adsorbed on graphene. For P1 we find a significant minority of the conformational ensemble possesses a helical structure, both in solution and when adsorbed, while P1A3 features mostly extended, random-coil conformations. In solution this helical P1 configuration is stabilised through favourable intra-peptide interactions, while the adsorbed structure is stabilised via interaction of four strongly-binding residues, identified from our metadynamics simulations, with the aqueous graphene interface. Our findings rationalise the performance of the P1 sequence as a known graphene binder. / veski

Kinetically controlled isothermal growth is fundamental to biological development, but it remains challenging to rationally design molecular systems that self-assemble isothermally into complex geometries via prescribed assembly and disassembly pathways. By exploiting the programmable chemistry of base pairing, sophisticated spatial and temporal control have both been demonstrated in DNA self-assembly, but largely as separate pursuits. This dissertation extends a new approach, called developmental self-assembly, that integrates temporal with spatial control by using a prescriptive molecular program to specify the kinetic pathways by which DNA molecules isothermally self-assemble into well-defined three-dimensional geometries. / Chemistry and Chemical Biology

<p>Biological systems have inspired interest in developing artificial molecular self-assembly techniques that imitate nature's ability to harness chemical forces to specifically position atoms within intricate assemblies. Of the biomolecules used to mimic nature's abilities, nucleic acids have gained special attention. Specifically, deoxyribonucleic acid is a stable molecule with a readily accessible code that exhibits predictable and programmable intermolecular interactions. These properties are exploited in the revolutionary structural DNA nanotechnology method known as scaffolded DNA origami. For DNA origami to establish itself as a widely used method for creating self-assembling, complex, functional materials, current limitations need to be overcome and new methods need to be established to move forward with developing structures for diverse applications in many fields. The limitations discussed in this dissertation include 1) pushing the scale of well-formed, fully-addressable origami to two and seven times the size of conventional origami, 2) testing cost-effective staple strand synthesis methods for producing pools of oligos for a specified origami, and 3) engineering mechanical properties using non-natural nucleotides in DNA assemblies. After accomplishing the above, we're able to design complex DNA origami structures that incorporate many of the current developments in the field into a useful material with applicability in wide-ranging fields, namely cell biology and photonics.</p> / Dissertation

Published Article / In the era of open innovation, the capability to conduct collaborative research and development has become a key indicator of absorptive capacity and innovation competitiveness. However, the literature addressing open innovation has a focus on developed economies. New evidence from the South African National R&D Survey, together with supplementary data, make it possible to gain a greater understanding of the structure of open innovation in nanotechnology, biotechnology and open source software in the South African context. Findings from a comparative analysis include: the identification of collaboration-intensive R&D networks whose structures are influenced by the characteristics of each technological platform; linkages between localized innovation networks and global innovation networks; and distinct patterns of expenditure, sectoral distribution and geographical location characterizing each of these technologies. The paper concludes with some suggestions for policy applications for these findings as well as directions for further research.

In this thesis I present a novel coarse-grained model of deoxyribonucleic acid (DNA). The model represents single-stranded DNA as a chain of rigid nucleotides, and includes potentials to represent chain connectivity, excluded volume, hydrogen-bonding and base stacking interactions. The parameterization of these interactions is justified by comparing the model's representation of a range of physical phenomena to experimental data. In particular, the geometrical structure and elastic moduli of duplex DNA, and the flexibility of single-stranded DNA, are shown to be physically reasonable. Additionally, the thermodynamics of single-stranded stacking, duplex hybridization, hairpin formation and more complex motifs are shown to agree well with experimental data. The model is optimized for capturing the thermodynamic and mechanical changes associated with duplex formation from single strands. Considerable attention is therefore given to ensuring that single-stranded DNA behaves physically, an approach which differs from previous attempts to model DNA. As a result, the model is the first in which an explicit stacking transition is present in single strands, and also the only coarse-grained model to date to capture both hairpin formation within a single strand and duplex formation between strands. The scope of the model is demonstrated by simulating DNA tweezers, an iconic nanodevice -- the first time that coarse-grained modelling has been applied to dynamic DNA nanotechnology. The simulations suggest that branch migration during toehold-mediated strand displacement -- a central feature of many nanomachines -- does not have a flat free-energy profile, as is generally assumed. This finding may help to explain the observed dependence of displacement rate on toehold length. Finally, the operation of a two-footed DNA walker on a single-stranded DNA track is considered. The model suggests that several aspects of the walker will reduce its efficiency, including a tendency to bind to an undesired site on the track. Several design modifications are suggested to improve the operation of the walker.

Nowadays, nanotechnology is becoming an inescapable part of everyday life. The big barrier in front of its rapid growth is our incapability of producing nanoscale materials in a reliable and cost-effective way. In fact, the current yield of nano-devices is very low (around 10 %), which makes fabrications of nano-devices very expensive and uncertain. To overcome this challenge, the first and most important step is to investigate how to control nano-structure synthesis variations. The main directions of reliability research in nanotechnology can be classified either from a material perspective or from a device perspective. The first direction focuses on restructuring materials and/or optimizing process conditions at the nano-level (nanomaterials). The other direction is linked to nano-devices and includes the creation of nano-electronic and electro-mechanical systems at nano-level architectures by taking into account the reliability of future products. In this dissertation, we have investigated two topics on both nano-materials and nano-devices. In the first research work, we have studied the optimization of one of the most important nanowire growth processes using statistical methods. Research on nanowire growth with patterned arrays of catalyst has shown that the wire-to-wire spacing is an important factor affecting the quality of resulting nanowires. To improve the process yield and the length uniformity of fabricated nanowires, it is important to reduce the resource competition between nanowires during the growth process. We have proposed a physical-statistical nanowire-interaction model considering the shadowing effect and shared substrate diffusion area to determine the optimal pitch that would ensure the minimum competition between nanowires. A sigmoid function is used in the model, and the least squares estimation method is used to estimate the model parameters. The estimated model is then used to determine the optimal spatial arrangement of catalyst arrays. This work is an early attempt that uses a physical-statistical modeling approach to studying selective nanowire growth for the improvement of process yield. In the second research work, the reliability of nano-dielectrics is investigated. As electronic devices get smaller, reliability issues pose new challenges due to unknown underlying physics of failure (i.e., failure mechanisms and modes). This necessitates new reliability analysis approaches related to nano-scale devices. One of the most important nano-devices is the transistor that is subject to various failure mechanisms. Dielectric breakdown is known to be the most critical one and has become a major barrier for reliable circuit design in nano-scale. Due to the need for aggressive downscaling of transistors, dielectric films are being made extremely thin, and this has led to adopting high permittivity (k) dielectrics as an alternative to widely used SiO₂ in recent years. Since most time-dependent dielectric breakdown test data on bilayer stacks show significant deviations from a Weibull trend, we have proposed two new approaches to modeling the time to breakdown of bi-layer high-k dielectrics. In the first approach, we have used a marked space-time self-exciting point process to model the defect generation rate. A simulation algorithm is used to generate defects within the dielectric space, and an optimization algorithm is employed to minimize the Kullback-Leibler divergence between the empirical distribution obtained from the real data and the one based on the simulated data to find the best parameter values and to predict the total time to failure. The novelty of the presented approach lies in using a conditional intensity for trap generation in dielectric that is a function of time, space and size of the previous defects. In addition, in the second approach, a k-out-of-n system framework is proposed to estimate the total failure time after the generation of more than one soft breakdown.

Self-assembled monolayers (SAMs) were investigated with regard to their application as templates to control processes down to the nanometre length scale. With applications of SAM for electrochemical nanotechnology in mind, the range of aspects studied comprises patterning on different length scales, behaviour of SAMs under the conditions of electrochemical metal deposition, and the influence of the head and tail groups on formation and structure of SAMs. On a micrometre scale, laser scanning lithography (LSL) was used to pattern SAM covered Au surfaces. With this technique, localized regions of a SAM are desorbed by scanning the focal spot of a laser beam. Thermal desorption occurs as a result of the high substrate temperature produced by the laser pulses. Patterns with line width as small as 0.9 µm were produced by LSL. It is demonstrated that SAM can not only be patterned by laser radiation but can also be rendered more passive as revealed by electrochemical metal deposition. Such blocking effect is explained by annealing of defects upon irradiation at the appropriate laser energy. This effect can block deposition of bulk copper particles, but does not prevent the underpotential deposition. Based on this passivation effect, large passivation areas can be created, which can be used as substrate for further nano/micro fabrication. The combination of SAM patterning and electrochemical metal deposition was also demonstrated to be an effective way to prepare superhydrophobic surfaces, exhibiting a contact angle of 165° (water droplet). Aiming for the generation of smaller structures, scanning tunneling microscopy (STM) is used as a tool to pattern SAMs. Several phenomena observed in STM based manipulation of SAMs are addressed. The first one is sweeping effect. Deposited metal particles on top of SAM and SAMs are swept by STM tip by choosing appropriate I/V parameters. The closer the tip (higher current, lower bias), the more effective it is. Molecularly resolved images confirm that after sweeping, the scanned area is still covered by SAM molecules. This is explained by diffusion. The sweeping process can be repeated, thus, resulting in a layer by layer etching. The second effect is field-induced desorption. Applying a positive voltage (2.5-5V), a SAM is damaged beneath the area of the tip. The damage depends not only on the bias applied, but also on the current setpoint right before applying the bias. The third effect is nanografting. Nanografting was observed that a SAM having a stronger assembling ability can replace the weaker one (matrix layer) in hexadecane solution by STM scanning under normal I/V parameters combination that are usually used for imaging. It is found that longer chain can replace the shorter chain thiol, alkanethiol can replace biphenyl thiol. This method can be applied to pattern SAM. Defects (punched holes) were created purposely on the SAMs covered Au surface and in situ STM was used to investigate the process of Under-Potential Deposition (UPD) and bulk metal deposition. Bulk metal deposition on punched holes depends on the size. Small scale patterning by punching is sufficient for applications based on UPD but not for bulk metal deposition. Several SAMs assembled on Au(111) surface (1-mercaptoundecanoic acid (MUA), Dodecyl Thiocyanate (C12SCN) and bis(pyrazol-1-yl)pyridine-substituted thiol (bpp-SH) and thiocyanate (bpp-SCN)) were investigated with the aim to expand the type of SAMs that can be used as template for further application, such as metal coordination. High quality thiolate monolayers formed by cleavage of the S-CN bond can be obtained on Au(111). Thus, organothiocyanates appear to be a promising alternative to thiols. Well-ordered MUA monolayers are formed in a few hours at the temperature range of 323-363 K by Physical Vapour Deposition (PVD). Self-assembled monolayers of bpp-SH and bpp-SCN on Au(111)/mica were studied with STM. Preparation conditions such as temperature, solvent, and contamination affect the formation of SAMs on Au(111) much more than other common thiols such as alkanethiols and biphenythiols.

Nanotechnology is an emerging field of engineering. Awareness needs to be fostered in the K-12 education system in order to sustain its expansion. As a current Algebra 1 teacher, I participated in the NASCENT research program to further my education in nanotechnology and find ways to integrate this content and practices in my Science Technology Engineering and Math (STEM) based Algebra 1 curriculum. During the research, I learned about surface tension of solids and liquids and its effects on materials' wetting properties. After completing the research program, I created a 2-week long project where students will replicate my experiences during this research. The purpose of this report is to investigate the need for the integration of nanotechnology in STEM classes and find ways to turn my research experience into real-world learning opportunities for my students. / text