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The promise to build structures atom by atom that would lead to devices or materials with tuned properties that surpass any material we encounter in the macroscale world inspires more researchers everyday to study nanotechnology. As a direct result of this interest in nanotechnology, manipulation systems with nano or sub-nano scale precision are required to position or pattern matter in smaller scales to study it. However, this manipulation task is not straightforward due to small scale physics, which reduces the effect of weight and inertia, the dominant forces in macroscale, and promotes other forces such as adhesion or electrostatic interactions. Hence, to understand nanoscale physics, the first step to take is to model and characterize the underlying principles. In this context, scanning probe microscopes (SPMs) are suitable tools for experimenting on nanoscale physics, in addition to being good candidates as nanomanipulation systems due to their ability to locally interact with the substrate using the end-effector that they utilize on the order of a few nanometers or below. On the other hand, using SPMs for nanomanipulation has drawbacks as well. Since they utilize a single end-effector to interact with the substrate, the manipulation process is serial hence slow with low throughput. Furthermore, having no real-time visual feedback and the non-linearity of the actuators decrease the precision and the repeatability of the positioning, hence decreasing the reliability of the manipulation. In order to consider SPMs as viable nanomanipulation tools, these challenges of speed and reliability should first be tackled by utilizing smarter algorithms and mechanisms. In this work, we demonstrate two case studies that are used for tackling the speed and reliability challenges of nanomanipulation. As the first case study, an AFM is utilized to position nanoparticles. In the AFM based mechanical contact manipulation of nanoparticles, we demonstrate automated control to increase speed and reliability. In order to achieve the automation, we present models to investigate the physics of nanoparticle manipulation using an AFM cantilever, and use these models to investigate the effect of cantilever selection to manipulation success. We demonstrate particle detection using line-scans and a contact loss detection algorithm using cantilever normal deflection data to decrease the number of images taken during manipulation. We also demonstrate through experimental results that it is possible to push and pull particles on a flat surface into defined patterns autonomously, using an AFM probe tip, and with an error less than the particle diameter, and with success rates as high as 87%. Moreover, an STM is utilized to manipulate surfaces using electrical pulses and high electric fields as a second case study of this thesis. During the STM based electrical non-contact manipulation, utilizing conductive AFM probes as STM end-effectors as a step towards a multiple probe approach is suggested to improve the speed and throughput of the STM manipulation. STM imaging of surfaces using STM tips and conductive AFM probes are demonstrated and algorithms for STM based electrical manipulation of surfaces is presented and experimentally verified. Furthermore, models for STM operation and manipulation using STM tips and AFM probes as end-effectors are developed and the effects of several design parameters on STM based imaging and manipulation that utilizes AFM probes and STM tips are investigated. In addition, a faster and more flexible controller is designed and implemented which allows instant switching between AFM and STM modes, when conductive AFM probes are utilized.

Effects of biomimetic micro-patterning of polymeric materials on their interfacial properties were studied experimentally. Micropillars of PDMS and SU-8 epoxy were fabricated through soft lithography and UV lithography techniques, respectively. PDMS pillars were topped by thin terminal films of the same material through dipping method with different thicknesses and viscosities. Adhesion and frictional properties of biomimetic microstructures were examined in two modes of contact, i.e. laid and conformal contact. In the first mode of contact, i.e. laid contact, the contact between adhesive and adherent is laid on top of the micro-protrusions or is in contact with side wall of micropillars. Adhesion properties of the smooth and patterned PDMS were characterized through micro-indentation test. Moreover, the friction properties of the smooth PDMS sample and PDMS micropillars with different aspect ratios were examined in unidirectional friction testing. JKR theory of continuum contact mechanics was utilized to interpret the obtained data. To study the effect of second mode of contact, peeling behaviour of a conformal contact between solidified liquid PDMS and SU-8 micropillars was monitored. Kendall’s model of elastic peeling was used to interpret the peeling data. It was found that patterning of the materials would decrease the real area of contact and accordingly adhesion and friction to the mating surface. Termination of the micropillars with a thin layer of the same material result in increment of adhesion as reduction of the real contact area could be compensated and the compliance of the near surface increases. Elastic energy dissipation as a result of enhanced compliance and crack trapping and crack propagation instabilities are the main reasons behind increment of adhesion of thin film terminated structures. Viscoelasticity of the terminal thin film remarkably increased the adhesion as a result of coupling mentioned mechanisms and viscoelastic loss on the surface. Decline of the overall friction could be tailored through use of different aspect ratios. Higher aspect ratios pillars show higher friction comparing to lower aspect ratio pillars. 550 folds enhancement of adhesion was observed for peeling of the PDMS tape from rigid micropillars with aspect ratio ranging from 0 to 6. It is concluded that for the lower aspect ratio micropillars, the elastic energy dissipation is playing the key role in adhesion enhancement. This role shifts toward side-wall friction during separation by increase in aspect ratio. These all give in hand a versatile tool to control and fine tune the interfacial properties of materials, whether they are concerned with adhesion or friction.

The work presented in this thesis is divided loosely into three main areas of interest: development of a novel method of solid-state nanopore fabrication; applications of this method to some of the open problems in the field; and analysis of nanopore data. The first of these occupies the majority of the research presented in this thesis, covering research dedicated to the development and characterization of a novel method of solid-state nanopore fabrication which achieves nanometer scale control over matter using simple and low cost circuitry. Termed controlled breakdown (CBD), this technique is in the process of revolutionizing the field of nanopore research, and in the few short years I have been part of its development it has seen adoption in nanopore labs across the globe, both academic and industrial. Due to the simple nature of CBD, this technique also enables novel applications of nanopores in device architectures that were inaccessible to the expensive and inflexible methods used previously. The second part of this thesis takes advantage of the unique opportunities presented by CBD to develop a device architecture comprising two nanopores in series. This nanodevice tackles one of the main problems standing between nanopores and the promise of cheap genomic analysis: control of the motion and conformation of the polymer both prior to and during translocation through the pore. Finally, because the field of nanopore research is still relatively young, very few tools are available which provide high-quality analysis of nanopore data. The last part of this thesis is dedicated to a thorough discussion of the complexities involved in analysing nanopore signals, as well as the development of several tools which directly address this knowledge gap.

Interacting cellular systems with nano-interfaces has shown great promise in promoting differentiation, regeneration, and stimulation. Functionalized nanostructures can serve as topological cues to mimic the extracellular matrix network to support cellular growth. Nanostructures can also generate signals, such as thermal, electrical, and mechanical stimulus, to trigger cellular stimulation. At this stage, the main challenges of applying nanostructures with biological systems are: (1) how to mimic the hierarchical structure of the ECM network in a 3D format and (2) how to improve the efficiency of the nanostructures while decreasing its invasiveness. To enable functional neuron regeneration after injuries, we have developed a 2D nanoladder scaffold, composed of micron size fibers and nanoscale protrusions, to mimic the ECM in the spinal cord. We have demonstrated that directional guidance during neuronal regeneration is critical for functional reconnection. We further transferred the nanoladder pattern onto biocompatible silk films. We established a self-folding strategy to fabricate 3D silk rolls, which is an even closer system to mimic the ECM of the spinal cord. As demonstrated by in vitro and in vivo experiments, such a scaffold can serve as a grafting bridge to guide axonal regeneration to desired targets for functional reconnection after spinal cord injuries. Benefited from the robust self-folding techniques, silk rolls can also be used for heterogeneous cell culture, providing a potential therapeutic approach for multiple tissue regeneration directions, such as bones, muscles, and tendons. For achieving neurostimulation, we have developed photoacoustic nanotransducers (PANs), which generate ultrasound upon excitation of NIR II nanosecond laser light. By surface functionalize PAN to bind to neurons, we have achieved an optoacoustic neuron stimulation process with a high spatial and temporal resolution, proved by in-vitro and in-vivo experiments. Such an application can enable non-invasive, optogenetics free and MRI compatible neurostimulation, which provides a new direction of gene-transfection free neuromodulation. Collectively, in this thesis, we have developed two systems to promote functional regeneration after injuries and stimulate neurons in a minimally invasive manner. By integrating those two functions, a potential new generation of the bioengineered scaffold can be investigated to enable functional and programmable control during the regeneration process.

Recently, magnetic nanoparticles are finding an increased use in biomedical applications and research. Nanobeads are widely used for cell separation, biosensing and cancer therapy, among others. Due to their properties, nanowires (NWs) are gaining ground for similar applications and, as with all biomaterials, their cytotoxicity is an important factor to be considered before conducting biological studies with them. In this work, the cytotoxic effects of nickel NWs (Ni NWs) were investigated in terms of cell viability and damage to the cellular membrane. Ni NWs with an average diameter of 30-34 nm were prepared by electrodeposition in nanoporous alumina templates. The templates were obtained by a two-step anodization process with oxalic acid on an aluminum substrate. Characterization of NWs was done using X-Ray diffraction (XRD) and energy dispersive X-Ray analysis (EDAX), whereas their morphology was observed with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Cell viability studies were carried out on human colorectal carcinoma cells HCT 116 by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) cell proliferation colorimetric assay, whereas the lactate dehydrogenase (LDH) homogenous membrane fluorimetric assay was used to measure the degree of cell membrane rupture. The density of cell seeding was calculated to obtain a specific cell number and confluency before treatment with NWs. Optical readings of the cell-reduced MTT products were measured at 570 nm, whereas fluorescent LDH membrane leakage was recorded with an excitation wavelength of 525 nm and an emission wavelength of 580 - 640 nm. The effects of NW length, cell exposure time, as well as NW:cell ratio, were evaluated through both cytotoxic assays. The results show that cell viability due to Ni NWs is affected depending on both exposure time and NW number. On the other hand, membrane rupture and leakage was only significant at later exposure times. Both cytotoxic assessment assays showed an earlier cytotoxic effect in case of shorter NWs, with longer ones having a more marked toxicity, albeit with a delay in time. These findings demonstrate that different levels of biocompatibility can be obtained with specific doses and properties of Ni NWs and can serve as guideline for future experiments.

Raman spectroscopy is among the most widely employed methods to investigate the properties of materials in several fields of study. Evolution in materials science allowed us to fabricate suitable substrates, at the nanoscale, capable to enhance the electromagnetic field of the signals coming from the samples which at this range turn out to be in most cases singles or a few molecules. This particular variation of the classical technique is called SERS (Surface Enanched Raman Spectroscopy). In this work, the enhancement of the electromagnetic field is obtained by manipulation of the optical properties of metals with respect to their size. By using electroless deposition (bottom up technique), gold and silver nanoparticles were deposited in nanostructured patterns obtained on silicon wafers by means of electron beam lithography (top down technique). Rhodamine 6G in aqueous solution at extremely low concentration (10-8 M) was absorbed on the resultant dimers and the collection of the Raman spectra demonstrated the high efficiency of the substrates.

The rational combination of dielectric and metallic nano particles brings novel optical properties to conventional subwavelength structures. This thesis introduces the optoplasmonic geometries demonstrating versatile ability in both far and near field modification within nano scale. Template-assisted self-assembly approaches are applied creating nano entities with titanium dioxide and gold nano spheres. A top-bottom mono hybrid unit and interdigitated array are developed. With the examination of the elastic and inelastic response of these hybrid materials, physical models are simulated to depict the scenario of varied geometry and combination of nano particles. In contrast to solely metal or dielectric particle arrays, this type of artificial material not only enhances the near electric field intensity within the metal nano cluster hot spots, but also expands the overall volume of enhanced electric field. Further study reveals that the additional enhancement and redistribution of near field are derived from the coupling between the nano gold cluster plasmon resonance and the in-plane diffractive mode of the dielectric array. The redirected emission profile of the fluorescent dyes within the hybrid array is explored.

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Research groups around the world are looking to develop a qubit protected from decoherence for achieving quantum advantage in computations. This would have huge impact on the modern world. The applications are many from drug development to cryptography and many more  elds. Indium-Arsenide Nanowires with an epitaxially matched thin  lm of lead grown with Select-Area-Growth could prove to be a platform for building scalable qubits. The work in this thesis is to create a device capable of measuring the superconductivity of the samples InAs-Pb grown at the Center for Quantum Devices, Niels Bohr Institute. The InAs semiconducting nanowires serves as one dimensional system that could host Majorana Zero Modes if coupled to a superconductor such as Pb. The MZMs emerges at the edges of the nanowires. The device created is a 4-probe device that should be used to measure the induced topological superconductivity inside the device. The project was able to such a device using electron beam lithography techniques and development of the fabrication process of InAs-Pb SAG NW Devices was furthered.