<p>The optical properties of biological tissue provide quantitative information about the physiological structure and chemical composition of a tissue sample. The investigation of tissue optical properties through Diffuse Reflectance Spectroscopy (DRS) is a rapid, non-invasive technique with extensive applications in healthcare diagnostics and therapeutics. Breast conservation surgery, a clinical practice performed for nearly 15,000 patients annually, requires accurate diagnosis of the tissue margin, the healthy layer of tissue surrounding the excised tumor. This margin assessment has traditionally been performed via post-operative pathology through one of multiple time-intensive processes that are performed after the surgery is completed. However, the margin assessment can also be rapidly performed by DRS, leading towards pathological evaluations concurrent with the excision surgery. </p><p>Presently, DRS probe designs are limited to laboratory settings. They include illumination and collection optical fibers, spectrometers, and CCD detectors, which all add to the complexity, cost, and size of a diagnostic system. Recently, DRS probes have been designed with Silicon photodetectors (Si PDs), including detector arrays that enable simultaneous DRS imaging of multiple tissue sites. The Si PDs reduce probe system complexity by replacing the cumbersome fiber-based collection probes and CCD detectors. </p><p>However, these monolithic Si PD probes are rigid and flat. When imaging non-planar tissue samples, a rigid probe may experience reduced accuracy from uneven tissue pressure and loss of contact with the tissue surface. A physically flexible DRS probe can improve sensing accuracy by conforming to a tissue surface with arbitrary curvature.</p><p>This thesis presents the design, fabrication, and test of flexible DRS Si PD probes constructed with thin film single crystalline silicon heterogeneously bonded to a flexible polymer substrate. The PDs have dark currents and responsivities comparable to high performance standard thickness Si PDs. The responsivity and zero bias dark current of the flexible PDs were evaluated while flat and while curved up to a 10 mm radius of curvature, with measured variations in responsivity (±0.61%) and dark current (±3 pA).</p><p>The flexible DRS probe was evaluated on benign and malignant breast tissue representative liquid phantoms. DRS measurements were performed with the flexible DRS probe on both liquid phantoms over a wavelength range of 470 – 600 nm at five radii of curvature: flat, 50 mm, 25 mm, 15 mm, and 10 mm. The optical contrast between the benign and malignant phantom DRS measurements ranged from 4.0-13.6% across all measured wavelengths for the flat test case and 5.9-15.5% while curved. For both phantoms at all wavelengths, the DRS signal increased in response to increasing curvature. The increase in reflectance signal ranged from 4.8-12.3% when the liquid phantom curvature was brought from flat to a 10 mm radius of curvature. The experimental results were then compared to theoretical reflectance values generated through a forward Monte Carlo model. The mean error between experiment and theory was 2.33% for the benign phantom and 1.23% for the malignant phantom. </p><p>Pixel-to-pixel crosstalk, the portion of diffusely reflected light that enters the tissue near one PD but is detected at a different PD, was also evaluated using the same test setup as for the DRS signal. The crosstalk signal also increases due to curvature, with an increase of 33.2-40.0% across all measured wavelengths for the benign phantom. The experimental crosstalk signal for the benign phantom was compared to a forward Monte Carlo model with mean error of 4.85%. The crosstalk could not be measured on the malignant phantom due to lower reflected light levels that were below the noise floor of the PD. </p><p>The flexible Si PD probe presented herein shows promising results for optical tissue analysis and feature extraction on both flat and curved tissue surfaces. This flexible probe technology facilitates conformal tissue DRS imaging, potentially in a clinical diagnostic device.</p> / Dissertation

Nanoparticles produced with surfaces functionalised by highly specific molecular tags are able to target aberrant cells and detect or eliminate them without causing damage to surrounding healthy tissues. Single-stranded DNA (ssDNA) and RNA which fold to form secondary or tertiary structures, termed aptamers, represent a new class of such molecular tags. The nanoparticles, in turn, may carry therapeutic payload or luminescent entities which enable elimination or visualisation of targeted cells respectively. This project presents fabrication and isolation of a surface-functionalised nanoparticle construct, namely aptamer-tagged silica nanoparticles. DNA aptamers were chosen with the intention to make them useful for clinical or diagnostic applications of targeting neoplastic cells. Indeed, the ssDNA applied here is known to bind mucin-1 which in turn is a biomarker found on the surface of metastatic breast cancer cells. The separation of the construct was made possible by the inclusion of oligonucleotide-bound superparamagnetic particles in the construct; these enabled separation by magnetic capture. This project investigates two approaches to fabrication of the construct. In the first approach, aptamers, oligonucleotides and magnetic particles are mixed in solution. In the second, silica nanoparticles are functionalised with aptamers, oligonucleotides are bound to magnetic particles and the resulting two parts are hybridised together. The first approach gives higher yields. This may suggest that binding of silica nanoparticles to aptamers may hinder aptamer hybridisation to oligonucleotide fragments, thus resulting in lower construct synthesis yields. However, it is not known yet how the yield changes upon addition of silica nanoparticles into the solution. Therefore, the second experimental approach provides a starting point for fabrication and purification of an anti-cancer drug targeting platform in a simple bench-top setting. In addition, this thesis discusses the fabrication of silica nanoparticles which were intended to constitute an element of the construct. The work on nanoparticle fabrication aimed to develop a quick and repeatable synthesis method which would result in monodisperse entities. Despite trying various experimental approaches, suitable particles could not be reproducibly obtained. Agglomeration was identified as a major obstacle in the silica nanoparticle production process. Finally, this project assesses whether the chosen aptamers bind to the metastatic breast cancer cells, which would be necessary if they were to be used for diagnosis or therapy. FACS analysis indeed indicate that ssDNA aptamers attach to the MCF7 cell line, but the optimum conditions for that attachment remain to be determined.

An iterative control algorithm (ICA) which uses an approximate inverse-hysteresis model is implemented to compensate for hysteresis to precisely fabricate features on a soft polymer substrate using an atomic force microscope (AFM). The AFM is an important instrument in micro/nanotechnology because of its ability to interrogate, manipulate, and fabricate objects at the micro/nanoscale. The AFM uses a piezoelectric actuator to position an AFM-probe tip relative to the sample surface in three dimensions. In particular, precision lateral control of the AFM-probe tip relative to the sample surface is needed to ensure high-performance operation of the AFM. However, precision lateral positioning of the AFM-probe tip is challenging due to significant positioning error caused by hysteresis effect. An ICA which incorporates an approximate inverse of the hysteresis behavior is proposed to compensate for the hysteresis-caused positioning error. The approach is applied to fabricate a feature using the AFM on a polycarbonate surface, and it is demonstrated that the maximum tracking error can be reduced to 0.225% of the displacement range, underscoring the benefits of the control method.

Modification of nanostructures via laser processing is of great interest for a wide range of applications such as aerospace and the storage of nuclear waste. The primary goal of this dissertation is to improve the understanding of nanostructures through two primary routes: the modification of aerogels and pulsed laser ablation in ethanol. A new class of materials, patterned aerogels, was fabricated by photopolymerizing selected regions of homogeneous aerogel monoliths using visible light. The characterization and fabrication of functionally graded, cellular and compositionally anisotropic aerogels and ceramics is discussed. Visible light was utilized due to it’s minimal absorption and scattering by organic molecules and oxide nanoparticles within wet gels. This allowed for the fabrication of deeply penetrating, well resolved patterns. Similarly, nanoporous monoliths with a typical aerogel core and a mechanically robust exterior ceramic layer were synthesized from silica aerogels cross-linked with polyacrylonitrile. Simple variations of the exposure geometry allowed fabrication of a wide variety of anisotropic materials without requiring layering or bonding. Nanoparticle solutions were prepared by laser ablation of metal foils (Fe and Mo) in ethanol. Ablation of Fe generated Fe3O4 and Fe3C nanoparticles which were superparamagnetic with a saturation magnetization Ms = 124 emu/g. Zero field cooled (ZFC) measurements collected at an applied field of 50 Oe displayed a maximum magnetic susceptibility at 120 K with a broad distribution. Field cooled (FC) measurements showed a thermal hysteresis indicative of temperature dependent magnetic viscosity. Pulsed laser ablation of a Mo foil in ethanol generated inhomogeneous nanoparticles where Mo and MoC coexisted within the same aggregate. Formation of these unique nanoparticles is likely due to phase separation that occurs when a high temperature carbide phase cools after the laser pulse terminates. Similarly, magnetic nanoparticle suspensions were generated by pulsed laser ablation of Fe and Mo in ethanol. The formation of several carbide phases with no discernable alloy formation was seen. A decrease in magnetization with a decrease in Fe concentration was seen which was reconciled with the decreased Fe content in the system. However, at Fe concentrations below ~ 40%, an increase in Ms and Hc was observed which was reconciled with the disappearance of the ε–Fe3C. TEM analysis showed the formation of core-shell nanoparticles and Energy Filtered TEM showed the distribution of Fe-based nanoparticles in the suspensions.

Electrospinning is a process by which polymer fibers can be produced using an electrostatically driven fluid jet. Electrospun fibers can be produced at the micro- or nano-scale and are, therefore, very promising for air filtration applications. However, because electrospun fibers are electrically charged, it is difficult to control the morphology of filtration media. Fiber size, alignment and uniformity are very important factors that affect filter performance. The focus of this project is to understand the relationship between filter morphology and performance and to develop new methods to create filtration media with optimum morphology. This study is divided into three focus areas: unimodal and bimodal microscale fibrous media with aligned, orthogonal and random fiber orientations; unimodal and bimodal nanoscale fibers in random orientations; bimodal micrometer and nanometer fiber media with orthogonally aligned orientations. The results indicate that the most efficient filters, which are those with the highest ratio of particle collection efficiency divided by pressure drop, can be obtained through fabricating filters in orthogonal layers of aligned fibers with two different fiber diameters. Moreover, our results show that increasing the number of layers increases the performance of orthogonally layered fibers. Also, controlling fiber spacing in orthogonally layered micrometer fiber media can be an alternative way to study the filtration performance. Finally, such coatings presented throughout this research study can be designed and placed up-stream, down-stream, and/or in between conventional filters.

In recent years, quasi-one-dimensional materials have attracted a lot of research attention due to their remarkable properties, and their potential as building blocks for nanoscale electronic and optoelectronic devices. A modified chemical vapor deposition (CVD) method has been used to synthesize ZnO nanowires. Electron microscopy and other characterization techniques show that nanowires having distinct morphologies when grown under different conditions. The effects of reaction parameters including reaction time, temperature, carrier gas flow rate, substrates and catalyst material upon the size, shape, and density of ZnO nanowire arrays have been investigated. Excitonic solar cells —including Gratzel-type cells, organic and hybrid organic/inorganic solar cells—are promising devices for inexpensive, large-scale solar energy conversion. Hybrid organic/inorganic solar cells are made from composites of conjugated polymers with nanostructure metal oxides, in which the polymer component serves the function of both light absorber and hole conductor, and the ZnO nanowire arrays act as the electron conductors. Organic solar cells have been fabricated from environmentally friendly water-soluble polymers and ZnO nanowire arrays.

ATP synthase is a ubiquitous transmembrane protein that utilises the free energy available from ion gradients across lipid membranes to synthesise adenosine triphosphate (ATP). It may be separated into two parts - the membrane-embedded (i.e. hydrophobic) FO and the hydrophilic F₁. Each undergoes a rotary motion. Single-molecule studies on the rotation of the isolated hydrophilic F₁ have been performed for many years; attempts to construct an experiment in which to view the rotation of the membrane-embedded F₁F_O complex under high space- and time- resolution (such as by attachment of a rotational probe) have not yet seen a satisfactory method emerge in the literature. Most particularly, a clear ability to generate and control a proton-motive force across the membrane in which the F₁F_O is sited is needed to probe ATP synthesis. This thesis presents the development of a candidate method for such single-molecule studies. By the use of a water-in-oil emulsion, giant unilamellar lipid vesicles are formed which entrap arbitrary components - including functionalised gold nanospheres of 60-100 nm diameter, which move freely in the internal space. A charge-based lipid fusion is developed, using mixtures of natural lipid extracts with anionic and cationic lipids. It is demonstrated that anionic giant vesicles fuse with cationic small vesicles with full content mixing and transfer of bilayer leaflets. It is shown that F₁F_O is functional in the cationic lipid mixture. Methods are shown to bind such a cationic proteoliposome to a surface and for it to fuse with an anionic giant vesicle containing functionalised gold nanospheres. Backscatter laser darkfield is used to search for rotation of the gold nanospheres under ATP hydrolysis conditions of the F₁F_O; unidirectional rotation is seen in one instance and other suggestive traces are shown with speculative analysis. Further work is proposed.

Doctor of Philosophy / Department of Chemical Engineering / Vikas Berry / Nanoscale materials invite immense interest from diverse scientific disciplines as these provide access to precisely understand the physical world at their most fundamental atomic level. In concert with this aim of enhancing our understanding of the fundamental behavior at nanoscale, this dissertation presents research on three nanomaterials: Gold nanoparticles (GNPs), Graphene and ultra-thin Boron Nitride sheets (UTBNSs). The three-fold goals which drive this research are: incorporating mobility in nanoparticle based single-electron junction constructs, developing effective strategies to functionalize graphene with nano-forms of metal, and exfoliating ultrathin sheets of Boron Nitride. Gold nanoparticle based electronic constructs can achieve a new degree of operational freedom if nanoscale mobility is incorporated in their design. We achieved such a nano-electromechanical construct by incorporating elastic polymer molecules between GNPs to form 2-dimensional (2-D) molecular junctions which show a nanoscale reversible motion on applying macro scale forces. This GNP-polymer assembly works like a molecular spring opening avenues to maneuver nano components and store energy at nano-scale. Graphene is the first isolated nanomaterial that displays single-atom thickness. It exhibits quantum confinement that enables it to possess a unique combination of fascinating electronic, optical, and mechanical properties. Modifying the surface of graphene is extremely significant to enable its incorporation into applications of interest. We demonstrated the ability of chemically modified graphene sheets to act as GNP stabilizing templates in solution, and utilized this to process GNP composites of graphene. We discovered that GNPs synthesized by chemical or microwave reduction stabilize on graphene-oxide sheets to form snow-flake morphologies and bare-surfaces respectively. These hybrid nano constructs were extensively studied to understand the effect and nature of GNPs’ interaction with graphene, and applied to address the challenge of dispersing bare-surfaced GNPs for efficient liquid-phase catalysis. We also revisited the functionalization of graphene and present a non-invasive surface introduction of interfaceable moieties. Isostructural to graphene, ultrathin BN sheet is another atomic-thick nanomaterial possessing a highly diverse set of properties inconceivable from graphene. Exfoliating UTBNSs has been challenging due to their exceptional intersheet-bonding and chemical-inertness. To develop applications of BN monolayers and evolve research, a facile lab-scale approach was desired that can produce processable dispersions of BN monolayers. We demonstrated a novel chlorosulfonic acid based treatment that resulted in protonation assisted layer-by-layer exfoliation of BN monolayers with highest reported yields till date. Further, the BN monolayers exhibited extensively protonated N centers, which are utilized for chemically interfacing GNPs, demonstrating their ability to act as excellent nano-templates. The scientific details obtained from the research shown here will significantly support current research activities and greatly impact their future applications. Our research findings have been published in ACS Nano, Small, Journal of Physical Chemistry Letters, MRS Proceedings and have gathered >45 citations.

M.Tech. (Chemistry, Faculty of Applied and Computer Science), Vaal University of Technology. / Complexes of alkyldithiocarbamate and thiuram have been extensively explored for various applications in the medical field. Thiuram and dithiocarbamate ligands were used to prepared complexes of cobalt and copper. The high abundance of sulfur in these ligands has resulted to be the preferred complexes for the synthesis of metal sulfide nanoparticles. All the prepared complexes were characterized using techniques such as IR and 1HNMR spectroscopy, elemental analysis, and thermogravimetric analysis. All the spectra data obtained were consistent with the coordination of the ligands through sulfur atom to the metal ion. The thermogravimetric analysis of all complexes decomposed to form metal sulfide, which really confirmed that all the complexes could be used to metal sulfide nanoparticles. All the prepared complexes were used to synthesize MxSy nanoparticles. The metal sulfide nanoparticles were successful prepared by thermal decomposition of the single-source precursor in hexadecylamine solution. The reaction parameter such as the concentration (1.0, 0.5, 0.25 and 0.125 g), reaction temperature (80, 130, 200, 250 °C) and the time (5, 10, 15, 20, 25 and 30) of the reactionwere varied to see their effect on the preparation of the nanoparticles. The prepared metal sulfide nanoparticles were characterized using techniques such as UV spectroscopy, photoluminescence spectroscopy, X-ray diffraction analysis and transmission electron microscopy. The concentration was found to have a profound effect in size and shape of the prepared nanoparticles. The nanoparticles prepared at various concentrations were dominated by sphere with an average size of 2-30 nm. The XRD pattern confirmed that the composition is not affected by the temperature. Thetemperature has a dramatic effect in size, shape and the stoichiometry of the reaction. This was confirmed by an increase in size as the temperature was increased, with the exception of cobalt sulfide nanoparticles that decrease in size while temperature was increase. The XRD pattern showed different composition as the temperature was varied. Time of the reaction was found to affect the particles size of the nanoparticle. The sizes of the nanoparticles were increase as the time of the reaction was prolonged.

This research was mainly focused on the design and optimization of aperture-based structures to achieve the greatest third harmonic conversion efficiency. It was discovered that by tuning the localized surface plasmon resonance to the fundamental beam wavelength, and by tuning the propagating surface plasmons resonance to the Bragg resonance of the aperture arrays, both the directivity and conversion efficiency of the third harmonic signal were enhanced. The influence of the gap plasmon resonance on the third harmonic conversion efficiency of the aperture arrays was also investigated. The resulted third harmonic generation (THG) from an array of annular ring apertures as a closed loop structure were compared to arrays of H-shaped, double nanohole and rectangular apertures as open-loop structures. The H-shaped structure had the greatest conversion efficiency at approximately 0.5 %. Moreover, it was discovered that the maximum THG did not result from the smallest gap; instead, the gap sizes where the scattering and absorption cross sections were equal, led to the greatest THG. The finite difference time domain (FDTD) simulations based on the nonlinear scattering theory were also performed. The simulation results were in good agreement with the experimental data. Moreover, a modified quantum-corrected model was developed to study the electron tunneling effect as a limiting factor of the THG from plasmonic structures in the sub-nanometer regime. / Graduate / 0544 / 0794 / 0752 / 0756 / mrnezami@gmail.com