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The focus of this dissertation is the study of measuring light not by energy transfer as is done with a standard photodetector such as a photographic film or charged coupled device, but rather by the forces which the light exerts on matter. In this manner we are able to replace or complement standard photodetector-based light detection techniques. One key attribute of force detection is that it permits the measurement of light over a very large range of frequencies including those which are difficult to access with standard photodetectors, such as the far IR and THz. The dissertation addresses the specific phenomena associated with optically induced force (OIF) detection in the near-field where light can be detected with high spatial resolution close to material interfaces. This is accomplished using a scanning probe microscope (SPM), which has the advantage of already having a sensitive force detector integrated into the system. The two microscopies we focus on here are atomic force microscopy (AFM) and nearfield scanning optical microscopy (NSOM). By detecting surface-induced forces or force gradients applied to a very small size probe (~ 20 nm diameter), AFM measures the force acting on the probe as a function of the tip-sample separation or extracts topography information. Typical NSOM utilizes either a small aperture (~ 50 150  nm diameter) to collect and/or radiate light in a small volume or a small scatterer (~ 20 nm diameter) in order to scatter light in a very small volume. This light is then measured with an avalanche photodiode or a photomultiplier tube. These two modalities may be combined in order to simultaneously map the local intensity distribution and topography of a sample of interest. A critical assumption made when performing iv such a measurement is that the distance regulation, which is based on surface induced forces, and the intensity distribution are independent. In other words, it is assumed that the presence of optical fields does not influence the AFM operation. However, it is well known that light exerts forces on the matter with which it interacts. This light-induced force may affect the atomic force microscope tip-sample distance regulation mechanism or, by modifying the tip, it may also indirectly influence the distance between the probe and the surface. This dissertation will present evidence that the effect of optically induced forces is strong enough to be observed when performing typical NSOM measurements. This effect is first studied on common experimental situations to show where and how these forces manifest themselves. Afterward, several new measurement approaches are demonstrated, which take advantage of this additional information to either complement or replace standard NSOM detection. For example, the force acting on the probe can be detected while simultaneously extracting the tip-sample separation, a measurement characteristic which is typically difficult to obtain. Moreover, the standard field collection with an aperture NSOM and the measurement of optically induced forces can be operated simultaneously. Thus, complementary information about the field intensity and its gradient can be, for the first time, collected with a single probe. Finally, a new scanning probe modality, multi-frequency NSOM (MF-NSOM), will be demonstrated. In this approach, the tuning fork is driven electrically at one frequency to perform a standard tip-sample distance regulation to follow the sample topography and optically driven at another frequency to measure the optically induced force. This novel technique provides a viable alternative to standard NSOM scanning and should be of particular interest in the long wavelength regime, e.g. far IR and THz.

Extracellular vesicles are important players in cell-to-cell communication and have the potential to be used as biomarkers for decease. The mechanical properties of extracellular vesicles is an active field of research, with new methods and models being developed. In this thesis, two samples of extracellular vesicles containing different levels of membrane protein expressions are investigated using atomic force microscopy. Three models for determining stiffness are applied to the samples: the Hertz model, an adhesion angle dependent model, and the modified Canham-Helfrich model. The Hertz model indicated a higher Young’s Modulus for vesicles without membrane proteins, but with large errors. The adhesion angle dependent model did not provide high enough sensitivity to determine any difference in stiffness between the two samples. The modified Canham-Helfrich model indicated a higher bending modulus for the vesicles with membrane proteins. The results highlight the importance of taking several measurements on each vesicle, in contrast to how the method is currently applied in research. / Extracellulära vesiklar är essentiella komponenter inom cell-till-cell-kommunikation, och har potentialen att kunna användas som sjukdomsmarkörer. Extracellulära vesiklars mekaniska egenskaper är ett aktivt forskningsfält där nya experimentella metoder och teoretiska modeller är under utveckling. I den här arbetet används atomkraftsmikroskopi för att undersöka de mekaniska egenskaperna av två prover av extracellulära vesiklar med olika mängd membranproteiner. Tre modeller för att utvärdera deras styvhet tillämpas: Hertz-modellen, en adhesionsvinkelberoende modell, och den modifierade Canham-Helfrichmodellen. Hertz-modellen indikerade högre elasticitetsmodul för provet med lägre antal membranprotein, men med stora fel i mätningarna. Den adhesionsvinkelbaserade modellen var inte känslig nog att påvisa några skillnader i styvhet mellan proverna. Den modifierade Canham-Helfrich-modellen indikerade att vesiklarna med membranprotein har högre böjmodul än veiklarna utan membranprotein. Resultaten understryker att det är viktigt att göra flertalet mätningar på varje vesikel, i kontrast mot hur modellen tillämpas i dagsläget.

A numerical model have been developed in order to describe and achieve deeper understanding of experimentally obtained I-V curves from Cu2O/ZnO p-n heterojunctions for potential use as future solar cell material. The model was created using the simulation software COMSOL Multiphysics® and their semiconductor module. To experimentally study the samples two approaches were taken: (1) macro-electrical measurements and (2) local I-V measurements using conductive AFM. The final model is one-dimensional, time dependent and with the ability to study photovoltaic effects of samples with different layer thickness at different voltage ramping speeds and different light irradiance. The model is also able to study the effects of using different contact materials by treating the contacts as ideal Schottky contacts. The dynamic behavior of a Cu_2O/ZnO heterojunction was studied by considering the systems response to a voltage step and the effect of changing the voltage ramping speed. The output from the step response, the current as a function of time, is varying a short time after a step has occurred before settling on to a steady value. The response also shows an overshoot of the current in the direction of the voltage step and the final steady value depends on whether the junction is conducting or not. The effects of this behavior on the shape of the I-V curves are witnessed when studying the different voltage ramping speeds. The voltage is ramped from 2 V to -2 V and back again for different speeds (V/s). The I-V curves have different shapes when sweeping the voltage in different directions and the magnitude increases with increasing speed. The photovoltaic effects were studied by applying different light irradiances. The behavior of the model agrees well with the theory for an ideal diode solar cell. An investigation was done of how the work function of the metal in contact with the Cu_2O affects the shape of the I-V curve under dark and illuminated conditions. The metal work function was changed from 4.5 eV to 6.5 eV in steps of 0.4 eV and does not affect the shape of the I-V curves much in dark after increasing it above 4.5 eV. The effects are more visible under illuminated conditions where a "step"-behavior appears for the lower values of the work function. Only one of the physical samples show a noticeable light effect. The macro-electrical measurement on this sample is compared with simulated results and are in qualitative agreement with each other. The agreement between the local electrical measurements and the simulated results is not as good with the current model.

InAs/InP multiwavelength quantum dash lasers are promising solutions to rising data loads in our telecommunications systems, as one laser chip can replace many lasers operating at a single wavelength. Quantum dashes are quasi-one-dimensional nanoparticles that offer equal or increased performance as laser gain media when compared to equivalent quantum well devices. InAs/InP quantum dashes are ideal for laser devices emitting in the C-band region, centred around 1550 nm. The quantum dashes in this thesis are epitaxially grown via the self assembled Stranski-Krastanow mode. Characterizing how structure and composition of these quantum dashes affect the energy level spacing and emission wavelengths is crucial for designing better performing telecommunications lasers. In this thesis a method for determining the average heights and widths of these nanoparticles from atomic force microscopy measurements of uncapped InAs/InGaAsP/InP quantum dashes is developed. Single quantum dash simulations are built in Crosslight Photonic Integrated Circuit Simulator (PICS3D) with the lowest energy transition tuned to photoluminescence peak wavelengths provided by National Research Council Canada. These simulations are used to determine the impact of quantum dash dimensions, compositions, and heterostructure changes to the overlap integrals and emission energies. Phosphorus concentration within the quantum dash and wetting layer can modify the predicted emission wavelength by ∼200 nm, and increasing quantum dash lengths beyond 200 nm has negligible effect on emission energy and energy level spacing. The sublayer thickness is increased from 0.1 to 1 nm, and shows that emission energy will increase for GaP sublayers and decrease for GaAs sublayers by up to 30 meV. The role of the wetting layer on energy level spacing is discussed and determined to increase the emission energy by ∼15 meV when the 0.5 nm wetting layer is removed for a 2 nm quantum dash. The role of As/P intermixing is investigated in three ways: by incorporating phosphorus concentration in (1) the quantum dash and wetting layer, (2) the wetting layer, and (3) the lower portion of the quantum dash without a wetting layer. There is negligible change in the overlap integral for these three cases with all other variables held constant, and the trends between each case remain the same. Further experimental analysis of buried InAs quantum dashes is recommended for compositional information. The implementation of variable strain profiles in this model is also recommended, in addition to developing vertically coupled quantum dash simulations. Finally, performing these simulations at varying temperatures will better represent the operating conditions of quantum dash lasers.

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There is a need for the development of new technologies for the early detection of disease. Diverse initiatives are underway in academia and the pharmaceutical and biotechnology industries to develop highly-sensitive, high-throughput methods to detect disease-relevant biomarkers at the single-cell level. Biomarkers can define the progress of a disease or efficacy of disease treatment, and can include nucleic acids (RNA, DNA), proteins, small molecules, or even specific cells. While discovery research in this area is accelerating, there are a number of current experimental limitations. Most existing methodologies require a relatively large sample size. Also, amplification-based detection technologies are destructive to sample, and errors in amplification can occur, leading to an incorrect diagnosis. Nanomaterial-based devices (nanodevices) offer the promise of label-free, amplification-free detection strategies. Such nanodevices could allow analysis of minute biological samples without the requirement for amplification or incorporation of reporter groups. Loss of sample, due to handling and processing would be minimized and the sample could be recovered for further analysis. Atomic force microscopy (AFM) allows topographic imaging and compressibility/elasticity measurement of biomolecules on solid supports. AFM can enable assays of ligand binding with single molecule detection capability. Certain nucleic acid types, in particular double-stranded (ds) RNA, can act as a biomarker for specific cancers (e.g. leukemia) and viral infection. dsRNA also is of interest since it is a conserved structural feature of precursors to gene-regulatory RNAs, including micro (mi) RNAs and short interfering (si) RNAs. This project demonstrates a single-step, label-free, amplification-free approach for detecting the interaction of biomolecules that bind and/or process dsRNA, using a nanomanipulated, self-assembled monolayer (SAM) of a ds[RNA-DNA] chimera as imprinting matrix, a reference nuclease as imprinting agent, and AFM for imprint-readout. The action of the dsRNA-specific enzyme, ribonuclease III (RNase III), as well as the binding of an inactive, dsRNA-binding RNase III mutant can be permanently recorded by the input-responsive action of a restriction endonuclease that cleaves an ancillary reporter site within the dsDNA segment. The resulting irreversible height change of the arrayed ds[RNA-DNA] chimera, as measured by atomic force microscopy, provides a distinct digital output for each type of input. These findings provide the basis for developing imprinting-based nano-biosensors, and reveal the versatility of AFM as a tool for characterizing the behaviour of highly-crowded biomolecules at the nanoscale. RNA-DNA heteroduplexes are biomarkers for specific inflammatory conditions of genetic origin, and also are the product of capture of an RNA (e.g., miRNA) by a complementary DNA sequence. The approach used here to detect RNA-DNA hybrids is based on the ability of alkylthiol-modified ssDNA molecules to form monolayers and nanomatrices on gold surfaces (as described above) with density-dependent thickness, which increases upon formation of RNA-DNA hybrids following addition of a complementary oligoribonucleotide. Changes in hybrid matrix thickness can be measured by AFM, using a reference monolayer. RNA-DNA hybrid formation as well as subsequent processing by RNase H can be observed as a height increase or decrease, respectively, of the monolayer. When Mg2+ is omitted to prevent RNA cleavage, but not protein binding, a significant height increase is observed. The height increase is not observed with the corresponding ssDNA or ssRNA nanomatrices, and only occurs with nanomatrices having a hybrid density above a defined threshold. The data indicate formation of a stable multimeric RNase H assembly on the hybrid nanomatrix which provides a robust signal that is nondestructive to the RNA. The implications of these findings are discussed with respect to development of novel detection methodologies for RNA, dsRNA, and RNA-DNA hybrids. / Chemistry

The heart, as a vital organ, must pump continuously to deliver oxygenated blood to the tissues of the body. The physical stress of pumping is supported by the extracellular matrix (ECM), a dynamic protein scaffold inside and around the heart. While a regulated ECM is required to maintain heart function, aberrant or excessive ECM remodelling, called fibrosis, is associated with disease states and is a hallmark of cardiovascular disease. One major trigger of cardiovascular disease is obesity, and fibrotic remodelling is known to occur in this context. In order to study the impact of increased body size on heart function and the molecular and biophysical characteristics of the ECM, a larval overgrowth model for obesity in the genetic model Drosophila melanogaster has been developed and characterised. This model produces giant larvae twice as heavy as their wildtype counterparts, and allows a unique opportunity to study changes in the cardiac ECM in a simple genetic model. Results demonstrate a remarkable ability of the ECM to accommodate this increase in size. The muscles of the heart are particularly robust, and there are no obvious observable defects to the matrix. Preliminary results suggest Collagen fibres are thicker and more disperse. When observing heart functionality, the cross-sectional area of the heart lumen is increased significantly in giant larvae, both at diastole and systole. However, giant larvae display defects in contraction of the heart tube, characterised by an inability to contract fully at systole. This results in a less than proportional increase in stroke volume, and an increase in heart rate. Heart function of giant larvae is clearly affected by the increase in body size. To quantify the impact to the biophysical structure of the ECM, an atomic force microscopy protocol is being developed. / Thesis / Master of Science (MSc) / A known side effect of cardiovascular disease is fibrosis of the heart, a form of pathological extracellular matrix (ECM) remodelling. Fibrosis causes the stiffening of heart muscle, leading to impaired cardiac function. One of the main risk factors for the development of cardiovascular disease is obesity, and fibrosis is known to occur in this context. I have characterised changes in the morphology and physiology of the heart in a Drosophila model for obesity. The resulting cardiac hypertrophy reveals significant plasticity in the heart ECM, while heart contraction and output is compromised.