The work presented in this thesis shows how tunneling spectroscopy techniques can be applied to metallic nanoparticles to obtain useful information about fundamental physical processes in nanoscopic length scales. At low temperatures, the discrete character of the energy spectrum of these particles, allows the study of spin-polarized current via resolved "electron-in-a-box" energy levels. In samples consisting of two ferromagnetic electrodes tunnel coupled to single aluminum nanoparticles, spin accumulation mechanisms are responsible for the observed spin-polarized current. The observed effect of an applied perpendicular magnetic field, relative to the magnetization orientation of the electrodes, indicates the suppression of spin precession in such small particles. More generally, in the presence of an external non-collinear magnetic field, it is the local field "felt" by the particle that determines the character of the tunnel current. This effect is also observed in the case where only one of the electrodes is ferromagnetic. In contrast to the non-magnetic case, ferromagnetic nanoparticles exhibit a much more complex energy spectrum, which cannot be accounted for, using the simple free-electron picture. It will be shown that interactions between quasi-particle excitations due to sequential electron tunneling and spin excitations in the particle are likely to play an important role in the observed temperature/voltage dependence of magnetic hysteresis loops.

In computed tomography (CT) cross-sectional images of the attenuation distribution within a slice are created by scanning radiographic projections of an object with a rotating X-ray source detector compound and subsequent reconstruction of the images from these projection data on a computer. CT can be made very fast by employing a scanned electron beam instead of a mechanically moving X-ray source. Now this principle was extended towards high-energy electron beam tomography with an electrostatic accelerator. Therefore a dedicated experimental campaign was planned and carried out at the Budker Insitute of Nuclear Physics (BINP), Novosibirsk. There we investigated the capabilities of BINP’s accelerators as an electron beam generating and scanning unit of a potential high-energy electron beam tomography device. The setup based on a 1 MeV ELV-6 (BINP) electron accelerator and a single detector. Besides tomographic measurements with different phantoms, further experiments were carried out concerning the focal spot size and repeat accuracy of the electron beam as well as the detector’s response time and signal to noise ratio.

We report the design and fabrication of a micro-mechanical oscillator for use in extremely small force detection experiments such as transverse force measurements of a moving vortex and Nuclear Magnetic Resonance Force Microscopy (NMRFM). We study the basic physics of the double torsional mechanical oscillator, and pursue double torsional oscillators with small spring constants, high resonance frequencies, and high quality factors. Using a series of semiconductor manufacturing techniques, especially using the electron-beam lithography technique, we successfully micro-fabricate double torsional mechanical oscillators from silicon-on-insulator wafers. We conduct characterization experiments to extract important parameters of a mechanical oscillator, including the resonance frequencies, spring constants, and quality factors. We focus on the four typical resonance modes of these oscillators, and then compare the force detection sensitivity of each mode. Eventually we apply these force sensitive oscillators to gold micro-mass measurements, and achieve very small mass detection. In the future we are going to continue to micro-fabricate thinner oscillators to reduce the spring constants, and improve the quality factors by designing more suitable geometric shapes and by pursuing annealing studies. Thus, we might be able to achieve single nuclear spin measurements using NMRFM. / text

<p>Electron beam therapy represents an underutilized area in radiation therapy. While electron radiation therapy has existed for many decades and electron beams with multiple energies are available on linear accelerators – the most common device to deliver radiation therapy – efforts to advance the field have been slow. In contrast, photon beam therapy has seen rapid advancements in the past decade, and has become the main modality for radiation therapy treatment. </p><p>This doctoral research project comprises the development of a novel treatment modality, dynamic electron arc radiotherapy (DEAR) that seeks to address challenges to clinical implementation of electron beam therapy by providing a technique that may be able to treat specific patient subsets with better outcomes than current techniques. This research not only focused on the development of DEAR, but also aimed to improve upon and introduce new tools and techniques that could translate to current clinical electron beam therapy practice. </p><p>The concept of DEAR is presented. DEAR represents a new conformal electron therapy technique with synchronized couch motion. DEAR utilizes the combination of gantry rotation, couch motion, and dose rate modulation to achieve desirable dose distributions in patient. The electron applicator is kept to minimize scatter and maintain narrow penumbra. The couch motion is synchronized with the gantry rotation to avoid collision between patient and the electron cone. </p><p>First, the feasibility of DEAR delivery was investigated and the potential of DEAR was demonstrated to improve dose distributions on simple cylindrical phantoms. DEAR was delivered on Varian’s TrueBeam linac in Research Mode. In conjunction with the recorded trajectory log files, mechanical motion accuracies and dose rate modulation precision were analyzed. Experimental and calculated dose distributions were investigated for a few selected energies (6 MeV and 9 MeV) and cut-out sizes (1x10 cm2 and 3x10 cm2 for a 15x15 cm2 applicator). Our findings show that DEAR delivery is feasible and has the potential to deliver radiation dose with high precision (RMSE of <0.1 MU, <0.1° gantry, and <0.1 cm couch positions) and good dose rate precision (1.6 MU/min). Dose homogeneity within ±2 % in large and curved targets can be achieved while comparable penumbra to a standard electron beam on a flat surface can be maintained. Further, DEAR does not require fabrication of patient-specific shields, which has hindered the widespread use of electron arc therapy. These benefits make DEAR a promising technique for conformal radiotherapy of superficial tumors.</p><p>Next, an accurate dose calculation framework for DEAR was developed since current commercial dose calculation systems cannot handle the dynamic nature of the DEAR. Comprehensive validations of vendor provided electron beam phase space files for Varian TrueBeam linacs against measurement data were assessed. In this framework, the Monte Carlo generated phase space files were provided by the vendor and used as input to the downstream plan-specific simulations including jaws, electron applicators, and water phantom computed in the EGSnrc environment. The phase space files were generated based on open field commissioning data. A subset of electron energies of 6, 9, 12, 16, and 20 MeV and open and collimated field sizes 3×3, 4×4, 5×5, 6×6, 10×10, 15×15, 20×20, and 25×25 cm2 were evaluated. Measurements acquired with a CC13 cylindrical ionization chamber and electron diode detector and simulations from this framework were compared for a water phantom geometry. The evaluation metrics include percent depth dose, orthogonal and diagonal profiles at depths R100, R50, Rp, and Rp+ for standard and extended source-to-surface distances (SSD), as well as cone and cut-out output factors. Agreement for the percent depth dose and orthogonal profiles between measurement and Monte Carlo were generally within 2% or 1 mm. The largest discrepancies were observed for depths within 5 mm from the phantom surface. Differences in field size, penumbra, and flatness for the orthogonal profiles at depths R100, R50, Rp, and Rp+ were within 1 mm, 1 mm, and 2%, respectively. Simulated and measured orthogonal profiles at SSDs of 100 and 120 cm showed the same level of agreement. Cone and cut-out output factors agreed well with maximum differences within 2.5% for 6 MeV and 1% for all other energies. Cone output factors at extended SSDs of 105, 110, 115, and 120 cm exhibited similar levels of agreement. The presented Monte Carlo simulation framework for electron beam dose calculations for Varian TrueBeam linacs for electron beam energies of 6 to 20 MeV for open and collimated field sizes from 3×3 to 25×25 cm2 were studied and results were compared to the measurement data with excellent agreement. </p><p>DEAR uses the superposition of many small fields for its delivery, as such accurate planning requires the knowledge of accurate small field dosimetry. Prior research has shown that previous versions of the clinically used eMC dose calculation algorithm (Varian Medical Systems, Inc., Palo Alto, CA) cannot accurately calculate small static electron fields, leading to discrepancies in the dose distributions and output. Further, the clinical treatment planning system, Eclipse, currently does not support the planning of dynamic electron radiation therapy. Therefore, the aforementioned validation was extended to small fields and compared to dose calculations from the treatment planning system.</p><p>Subsequently, small field optimization was explored. Monte Carlo simulations were performed using validated Varian TrueBeam phase space files for electron beam energies of 6, 9, 12, and 16 MeV and square (1x1, 2x2, 3x3, 4x4, and 5x5 cm2) and circular (1, 2, 3, 4, and 5 cm diameter) fields. Resulting dose distributions (kernels) were used for subsequent calculations. The following analyses were performed: (1) Comparison of composite square fields and reference 10x10 cm2 dose distributions and (2) Scanning beam deliveries for square and circular fields realized as the convolution of kernels and scanning pattern. Preliminary beam weight and pattern optimization were also performed. Two linear scans of 10 cm with/without overlap were modeled. Comparison metrics included depth and orthogonal profiles at dmax. (1) Composite fields regained reference depth dose profiles for most energies and fields within 5%. Smaller kernels and higher energies increased dose in the build-up and Bremsstrahlung region (30%, 16 MeV and 1x1 cm2), while reference dmax was maintained for all energies and composite fields. Smaller kernels (<2x2 cm2) maintained penumbra and field size within 0.2 cm, and flatness within 2 and 4% in the cross-plane and in-plane direction, respectively. Deterioration of penumbra for larger kernels (5x5 cm2) was observed. Balancing desirable dosimetry and efficiencies suggests that smaller kernels should be used at the target edges and larger kernels in the center of the target. (2) Beam weight optimization improves cross-plane penumbra (0.2 cm) and increases the field size (0.4 cm) on average. In-plane penumbra and field size remain unchanged. Overlap depends on kernel size and optimal overlap results in flatness ±2%. Dynamic electron beam therapy in virtual scanning mode is feasible by employing small fields to achieve desired dose distributions and acceptable efficiencies.</p><p>Further, tools to generally improve upon limitations in Monte Carlo simulations for electron beams were investigated. The phase space file contains a finite number of particle histories and can have very large file size, yet still contains inherent statistical noises. A characterization of the phase space file was investigated to overcome its inherent limitations. To characterize the phase space file, distributions for energy, position, and direction of all particles types were analyzed as piece-wise parameterized functions of radius. Subsequently, a pseudo phase space file was generated based on this characterization. Validation was assessed by directly comparing the original and pseudo phase space file, and by comparing the resulting dose distributions from Monte Carlo simulations using both phase space files. Monte Carlo simulations were run for energies 6, 9, 12, and 16 MeV and all standard field sizes 6x6, 10x10, 15x15, 20x20, and 25x25 cm2. Percent depth dose and orthogonal profiles at depths R100, R50, and Rp were evaluated. Histograms of the original and pseudo phase space file agree very well with correlation coefficients greater than 0.98 for all particle attributes. Dosimetric comparison between original and pseudo dose distributions yielded agreement within 2%/1mm for PDDs and profiles at all depths for all field sizes 6x6, 10x10, 15x15, 20x20, and 25x25 cm2 and energies 6, 9, 12, and 16 MeV. Phase space files were found to be successfully characterized by piece-wise distributions for energy, position, and direction as parameterized functions of radius and polar angle. This facilitates generation of sufficient particles at any statistical precisions.</p><p>Additionally, new hardware for improved DEAR capability was investigated. Few leaf electron collimators (FLEC) or electron MLCs (eMLC) are highly desirable for dynamic electron beam therapies as they produce multiple apertures within a single delivery to achieve conformal dose distributions. However, their clinical implementation has been challenging. Alternatively, multiple small apertures in a single cut-out with variable jaw sizes could be utilized in a single dynamic delivery. A Monte Carlo simulation study was performed to investigate the dosimetric characteristics of such an arrangement. Investigated quantities included: Energy (6 and 16 MeV), jaw size (1x1 to 22x22 cm2; centered to aperture), applicator/cut-out (15x15 cm2), aperture (1x1, 2x2, 3x3, and 4x4 cm2), and aperture placement (on/off central axis). Three configurations were assessed: (a) single aperture on-axis, (b) single aperture off-axis, and (c) multiple apertures. Reference was configuration (a) with the standard jaw size. Aperture placement and jaw size were optimized to maintain reference dosimetry and minimize leakage through unused apertures to <5%. Comparison metrics included depth dose and orthogonal profiles. Configuration (a) and (b): Jaw openings were reduced to 10x10 cm2 without affecting dosimetry (gamma 2%/1mm) regardless of on- or off-axis placement. For smaller jaw sizes, reduced surface (<2%, 5% for 1x1 cm2 aperture) and increased Bremsstrahlung (<2%, 10% for 1x1 cm2 aperture) dose was observed. Configuration (c): Optimal aperture placement was in the corners (order: 1x1, 4x4, 2x2, 3x3 cm2 for quadrants I, II, III, and IV) and jaw size were 2x2, 2x2, 3x3, and 7x7 cm2 and 7x7, 7x7, 10x10, and 10x10 cm2 for apertures: 1x1, 2x2, 3x3, 4x4 cm2 and energies 6 and 16 MeV, respectively. Asymmetric leakage was found from upper and lower jaws. Leakage was generally within 5% with a maximum of 10% observed for the 1x1 cm2 aperture irradiation. Multiple apertures in a single cut-out with variable jaw size can be used in a single dynamic delivery, thus providing a practical alternative to FLEC or eMLC.</p><p>Based on all the results from this project, DEAR has been found to be a feasible technique and demonstrates the potential to improve electron therapy.</p> / Dissertation

This dissertation describes the development of a new method for increasing the resolution of the current protein microarray technology, down to the single molecule detection level. By using a technique called size-dependent self-assembly, different proteins can be bound to different sized fluorescent nanostructures, and then located on a patterned silicon substrate based on the sized pattern which is closest to the size of the bead diameter.The protein nanoarray was used to detect antibody-antigen binding, specifically anti-mouse IgG binding to mouse IgG. The protein nanoarray is designed with the goal of analyzing rare proteins. However, common proteins, such as IgG, are used in the initial testing of the array functionality. Mouse IgG, representing rare proteins, is conjugated to fluorescent beads and the beads are immobilized on a patterned silicon surface. Then anti-mouse IgG binds to the mouse IgG on the immobilized beads. The binding of the antibody, anti-mouse IgG, to the antigen, mouse IgG is determined by fluorescent signal attenuation.The first objective was to bind charged nanoparticles, conjugated with proteins, to an oppositely charged silicon substrate. Binding of negatively charged gold nanoparticles (AuNP), conjugated with mouse IgG, to a positively charged silicon surface was successful.The second objective was to demonstrate the method of size-dependent self-assembly at the nanometer scale (<100 >nm). Different-sized, carboxylated, fluorescent beads and AuNP, which were conjugated with proteins, were serially added to a patterned polymethyl methacrylate (PMMA) coated silicon surface. Size-dependent self-assembly was successfully demonstrated, down to the nanometer scale.The final objective was to obtain a signal from antibody-antigen binding within the protein array. Conjugated fluorescent beads were bound to e-beam patterns and signal attenuation was measured when the antibodies bound to the conjugated beads. The size-dependent self-assembly is a valuable new method that can be used for the detection and quantification of proteins.

Aim and tasks of the work. The aim of this work is to investigate insufficiently analyzed variants of the electrodynamic super-wide-band slow-wave structures, create their models, improve methods of analysis, analyze properties of the systems and reveal potentiality of the traveling-wave cathode-ray tubes, slow-wave structures. In order to achieve the aim it is necessary: 1. To improve method for evaluation of non-linear distortions in the traveling-wave cathode-ray tubes and reveal possibilities of reduction of non-linear distortions. 2. To create models of the insufficiently analyzed variants of slow-wave structures and reveal properties of the slow-wave structures. 3. To reveal influence of periodical non-homogeneities on properties of slow-wave structures, simulate and reveal influence of transitions to properties of slow-wave structures and traveling-wav cathode-ray tubes. 4. To make investigation of potentiality of slow-wave structures and traveling-wave cathode-ray tubes and select variants of slow-wave structures that can guarantee wide band and high operating speed of the traveling-wave cathode-ray tubes. Scientific novelty and practical value. Models of insufficiently simulated slow-wave structures were created and their properties were analyzed. According to analysis and modeling results, variants of systems were selected that can guarantee the wide pass-band and high operating speed of the traveling-wave cathode-ray tubes. Using finite element method calculation... [to full text]

Aim and tasks of the work. The aim of this work is to investigate insufficiently analyzed variants of the electrodynamic super-wide-band slow-wave structures, create their models, improve methods of analysis, analyze properties of the systems and reveal potentiality of the traveling-wave cathode-ray tubes, slow-wave structures. In order to achieve the aim it is necessary: 1. To improve method for evaluation of non-linear distortions in the traveling-wave cathode-ray tubes and reveal possibilities of reduction of non-linear distortions. 2. To create models of the insufficiently analyzed variants of slow-wave structures and reveal properties of the slow-wave structures. 3. To reveal influence of periodical non-homogeneities on properties of slow-wave structures, simulate and reveal influence of transitions to properties of slow-wave structures and traveling-wav cathode-ray tubes. 4. To make investigation of potentiality of slow-wave structures and traveling-wave cathode-ray tubes and select variants of slow-wave structures that can guarantee wide band and high operating speed of the traveling-wave cathode-ray tubes. Scientific novelty and practical value. Models of insufficiently simulated slow-wave structures were created and their properties were analyzed. According to analysis and modeling results, variants of systems were selected that can guarantee the wide pass-band and high operating speed of the traveling-wave cathode-ray tubes. Using finite element method calculation... [to full text]

Two experiments explore the application of plasmonic nanoparticles to cellular pathology. The first devised a platform by which gold-silver nanoparticles act as differentiable labels for cell surface receptors under dark field imaging. By conjugating particles of various constitutions with receptor-targeting antibodies, particles scatter characteristically according to their plasmon peak. The second experiment programmed receptor placement via the patterning of two substrates and used the binding of SERS nanoparticles to explore the quantification of such targets at high-density. On one substrate, anchor pairs established receptors at specified distances in order to define the relationship between scattering intensity and the distance between SERS particles. On the second, anchor regions are filled with increasing densities of receptors and the particle-saturated substrates are probed to relate scattering intensity to particle density. This should discover the density-threshold between linear and non-linear scattering and inform the quantification of particles in the exponential density regime.

Two experiments explore the application of plasmonic nanoparticles to cellular pathology. The first devised a platform by which gold-silver nanoparticles act as differentiable labels for cell surface receptors under dark field imaging. By conjugating particles of various constitutions with receptor-targeting antibodies, particles scatter characteristically according to their plasmon peak. The second experiment programmed receptor placement via the patterning of two substrates and used the binding of SERS nanoparticles to explore the quantification of such targets at high-density. On one substrate, anchor pairs established receptors at specified distances in order to define the relationship between scattering intensity and the distance between SERS particles. On the second, anchor regions are filled with increasing densities of receptors and the particle-saturated substrates are probed to relate scattering intensity to particle density. This should discover the density-threshold between linear and non-linear scattering and inform the quantification of particles in the exponential density regime.

This thesis addresses nanostructure fabrication techniques based on electron beam lithography, which is the most widely employed nanofabrication techniques for R&D and for the prototyping or production of photo-mask or imprint mold. The focus is on the study of novel resist and development process, as well as pattern transfer procedure after lithography. Specifically, this thesis investigates the following topics that are related to either electron beam resists, their development, or pattern transfer process after electron beam lithography: (1) The dry thermal development (contrary to conventional solvent development) of negative electron beam resists polystyrene (PS) to achieve reasonably high contrast and resolution. (2) The solvent development for polycarbonate electron beam resist, which is more desirable than the usual hot aqueous solution of NaOH developer, to achieve a low contrast that is ideal for grayscale lithography. (3) The fabrication of metal nanostructure by electron beam lithography and dry liftoff (contrary to the conventional liftoff using a strong solvent or aqueous solution), to achieved down to ~50 nm resolution. (4) The study a novel electron beam resist poly(sodium 4-styrenesulfonate) (sodium PSS) that is water soluble and water developable, to fabricate the feature size down to ~ 40 nm. And finally, (5) The fabrication of gold nanostructure on a thin membrane, which will be used as an object for novel x-ray imaging, where we developed the fabrication process for silicon nitride membrane, electroplating of gold, and pattern transfer after electron beam lithography using single layer resist and tri-layer resist stack.