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PhD (Physics) / Department of Physics / Understanding how and why superconductivity (SC) occurs in a given material has been very challenging for physicists for more than a hundred years, notwithstanding the major milestones, such as the London theory, the Landau-Ginzburg theory, and the BCS theory. The extreme challenge to predict the occurrence of SC is symbolized by the long string of unanticipated but breathtaking advances, i.e., the unexpected discoveries of cuprates and Fe-pnictides being the dramatic modern examples. Because of their incompatibility, the nucleation of SC near a ferromagnet is di cult and has never been realized except for the case that another superconductor provides proximity-boosted Cooper pairs. This perceived necessity to start with another superconductor is engrained in the exten- sive study of the proximity e ect in superconductor/ferromagnet (S/F) powder sample, where all the structures involve a superconductor with either stable or metastable struc- ture. Compounding the di culty, it is also generally recognized that SC with substantial Tc is favourable in low dimensionality because of strong quantum uctuation. In this thesis, we report a serendipitous nding of SC that emerges under the most implausible circumstances in low eld microwave absorption measurement. This new revelation may lead to unconventional avenues to explore novel SC for applications in superconducting spintronics. By means of a varienty of techniques, including EPR, SEM, FTIR, PPMS/VSM and XRD, nanonickel incorporated YBCO in di erent weighting factors have been studied. With its complex chemical structure and magnetic properties, Ni-YBCO is far from well understood and the magentic behavior of the system under di erent conditions is investi- gated. From the dilute mixture of nanonickel particles, it is found that groups of normal Josephson junctions (JJs) and JJs due to YBCO-nickel-YBCO interparticle weaklinks form as nickel is ferromagnetic. We experimentally show, for the rst time multiple phase reversals in the non-resonant microwave absorption (NRMA) spectra from Ni-YBCO pos- sibly, due to the formation of JJs. We also show that these multiple phase reversals then vii depend on microwave power and temperature. We argue that microwave power induced coherence among some groups of JJs and breaking of some of the weaker JJs can then lead to the disappearance of multiple phase reversals at higher microwave power levels. Further, we also report a role of pair breaking e ects that shall give a linear eld de- pendence of the derivative microwave absorption signal, which is essentially the NRMA signal. This pair-breaking e ect dominates at temperatures closer to Tc as expected thermodynamically. The presence of two peaks in the system, results in high permeability ferromagnet which acts as a magnetic short circuit for magnetic ux density and creates low reluctance path. A transition from normal to anomalous does not occur in this work, because of the possibility of junction in the sample. As predictable at the region around the origin where the weaklinks are supposed to be very strong for a very low doping or low nanonickel addition ( 0.5 % wt), not much e ect was observed. However, when the nanonickel addition is increased to 2 % and 3% we see a signi cant change in the magnetization and the associated hysteresis, indicating ux pinning. / NRF

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Much of recent progress in medical research and diagnostics has been enabled through the advances in molecular analysis technologies, which now permit the detection and analysis of single molecules with high sensitivity and specificity. Assay sensitivity is fundamentally limited by the efficiency of the detection method used for read-out. Inefficient detection systems are usually compensated for by molecular amplification at the cost of elevated assay complexity. This thesis presents microfluidic automation and digital quantification of targeted nucleic acid detection methods based on padlock and selector probes and rolling circle amplification (RCA). In paper I, the highly sensitive, yet complex circle-to-circle amplification assay was automated on a digital microfluidic chip. In paper II, a new RCA product (RCP) sensing principle was developed based on resistive pulse sensing that allows label free digital RCP quantification. In paper III, a microfluidic chip for spatial RCP enrichment was developed, which enables the detection of RCPs with an unprecedented efficiency and allows for deeper analysis of enriched RCPs through next generation sequencing chemistry. In paper IV, a smart phone was converted into a multiplex fluorescent imaging device that enables imaging and quantification of RCPs on slides as well as within cells and tissues. KRAS point mutations were detected (i) in situ, directly in tumor tissue, and (ii) by targeted sequencing of extracted tumor DNA, imaged with the smart phone RCP imager. This thesis describes the building blocks required for the development of highly sensitive low-cost RCA-based nucleic acid analysis devices for utilization in research and diagnostics.

This thesis focuses on inductive base sensor design at MHz range frequency. The background theory, design, experiments and results for a new magnetic particles sensor is presented. A new magnetic sensor based on a planar coil was investigated for DNA pathogen detection. Change in inductance of the planar coil due to the presence of magnetic particles with varying mass was measured. The experimental set-up consisted of different sized planar coil with associated electronics for inductance measurements. The best sensor performance was accomplished using two different inductors while oscillating at frequencies 2.4MHz using 9.5μH inductor and 7.2MHz with 85μH inductor. The sensor has very large signal to noise ratio (580×103), while the average amount of frequency drift was 0.58. This sensor was tested with various types of magnetic particles. In addition, iron-oxide nanoparticles were synthesized through water in oil microemulsion method and with an average size of 25nm. The best sensitivity achieved for detection of 50μg iron-oxide particles was with the bead size of 10nm. 81Hz frequency shift was attained in regard to that amount of particles. This research shows that increasing the resonance frequency to 7.2MHz can cause the larger output signal difference (frequency shift) in the presence of magnetic particles; however, the sensor stability is the most important factor for determining the detection resolution and sensitivity. The sensitivity is better if the sensor can detect smaller amount of magnetic sample. The results of this research demonstrate that while the sample consists of smaller size particles, the sensor can detect the lower amount of sample. This is due to the heating effect of nanoparticles. On the other hand the sample distance from the sensor has a major impact on the sensitivity too; the shorter the distance, the higher the sensitivity. This technique can potentially be extended to detect several different types of bacterial pathogens and can be modified for multiplex quantitative detection. This sensing technique will be incorporated into a handheld, disposable microfluidic chip for point-of-care diagnostics for sexually transmitted diseases.

Les nanoémulsions huile dans eau (H/E) sont utilisées depuis plus de 50 ans en clinique humaine comme source de lipides en nutrition parentérale. Si cette dernière décennie a vu émerger la mise à profit de cette forme comme véhicule de substances actives lipophiles, l’utilisation des nanoémulsions comme vecteur d'agents thérapeutique ou diagnostique reste encore sous-exploitée. L’objectif de cette thèse a été le développement d'une plateforme de nanoémulsions comme vecteur alternatif aux nanosystèmes classiquement utilisés. Deux applications ont été visées : le diagnostic de la plaque vulnérable d'athérosclérose et le traitement de la maladie de Parkinson. Les nanoémulsions ont été fonctionnalisées avec des anticorps humanisés dirigés contre l’athérome et chargées avec des particules magnétiques pour servir d’agent de contraste moléculaire pour l’imagerie par résonance magnétique (IRM) et pour une nouvelle technique : l’imagerie par particules magnétique (IPM). L'efficacité du nanosystème pour le ciblage de la plaque a été démontré sur des souris athéromateuses. L’inclusion de chromophores lipophiles originaux et ultrabrillants ainsi que la possibilité d'incorporer des substances actives ont permis d’ouvrir la voie vers le développement de formulations multimodales et théranostiques. Les nanoémulsions thérapeutiques contre Parkinson ont été développées pour rétablir le pH lysosomal des neurones dopaminergiques par l'encapsulation d'un polymère (PLGA). Ce défaut d’acidification favorise la mort cellulaire par l’accumulation de déchets dans les neurones. La formulation a été optimisée pour le passage intracérébral par voie intraveineuse ou intranasale. Les résultats montrent un passage cérébral in vivo par voie intraveineuse avec une confirmation in vitro de la régénération du pH. Les perspectives de ce travail sont la poursuite de la plateforme et l'ouverture vers de nouvelles applications comme l'hyperthermie magnétique dans les cancers. / Oil in water (O/W) nanoemulsions have been used for over 50 years in human clinics as a lipids source in parenteral nutrition. Even if nanoemulsions have recently emerged as vehicles for lipophilic active pharmaceutical ingredient (API) their use as a therapeutic or diagnostic agent is still under-exploited. The objective of this Ph.D thesis was to develop an nanoemulsions platform as an alternative to conventionally used nanosystems. In this work, 2 applications have been studied: the diagnosis of vulnerable plaque in atherosclerosis, and the treatment of Parkinson's disease. Nanoemulsions have been functionalized with humanized antibody targeting atheroma and loaded with magnetic particles as molecular contrast agents for magnetic resonance imaging (MRI) and an emerging technique: magnetic particle imaging (MPI). The successful plaque targeting has been demonstrated in atheromatous mice. The inclusion of original and ultra-bright lipophilic chromophores as well as the loading of API have paved the way to the development of multimodal and theranostic formulations. Therapeutic nanoemulsions against Parkinson’s disease have been developed to restore lysosomal pH of dopaminergic neurons with acidic polymer (PLGA). Acidification dysfunction leads to cell death due to the accumulation of waste inside neurons. The formulation has been optimized for brain delivery through intravenous or intranasal administration. The results show brain delivery in vivo trough intravenous injection associated with a pH rescue in vitro. The perspectives will focus on optimizing this platform and use it for new applications such as magnetic hyperthermia in cancers.

Iron oxide nanoparticles are of great interest as contrast agents for research and potentially clinical molecular magnetic resonance imaging (MRI). Biochemically modifying the surface coatings of the particles with proteins and polysaccharides enhances their utility by improving cell receptor specificity, increasing uptake for cell labeling and adding therapeutic molecules. Together with the high contrast they produce in MR images, these characteristics promise an expanding role for iron oxide nanoparticles and molecular MR imaging for studying, diagnosing and treating diseases at the molecular level. However, these contrast agents produce areas of signal loss with traditional MRI sequences that are not specific to the nanoparticles and cannot easily quantify the contrast agent concentration. With the expanding role of iron oxide nanoparticles in molecular imaging, new methods are needed to produce a quantitative contrast that is specific to the iron oxide nanoparticle. This dissertation presents a new method for detecting and quantifying iron oxide nanoparticles using an adiabatic preparation pulse and the failure of the adiabatic condition for spins diffusing near the particles. In the first aim, the theoretical foundation of the work is presented, and a Monte Carlo simulation supporting the proposed mechanism of the contrast is described. Adiabatic pulse prepared imaging sequences are also developed for imaging at 3 Tesla and 9.4 Tesla to highlight the translational potential of the approach for clinical examinations and scientific research, and the linear correlation of the contrast with iron concentration ideal for quantification is presented. Further, the physical characteristics of the nanoparticles and the parameters of the MRI sequence are modified to characterize the approach. In the second aim, the contrast is characterized in more realistic phantoms and in vitro, and a method to more accurately quantify nanoparticle concentration in the presence of magnetization transfer is presented. Finally, accelerated imaging methods are implemented to acquire the adiabatic contrast in a time compatible with in vivo imaging, and the technique is evaluated in an in vivo model of quantitative iron oxide nanoparticle imaging. Together, these aims present a method using an adiabatic preparation pulse to generate an MR contrast based on the microscopic magnetic field gradients surrounding the iron oxide nanoparticles that is suitable for in vivo quantitative, molecular imaging.

Present and future demonstrator designs were used to demonstrate the quality assurance of welds. The NDT methods tested on prototype demonstrator parts are: visual inspection, radius gauges, throat size gauge, liquid-penetrant testing, magnetic particle testing and ultrasonics with pulse echo and phased array. The other methods like eddy current, time of flight diffraction, radiography, impression test, macro test and infrared thermographs are currently being analyzed along with their inspection costs.   The control plans for present and future designs with corresponding present and future NDT methods are suggested to minimize a shift in process. Magnetic particle testing revealed a lack of fusion and cracks for fillet welds, whereas ultrasonic pulse echo and phased array identified an internal lack of fusion, inner pores/slag inclusions on butt welds. Ultrasonic PAUT & TOFD could be used for accurate defect identification and thermography for online identification of lack of penetration, depth of penetration and weld parameters. / Weight reduction by improved weld quality (WIQ)