Influence of surface functionalization on the behavior of silica nanoparticles in biological systems

Personalized nanomedicine has been shown to provide advantages over traditional clinical imaging, diagnosis, and conventional medical treatment. Using nanoparticles can enhance and clarify the clinical targeting and imaging, and lead them exactly to the place in the body that is the goal of treatment. At the same time, one can reduce the side effects that usually occur in the parts of the body that are not targets for treatment. Nanoparticles are of a size that can penetrate into cells. Their surface functionalization offers a way to increase their sensitivity when detecting target molecules. In addition, it increases the potential for flexibility in particle design, their therapeutic function, and variation possibilities in diagnostics. Mesoporous nanoparticles of amorphous silica have attractive physical and chemical characteristics such as particle morphology, controllable pore size, and high surface area and pore volume. Additionally, the surface functionalization of silica nanoparticles is relatively straightforward, which enables optimization of the interaction between the particles and the biological system. The main goal of this study was to prepare traceable and targetable silica nanoparticles for medical applications with a special focus on particle dispersion stability, biocompatibility, and targeting capabilities. Nanoparticle properties are highly particle-size dependent and a good dispersion stability is a prerequisite for active therapeutic and diagnostic agents. In the study it was shown that traceable streptavidin-conjugated silica nanoparticles which exhibit a good dispersibility could be obtained by the suitable choice of a proper surface functionalization route. Theranostic nanoparticles should exhibit sufficient hydrolytic stability to effectively carry the medicine to the target cells after which they should disintegrate and dissolve. Furthermore, the surface groups should stay at the particle surface until the particle has been internalized by the cell in order to optimize cell specificity. Model particles with fluorescently-labeled regions were tested in vitro using light microscopy and image processing technology, which allowed a detailed study of the disintegration and dissolution process. The study showed that nanoparticles degrade more slowly outside, as compared to inside the cell. The main advantage of theranostic agents is their successful targeting in vitro and in vivo. Non-porous nanoparticles using monoclonal antibodies as guiding ligands were tested in vitro in order to follow their targeting ability and internalization. In addition to the targeting that was found successful, a specific internalization route for the particles could be detected. In the last part of the study, the objective was to clarify the feasibility of traceable mesoporous silica nanoparticles, loaded with a hydrophobic cancer drug, being applied for targeted drug delivery in vitro and in vivo. Particles were provided with a small molecular targeting ligand. In the study a significantly higher therapeutic effect could be achieved with nanoparticles compared to free drug. The nanoparticles were biocompatible and stayed in the tumor for a longer time than a free medicine did, before being eliminated by renal excretion. Overall, the results showed that mesoporous silica nanoparticles are biocompatible, biodegradable drug carriers and that cell specificity can be achieved both in vitro and in vivo.

Surface studies of limestones and dolostones : characterisation using various techniques and batch dissolution experiments with hydrochloric acid solutions

In this thesis, stepwise titration with hydrochloric acid was used to obtain chemical reactivities and dissolution rates of ground limestones and dolostones of varying geological backgrounds (sedimentary, metamorphic or magmatic). Two different ways of conducting the calculations were used: 1) a first order mathematical model was used to calculate extrapolated initial reactivities (and dissolution rates) at pH 4, and 2) a second order mathematical model was used to acquire integrated mean specific chemical reaction constants (and dissolution rates) at pH 5. The calculations of the reactivities and dissolution rates were based on rate of change of pH and particle size distributions of the sample powders obtained by laser diffraction. The initial dissolution rates at pH 4 were repeatedly higher than previously reported literature values, whereas the dissolution rates at pH 5 were consistent with former observations. Reactivities and dissolution rates varied substantially for dolostones, whereas for limestones and calcareous rocks, the variation can be primarily explained by relatively large sample standard deviations. A list of the dolostone samples in a decreasing order of initial reactivity at pH 4 is: 1) metamorphic dolostones with calcite/dolomite ratio higher than about 6% 2) sedimentary dolostones without calcite 3) metamorphic dolostones with calcite/dolomite ratio lower than about 6% The reactivities and dissolution rates were accompanied by a wide range of experimental techniques to characterise the samples, to reveal how different rocks changed during the dissolution process, and to find out which factors had an influence on their chemical reactivities. An emphasis was put on chemical and morphological changes taking place at the surfaces of the particles via X-ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscopy (SEM). Supporting chemical information was obtained with X-Ray Fluorescence (XRF) measurements of the samples, and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) and Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) measurements of the solutions used in the reactivity experiments. Information on mineral (modal) compositions and their occurrence was provided by X-Ray Diffraction (XRD), Energy Dispersive X-ray analysis (EDX) and studying thin sections with a petrographic microscope. BET (Brunauer, Emmet, Teller) surface areas were determined from nitrogen physisorption data. Factors increasing chemical reactivity of dolostones and calcareous rocks were found to be sedimentary origin, higher calcite concentration and smaller quartz concentration. Also, it is assumed that finer grain size and larger BET surface areas increase the reactivity although no certain correlation was found in this thesis. Atomic concentrations did not correlate with the reactivities. Sedimentary dolostones, unlike metamorphic ones, were found to have porous surface structures after dissolution. In addition, conventional (XPS) and synchrotron based (HRXPS) X-ray Photoelectron Spectroscopy were used to study bonding environments on calcite and dolomite surfaces. Both samples are insulators, which is why neutralisation measures such as electron flood gun and a conductive mask were used. Surface core level shifts of 0.7 ± 0.1 eV for Ca 2p spectrum of calcite and 0.75 ± 0.05 eV for Mg 2p and Ca 3s spectra of dolomite were obtained. Some satellite features of Ca 2p, C 1s and O 1s spectra have been suggested to be bulk plasmons. The origin of carbide bonds was suggested to be beam assisted interaction with hydrocarbons found on the surface. The results presented in this thesis are of particular importance for choosing raw materials for wet Flue Gas Desulphurisation (FGD) and construction industry. Wet FGD benefits from high reactivity, whereas construction industry can take advantage of slow reactivity of carbonate rocks often used in the facades of fine buildings. Information on chemical bonding environments may help to create more accurate models for water-rock interactions of carbonates.

Energy and raw material consumption analysis of powder bed fusion: case study: CNC machining and laser additive manufacturing

Laser additive manufacturing (LAM), known also as 3D printing, is a powder bed fusion (PBF) type of additive manufacturing (AM) technology used to manufacture metal parts layer by layer by assist of laser beam. The development of the technology from building just prototype parts to functional parts is due to design flexibility. And also possibility to manufacture tailored and optimised components in terms of performance and strength to weight ratio of final parts. The study of energy and raw material consumption in LAM is essential as it might facilitate the adoption and usage of the technique in manufacturing industries. The objective this thesis was find the impact of LAM on environmental and economic aspects and to conduct life cycle inventory of CNC machining and LAM in terms of energy and raw material consumption at production phases. Literature overview in this thesis include sustainability issues in manufacturing industries with focus on environmental and economic aspects. Also life cycle assessment and its applicability in manufacturing industry were studied. UPLCI-CO2PE! Initiative was identified as mostly applied exiting methodology to conduct LCI analysis in discrete manufacturing process like LAM. Many of the reviewed literature had focused to PBF of polymeric material and only few had considered metallic materials. The studies that had included metallic materials had only measured input and output energy or materials of the process and compared to different AM systems without comparing to any competitive process. Neither did any include effect of process variation when building metallic parts with LAM. Experimental testing were carried out to make dissimilar samples with CNC machining and LAM in this thesis. Test samples were designed to include part complexity and weight reductions. PUMA 2500Y lathe machine was used in the CNC machining whereas a modified research machine representing EOSINT M-series was used for the LAM. The raw material used for making the test pieces were stainless steel 316L bar (CNC machined parts) and stainless steel 316L powder (LAM built parts). An analysis of power, time, and the energy consumed in each of the manufacturing processes on production phase showed that LAM utilises more energy than CNC machining. The high energy consumption was as result of duration of production. Energy consumption profiles in CNC machining showed fluctuations with high and low power ranges. LAM energy usage within specific mode (standby, heating, process, sawing) remained relatively constant through the production. CNC machining was limited in terms of manufacturing freedom as it was not possible to manufacture all the designed sample by machining. And the one which was possible was aided with large amount of material removed as waste. Planning phase in LAM was shorter than in CNC machining as the latter required many preparation steps. Specific energy consumption (SEC) were estimated in LAM based on the practical results and assumed platform utilisation. The estimated platform utilisation showed SEC could reduce when more parts were placed in one build than it was in with the empirical results in this thesis (six parts).

Analytic evaluation of three-phase short circuit demagnetization and hysteresis loss risk in rotor-surface-magnet Permanent-Magnet Synchronous Machines

Permanent magnet synchronous machines (PMSM) have become widely used in applications because of high efficiency compared to synchronous machines with exciting winding or to induction motors. This feature of PMSM is achieved through the using the permanent magnets (PM) as the main excitation source. The magnetic properties of the PM have significant influence on all the PMSM characteristics. Recent observations of the PM material properties when used in rotating machines revealed that in all PMSMs the magnets do not necessarily operate in the second quadrant of the demagnetization curve which makes the magnets prone to hysteresis losses. Moreover, still no good analytical approach has not been derived for the magnetic flux density distribution along the PM during the different short circuits faults. The main task of this thesis is to derive simple analytical tool which can predict magnetic flux density distribution along the rotor-surface mounted PM in two cases: during normal operating mode and in the worst moment of time from the PM’s point of view of the three phase symmetrical short circuit. The surface mounted PMSMs were selected because of their prevalence and relatively simple construction. The proposed model is based on the combination of two theories: the theory of the magnetic circuit and space vector theory. The comparison of the results in case of the normal operating mode obtained from finite element software with the results calculated with the proposed model shows good accuracy of model in the parts of the PM which are most of all prone to hysteresis losses. The comparison of the results for three phase symmetrical short circuit revealed significant inaccuracy of the proposed model compared with results from finite element software. The analysis of the inaccuracy reasons was provided. The impact on the model of the Carter factor theory and assumption that air have permeability of the PM were analyzed. The propositions for the further model development are presented.