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.

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.

The effect of cationic-anionic polyelectrolyte multilayer surface treatment on inkjet ink spreading and print quality

The focus of the work reported in this thesis was to study and to clarify the effect of polyelectrolyte multilayer surface treatment on inkjet ink spreading, absorption and print quality. Surface sizing with a size press, film press with a pilot scale coater, and spray coating, have been used to surface treat uncoated wood-free, experimental wood-free and pigmentcoated substrates. The role of the deposited cationic (polydiallydimethylammonium chloride, PDADMAC) and anionic (sodium carboxymethyl cellulose, NaCMC) polyelectrolyte layers with and without nanosilica, on liquid absorption and spreading was studied in terms of their interaction with water-based pigmented and dye-based inkjet inks. Contact angle measurements were made in attempt to explain the ink spreading and wetting behavior on the substrate. First, it was noticed that multilayer surface treatment decreased the contact angle of water, giving a hydrophilic character to the surface. The results showed that the number of cationic-anionic polyelectrolyte layers or the order of deposition of the polyelectrolytes had a significant effect on the print quality. This was seen for example as a higher print density on layers with a cationic polyelectrolyte in the outermost layer. The number of layers had an influence on the print quality; the print density increased with increasing number of layers, although the increase was strongly dependent on ink formulation and chemistry. The use of nanosilica clearly affected the rate of absorption of polar liquids, which also was seen as a higher density of the black dye-based print. Slightly unexpected, the use of nanosilica increased the tendency for lateral spreading of both the pigmented and dye-based inks. It was shown that the wetting behavior and wicking of the inks on the polyelectrolyte coatings was strongly affected by the hydrophobicity of the substrate, as well as by the composition or structure of the polyelectrolyte layers. Coating only with a cationic polyelectrolyte was not sufficient to improve dye fixation, but it was demonstrated that a cationic-anionic-complex structure led to good water fastness. A threelayered structure gave the same water fastness values as a five-layered structure. Interestingly, the water fastness values were strongly dependent not only on the formed cation-anion polyelectrolyte complexes but also on the tendency of the coating to dissolve during immersion in water. Results showed that by optimizing the chemistry of the layers, the ink-substrate interaction can be optimized.

Metal oxides prepared through the nanocasting approach-mechanistic study, surface interactions and applications in separation

Mesoporous metal oxides are nowadays widely used in various technological applications, for instance in catalysis, biomolecular separations and drug delivery. A popular technique used to synthesize mesoporous metal oxides is the nanocasting process. Mesoporous metal oxide replicas are obtained from the impregnation of a porous template with a metal oxide precursor followed by thermal treatment and removal of the template by etching in NaOH or HF solutions. In a similar manner to the traditional casting wherein the product inherits the features of the mold, the metal oxide replicas are supposed to have an inverse structure of the starting porous template. This is however not the case, as broken or deformed particles and other structural defects have all been experienced during nanocasting experiments. Although the nanocasting technique is widely used, not all the processing steps are well understood. Questions over the fidelity of replication and morphology control are yet to be adequately answered. This work therefore attempts to answer some of these questions by elucidating the nanocasting process, pin pointing the crucial steps involved and how to harness this knowledge in making wholesome replicas which are a true replication of the starting templates. The rich surface chemistry of mesoporous metal oxides is an important reason why they are widely used in applications such as catalysis, biomolecular separation, etc. At times the surface is modified or functionalized with organic species for stability or for a particular application. In this work, nanocast metal oxides (TiO2, ZrO2 and SnO2) and SiO2 were modified with amino-containing molecules using four different approaches, namely (a) covalent bonding of 3-aminopropyltriethoxysilane (APTES), (b) adsorption of 2-aminoethyl dihydrogen phosphate (AEDP), (c) surface polymerization of aziridine and (d) adsorption of poly(ethylenimine) (PEI) through electrostatic interactions. Afterwards, the hydrolytic stability of each functionalization was investigated at pH 2 and 10 by zeta potential measurements. The modifications were successful except for the AEDP approach which was unable to produce efficient amino-modification on any of the metal oxides used. The APTES, aziridine and PEI amino-modifications were fairly stable at pH 10 for all the metal oxides tested while only AZ and PEI modified-SnO2 were stable at pH 2 after 40 h. Furthermore, the functionalized metal oxides (SiO2, Mn2O3, ZrO2 and SnO2) were packed into columns for capillary liquid chromatography (CLC) and capillary electrochromatography (CEC). Among the functionalized metal oxides, aziridinefunctionalized SiO2, (SiO2-AZ) showed good chemical stability, and was the most useful packing material in both CLC and CEC. Lastly, nanocast metal oxides were synthesized for phosphopeptide enrichment which is a technique used to enrich phosphorylated proteins in biological samples prior to mass spectrometry analysis. By using the nanocasting technique to prepare the metal oxides, the surface area was controlled within a range of 42-75 m2/g thereby enabling an objective comparison of the metal oxides. The binding characteristics of these metal oxides were compared by using samples with different levels of complexity such as synthetic peptides and cell lysates. The results show that nanocast TiO2, ZrO2, Fe2O3 and In2O3 have comparable binding characteristics. Furthermore, In2O3 which is a novel material in phosphopeptide enrichment applications performed comparably with standard TiO2 which is the benchmark for such phosphopeptide enrichment procedures. The performance of the metal oxides was explained by ranking the metal oxides according to their isoelectric points and acidity. Overall, the clarification of the nanocasting process provided in this work will aid the synthesis of metal oxides with true fidelity of replication. Also, the different applications of the metal oxides based on their surface interactions and binding characteristics show the versatility of metal oxide materials. Some of these results can form the basis from which further applications and protocols can be developed.