Functionalization and characterization of magnetic nanoparticles for biomedical applications

Die vorliegende Arbeit beschäftigt sich mit der Oberflächenfunktionalisierung von MnO Nanopartikeln (NP). Durch die Verwendung und Verbesserung verschiedener Polymere durch die Einbindung von Poly (Ethylen Glycol) (PEG), gelang es, die Löslichkeit dieser Nanopartikel in wässrigen Lösungen sowie in Körperflüssigkeiten zu erhöhen. Zusätzlich konnten diese Nanopartikel deutlich besser steril filtriert werden und zeigten eine erhöhte Aktivität alsrnKontrastmittel im MRT. Vorläufige Ergebnisse für die Verwendung von Silika als Schutzhülle für MnO NP werden ebenfalls kurz erläutert. Die verwendeten Polymere besaßen dabei zugängliche Aminogruppen, die eine weitere Funktionalisierung durch Bio-aktiver Gruppen ermöglichte. Der Nachweis einer erfolgreichen Bindung durch verschiedene Methoden wie SDS-PAGE, Western- und Northern Blot sowie die Verwendung unterschiedlicher FluoreszenzMessungen wird ebenfalls diskutiert. MnO NP und anderer magnetischer NP werden weiterhin auf ihr toxisches Verhalten gegenüber Caki1 und HeLa Zellen getestet. Dabei zeigte sich, dass MnO NP, im Gegensatz zu einigen Kupferoxiden, quasi nicht toxisch waren und das Proliferationsverhalten dieser Zellen quasi nicht beeinflussten. Weiterhin wurde ein Fluoreszenzfarbstoff, konkret Protoporphyrin IX, an die Oberfläche von MnO NP angebracht.Diese konnten dann erfolgreich als Kontrastmittel in der MRT verwendet werden und zeigten vielversprechende Ergebnisse für die Photodynamische Therapie. Desweiteren wird die Synthese des Antikörpers gegen p53 ausführlich erläutert. Dabei wurde genau darauf geachtet,dass dieser Antikörper dann an MnO NP gebunden werden kann.

Functional polymer based nanoparticles : development of defined complex structures as basis for in-vitro and in-vivo applications

In Rahmen der vorliegenden Arbeit wurde ein neuartiger Zugang zu einer Vielzahl von Polymerstrukturen auf Basis des klinisch zugelassenen Polymers Poly(N-(2-Hydroxypropyl)-methacrylamide) (PHPMA) entwickelt. Der synthetische Zugang beruht zum einen auf der Verwendung von Reaktivesterpolymeren und zum anderen auf der Reversible Addition Fragmentation Chain Transfer (RAFT) Polymerisationsmethode. Diese Form einer kontrollierten radikalischen Polymerisation ermöglichte es, neben der Synthese von besser definierten Homopolymeren auch statistische und Blockcopolymere herzustellen. Die Reaktivesterpolymere können durch einfache Aminolyse in HPMA-basierte Systeme überführt werden. Somit können sie als eine vielversprechende Basis zur Synthese von umfangreichen Polymerbibliotheken angesehen werden. Die hergestellten Polymere kombinieren verschiedene Funktionalitäten bei konstantem Polymerisationsgrad. Dies ermöglicht eine Optimierung auf eine gezielte Anwendung hin ohne den Parameter der Kettenlänge zu verändern.rnIm weiteren war es durch Verwendung der RAFT Polymerisation möglich partiell bioabbaubare Blockcopolymere auf Basis von Polylactiden und HPMA herzustellen, in dem ein Kettentransferreagenz (CTA) an ein wohl definiertes Polylactid Homopolymer gekoppelt wurde. Diese Strukturen wurden in ihrer Zusammensetzung variiert und mit Erkennungsstrukturen (Folaten) und markierenden Elementen (Fluoreszenzfarbstoffe und +-emittierenden Radionukleide) versehen und im weiteren in vitro und in vivo evaluiert.rnAuf Grund dieser Errungenschaften war es möglich den Einfluss der Polymermikrostruktur auf das Aggregationsverhalten hin mittel Lichtstreuung und Fluoreszenzkorrelationsspektroskopie zu untersuchen. Es konnte gezeigt werden, dass erst diese Informationen über die Überstrukturbildung die Kinetik der Zellaufnahme erklären können. Somit wurde die wichtige Rolle von Strukturwirkungsbeziehungen nachgewiesen.rnSomit konnte neben der Synthese, Charakterisierung und ersten biologischen Evaluierungen ein Beitrag zum besseres Verständnis zur Interaktion von polymeren Partikeln mit biologischen Systemen geleistet werden.

Functional poly(phosphoester)s : the olefin metathesis route

Diese Dissertation zeigt zum ersten Mal den Ansatz gesättigte und ungesättigte Poly(Phosphorester) herzustellen, deren Polymergerüst und Seitenketten durch präzises Anbring-en von funktionellen und/oder solubilisierenden Gruppen modifiziert werden können. Durch Kombinieren der Vorteile der Olefinmetathese mit der Vielseitigkeit der Phos-phorchemie, eröffnet dieser variable Ansatz den Zugang zu einer neuen Klasse ungesättigter Poly-phosphate. Die zu Grunde liegende Idee ist das maßgeschneiderte Anpassen der Architektur und der Mikrostruktur dieser Polymere. Lineare, verzweigte, markierte und telechele Poly(Phosphorester) können in großem Maßstab mit hohen Funktionalisierungsgrad hergestellt werden.rnEiner der größten Vorteile dieses Ansatzes ist es, das Polymerrückrat modifizieren zu können, was weder bei der Ringöffnungs- noch bei klassischen Polymerisationen möglich ist, bei denen nur eine limitierte Anzahl an Monomeren existieren.rnDie Eigenschaften des Phosphors werden in neue Polymerarchitekturen übertragen, was von Nutzen für flammenhemmenden Materialen und Anwendung bei Gewebetherapeutika ist. Diese Doktorarbeit führt auch einzigartige Poly(Phosphorester) ein, welche im Feld der Op-toelektronik als Sauerstofffänger eingesetzten werden können. Die beschriebenen Synthese-vorschriften können einfach in größeren Maßstab durchgeführt werden und sind vielversprechend für industrielle Anwendungen, da ungesättigte Polyester einen sehr wichtigen Markt repräsentieren.

Novel materials for direct X-ray detectors based on semiconducting organic polymers

Conventional inorganic materials for x-ray radiation sensors suffer from several drawbacks, including their inability to cover large curved areas, me- chanical sti ffness, lack of tissue-equivalence and toxicity. Semiconducting organic polymers represent an alternative and have been employed as di- rect photoconversion material in organic diodes. In contrast to inorganic detector materials, polymers allow low-cost and large area fabrication by sol- vent based methods. In addition their processing is compliant with fexible low-temperature substrates. Flexible and large-area detectors are needed for dosimetry in medical radiotherapy and security applications. The objective of my thesis is to achieve optimized organic polymer diodes for fexible, di- rect x-ray detectors. To this end polymer diodes based on two different semi- conducting polymers, polyvinylcarbazole (PVK) and poly(9,9-dioctyluorene) (PFO) have been fabricated. The diodes show state-of-the-art rectifying be- haviour and hole transport mobilities comparable to reference materials. In order to improve the X-ray stopping power, high-Z nanoparticle Bi2O3 or WO3 where added to realize a polymer-nanoparticle composite with opti- mized properities. X-ray detector characterization resulted in sensitivties of up to 14 uC/Gy/cm2 for PVK when diodes were operated in reverse. Addition of nanoparticles could further improve the performance and a maximum sensitivy of 19 uC/Gy/cm2 was obtained for the PFO diodes. Compared to the pure PFO diode this corresponds to a five-fold increase and thus highlights the potentiality of nanoparticles for polymer detector design. In- terestingly the pure polymer diodes showed an order of magnitude increase in sensitivity when operated in forward regime. The increase was attributed to a different detection mechanism based on the modulation of the diodes conductivity.

Boron nitride nanotubes : synthesis, characterization, functionalization, and potential applications

Boron nitride nanotubes (BNNTs) are structurally similar to carbon nanotubes (CNTs), but exhibit completely different physical and chemical properties. Thus, BNNTs with various interesting properties may be complementary to CNTs and provide an alternative perspective to be useful in different applications. However, synthesis of high quality of BNNTs is still challenging. Hence, the major goals of this research work focus on the fundamental study of synthesis, characterizations, functionalization, and explorations of potential applications. In this work, we have established a new growth vapor trapping (GVT) approach to produce high quality and quantity BNNTs on a Si substrate, by using a conventional tube furnace. This chemical vapor deposition (CVD) approach was conducted at a growth temperature of 1200 °C. As compared to other known approaches, our GVT technique is much simpler in experimental setup and requires relatively lower growth temperatures. The as-grown BNNTs are fully characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), electron energy loss spectroscopy (EELS), Energy Filtered Mapping, Raman spectroscopy, Fourier Transform Infra Red spectroscopy (FTIR), UV-Visible (UV-vis) absorption spectroscopy, etc. Following this success, the growth of BNNTs is now as convenient as growing CNTs and ZnO nanowires. Some important parameters have been identified to produce high-quality BNNTs on Si substrates. Furthermore, we have identified a series of effective catalysts for patterned growth of BNNTs at desirable or pre-defined locations. This catalytic CVD technique is achieved based on our finding that MgO, Ni or Fe are the good catalysts for the growth of BNNTs. The success of patterned growth not only explains the role of catalysts in the formation of BNNTs, this technique will also become technologically important for future device fabrication of BNNTs. Following our success in controlled growth of BNNTs on substrates, we have discovered the superhydrophobic behavior of these partially vertically aligned BNNTs. Since BNNTs are chemically inert, resistive to oxidation up to ~1000°C, and transparent to UV-visible light, our discovery suggests that BNNTs could be useful as self-cleaning, insulating and protective coatings under rigorous chemical and thermal conditions. We have also established various approaches to functionalize BNNTs with polymeric molecules and carbon coatings. First, we showed that BNNTs can be functionalized by mPEG-DSPE (Polyethylene glycol-1,2-distearoyl-sn-glycero-3-phosphoethanolamine), a bio-compatible polymer that helps disperse and dissolve BNNTs in water solution. Furthermore, well-dispersed BNNTs in water can be cut from its original length of >10µm to(>20hrs). This success is an essential step to implement BNNTs in biomedical applications. On the other hand, we have also succeeded to functionalize BNNTs with various conjugated polymers. This success enables the dispersion of BNNTs in organic solvents instead of water. Our approaches are useful for applications of BNNTs in high-strength composites. In addition, we have also functionalized BNNTs with carbon decoration. This was performed by introducing methane (CH4) gas into the growth process of BNNT. Graphitic carbon coatings can be deposited on the side wall of BNNTs with thicknesses ranging from 2 to 5 nm. This success can modulate the conductivity of pure BNNTs from insulating to weakly electrically conductive. Finally, efforts were devoted to explore the application of the wide bandgap BNNTs in solar-blind deep UV (DUV) photo-detectors. We found that photoelectric current generated by the DUV light was dominated in the microelectrodes of our devices. The contribution of photocurrent from BNNTs is not significant if there is any. Implication from these preliminary experiments and potential future work are discussed.

MAGNETO-PHOTONIC CRYSTALS FOR OPTICAL SENSING APPLICATIONS

Among the optical structures investigated for optical sensing purpose, a significant amount of research has been conducted on photonic crystal based sensors. A particular advantage of photonic crystal based sensors is that they show superior sensitivity for ultra-small volume sensing. In this study we investigate polarization changes in response to the changes in the cover index of magneto-optic active photonic band gap structures. One-dimensional photonic-band gap structures fabricated on iron garnet materials yield large polarization rotations at the band gap edges. The enhanced polarization effects serve as an excellent tool for chemical sensing showing high degree of sensitivity for photonic crystal cover refractive index changes. The one dimensional waveguide photonic crystals are fabricated on single-layer bismuth-substituted rare earth iron garnet films ((Bi, Y, Lu)3(Fe, Ga)5O12 ) grown by liquid phase epitaxy on gadolinium gallium garnet substrates. Band gaps have been observed where Bragg scattering conditions links forward-going fundamental waveguide modes to backscattered high-order waveguide modes. Large near-band-edge polarization rotations which increase progressively with backscattered-mode order have been experimentally demonstrated for multiple samples with different composition, film thickness and fabrication parameters. Experimental findings are supported by theoretical analysis of Bloch modes polarization states showing that large near stop-band edge rotations are induced by the magneto-photonic crystal. Theoretical and experimental analysis conducted on polarization rotation sensitivity to waveguide photonic crystal cover refractive index changes shows a monotonic enhancement of the rotation with cover index. The sensor is further developed for selective chemical sensing by employing Polypyrrole as the photonic crystal cover layer. Polypyrrole is one of the extensively studied conducting polymers for selective analyte detection. Successful detection of aqueous ammonia and methanol has been achieved with Polypyrrole deposited magneto-photonic crystals.

Query Technologies and Applications for Program Comprehension

Industrial software systems are large and complex, both in terms of the software entities and their relationships. Consequently, understanding how a software system works requires the ability to pose queries over the design-level entities of the system. Traditionally, this task has been supported by simple tools (e.g., grep) combined with the programmer's intuition and experience. Recently, however, specialized code query technologies have matured to the point where they can be used in industrial situations, providing more intelligent, timely, and efficient responses to developer queries. This working session aims to explore the state of the art in code query technologies, and discover new ways in which these technologies may be useful in program comprehension. The session brings together researchers and practitioners. We survey existing techniques and applications, trying to understand the strengths and weaknesses of the various approaches, and sketch out new frontiers that hold promise.

DNA-Grafted Supramolecular Polymers: Helical Ribbon Structures Formed by Self-Assembly of Pyrene-DNA Chimeric Oligomers

The controlled arraying of DNA strands on adaptive polymeric platforms remains a challenge. Here, the noncovalent synthesis of DNA-grafted supramolecular polymers from short chimeric oligomers is presented. The oligomers are composed of an oligopyrenotide strand attached to the 5′-end of an oligodeoxynucleotide. The supramolecular polymerization of these oligomers in an aqueous medium leads to the formation of one-dimensional (1D) helical ribbon structures. Atomic force and transmission electron microscopy show rod-like polymers of several hundred nanometers in length. DNA-grafted polymers of the type described herein will serve as models for the development of structurally and functionally diverse supramolecular platforms with applications in materials science and diagnostics.

Hierarchical self-assembly of the DNA-grafted supramolecular polymers

Conjugation of functional entities with a specific set of optical, mechanical or biological properties to DNA strands allows engineering of sophisticated DNA-containing architectures. Among various hybrid systems, DNA-grafted polymers occupy an important place in modern materials science. In this contribution we present the non-covalent synthesis and properties of DNA-grafted linear supramolecular polymers (SPs), which are assembled in a controllable manner from short chimeric DNA-pyrene oligomers. The synthetic oligomers consist of two parts: a 10 nucleotides long DNA chain and a covalently attached segment of variable number of phosphodiester-linked pyrenes. The temperature-dependent formation of DNA-grafted SPs is described by a nucleation-elongation mechanism. The high tendency of pyrenes to aggregate in water, leads to the rapid formation of SPs. The core of the assemblies consists of stacked pyrenes. They form a 1D platform, to which the DNA chains are attached. Combined spectroscopic and microscopic studies reveal that the major driving forces of the polymerization are π-stacking of pyrenes and hydrophobic interactions, and DNA pairing contributes to a lesser extent. AFM and TEM experiments demonstrate that the 1D SPs appear as elongated ribbons with a length of several hundred nanometers. They exhibit an apparent helical structure with a pitch-to-pitch distance of 50±15 nm. Since DNA pairing is a highly selective process, the ongoing studies are aimed to utilize DNA-grafted SPs for the programmable arrangement of functional entities. For example, the addition of non-modified complementary DNA strands to the DNA-grafted SPs leads to the cooperative formation of higher-order assemblies. Also, our experiments suggest that the fluorescent pyrene core of 1D ribbons serves as an efficient donor platform for energy transfer applications.

Hierarchical self-assembly of the DNA-grafted supramolecular polymers

Conjugation of functional entities with a specific set of optical, mechanical or biological properties to DNA strands allows engineering of sophisticated DNA-containing architectures. Among various hybrid systems, DNA-grafted polymers occupy an important place in modern materials science. In this contribution we present the non-covalent synthesis and properties of DNA-grafted linear supramolecular polymers (SPs), which are assembled in a controllable manner from short chimeric DNA-pyrene oligomers. The synthetic oligomers consist of two parts: a 10 nucleotides long DNA chain and a covalently attached segment of variable number of phosphodiester-linked pyrenes. The temperature-dependent formation of DNA-grafted SPs is described by a nucleation-elongation mechanism. The high tendency of pyrenes to aggregate in water, leads to the rapid formation of SPs. The core of the assemblies consists of stacked pyrenes. They form a 1D platform, to which the DNA chains are attached. Combined spectroscopic and microscopic studies reveal that the major driving forces of the polymerization are π-stacking of pyrenes and hydrophobic interactions, and DNA pairing contributes to a lesser extent. AFM and TEM experiments demonstrate that the 1D SPs appear as elongated ribbons with a length of several hundred nanometers. They exhibit an apparent helical structure with a pitch-to-pitch distance of 50±15 nm. Since DNA pairing is a highly selective process, the ongoing studies are aimed to utilize DNA-grafted SPs for the programmable arrangement of functional entities. For example, the addition of non-modified complementary DNA strands to the DNA-grafted SPs leads to the cooperative formation of higher-order assemblies. Also, our experiments suggest that the fluorescent pyrene core of 1D ribbons serves as an efficient donor platform for energy transfer applications.

Influence of polymers on microstructure and adhesive strength of cementitious tile adhesive mortars

The impact of polymer modification on the physical properties of cementitious mortars is investigated using a multimethod approach. Special emphasis is put on the identification and quantification of different polymer components within the cementitious matrix. With respect to thin-bed applications, particularly tile adhesives, the spatial distributions of latex, cellulose ether (CE), polyvinyl alcohol (PVA), and cement hydration products can be quantified. It is shown that capillary forces and evaporation induce water fluxes in the interconnected part of the pore system, which transport CE, PVA, and cement ions to the mortar interfaces. In contrast, the distribution of latex remains homogeneous. In combination with results from qualitative experiments, the quantitative findings allow reconstruction of the evolution from fresh to hardened mortar, including polymer film formation, cement hydration, and water migration. The resulting microstructure and the failure modes can be correlated with the final adhesive strength of the tile adhesive. The results demonstrate that skinning prior to tile inlaying can strongly reduce wetting properties of the fresh mortar and lower final adhesive strength.

Efficient Deployment of Mobile Detectors for Security Applications

We present a real-world problem that arises in security threat detection applications. The problem consists of deploying mobile detectors on moving units that follow predefined routes. Examples of such units are buses, coaches, and trolleys. Due to a limited budget not all available units can be equipped with a detector. The goal is to equip a subset of units such that the utility of the resulting coverage is maximized. Existing methods for detector deployment are designed to place detectors in fixed locations and are therefore not applicable to the problem considered here. We formulate the planning problem as a binary linear program and present a coverage heuristic for generating effective deployments in short CPU time. The heuristic has theoretical performance guarantees for important special cases of the problem. The effectiveness of the coverage heuristic is demonstrated in a computational analysis based on 28 instances that we derived from real-world data.

Development of Robotized Laser Welding Applications for Joining Thin Sheets

Laser Welding (LW) is more often used in manufacturing due to its advantages, such as accurate control, good repeatability, less heat input, opportunities for joining of special materials, high speed, capability to join small dimension parts etc. LW is dedicated to robotized manufacturing, and the fabrication cells are using various level of flexibility, from specialized robots to very flexible setups. This paper features several LW applications using two industrially-scaled manufacturing cells at UPM Laser Centre (CLUPM) of Polytechnical University of Madrid (Universidad Politécnica de Madrid). The one dedicated to Remote Laser Welding (RLW) of thin sheets for automotive and other sectors uses a CO2 laser of 3500 W. The second has a high flexibility, is based on a 6-axis ABB robot and a Nd:YAG laser of 3300 W, and is meant for various laser processing methods, including welding. After a short description of each cell, several LW applications experimented at CLUPM and recently implemented in industry are briefly presented: RLW of automotive coated sheets, LW of high strength automotive sheets, LW vs. laser hybrid welding (LHW) of Double Phase steel thin sheets, and LHW of thin sheets of stainless steel and carbon steel (dissimilar joints). The main technological issues overcame and the critical process parameters are pointed out. Conclusions about achievements and trends are provided.

Reduced order models for industrial thermo-fluid problems

A new method is presented to generate reduced order models (ROMs) in Fluid Dynamics problems of industrial interest. The method is based on the expansion of the flow variables in a Proper Orthogonal Decomposition (POD) basis, calculated from a limited number of snapshots, which are obtained via Computational Fluid Dynamics (CFD). Then, the POD-mode amplitudes are calculated as minimizers of a properly defined overall residual of the equations and boundary conditions. The method includes various ingredients that are new in this field. The residual can be calculated using only a limited number of points in the flow field, which can be scattered either all over the whole computational domain or over a smaller projection window. The resulting ROM is both computationally efficient(reconstructed flow fields require, in cases that do not present shock waves, less than 1 % of the time needed to compute a full CFD solution) and flexible(the projection window can avoid regions of large localized CFD errors).Also, for problems related with aerodynamics, POD modes are obtained from a set of snapshots calculated by a CFD method based on the compressible Navier Stokes equations and a turbulence model (which further more includes some unphysical stabilizing terms that are included for purely numerical reasons), but projection onto the POD manifold is made using the inviscid Euler equations, which makes the method independent of the CFD scheme. In addition, shock waves are treated specifically in the POD description, to avoid the need of using a too large number of snapshots. Various definitions of the residual are also discussed, along with the number and distribution of snapshots, the number of retained modes, and the effect of CFD errors. The method is checked and discussed on several test problems that describe (i) heat transfer in the recirculation region downstream of a backwards facing step, (ii) the flow past a two-dimensional airfoil in both the subsonic and transonic regimes, and (iii) the flow past a three-dimensional horizontal tail plane. The method is both efficient and numerically robust in the sense that the computational effort is quite small compared to CFD and results are both reasonably accurate and largely insensitive to the definition of the residual, to CFD errors, and to the CFD method itself, which may contain artificial stabilizing terms. Thus, the method is amenable for practical engineering applications. Resumen Se presenta un nuevo método para generar modelos de orden reducido (ROMs) aplicado a problemas fluidodinámicos de interés industrial. El nuevo método se basa en la expansión de las variables fluidas en una base POD, calculada a partir de un cierto número de snapshots, los cuales se han obtenido gracias a simulaciones numéricas (CFD). A continuación, las amplitudes de los modos POD se calculan minimizando un residual global adecuadamente definido que combina las ecuaciones y las condiciones de contorno. El método incluye varios ingredientes que son nuevos en este campo de estudio. El residual puede calcularse utilizando únicamente un número limitado de puntos del campo fluido. Estos puntos puede encontrarse dispersos a lo largo del dominio computacional completo o sobre una ventana de proyección. El modelo ROM obtenido es tanto computacionalmente eficiente (en aquellos casos que no presentan ondas de choque reconstruir los campos fluidos requiere menos del 1% del tiempo necesario para calcular una solución CFD) como flexible (la ventana de proyección puede escogerse de forma que evite contener regiones con errores en la solución CFD localizados y grandes). Además, en problemas aerodinámicos, los modos POD se obtienen de un conjunto de snapshots calculados utilizando un código CFD basado en la versión compresible de las ecuaciones de Navier Stokes y un modelo de turbulencia (el cual puede incluir algunos términos estabilizadores sin sentido físico que se añaden por razones puramente numéricas), aunque la proyección en la variedad POD se hace utilizando las ecuaciones de Euler, lo que hace al método independiente del esquema utilizado en el código CFD. Además, las ondas de choque se tratan específicamente en la descripción POD para evitar la necesidad de utilizar un número demasiado grande de snapshots. Varias definiciones del residual se discuten, así como el número y distribución de los snapshots,el número de modos retenidos y el efecto de los errores debidos al CFD. El método se comprueba y discute para varios problemas de evaluación que describen (i) la transferencia de calor en la región de recirculación aguas abajo de un escalón, (ii) el flujo alrededor de un perfil bidimensional en regímenes subsónico y transónico y (iii) el flujo alrededor de un estabilizador horizontal tridimensional. El método es tanto eficiente como numéricamente robusto en el sentido de que el esfuerzo computacional es muy pequeño comparado con el requerido por el CFD y los resultados son razonablemente precisos y muy insensibles a la definición del residual, los errores debidos al CFD y al método CFD en sí mismo, el cual puede contener términos estabilizadores artificiales. Por lo tanto, el método puede utilizarse en aplicaciones prácticas de ingeniería.