Dissertations / Theses on the topic 'Electrostatic Assembly'

The design of biocompatible synthetic surfaces is an important issue for medical applications. Surface modification techniques provide good approaches to control the interactions between living systems and implanted materials by modifying the surface characteristics. This thesis work demonstrates the feasibility and effectiveness of the novel and low-cost electrostatic self-assembly (ESA) technique for the manufacturing of biocompatible thin film coatings. The ESA process is based on the alternating adsorption of molecular layers of oppositely charged polymers/nanoparticles, and can be applied in the fabrication of well-organized multilayer thin films possessing various biocompatible properties. ESA multilayer assemblies incorporating various biomaterials including metal oxides and polymers were fabricated, the uniformity, thickness, layer-by-layer linearity, and surface morphology of the films were characterized by UV/vis spectroscopy, ellipsometry, and AFM imaging. Preliminary biocompatibility testing was conducted, concentrating on contact angle surface characterization and the in vitro measurements of protein adsorption. The use of Fourier Transform Infrared Reflection-Absorption Spectroscopy (FT-IRAS) for the investigation of the protein adsorption behavior upon the ESA multilayer films is presented.
Master of Science

The Electrostatic Self-Assembly (ESA) technique possesses great advantages over traditional thin film fabrication methods, making it an excellent choice for a number of applications in the fields of linear and nonlinear optics, electronics, sensing and surface coatings. The feasibility of fabricating linear optical interference filters by ESA methods is demonstrated in this thesis work. Basic single-anion/single-cation ESA films are synthesized and their optical parameters -- refractive index and average thickness for individual bilayer -- are investigated to provide a basis for the in-depth design of optical filters. High performance dielectric stack filters and narrowband and wideband antireflection coatings are designed using TFCalc simulation software and are fabricated by ESA. Both bulk film sensitivity and layer sensitivity to manufacturing errors are provided. The significant agreement between simulation and experiment demonstrates the strong capability of ESA to precisely control the refractive index and produce excellent thin film filters. The performance of optical thin film filters is largely enhanced compared to the results of previous methods. The experiment results indicate that the ESA process may be used to fabricate optical filters and other optical structures that require precise index profile control.
Master of Science

This study concentrates on two of the main processes involved in the fabrication of electrostatic valve assembly, thick resist photolithography and wet chemical etching of a polyamide film. The electrostatic valve has different orifice diameters of 25, 50, 75 and 100 μm. These orifice holes are to be etched in the silicon wafer with deep reactive ion etching. The photolithography process is developed to build a mask of 15 μm thick resist pattern on silicon wafer. This photo layer acts as a mask for deep reactive ion etching. Wet chemical etching process is developed to etch kapton polyamide film. This etched film is used as a stand off, gap between two electrodes of the electrostatic valve assembly. The criterion is to develop the processed using standard industry tools. Pre post etch effects, such as, surface roughness, etching pattern, critical dimensions on the samples are measured with Veeco profilometer.
M.S.
Other
Engineering and Computer Science
Electrical Engineering MSEE

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2005.
Includes bibliographical references (p. 187-193).
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Ionic colloidal crystals are here defined as multicomponent ordered colloidal structures stabilized by attractive electrostatic interactions. These crystals are colloidal analogues to ionic materials including zincblende, rocksalt, cesium chloride, and fluorite. A thermodynamic study revealed that the screening ratio, charge ratio, and monodispersity are critical parameters in ionic colloidal crystal (ICC) formation. Experimentally, small ordered regions were observed under ideal thermodynamic conditions. However, no larger crystalline regions were found in these samples. The kinetics of ICC formation was studied using a variety of computational techniques, including Brownian dynamics, Monte Carlo, and a Newton's method solver. These techniques have each elucidated properties and processing conditions that are important to crystallization. The Brownian dynamics and Monte Carlo simulations showed that the previous experiments were highly undercooled. Furthermore, a narrow crystallization window was found, demonstrating the need to create particle systems that meet the narrow parameter space where ICCs should be stable. Pair interaction potentials were evaluated for their accuracy using a Poisson-Boltzmann (PB) equation solver. The PB solver was also used to further refine crystalline formation energies so that systems can be more accurately tailored. A surprising result from the PB solver showed that the lowest formation energy occurs when the quantity of surface charges on both particles are equal. Although this result is not predicted by any colloidal pair potentials, it was verified experimentally. This further illustrates that thermal mobility in these systems can be sufficient to maintain a stable solution despite attractive electrostatic interactions. Tailoring particle systems to balance the thermal and electrostatic interactions should allow widespread crystallization. However, these conditions require highly monodisperse particles to be fabricated with controlled surface charge and sizes. Currently these particles are not widely available and further research in this area should aid in the full realization of the ICC concept. In conclusion, all results are integrated to predict which particle systems should be produced to allow the formation of large ordered structures.
by Garry R. Maskaly.
Ph.D.

This thesis is focused on the links between charge transfer (CT) at metalorganic (MO) interfaces, creation of surface dipoles and two-dimensional supra- molecular assembly. Although several examples can be found in the literature where molecular self-assembly on surfaces was in uenced by the formation of interfacial dipoles, only in a few cases were the results fully rationalised and only a posteriori. The MO interface resulting from the deposition of the molecules used for these studies (chosen for their relevance as building blocks for applications in organic opto-electronic, photovoltaic, or proposed organic spintronics devices) is usually very complex. This is mainly due to the chemical structure of these molecules and to their strong interaction with the substrate. A clear identification of the different fundamental processes (such as CT and formation of interfacial dipoles) is thus highly difficult. The approach followed in this thesis is markedly different: specific molecules were rationally designed and subsequently synthesised in order to obtain model systems where the different parameters could be clearly isolated and identified. The presented work is the result of a close collaboration with other two research groups: the organic synthetic chemistry group of Prof. D. Bonifazi and the theoretical group of Prof. A. De Vita. The study was addressed through a complementary multi-disciplinary theoretical and experimental investigation, including the synthesis of new molecules, the analysis of their self-assembly by scanning tunnelling microscopy and spectroscopy and the use of density functional theory calculations and Monte Carlo simulations for the theoretical modelling of the systems. A balance between omnipresent short-range van der Waals attractive forces and long-range repulsive interactions generated by CT at MO interfaces was found to be responsible for the spontaneous formation of novel classes of supramolecular structures. By selecting different metal substrates and by carefully modifying the molecular species through chemical synthesis, the CT was selectively inhibited or enabled. This strategy represents a new paradigm for predicting and controlling the molecular self-assembly at surfaces. Conversely, the appearance of specific molecular linkage patterns is used to reveal the occurrence of CT and provides a novel means for obtaining crucial information on the electronic properties and the energy level alignment of MO interfaces.

The pick-and-place of components to build up complex working machines, such as the robotic arms on automotive assembly lines, has been integral to the enormous success and complexity of modern heavy industry. Modern nanomanufacturing stands in stark contrast to this strategy, reliant instead on the two-dimensional patterning of radiation-sensitive resists to build high-density machines of relative simplicity. The driving goal of our research has thus been to develop a new method of manipulation that would allow the pick-and-place of nanoscale components to mirror that of the assembly lines. A manipulator that could reliably perform this process would open the door to a new age of complex nanomachines. After analysing the current state-of-the-art in nano-object manipulation, we decided to utilise a combination of voltage-driven electric fields with chemically functional monolayers to achieve this goal. The mechanism was intended to be highly compatible with a Scanning Probe Microscope-style tip that could act as the manipulator tool on such an assembly line. This led to the design of several devices that were intended to capture single nanoparticles from a colloidal suspension, which had a negative surface charge in solution. We used numerical simulations using the Guoy-Chapman model of ionic solutions to determine what electrical and geometrical parameters would create the best devices single particle selectivity. We then describe the fabrication of devices using nanolithography techniques including electron-beam lithography, thin-film deposition and etching. Scanning electron microscopy of these devices after voltage-driven assembly showed that the mechanism had very limited success with few incidences of nanoparticle funnelling. This led through several different troubleshooting analyses of the mechanism that identified a myriad of issues affecting these devices. Ultimately we successfully created a radical new approach that incorporated hydrophobic monolayers with polar surfaces. This method exploited the hydrophobic interaction to overcome the hydrostatic barrier and resulted in repeatable single-particle assembly onto devices in sub 5-minute timeframes. Another aspect identified in this work was that the electronic state of nano-objects and monolayers on device surfaces is very important, but is difficult to pinpoint even when data sheets are available. We developed an emerging method of open-loop Dual-Harmonic Kelvin Probe Microscopy to identify these materials by their electronic surface potentials, successfully performing measurements in electrolytes where nanomanipulation would take place. This line of research led to novel considerations of how the size of the nanoparticles fundamentally distorts KPM measurements. We identify this as an important and often ignored effect that must be considered when using probes to differentiate between different materials at the nanoscale.

Stent is one of the coronary angioplasty techniques that expands the narrowed coronary arteries due to the accumulation of fat, cholesterol and other substances in the lumen of the arteries. The major complication of stent is restenosis. Current development of drug-eluting stents shows successfully reduce the occurrence of restenosis. Other than using drugs, electrostatic self assembled (ESAd) thin films may be the potential candidates to prevent restenosis.

ESA is a process to fabricate thin films bases on the electrostatic attraction between two oppositely charges. We used this technique to fabricate four PVP films and four PEI films. All films were exanimated by XPS and AFM. XPS data showed our coatings were successfully fabricated on substrates. AFM images revealed PVP coating was uniform, but PEI coatings had different morphologies due to diffusion and pH during the process.

Three preliminary hemocompatibility testes were performed to evaluate the hemocompatibility of the coatings. Platelet adhesion study showed the thin films inhibited platelet adhesion. All thin films were able to inhibit coagulation and were less cytotoxic. The studies suggested the ESA films were potentially hemocompatible.
Master of Science

This dissertation demonstrates the feasibility of using novel electrostatic self-assembly (ESA) methods to fabricate linear and nonlinear optical thin films and components. The ESA process involves the layer-by-layer alternate adsorption of anionic and cationic complexes from aqueous solutions. Selection of the molecules in each layer, their orientation at the molecular level, and the order in which the layers are assembled determine the film's bulk optical, electronic, magnetic, thermal, mechanical and other properties. In this work, the capability of nanoscale control over film optical properties allowed the fabrication of complicated refractive index profiles required for linear optical interference filters. The inherent ordered nature of ESA films yielded extremely stable noncentrosymmetric thin films for second-order nonlinear optical applications. The ESA technique offers numerous advantages over conventional thin film fabrication methods and offers great potential in commercial applications such as reflectance and AR filters, EO waveguides and modulators and other optoelectronic devices. The structure of each monolayer in ESA films is dependent on the processing parameters, producing subsequent variations in bulk film properties both intentionally and incidentally. As this method is still in its infancy, variations in ESA processing methods, including process automation, are considered first in this document. These results allowed carefully controlled refractive index experiments and the synthesis of both step and graded index structures, several microns thick. Dielectric stack, Rugate, and antireflection optical interference filters were designed, synthesized and demonstrated. c(2) films of both commercially available polymer dyes and novel polymers designed specifically for the ESA process were demonstrated using second harmonic generation. UV/vis spectroscopy, ellipsometry and atomic force microscopy analysis are presented.
Ph. D.

Supramolecular self-assembly on metallic surfaces is the ideal playground for studying a variety of physical and chemical phenomena. Adsorbed molecules will diffuse and self-organise to form assemblies dictated by their functionalities, while the more or less pronounced metal reactivity will accordingly affect both the supramolecular patterns and the interfacial chemistry. Besides structural aspects, electronic properties are central in determining the energy level alignment at the heterojunction and, thus, the performance of organic-based devices. Notably, charge reorganisation at the metal-organic interface will produce surface dipoles, whose effect is to add electrostatic repulsion to the dispersion-driven supramolecular self-assembly and to change the work function of the surface. Herein, the relation between charge migration (i.e., the creation of surface dipoles) and molecular self-assembly is addressed by studying the behaviour of on-purpose designed molecular units on selected metals. We will show that choosing the substrate on the basis of its work function can selectively allow or inhibit the transfer of charge from the organic material to the electrode. When charge transfer occurs, the growing supramolecular structures exhibit a phase modulation driven by the presence of competing interactions. Moreover, the introduction of reactive moieties in formerly inert tectons will be identified as a suitable strategy for promoting the formation of interfacial dipoles upon surface-mediated chemical reactions. Our work paves the way for a more rational approach to the design of metal-organic systems, as we speculate that charge transfer effects and surface chemistry can be predicted at the stage of molecular design, at variance with the current trial and error approach used in the field of organic electronics. This thesis is based on multiscale theoretical modelling of selected metalmolecule couples and it is the result of a fruitful collaboration with the groups of Prof Davide Bonifazi (Université de Namur) and Prof Giovanni Costantini (University of Warwick).

Polymer/inorganic nanoparticle hybrid thin films, primarily composed of functional inorganic nanoparticles, are of great interest to researchers because of their interesting electronic, photonic, and optical properties. In the past two decades, layer-by-layer (LbL) assembly has become one of the most powerful techniques to fabricate such hybrid thin films. This method offers an easy, inexpensive, versatile, and robust fabrication technique for multilayer formation, with precisely controllable nanostructure and tunable properties. In this thesis, various ways to control the structure of hybrid thin films, primarily composed of polyelectrolytes and indium tin oxide (ITO), are the main topics of study. ITO is one of the most widely used conductive transparent oxides (TCOs) for applications such as flat panel displays, photovoltaic cells, and functional windows. In this work, polyethyleneimine (PEI) was used to stabilize the ITO suspensions and improve the film buildup rate during the LbL assembly of poly(sodium 4-styrenesulfonate) (PSS) and ITO. The growth rate was doubled due to the stronger interaction forces between the PSS and PEI-modified ITO layer. The assembly of hybrid films was often initiated by a polyelectrolyte precursor layer, and the characteristics of the precursor layer were found to significantly affect the assembly of the hybrid thin films. The LbL assembly of ITO nanoparticles was realized on several substrates, including cellulose fibers, write-on transparencies, silicon wafers, quartz crystals, and glasses. By coating the cellulose fibers with ITO nanoparticles, a new type of conductive paper was manufactured. By LbL assembly of ITO on write-on transparencies, transparent conductive thin films with conductivity of 10⁻⁴ S/cm and transparency of over 80 % in the visible range were also prepared. As a result of this work on the mechanisms and applications of LbL grown films, the understanding of the LbL assembly of polyelectrolytes and inorganic nanoparticles was significantly extended. In addition to working with ITO nanoparticles, this thesis also demonstrated the ability to grow bicomponent [PEI/SiO₂]n thin films. It was further demonstrated that under the right pH conditions, these films can be grown exponentially (e-LbL), resulting in much thicker films, consisting of mostly the inorganic nanoparticles, in much fewer assembly steps than traditional linearly grown films (l-LbL). These results open the door to new research opportunities for achieving structured nanoparticle thin films, whose functionality depends primarily on the properties of the nanoparticles.

Experiments show that MgSO4 salt has a non-monotonic effect as a function of MgSO4 concentration on the ejection of DNA from bacteriophage lambda. There is a concentration, N0, at which the minimum amount of DNA is ejected. At lower or higher concentrations, more DNA is ejected. We propose that this non-monotonic behavior is due to the overcharging of DNA at high concentration of Mg⁺² counterions. As the Mg⁺² concentration increases from zero, the net charge of ejected DNA changes its sign from negative to positive. N0 corresponds to the concentration at which DNA is neutral. Our theory fits experimental data well. The DNA-DNA electrostatic attraction is found to be -0.004 kBT/nucleotide. Simulations of DNA-DNA interaction of a hexagonal DNA bundle support our theory. They also show the non-monotonic DNA-DNA interaction and reentrant behavior of DNA condensation by divalent counterions. Three problems in understanding the capsid assembly for a retrovirus are studied: First, the way in which the viral membrane affects the structure of in vivo assembled HIV-1 capsid is studied. We show that conical and cylindrical capsids have similar energy at high surface tension of the viral membrane, which leads to the various shapes of HIV-1 capsids. Secondly, the problem of RNA genome packaging inside spherical viruses is studied using RNA condensation theory. For weak adsorption strength of capsid protein, most RNA genomes are located at the center of the capsid. For strong adsorption strength, RNA genomes peak near the capsid surface and the amount of RNA packaged is proportional to the capsid area instead its volume. Theory fits experimental data reasonably well. Thirdly, the condensation of RNA molecules by nucleocapsid (NC) protein is studied. The interaction between RNA molecules and NC proteins is important for the reverse transcription of viral RNA which relates to the viral infectivity. For strong adsorption strength of the NC protein, there is a screening effect by RNA molecules around a single NC protein.

The exploitation of colloidal building blocks with morphological and functional anisotropy facilitates the generation of complex structures with unique properties, which are not exhibited by isotropic particle assemblies. Herein, we demonstrate an easy and scalable bottom-up approach for the programmed assembly of hairy oppositely charged homogeneously decorated and Janus particles based on electrostatic interactions mediated by polyelectrolytes grafted onto their surface. Two different assembly routes are proposed depending on the target structures: raspberry-like/half-raspberry-like or dumbbell-like micro-clusters. Ultimately, stable symmetric and asymmetric microstructures could be obtained in a well-controlled manner for the homogeneous–homogeneous and homogeneous–Janus particle assemblies, respectively. The spatially separated functionalities of the asymmetric Janus particle-based micro-clusters allow their further assembly into complex hierarchical constructs, which may potentially lead to the design of materials with tailored plasmonics and optical properties.

The electrostatic self-assembly (ESA) method presents an effective application in the field of biosensing due to the uniform nanoscale structure. In previous research, a single mode fiber (SMF) sensor system had been investigated for the thin-film measurement due to the high fringe visibility. However, compared with a SMF sensor system, a multimode fiber (MMF) sensor system is lower-cost and has larger sensing area (the fiber core), providing the potential for higher sensing efficiency.

In this thesis, a multimode fiber-optic sensor has been developed based on extrinsic Fabry-Perot interferometry (EFPI) for the measurement of optical thickness in self-assembled thin film layers as well as for the immunosensing test. The sensor was fabricated by connecting a multimode fiber (MMF) and a silica wafer. A Fabry-Perot cavity was formed by the reflections from the two interfaces of the wafer. The negatively charged silica wafer could be used as the substrate for the thin film immobilization scheme. The sensor is incorporated into the white-light interferometric system. By monitoring the optical cavity length increment, the self-assembled thin film thickness was measured; the immunoreaction between immunoglobulin G (IgG) and anti-IgG was investigated.
Master of Science

DNA is the substance that encodes the genetic information that cells need to replicate and to produce proteins. The detection of DNA sequences is of great importance in a broad range of areas including genetics, pathology, criminology, pharmacogenetics, public health, food safety, civil defense, and environmental monitoring. However, the established techniques suffer from a number of problems such as the bulky size, high equipment costs, and time-consuming algorithms so that they are limited to research laboratories and cannot be applied for in-vivo situations. In our research, we developed a novel sensing scheme for DNA sequence detection, featuring sequence specificity, cost efficiency, speed, and ease of use. Without the need for labels or indicators, it may be ideal for direct in-cell application. The principle is simple. With capture DNA immobilized onto the probe by layer-by-layer selfassembly, the hybridization of a complementary strand of target DNA increases the optical thickness of the probe. Three kinds of sensors were developed. The optical fiber tip sensor has been demonstrated with good specificity and high sensitivity for target DNA quantities as small as 1.7 ng. To demonstrate the potential of this structure for practical applications, tularemia bacteria were tested. Two other micrometric structures were designed with specific advantages for different applications. The micro-fiber Bragg grating interferometer (Micro-FBGI) has the intrinsic temperature compensation capability. The micro-intrinsic Fabry-Perot interferometer (Micro-IFPI)features simple signal processing due to its simple configuration. Successful DNA immobilization and hybridization have been demonstrated onto the 25μm Micro-IFPI. Both structures have great potential for nanometric protrusion, allowing future in-cell DNA direct detection. In addition, its quick response time leads to the potential for express diagnosis. What's more, the idea of nanoscale probe has a broad impact in scanning near-field optical microscopy (SNOM), intracellular surgery in cell sensing, manipulation, and injection.
Ph. D.

La cellulose étant l'un des biopolymères les plus abondants, elle est employée dans ce travail de thèse sous sa forme nano-fibrille (2 à 5nm de diamètre et plusieurs microns de long) pour préparer des nanomatériaux durables. Les microfibrilles de cellulose (MFC) chargées positivement ou négativement sont assemblées en couches minces dans ces nanomatériaux par la méthode « Layer by Layer » (LbL) par trempage, pulvérisation ou spin assisté. Les différences entre ces films LbL à base de MFC et les films LbL à base de polymères standards sont discutées brièvement et sont reliées à la forme nanofibrillaire de la cellulose. Les MFC réagissent comme des nano-objets anisotropes et rigides. Les films LbL de MFC sont ensuite intégrés à des membranes de séparation, entre la couche polymérique de séparation et le support poreux, pour améliorer le débit à travers ces membranes. Ces films minces sont également déposés sur des aérogels de cellulose pour améliorer la stabilité de ces aérogels en milieu aqueux. Dans les deux applications, les résultats était encouragent et montre une validation de principe
Cellulose, one of the most abundant biopolymers, is used in this PhD work in its nanofibrillated form, 2-5 nm in diameter and microns long, to prepare sustainable nanomaterials. Both positively and negatively charged microfibrillated celluloses (MFC) are assembled in these nanomaterials using the versatile Layer by Layer (LbL) assembly methods: dipping, spray assisted-deposition and spin-assisted deposition. A brief comparison between the MFC based LbL assembled films and the standard polymeric LbL films is carried out. Thedifferences between the two species are related to the fibrillar form of cellulose. MFC behaves like rigid anisotropic nano-objects. MFC LbL assembled films are then integrated in separation membranes between active polymeric separation layers and a mechanically stable porous support to improve the flux through these membranes. MFC LbL assembled films are also coated on cellulosic aerogels to improve the wet stability of these aerogels. In both cases, results were encouraging and showed a proof of concept

The dispersion of graphene in 1,2-dichloroethane (DCE), its subsequent attachment at the water-DCE interface and the reduction of oxygen at the water-DCE interface proceeding via interfacial graphene have been investigated. Using addition of an electrolyte which screens surface charge, it was found that electrostatic repulsions play a significant role in determining the kinetic stability of lyophobic non-aqueous graphene dispersions. The onset of aggregation was determined and it was found that dispersions prepared from higher-oxygen content graphite were more stable than those prepared from lower-oxygen content graphite, indicating that oxygen content is important in determining the surface charge on graphene in non-aqueous dispersion. The presence of organic electrolyte was also found to promote assembly of graphene into a coherent film at the liquid-liquid interface. Measurement of the liquid-liquid interfacial tension and three-phase contact angle revealed that the energetics of particle attachment did not change in the presence of organic electrolyte, thus indicating a mechanism of inter-particle electrostatic repulsion minimisation through surface charge screening. Interfacial graphene was found to display a catalytic effect toward the oxygen reduction reaction at the water-DCE interface. A bipolar cell was developed which showed that this reaction occurs heterogeneously, with graphene acting as a conduit for electrons across the water-DCE interface.

Les nanoparticules d'argent, déjà largement utilisées en catalyse, optique et électronique, trouvent aujourd'hui de nouvelles applications comme l'imagerie, la photonique ou la détection chimique et biochimique. Parmi ces applications, certaines requièrent des morphologies particulières comme des bâtonnets ou des disques (films conducteurs, spectroscopie Raman exaltée) quand d'autres impliquent principalement une surface spécifique importante comme par exemple en catalyse hétérogène. Les nanoparticules métalliques anisotropes sont classiquement réalisées en deux étapes, séparant la formation des germes et la croissance de ceux-ci, afin de mieux en contrôler la morphologie mais la séparation en deux étapes rend le transfert à l'échelle industrielle délicat à cause des longues périodes d'incubation et de lavage nécessaires. Nous avons choisi de nous intéresser à la synthèse dirigée de nanoparticules anisotropes, en particulier des nanodisques d'argent, ainsi que leur assemblage, en solution et sur des surfaces. Dans nos travaux, nous avons retenu une approche permettant de réaliser les deux étapes de la formation de nanodisques d'argent dans un même milieu réactionnel. Le principe repose sur l'utilisation de deux réducteurs, l'un faible et l'autre fort, dont les cinétiques de réduction très différentes permettent le contrôle de l'anisotropie. Cette méthode est simple et permet de réduire le temps de synthèse mais nécessite un bon contrôle des différents paramètres expérimentaux. Le temps entre l'ajout des deux réducteurs détermine notamment la morphologie des objets formés. Il existe en réalité une gamme optimale pour ce temps qui dépend particulièrement de la température de la synthèse. Afin de faire varier les propriétés optiques de ces nanodisques, différentes stratégies peuvent être envisagées. Notre choix s'est tourné vers la formation d'assemblages, en solution dans un premier temps, puis sur des surfaces par des méthodes de dépôt. L'adsorption de molécules organiques bifonctionnelles peut permettre de réaliser des assemblages en solution : une des fonctions a une affinité avec l'argent et l'autre interagit avec les fonctions libres des autres nanoparticules grâce à des liaisons hydrogène ou électrostatiques par exemple. Les assemblages peuvent également être réalisés sur des surfaces. Nous nous sommes tournés vers des méthodes de dépôts originales, qui permettent des assemblages dirigés des nanodisques par voie électrostatique. Nous avons démontré que ces assemblages sont de bons candidats pour développer des substrats SERS micro-structurés
Silver nanoparticles, used extensively in catalysis, optics and electronics, are now emerging in new applications such as imaging, photonics or chemical and biochemical detection. Among these applications, some require particular morphologies such as rods or disks (conductive films, enhanced Raman spectroscopy) while others mainly involve a large specific surface area such as in heterogeneous catalysis. Anisotropic metal nanoparticles are traditionally produced in two stages, separating the formation of seeds and their growth, in order to better control their morphology. However, the two-stage synthesis makes the transfer on industrial scale difficult because of the long incubation time and the washing steps required. In this context, we decided to focus on the synthesis of anisotropic nanoparticles, in particular silver nanodisks, as well as their assembly in solution and on surfaces. In our work, we adopted an approach that allows to carry out the two stages of the formation of silver nanodisks in the same reaction medium. The principle is based on the use of two reducers, one weak and one strong, with different kinetic reduction rates, allowing the control of anisotropy. This method is simple and fast but requires good control of the experimental parameters. The time between the addition of the two reducers determines the morphology of the formed objects. There is actually an optimal range for this time, which depends particularly on the temperature of the synthesis. In order to vary the optical properties of these nanodisks, different strategies can be considered. We chose to form assemblies both in solution and on surfaces by different deposition techniques. The adsorption of bifunctional organic molecules can provoke the formation of assemblies in solution: one function has an affinity with silver and the other interacts with the free functions of the other nanoparticles through hydrogen or electrostatic bonds for example. Assemblies can also be made on surfaces. We have been working on original deposition method, which allow an oriented assembly of nanodisks through electrostatic forces.We have demonstrated that these assemblies are good candidates for developing micro-structured SERS substrates

Grâce à leurs propriétés physiques/chimiques uniques, les nanoparticules colloïdales sont au cœur de nombreuses applications innovantes. Afin de faciliter leur caractérisation ou de les intégrer dans des dispositifs fonctionnels, il est nécessaire de les assembler de manière dirigée sur des surfaces solides. Dans ce contexte, l’objectif de cette thèse est de mieux comprendre et d’optimiser la technique de nanoxérographie, méthode d’assemblage dirigé où des nanoparticules sont piégées sur des motifs de charges électrostatiques. Après un premier travail consistant à améliorer le procédé de nanoxérographie, trois problématiques spécifiques ont été adressées : (i) l’assemblage de particules micrométriques. Le couplage de simulations numériques et de manipulations expérimentales a permis d’identifier les paramètres clés de l’assemblage de telles particules colloïdales et d’élargir (facteur 100) la gamme de tailles de particules assemblables par nanoxérographie. (ii) l’analyse de l’assemblage multicouche. Par le biais de nanoparticules modèles luminescentes et par la mise en place d’un nouveau protocole d’assemblage, les critères clés génériques pour l’assemblage 3D de colloïdes par nanoxérographie ont été dégagés. (ii) l’assemblage dirigé de nanogels sensibles à un stimulus environnemental extérieur. L’utilisation d’un protocole d’assemblage optimisé a permis d’élaborer des assemblages de nanogels interactifs avec leur environnement et du faire du tri sélectif de ces nanoparticules sur une même surface
Owing to their unique physico-chemical properties, colloidal nanoparticles are building blocks for the creation of plentiful innovative devices. In order to make easier their characterization and to incorporate them into functional nano-devices, it is necessary to perfectly control their directed assemblies onto solid surfaces. In this context, this thesis’ purpose is to simultaneously better understand and optimize the nanoxerography method, which allows electrostatic and selective directing assemblies of nanoparticles onto charged patterns. After an optimization of the nanoxerography process, three specific problematics have been addressed: (1) micron-sized particles assembly. The combined use of numerical simulations and experiments enabled to unveil the key parameters involved in micron-sized particles assembly and to expend the particle size range foreseeable for an assembly by nanoxerography (factor 100). (2) the 3D assembly analysis. The influence of diverse parameters on the 3D assembly of luminescent model nanoparticles was quantified by using a new assembly protocol. The results gave the generic key criterions for the 3D assembly of colloids by nanoxerography. (3) directed assembly of nanogels sensitive to an external environmental stimulus. The use of an optimized protocol allowed elaborating nanogels assemblies interactive with their environment and to sort these nanoparticles onto the same surface

The ability of quantum dots to confine single charges at discrete energy levels makes them a promising platform for novel electronic and optoelectronic devices. Self-assembled quantum dots are of considerable interest because their size, shape, and material can be controlled during growth. These properties influence the confinement potential, thereby controlling the energy levels of the dot. However, the method of growth does not allow for positioning of the quantum dots which end up randomly distributed over the sample surface, making it difficult for lithographic techniques to access the quantum dots to perform either charge transport or charge sensing measurements so that single dot properties can be measured. An atomic force microscope (AFM) can be used to spatially access individual dots, and by applying a voltage between cantilever tip and back-electrode, the energy levels of individual dots can be measured as electrons are added to the dot one-by-one in the Coulomb blockade regime. The oscillating cantilever in these experiments is responsible for both loading the dots through electrical gating and also detecting tunneling events through a change in cantilever resonance frequency and/or cantilever dissipation. We use an AFM to measure the energy levels in few electron self-assembled InAs quantum dots. The charging energy, level spacing, and shell structure of single dots are extracted experimentally. We compare our results to a theoretical model that describes in detail the mechanism behind the dissipative electrostatic interaction due to the tunneling single-electrons.Examples of the electrostatic influence of the environment on the dots are also presented, and a method for using an AFM for characterizing electrostatic noise is demonstrated. Charge fluctuations are known to compromise the operation of electronic devices, especially for electrical components which are built in the micron and nano regime. Super bandgap irradiation leads to generation-recombination noise over the sample surface but not over the self-assembled quantum dots. We measure the generation-recombination noise with an AFM and compare the noise on and off the dot to show sub-20~nm spatial resolution, demonstrating the ability of AFM for characterizing noise arising from charge fluctuations within the sample with high spatial resolution.
La propriété qu'ont les points quantiques de confiner des charges élémentaires à des niveaux discrets d'énergie en font une plate-forme prometteuse pour la conception de nouveaux appareils électroniques et opto-électroniques. Les points quantiques auto-assemblés sont d'autant plus intéressants puisque leur taille, forme et matériau peuvent être contrôlés lors de leur croissance. Ces propriétés influencent le potentiel de confinement modifiant ainsi les niveaux d'énergies du point quantique. Toutefois, cette méthode de croissance ne permet pas de positionner les points quantiques et ceux-ci se retrouvent distribués aléatoirement sur la surface de l'échantillon. Cela rend difficile l'accès aux points quantiques par des techniques lithographiques pour effectuer des mesures de transport ou de détection de charge permettant d'en déterminer les propriétés.Un microscope à force atomique (AFM) permet d'accéder spatialement à des points quantiques individuels et en appliquant une tension électrique entre la pointe du cantilever et une électrode arrière, leurs niveaux d'énergies peuvent être mesurés au fur et à mesure que des électrons sont ajoutés dans un régime de blocage de Coulomb. Dans ces expériences, le cantilever oscillant est responsable simultanément du chargement des points par l'application d'une tension de grille et de la détection du passage d'électron par « effet tunnel » par un changement de fréquence de résonance et/ou de dissipation du cantilever.Nous utilisons un AFM pour mesurer les niveaux d'énergie dans des points quantiques à quelques électrons d'InAs auto-assemblés. L'énergie de chargement, l'espacement des niveaux et la configuration électronique de points individuels sont obtenus expérimentalement. Nous comparons nos résultats à un modèle théorique qui décrit en détail le mécanisme derrière l'interaction électrostatique dissipative due au passage d'électrons par « effet tunnel ».Des exemples de l'influence électrostatique de l'environnement sur les points quantiques sont aussi présentés, ainsi qu'une méthode pour utiliser l'AFM pour caractériser le bruit électrostatique. Les fluctuations de charge sont connues pour compromettre le bon fonctionnement des appareils électroniques et particulièrement des composants micro et nanométriques. L'irradiation de larges bandes d'énergie interdites produit un bruit de génération et de recombinaison à la surface de l'échantillon, mais pas sur les points quantiques auto-assemblés. Nous mesurons ce bruit avec un AFM et comparons les résultats obtenus sur la surface du point quantique et en dehors en démontrant qu'une résolution spatiale inférieure à 20 nm est réalisée. Nous démontrons ainsi qu'un AFM permet de caractériser le bruit provenant des fluctuations de charge d'un échantillon avec une haute résolution spatiale.

Doctor of Philosophy
Department of Physics
Jeremy D. Schmit
Diseases such as Alzheimer’s, Parkinson’s, eye lens cataracts, and Type 2 diabetes are the results of protein aggregation. Protein aggregation is also a problem in pharmaceutical industry for designing protein based drugs for long term stability. Disordered states such as precipitates and gels and ordered states such as crystals, micro tubules and capsids are both possible outcomes of protein–protein interaction. To understand the outcomes of protein–protein interaction and to find the ways to control forces, it is required to study both kinetic and equilibrium factors in protein–protein interactions. Salting in/salting out and Hofmeister effects are familiar terminologies used in protein science field from more than a century to represent the effects of salt on protein solubility, but they are yet to be understood theoretically. Here, we build a theory accounting both attractive and repulsive electrostatic interactions via the Poisson Boltzmann equation, ion–protein binding via grand cannonical partition function and implicit ion–water interaction using hydrated ion size, for describing salting in/salting out phenomena and Hofmeister and/or salt specific effect. Our model free energy includes Coulomb energy, salt entropy and ion–protein binding free energy. We find that the salting in behavior seen at low salt concentration near the isoelectric point of the protein is the output of Coulomb energy such that the addition of salt not only screens dipole attraction but also it enhances the monopole repulsion due to anion binding. The salting out behavior appearing after salting in at high salt concentration is due to a salt mediated depletion interaction. We also find that the salting out seen far from the isoelectric point of the protein is dominated by the salt entropy term. At low salt, the dominant effect comes from the entropic cost of confining ions within the aggregates and at high salt, the dominant effect comes from the entropy gain by ions in solution by enhancing the depletion attraction. The ion size has significant effects on the entropic term which leads to the salt specificity in the protein solubility. Crystal growth of anisotropic and fragile molecules such as proteins is a challenging task because kinetics search for a molecule having the correct binding state from a large ensemble of molecules. In the search process, crystal growth might suffer from a kinetic trap called self–poisoning. Here, we use Monte Carlo simulation to show why protein crystallization is vulnerable to the poisoning and how one can avoid such trap or recover crystal growth from such trap during crystallization. We show that self–poisoning requires only three minimal ingredients and these are related to the binding affinity of a protein molecule and its probability of occurrence. If a molecule attaches to the crystal in the crystallographic state then its binding energy will be high but in protein system this happens with very low probability (≈ 10−5). On the other hand, non–crystallographic binding is energetically weak, but it is highly probable to happen. If these things are realized, then it will not be surprising to encounter with self–poisoning during protein crystallization. The only way to recover or avoid poisoning is to alter the solution condition slightly such as by changing temperature or salt concentration or protein concentration etc.

A novel cyclopentadienylruthenium(II) thiolato Schiff base, [Ru(SC6H4NC(H)C6H4OCH2CH2SMe)(&eta
5-C2H5]2 was synthesized and deposited as a selfassembled monolayer (SAM) on a gold electrode. Effective electronic communication between the Ru(II) centers and the gold electrode was established by electrostatically cycling the Shiff base-doped gold electrode in 0.1 M NaOH from -200 mV to +600 mV. The SAMmodified gold electrode (Au/SAM) exhibited quasi-reversible electrochemistry. The integrity of this electro-catalytic SAM, with respect to its ability to block and electro-catalyze certain Faradaic processes, was interrogated using Cyclic and Osteryoung Square Wave voltammetric experiments. The formal potential, E0', varied with pH to give a slope of about - 34 mV pH-1. The surface concentration, &Gamma
, of the ruthenium redox centers was found to be 1.591 x 10-11 mol cm-2. By electrostatically doping the Au/SAM/Horseradish peroxidase at an applied potential of +700 mV vs Ag/AgCl, a biosensor was produced for the amperometric analysis of hydrogen peroxide, cumene hydroperoxide and tert-butylhydroperoxide. The electrocatalytic-type biosensors displayed typical Michaelis-Menten kinetics with their limits of detection of 6.45 &mu
M, 6.92 &mu
M and 7.01 &mu
M for hydrogen peroxide, cumene hydroperoxide and tert-butylhydroperoxide respectively.

Cellulose is the most abundant biopolymer on Earth as it is found in every plant cell wall; therefore, it represents one of the most promising natural resources for the fabrication of sustainable materials. In plants, cellulose is mainly used for structural integrity, however, some species organise cellulose in helicoidal nano-architectures generating strong iridescent colours. Recent research has shown that cellulose nanocrystals, CNCs, isolated from natural fibres, can spontaneously self-assemble into architectures that resemble the one producing colouration in plants. Therefore, CNCs are an ideal candidate for the development of new photonic materials that can find use to substitute conventional pigments, which are often harmful to humans and to the environment. However, various obstacles still prevent a widespread use of cellulose-based photonic structures. For instance, while the CNC films can display a wide range of colours, a precise control of the optical appearance is still difficult to achieve. The intrinsic low thermal stability and brittleness of cellulose-based films strongly limit their use as photonic pigments at the industrial scale. Moreover, it is challenging to integrate them into composites to obtain further functionality while preserving their optical response. In this thesis, I present a series of research contributions that make progress towards addressing these challenges. First, I use an external magnetic field to tune the CNC films scattering response. Then, I demonstrate how it is possible to tailor the optical appearance and the mechanical properties of the films as well as to enhance their functionality, by combining CNCs with other polymers. Finally, I study the thermal properties of CNC films to improve the retention of the helicoidal arrangement at high temperatures and to explore the potential use of this material in industrial fabrication processes, such as hot-melt extrusion.

碩士
國立成功大學
化學工程學系碩博士班
93
In this study, electrostatic layer-by-layer (ELBL) deposition technique was successfully utilized to assemble 20 bilayers of polyelectrolyte and nanocrystalline TiO2 particles. Particle size and zeta potential measurements revealed that the charge of two kinds of nanocrystalline TiO2 (Alfa Aesar TiO2, Degussa P25) may be controlled by varying pH value of solution. Furthermore, the sequential buildup of polyelectrolyte and TiO2 nanocrystalline on glass substrate was evidenced by quartz crystal microbalance (QCM) measurement. By analyzing surface morphology, cross-section structure, roughness, surface area, pore size distribution, porosity, and dye loading of the sintered nanocomposite films, ELBL assembly finds the potential for fabricating photoelectrode of DSSCs. A problematic issue, however, is that polyelectrolyte can not be completely removed. The residuals of polyelectrolyte left in the final TiO2 film seem to greatly affect the characteristics of the electrode. One of the purposes of this study is to reveal the difference in the feature of the mesoporous photoelectrodes resulting from this method and the conventional spin and doctor blade coating methods. The experimental results obtained so far show that thin films of more uniform thickness and surface morphology can be achieved by ELBL assembly. However, the results of surface area, pore size distribution, and dye loading were subjected to uncertainty. This may be due to the residuals of polyelectrolyte in the TiO2 films. Further studies are desirable to reveal the superiority of ELBL assembly in fabricating photoelectrodes.

The modification of surfaces with thin films is widely used to tailor physical and chemical properties of surfaces. This approach can provide "smart" surfaces with desired tunable properties. Polymer brushes represent a class of thin films, where the polymer chains are chemically end-grafted to the substrate. The chain functionality can be tailored by chemical composition, which allows the brushes to respond to external stimuli. In addition, polymer brushes may sterically stabilize colloids. Thus, polymer brushes are suitable candidates as a matrix for the incorporation of inorganic nanoparticles, like gold nanoparticles (AuNPs). AuNPs induce optical properties due to their surface plasmon resonance (SPR), which results in smart nanocomposite materials with tunable optical properties for the application as colorimetric sensors. The ability to control the particle amount and distribution within a brush matrix has a strong impact on fabrication of colorimetric sensors with optical properties on demand. In order to achieve brush/AuNP composites with desired properties, the thesis focuses on the impact of electrostatic interaction and hydrogen bonding on the formation of brush/AuNP composite materials. Here, pH-sensitive AuNPs are embedded into strong cationic and non-ionic polymer brushes. The electrostatic interactions and hydrogen bondings are tuned by changing the surface charge of the AuNPs through variations of pH value, while the charges of the brushes are not affected. The first part of the present thesis presents the assembly of pH-sensitive AuNPs into cationic polyelectrolyte brushes. In particular, the synergistic use of different characterization techniques clarify directly and indirectly effects of the electrostatic interaction on the structure, morphology and sensitivity of cationic brush/AuNP composites. The second part discusses the influence of using a non-ionic polymer brush on the assembly of pH-sensitive AuNPs. It is shown, that the nature of polymer brush has a crucial impact on the stabilization of incorporated AuNPs. This work demonstrates a novel approach to incorporate negatively charged AuNPs into non-ionic polymer brushes by using an electric field. Finally, the quality of brush/AuNP composites was experimental evaluated in terms of the long-term stability for the future prospect as colorimetric sensors. The thesis presents a fundamental understanding of smart coatings, where the particle-particle interaction as well as particle-brush interaction can be simply controlled by variation in pH value and governs their structure and responsive behavior.

Gyroscopes sense angular speed of the body on which they are mounted. Traditional mechanical gyroscopes are big, bulky, expensive, and hence limited to a few applications. With the advent of Micro-Electro-Mechanical Systems (MEMS), the size and cost of gyroscopes have reduced by orders of magnitude, which has led to their deployment on systems that traditionally did not employ inertial units. Today, Internet of Moving Things (IoMT), automobiles, and consumer electronics gadgets such as cell phones, pads, laptops, gaming consoles, etc., use MEMS accelerometers and gyroscopes. Despite their commercial deployment and success, MEMS accelerometer and gyroscopes remain an active area of research and development because of their growing potential of applications and newer technologies for increasing their functionality and reducing their cost. This work focuses on the complete design, fabrication, device level packaging, and characterization of two different types of MEMS gyroscopes|a dual mass electrostatic vibratory gyroscope and an electromagnetic ring gyroscope. We start by establishing a closed-form mathematical expression for gyroscope sensitivity relating to different design parameters. From the analysis, we present a case study on the effect of mismatch between the actuation frequency and the drive resonant frequency on the sensitivity of the gyroscope. Towards fabrication of MEMS electrostatic gyroscopes, we discuss several fabrication challenges involved in using the traditional SOI-on-glass method. Particularly, the alignment and residual stress issues are discussed in detail. Subsequently, we describe a modified SOI-on-glass fabrication method that success-fully overcomes these issues. A novel hybrid wafer bonding method is presented in conjunction with the modi ed SOI-on-glass process. The proposed process flow is demonstrated by realizing several capacitive MEMS structures. Subsequently, the fabricated devices are characterized for their electrical and mechanical responses showing negligible process-induced stresses. Further, we characterize some of the test-structures for their dynamic response under different ambient pressures. We report on the resonant frequency modulation of inertial MEMS structures due to squeeze lm stiffness over a range of working pressures. We show with experimental measurements and analytical calculations how the pressure-dependent air springs (squeeze lm stiffness) change the resonant frequency of an inertial MEMS structure by as much as five times. A detailed experimental methodology is discussed for finding static stiffness using AFM (Atomic Force Microscopy). Further, dynamic measurements are presented using a non-contact Laser Doppler Vibrometer under varying pressures. The experimental observations are compared with theoretical and FEM models. Finally, we implement the proposed SOI-on-glass fabrication method to fabricate a dual mass, single-axis, folded tuning fork, electrostatic gyroscope. We rigorously characterize the gyroscope structures for their electrical and mechanical response at the die level. We have also developed a drive and sense pre-amplifier circuit for electrostatic gyroscopes. Thus-fabricated gyroscopes have been packaged, and characterized at the device level with rates of rotation from 1 /s to 35 /s, giving a rate sensitivity of 60 V/ /s with a linearity of 99.9%. In a parallel development, we have also fabricated an electromagnetic ring gyroscope that exploits the inherent symmetry of the ring structure and uses relatively low voltage to produce sufficient electromagnetic force for actuation. The electromagnetic ring gyroscope realized in this work requires very thin Al electrical tracks on a suspended ring structure of Si and on the suspensions for electromagnetic actuation and sensing. The process innovation implemented here is a single wafer process with a patented technique (arising from this work) for electromigration preventive layer. The gyroscope thus fabricated has been packaged and characterized giving a sensitivity of 0.04 V/ /s. Although there is a fair amount of modelling and analysis presented in this thesis, the emphasis here is not on such analysis but on physical realization of the gyroscope. Consequently most of the innovations in this work are in fabrication processes and methods. The actual realization of an electrostatic gyroscope is a challenging task, particularly, in a university fab. We have been able to successfully fabricate and test two types of gyroscopes. The entire fabrication and characterization reported in this work has been carried out at the National Nano Fabrication Centre, Micro Nano Characterization Facility of the Centre for Nano Science and Engineering, IISc.
NPMASS

This dissertation presents chemical sensors that are based on an emerging optical fiber sensing technology for the determination of the presence and concentration of hydrogen peroxide (H2O2) at low concentrations. The motivation to determine hydrogen peroxide lies on the fact that this chemical species is generated as a by-product of the operation of hydrogen-based polymer electrolyte membrane fuel cells (PEMFCs), and the presence and formation of this peroxide has been associated with the chemical degradation that results in low durability of PEMFCs. Currently, there are no techniques that allow the hydrogen peroxide to be determined in situ in PEMFCs in a reliable manner, since the only report of this type of measurement was performed using electrochemical techniques, which can be affected by the environmental conditions and that can alter the proper operation of the PEMFCs. The sensors presented in this dissertation are designed to detect the presence and quantify hydrogen peroxide in solution at the conditions at which PEMFCs operate. Since they are made using fused silica optical fibers and are based on a spectroscopic technique to perform the detection of H2O2 , they are not affected by the electromagnetic fields or the harsh chemical environment inside PEMFCs. In addition, they are able to still detect the presence of H2O2 at the operating temperatures. The construction of the sensing film on the tip of an optical fiber and its small size (125 µm diameter), make the sensors here developed an ideal solution for being deployed in situ in PEMFCs, ensuring that they would be minimally invasive and that the operation of the fuel cell would not be compromised by the presence of the sensor. The sensors developed in this dissertation not only present design characteristics that are applicable to PEMFCs, they are also suitable for applications in other fields such as environmental, defense, and biological processes.
Graduate
0548
0756
0791
jfbotero@gmail.com

The Magnetospheric Multiscale mission led by NASA has been designed to study the micro-physics of Magnetic Reconnection in Earth's magnetosphere by using four identical spacecrafts with instruments with high temporal and spatial resolutions. Among these instruments are the Dual Ion Spectrometers (DIS) engineered to measure the 3D distribution of ion flux in space. The detector assembly of the DIS consists of Micro-Channel Plates (MCP) mounted in Chevron configuration. Centre d'Etude Spatiale des Rayonnements (CESR), Toulouse is responsible for the provision and testing of all fifty MCP pairs for this mission. The goal of the work was to participate in the testing and characterization of the first prototype of the MCPs. It was achieved by understanding the working and characteristics of the MCPs in general and getting familiar with the detector assembly of the DIS i.e. the MCP pair and the detector circuit board in particular. To perform the testing, it was necessary to understand the testing system as well. These topics are described in this report along with the testing procedure and the data analysis. The testing procedure was developed eventually after facing several problems during the testing. MCP pair characteristics like pulse height distributions, gain, resistance and the MCP operating voltages for the mission were determined on analyzing the data. Crosstalk was found in the circuit board of the detector assembly and has also been discussed.
Validerat; 20101217 (root)

博士
國立交通大學
應用化學系碩博士班
103
Conventional cancer treatments have many limitations which often fail to completely eradicate the tumor and cause damages to normal cells. Photodynamic therapy (PDT), by the excitation of photosensitizers with light to generate reactive oxygen species (ROSs) such as 1O2, has emerged as a noninvasive technique for cancer theranostics. However, the clinical use of many photosensitizers has been challenged by their nonspecific damage to normal tissues, environmental degradation and hydrophobicity...etc. To overcome the existing limitation and to enhance the selectivity of photodynamic therapy, we developed a simple electrostatic adsorption strategy to fabricate silica nanocomposite (Apt-MB-Si NPs) by sequentially functionalizing MUC1 aptamer for tumor targeting and hydrophilic photosensitizer methylene blue (MB) for the PDT application. We found effective generation of singlet oxygen could be achieved with low PS dosage and short irradiation time by current strategy.

Title: The study of the association behaviour of the amphiphilic copolymers in solutions containing low molar compounds by means of computer simulations. Author: Mgr. Karel Šindelka Department: Faculty of Science, Charles University Supervisor: Doc. Ing. Zuzana Limpouchová, Csc. Abstract This doctoral thesis focuses on the study of electrostatic self- and co-assembly in complex polymer solutions containing polyelectrolyte (PE) block copolymers together with surfactants, neutral homopolymers, or oppositely charged PEs using the dissipative particle dynamics (DPD). It was shown that the electro- static self-assembly depends not only on the cooperative interactions of oppo- sitely charged PE chains, but also on the amphiphilicity of PE species or on the polymer block compatibility, among other properties. PEs with incompatible blocks create well-defined core-shell structures, while large ill-defined crew-cut aggregates form from PEs with compatible blocks In non-stoichiometric mixtures of PEs with incompatible blocks, co-assembled nanoparticles are smaller than in stoichiometric mixtures and are charged. The destabilization of larger aggregates depends on how the PE charge surplus is introduced: the effect is strongest when the density of the surplus PE charge on the PE chains is increased and weakest when the...

In earlier research in our lab, the manipulation of microtubules on gold patterned silicon wafers was achieved by E-beam lithography, Poly (ethylene glycol) self assembled monolayers (PEG-SAMs) and electrophoresis. To develop a technique for delicate single microtubule manipulation, further studies need to be done on PEG-SAMs and electrophoresis. As a foundation of this goal, we examined the electric field in an aqueous solution between two planar electrodes and the compatibility of the antifouling property of PEG-SAMs with the electric field. For this purpose, the distribution of microbeads was analyzed using a Boltzmann distribution. The amount of adsorbed microtubules on a PEG-SAM was examined to test the compatibility of the antifouling property of a PEG-SAM with concomitant exposure to electric field. It is shown that the product of the electric field and the effective charge of the microbead does not have a linear relation with the applied electric potential but an exponentially increasing function with respect to the potential. The antifouling property of the PEG-SAM was not retained after an exposure to the electric field.

博士
國立清華大學
化學工程學系
102
Polyamidoamine (PAMAM) dednrimer bearing well-defined number of amine groups can be protonated under physiological or acidic condition to generate the macrocations capable of forming electrostatic complex (called “dendriplex”) with DNA for gene delivery. Using small angle X-ray scattering (SAXS) and small angle neutron scattering (SANS), here we constructed the morphological map of the complex of DNA with PAMAM dendrimer of generation four (G4) in terms of the dendrimer charge density and the nominal N/P ratio given by the feed molar ratio of dendrimer amine group to DNA phosphate group. With the increase of dendrimer charge density under a given nominal N/P ratio, the structure was found to transform from square columnar phase (in which the DNA chains packed in square lattice were locally straightened) to hexagonally-packed DNA superhelices (in which the DNA chains organizing in a hexagonal lattice twisted moderately into superhelices) and finally to beads-on-string structure (in which DNA wrapped around the dendrimer to form nuclesome-like array). The phase transition sequence was understood from the balance between the bending energy of DNA and the free energy of charge matching governed by the entropic gain from counterion release. Decreasing nominal N/P ratio under fixed dendrimer charge density was found to exert the same effect as increasing dendrimer charge density; that is, the structure with higher DNA curvature tended to form at lower nominal N/P ratio, in particular for the dendriplex with low dendrimer charge density. The effect of N/P ratio was attributed to the tendency of the system to increase the translational entropy of the counterions released to the bulk solution by reducing the concentration of free DNA or dendrimer remained in the solution. The experimental results presented here thus demonstrated the crucial role of counterion entropy in the structural formation of DNA-dendrimer complexes, and this entropic contribution was governed by the dendrimer charge density, the nominal N/P ratio, and the initial concentrations of DNA and dendrimer used for complex preparation. The dominant role of counterion entropy was further verified by examining the effect of protonic acid on the nanostructure of the dendriplex, where the dendrimer was also protonated by multivalent acids, including H2SO4 and H3PO4.

Tese de doutoramento em Ciências Farmacêuticas, na especialidade de Tecnologia Farmacêutica, apresentada à Faculdade de Farmácia da Universidade de Coimbra
Resveratrol (RSV) has been one of the most and extensively investigated polyphenols in the last recent years, owing to its broad-spectrum of promising therapeutic activities. It is extremely attractive for prevention or therapy where a magnitude of pathophysiological pathways is affected, making it a promising molecule for fighting cancer, diabetes and neurodegenerative diseases, amongst other targets. However, its therapeutic potential is strongly limited by its physicochemical properties, mainly its low aqueous solubility and stability, and its poor pharmacokinetics profile, which seriously compromise its oral bioavailability. RSV formulations, mainly available as nutritional supplements, are classic pharmaceutical dosage forms such as powders, tablets and hard gelatin capsules, to be administrated by the oral route. These formulations are often produced under uncontrolled processing procedures and using RSV with uncontrolled origin, which have shown to be not efficient. To achieve an optimal response of RSV, new strategies are required to enhance its bioavailability and reduce its perceived toxicity. New delivery systems are sought out as valid alternatives to circumvent the limitations of the physicochemical characteristics and pharmacokinetics of RSV. An alternative formulation strategy to tackle this challenge includes the development of a safe and effective RSV formulation, using new drug delivery systems, among which nanotechnology assumes nowadays a prominent position. Layer-by-Layer (LbL) self-assembly is an emergent nanotechnology, which is based on the design of tunable onion-like multilayered nanoarchitectures, composed of oppositely charged polyelectrolytes (PEs), upon the surface of low soluble drug nanocores, as RSV. This nanotechnology affords a versatile control over key formulation parameters, which are able to ultimately promote an improved pharmacokinetics profile. Facing these potentialities, in this work we aim the development of RSV-loaded LbL nanoformulations capable of improving the bioavailability of this Biopharmaceutics Classification System (BCS) class II drug, by using Wistar rats as the animal model. The research work of this thesis started with the development of a top-down LbL technique using a washless approach aiming the nanoencapsulation of ibuprofen (IBF), which was used in this stage of the work as a model BCS class II drug. For each saturated layer deposition, PE concentration was assessed by the design of PE titration curves. The LbL nanoshells were constituted by the PEs pair cationic polyallylamine hydrochloride (PAH)/anionic polystyrene sulfonate (PSS), up to the achievement of 2.5, 5.5 and 7.5 PE bilayers. IBF LbL nanoparticles (NPs) covered with 7.5 PAH/PSS bilayers evidenced to be stable aqueous nanocolloids of this model drug, as well as biocompatible. Moreover, a controlled release of IBF from LbL NPs was accomplished under simulated intestinal conditions (from 5 h up to 7 days), according to the number of coating bilayers, which attributed to these structures the capacity to improve biopharmaceutical parameters of BCS class II drugs, as RSV. Considering the knowledge acquired in the development of the aforementioned LbL NPs, novel LbL NPs were performed towards the nanoencapsulation of RSV. In this work, RSV nanoprecipitation followed by LbL self-assembly of PE, using a washless approach, was performed by applying the PE pair cationic PAH/anionic dextran sulfate (DS), by tracing, likewise, titration curves. Aqueous RSV nanocores and RSV LbL nanoformulations with a 2.5 (RSV-(PAH/DS)2.5 NPs), 5.5 (RSV-(PAH/DS)5.5 NPs) and 7.5 (RSV-(PAH/DS)7.5 NPs) bilayers were developed for the first time. Homogenous particle size distributions at the desired nanoscale interval, good colloidal and chemical stabilizations, high encapsulation efficiency, along with an excellent biocompatibility were verified. Those LbL NPs promoted a controlled release of RSV dependently of the number of PE bilayers under simulated gastrointestinal conditions, particularly in the intestine medium, which greatly highlighted their biopharmaceutical advantage. Our findings evidently pointed out that LbL PAH/DS-based NPs constitute a rational strategy for the oral administration of RSV in vivo. Lastly, the bioavailability of the LbL nanoformulation composed of 5.5 bilayers of PAH and DS, previously developed, was performed using Wistar rats. We investigated the bioavailability of this LbL nanoformulation in comparison to the respective nanoformulation without LbL coatings (RSV nanocores) and the free RSV suspension, by pharmacokinetic studies following oral dosing to Wistar rats (20 mg/kg). For this study, due to the key role of the bioanalytical method in the in vivo data acquisition, a rapid, selective, and sensitive HPLC–DAD method has been successfully optimized and fully validated to confidently quantify RSV levels in rat plasma matrix, together with the optimization of the sample preparation procedure. Moreover, the chemical stability of RSV was assured for 24 h in simulated gastric and intestinal fluids with enzymes. Concerning the pharmacokinetic study, besides some weaknesses have been identified regarding the behaviour of the LbL shell after oral administration in Wistar rats, our results fully demonstrated, for the first time, that LbL NPs significantly enhanced the systemic exposure of RSV. Such data emphasized thus the biopharmaceutical advantage of LbL NPs over the free drug, suggesting them as a potential oral drug delivery system for RSV. In conclusion, with this research work we present evidence that RSV nanoencapsulation by LbL self-assembly nanotechnology constitutes a promising strategy to enhance the bioavailability of RSV after oral administration, offering great prospective to enlarge its potential preventive and therapeutic applications.
O resveratrol (RSV) tem sido um dos polifenois que nos últimos anos mais foi investigado devido ao seu alargado potencial terapêutico. É extremamente interessante na prevenção e terapia, quando várias vias fisiopatológicas são afetadas, tornando-a uma molécula promissora para combater, entre outras patologias, o cancro, a diabetes e as doenças neurodegenerativas. Contudo, o seu potencial terapêutico é fortemente limitado pelas suas propriedades físico-químicas, sobretudo a sua baixa solubilidade aquosa e estabilidade, bem como pelo seu perfil farmacocinético fraco, que comprometem gravemente a sua biodisponibilidade oral. As formulações de RSV, disponíveis principalmente sob a forma de suplementos nutricionais, são formas farmacêuticas clássicas, tais como pós, comprimidos e cápsulas de gelatina dura, que se destinam a ser administrados pela via oral. Estas formas farmacêuticas são frequentemente produzidas através de procedimentos de fabrico sem controlo de qualidade e com RSV de origem não controlada, o que compromete a sua eficácia. Por forma a obter uma resposta ótima ao RSV, são necessárias novas estratégias para aumentar a sua biodisponibilidade e reduzir a sua toxicidade. Novos sistemas de libertação são necessários como alternativas válidas para ultrapassar as limitações inerentes às características físico-químicas e farmacocinéticas do RSV. Uma estratégia de formulação alternativa para responder a esse desafio inclui o desenvolvimento de uma formulação de RSV segura e eficaz, utilizando novos sistemas de libertação, entre os quais a nanotecnologia assume atualmente uma posição proeminente. A “auto-montagem por camada-a-camada” (LbL) é uma nanotecnologia emergente, que se baseia na conceção de nanoarquitecturas em multicamadas reguláveis, semelhantes à estrutura de uma cebola, compostas por polielectrólitos (PEs) carregados com cargas opostas, sob a superfície de nanonúcleos de fármacos de baixa solubilidade, como o RSV. Esta nanotecnologia oferece um controlo versátil sobre os principais parâmetros de formulação, que são capazes de, em última instância, melhorar o perfil farmacocinético. Face a estas potencialidades, com este trabalho pretende-se o desenvolvimento de nanoformulações de LbL carregadas com RSV capazes de melhorar a biodisponibilidade deste fármaco da classe II do Sistema de Classificação Biofarmacêutica (BCS), usando ratos Wistar como modelo animal. O trabalho de investigação desta tese começou pelo desenvolvimento de uma técnica de LbL, sob a vertente “top-down”, realizada usando uma abordagem sem lavagens que visou a nanoencapsulação de ibuprofeno (IBF), fármaco que foi usado nesta fase do trabalho como um fármaco modelo da classe II do BCS. Para cada deposição de camada saturada, a concentração de PE foi avaliada pela conceção de curvas de titulação de PEs. As nanocápsulas de LbL foram constituídas pelo par de PEs catiónico cloridrato de polialilamina (PAH) / aniónico poliestireno sulfonato (PSS), até à deposição de 2.5 (IBF-(PAH/PSS)2.5NPs), 5.5 (IBF-(PAH/PSS)5.5NPs) e 7.5 (IBF-(PAH/PSS)7.5NPs) bicamadas de PEs. As nanopartículas (NPs) de LbL de IBF revestidas com 7.5 bicamadas de PAH/PSS evidenciaram ser nanocolóides aquosos estáveis deste fármaco modelo, bem como serem biocompatíveis. Além disso, uma libertação controlada do IBF das NPs de LbL foi conseguida sob condições intestinais simuladas (de 5 h até 7 dias), de acordo com o número de bicamadas de revestimento, atribuindo a essas estruturas a capacidade de melhorar os parâmetros biofarmacêuticos de fármacos da classe II do BCS, como o RSV. Considerando o conhecimento adquirido aquando do desenvolvimento das NPs anteriormente referidas, novas NPs de LbL foram concebidas com vista à nanoencapsulação de RSV. Nesta fase do trabalho, a nanoprecipitação de RSV seguida de LbL de PEs, usando a abordagem sem lavagens, foi realizada aplicando o PE catiónico PAH / PE aniónico sulfato de dextrano (DS), pelo desenho, da mesma forma, de curvas de titulação. Os nanonúcleos de RSV aquosos e as nanoformulações de LbL de RSV com 2.5 (RSV-(PAH/DS)2.5NPs), 5.5 (RSV-(PAH/DS)5.5NPs) e 7.5 (RSV-(PAH/DS)7.5NPs) bicamadas foram desenvolvidos pela primeira vez. Verificou-se a obtenção de distribuições homogéneas de tamanho de partícula no intervalo da nanoescala desejado, boa estabilização coloidal e química, elevada eficiência de encapsulação, juntamente com uma excelente biocompatibilidade. Estas NPs de LbL promoveram uma libertação controlada do RSV, que mostrou ser dependente do número de bicamadas de PEs sob condições gastrointestinais simuladas, particularmente no meio intestinal, evidenciando fortemente a sua vantagem biofarmacêutica. Os nossos resultados apontaram, de forma evidente, que as NPs de LbL formadas por PAH/DS constituem uma estratégia racional para a administração oral de RSV in vivo. Por fim, a biodisponibilidade da nanoformulação de LbL composta por 5.5 bicamadas de PAH e DS, desenvolvida anteriormente, foi realizada em ratos Wistar. A biodisponibilidade dessas nanoformulação de LbL foi investigada, em comparação com a respetiva nanoformulação sem revestimentos de LbL (nanonúcleos de RSV) e a suspensão de RSV livre, através de estudos farmacocinéticos após administração oral das nanoformulações a ratos Wistar (20 mg/kg). Para este estudo, devido ao papel fundamental do método bioanalítico na aquisição de dados referentes ao ensaio in vivo, um método HPLC-DAD rápido, seletivo e sensível foi otimizado com sucesso e totalmente validado para quantificar com rigor os níveis de RSV na matriz de plasma de rato, juntamente com a otimização do procedimento de preparação da amostra. Além disso, a estabilidade química do RSV foi assegurada durante 24 h em fluidos gástrico e intestinal simulados contendo enzimas. No que diz respeito ao estudo farmacocinético, apesar de terem sido identificados alguns pontos fracos quanto ao comportamento do revestimento de LbL após a administração oral em ratos Wistar, os nossos resultados demonstraram, pela primeira vez, que as NPs de LbL aumentaram significativamente a exposição sistémica do RSV. Tais dados enfatizaram, portanto, a vantagem biofarmacêutica das NPs de LbL sobre o fármaco livre, sugerindo-as como um potencial sistema de libertação oral para RSV. Em conclusão, com este trabalho de investigação, apresentamos evidências de que a nanoencapsulação do RSV pela nanotecnologia de LbL constitui uma estratégia promissora para aumentar a biodisponibilidade do RSV após a administração oral, oferecendo excelente potencial para aumentar as suas potenciais aplicações preventivas e terapêuticas.
Fundação para a Ciência e Tecnologia (FCT) -Programa QREN - POPH/FSE - bolsa de doutoramento SFRH/BD/109261/2015