No / (51)Cr-labeled, superparamagnetic, iron oxide nanoparticles ((51)Cr-SPIOs) and (65)Zn-labeled CdSe/CdS/ZnS-quantum dots ((65)Zn-Qdots) were prepared using an easy, on demand, exchange-labeling technique and their particokinetic parameters were studied in mice after intravenous injection. The results indicate that the application of these heterologous isotopes can be used to successfully mark the nanoparticles during initial distribution and organ uptake, although the (65)Zn-label appeared not to be fully stable. As the degradation of the nanoparticles takes place, the individual transport mechanisms for the different isotopes must be carefully taken into account. Although this variation in transport paths can bring new insights with regard to the respective trace element homeostasis, it can also limit the relevance of such trace material-based approaches in nanobioscience. By monitoring (51)Cr-SPIOs after oral gavage, the gastrointestinal non-absorption of intact SPIOs in a hydrophilic or lipophilic surrounding was measured in mice with such high sensitivity for the first time. After intravenous injection, polymer-coated, (65)Zn-Qdots were mainly taken up by the liver and spleen, which was different from that of ionic (65)ZnCl2. Following the label for 4 weeks, an indication of substantial degradation of the nanoparticles and the release of the label into the Zn pool was observed. Confocal microscopy of rat liver cryosections (prepared 2 h after intravenous injection of polymer-coated Qdots) revealed a colocalization with markers for Kupffer cells and liver sinusoidal endothelial cells (LSEC), but not with hepatocytes. In J774 macrophages, fluorescent Qdots were found colocalized with lysosomal markers. After 24 h, no signs of degradation could be detected. However, after 12 weeks, no fluorescent nanoparticles could be detected in the liver cryosections, which would confirm our (65)Zn data showing a substantial degradation of the polymer-coated CdSe/CdS/ZnS-Qdots in the liver.

No / During the last decades of nanoparticles research, many nanomaterials have been developed for applications in the field of bio-labelling. For the visualization of transport processes in the body, organs and cells, luminescent quantum dots (QDs) make for highly useful diagnostic tools. However, intercellular routes, bio-distribution, metabolism during degradation or quantification of the excretion of nanoparticles, and the study of the biological response to the QDs themselves are areas which to date have not been fully investigated. In order to aid in addressing those issues, CdSe/CdS/ZnS QDs were radioactively labelled, which allows quantification of the QD concentration in the whole body or in ex vivo samples by gamma-counting. However, the synthesis of radioactively labelled QDs is not trivial since the coating process must be completely adapted, and material availability, security and avoidance of radioactive waste must be considered. In this contribution, the coating of CdSe/CdS QDs with a radioactive (65)ZnS shell using a modified, operator-safe, SILAR procedure is presented. Under UV illumination, no difference in the photoluminescence of the radioactive and non-radioactive CdSe/CdS/ZnS colloidal solutions was observed. Furthermore, a down-scaled synthesis for the production of very small batches of 5 nmol QDs without loss in the fluorescence quality was developed. Subsequently, the radio-labelled QDs were phase transferred by encapsulation into an amphiphilic polymer. gamma-counting of the radioactivity provided confirmation of the successful labelling and phase transfer of the QDs.

Yes

Ion-selective polymeric optical sensors – ion optodes – are a promising alternative to ion-selective electrodes and fluorescent dyes for analytical and biological applications, e.g. extra- and intracellular measurements. They are non-toxic, highly selective robust probes for ionic fluxes monitoring. A large-scale fabrication of ion optodes using a solvent displacement method is introduced. This method is a single-batch process that does not require any additional steps. The influence of numerous parameters, e.g. surfactant concentration, solvent nature and membrane concentration, on the average size of the synthesized optodes was studied. The solvent displacement method allows control of the particle size in 200 nm to 30 μm range. Ion optodes selective for sodium, potassium, and calcium cations were prepared and calibrated for hydrogen (pH), sodium, potassium, and calcium. Fabricated sensors demonstrated excellent selectivity, low drift, high stability and reproducibility. Further studies of ion-optodes of different sizes but the same chemical composition revealed a significant shift in their response function. This bias is clearly seen for all fabricated optodes. A strong correlation between a calculated specific surface area and the apparent ion-exchange constant was observed. Considering this, it may be hypothesized that the surface phenomena are contributing to the overall optode response resulting in the observed effect. As a consequence, the response models, developed for the macroscopic ion optodes, cannot be easily applied to the probes at micron- and nano-scale. A primary concern for continuous sensing application of optical sensors is photobleaching of lipophilic fluorescent dye which prevents quantitative fluorescence measurements. Quantum dots, known for their high photostability, brightness and broad excitation spectra with narrow emission bands, were incorporated into polymeric matrix. They excited a fluorophore indirectly, thus, reducing its photobleaching and increasing sensors life-time. We created a composite, quantum dots doped, polymeric sensor that can be integrated into high-throughput detection platforms, such as flow cytometry, chip-based micro-total analysis system technologies, or bundled optical fiber arrays. Ultimately, a fabricated ion-optode was introduced into a Boolean logic gate serving as a reporting microparticle. It responded to the pH changes generated in situ by the enzyme logic system. The present work aimed scaling down the size of biocomputing functional units which might reach the information processing by single molecules associated with signal-transducing single nanoparticles. / Graduation date: 2012

Le développement des nanoparticules fluorescentes, appelées quantum dots (QDs) est devenu l'un des domaines les plus prometteurs de la science des matériaux. Dans cette étude une procédure de synthèse de QDs a été mise au point, comprenant la synthèse de noyaux ultra-minces de CdSe, la purification de noyau haute performance, le revêtement central avec une coquille épitaxiale en ZnS. Cette approche a permis d’obtenir des QDs d’une taille de 3,7 nm possédant un rendement quantique supérieur à 70%. Les QDs développés ont été utilisés pour concevoir des conjugués de QDs compacts avec les nouveaux dérivés d'acridine, ayant une affinité élevée pour le G-quadruplex des télomères, ainsi que leur effet inhibiteur sur la télomérase, une cible importante du traitement du cancer. Les résultats de cette étude ouvrent la voie à l'ingénierie de nanosondes multifonctionnelles possédant une meilleure pénétration intracellulaire, une plus forte brillance et une stabilité colloïdale plus importante. / Development of the fluorescent nanoparticles referred to as quantum dots (QDs) has become one of the most promising areas of materials sciences. In this study, a procedure of synthesis of QDs, which includes the synthesis of ultrasmall CdSe cores, high-performance purification, core coating with an epitaxial ZnS shell has been developed. This approach has allowed obtaining 3.7-nm QDs with a quantum yield exceeding 70%. The QDs have been used: to engineer compact conjugates of QDs with the novel acridine derivatives, which have a high affinity for the telomere G-quadruplex; to demonstrate their inhibitory effect on telomerase, an important target of anticancer therapy; and to accelerate transmembrane penetration of ultrasmall QDs into cancer cells while retaining a high brightness and colloidal stability. The results of this study pave the way to the engineering of multifunctional nanoprobes with improved intracellular penetration, brightness, and colloidal stability.

Para o desenvolvimento dos sensores aqui descritos foram utilizados materiais inovadores considerando relatos atuais da literatura, materiais estes: óxido de grafeno, óxido de grafeno reduzido, nanocompósitos de grafeno e nanopartículas (ródio, antimônio e sílica mesoporosa desordenada), materiais híbridos a base de grafeno e quantum dots de CdTe, além de biossensores incorporando a enzima lacase. Estes materiais foram sintetizados utilizando metodologias específicas e caracterizados por diversas técnicas analíticas como microscopia eletrônica de transmissão de alta resolução, microscopia de força atômica, espectroscopia Raman, difração de raios-X, espectroscopias de UV-Vis e fotoluminescência, e técnicas eletroquímicas. Posteriormente, os materiais foram utilizados para modificação em eletrodos de carbono vítreo e utilizados na determinação de interferentes endócrinos (os hormônios estriol e 17β-estradiol) como sensores eletroquímicos em amostras ambientais e clínicas. Em essência, os eletrodos desenvolvidos apresentaram importantes vantagens, tais como alta sensibilidade, boa reprodutibilidade, simples instrumentação, fácil preparação e procedimentos analíticos rápidos, apresentando baixos limites de detecção, na ordem de picomolar e nanomolar, com baixa taxa de interferência de outras espécies na mesma matriz da amostra. Concluindo assim que as técnicas eletroquímicas podem ser facilmente aplicadas na determinação de interferentes endócrinos em amostras reais. / For the development of the sensors described here innovators materials were used considering current literature reports, these materials: Graphene oxide, reduced graphene oxide, nanocomposites graphene and nanoparticles (rhodium and antimony), hybrid materials of graphene and CdTe quantum dots, and biosensors incorporating the laccase enzyme. These materials were synthesized using specific methodologies and characterized by several analytical techniques such as transmission electron microscopy, high resolution transmission electron microscopy, atomic force microscopy, Raman spectroscopy, X-ray diffraction, UV-Vis and photoluminescence spectroscopy and electrochemical techniques. Subsequently, the materials were used for modification of glassy carbon electrodes to the determination of endocrine disruptors (estriol and 17β-estradiol hormone) as electrochemical sensors for environmental and clinical samples. In essence, developed electrodes showed important advantages such as high sensitivity, good reproducibility, simple instrumentation, easy preparation and quick analytical procedures, with low detection limits in the range of picomolar and nanomolar, low interference rate of other species in same matrix sample. Finally, electrochemical techniques can be easily applied in the determination of endocrine disruptors in real samples.

<p>This thesis addresses electron spin phenomena in semi-conductor quantum dots/anti-dots from a computational perspective. In the first paper (paper I) we have studied spin-dependent transport through open quantum dots, i.e., dots strongly coupled to their leads, within the Hubbard model. Results in this model were found consistent with experimental data and suggest that spin-degeneracy is lifted inside the dot – even at zero magnetic field.</p><p>Similar systems were also studied with electron-electron effects incorporated via Density Functional Theory (DFT) in paper III. Within DFT we found a significant spin-polarisation in the dot at low electron densities. As the electron density increases the spin polarisation in the dot gradually diminishes. These findings are consistent with available experimental observations. Notably, the polarisation is qualitatively different from the one found in the Hubbard model – this indicates that the simplified approach to electronelectron interaction in the Hubbard model might not always be reliable.</p><p>In paper II we propose a spin-filter device based on resonant backscattering of edge states against a quantum anti-dot embedded in a quantum wire. A magnetic field is applied and the spin up/spin down states are separated through Zeeman splitting. Their respective resonant states may be tuned so that the device can be used to filter either spin in a controlled way.</p> / Report code: LIU-Tek-Lic 2005:65

Near-field optical microscopy has attracted remarkable attention, as it is the only technique that allows the investigation of local optical properties with a resolution far below the diffraction limit. Especially, the scattering-type near-field optical microscopy allows the nondestructive examination of surfaces without restrictions to the applicable wavelengths. However, its usability is limited by the availability of appropriate light sources. In the context of this work, this limit was overcome by the development of a scattering-type near-field microscope that uses a widely tunable free-electron laser as primary light source. In the theoretical part, it is shown that an optical near-field contrast can be expected when materials with different dielectric functions are combined. It is derived that these differences yield different scattering cross-sections for the coupled system of the probe and the sample. Those cross-sections define the strength of the near-field signal that can be measured for different materials. Hence, an optical contrast can be expected, when different scattering cross-sections are probed. This principle also applies to vertically stacked or even buried materials, as shown in this thesis experimentally for two sample systems. In the first example, the different dielectric functions were obtained by locally changing the carrier concentration in silicon by the implantation of boron. It is shown that the concentration of free charge-carriers can be deduced from the near-field contrast between implanted and pure silicon. For this purpose, two different experimental approaches were used, a non-interferometric one by using variable wavelengths and an interferometric one with a fixed wavelength. As those techniques yield complementary information, they can be used to quantitatively determine the effective carrier concentration. Both approaches yield consistent results for the carrier concentration, which excellently agrees with predictions from literature. While the structures of the first system were in the micrometer regime, the capability to probe buried nanostructures is demonstrated at a sample of indium arsenide quantum dots. Those dots are covered by a thick layer of gallium arsenide. For the first time ever, it is shown experimentally that transitions between electron states in single quantum dots can be investigated by near-field microscopy. By monitoring the near-field response of these quantum dots while scanning the wavelength of the incident light beam, it was possible to obtain characteristic near-field signatures of single dots. Near-field contrasts up to 30 % could be measured for resonant excitation of electrons in the conduction band of the indium arsenide dots.

This research focuses on generating, isolating, and characterizing nanophase gold clusters with diameters below two nanometers. In this size regime, the metal cores exhibit electronic and optical properties very different from those of colloidal and bulk gold, arising from quantum size confinement. The unoccupied molecular orbitals of the cores are known to accept electrons, analogous to a capacitor, but with discrete electrochemical potentials. This work describes the novel production of gold clusters with structurally rigid benzenethiolate bound to the surface, rather than typically used alkanethiolates. The Aux(benzenethiolate)y clusters are anionic and charged balanced by tetraoctylammonium cations. They are enriched in ~1.5 nm diameter cores, compared to a dominance of 1.7 nm cores when alkanethiols are used during synthesis. The Aux(benzenethiolate)y clusters are more likely to form bulk crystals and possess enhanced electrochemistry relative to Aux(alkylthiolate)y clusters. They are characterized by x-ray diffraction, carbon and proton NMR, FTIR, optical spectroscopy, mass spectrometry, elemental analysis, and thermogravimetric analysis. The etching of clusters in the presence of hydrogen peroxide and excess benzenethiol to yield smaller 1.1 nm clusters is reported for the first time in this work. These 1.1 nm clusters have a rich optical spectrum with clear electronic transitions at room temperature and orient spontaneously when deposited from solution. This oxidative etching process was applied to alkanethiolate clusters, converting ~2.0 nm polydisperse clusters into smaller clusters. This offers the potential to produce smaller gold clusters with more available charge states and may allow increase the types of thiols that can be bound to the surface of gold monolayer protected clusters (MPCs), known also as quantum dots. The use of the bulky thiol, tert-butylmercaptan to produce 1.5 nm core gold clusters is also reported, indicating sterically hindered alkanethiols can play a role in limiting the size of Aux(alkylthiolate)y clusters. These clusters were characterized by x-ray diffraction, proton NMR, FTIR, optical spectroscopy, and mass spectrometry. The clusters are potentially useful for thiolate exchange reactions to produce new types of Aux(thiolate)y clusters.

Despite significant developments in imaging modalities and therapeutics, cancer mortality rates remain unchanged. Detecting cancer before it has spread to other organs improves patient outcome dramatically. Therefore, greater emphasis must be placed on developing novel technology for early cancer detection and disease monitoring. Nanometer-sized materials have unique optoelectronic and magnetic properties. In particular, semiconductor quantum dots (QD) are a new class of fluorophores that are bright, photostable, and can be simultaneously excited to emit different wavelengths of light. Magnetic iron oxide nanoparticles are another class of unique nanomaterials that exhibit superparamagnetism and are strongly magnetized only in the presence of a magnetic field. In this dissertation, we describe the integration of semiconductor QDs and magnetic iron oxide nanoparticles and potential applications for (i) early detection of cancer biomarkers through routine screening, and (ii) disease monitoring through the capture and analysis of rare circulating tumor cells. First, we describe the development of integrated magneto-optical beads that can be optically encoded and magnetically separable for isolating low amounts of biomolecules from solution. Second, we demonstrate improved detection sensitivity by combining immunomagnetic beads and highly luminescent nanoparticles in a sandwich assay. Next, we describe integration of magnetic and QD nanotechnology for the selective capture and molecular profiling of rare cells. We demonstrate the ability to spectroscopically determine relative molecular levels of markers to identify invasive cells. As disease monitoring requires the analysis of patient blood samples, we have also studied nanoparticle-cell interactions using QDs to determine nanoparticle behavior in whole blood as a function of surface coatings. We observed that anionic nanoparticles with carboxylic acid groups (-COOH) were strongly associated with leukocytes, but interestingly this association was cell specific. Hydroxyl-modified QDs (QD-OH) suppressed binding and uptake by leukocytes as efficiently as PEG-modified QDs. The integration of nanotechnologies represents a new and exciting approach that has the potential to push the limits of detection sensitivity and permit isolation and profiling of multiple biomarkers from large sample volumes.