Fluorescence molecular imaging has been triggering interest in the scientific community for the last decade due to its great potential for improved early cancer detection and image-guided treatment. Semiconductor nanoparticles, also known as quantum dots, have been identified as potential contrast agents for molecular imaging, but there is a lack of quantitative contrast optimization studies that would enable precise and robust dosimetry calculations. These calculations are crucial to determine the feasibility, risk and cost of any contrast-enhanced clinical imaging procedure. This thesis presents a first attempt at developing a quantitative dosimetry framework for quantum dot-based contrast-enhanced fluorescence molecular imaging, by combining novel experimental methods and validated mathematical models. Three studies were completed to develop the dosimetry framework. In the first study, we design a novel homogenized optical tissue phantom approach to investigate with precision the effects of various photophysical parameters, such as the excitation and emission wavelengths, tissue absorption and scattering coefficient spectra, tissue autofluorescence spectra, target fluorescence spectra and target depth, on the detected contrast. In the second study, we use the approach to investigate the influence of tissue optical absorption and scattering on contrast behavior for various ex vivo tissue samples, and develop performance metrics to quantify the optimization results. In the third study, we perform vascular fluorescence contrast-enhanced imaging in the dorsal skinfold window chamber mouse model to investigate the effects of pharmacokinetics, blood absorption, vessel diameter and injected dose on the detected contrast. We also describe the relationship between the injected volume and vascular contrast, and transfer the performance metrics developed previously to estimate the minimum injection dose under various conditions. These studies are expected to serve as a stepping stone to further develop contrast optimization and dosimetry models for the emerging field of fluorescence molecular imaging.

Fluorescence molecular imaging has been triggering interest in the scientific community for the last decade due to its great potential for improved early cancer detection and image-guided treatment. Semiconductor nanoparticles, also known as quantum dots, have been identified as potential contrast agents for molecular imaging, but there is a lack of quantitative contrast optimization studies that would enable precise and robust dosimetry calculations. These calculations are crucial to determine the feasibility, risk and cost of any contrast-enhanced clinical imaging procedure. This thesis presents a first attempt at developing a quantitative dosimetry framework for quantum dot-based contrast-enhanced fluorescence molecular imaging, by combining novel experimental methods and validated mathematical models. Three studies were completed to develop the dosimetry framework. In the first study, we design a novel homogenized optical tissue phantom approach to investigate with precision the effects of various photophysical parameters, such as the excitation and emission wavelengths, tissue absorption and scattering coefficient spectra, tissue autofluorescence spectra, target fluorescence spectra and target depth, on the detected contrast. In the second study, we use the approach to investigate the influence of tissue optical absorption and scattering on contrast behavior for various ex vivo tissue samples, and develop performance metrics to quantify the optimization results. In the third study, we perform vascular fluorescence contrast-enhanced imaging in the dorsal skinfold window chamber mouse model to investigate the effects of pharmacokinetics, blood absorption, vessel diameter and injected dose on the detected contrast. We also describe the relationship between the injected volume and vascular contrast, and transfer the performance metrics developed previously to estimate the minimum injection dose under various conditions. These studies are expected to serve as a stepping stone to further develop contrast optimization and dosimetry models for the emerging field of fluorescence molecular imaging.

In dieser Arbeit wurden sphärische Gold Nanopartikel (NP) mit einem Durchmesser größer ~ 2 nm, Gold Quantenpunkte (QDs) mit einem Durchmesser kleiner ~ 2 nm sowie Gold Nanostäbchen (NRs) unterschiedlicher Länge hergestellt und optisch charakterisiert. Zudem wurden zwei neue Synthesevarianten für die Herstellung thermosensitiver Gold QDs entwickelt werden. Sphärische Gold NP zeigen eine Plasmonenbande bei ~ 520 nm, die auf die kollektive Oszillation von Elektronen zurückzuführen ist. Gold NRs weisen aufgrund ihrer anisotropen Form zwei Plasmonenbanden auf, eine transversale Plasmonenbande bei ~ 520 nm und eine longitudinale Plasmonenbande, die vom Länge-zu-Durchmesser-Verhältnis der Gold NRs abhängig ist. Gold QDs besitzen keine Plasmonenbande, da ihre Elektronen Quantenbeschränkungen unterliegen. Gold QDs zeigen jedoch aufgrund diskreter Energieniveaus und einer Bandlücke Photolumineszenz (PL). Die synthetisierten Gold QDs besitzen eine Breitbandlumineszenz im Bereich von ~ 500-800 nm, wobei die Lumineszenz-eigenschaften (Emissionspeak, Quantenausbeute, Lebenszeiten) stark von den Herstellungs-bedingungen und den Oberflächenliganden abhängen. Die PL in Gold QDs ist ein sehr komplexes Phänomen und rührt vermutlich von Singulett- und Triplett-Zuständen her. Gold NRs und Gold QDs konnten in verschiedene Polymere wie bspw. Cellulosetriacetat eingearbeitet werden. Polymernanokomposite mit Gold NRs wurden erstmals unter definierten Bedingungen mechanisch gezogen, um Filme mit optisch anisotropen (richtungsabhängigen) Eigenschaften zu erhalten. Zudem wurde das Temperaturverhalten von Gold NRs und Gold QDs untersucht. Es konnte gezeigt werden, dass eine lokale Variation der Größe und Form von Gold NRs in Polymernanokompositen durch Temperaturerhöhung auf 225-250 °C erzielt werden kann. Es zeigte sich, dass die PL der Gold QDs stark temperaturabhängig ist, wodurch die PL QY der Proben beim Abkühlen (-7 °C) auf knapp 30 % verdoppelt und beim Erhitzen auf 70 °C nahezu vollständig gelöscht werden konnte. Es konnte demonstriert werden, dass die Länge der Alkylkette des Oberflächenliganden einen Einfluss auf die Temperaturstabilität der Gold QDs hat. Zudem wurden verschiedene neuartige und optisch anisotrope Sicherheitslabels mit Gold NRs sowie thermosensitive Sicherheitslabel mit Gold QDs entwickelt. Ebenso scheinen Gold NRs und QDs für die und die Optoelektronik (bspw. Datenspeicherung) und die Medizin (bspw. Krebsdiagnostik bzw. -therapie) von großem Interesse zu sein. / In this thesis, the synthesis and optical characterization of spherical gold nanoparticles (NP) with diameters larger than ~ 2 nm, gold quantum dots (QDs) with diameters smaller than ~ 2 nm and gold nanorods (NRs) with different lengths are presented. In addition, a novel one-pot synthesis for the preparation of thermosensitive gold QDs is introduced. Gold NP solutions appear red colored due to their strong absorption in the visible range at ~ 520 nm. This absorption band is a result of surface plasmon resonance, which is caused by the coherent oscillation of conduction band electrons induced by an electromagnetic field. In contrast to spherical gold NPs, gold NRs show two surface plasmon bands due to their anisotropic shape, a transverse plasmon band at ~ 520 nm and a longitudinal plasmon band depending on the aspect ratio (length-to-width-ratio) of the gold NRs. If the size of the gold NPs decreases to values below ~ 2 nm, quantum-size confinement occurs and the surface plasmon band disappears. Additionally, the overlap between conduction band and valence band disappears, discrete electronic levels arise and a band gap is created. As a consequence of quantum confinement, the gold QDs show photoluminescence (PL) upon UV-irradiation. The gold QDs synthesized via the one-pot synthesis exhibit a broadband luminescence between 500 nm and 800 nm. The luminescence properties (emission peak, quantum yield, lifetime) strongly depend on the synthetic parameters like reaction temperature, stoichiometry and the surface ligand. Gold NRs and gold QDs were incoroporated into different polymers (e.g. cellulose triacetate). Polymer nanocomposite films showing optical anisotropy are obtainded by stretching polymer films containing gold NRs uniaxial in a tensile test machine. In addition to the optical characterization of gold NRs and QDs, their thermal behavior in solution as well as in different nanocomposites is studied. A shortening of the gold NRs or a transformation into spherical gold NP is observed, if the polymer nanocomposites containing gold NRs are heated above a temperature of 200 °C. The PL of the synthesized gold QDs strongly depends on the ambient temperature. An increase of PL quantum yield (QY) and PL lifetime occur, if the solutions are cooled. The best PL QY of 16.6 % was observed for octadecyl mercaptan capped gold QDs at room temperature, which could be improved to 28.6 % when cooling the solutions to -7 °C. Furthermore, optically anisotropic security labels containing gold NRs and thermosensitive security devices containing gold QDs are developed. Due to their unique optical properties, gold NRs and QDs are interesting candidates for optoelectronical as well as data storage devices and medical applications like biomedical imaging or cancer therapy.

Nanodalelės jau taikomos komerciniuose produktuose ir diegiamos į naujus diagnostikos bei gydymo metodus. Nepaisant to, jų prasiskverbimas per apsauginius organizmo barjerus, lokalizacija organizme, pasišalinimo savybės ir ilgalaikio susikaupimo rizika nėra pakankamai ištirtos. Šios žinios reikalingos tiek naujų medicinos priemonių kūrimui, tiek ir toksikologiniam produktų įvertinimui. Darbe optiniais metodais buvo tiriama puslaidininkinių nanodalelių – CdSe/ZnS-mPEG kvantinių taškų (KT) – migracija eksperimentinių gyvūnų audiniuose in vivo, įvedant juos skirtingais būdais į organizmą. Disertacijoje nagrinėjamas KT judėjimas audinių tarpląstelinėje terpėje, jų kaupimasis skirtingose ląstelėse, prasiskverbimas per kraujagyslių, odos bei placentos barjerus. Rezultatai rodo, kad KT migruoja organizme kitaip nei daugelis medicinoje taikomų organinių junginių. Į kraujotaką patekę neprasiskverbia per daugumos kraujagyslių sienelę ir nesikaupia atitinkamuose audiniuose. Tai sudaro sąlygas naudoti KT kraujotakos vaizdinimui, angiogenezės bei kraujagyslių pažaidų tyrimuose. Parodyta, kad KT audiniuose sulaikomi tankių skaidulinių pluoštų, pvz., bazinės membranos, ir tai sąlygoja jų nepatekimą į plaukų folikulus, prakaito bei riebalų liaukas, periferinius nervus, raumenines skaidulas. Tikimasi, kad šie rezultatai padės aiškintis KT pernašos per biologinius barjerus mechanizmus, leis tiksliau įvertinti jų taikymo saugumą bei praplės KT panaudojimo biomedicinoje galimybes. / Nanoparticles (NP) are already in the composition of commercial products. New methods for medical diagnostics and therapy based on NP are developed. However the mechanisms of NP penetration through protective human barriers, biodistribution in the body, clearance properties and long-term accumulation risk remain undiscovered. This knowledge is needed to optimize biomedical applications of NP and to estimate nanotoxicological effects. This thesis investigates the migration of semiconductor NP – CdSe/ZnS-mPEG quantum dots (QD) in the tissues of experimental animals in vivo by the means of optical methods. The diffusion of QD in extracellular matrix, accumulation in different cell types, and penetration through the barriers of vessel walls, skin and placenta are analyzed. Main results show, that QD migration pathways in the body are distinct form the conventional organic drugs. QD are not transferred through the wall of most blood vessels and don‘t extravasate into the tissues. It can be used for imaging of blood vessels, angiogenesis and vessel damage research. It is shown, that QD diffusion in the tissues is limited by dense tissue fiber layers, e.g. basement membrane, and it retains QD from passage to epidermis, hair follicles, dermal glands, nerves and muscle cells. These results can be used to explore the mechanisms of biological barriers, contribute to the estimation of QD safety and expand the application areas of QD in biomedicine.

Nanoparticles (NP) are already in the composition of commercial products. New methods for medical diagnostics and therapy based on NP are developed. However the mechanisms of NP penetration through protective human barriers, biodistribution in the body, clearance properties and long-term accumulation risk remain undiscovered. This knowledge is needed to optimize biomedical applications of NP and to estimate nanotoxicological effects. This thesis investigates the migration of semiconductor NP – CdSe/ZnS-mPEG quantum dots (QD) in the tissues of experimental animals in vivo by the means of optical methods. The diffusion of QD in extracellular matrix, accumulation in different cell types, and penetration through the barriers of vessel walls, skin and placenta are analyzed. Main results show, that QD migration pathways in the body are distinct form the conventional organic drugs. QD are not transferred through the wall of most blood vessels and don‘t extravasate into the tissues. It can be used for imaging of blood vessels, angiogenesis and vessel damage research. It is shown, that QD diffusion in the tissues is limited by dense tissue fiber layers, e.g. basement membrane, and it retains QD from passage to epidermis, hair follicles, dermal glands, nerves and muscle cells. These results can be used to explore the mechanisms of biological barriers, contribute to the estimation of QD safety and expand the application areas of QD in biomedicine. / Nanodalelės jau taikomos komerciniuose produktuose ir diegiamos į naujus diagnostikos bei gydymo metodus. Nepaisant to, jų prasiskverbimas per apsauginius organizmo barjerus, lokalizacija organizme, pasišalinimo savybės ir ilgalaikio susikaupimo rizika nėra pakankamai ištirtos. Šios žinios reikalingos tiek naujų medicinos priemonių kūrimui, tiek ir toksikologiniam produktų įvertinimui. Darbe optiniais metodais buvo tiriama puslaidininkinių nanodalelių – CdSe/ZnS-mPEG kvantinių taškų (KT) – migracija eksperimentinių gyvūnų audiniuose in vivo, įvedant juos skirtingais būdais į organizmą. Disertacijoje nagrinėjamas KT judėjimas audinių tarpląstelinėje terpėje, jų kaupimasis skirtingose ląstelėse, prasiskverbimas per kraujagyslių, odos bei placentos barjerus. Rezultatai rodo, kad KT migruoja organizme kitaip nei daugelis medicinoje taikomų organinių junginių. Į kraujotaką patekę neprasiskverbia per daugumos kraujagyslių sienelę ir nesikaupia atitinkamuose audiniuose. Tai sudaro sąlygas naudoti KT kraujotakos vaizdinimui, angiogenezės bei kraujagyslių pažaidų tyrimuose. Parodyta, kad KT audiniuose sulaikomi tankių skaidulinių pluoštų, pvz., bazinės membranos, ir tai sąlygoja jų nepatekimą į plaukų folikulus, prakaito bei riebalų liaukas, periferinius nervus, raumenines skaidulas. Tikimasi, kad šie rezultatai padės aiškintis KT pernašos per biologinius barjerus mechanizmus, leis tiksliau įvertinti jų taikymo saugumą bei praplės KT panaudojimo biomedicinoje galimybes.

No description available.

Liquid crystals (LCs) are an interesting class of materials that are attracting significant attention due to their ever-growing applications in a wide variety of fields such as liquid crystal display (LCD) technology, materials science and bioscience. In recent years, along with the developments of materials at the nanoscale, doping LCs with nanoparticles (NPs) has emerged as a very promising approach for improving LC properties. Nanoparticle additives can introduce novel effects on optical and electro-optical properties of nematic liquid crystals (N-LCs), such as altered molecular alignment, faster response time and increased efficiency. This thesis studies the impacts that the inclusion of metallic NPs made of gold or semiconductor CdSe quantum dots (QDs), have on optical and electro-optical properties of N-LCs. Using polarized optical microscopy and detailed capacitance and transmittance measurements of nematic mixtures in electro-optic test cells, characteristics such as optical texture, phase transition temperatures, switching voltages and dielectric anisotropy are investigated in pure as well as doped samples. Surface ligands in NPs and their chemical functionalization play an important role in the LC-NP interactions, largely by determining the dispersibility of NPs and stability of the nanocomposites. One important objective of this thesis is to investigate and prepare a series of gold nanoparticles (Au NPs) with specially formulated robust coatings that maximizes solubility and stability in LC medium. Silanization of NPs is developed as a method to overcome the stability challenge. The functionalization of silanized NPs with aliphatic ligands or liquid crystalline molecules, provides chemically and thermally stable NPs with hydrophobic and structurally compatible surfaces required for dispersion in N-LCs. After complete characterization the synthesized particles are used to make the new nematic nanocomposites. By analysis of the structure-property relationships governing LC-nanomaterial composites and by comparison of new results and data from previous studies on other types of NPs, this thesis will further reveal the mechanism of the interrelations between host LC molecules and NP, considering the role of variables such as core composition, size and surface chemistry of NPs (e.g. siloxane shell, aliphatic ligand vs. liquid crystalline ligand) in achieving stable LC composites with desired optical and electro-optical properties.

Fluorescent carbon dots (C-dots) are well known for their low cell-cytotoxicity, biocompatibility, low preparation cost, excitation dependent photoluminescence, and excellent photostability. Typically, raw C-dots have low quantum efficiency and thus researchers have been utilizing biocompatible polymers such as polyethylene glycol (PEG) as a passivation agent in order to increase fluorescence signal. In this work, we report fluorescent self-passivated carbon nanodots (CNDs) synthesized from PEG by using it as a carbon source as well as a passivating agent. Importantly, the addition of graphene quantum dots (GQDs) during the synthesis of self-passivated CNDs can tune photoluminescence property. The results of bioimaging and cytotoxicity test of self-passivated CNDs hold promises for biomedicine applications.

In recent years, semiconductor quantum dots (QDs) have arisen as a new class of fluorescent probes that possess unique optical and electronic properties well-suited for single-molecule imaging of dynamic live cell processes. Nonetheless, the large size of conventional QD-ligand constructs has precluded their widespread use in single-molecule studies, especially on cell interiors. A typical QD-ligand construct can range upwards of 35 nm in diameter, well exceeding the size threshold for cytosolic diffusion and posing steric hindrance to binding cell receptors. The objective of this research is to develop tagging strategies that allow QD-ligand conjugates to specifically bind their target proteins while maintaining a small overall construct size. To achieve this objective, we utilize the HaloTag protein (HTP) available from Promega Corporation, which reacts readily with a HaloTag ligand (HTL) to form a covalent bond. When HaloTag ligands are conjugated to size-minimized multidentate polymer coated QDs, compact QD-ligand constructs less than 15 nm in diameter can be produced. These quantum dot-HaloTag ligand (QD-HTL) conjugates can then be used to covalently bind and track cellular receptors genetically fused to the HaloTag protein. In this study, size-minimized quantum dot-HaloTag ligand conjugates are synthesized and evaluated for their ability to bind specifically to purified and cellular HTP. The effect of QD-HTL surface modifications on different types of specific and nonspecific cellular binding are systematically investigated. Finally, these QD-HTL conjugates are utilized for single-molecule imaging of dynamic live cell processes. Our results show that size-minimized QD-HTLs exhibit great promise as novel imaging probes for live cell imaging, allowing researchers to visualize cellular protein dynamics in remarkable detail.

In the field of spintronics there is a strong need for an efficient spin-polarizing device. To that end, two basic devices are proposed: a series of Aharonov-Bohm (AB) rings linked in series with intermediate quantum dots (IQD) and the quantum dot spin polarizer (QDSP). In each case the system is built of quantum dots (QD), each of which can be Zeeman split with a tunable external magnetic field. Spin neutral input and output leads are also attached to each system. The Tight Binding Approximation (TBA) is used to model each system. Mathematica is used to solve the systems generated by TBA, so that the transmission or reflection of a system can be evaluated. We find that a series of AB rings provides for wide, energetically separated, spin polarized conduction bands. The QDSP provides physical separation of spin polarized electrons, making a spin polarized base current possible. / Methods of analysis -- The Aharonov-Bohm ring -- The quantum dot spin-polarizer. / Department of Physics and Astronomy