Radiosensitization is a novel targeted therapy strategy where chemical compounds are being explored to enhance the sensitivity of the tissue to the effects of ionizing radiation. Among the different radiosensitizers alternatives, nanomaterials have shown promising results by enhancing tumor injury through the production of free radicals and reactive oxygen species (ROS). In this work, Gold-supported titania (Au@TiO2) nanocomposites were synthesized through an innovative strategy using X-ray irradiation, and their potential as radiosensitizers was investigated. Radiosensitization of Au@TiO2 nanocomposites was assessed by monitoring the decomposition of Methylene Blue (MB) under X-ray irradiation in the presence of the nanomaterial. Radiosensitization of Au@TiO2 was thoroughly investigated as a function of parameters such as Au loading, TiO2 particle size, nanomaterial concentration, different irradiation voltages, and dose rates. Results showed that the presence of Au@TiO2 increases significantly the absorbed dose, thus enhancing MB decomposition. The mechanism behind Au@TiO2 radiosensitization relies on their interaction with X-rays. TiO2 produces reactive ROS whereas Au leads to the generation of photoelectrons and Auger electrons upon exposure to X-rays. These species lead to an enhanced degradation rate of the dye, a feature that could translate to cancerous cells damage with minimal side effects. The radiosensitization effect of Au@TiO2 nanocomposites was also tested in biological settings using Microcystis Aeruginosa cells. The results showed an increase in cell damage when irradiated in the presence of Au@TiO2 nanocomposites. Au@TiO2 nanocomposites were fabricated using X-ray radiolytic synthesis, a method that diverges from conventional fabrication processes and leads to negligible by-product formation, an important feature for medical and catalytic applications. In this work, Au nanoparticles are supported on TiO2 with a mean particle size of either 6.5 nm or 21.6 nm, using different ligands such as NaOH or urea, and under different absorbed doses to determine the effects of these parameters on the nanomaterials’ characteristics. Overall, Au@TiO2 synthesized by X-rays showed remarkable promise as radiosensitizers, a concept relevant to a number of medical, biological and environmental applications.

The bacterial meningitis caused by Neisseria meningitidis is responsible for considerable morbidity and mortality throughout the world. Given the limitations of existing diagnostic tests and the severity of the illness associated with the disease, there is a clear requirement for a rapid and specific diagnostic assay. This thesis describes the development of nanoparticle based tests for the detection of Neisseria meningitidis specific cell surface markers. As an initial target antigen, a recombinant form of highly conserved outer membrane protein, OMP85 was used. Within the OMP85 protein sequence, a predicted antigenic sequence between residues 720 and 745 was identified and found to be unique to this organism. This amino acid sequence was synthesised as peptide (SR1) with a gly-gly-cysteine spacer sequence at the N-terminus using t-boc chemistry. Also, the major virulence factor, capsular polysaccharide of N. meningitidis serogroup B bacteria was purified. Polyclonal antibodies were raised against purified OMP85 antigen in rabbits and against SR1 peptide and also against formalin inactivated N. meningitidis serogroup B whole cell bacteria in sheep. This panel of different antibodies including the commercial anti-capsular monoclonal antibodies were examined for cross reactivity against a range of closely related Gram negative bacteria. Based on these cross-reactivity studies, a highly specific anti-NM antibody was developed following purification of the anti-SR1 antiserum by immuno-affinity chromatography. Purified OMP85 antigen and anti-OMP85 antibody were successfully conjugated on 13, 30, 40, 50 and 60 nm gold nanoparticles by an electrostatic adsorption method. Coupling of the gold nanoparticles results in a shift of the respective surface plasmon peak toward longer wavelengths (in the range of 600-800 nm) resulting in a change of the colour of the colloidal suspension from red to purple to blue. An attempt was made to develop a rapid diagnostic assay based on gold nanoparticle induced colour shift assay for N. meningitidis by utilising the specific interaction of OMP85 and anti-OMP85 antibody conjugated to gold nanoparticles as a model system. However, this system was not reproducible and is likely to be due to problems with stability of gold nanoparticles during the conjugation process. As an alternative approach, a highly selective quartz crystal microbalance (QCM)-based immunosensor was designed using the same OMP85/anti-OMP85 antibody system. A method was developed using polyvinylidene fluoride (PVDF) coated QCM crystals with protein A for the directional orientation of the antibodies. To further enhance the sensitivity of the test, OMP85-conjugated gold nanoparticles were used as signal amplification probes for the reproducible detection of the target down to 300 ng/mL, corresponding to a five fold increase in sensitivity compared to detection of OMP85 antigen alone. Also, this sensor has successfully been employed to detect whole cell bacteria at a concentration as low as 100 cfu/mL. Thus, in this study using the real-time QCM measurements, a novel strategy has been developed for the sensitive detection of both N. meningitidis bacteria and the protein antigen at very low concentrations, using gold nanoparticles as signal amplification probes.

Injection of a mixture of HAuCl4 and cellulose dissolved in the ionic liquid (IL) 1-butyl-3-methylimidazolium chloride [Bmim]Cl into aqueous NaBH4 leads to colloidal gold nanoparticle/cellulose hybrid precipitates. This process is a model example for a very simple and generic approach towards (noble) metal/cellulose hybrids, which could find applications in sensing, sterile filtration, or as biomaterials.

Development of a simple, specific, sensitive and rapid RNA microchip for detection of Head and Neck Cancer (HNC) mRNA, pathogenic bacteria and dengue virus (DENV) RNA is reported. By use of nucleases and polymerases specific RNAs are selectively labeled and detected without separation, reverse transcription and or polymerase chain reaction. This is accomplished by designing specific Hybrid probes consisting of DNA-2’-O-Me-RNA-DNA regions to target the RNA of interest. Upon hybridization with the target RNA, RNase H digestion is used to remove the 3’- RNA sequences which exposes the template for Klenow extension with reporter molecules such as hapten or fluorophore labels. This novel RNA microchip is fast (ca. 1 h detection time), selective as individual RNAs are detected in a synthetic mixture and total RNA mixtures, specific for single nucleotide polymorphisms (SNPs) discrimination and sensitive up to attomole level for chemiluminescence detection and lower femtomole for gold nanoparticles (AuNPs) and silver staining method. Using chemiluminescence, HNC biomarkers, VCAM1 and IL8 are specifically labeled and detected in the presence of thousands of other mRNAs in cancer cell lines and human colon cancer total RNA without interference. Furthermore, the method is highly specific as shown with DENV SNPs discrimination. Moreover, we report rapid (ca 1hour), selective, specific multi-marker detection of pathogenic mRNAs and HNC mRNAs using AuNPs-silver staining on the RNA microchip. Streptavidin gold nanoparticles technology has a potential in the analysis of specific mRNAs in a wide array of field including infectious diseases diagnosis, viral infections, food safety, gene expression profiling and cancer detection. A simple and rapid NaOH RNA extraction procedure was developed for E. coli total RNA extraction with specific results on the RNA microchip using both chemiluminescence and AuNPs silver staining. This extraction avoids the use of commercial RNA purification kits thus reducing the cost. Furthermore, visual detection on the RNA microchip is simple, does not require electricity or special equipment, and therefore is a good candidate for field diagnostics with minimum resources.

X-ray fluorescence is a well-understood phenomenon in which irradiation of certain materials, such as gold, with x-rays causes the emission of secondary x-rays with characteristic energies. By performing computed tomography using these fluorescence x-rays, the material of interest can be imaged inside an object. Our research group has already demonstrated that x-ray fluorescence computed tomography (XFCT) imaging using a typical 110 kVp microfocus x-ray tube is feasible for a small animal-sized object containing a distribution of a solution of low concentration gold nanoparticles. The primary goal of this thesis work was to study the effect of source x-ray energy spectra on gold fluorescence detection using the XFCT system. A computational approach using the Monte Carlo method was used. First, a computational model was created using the Monte Carlo N-Particle (MCNP) transport code based on the experimental setup of the pre-existing XFCT system. Simulations were run to verify the validity of the MCNP model as an accurate representation of the actual system by means of comparison with experimentally-obtained data. Finally, the model was used for further purely computational work. In the MCNP model, the source spectrum was changed to reflect several theoretical and experimentally obtained options. The effect of these changes on gold fluorescence production was documented and quantified using the signal-to-background ratio and other qualitative measures. The results from this work provided clues on how to improve the detection of fluorescence photons from gold nanoparticle-loaded objects using the XFCT system. This will benefit future research on the development of the XFCT system in the context of making it more feasible for gold nanoparticle-based preclinical molecular imaging applications.

In this study, conjugated monomers containing fluorene units / 2-(9,9-dihexyl-2-(thiophen-2-yl)-9H-fluoren-7-yl)thiophene (TFT) and 5-(9,9-dihexyl-2-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-9H-fluoren-7-yl)-2,3dihydrothieno[3,4b ][1,4] dioxine (EFE) were synthesized on the basis of donor-acceptor-donor approach and their electrochemical polymerization were achieved via potential cycling. Optical and electrochemical properties of their corresponding polymers, poly(2-(9,9-dihexyl-2-(thiophen-2-yl)-9H-fluoren-7-yl)thiophene) PTFT, and poly(5-(9,9-dihexyl-2-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-9H-fluoren-7-yl)-2,3dihydrothieno[3,4b ][1,4] dioxine) PEFE, were investigated and it was found that polymer films exhibited quasi-reversible redox behavior (Epox= 1.10 V for PTFT, Epox = 0.70 V and 1.00 V for PEFE) accompanied with a reversible electrochromic behavior, yellow to dark green for PTFT, yellow to parliament blue for PEFE. Their band gap values (Eg) were found to be 2.36 eV and 2.26 eV for PTFT and PEFE, respectively. Furthermore, gold nanoparticles (AuNP) were prepared and their interaction with polymer films, PTFT and PEFE, were investigated using spectroscopic techniques. The fluorescence properties of the polymers and their composites, prepared by the interaction of AuNP with polymers, were also investigated.

Gold nanoparticles strongly absorb and scatter visible and near infrared light because of the strongly enhanced electric fields at the surface. This provides the potential of designing novel optically active reagents for simultaneous molecular imaging and photothermal cancer therapy. In this thesis, gold nanospheres and nanorods conjugated with anti-epidermal growth factor receptor (anti-EGFR) antibodies that specifically target EGFR on the cell surface are shown to be used for dual diagnostics and therapy. Using micro-absorption spectroscopy and light scattering imaging, cancerous (HOC 313 and HSC 3) and noncancerous cells (HaCat) can be differentiated due to the overexpression of EGFR on the surface of cancer cells. By irradiating the cells with a CW laser, selective photothermal cancer therapy is realized in visible region by using gold nanospheres and in near infrared region by using gold nanorods. The use of nanorods allow for in vivo therapy due to the fact that their absorption is in the near infrared region at which the laser light meets less interference from the tissue absorption. In addition, the catalytic effect of gold nanoparticles on the oxidization of NADH to NAD+ is investigated. The addition of gold nanoparticles is found to quench the NADH fluorescence intensities but has no effect on the fluorescence lifetime. This suggests that the fluorescence quenching is not due to coupling with the excited state, but due to changing the ground state of NADH. The intensity of the 340 nm absorption band of NADH is found to decrease while that of the 260 nm band of NAD+ is found to increase as the concentration of gold nanoparticles increase. This conversion reaction is further supported by nuclear magnetic resonance and mass spectroscopy. The linear relationship between the initial reaction rate of NADH and the concentration of gold nanoparticles strongly supports that NADH is surface catalyzed by the gold nanoparticles. The catalytic property of this important reaction might have important future applications in biological and medical fields.

This thesis focuses on development of novel nanomaterials, including semiconductor quantum dots (QDs) and gold nanoparticles (AuNPs), for fabricating white-light emitting devices and assaying thiols in biological and environmental samples. The thesis mainly contains two divisions. One demonstrates synthesis, optical properties and white-light emissions of alloyed quantum dots and their application to light-emitting devices. The other describes to combine functionalized gold nanoparticles with capillary electrophoresis and accomplish high selectivity and ultrasensitive detection for thiols. First, through one-step aqueous synthesis, alloyed ZnxCd1¡VxSe QDs have been successfully prepared at low temperatures by reacting a mixture of Cd(ClO4)2 and Zn(ClO4)2 with NaHSe using 3-mercaptopropionic acid as a surface-stabilizing agent. The optical properties and composition of the alloyed QDs were highly dependent on the molar ratio of Zn2+ to Cd2+. With the increase in Zn content, a systematic blue shift occurred in the first exciton absorption and band edge emission. Moreover, X-ray diffraction peaks of the alloyed QDs systematically shifted to larger angles simultaneously. These systematic shifts indicated the formation of the alloyed QDs. Interestingly, among these alloyed QDs, Zn0.93Cd0.07Se QDs exhibited white-light emission with quantum yields of 12%. In addition, we discovered that we could adjust the relative strength of the band edge and trap state emissions by controlling the reaction time, thereby attain white-light-emitting QDs. Finally, we blended alloyed QDs with ultraviolet-transparent polydimethylsiloxane (PDMS) to develop a white-light, solid-state lighting device by using a 365-nm UV lamp as the pump source. In the other part of this thesis, we proposed a method for selective enrichment of thiols using Tween 20-capped gold nanoparticles (AuNPs) prior to capillary electrophoresis coupled with laser-induced fluorescence (CE-LIF). By forming Au-S bonds, Tween 20-AuNPs can selectively extract thiols from a complicated matrix. A Tween 20 capping layer not only suppresses nonspecific adsorption, but also enables NPs to disperse in a highly-salinity solution. For analyses of aminothiols, after extraction and centrifugation, thioglycollic acid was utilized to remove aminothiols that attached to the NP surfaces. The extracted aminothiols was derivatized with o-phthalaldehyde (OPA) followed by CE-LIF. The use of this nanoprobe provided approximately 11-, 282-, and 21-fold sensitivity improvements for homocysteine (HCys), glutathione (GSH), and £^-glutamylcysteine (GluCys), respectively. Furthermore, the limits of detection (LODs) at a signal-to-noise ratio of 3 for HCys, GSH, and GluCys are 4013, 80, and 383 pM, respectively. A practical analysis of aminothiols in human urine sample has been accomplished by our proposed method. For another application to determining thiol-containing peptides, we use dithiothreitol to remove thiol-containing peptides from the NP surface through ligand exchange. The released peptides are selectively derivatized with OPA to form tricyclic isoindole derivatives. After injecting a large sample volume, the sensitivity of these peptides was improved by stacking them via using polyethylene oxide (PEO) as additive for on-line concentration and separation. As a result, LODs for GSH, GluCys, and phytochelatins (PC2 ~ PC4) were down to 0.1-6 pM. The proposed method has the lowest LODs for five peptides compared to other reported methods, and it also detect dissolve thiols in seawater in practice. Our proposed method is capable of ultrasensitive detection for thiols in biological and environmental samples.

The electro-optical properties of the ZnO/Si heterojunction embedded with self-assembled gold nanoparticles on patterned silicon substrate are investigated in this master thesis. High quality n-type ZnO film is deposited on patterned p-type silicon substrate by radio-frequency sputtering to form a ZnO/Si pn junction. The patterned silicon substrates are prepared by ICP-RIE using self-assembled nickel metal dot and silicon dioxide as etching mask. The optimum ICP process conditions of silicon nanopillars are CF4/Ar ~ 40/40 sccm and bias/RF power 400/400 W. Silicon nanopillars of diameter ~ 50 nm and height 100~400 nm are formed on the substrate surface. ZnO film is then deposited of a growth rate ~ 12 nm/min at the substrate temperature = 200oC. The plasmonic effects on the electro-optical properties, including photoluminescence (PL), reflection, and electrical characteristics, are studied by adding self-assembled gold nanoparticles within the ZnO film. The self-assembled gold nanoparticles are formed by thermal deposition and rapid thermal annealing at 700oC. The gold nanoparticles are observed by scanning electron microscopy (SEM) and particles of diameter about 100 nm. The PL intensity of ZnO is enhanced more than ten times at the peak wavelength = 380 nm by adding the gold nanoparticles and silicon nanopillars. Strong blue emission light could be saw with the naked eyes. For the electric characteristics, self-assembled gold nanoparticles in patterned ZnO/Si heterojunction show photoelectric conversion phenomenon because of high electromagnetic absorption and plasmonic effects.

Understanding and manipulating nanosized particles is crucial for the advancement of nanotechnology research. Dependent light scattering of noble metals can be used to achieve new material responses that can be used in different applications. Dependent light scattering of nanoparticles allows the understanding of orientation and location of closely positioned particles. Besides, dependently scattering metallic particles create significantly enhanced near fields and high absorption rates when excited at their plasmon resonance. It is used for spectrally selective heating and melting of nanosized particles as a nanomanufacturing method. With numerical methods dependent scattering properties of particles can be obtained. In this study, the dependent optical absorption efficiencies of metallic nanoparticles are obtained with the newly developed Integrated Poynting Vector Approach (IPVA). This is used in conjunction with a numerical light scattering solution tool DDSCAT. Results indicate that IPVA and DDSCAT together can be used for the estimation of scattering and absorption of nanoparticles affected by the near field of other particles in their close vicinity. The method is suggested to be suitable for the understanding of physical mechanisms behind dependent scattering prior to experiments that require lots of effort and resources.