The stability of pharmaceutical formulations in non-aqueous media is poorly understood. In order to discover which factors affect the stability, screening studies using a statistical Design of Experiment approach was adopted and revealed that; solid concentration, solvent, solid and surfactant types all have significant effects on the stability of the sol. In addition a number of factors, such as water concentration in combination with the solvent, were found be significant. The factors of water and then surfactant in combination with solvent and solid have been further investigated, by use of sedimentation, rheology and electrophoretic measurements. It was found that for hydrophilic pharmaceutical particles, water contamination had the largest impact on the sols' properties, particularly where the solvent had only limited water miscibility. The least impact was found with a hydrophobic particle and a water miscible solvent. In the absence of any water in the solvent, the anionic surfactant AOT was found to be an effective surfactant for most systems at stabilising the sols. Electrophoretic measurements revealed that the addition of AOT most cases reversed the charge of the particles to that observed in water. However, the surfactants 12-hydroxysteric acid and Brij-35 were found to be more effective than AOT at stabilising the systems against the effect of water contamination in the solvent. By addition of these surfactants it was possible to stop the catastrophic irreversible aggregation which resulted from water contamination. After the addition of surfactant, water had the effect of causing the suspensions to visibly thicken, but aggregation did not occur This study shows that the stabilisation of pharmaceutical dispersions is complex and there is no universal route to achieve this. However, for hydrophilic particles dispersed in a water immiscible non-polar solvent the effect of water in the solvent lead to aggregation of the particles, presumable due to capillary bridging effects; addition of a surfactant can help to mitigate these effects.

Metallomics approaches based on the combined use of elemental and molecular mass spectrometry for arsenic speciation analysis in phytoremediating plants, marine algae, cut tobacco and cigarette smoke total particulate matter have been developed. Size-exclusion chromatography (SEC)-ICP-MS is proposed to use as a powerful tool for selecting both the appropriate extractant as well as optimum extraction conditions. Comparative SEC-ICP-MS As profiles and total As concentrations in the extracts were used to identify the optimum condition for As speciation studies as a compromise between extraction efficiency and preservation of compound identity. Methodologies have been developed to gain a better grasp of the factors involved in the uptake and distribution of As in the hydroponically grown Arabidopsis thaliana. The effect of the presence of Se on the As and Hg incorporated into the leaves was investigated here for the first time; Se in the growing media was found not to affect As and Hg concentrations in the leaves. Results also revealed the presence of small amounts of As-PC3, As-PC4 and As-PC5 complexes in the leaves, which were characterized by ESI-Orbitrap MS to minimize ambiguity in species identification. The application of an in vitro dialysis method for predicting the As bioaccessibility in selected edible marine algae, was investigated here for the first time. Results showed low As dialyzability (10-20%) and no transformation of As species, primarily arsenosugars, observed following in vitro gastrointestinal digestion. Knowledge of the distribution of arsenic species in cut tobacco, obtained by sequential extraction, provides an insight into the transformation of arsenic species during the combustion process when the cigarette is burnt. The combustion of organic compounds present in tobacco resulted in the change of redox state and As-species distribution in tobacco smoke. Both the hyphenated MS and XANES techniques were used to obtain information about arsenic speciation in smoke condensates. The results showed that the tobacco smoke contained a mixture of As(III) and As(V); As(III) being found as arsenite and, possibly, thio-arsenite by HPLC-ICP-MS. The reduction of As(V) to As(III) during dynamic cigarette smoke formation can be explained by the overall smoke redox properties in accordance with the cigarette combustion process.

Electrochemical biosensors have long been used for measuring pH changes in complex biological samples. This research work involves investigating iridium sensors as a potential tool for detecting viral RNA by means of pH sensing during transcription mediated amplification (TMA). The iridium oxide film was formed on gold wire by electrochemical deposition. When complementary DNA/RNA bases are hybridized, they release a pyrophosphate molecule which is eventually hydrolyzed, contributing to the pH change during the TMA reaction which in turn is measured in voltage (mV) by the iridium sensor. Firstly a standard method for bacteriophage MS2 RNA amplification method was established. A Real Time PCR assay for MS2 RNA using TaqMan probe chemistry was used to quantify the MS2 RNA and used as a gold standard for later project. We then used transcription mediated amplification (TMA) technique using reverse transcriptase and RNA polymerase enzymes for producing MS2 RNA amplicons and resulting protons generated during amplification were measured with iridium sensors. The iridium oxide sensor showed linear pH potential response and showed a near ideal Nernstian behaviour in the pH range 2 – 12 with a slope of -60mV/pH. Since TMA is an isothermal amplification technique the iridium sensors produced reproducible and reliable measurements. To increase the cation selective permeability and inhibit possible interferences the iridium oxide sensor was coated with 5% Nafion. The sensor showed the same linearity in voltage response against RNA concentrations in protein enriched samples (20 mg/ml albumin) compare to RNA in water. The iridium oxide sensor was a rapid method of viral RNA detection as the detection time for MS2 RNA was 10 minutes. The lower limit of detection of the iridium sensor was 5ng of MS2 RNA which was comparable to the established real time PCR sensitivity. To further enhance the sensor’s the sensitivity the iridium oxide sensor was prepared on a 3 mm × 3 mm glass slide which increased the slope for 5 ng of MS2 RNA from 3.25mV/min to 4.07mV/min resulting in an improved limit of detection.

The magnitude and significance of crude oil fouling have led to a number of studies; however, the fundamentals of the complex fouling process are not fully understood. This thesis describes the use of the high chemical specificity, imaging capabilities and fast acquisition times offered by advanced vibrational spectroscopic techniques to characterise and understand the physicochemical behaviour of these complex materials. Rapid and reliable methodologies are developed to provide an important chemical characterisation tool which will advance research into crude oil fouling. An emerging and powerful imaging technique based on Fourier transform infrared (FTIR) spectroscopy is applied for the first time to the characterisation of deposited foulants and asphaltenes. Attenuated total reflection (ATR)-FTIR spectroscopic imaging has the advantage of being a non-destructive analytical technique and most importantly, is able to provide both chemical and spatial information about a sample. The novel application, of combining macro and micro ATR modes in FTIR imaging, yields important information about the spatial distribution of different components in deposited foulants and laboratory-extracted asphaltenes. Clusters of chemically different compounds in crude oil deposits from the refinery, such as asphaltenes, carbonates, sulphates, sulfoxides, oxalates and even “coke-like” materials, were identified and analysed. A lab-made aperture is utilised in the macro ATR diamond accessory to correct spectral distortions that occur for high refractive index materials. This approach has been extended to monitor the heating of crude oil in situ and the onset of asphaltene deposition was determined. Micro ATRFTIR imaging of the particulates formed in the crude oil after heating has identified seven chemically different species, namely, silicates, amides, sulphates, carbonates, sulfoxides, vitrinite compounds and “coke-like” materials which are products of different reactions in fouling. The complementary use of Raman and FTIR spectroscopy has been demonstrated to characterise the carbon structures in asphaltenes. The ID/IG and IV/IG parameters derived from the Raman spectra on real deposits showed that it has more ordered structures compared to petroleum asphaltenes which may be linked to the ageing effects of the deposit in heat exchangers. The ATR-FTIR spectra of petroleum asphaltenes suggest that the shape of an average asphaltene is more similar to a wide continental model than the archipelago model.

Multi walled carbon nanotubes (MWCNTs) possess properties that make them particularly relevant for sensing applications in both the gas and liquid phase. This study presents an evaluation of cheap readily available CVD grown MWCNTs for use as fire gas sensors. Current fire detectors exploit heat and smoke detectors and it is hoped that the inclusion of gas detectors will increase the speed and reliability of detection. In order to prepare a variety of different MWCNTs a range of CVD synthesis were employed including an injected catalyst method where MWCNTs grew in dense mats from quartz substrates, MWCNTs were also synthesised using a sputtered Fe catalyst layer with acetylene as the carbon source which enabled control over the positioning of the growth. In each case, the growth parameters were varied until aligned growth was achieved. Doping of MWCNTs was also carried out as this may enhance and enable some control over the electrical properties of the CNTs; nitrogen was also added as a dopant by including 1,4-diazine as a precursor, and the effects on morphology of the MWCNTs produced were studied. The chemistry of the surface is also known to affect the sensing properties of CNTs. A batch of MWCNTs produced via the injected catalyst method were purifed by acid reflux, base washing and high temperature vacuum annealing, then modified with platinum or palladium metal nanoparticles via a reduction of the metal salts under hydrogen. MWCNTs were also coated with the polymer polyethyleneimine and with copperphthalocyanine. Prototype sensor devices were fabricated by electrophoretic deposition of these modified MWCNTs, and gas testing was carried out with the gases NO2, NH3, CO, H2 and C3H6. The mechanisms of sensing were investigated by repeating the tests at different temperatures, which revealed which sensing mechanisms were dominant and responses were compared between the differently modified MWCNTs. Sensor response was also investigated with a series of vapours to probe the dispersive and polar interactions on the MWCNT walls.

We have designed and developed a novel form of biosensor with implications to both the understanding of the mechanistics of the cell function and as a biomedical diagnostic tool. As part of a platform of technologies orientated to single cell proteomics, this project focuses on the development of single molecule microarrays (SMM), which is intended to produce proteome snap shots of individual cells. The single cell proteomics platform includes technologies for microfluidics based live cell analysis, manipulation, lysis and analysis of the proteome of a single cell. Analysis of single cells to high and detailed resolution will provide both quantitative and qualitative information on discrete events and protein dynamics, usually overlooked through ensemble measurements of large populations of inhomogeneous cells. With the aim of developing a quantitative and qualitative tool oriented to single cell proteomics; we present an antibody microarray capable of simultaneous quantification of multiple proteins to the single molecule level. The principle enhancements of design enabling the capabilities described are based around single molecule detection of fluorescently labelled analytes bound to affinity patches of antibodies; the affinity patches are limited to the microscope field of view and incorporated into microfluidic devices, detection is performed with a single resolution through the use of total internal reflection fluorescence (TIRF) microscopy. The cell is handled and lysed in a microfluidic device to minimize dilution of the sample, so that the greater majority of analyte is bound to the sensing surface at equilibrium and so detectable at the surface through TIRF evanescent wave. This technology also bears significance for the detection of many forms of analyte, such as glycan profiling, direct mRNA quantification and the analysis of post translational modification (PTM). The SMM produces rapid snap shots of a proteome; this makes it suitable for rapidly changing and dynamic cell signalling cascades, of which PTM makes a significant contribution to cell fate. We present here the basic principles of design and the initial testing of the design and current setup. Also discussed are intensions and capabilities for the technology, as well inevitable potential pitfalls and intrinsic limitations.

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