The ability to directly monitor biomolecular interactions (e.g. DNA-DNA, RNA-DNA, protein-protein) in real-time is of great importance to many areas of biology and medicine. At the cellular level, very few molecules can be responsible for inducing a significant biological response and there remains an urgent need for highly sensitive optical methods able to both identify and spatially track multiple target biomolecules simultaneously in complex and dynamic biological environments. To address this challenge we propose to develop a unique multi-imaging platform capable of monitoring large numbers of individual, freely moving nanoparticles and monitoring their interactions with target molecules and other nanoparticles. This new technology will initially be applied to the multiplexed detection of microRNAs with the distinct advantage of not requiring either target pre-modification or subsequent amplification steps to achieve the sensitivities necessary for the direct analysis of genomic RNA samples. The research takes advantage of the electronic properties of metallic nanoparticles that are associated with greatly enhancing the intensity of various types of spectroscopic signals such as scattering, Raman and fluorescence. These signals are highly responsive to changes in the immediate environment around each nanoparticle with Raman in particular providing a molecular fingerprint useful for identification. However, typical investigations involve applying only one of these spectroscopic modalities and either looking at select individual particles immobilised on a surface or acquiring an ensemble-averaged spectrum of the bulk sample. Imaging is a particularly powerful and intuitive approach for investigating complex systems. The radically different multi-spectroscopic methodology proposed here enabling the high-throughput visualisation of individual particles along with rapid optical discrimination between different particles sizes and clusters is expected to have a far-reaching impact. In addition to creating a powerful tool for bioanalytical investigation, this research will open up significant new opportunities to physicists, chemists and engineers interested in the functionalisation and assembly of nanoparticles to create next generation materials and devices.

Nanotechnology is rapidly expanding, and is forecast to become a trillion dollar industry in the near future. It is inevitable that as nanotechnology applications increase, increasing amounts of manufactured nanoparticles (mNPs) will be released into the environment. The environmental and human health implications of the release of most of the huge range of possible particle types are as yet largely unknown, but in the context of groundwaters, apart from implications for the drinking of contaminated water, there is also a potentially serious threat to indigenous bacterial populations, including those that are involved with attenuating contaminants. Thus it is very important to develop methods for assessing the mobility of mNPs in the various environmental compartments, including groundwaters. The movement of charged interacting particles through variably-sized rock pore systems where the pore walls are also charged is complex to predict. Preliminary experiments indicate that aggregation followed by straining and various attachment processes occur, depending on both particle/rock combinations and chemical conditions, but quantification/prediction is not possible without resolving some difficult surface measurement issues. However, such problems are common in a range of commercial applications, and consequently Malvern Instruments (MI), the leading particle characterization instrument manufacturer, has been developing new approaches that offer the possibility of tackling some of these problems. This project, therefore, aims to apply these new approaches to experimental metal oxide mNP / sandstone systems in order to help develop a conceptual model of the interactions of mNPs and rock, and from this to use the measured parameter values in a quantitative representation of the system appropriate for use in pollution risk assessment. The model developed should also be of direct use in cases where mNPs are used in groundwater remediation (though this will be rare until the health issues are more fully understood). The project will include laboratory, field, and computer modelling aspects. Besides facilitating access to a rapidly expanding research area, it will provide training in a specialization lacking in the water industry, and also develop the transferable skills and insights necessary for any groundwater contamination career.

A radical new technique is proposed for in-line process particle measurement at sizes from 0.1micron to 10micron and concentrations up to 50% by volume without interfering in the process. The method involves calculation of optical refractive index of the suspension from critical angle measurements at several wavelengths. This technique requires no light passage through the suspension so its turbidity does not restrict the method. In practice, the critical angle is not clearly marked for turbid suspensions but there is a substantial variation of reflectance in the vicinity of the critical angle.Measuring the suspension refractive index has significant advantages over other widely used non-invasive methods of particle analysis such as spectral extinction and laser diffraction: - The relationship between refractive index and volume fraction is linear for volumetric concentrations up to 50%.- Mie scattering theory can be used to calculate the refractive index of concentrated suspensions of spheres. - Suspension refractive index is sensitive to particle size and size distribution.

This proposal seeks to obtain funding for partially supporting the first UK-China Particle Technology Forum (1-3 April 2007) initiated by the investigators in collaboration with the Particle Technology Subject Group (PTSG) of the Institution of Chemical Engineers (IChemE) and The Particle Characterisation Interest Group (PCIG) of the Royal Society of Chemistry (RSC), supported by a number of industrialists representing various industrial sectors. The aims of the UK-China Particle Technology Forum are to enhance communications between scientists and engineers from both academic institutions and industrial companies of the two countries, to establish a platform to foster new and substantial collaborations, and to identify and address common challenges in the area of particle technology.The UK-China Particle Technology Forum is timely and aligns very well with the government strategies to establishing a partnership in various areas including education, energy, environment, aerospace, e-science and drug development, where particle technology plays key roles.

We use a vast range of products directly or indirectly in everyday life. These range from soups to baby-foods to feed us; paints and coating products to provide robust structural materials; plastics and composites to create many products; and pharmaceutical drugs to fight disease. They share a similar manufacturing method in which raw materials (or reagents) are combined through physical or chemical means, and known as a 'process'. This takes place in a 'process vessel', which is often sealed, under pressure and at elevated temperature. Critical aspects of such processes are efficiency, product quality, energy use and emissions impact. The core aim of this project is to stimulate new sensing products that can enhance these aspects and exploit their markets through licences.The project builds upon our background science and experimental technology, which an estimation of the internal (invisible) distribution of process materials. These innovations harness two principles: spectroscopy - the identification of specific materials; and, tomography - the identification of the distribution of components within the process vessel (similar to methods to 'see inside' human bodies for medical diagnosis). Electrical energy using a 'compressed wide-band' is used, both to give the 'spectral' coverage and to provide fast response to suit dynamic processes. The project aims to provide a demonstration level for specific trial applications; to offer licensees a clear path for onward development into the two product forms: a 'point sensor' form, to identify materials in its immediate vicinity; and a 'zone sensor' form, to identify the distribution of specific materials. Increased knowledge empowers design and/or control to deliver major benefits to process end users: increased productivity and product quality, reductions in emissions and waste products, reduced energy demand and resulting carbon impacts. In illustration we can consider the advantages offered in two product examples. Pharmaceutical compounds are produced using crystallisation processes which are highly variable and can have poor yields such that some batches may not meet tight product specifications. This results in waste of energy, raw materials, and in the costly disposal of the useless out-of specification product. Here a Spec_zone sensor can transform 'process-knowledge' to allow 'smarter control, and gain a major increase in 'on-specification' yield, gaining obvious major benefits. These are very high value products and hence financial business savings can be large. The manufacture of foodstuffs follows a conventional recipe: such as mixing and cooking natural ingredients such as chopped vegetables in water. Unwanted objects in the product such as natural materials such as stalks and large seeds, and unnatural materials such as small pieces of metal or plastic are a possibility. Although these may be unpleasant for adults in products such as soups (but still present a serious 'brand' quality issue for the manufacturer) they may be dangerous if present in baby-foods. It is easy to find metals, using x-ray detectors on a pipeline, but much more difficult to find small objects, such small pieces of plastic or wood which can be detected by the 'wide-band' Spec_point sensor.In conclusion the ability to estimate the presence and concentration of specific materials and their distribution offers major benefits in effective process management. The project will provide demonstrations and concept details to enable licensees to develop future products, based on the Spec_point and Spec_zone concepts. It will include detailed application sectors studies to highlight potential early adopters. It is supported by two instrumentation suppliers who have expressed a keen interest in evaluation, and both have diverse markets and customers who are likely to be involved in evaluations.