Spectroscopic analysis of single nanoparticles for drug delivery

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The use of nanoparticles as vehicles for targeted drug delivery offers significant clinical benefits and is the subject of considerable research by all of the major pharmaceutical companies. For example cancer therapies involving highly toxic agents can be targeted at tumours much more precisely than is possible using standard formulations, greatly reducing the overall dose and resultant side-effects, and vaccines based on genetic materials can be loaded into viral vectors to stimulate the immune response in cells and increase therapeutic benefit. The detailed study of drug loading and release by nanoparticles in fluid suspension is an outstanding challenge however, and new measurements techniques are required to advance the development of drug delivery nanomaterials and to lower the barriers to clinical uptake of new nanomedicines. Techniques that allow quantitative and chemically specific measurement of single nanoparticles in solution are particularly powerful in this regard as they give the clearest picture of the composition of the particles in an administrable form.This project will build on the group's previous work on the characterisation of single nanoparticles in fluids using optical microcavity devices. Specifically the project will investigate the degree to which enhanced Raman spectroscopy can be performed on nanoparticles trapped in the microcavities by optical tweezing. There are two different approaches that we hope to explore during the project, based on resonant cavity enhancement of the excitation field and enhancement of the Raman scattered field. The former approach is expected to reduce background signals and allow for calibration-free measurement of the mass of drugs loaded, while the latter approach is expected to allow the study of smaller particles and provide a higher signal-to-noise ratio. The methodology will involve the design and engineering of microcavity mirrors which have the necessary reflectivity spectrum, the construction of the microcavities inside a flow cell (this is an adaptation of existing apparatus) and the construction of a suitable light collection system with high sensitivity, including a low noise spectrograph and single photon detection apparatus. The project will then involve the demonstration of the technique by characterising test samples, starting with simple nanoparticles such as solid silica, which show strong and well-defined Raman signatures, and later moving on to mesoporous particles with and without additional chemical species loaded into them.The project is supported by Oxford HighQ Ltd who provide CASE top-up funding. Oxford HighQ Ltd are a spin-out from the research group, developing commercial instruments for nanomedicine research and other microcavity-enhanced sensing applications. The company is based at the Begbroke Science Park, to which there is a regular shuttle-bus service from the university laboratory. Through the industrial supervisor, CTO Dr Aurelien Trichet, the company will provide advice regarding unmet need in the field of nanoparticle characterisation and links with nanomedicine research groups for accessing samples, as well as offering a potential route for commercialisation of project outputs.This project falls within the EPSRC Healthcare Technologies Theme.