Cryogenic electron microscopy for native state analysis of nanoparticles in liquids

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The success of a nanoparticle system designed for a specific application is contingent on controlling the interfacial chemistry (e.g. colloidal stability, overall size, etc). To truly understand this, we require approaches to probe and understand the interactions between nanoparticles and the environments they are dispersed in.This project will focus on developing methods to characterise nanoparticles dispersed in liquids. Electron microscopy is ideally suited to the analysis of nanoparticles, with the required spatial resolution to investigate the size and structure of nanoparticles, and the associated analytical tools, energy dispersive X-ray (EDX) and electron energy loss (EEL) spectroscopies, which provide composition and bonding information at the single particle level. The limitation, however, is the vacuum level required in an electron microscope therefore necessitates dry samples. This project will utilise a biological sample preparation approach where nanoparticles dispersed in a liquid are frozen and then analysed in an electron microscope at cryogenic temperatures, with the analytical capabilities used to probe the interactions between different nanoparticles, and between the nanoparticles and components of the liquid media they are suspended in.Two types of cryogenic (cryo-) electron microscopy will be investigated in this project; (scanning) transmission electron microscopy ((S)TEM) and focused ion beam scanning electron microscopy (FIB-SEM), with the limits of the techniques applied to frozen samples established. Rigorous characterisation of nanoparticles will enable understanding of their impact and prediction of behaviour. Two nanoparticle systems with biomedical applications will be used as model systems; for representative analysis this characterisation must be conducted in biologically relevant liquid media, and at the scale of the individual nanoparticle. The outcome of the project will be understanding the structure and dispersion of two model nanoparticle system when suspended in liquids, and the development and assessment of this nanoscale analytical approach, which can then be applied to further systems of importance.