Development of "super-resolution" cryogenic chemical imaging

Our bodies process a wide range of small molecules including dietary nutrients and pharmaceutical drugs. The ability to map accurately where these molecules accumulate within tissues is critical for understanding health and disease. It has, however, been challenging to achieve this goal with a high enough spatial resolution to image intact molecules inside single cells. We propose to overcome this technical limitation by improving a chemical imaging technology called cryogenic OrbiSIMS. First, we will improve the resolution of cryogenic OrbiSIMS via optimisation of the instrument and the sample preparation. Second, we will develop a series of markers to label cellular structures in order to provide OrbiSIMS images with meaningful biological landmarks. And third, we will expand the usefulness of some of these markers to other chemical imaging platforms. Using this three-pronged approach, we aim to remove critical obstacles to the wide adoption of chemical imaging in biomedical and pharmaceutical research.