Improvements in high-yield detection and localisation of cholesterol in murine brains using water cluster beam secondary ion mass spectrometry

Cholesterol is an example of a neutral lipid which is widely implicated in a number of neurological and other physiological processes. However, it is difficult to detect and precisely locate in situ using mass spectrometry imaging techniques due to low sensitivity and matrix suppression by co-localised lipids. Here we present an application of large water gas cluster ion beams (GCIB) to the task of cholesterol analysis and localisation in rodent brains using secondary ion mass spectrometry (SIMS). Optimum GCIB parameters were established through cholesterol standard analysis. These clusters were then used to analyse whole brain sections with minimal need for sample preparation and no additional matrix application or derivatisation procedures. Molecular images show that cholesterol is distributed across the whole area of the brain with variation in intensities. Additionally, large water clusters were shown to simultaneously maximise secondary ion yields while reducing matrix effects for in situ cholesterol analysis.