The construction and implementation of a dedicated beam line facility for ion beam bioimaging

Abstract

Observation of the interior structure of cells and sub-cellular organelles at high spatial resolutions are necessary for determining the functioning mechanism of biological cells. Conventional optical microscopy has limited resolution due to unavoidable diffraction limits of light, and electron microscopy is only useful when imaging very thin sections due to excessive electron/electron scattering. However, as the resolution of microbeam system gradually improves, microscopy using MeV ions can play a major role in the imaging of whole cells primarily due to the ability of fast ions to penetrate whole cells while maintaining the spatial resolution. The thesis discussed the construction and implementation of a dedicated high resolution MeV ion beam microscopy, which is able to focus MeV protons and helium ions to a spot size of around 25 nm. The facility is designed to utilize a variety of techniques, including high resolution Scanning Transmission Ion Microscopy (STIM), Forward Scattered Transmission Ion Microscopy (FSTIM) and Proton Induced Fluorescence (PIF). STIM and FSTIM imaging has already been optimized, with the capability of imaging buried structures in a whole cell at a spatial resolution of sub-50 nm. Complimentarily to Helium Ion Microscopy, both sub surface structures and surface structures can be imaged at nanometer resolution. The development of high resolution PIF imaging is also discussed, with preliminary results showing great potential of using PIF to image specifically labeled structures at a sub-100 nm resolution. In the meantime, several biomedical imaging applications using these techniques are presented in details.