Quantitative Modeling of High-Energy Electron Scattering in Thick Samples Using Monte Carlo Techniques

Cryo-electron microscopy (cryo-EM) is a powerful tool for imaging biological samples but is typically limited by sample thickness, which is restricted to a few hundred nanometers depending on the electron energy. However, there is a growing need for imaging techniques capable of studying biological samples up to 10 mu m in thickness while maintaining nanoscale resolution. This need motivates the use of mega-electron-volt scanning transmission electron microscopy (MeV-STEM), which leverages the high penetration power of MeV electrons to generate high-resolution images of thicker samples. In this study, we employ Monte Carlo simulations to model electron-sample interactions and explore the signal decay of imaging electrons through thick specimens. By incorporating material properties, interaction cross-sections for energy loss, and experimental parameters, we investigate the relationship between the incident and transmitted beam intensities. Key factors such as detector collection angle, convergence semi-angle, and the material properties of samples were analyzed. Our results demonstrate that the relationship between incident and transmitted beam intensities follows the Beer-Lambert law over thicknesses ranging from a few microns to several tens of microns, depending on material composition, electron energy, and collection angles. The linear depth of silicon dioxide reaches 3.9 mu m at 3 MeV, about 6 times higher than that at 300 keV. Meanwhile, the linear depth of amorphous ice reaches 17.9 mu m at 3 MeV, approximately 11.5 times higher than that at 300 keV. These findings are crucial for advancing the study of thick biological and semiconductor samples using MeV-STEM.