Low Voltage Electron Microscopy: Enabling advances in the preparation and imaging of biological thin sections

Electron microscopy (EM), particularly Transmission Electron Microscopy (TEM), is a crucial tool for studying biological samples. Traditional TEM requires high-voltage systems and extensive sample processing, including fixation, dehydration, and heavy metal staining, which enhance contrast but it is time-consuming and toxic. Despite advancements, the protocols have remained largely unchanged for over 50 years. Heavy metals like uranyl acetate (UA) are commonly used but are toxic and radiogenic. An alternative approach is Low Voltage Electron Microscopy (LVEM), which uses lower energies to enhance contrast. LVEM systems offer improved imaging contrast and lower costs compared to HV-TEM. This study explored the potential of LVEM for imaging macrophages interacting with viruses and nanoparticles, comparing different staining protocols, including those with and without UA. LVEM provided satisfactory image quality while simplifying staining procedures.