Recent advances in electron microscopy for the diagnosis and research of glomerular diseases

Recent technical advances in the detection of backscattered electrons during scanning electron microscopy (SEM) have improved resolution and have provided several new technologies for research and clinical practice in kidney disease. The advances include three-dimensional (3D) electron microscopy (3D-EM), correlative light and electron microscopy (CLEM), low-vacuum SEM (LVSEM), and scanning transmission electron microscopy (STEM). 3D-EM analysis used to be laborious, but recently three different technologies, serial block-face SEM, focused ion beam SEM, and array tomography, have made 3D-EM easier by automating sectioning and the subsequent image acquisition in an SEM. CLEM is a method to correlate light microscopic images, especially immunofluorescent and electron microscopy images, providing detailed ultrastructure of the area of interest where the immunofluorescent marker is located. LVSEM enables the use of SEM on materials with poor electron conductivity. For example, LVSEM makes it possible for high resolution, 3D observation of paraffin sections. Finally, STEM is a method to observe ultrathin sections with improved resolution by using the focused electron beam scanning used in SEM and not the broad electron beam used in transmission electron microscopy. These technical advances in electron microscopy are promising to provide plenty of novel insights for understanding the pathogenesis and diagnosis of various glomerular diseases.