This study demonstrated the applicability of Scanning Electron Microscopy (SEM) for the observation of amyloid fibrils without staining. As model specimens, two types of amyloid fibrils with different shapes and chemical compositions were controllably synthesized from hen lysozyme. The apparent fibril widths in the SEM images were considerably larger than the original diameters analyzed by the conventional techniques of Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM). Although this broadening, which depends on the chemical nature of the fibril, is not desirable for detailed imaging, it makes SEM sensitive to fibrils several micrometers in length and as thin as 3.5 nm. Note that the sensitivity also contributed to clearly distinguishing amyloid fibrils from salt microcrystals in SEM images. These results suggest the considerable applicability of SEM for the imaging of amyloid fibrils, even in contaminated samples.

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