Silicon grids with electron-transparent SiO.sub.2 windows for use as substrates for high-resolution transmission electron microscopy of chemically-modified SiO.sub.2 surfaces are fabricated by forming an oxide layer on a silicon substrate. An aperture is defined in the silicon substrate by etching the substrate to the oxide layer. A single substrate can include a plurality of apertures that are in respective frame regions that are defined by one or more channels in the substrate. Tabs are provided to secure the frame regions to the substrate, and the tabs are readily broken to obtain a particular frame region. Conductive or other features can be defined on the oxide layers prior to separation of the frame regions from the substrate.