Silicon grids with electron-transparent SiO2 windows for use as substrates for high-resolution transmission electron microscopy of chemically-modified SiO2 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. Structural or chemical functionalizations can be provided, and surface interactions observed via TEM.