Fabricating a nanopore sensor includes depositing a first and second oxide layers on first and second sides of a sapphire substrate. The second oxide layer is patterned to form an etch mask having a mask opening in the second oxide layer. A crystalline orientation dependent wet anisotropic etch is performed on the second side of the sapphire substrate using the etch mask to form a cavity having sloped side walls through the sapphire substrate to yield an exposed portion of the first oxide layer, each of the sloped side walls being a crystalline facet aligned with a respective crystalline plane of the sapphire substrate. A silicon nitride layer is deposited on the first oxide layer. The exposed portion of the first oxide layer in the cavity is removed, thereby defining a silicon nitride membrane in the cavity. An opening is formed through the silicon nitride membrane.