Implementations of the disclosure provide a method of fabricating an image sensor device. The method includes forming first trenches in a first photoresist layer using a first photomask having a first pattern to expose a first surface of a substrate, directing ions into the exposed first substrate through the first trenches to form first isolation regions in the substrate, removing the first photoresist layer, forming second trenches in a second photoresist layer using a second photomask having a second pattern to expose a second surface of the substrate, the second pattern being shifted diagonally from the first pattern by half mask pitch, directing ions into the exposed second surface through the second trenches to form second isolation regions in the substrate, the first and second isolation regions being alternatingly disposed in the substrate, and the first and second isolation regions defining pixel regions therebetween, and removing the second photoresist layer.