An image sensor includes a sensor portion and an ASIC portion bonded to the sensor portion. The sensor portion includes a first substrate having radiation-sensing pixels, a first interconnect structure, a first isolation layer, and a first dielectric layer. The ASIC portion includes a second substrate, a second isolation layer, and a second dielectric layer. The material compositions of the first and second isolation layers and the first and second dielectric layers are configured such that the first and second isolation layers may serve as barrier layers to prevent copper diffusion into oxide. The first and second isolation layers may also serve as etching-stop layers in the formation of the image sensor.