An example image sensor structure includes an image layer. The image layer includes an array of light detectors disposed therein. A device stack is disposed over the image layer. An array of light guides is disposed in the device stack. Each light guide is associated with at least one light detector of the array of light detectors. A passivation stack is disposed over the device stack. The passivation stack includes a bottom surface in direct contact with a top surface of the light guides. An array of nanowells is disposed in a top layer of the passivation stack. Each nanowell is associated with a light guide of the array of light guides. A crosstalk blocking metal structure is disposed in the passivation stack. The crosstalk blocking metal structure reduces crosstalk within the passivation stack.