An image sensor structure including an image stack disposed over a device stack. The image stack includes a plurality of light detectors. A first optical filter stack is disposed over the image stack. The first optical filter stack includes a light guide layer. Light pipe cavities are disposed in the light guide layer. Each light pipe cavity is associated with a light detector. Each light pipe cavity has an aspect ratio that is greater than about 2.5 to about 1. A nanowell layer is disposed over the first optical filter stack. Nanowells are disposed in the nanowell layer. Each nanowell is associated with a light detector.