Two or more color data can be combined to form a new data source to enhance sensitivity to defocus signal. Defocus detection can be performed on the newly formed data source. In a setup step, a training wafer can be used to select the best color combination, and obtain defocus detection threshold. This can include applying a segment mask, calculating mean intensities of the segment, determining a color combination that optimizes defocus sensitivity, and generating a second segment mask based on pixels that are above a threshold to sensitivity. In a detection step, the selected color combination is calculated, and the threshold is applied to obtain defocus detection result.