An imaging system is configured with an autofocus operation that refocuses multiple cameras of the imaging system on detected features of interest, instead of on the whole image of the sample. Focus measures are calculated on the detected features, and then aggregated to focus distances of actuator moving the camera array, the sample stage, or individual cameras based on a maximization of detected features to be in focus. After the refocus, the imaging system recaptures new images and analyzes features on the new images to generate statistical characterization of the sample based on the classification of the features.