Abstract: The disclosure provides methods, systems and related software, for automated or semi-automated sorting and/or isolating cells with visually distinguishable phenotypes. In some embodiments, the methods comprise providing a plurality cells with a photo-activatable detectable marker in their respective nuclei. The plurality of cells are imaged and, based on the image, the status for one or more visually identifiable phenotypes are determined. Cells determined to have the desired phenotype status are specifically exposed to a light wavelength for a time sufficient to uniquely activate the photo-activatable detectable marker in the individual cells with the desired phenotype status. The cells are then sorted on the basis of the activated detectable marker. The disclosure also provides methods for preparation and isolation of nuclei from fixed, adherent cells for analysis.