The present disclosure concerns novel methods for analyzing biological samples using photo-cleavable moieties that facilitate target detection and/or biomarker isolation. In some embodiments, the method concerns using a probe comprising a photo-cleavable moiety and a selective irradiation technique for activating/cleaving the photo-cleavable moiety thereby providing facile isolation of the probe or probe components. Also disclosed herein is a system and kit for implementing the methods disclosed herein.