Laser-emission imaging of nuclear biomarkers for high-contrast cancer screening and immunodiagnosis

Detection of nuclear biomarkers, such as nucleic acids and nuclear proteins, is critical for early-stage cancer diagnosis and prognosis. Conventional methods relying on morphological assessment of cell nuclei in histopathology slides may be subjective, whereas colorimetric immunohistochemical and fluorescence-based imaging are limited by strong light absorption, broad emission bands and low contrast. Here, we describe the development and use of a scanning laser-emission-based microscope that maps lasing emissions from nuclear biomarkers in human tissues. Forty-one tissue samples from 35 patients labelled with site-specific and biomarker-specific antibody-conjugated dyes were sandwiched in a Fabry-Perot microcavity while an excitation laser beam built a laser-emission image. We observed multiple subcellular lasing emissions from cancer cell nuclei, with a threshold of tens of mu J mm(-2), submicrometre resolution (<700 nm), and a lasing band in the few-nanometre range. Different lasing thresholds of nuclei in cancer and normal tissues enabled the identification and multiplexed detection of nuclear proteomic biomarkers, with high sensitivity for early-stage cancer diagnosis. Laser-emission-based cancer screening and immunodiagnosis might find use in precision medicine and facilitate research in cell biology.