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… Click to show full abstract
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–Pérot 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 μJ 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.A scanning laser-emission-based microscope enables submicrometre-resolution mapping of nuclear biomarkers and the diagnosis of early-stage lung cancer in tissue samples from patients.
               
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