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.

核酸和核蛋白等核生物标志物的检测对于早期癌症诊断和预后至关重要。依赖于组织病理学载玻片中细胞核形态学评估的传统方法可能是主观的，而比色免疫组织化学和基于荧光的成像则受到强光吸收、宽发射带和低对比度的限制。在这里，我们描述了基于扫描激光发射的显微镜的开发和使用，该显微镜可绘制人体组织中核生物标志物的激光发射图。来自 35 名患者的 41 个组织样本被标记有位点特异性和生物标志物特异性抗体偶联染料，这些样本被夹在法布里-珀罗微腔中，同时激发激光束构建激光发射图像。我们观察到来自癌细胞核的多个亚细胞激光发射，其阈值为数十μJ mm ^-2 、亚微米分辨率（<700 nm）以及几纳米范围内的激光带。癌症和正常组织中细胞核的不同激光阈值使得能够识别和多重检测核蛋白质组生物标志物，对早期癌症诊断具有高灵敏度。基于激光发射的癌症筛查和免疫诊断可能会在精准医学中得到应用，并促进细胞生物学的研究。