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.

诸如核酸和核蛋白之类的核生物标志物的检测对于早期癌症的诊断和预后至关重要。依靠组织病理切片中细胞核的形态学评估的常规方法可能是主观的，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位患者的41个组织标本被标记有位点特异性和生物标志物特异性抗体结合的染料夹在Fabry-Pérot微腔中，同时激发激光束建立了激光发射图像。我们观察到癌细胞核产生了多个亚细胞激光发射，^-2，亚微米分辨率（<700 nm），并且激光波段在几纳米范围内。癌症和正常组织中不同的核激射阈值使得能够鉴定和多重检测核蛋白质组学生物标记物，并且对早期癌症诊断具有很高的敏感性。基于激光发射的癌症筛查和免疫诊断可能会在精密医学中找到用途，并促进细胞生物学的研究。