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.
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Acknowledgements
We acknowledge the support from the National Science Foundation (ECCS-1607250), the National Institutes of Health (NIBIB-1R21EB016783) and the National Natural Science Foundation of China (grant no. 61471254). We thank the support of the Molecular Imaging Analysis Lab at the University of Michigan for cryostats and confocal microscopy. We also thank W.-H. Weng from Harvard Medical School for pathology assistance.
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Y.-C.C. and X.F. conceived the research; Y.-C.C., X.T. and X.F. designed the experiments; Y.-C.C. and Q.C. performed the experiments; Q.S. developed the coding for the 2D scanning system; W.W. and X.F. designed, fabricated and characterized the optical mirrors and cavities. Y.-C.C. and X.F. analysed data and wrote the paper.
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Lasing emissions from nuclear biomarkers in the nucleus of a lung-cancer cell.
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Chen, YC., Tan, X., Sun, Q. et al. Laser-emission imaging of nuclear biomarkers for high-contrast cancer screening and immunodiagnosis. Nat Biomed Eng 1, 724–735 (2017). https://doi.org/10.1038/s41551-017-0128-3
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DOI: https://doi.org/10.1038/s41551-017-0128-3
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