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Graphene-Based Confocal Refractive Index Microscopy for Label-Free Differentiation of Living Epithelial and Mesenchymal Cells

  • Lixun Sun
    Lixun Sun
    Nanophotonics Research Centre, Shenzhen Key Laboratory of Micro-Scale Optical Information Technology, Shenzhen University, Shenzhen 518060, China
    More by Lixun Sun
  • Yijia Wang
    Yijia Wang
    Laboratory of Oncologic Molecular Medicine, Tianjin Union Medical Center, Tianjin 300121, China
    More by Yijia Wang
  • Huiqin Zhang
    Huiqin Zhang
    Institute of Modern Optics, Nankai University, Tianjin 300071, China
    More by Huiqin Zhang
  • Changjun Min
    Changjun Min
    Nanophotonics Research Centre, Shenzhen Key Laboratory of Micro-Scale Optical Information Technology, Shenzhen University, Shenzhen 518060, China
    More by Changjun Min
  • Yuquan Zhang
    Yuquan Zhang
    Nanophotonics Research Centre, Shenzhen Key Laboratory of Micro-Scale Optical Information Technology, Shenzhen University, Shenzhen 518060, China
    More by Yuquan Zhang
  • Chonglei Zhang
    Chonglei Zhang
    Nanophotonics Research Centre, Shenzhen Key Laboratory of Micro-Scale Optical Information Technology, Shenzhen University, Shenzhen 518060, China
  • Ziqiang Xin
    Ziqiang Xin
    Nanophotonics Research Centre, Shenzhen Key Laboratory of Micro-Scale Optical Information Technology, Shenzhen University, Shenzhen 518060, China
    More by Ziqiang Xin
  • Siwei Zhu
    Siwei Zhu
    Laboratory of Oncologic Molecular Medicine, Tianjin Union Medical Center, Tianjin 300121, China
    More by Siwei Zhu
  • Yong Yang*
    Yong Yang
    Institute of Modern Optics, Nankai University, Tianjin 300071, China
    *E-mail: [email protected] (Y.Y.).
    More by Yong Yang
  • Ronald E. Burge
    Ronald E. Burge
    Cavendish Laboratory, University of Cambridge, Madingley Road, Cambridge CB3 0HE, U.K.
  • Xiaocong Yuan*
    Xiaocong Yuan
    Nanophotonics Research Centre, Shenzhen Key Laboratory of Micro-Scale Optical Information Technology, Shenzhen University, Shenzhen 518060, China
    *E-mail: [email protected] (X.Y.).
Cite this: ACS Sens. 2020, XXXX, XXX, XXX-XXX
Publication Date (Web):January 13, 2020
https://doi.org/10.1021/acssensors.9b02340
Copyright © 2020 American Chemical Society
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Abstract

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Label-free imaging and investigation of living cells are significant for many biomedical studies. It has been challenging to detect the epithelial–mesenchymal transition of cells in situ without affecting cellular activity. Here, we present a common-path differential confocal microscope based on the polarization-sensitive absorption of graphene to realize high-performance refractive index imaging and differentiation of living colorectal cancer cells (HCT116) with large detecting depth (1.29 μm), excellent refractive index resolution (2.86 × 10–5 RIU), and high spatial resolution (727 nm) simultaneously. Compared with epithelial (parental HCT116) cells, mesenchymal (paclitaxel-resistant HCT116) cells manifest generally lower refractive index values through the refractive index statistics, which is due to the stronger migration ability and weaker surface adherence of mesenchymal cells. The graphene-based microscopy provides an effective label-free approach to high-resolution imaging and study of living cell kinetics, and we expect it to be widely used in the research fields of pathology, tumorigenesis, and chemotherapy.

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The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acssensors.9b02340.

  • Materials; refractive index sensing theory of graphene in prism-coupled optical structure; determination of the imaging spatial resolution; full-length western blotting results; cell thickness measurement of parental and resistant cells; more groups of refractive index imaging and comparison for parental and resistant cells; and cell localization by staining parental cells with CM-Dil (PDF)

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