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Issue 21, 2019
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Multiplexed immunophenotyping of circulating exosomes on nano-engineered ExoProfile chip towards early diagnosis of cancer

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Abstract

Circulating exosomes have been studied as a promising biomarker for non-invasive cancer diagnosis, as they are implicated in tumor initiation, progression, and metastasis. However, the clinical significance of circulating exosomes has not been revealed thoroughly, due to the technical limitation in sensitive and multiplexed detection of cargoes on exosomes, such as proteins and nucleic acids. Herein we developed an integrated exosome profiling platform (ExoProfile chip) to afford superior sensitivity and multiplexed capability for quantitative detection of a panel of surface protein markers on exosomes. To achieve this goal, we innovatively constructed 3D porous serpentine nanostructures via patterned colloidal self-assembly to provide enormous reaction sites and improve biosensing efficiency of exosomes. Meanwhile, the switchable microfluidic design enabled the simultaneous detection of eight markers on single addition of exosome samples. The ExoProfile chip was validated with purified exosomes from SKOV3 cells, which yielded a limit of detection of 21 exosomes per μL. We applied the ExoProfile chip to clinical analysis of circulating exosomes using only 10 μL ovarian cancer plasma and completing the analysis within 3 h. The diagnostic power of seven markers (EGFR, HER2, CA125, FRα, CD24, EpCAM, and CD9 plus CD63) were evaluated with receiver operator characteristic curve and heatmap clustering. Compared to single biomarker, the combined assessment of a biomarker panel was demonstrated to display improved accuracy in distinguishing early and late stage cancer. The results suggested the ExoProfile chip as a promising platform for molecular fingerprinting of circulating exosomes towards early cancer diagnosis.

Graphical abstract: Multiplexed immunophenotyping of circulating exosomes on nano-engineered ExoProfile chip towards early diagnosis of cancer

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Publication details

The article was received on 25 Feb 2019, accepted on 19 Apr 2019 and first published on 22 Apr 2019


Article type: Edge Article
DOI: 10.1039/C9SC00961B
Chem. Sci., 2019,10, 5495-5504
  • Open access: Creative Commons BY-NC license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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    Multiplexed immunophenotyping of circulating exosomes on nano-engineered ExoProfile chip towards early diagnosis of cancer

    P. Zhang, X. Zhou and Y. Zeng, Chem. Sci., 2019, 10, 5495
    DOI: 10.1039/C9SC00961B

    This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

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