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Programmable DNA-responsive microchip for the capture and release of circulating tumor cells by nucleic acid hybridization

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Abstract

The detection and analysis of circulating tumor cells (CTCs) from patients´ blood is important to assess tumor status; however, it remains a challenge. In the present study, we developed a programmable DNA-responsive microchip for the highly efficient capture and nondestructive release of CTCs via nucleic acid hybridization. Transparent and patternable substrates with hierarchical architectures were integrated into the microchip with herringbone grooves, resulting in greatly enhanced cell-surface interaction via herringbone micromixers, more binding sites, and better matched topographical interactions. In combination with a high-affinity aptamer, target cancer cells were specifically and efficiently captured on the chip. Captured cancer cells were gently released from the chip under physiological conditions using toehold-mediated strand displacement, without any destructive factors for cells or substrates. More importantly, aptamer-containing DNA sequences on the surface of the retrieved cancer cells could be further amplified by polymerase chain reaction (PCR), facilitating the detection of cell surface biomarkers and characterization of the CTCs. Furthermore, this system was extensively applied to the capture and release of CTCs from patients´ blood samples, demonstrating a promising high-performance platform for CTC enrichment, release, and characterization.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (NSFC) (Nos. 21432008, 91413109 and 21575110). China Postdoctoral Innovative Talent Support Program of China (No. BX201700176).

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  1. Shan Guo and Haiyan Huang contributed equally to this work.

Authors and Affiliations

  1. College of Chemistry and Molecular Sciences, the Institute for Advanced Studies of Wuhan University, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University, Wuhan, 430072, China

    Shan Guo, Haiyan Huang, Yuqi Chen, Zhuoran Jiang & Xiang Zhou

  2. Zhongnan Hospital, Wuhan University, Wuhan, 430072, China

    Xujing Deng & Songmei Liu

  3. Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China

    Min Xie & Weihua Huang

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  1. Shan Guo
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  2. Haiyan Huang
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  3. Xujing Deng
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  4. Yuqi Chen
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  6. Min Xie
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Correspondence to Weihua Huang or Xiang Zhou.

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Programmable DNA-responsive microchip for the capture and release of circulating tumor cells by nucleic acid hybridization

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Guo, S., Huang, H., Deng, X. et al. Programmable DNA-responsive microchip for the capture and release of circulating tumor cells by nucleic acid hybridization. Nano Res. 11, 2592–2604 (2018). https://doi.org/10.1007/s12274-017-1885-8

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  • DOI: https://doi.org/10.1007/s12274-017-1885-8

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