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A nanoflow cytometric strategy for sensitive ctDNA detection via magnetic separation and DNA self-assembly

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Abstract

Circulating tumor DNA (ctDNA) is a tumor-derived fragmented DNA in the bloodstream that is not associated with cells. It has been greatly focused in the recent decade because of its potential clinical utility for liquid biopsies. Development of ctDNA analytical techniques with high sensitivity and cost-efficiency will undoubtedly promote the clinical spread of ctDNA testing. In this paper, we propose a novel flow cytometry–based ctDNA sensing strategy which combines enzyme-free amplification and magnetic separation. The target DNA is capable of triggering a hybridization chain reaction, producing a fluorescent long linear assembly of DNA, which can be further captured by magnetic beads to present fluorescent signals using flow cytometry. In comparison with some conventional methods, our strategy has the advantages of easy operation and cost-efficiency, and thereby shows a promising application in clinical diagnosis.

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Funding

This work is financially supported by the National Key R&D Program of China (2018YFC0115705), Youth Innovation Promotion Association CAS (2015261), the National Natural Science Foundation of China (Grant No. 31500805, 81873539, 21575088), “333 High-level Talents Training Project of Jiangsu Province,” and Science and Technology Program of Suzhou (SYG201508).

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Authors and Affiliations

  1. Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University, Shanghai, 200444, China

    Zhai Xingwei, Li Jingwen, Cao Ya, Zhu Xiaoli & Chen Guifang

  2. CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, Jiangsu, China

    Zhai Xingwei, Li Jingwen, Tang Yuguo & Han Kun

  3. University of Chinese Academy of Sciences, Beijing, 100049, China

    Tang Yuguo & Han Kun

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  1. Zhai Xingwei
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  2. Li Jingwen
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Correspondence to Chen Guifang or Han Kun.

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Zhai, X., Li, J., Cao, Y. et al. A nanoflow cytometric strategy for sensitive ctDNA detection via magnetic separation and DNA self-assembly. Anal Bioanal Chem 411, 6039–6047 (2019). https://doi.org/10.1007/s00216-019-01985-x

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