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An enzyme-free turn-on fluorescent strategy for nucleic acid detection based on hybridization chain reaction and transferable silver nanoclusters

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Abstract

A fluorescence biosensor has been developed based on hybridisation chain reaction (HCR) amplification coupled with silver nanoclusters (AgNCs) for nucleic acid detection. The fluorescence was activated via end-to-end transfer of dark AgNCs caged within a DNA template to another DNA sequence that could enhance their red fluorescence emission at 611 nm. Such cluster-transfer approach allows us to introduce fluorogenic AgNCs as external signal transducers, thereby enabling HCR to perform in a predictable manner. The resulted HCR-AgNC biosensor was able to detect target DNA with a detection limit of 3.35 fM, and distinguish the DNA target from single-base mismatch sequences. Moreover, the bright red fluorescence emission was detectable with the naked eye, with concentration of target DNA down to 1 pM. The biosensor also performed well in human serum samples with good recovery. Overall, our cluster-transfer approach provides a good alternative to construct HCR-AgNC assay with less risk of circuit leakage and produce AgNCs in a controllable manner.

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Acknowledgements

ZWW. acknowledges the Faculty of Science and Engineering, University of Nottingham Malaysia, for sponsoring his PhD study. ZWW. also acknowledges Dr Nur Aliana Hidayah Mohamed (Universiti Teknologi MARA) for her support in providing the human serum sample used in this work.

Funding

This work was supported by the Fundamental Research Grant Scheme (FRGS) under the project code: FRGS/1/2018/STG07/UNIM/02/2.

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Authors and Affiliations

  1. School of Pharmacy, Faculty of Science and Engineering, University of Nottingham Malaysia, Jalan Broga, 43500, Semenyih, Selangor Darul Ehsan, Malaysia

    Zheng Wei Wong & Siu Yee New

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  1. Zheng Wei Wong
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  2. Siu Yee New
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Contributions

ZWW and SYN have contributed equally: conceptualisation, writing — original draft and revision. ZWW: data curation, formal analysis, investigation, methodology, project administration, software and visualization. SYN: funding acquisition, resources, supervision and validation.

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Correspondence to Siu Yee New.

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The study involving human serum was reviewed and approved by the Science and Engineering Research Ethics Committee of the University of Nottingham Malaysia.

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Wong, Z.W., New, S.Y. An enzyme-free turn-on fluorescent strategy for nucleic acid detection based on hybridization chain reaction and transferable silver nanoclusters. Microchim Acta 190, 16 (2023). https://doi.org/10.1007/s00604-022-05591-0

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