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Nucleic acid hybridization on an electrically reconfigurable network of gold-coated magnetic nanoparticles enables microRNA detection in blood

Abstract

There is intense interest in quantifying the levels of microRNA because of its importance as a blood-borne biomarker. The challenge has been to develop methods that can monitor microRNA expression both over broad concentration ranges and in ultralow amounts directly in a patient’s blood. Here, we show that, through electric-field-induced reconfiguration of a network of gold-coated magnetic nanoparticles modified by probe DNA (DNA–Au@MNPs), it is possible to create a highly sensitive sensor for direct analysis of nucleic acids in samples as complex as whole blood. The sensor is the first to be able to detect concentrations of microRNA from 10 aM to 1 nM in unprocessed blood samples. It can distinguish small variations in microRNA concentrations in blood samples of mice with growing tumours. The ultrasensitive and direct detection of microRNA using an electrically reconfigurable DNA–Au@MNPs network makes the reported device a promising tool for cancer diagnostics.

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Fig. 1: Schematic representation of the steps involved in the proposed sensing strategy for detecting miRNA.
Fig. 2: Determination of the sensitivity for electrochemical measurement of the concentration of synthetic miR-21.
Fig. 3: Target concentration-dependence and reproducibility of change in the square wave current through 10 cycles of square wave voltammetry.
Fig. 4: Analysis of RNA samples extracted from human lung cancer cells.
Fig. 5: Detection of miR-21 in xenograft mouse model with human lung cancer.

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Acknowledgements

The authors acknowledge support from the UNSW Mark Wainwright Analytical Centre, Biological Resources Imaging Laboratory and Electron Microscope Unit. The authors also acknowledge assistance from K. Kimpton with in vivo mouse experiments. The authors acknowledge funding from the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology (J.J.G. and M.K.; CE140100036), the ARC Laureate Fellowship (J.J.G.; FL150100060) programme, a National Health and Medical Research Council programme grant (M.K. and J.J.G.; APP1091261) and an NHMRC Principal Research Fellowship (M.K.; APP1119152). J.M. is supported by a Cancer Institute NSW Career Development Fellowship.

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R.T. and J.J.G. designed the experiments, performed data interpretation and wrote the manuscript. R.T. performed the experiments and analysed the data. J.M. performed miR-21 inhibitor transfections and in vivo experiments, with assistance from M.L.G. N.A. and R.D.T. performed the electron microscopy. J.M. and M.K. provided scientific and technical support and data interpretation in biological experiments. W.S. and E.B. provided scientific support in the creation and investigation of the hypothesis for the mechanism of detection. D.B.H. provided scientific support in performing calculations required for the design of experiments. All authors reviewed the manuscript.

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Correspondence to John Justin Gooding.

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Tavallaie, R., McCarroll, J., Le Grand, M. et al. Nucleic acid hybridization on an electrically reconfigurable network of gold-coated magnetic nanoparticles enables microRNA detection in blood. Nature Nanotech 13, 1066–1071 (2018). https://doi.org/10.1038/s41565-018-0232-x

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