Cycling of rational hybridization chain reaction to enable enzyme-free DNA-based clinical diagnosis

Xu, G., Zhao, H., Reboud, J. and Cooper, J. M. (2018) Cycling of rational hybridization chain reaction to enable enzyme-free DNA-based clinical diagnosis. ACS Nano, 12(7), pp. 7213-7219. (doi:10.1021/acsnano.8b03183) (PMID:29965722) (PMCID:PMC6070952)

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Abstract

In order to combat the growing threat of global infectious diseases, there is the need for rapid diagnostic technologies that are sensitive and that can provide species specific information (as might be needed to direct therapy as resistant strains of microbes emerge). Here, we present a convenient, enzyme-free amplification mechanism for a rational hybridization chain reaction (HCR), which is implemented in a simple format for isothermal amplification and sensing, applied to the DNA-based diagnosis of Hepatitis B virus (HBV) in 54 patients. During the cycled amplification process, DNA monomers self-assemble in an organized and controllable way, only when a specific target HBV sequence is present. This mechanism is confirmed using super-resolution Stochastic Optical Reconstruction Microscopy (STORM). The enabled format is designed in a manner analogous to an enzyme-linked immunosorbent assay (ELISA), generating coloured products with distinct tonality and with a limit of detection of ca. 5 copies/reaction. This routine assay also showed excellent sensitivity (>97%) in clinical samples demonstrating the potential of this convenient, low cost, enzyme-free method for use in low resource settings.

Item Type:Articles
Additional Information:Also funded by ERC 340117.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Zhao, Hang and Cooper, Professor Jonathan and Reboud, Dr Julien and Xu, Mr Gaolian
Authors: Xu, G., Zhao, H., Reboud, J., and Cooper, J. M.
College/School:College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:ACS Nano
Publisher:American Chemical Society
ISSN:1936-0851
ISSN (Online):1936-086X
Published Online:02 July 2018
Copyright Holders:Copyright © 2018 American Chemical Society
First Published:First published in ACS Nano 12(7):7213-7219
Publisher Policy:Reproduced under a Creative Commons License
Data DOI:10.5525/gla.researchdata.632

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
553521Next Generation Analytical Tools: Application to Protein Oxidations that affect Human Health and WellbeingJonathan CooperEngineering and Physical Sciences Research Council (EPSRC)EP/I017887/1ENG - BIOMEDICAL ENGINEERING
617021Advanced Diagnostics using PhononicsJonathan CooperEngineering and Physical Sciences Research Council (EPSRC)EP/K027611/1ENG - BIOMEDICAL ENGINEERING

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