Rational design of DNA nanostructures for single molecule biosensing

Abstract

The ability to detect low concentrations of biomarkers in patient samples is one of the cornerstones of modern healthcare. In general, biosensing approaches are based on measuring signals resulting from the interaction of a large ensemble of molecules with the sensor. Here, we report a biosensor platform using DNA origami featuring a central cavity with a target-specific DNA aptamer coupled with a nanopore read-out to enable individual biomarker detection. We show that the modulation of the ion current through the nanopore upon the DNA origami translocation strongly depends on the presence of the biomarker in the cavity. We exploit this to generate a biosensing platform with a limit of detection of 3 nM and capable of the detection of human C-reactive protein (CRP) in clinically relevant fluids. Future development of this approach may enable multiplexed biomarker detection by using ribbons of DNA origami with integrated barcoding.

Metadata

Item Type:	Article
Authors/Creators:	Raveendran, M https://orcid.org/0000-0003-3968-3673 Lee, AJ https://orcid.org/0000-0003-2268-4645 Sharma, R https://orcid.org/0000-0003-1928-216X Wälti, C https://orcid.org/0000-0001-9286-5359 Actis, P https://orcid.org/0000-0002-7146-1854
Copyright, Publisher and Additional Information:	© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Dates:	Accepted: 31 July 2020 Published (online): 1 September 2020 Published: 1 September 2020
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Electronic & Electrical Engineering (Leeds) > Pollard Institute (Leeds)
Funding Information:	Funder Grant number Royal Society RG160273 EPSRC (Engineering and Physical Sciences Research Council) EP/S01764X/1
Depositing User:	Symplectic Publications
Date Deposited:	03 Aug 2020 13:21
Last Modified:	02 Jan 2025 13:08
Status:	Published
Publisher:	Springer Nature
Identification Number:	10.1038/s41467-020-18132-1
Related URLs:	Dataset
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:163949