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Controlling the bioreceptor spatial distribution at the nanoscale for single molecule counting in microwell arrays

Abstract:
The ability to detect low concentrations of protein biomarkers is crucial for the early-stage detection of many diseases and therefore indispensable for improving diagnostic devices for healthcare. Here, we demonstrate that by integrating DNA nanotechnologies like DNA origami and aptamers, we can design innovative biosensing concepts for reproducible and sensitive detection of specific targets. DNA origami structures decorated with aptamers were studied as a novel tool to structure the biosensor surface with nanoscale precision in a digital detection bioassay, enabling control of the density, orientation, and accessibility of the bioreceptor to optimize the interaction between target and aptamer. DNA origami was used to control the spatial distribution of an in-house-generated aptamer on superparamagnetic microparticles, resulting in an origami-linked digital aptamer bioassay to detect the main peanut antigen Ara h1 with 2-fold improved signal-to-noise ratio and 15-fold improved limit of detection compared to a digital bioassay without DNA origami. Moreover, the sensitivity achieved was 4 orders of magnitude higher than commercially available and literature-reported enzyme-linked immunosorbent assay techniques. In conclusion, this novel and innovative approach to engineer biosensing interfaces will be of major interest to scientists and clinicians looking for new molecular insights and ultrasensitive detection of a broad range of targets, and, for the next generation of diagnostics.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1021/acssensors.9b00877

Authors


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Institution:
University of Oxford
Division:
MPLS
Department:
Physics
Sub department:
Condensed Matter Physics
Role:
Author
ORCID:
0000-0002-7144-662X


Publisher:
American Chemical Society
Journal:
ACS Sensors More from this journal
Volume:
4
Issue:
9
Pages:
2327-2335
Publication date:
2019-08-22
Acceptance date:
2019-08-22
DOI:
ISSN:
2379-3694


Language:
English
Keywords:
Pubs id:
pubs:1048254
UUID:
uuid:b13b2dab-4bca-4fcd-9f8d-64b1dbcc8091
Local pid:
pubs:1048254
Source identifiers:
1048254
Deposit date:
2019-08-30

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