Gold–Oligonucleotide Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid Sequences

Enteroviruses are ubiquitous mammalian pathogens that can produce mild to life-threatening disease. We developed a multimodal, rapid, accurate and economical point-of-care biosensor that can detect nucleic acid sequences conserved amongst 96% of all known enteroviruses. The biosensor harnesses the p...

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Main Authors: Veeren M. Chauhan, Mohamed M. Elsutohy, C. Patrick McClure, William L. Irving, Neil Roddis, Jonathan W. Aylott
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Biosensors
Subjects:
Online Access:https://www.mdpi.com/2079-6374/11/7/238
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author Veeren M. Chauhan
Mohamed M. Elsutohy
C. Patrick McClure
William L. Irving
Neil Roddis
Jonathan W. Aylott
author_facet Veeren M. Chauhan
Mohamed M. Elsutohy
C. Patrick McClure
William L. Irving
Neil Roddis
Jonathan W. Aylott
author_sort Veeren M. Chauhan
collection DOAJ
description Enteroviruses are ubiquitous mammalian pathogens that can produce mild to life-threatening disease. We developed a multimodal, rapid, accurate and economical point-of-care biosensor that can detect nucleic acid sequences conserved amongst 96% of all known enteroviruses. The biosensor harnesses the physicochemical properties of gold nanoparticles and oligonucleotides to provide colourimetric, spectroscopic and lateral flow-based identification of an exclusive enteroviral nucleic acid sequence (23 bases), which was identified through in silico screening. Oligonucleotides were designed to demonstrate specific complementarity towards the target enteroviral nucleic acid to produce aggregated gold–oligonucleotide nanoconstructs. The conserved target enteroviral nucleic acid sequence (≥1 × 10<sup>−7</sup> M, ≥1.4 × 10<sup>−14</sup> g/mL) initiates gold–oligonucleotide nanoconstruct disaggregation and a signal transduction mechanism, producing a colourimetric and spectroscopic blueshift (544 nm (purple) > 524 nm (red)). Furthermore, lateral-flow assays that utilise gold–oligonucleotide nanoconstructs were unaffected by contaminating human genomic DNA, demonstrated rapid detection of conserved target enteroviral nucleic acid sequence (<60 s), and could be interpreted with a bespoke software and hardware electronic interface. We anticipate that our methodology will translate in silico screening of nucleic acid databases to a tangible enteroviral desktop detector, which could be readily translated to related organisms. This will pave the way forward in the clinical evaluation of disease and complement existing strategies to overcome antimicrobial resistance.
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spelling doaj.art-6c8166c260614659998af9eb8eb529692023-11-22T03:20:03ZengMDPI AGBiosensors2079-63742021-07-0111723810.3390/bios11070238Gold–Oligonucleotide Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid SequencesVeeren M. Chauhan0Mohamed M. Elsutohy1C. Patrick McClure2William L. Irving3Neil Roddis4Jonathan W. Aylott5School of Pharmacy, Boots Science Building, University of Nottingham, Nottingham NG7 2RD, UKSchulich School of Engineering, University of Calgary, Calgary, AB T2N 4V8, CanadaQueen’s Medical Centre, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UKQueen’s Medical Centre, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UKTBG Solutions Ltd. 3A Midland Court, Barlborough Links, Barlborough, Chesterfield, Derbyshire S43 4UL, UKSchool of Pharmacy, Boots Science Building, University of Nottingham, Nottingham NG7 2RD, UKEnteroviruses are ubiquitous mammalian pathogens that can produce mild to life-threatening disease. We developed a multimodal, rapid, accurate and economical point-of-care biosensor that can detect nucleic acid sequences conserved amongst 96% of all known enteroviruses. The biosensor harnesses the physicochemical properties of gold nanoparticles and oligonucleotides to provide colourimetric, spectroscopic and lateral flow-based identification of an exclusive enteroviral nucleic acid sequence (23 bases), which was identified through in silico screening. Oligonucleotides were designed to demonstrate specific complementarity towards the target enteroviral nucleic acid to produce aggregated gold–oligonucleotide nanoconstructs. The conserved target enteroviral nucleic acid sequence (≥1 × 10<sup>−7</sup> M, ≥1.4 × 10<sup>−14</sup> g/mL) initiates gold–oligonucleotide nanoconstruct disaggregation and a signal transduction mechanism, producing a colourimetric and spectroscopic blueshift (544 nm (purple) > 524 nm (red)). Furthermore, lateral-flow assays that utilise gold–oligonucleotide nanoconstructs were unaffected by contaminating human genomic DNA, demonstrated rapid detection of conserved target enteroviral nucleic acid sequence (<60 s), and could be interpreted with a bespoke software and hardware electronic interface. We anticipate that our methodology will translate in silico screening of nucleic acid databases to a tangible enteroviral desktop detector, which could be readily translated to related organisms. This will pave the way forward in the clinical evaluation of disease and complement existing strategies to overcome antimicrobial resistance.https://www.mdpi.com/2079-6374/11/7/238gold nanoparticlesoligonucleotidesgold–oligonucleotide nanoconstructslateral flow assayenterovirusvirus
spellingShingle Veeren M. Chauhan
Mohamed M. Elsutohy
C. Patrick McClure
William L. Irving
Neil Roddis
Jonathan W. Aylott
Gold–Oligonucleotide Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid Sequences
Biosensors
gold nanoparticles
oligonucleotides
gold–oligonucleotide nanoconstructs
lateral flow assay
enterovirus
virus
title Gold–Oligonucleotide Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid Sequences
title_full Gold–Oligonucleotide Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid Sequences
title_fullStr Gold–Oligonucleotide Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid Sequences
title_full_unstemmed Gold–Oligonucleotide Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid Sequences
title_short Gold–Oligonucleotide Nanoconstructs Engineered to Detect Conserved Enteroviral Nucleic Acid Sequences
title_sort gold oligonucleotide nanoconstructs engineered to detect conserved enteroviral nucleic acid sequences
topic gold nanoparticles
oligonucleotides
gold–oligonucleotide nanoconstructs
lateral flow assay
enterovirus
virus
url https://www.mdpi.com/2079-6374/11/7/238
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