Modular DNA origami-based electrochemical detection of DNA and proteins

Bibliographic Details
Title:	Modular DNA origami-based electrochemical detection of DNA and proteins
Authors:	Jeon, Byoung-jin, Guareschi, Matteo M., Stewart, Jaimie M., Wu, Emily, Gopinath, Ashwin, Arroyo-Currás, Netzahualcóyotl, Dauphin-Ducharme, Philippe, Plaxco, Kevin W., Lukeman, Philip S., Rothemund, Paul W. K.
Publication Year:	2023
Collection:	Condensed Matter Physics (Other) Quantitative Biology
Subject Terms:	Physics - Biological Physics, Condensed Matter - Mesoscale and Nanoscale Physics, Condensed Matter - Soft Condensed Matter, Quantitative Biology - Biomolecules
More Details:	The diversity and heterogeneity of biomarkers has made the development of general methods for single-step quantification of analytes difficult. For individual biomarkers, electrochemical methods that detect a conformational change in an affinity binder upon analyte binding have shown promise. However, because the conformational change must operate within a nanometer-scale working distance, an entirely new sensor, with a unique conformational change, must be developed for each analyte. Here, we demonstrate a modular electrochemical biosensor, built from DNA origami, which is easily adapted to diverse molecules by merely replacing its analyte binding domains. Instead of relying on a unique nanometer-scale movement of a single redox reporter, all sensor variants rely on the same 100-nanometer scale conformational change, which brings dozens of reporters close enough to a gold electrode surface that a signal can be measured via square wave voltammetry, a standard electrochemical technique. To validate our sensor's mechanism, we used single-stranded DNA as an analyte, and optimized the number of redox reporters and various linker lengths. Adaptation of the sensor to streptavidin and PDGF-BB analytes was achieved by simply adding biotin or anti-PDGF aptamers to appropriate DNA linkers. Geometrically-optimized streptavidin sensors exhibited signal gain and limit of detection markedly better than comparable reagentless electrochemical sensors. After use, the same sensors could be regenerated under mild conditions: performance was largely maintained over four cycles of DNA strand displacement and rehybridization. By leveraging the modularity of DNA nanostructures, our work provides a straightforward route to the single-step quantification of arbitrary nucleic acids and proteins. Comment: 14 pages in main, 6 figures; 16 pages in supplementary information, 8 figures, 6 tables
Document Type:	Working Paper
Access URL:	http://arxiv.org/abs/2312.06554
Accession Number:	edsarx.2312.06554
Database:	arXiv

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Items	– Name: Title Label: Title Group: Ti Data: Modular DNA origami-based electrochemical detection of DNA and proteins – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Jeon%2C+Byoung-jin%22">Jeon, Byoung-jin</searchLink><br /><searchLink fieldCode="AR" term="%22Guareschi%2C+Matteo+M%2E%22">Guareschi, Matteo M.</searchLink><br /><searchLink fieldCode="AR" term="%22Stewart%2C+Jaimie+M%2E%22">Stewart, Jaimie M.</searchLink><br /><searchLink fieldCode="AR" term="%22Wu%2C+Emily%22">Wu, Emily</searchLink><br /><searchLink fieldCode="AR" term="%22Gopinath%2C+Ashwin%22">Gopinath, Ashwin</searchLink><br /><searchLink fieldCode="AR" term="%22Arroyo-Currás%2C+Netzahualcóyotl%22">Arroyo-Currás, Netzahualcóyotl</searchLink><br /><searchLink fieldCode="AR" term="%22Dauphin-Ducharme%2C+Philippe%22">Dauphin-Ducharme, Philippe</searchLink><br /><searchLink fieldCode="AR" term="%22Plaxco%2C+Kevin+W%2E%22">Plaxco, Kevin W.</searchLink><br /><searchLink fieldCode="AR" term="%22Lukeman%2C+Philip+S%2E%22">Lukeman, Philip S.</searchLink><br /><searchLink fieldCode="AR" term="%22Rothemund%2C+Paul+W%2E+K%2E%22">Rothemund, Paul W. K.</searchLink> – Name: DatePubCY Label: Publication Year Group: Date Data: 2023 – Name: Subset Label: Collection Group: HoldingsInfo Data: Condensed Matter<br />Physics (Other)<br />Quantitative Biology – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22Physics+-+Biological+Physics%22">Physics - Biological Physics</searchLink><br /><searchLink fieldCode="DE" term="%22Condensed+Matter+-+Mesoscale+and+Nanoscale+Physics%22">Condensed Matter - Mesoscale and Nanoscale Physics</searchLink><br /><searchLink fieldCode="DE" term="%22Condensed+Matter+-+Soft+Condensed+Matter%22">Condensed Matter - Soft Condensed Matter</searchLink><br /><searchLink fieldCode="DE" term="%22Quantitative+Biology+-+Biomolecules%22">Quantitative Biology - Biomolecules</searchLink> – Name: Abstract Label: Description Group: Ab Data: The diversity and heterogeneity of biomarkers has made the development of general methods for single-step quantification of analytes difficult. For individual biomarkers, electrochemical methods that detect a conformational change in an affinity binder upon analyte binding have shown promise. However, because the conformational change must operate within a nanometer-scale working distance, an entirely new sensor, with a unique conformational change, must be developed for each analyte. Here, we demonstrate a modular electrochemical biosensor, built from DNA origami, which is easily adapted to diverse molecules by merely replacing its analyte binding domains. Instead of relying on a unique nanometer-scale movement of a single redox reporter, all sensor variants rely on the same 100-nanometer scale conformational change, which brings dozens of reporters close enough to a gold electrode surface that a signal can be measured via square wave voltammetry, a standard electrochemical technique. To validate our sensor's mechanism, we used single-stranded DNA as an analyte, and optimized the number of redox reporters and various linker lengths. Adaptation of the sensor to streptavidin and PDGF-BB analytes was achieved by simply adding biotin or anti-PDGF aptamers to appropriate DNA linkers. Geometrically-optimized streptavidin sensors exhibited signal gain and limit of detection markedly better than comparable reagentless electrochemical sensors. After use, the same sensors could be regenerated under mild conditions: performance was largely maintained over four cycles of DNA strand displacement and rehybridization. By leveraging the modularity of DNA nanostructures, our work provides a straightforward route to the single-step quantification of arbitrary nucleic acids and proteins.<br />Comment: 14 pages in main, 6 figures; 16 pages in supplementary information, 8 figures, 6 tables – Name: TypeDocument Label: Document Type Group: TypDoc Data: Working Paper – Name: URL Label: Access URL Group: URL Data: <link linkTarget="URL" linkTerm="http://arxiv.org/abs/2312.06554" linkWindow="_blank">http://arxiv.org/abs/2312.06554</link> – Name: AN Label: Accession Number Group: ID Data: edsarx.2312.06554
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RecordInfo	BibRecord: BibEntity: Subjects: – SubjectFull: Physics - Biological Physics Type: general – SubjectFull: Condensed Matter - Mesoscale and Nanoscale Physics Type: general – SubjectFull: Condensed Matter - Soft Condensed Matter Type: general – SubjectFull: Quantitative Biology - Biomolecules Type: general Titles: – TitleFull: Modular DNA origami-based electrochemical detection of DNA and proteins Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Jeon, Byoung-jin – PersonEntity: Name: NameFull: Guareschi, Matteo M. – PersonEntity: Name: NameFull: Stewart, Jaimie M. – PersonEntity: Name: NameFull: Wu, Emily – PersonEntity: Name: NameFull: Gopinath, Ashwin – PersonEntity: Name: NameFull: Arroyo-Currás, Netzahualcóyotl – PersonEntity: Name: NameFull: Dauphin-Ducharme, Philippe – PersonEntity: Name: NameFull: Plaxco, Kevin W. – PersonEntity: Name: NameFull: Lukeman, Philip S. – PersonEntity: Name: NameFull: Rothemund, Paul W. K. IsPartOfRelationships: – BibEntity: Dates: – D: 11 M: 12 Type: published Y: 2023
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