Modular DNA origami-based electrochemical detection of DNA and proteins
| 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 |
| Description not available. |