{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T18:40:37Z","timestamp":1792608037106,"version":"4.5.0"},"reference-count":64,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"43","funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canada Foundation for Innovation"},{"name":"Ignite Program"},{"name":"STAIR"},{"name":"NSERC USRA"},{"name":"CGRS"},{"name":"UBC"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,10,23]]},"abstract":"<jats:p>\n                    Despite decades of progress in aptamer engineering, the development of a single, modular signaling architecture capable of transducing target recognition into a measurable output across structurally diverse analytes remains an unmet challenge in biosensing. We report the Competitor Bridge Aptamer (CoBrA) framework: a modular DNA tridomain architecture that functionally isolates target recognition from signal transduction. Unlike conventional sensors where signal output depends on unpredictable aptamer folding, the CoBrA system uses an aptamer switch to trigger a predictable, concerted spatial displacement between signaling end points. By leveraging computational simulations and energetic balancing, we systematically optimized the CoBrA framework to consolidate recognition, displacement, and ratiometric signaling within a single, minimal-component system. Using the dopamine and cortisol aptamers as models, we demonstrate strong thermodynamic and kinetic synchronization between the Cy3 and Cy5 channels across both targets for dopamine (Cy3:\n                    <jats:italic toggle=\"yes\">K<\/jats:italic>\n                    <jats:sub>d<\/jats:sub>\n                    \u00a0=\u00a013.3\u00a0\u00b1\u00a03.2 \u03bcM, \u03c4\u00a0=\u00a0447\u00a0\u00b1\u00a031 seconds; Cy5:\n                    <jats:italic toggle=\"yes\">K<\/jats:italic>\n                    <jats:sub>d<\/jats:sub>\n                    \u00a0=\u00a024.0\u00a0\u00b1\u00a03.3 \u03bcM, \u03c4\u00a0=\u00a0537\u00a0\u00b1\u00a022 seconds) and cortisol (Cy3:\n                    <jats:italic toggle=\"yes\">K<\/jats:italic>\n                    <jats:sub>d<\/jats:sub>\n                    \u00a0=\u00a036.6\u00a0\u00b1\u00a03.9 \u03bcM, \u03c4\u00a0=\u00a0205\u00a0\u00b1\u00a07 seconds; Cy5:\n                    <jats:italic toggle=\"yes\">K<\/jats:italic>\n                    <jats:sub>d<\/jats:sub>\n                    \u00a0=\u00a030.7\u00a0\u00b1\u00a05.5 \u03bcM, \u03c4\u00a0=\u00a0259\u00a0\u00b1\u00a04 seconds) in buffer, serum, and artificial cerebrospinal fluid. Because the signaling event is a predictable, geometry-defined change rather than a fluorescence-specific phenomenon, this architecture is in principle adaptable to surface-based transduction modalities, including electrochemical, field-effect transistor, and plasmonic readouts.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeh8187","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T18:01:42Z","timestamp":1792605702000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Spatial decoupling of recognition and signaling in aptamer switches via tri-strand intermolecular competition"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6294-5073","authenticated-orcid":true,"given":"Albert Zehan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of British Columbia, Vancouver V6T1Z1, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean W.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of British Columbia, Vancouver V6T1Z1, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conrad H. T.","family":"Belzberg","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of British Columbia, Vancouver V6T1Z1, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5047-8382","authenticated-orcid":true,"given":"Amani A.","family":"Hariri","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of British Columbia, Vancouver V6T1Z1, British Columbia, Canada."},{"name":"Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver V6T1Z3, British Columbia, Canada."},{"name":"School of Biomedical Engineering, University of British Columbia, Vancouver V6T2B9, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.199"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2200121"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.200"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00239-015-9708-6"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c00848"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202318665"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/acssensors.8b00516"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202008663"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/acssensors.3c02004"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c09576"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg764"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/415697"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200461848"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/ac403235y"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja056555h"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2016.07.010"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/acssensors.5c03582"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2020.112798"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja804119s"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13137-x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202304410"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf1346"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao6750"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.7b00634"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja028962o"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38105-4"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","unstructured":"Y. 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Tinnefeld Brownian DNA computing. bioRxiv 671330 [Preprint] (2025); https:\/\/doi.org\/10.1101\/2025.08.21.671330.","DOI":"10.1101\/2025.08.21.671330"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202305186"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1021\/nl103427w"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3804"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02028-8"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b08671"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b05412"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1021\/acssensors.3c00509"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.3390\/bios13040434"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.2184"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.2006.01706.x"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-021-00832-8"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aeh8187","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T18:02:35Z","timestamp":1792605755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aeh8187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,23]]},"references-count":64,"journal-issue":{"issue":"43","published-print":{"date-parts":[[2026,10,23]]}},"alternative-id":["10.1126\/sciadv.aeh8187"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aeh8187","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,23]]},"assertion":[{"value":"2026-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaeh8187"}}