{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T16:05:18Z","timestamp":1789488318373,"version":"build-2803163510"},"reference-count":44,"publisher":"American Chemical Society (ACS)","issue":"36","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["PREPARE-OC- Dx-2024-009"],"award-info":[{"award-number":["PREPARE-OC- Dx-2024-009"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001352","name":"National University of Singapore","doi-asserted-by":"publisher","award":["A-0000065-97-00"],"award-info":[{"award-number":["A-0000065-97-00"]}],"id":[{"id":"10.13039\/501100001352","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Surrogate in vitro assays have enabled the scalable testing of neutralizing antibodies to SARS-CoV-2 as a toolbox to manage the post-COVID-19 situation and future outbreaks. However, most surrogate assays use a competitive format to mimic the blocking event between the receptor binding domain (RBD) and the human angiotensin-converting enzyme 2 (ACE2) receptor. This signal \u201cturn-off\u201d format has a narrow dynamic range and is semiquantitative at best. In this proof-of-concept work, we introduce a signal \u201cturn-on\u201d dual antigen assay based on the proximity activation of a pair of RBD-oligonucleotide initiator probes upon bridging by the target antibody. Three well-characterized SARS-CoV-2 variants, i.e., 2019 (wild-type), Delta (B.1.617.2), and Omicron (B.1.1.529), were tested against three commercial antibodies with known RBD-binding and ACE2-blocking profiles. The DNA proximity assay (DPA) results correlated with the ability of the antibodies to block ACE2 instead of their binding to the RBD. Moreover, the single-step, wash-free property of DPA enabled quantification using the kinetic rate of fluorescence signal generation which was more robust than conventional end-point measurements. The DPA achieved good analytical performance with ng\/mL detection limit and high assay precision (&amp;lt;5% interassay coefficient of variation), as well as good spike-and-recovery and dilution linearity in serum matrix. The test outcome from three sets of validated vaccine time-series samples were concordant with reference values, demonstrating the potential clinical utility of the DPA platform.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c01340","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:09:56Z","timestamp":1788534596000},"page":"26421-26429","source":"Crossref","is-referenced-by-count":0,"title":["A Signal Turn-On\nDNA Proximity Assay That Correlates\nwith SARS-CoV-2 Blocking Antibody Levels"],"prefix":"10.1021","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4890-1652","authenticated-orcid":true,"given":"Yan Shan","family":"Ang","sequence":"first","affiliation":[{"name":"National University of Singapore , , , ,","place":["Singapore, Singapore, 117585"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7579-6347","authenticated-orcid":true,"given":"Lin-Yue Lanry","family":"Yung","sequence":"additional","affiliation":[{"name":"National University of Singapore , , , ,","place":["Singapore, Singapore, 117585"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"issue":"16","key":"2026091511084080300_cit1","doi-asserted-by":"publisher","first-page":"15231","DOI":"10.1021\/acsnano.2c12584","article-title":"The mRNA Vaccine Revolution: COVID-19\nHas Launched the Future of\nVaccinology","volume":"17","author":"Ye","year":"2023","journal-title":"ACS Nano"},{"issue":"10359","key":"2026091511084080300_cit2","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1016\/S0140-6736(22)01585-9","article-title":"The Lancet Commission on Lessons\nfor the Future from the COVID-19 Pandemic","volume":"400","author":"Sachs","year":"2022","journal-title":"Lancet"},{"issue":"7","key":"2026091511084080300_cit3","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/s41576-021-00360-w","article-title":"Testing at Scale during the COVID-19 Pandemic","volume":"22","author":"Mercer","year":"2021","journal-title":"Nat. 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Med."},{"issue":"2","key":"2026091511084080300_cit10","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.cell.2020.12.015","article-title":"COVID-19-Neutralizing\nAntibodies Predict Disease Severity and Survival","volume":"184","author":"Garcia-Beltran","year":"2021","journal-title":"Cell"},{"issue":"3","key":"2026091511084080300_cit11","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1021\/acssensors.0c02621","article-title":"COVID-19 Antibody Tests and Their Limitations","volume":"6","author":"Liu","year":"2021","journal-title":"ACS Sens."},{"issue":"9","key":"2026091511084080300_cit12","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1038\/s41587-020-0631-z","article-title":"A SARS-CoV-2 Surrogate\nVirus Neutralization Test Based on Antibody-Mediated Blockage of ACE2\u2013Spike\nProtein\u2013Protein Interaction","volume":"38","author":"Tan","year":"2020","journal-title":"Nat. Biotechnol."},{"issue":"10","key":"2026091511084080300_cit13","doi-asserted-by":"publisher","first-page":"4504","DOI":"10.1021\/acs.analchem.2c00062","article-title":"Rapid and Quantitative In Vitro Evaluation of SARS-CoV-2 Neutralizing\nAntibodies and Nanobodies","volume":"94","author":"Wu","year":"2022","journal-title":"Anal. Chem."},{"issue":"1","key":"2026091511084080300_cit14","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/s43856-021-00045-9","article-title":"A Rapid\nSimple Point-of-Care Assay for the Detection of SARS-CoV-2 Neutralizing\nAntibodies","volume":"1","author":"Kongsuphol","year":"2021","journal-title":"Commun. Med."},{"issue":"2","key":"2026091511084080300_cit15","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10293","article-title":"Finger Stick Blood Test to Assess\nPostvaccination SARS-CoV-2 Neutralizing Antibody Response against\nVariants","volume":"7","author":"Lim","year":"2022","journal-title":"Bioeng. Transl. 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Commun."},{"issue":"43","key":"2026091511084080300_cit32","doi-asserted-by":"publisher","first-page":"15275","DOI":"10.1073\/pnas.0407024101","article-title":"Triggered Amplification\nby Hybridization Chain Reaction","volume":"101","author":"Dirks","year":"2004","journal-title":"Proc. Natl.\nAcad. Sci. U. S. A."},{"key":"2026091511084080300_cit33","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2022.114727","article-title":"Enzyme-Free\nand Isothermal Discrimination of microRNA Point Mutations Using a\nDNA Split Proximity Circuit with Turn-on Fluorescence Readout","volume":"217","author":"Ang","year":"2022","journal-title":"Biosens. Bioelectron."},{"issue":"30","key":"2026091511084080300_cit34","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202500575","article-title":"DNA-Programmed\nReaction to Evaluate\nSpecific IgE for Allergy Point-of-Care Testing","volume":"21","author":"Ang","year":"2025","journal-title":"Small"},{"issue":"15","key":"2026091511084080300_cit35","doi-asserted-by":"publisher","first-page":"10454","DOI":"10.1021\/acsnano.3c11435","article-title":"Protein-to-DNA Converter with High Signal Gain","volume":"18","author":"Ang","year":"2024","journal-title":"ACS Nano"},{"issue":"8","key":"2026091511084080300_cit36","doi-asserted-by":"publisher","first-page":"3928","DOI":"10.1021\/acssensors.4c00370","article-title":"One-Pot\nDetection of Proteins Using\na Two-Way Extension-Based Assay with Cas12a","volume":"9","author":"Gao","year":"2024","journal-title":"ACS Sens."},{"issue":"1","key":"2026091511084080300_cit37","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/s41467-024-54916-5","article-title":"The Molecular\nReach of Antibodies Crucially Underpins Their Viral Neutralisation\nCapacity","volume":"16","author":"Huhn","year":"2025","journal-title":"Nat. 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Chem."},{"issue":"1","key":"2026091511084080300_cit40","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2023.2174779","article-title":"Real-Life\nEffectiveness of COVID-19 Vaccine during the Omicron Variant-Dominant\nPandemic: How Many Booster Doses Do We Need?","volume":"12","author":"Sritipsukho","year":"2023","journal-title":"Emerg. Microbes Infect."},{"key":"2026091511084080300_cit41","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2021-069761","article-title":"Clinical Severity\nof, and Effectiveness of mRNA Vaccines against, Covid-19 from Omicron,\nDelta, and Alpha SARS-CoV-2 Variants in the United States: Prospective\nObservational Study","volume":"376","author":"Lauring","year":"2022","journal-title":"BMJ."},{"issue":"16","key":"2026091511084080300_cit42","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1056\/NEJMoa2119451","article-title":"Covid-19 Vaccine\nEffectiveness against the Omicron (B.1.1.529) Variant","volume":"386","author":"Andrews","year":"2022","journal-title":"N. Engl. J. Med."},{"issue":"4","key":"2026091511084080300_cit43","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202305774","article-title":"Fluorescence-Quenching\nLateral Flow Immunoassay for\n\u201cTurn-On\u201d and Sensitive Detection of Anti-SARS-Cov-2\nNeutralizing Antibodies in Human Serum","volume":"11","author":"Bian","year":"2024","journal-title":"Adv.\nSci."},{"issue":"10","key":"2026091511084080300_cit44","doi-asserted-by":"publisher","first-page":"5407","DOI":"10.1021\/acs.analchem.5c00666","article-title":"Advances in Surrogate Neutralization Tests for High-Throughput\nScreening and the Point-of-Care","volume":"97","author":"Streif","year":"2025","journal-title":"Anal. Chem."}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.6c01340","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/36\/26421\/68377039\/acs.analchem.6c01340.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/36\/26421\/68377039\/acs.analchem.6c01340.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:31:33Z","timestamp":1789486293000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/98\/36\/26421\/5420770\/A-Signal-Turn-On-DNA-Proximity-Assay-That"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,4]]},"references-count":44,"journal-issue":{"issue":"36","published-online":{"date-parts":[[2026,9,4]]},"published-print":{"date-parts":[[2026,9,15]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.6c01340","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,4]]}}}