{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T23:16:15Z","timestamp":1788218175123,"version":"build-2803163510"},"reference-count":39,"publisher":"American Chemical Society (ACS)","issue":"33","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/na","name":"The National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFF0710200"],"award-info":[{"award-number":["2022YFF0710200"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Fujian Provincial Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2025J01017"],"award-info":[{"award-number":["2025J01017"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"The National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22074127"],"award-info":[{"award-number":["22074127"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"The National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22193053"],"award-info":[{"award-number":["22193053"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Accurate single-molecule quantification of biomolecular targets is essential for ultrasensitive bioanalysis and early disease diagnostics. Single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS) enables the detection of individual metal nanoparticles with high accuracy, sensitivity, and excellent elemental selectivity, making it an attractive platform for nanoparticle-based bioanalysis. However, its application to single-molecule counting of biomolecules remains limited. Herein, we report a monovalent nanotag-mediated strategy for single-molecule counting of biomolecules by using SP-ICP-MS. We constructed monovalent DNA-functionalized gold nanoparticles (mDNA-AuNPs), each carrying a single DNA strand designed for target-specific DNA hybridization or aptamer-mediated protein recognition, thereby enabling well-defined 1:1 interaction with target molecules and AuNP release. We first validated the feasibility of this strategy using DNA targets via a strand displacement-mediated release mechanism. We subsequently extended the method to thrombin detection through a binding-induced aptamer conformation switching and nanotag release process. This strategy provides a promising platform for single-molecule counting and expands the applicability of SP-ICP-MS for ultrasensitive biomolecular detection.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c03409","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:01:48Z","timestamp":1786348908000},"page":"24430-24438","source":"Crossref","is-referenced-by-count":0,"title":["Monovalent\nTargeting Nanotag-Mediated Single-Molecule\nCounting by SP-ICP-MS"],"prefix":"10.1021","volume":"98","author":[{"given":"Yingyan","family":"Xie","sequence":"first","affiliation":[{"name":"Xiamen University , , , ,","place":["Xiamen, Fujian, China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Xiamen University , , , ,","place":["Xiamen, Fujian, China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyang","family":"Fang","sequence":"additional","affiliation":[{"name":"Xiamen University , , , ,","place":["Xiamen, Fujian, China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naijie","family":"Wei","sequence":"additional","affiliation":[{"name":"Xiamen University , , , ,","place":["Xiamen, Fujian, China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinran","family":"Peng","sequence":"additional","affiliation":[{"name":"Xiamen University , , , ,","place":["Xiamen, Fujian, China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5166-4048","authenticated-orcid":true,"given":"Qiuquan","family":"Wang","sequence":"additional","affiliation":[{"name":"Xiamen University , , , ,","place":["Xiamen, Fujian, China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6608-6044","authenticated-orcid":true,"given":"Xiaowen","family":"Yan","sequence":"additional","affiliation":[{"name":"Xiamen University , , , ,","place":["Xiamen, Fujian, China, 361005"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"issue":"6","key":"2026083118453838000_cit1","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1038\/nbt.1641","article-title":"Single-molecule enzyme-linked immunosorbent\nassay detects serum proteins at subfemtomolar concentrations","volume":"28","author":"Rissin","year":"2010","journal-title":"Nat. Biotechnol."},{"issue":"2","key":"2026083118453838000_cit2","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1021\/acs.jafc.1c06808","article-title":"Recent Progress on\nSingle-Molecule Detection Technologies for Food Safety","volume":"70","author":"Su","year":"2022","journal-title":"J. Agric. Food Chem."},{"issue":"38","key":"2026083118453838000_cit3","doi-asserted-by":"publisher","first-page":"11354","DOI":"10.1002\/anie.201600495","article-title":"Single-Molecule Sensors:\nChallenges and Opportunities for Quantitative\nAnalysis","volume":"55","author":"Gooding","year":"2016","journal-title":"Angew. Chem., Int. Ed."},{"issue":"3","key":"2026083118453838000_cit4","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1093\/abbs\/gmx146","article-title":"Single-molecule manipulation and detection","volume":"50","author":"Zhao","year":"2018","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"2026083118453838000_cit5","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1016\/j.ijbiomac.2022.04.038","article-title":"Single molecule\ndetection; from microscopy\nto sensors","volume":"209","author":"Chauhan","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"issue":"8009","key":"2026083118453838000_cit6","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/s41586-024-07218-1","article-title":"Digital colloid-enhanced\nRaman spectroscopy by single-molecule counting","volume":"628","author":"Bi","year":"2024","journal-title":"Nature"},{"issue":"12","key":"2026083118453838000_cit7","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1039\/b106387c","article-title":"A novel combination\nof immunoreaction and ICP-MS as a hyphenated technique for the determination\nof thyroid-stimulating hormone (TSH) in human serum","volume":"16","author":"Zhang","year":"2001","journal-title":"J. Anal. At. Spectrom."},{"issue":"3","key":"2026083118453838000_cit8","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1021\/ac061269p","article-title":"Detection\nof multiple proteins on one spot by laser ablation inductively coupled\nplasma mass spectrometry and application to immuno- microarray with\nelement-tagged antibodies","volume":"79","author":"Hu","year":"2007","journal-title":"Anal. Chem."},{"issue":"16","key":"2026083118453838000_cit9","doi-asserted-by":"publisher","first-page":"6813","DOI":"10.1021\/ac901049w","article-title":"Mass Cytometry:\nTechnique for Real Time Single Cell Multitarget Immunoassay Based\non Inductively Coupled Plasma Time-of-Flight Mass Spectrometry","volume":"81","author":"Bandura","year":"2009","journal-title":"Anal. Chem."},{"issue":"4","key":"2026083118453838000_cit10","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1021\/ac902163x","article-title":"Absolute quantification of intact\nproteins via 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid-10-maleimidoethylacetamide-europium\nlabeling and HPLC coupled with species-unspecific isotope dilution\nICPMS","volume":"82","author":"Yan","year":"2010","journal-title":"Anal. Chem."},{"issue":"22","key":"2026083118453838000_cit11","doi-asserted-by":"publisher","first-page":"5130","DOI":"10.1002\/anie.201101087","article-title":"Lanthanide-coded\nprotease-specific\npeptide-nanoparticle probes for a label-free multiplex protease assay\nusing element mass spectrometry: a proof-of-concept study","volume":"50","author":"Yan","year":"2011","journal-title":"Angew. Chem., Int. 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Chem."},{"issue":"5","key":"2026083118453838000_cit14","doi-asserted-by":"publisher","first-page":"3769","DOI":"10.1021\/acs.analchem.9b05105","article-title":"Amplification Strategy of Silver\nNanoclusters with a Satellite-Nanostructure for Substrate-Free Assay\nof Alkaline Phosphatase by ICP-MS","volume":"92","author":"Liu","year":"2020","journal-title":"Anal. Chem."},{"issue":"7","key":"2026083118453838000_cit15","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1021\/acschemneuro.0c00816","article-title":"Screening Platform\nBased on Inductively Coupled Plasma Mass Spectrometry for \u03b2-Site\nAmyloid Protein Cleaving Enzyme 1 (BACE1) Inhibitors","volume":"12","author":"Jin","year":"2021","journal-title":"ACS Chem. Neurosci."},{"issue":"2","key":"2026083118453838000_cit16","doi-asserted-by":"publisher","first-page":"74","DOI":"10.46770\/AS.2024.078","article-title":"Covalent Targeting\nDrug Mediated Specific Lanthanide Tagging Towards In Situ Bruton\u2019s\nTyrosine Kinase Quantification Using ICP-MS","volume":"45","author":"Yan","year":"2024","journal-title":"At. Spectrosc."},{"issue":"5","key":"2026083118453838000_cit17","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1002\/anie.201206903","article-title":"Absolute and relative\nquantification of multiplex DNA assays based on an elemental labeling\nstrategy","volume":"52","author":"Han","year":"2013","journal-title":"Angew. Chem., Int. 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Protoc."},{"key":"2026083118453838000_cit23","volume-title":"Analysis\nOf 10 Nm Gold\nNanoparticles Using The Agilent 7800 ICP-MS","author":"Woods","year":"2017"},{"issue":"71","key":"2026083118453838000_cit24","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202402289","article-title":"A CH 4 -Driven Ion Cloud-Stretched\nApproach Enables ICP- q MS for\nMultiplex Single-Cell Analysis","volume":"30","author":"Lv","year":"2024","journal-title":"Chem. Eur. J."},{"issue":"15","key":"2026083118453838000_cit25","doi-asserted-by":"publisher","first-page":"3462","DOI":"10.1002\/anie.201006838","article-title":"One-step homogeneous\nDNA assay with single-nanoparticle detection","volume":"50","author":"Han","year":"2011","journal-title":"Angew. Chem., Int. Ed."},{"issue":"7","key":"2026083118453838000_cit26","doi-asserted-by":"publisher","first-page":"3541","DOI":"10.1021\/ac404245z","article-title":"Multiplex DNA assay\nbased on nanoparticle probes by single particle inductively coupled\nplasma mass spectrometry","volume":"86","author":"Zhang","year":"2014","journal-title":"Anal. Chem."},{"issue":"24","key":"2026083118453838000_cit27","doi-asserted-by":"publisher","first-page":"8381","DOI":"10.1021\/acs.analchem.1c01447","article-title":"Single-Nanoparticle\nICP-MS for Sensitive Detection of Uracil-DNA Glycosylase Activity","volume":"93","author":"Li","year":"2021","journal-title":"Anal. Chem."},{"issue":"44","key":"2026083118453838000_cit28","doi-asserted-by":"publisher","first-page":"15433","DOI":"10.1021\/acs.analchem.2c03367","article-title":"Single Nanoparticle\nCounting-Based Liquid Biopsy for Cancer Diagnosis","volume":"94","author":"Jiang","year":"2022","journal-title":"Anal. Chem."},{"issue":"7","key":"2026083118453838000_cit29","doi-asserted-by":"publisher","first-page":"5286","DOI":"10.1021\/acs.analchem.9b05838","article-title":"Direct Infusion\nICP-qMS of Lined-up Single-Cell Using an Oil-Free Passive Microfluidic\nSystem","volume":"92","author":"Zhou","year":"2020","journal-title":"Anal. Chem."},{"issue":"3","key":"2026083118453838000_cit30","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1021\/acs.chemrev.2c00350","article-title":"Reagents\nfor Mass Cytometry","volume":"123","author":"Arnett","year":"2023","journal-title":"Chem. Rev."},{"issue":"6","key":"2026083118453838000_cit31","doi-asserted-by":"publisher","first-page":"4904","DOI":"10.1021\/jacs.4c13706","article-title":"Breaking Barcode Limits:\nMetal Nanoparticle Lego Brick Self-Assembly for High-Throughput Screening","volume":"147","author":"Huang","year":"2025","journal-title":"J. Am. Chem. Soc."},{"issue":"1","key":"2026083118453838000_cit32","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1007\/s00604-019-4057-6","article-title":"Aggregation-based\ndetermination of mercury(II) using DNA-modified single gold nanoparticle,\nT-Hg(II)-T interaction, and single-particle ICP-MS","volume":"187","author":"Xing","year":"2019","journal-title":"Microchim. Acta."},{"issue":"29","key":"2026083118453838000_cit33","doi-asserted-by":"publisher","first-page":"11876","DOI":"10.1021\/ja304118z","article-title":"Designed diblock oligonucleotide\nfor the synthesis of spatially isolated and highly hybridizable functionalization\nof DNA-gold nanoparticle nanoconjugates","volume":"134","author":"Pei","year":"2012","journal-title":"J.\nAm. Chem. Soc."},{"issue":"1","key":"2026083118453838000_cit34","doi-asserted-by":"publisher","DOI":"10.1038\/am.2014.131","article-title":"Clicking DNA to gold nanoparticles:\npoly-adenine-mediated formation of monovalent DNA-gold nanoparticle\nconjugates with nearly quantitative yield","volume":"7","author":"Yao","year":"2015","journal-title":"NPG\nAsia Mater."},{"issue":"8","key":"2026083118453838000_cit35","doi-asserted-by":"publisher","first-page":"785","DOI":"10.3390\/s6080785","article-title":"Aptamer Based Microsphere\nBiosensor for Thrombin Detection","volume":"6","author":"Zhu","year":"2006","journal-title":"Sensors"},{"key":"2026083118453838000_cit36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.aca.2014.04.055","article-title":"Aptamer\nbinding assays for proteins:\nThe thrombin example A review","volume":"837","author":"Deng","year":"2014","journal-title":"Anal. Chim. Acta"},{"key":"2026083118453838000_cit37","doi-asserted-by":"publisher","first-page":"4771","DOI":"10.1021\/ja028962o","article-title":"Structure-Switching\nSignaling Aptamers","volume":"125","author":"Nutiu","year":"2003","journal-title":"J.\nAm. Chem. Soc."},{"key":"2026083118453838000_cit38","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1016\/j.compbiolchem.2018.11.030","article-title":"Label-free optical\nbiosensor for target detection based on simulation-assisted catalyzed\nhairpin assembly","volume":"78","author":"Zhang","year":"2019","journal-title":"Comput. Biol. Chem."},{"issue":"4","key":"2026083118453838000_cit39","doi-asserted-by":"publisher","first-page":"253","DOI":"10.3390\/bios12040253","article-title":"Nanomaterial-Based\nLabel-Free Electrochemical Aptasensors\nfor the Detection of Thrombin","volume":"12","author":"Yousef","year":"2022","journal-title":"Biosensors"}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.6c03409","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/33\/24430\/66469449\/acs.analchem.6c03409.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/33\/24430\/66469449\/acs.analchem.6c03409.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T22:45:47Z","timestamp":1788216347000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/98\/33\/24430\/5250985\/Monovalent-Targeting-Nanotag-Mediated-Single"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":39,"journal-issue":{"issue":"33","published-online":{"date-parts":[[2026,8,10]]},"published-print":{"date-parts":[[2026,8,25]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.6c03409","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]}}}