{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:16:58Z","timestamp":1788412618677,"version":"build-2803163510"},"reference-count":69,"publisher":"American Chemical Society (ACS)","issue":"1","license":[{"start":{"date-parts":[[2015,12,16]],"date-time":"2015-12-16T00:00:00Z","timestamp":1450224000000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["0546165"],"award-info":[{"award-number":["0546165"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM079613"],"award-info":[{"award-number":["GM079613"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD078678"],"award-info":[{"award-number":["HD078678"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Botulinum neurotoxins (BoNTs) are the most lethal toxin known to human. Biodefense requires early and rapid detection of BoNTs. Traditionally, BoNTs can be detected by looking for signs of botulism in mice that receive an injection of human material, serum or stool. While the living animal assay remains the most sensitive approach, it is costly, slow and associated with legal and ethical constrains. Various biochemical, optical and mechanical methods have been developed for BoNTs detection with improved speed, but with lesser sensitivity. Here, we report a novel nanopore-based BoNT type B (BoNT-B) sensor that monitors the toxin\u2019s enzymatic activity on its substrate, a recombinant synaptic protein synaptobrevin 2 derivative. By analyzing the modulation of the pore current caused by the specific BoNT-B-digested peptide as a marker, the presence of BoNT-B at a subnanomolar concentration was identified within minutes. The nanopore detector would fill the niche for a much needed rapid and highly sensitive detection of neurotoxins, and provide an excellent system to explore biophysical mechanisms for biopolymer transportation.<\/jats:p>","DOI":"10.1021\/am5056596","type":"journal-article","created":{"date-parts":[[2014,12,16]],"date-time":"2014-12-16T07:07:11Z","timestamp":1418713631000},"page":"184-192","source":"Crossref","is-referenced-by-count":64,"title":["Nanopore\nSensing of Botulinum Toxin Type B by Discriminating an Enzymatically\nCleaved Peptide from a Synaptic Protein Synaptobrevin 2 Derivative"],"prefix":"10.1021","volume":"7","author":[{"given":"Yong","family":"Wang","sequence":"first","affiliation":[{"name":"University of Missouri , and Dalton Cardiovascular Research Center, , and Dalton Cardiovascular Research Center, and Dalton Cardiovascular Research Center, , , ,","place":["Columbia, Missouri, United States, 65211"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vedrana","family":"Montana","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham , Center for Glial Biology in Medicine, Atomic Force Microscopy & Nanotechnology Laboratories, Civitan International Research Center, Evelyn F. McKnight Brain Institute, , , ,","place":["Birmingham, Alabama, United States, 35294"]},{"name":"University of Rijeka , , ,","place":["Rijeka, Croatia, 51000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Grubis\u030cic\u0301","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham , Center for Glial Biology in Medicine, Atomic Force Microscopy & Nanotechnology Laboratories, Civitan International Research Center, Evelyn F. McKnight Brain Institute, , , ,","place":["Birmingham, Alabama, United States, 35294"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Randy F.","family":"Stout","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham , Center for Glial Biology in Medicine, Atomic Force Microscopy & Nanotechnology Laboratories, Civitan International Research Center, Evelyn F. McKnight Brain Institute, , , ,","place":["Birmingham, Alabama, United States, 35294"]},{"name":"Albert Einstein College of Medicine , , Bronx, , ,","place":["New York, New York, United States, 10461"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Parpura","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham , Center for Glial Biology in Medicine, Atomic Force Microscopy & Nanotechnology Laboratories, Civitan International Research Center, Evelyn F. McKnight Brain Institute, , , ,","place":["Birmingham, Alabama, United States, 35294"]},{"name":"University of Rijeka , , ,","place":["Rijeka, Croatia, 51000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Qun","family":"Gu","sequence":"additional","affiliation":[{"name":"University of Missouri , and Dalton Cardiovascular Research Center, , and Dalton Cardiovascular Research Center, and Dalton Cardiovascular Research Center, , , ,","place":["Columbia, Missouri, United States, 65211"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,12,16]]},"reference":[{"key":"2026090300400625900_cit1","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1128\/mr.56.1.80-99.1992","article-title":"Properties and Use\nof Botulinum Toxin and Other Microbial Neurotoxins in Medicine","volume":"56","author":"Schantz","year":"1992","journal-title":"Microbiol. 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Sci."},{"key":"2026090300400625900_cit9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0092-8674(05)80077-7","article-title":"Membrane Fusion Machinery: Insights\nfrom Synaptic Proteins","volume":"75","author":"Sudhof","year":"1993","journal-title":"Cell"},{"issue":"Suppl 1","key":"2026090300400625900_cit10","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1002\/(SICI)1099-1263(199912)19:1+<S13::AID-JAT607>3.0.CO;2-3","article-title":"Rapid Microplate Assay\nfor Monitoring Botulinum Neurotoxin B Catalytic Activity","volume":"19","author":"Keller","year":"1999","journal-title":"J. Appl. Toxicol."},{"key":"2026090300400625900_cit11","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0022-1759(02)00030-3","article-title":"Rapid and Sensitive Detection of Biological Warfare\nAgents Using Time-Resolved Fluorescence Assays","volume":"263","author":"Peruski","year":"2002","journal-title":"J. Immunol. Methods"},{"key":"2026090300400625900_cit12","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.pep.2004.05.009","article-title":"The C-Terminus of\nBotulinum Neurotoxin Type A Light Chain Contributes to Solubility,\nCatalysis, and Stability","volume":"37","author":"Baldwin","year":"2004","journal-title":"Protein Expression\nPurif."},{"key":"2026090300400625900_cit13","doi-asserted-by":"crossref","first-page":"13621","DOI":"10.1073\/pnas.2233819100","article-title":"Botulinum Toxin Type B Micromechanosensor","volume":"100","author":"Liu","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U. S. 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A."},{"key":"2026090300400625900_cit17","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1146\/annurev.anchem.1.031207.112818","article-title":"Nanoscopic\nPorous Sensors","volume":"1","author":"Kasianowicz","year":"2008","journal-title":"Annu. Rev. Anal. Chem."},{"key":"2026090300400625900_cit18","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/35093038","article-title":"Stochastic Sensors\nInspired by Biology","volume":"413","author":"Bayley","year":"2001","journal-title":"Nature"},{"key":"2026090300400625900_cit19","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1039\/B907735A","article-title":"Single Molecule Sensing by Nanopores\nand Nanopore Devices","volume":"135","author":"Gu","year":"2010","journal-title":"Analyst"},{"key":"2026090300400625900_cit20","doi-asserted-by":"crossref","first-page":"2360","DOI":"10.1039\/b813796j","article-title":"Nanopore Analytics:\nSensing of Single Molecules","volume":"38","author":"Howorka","year":"2009","journal-title":"Chem. Soc. Rev."},{"key":"2026090300400625900_cit21","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nnano.2009.12","article-title":"Continuous Base Identification\nfor Single-Molecule Nanopore DNA Sequencing","volume":"4","author":"Clarke","year":"2009","journal-title":"Nat. Nanotechnol."},{"key":"2026090300400625900_cit22","doi-asserted-by":"crossref","first-page":"14325","DOI":"10.1073\/pnas.1415944111","article-title":"Single-Molecule Investigation of\nG-Quadruplex Folds of the Human Telomere Sequence in a Protein Nanocavity","volume":"111","author":"An","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026090300400625900_cit23","doi-asserted-by":"crossref","first-page":"8354","DOI":"10.1021\/jp0775911","article-title":"Encapsulating a\nSingle G-Quadruplex Aptamer in a Protein Nanocavity","volume":"112","author":"Shim","year":"2008","journal-title":"J. Phys. Chem. B"},{"key":"2026090300400625900_cit24","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1093\/nar\/gkn968","article-title":"Single-Molecule Detection of Folding and Unfolding\nof the G-Quadruplex Aptamer in a Nanopore Nanocavity","volume":"37","author":"Shim","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2026090300400625900_cit25","doi-asserted-by":"crossref","first-page":"5883","DOI":"10.1038\/srep05883","article-title":"Single Molecule Investigation of\nAg+ Interactions with Single Cytosine-, Methylcytosine-\nand Hydroxymethylcytosine-Cytosine Mismatches in a Nanopore","volume":"4","author":"Wang","year":"2014","journal-title":"Sci. Rep."},{"key":"2026090300400625900_cit26","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/nbt.2147","article-title":"Automated\nForward and Reverse Ratcheting of DNA in a Nanopore at 5-\u00c5 Precision","volume":"30","author":"Cherf","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"2026090300400625900_cit27","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/nbt.2950","article-title":"Decoding Long Nanopore Sequencing Reads of Natural\nDNA","volume":"32","author":"Laszlo","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"2026090300400625900_cit28","first-page":"668","article-title":"Nanopore-based Detection of Circulating Micrornas in Lung Cancer\nPatients","volume":"6","author":"Wang","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"2026090300400625900_cit29","doi-asserted-by":"crossref","first-page":"11372","DOI":"10.1039\/C4NR03195D","article-title":"Probing Molecular Pathways for DNA Orientational Trapping, Unzipping\nand Translocation in Nanopores by Using a Tunable Overhang Sensor","volume":"6","author":"Wang","year":"2014","journal-title":"Nanoscale"},{"key":"2026090300400625900_cit30","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1529\/biophysj.104.057406","article-title":"Interactions of Peptides\nwith a Protein Pore","volume":"89","author":"Movileanu","year":"2005","journal-title":"Biophys. J."},{"key":"2026090300400625900_cit31","doi-asserted-by":"crossref","first-page":"3885","DOI":"10.1038\/srep03885","article-title":"Slowing Down Single-Molecule Trafficking through a\nProtein Nanopore Reveals Intermediates for Peptide Translocation","volume":"4","author":"Mereuta","year":"2014","journal-title":"Sci. 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Biotechnol."},{"key":"2026090300400625900_cit37","doi-asserted-by":"crossref","first-page":"2781","DOI":"10.1021\/ja2105653","article-title":"Protein Detection by Nanopores Equipped\nwith Aptamers","volume":"134","author":"Rotem","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"2026090300400625900_cit38","doi-asserted-by":"crossref","first-page":"9814","DOI":"10.1021\/nn404435v","article-title":"Engineered Nanopore of Phi29 DNA-Packaging\nMotor for Real-Time Detection of Single Colon Cancer Specific Antibody\nin Serum","volume":"7","author":"Wang","year":"2013","journal-title":"ACS Nano"},{"key":"2026090300400625900_cit39","doi-asserted-by":"crossref","first-page":"6324","DOI":"10.1021\/ja9004893","article-title":"Real-Time Monitoring of Peptide Cleavage Using a Nanopore Probe","volume":"131","author":"Zhao","year":"2009","journal-title":"J. Am. Chem. 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A."},{"key":"2026090300400625900_cit58","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1039\/b911525k","article-title":"Simultaneous Quantification\nof Five Bacterial and Plant Toxins from Complex Matrices Using a Multiplexed\nFluorescent Magnetic Suspension Assay","volume":"134","author":"Pauly","year":"2009","journal-title":"Analyst"},{"key":"2026090300400625900_cit59","first-page":"491","article-title":"Detection of Botulinum\nToxins: Micromechanical and Fluorescence-Based Sensors","volume":"46","author":"Parpura","year":"2005","journal-title":"Croat. Med. J."},{"key":"2026090300400625900_cit60","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1080\/10408410701364562","article-title":"Botulism Diagnostics: From Clinical Symptoms to in\nVitro Assays","volume":"33","author":"Cai","year":"2007","journal-title":"Crit. Rev. 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