{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T02:12:04Z","timestamp":1776132724143,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,10,3]],"date-time":"2021-10-03T00:00:00Z","timestamp":1633219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytometry Pt A"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sensitive and quantitative detection of molecular biomarkers is crucial for the early diagnosis of diseases like metabolic syndrome and cancer. Here we present a single\u2010molecule sandwich immunoassay by imaging the number of single nanoparticles to diagnose aggressive prostate cancer. Our assay employed the photo\u2010stable upconversion nanoparticles (UCNPs) as labels to detect the four types of circulating antigens in blood circulation, including glypican\u20101 (GPC\u20101), leptin, osteopontin (OPN), and vascular endothelial growth factor (VEGF), as their serum concentrations indicate aggressive prostate cancer. Under a wide\u2010field microscope, a single UCNP doped with thousands of lanthanide ions can emit sufficiently bright anti\u2010Stokes' luminescence to become quantitatively detectable. By counting every single streptavidin\u2010functionalized UCNP which specifically labeled on each sandwich immune complex across multiple fields of views, we achieved the Limit of Detection (LOD) of 0.0123\u2009ng\/ml, 0.2711\u2009ng\/ml, 0.1238\u2009ng\/ml, and 0.0158\u2009ng\/ml for GPC\u20101, leptin, OPN and VEGF, respectively. The serum circulating level of GPC\u20101, leptin, OPN, and VEGF in a mixture of 10 healthy normal human serum was 25.17\u2009ng\/ml, 18.04\u2009ng\/ml, 11.34\u2009ng\/ml, and 1.55\u2009ng\/ml, which was within the assay dynamic detection range for each analyte. Moreover, a 20% increase of GPC\u20101 and OPN was observed by spiking the normal human serum with recombinant antigens to confirm the accuracy of the assay. We observed no cross\u2010reactivity among the four biomarker analytes, which eliminates the false positives and enhances the detection accuracy. The developed single upconversion nanoparticle\u2010assisted single\u2010molecule assay suggests its potential in clinical usage for prostate cancer detection by monitoring tiny concentration differences in a panel of serum biomarkers.<\/jats:p>","DOI":"10.1002\/cyto.a.24504","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T21:05:04Z","timestamp":1632949504000},"page":"400-410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Upconversion nanoparticle\u2010assisted single\u2010molecule assay for detecting circulating antigens of aggressive prostate cancer"],"prefix":"10.1002","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7886-7144","authenticated-orcid":false,"given":"Yinghui","family":"Chen","sequence":"first","affiliation":[{"name":"Institute for Biomedical Materials and Devices, School of Mathematical and Physical Sciences, Faculty of Science University of Technology Sydney  New South Wales Australia"},{"name":"ARC Research Hub for Integrated Device for End\u2010user Analysis at Low\u2010levels (IDEAL), Faculty of Science University of Technology Sydney  New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Shimoni","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Materials and Devices, School of Mathematical and Physical Sciences, Faculty of Science University of Technology Sydney  New South Wales Australia"},{"name":"ARC Research Hub for Integrated Device for End\u2010user Analysis at Low\u2010levels (IDEAL), Faculty of Science University of Technology Sydney  New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guan","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Materials and Devices, School of Mathematical and Physical Sciences, Faculty of Science University of Technology Sydney  New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shihui","family":"Wen","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Materials and Devices, School of Mathematical and Physical Sciences, Faculty of Science University of Technology Sydney  New South Wales Australia"},{"name":"ARC Research Hub for Integrated Device for End\u2010user Analysis at Low\u2010levels (IDEAL), Faculty of Science University of Technology Sydney  New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayan","family":"Liao","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Materials and Devices, School of Mathematical and Physical Sciences, Faculty of Science University of Technology Sydney  New South Wales Australia"},{"name":"ARC Research Hub for Integrated Device for End\u2010user Analysis at Low\u2010levels (IDEAL), Faculty of Science University of Technology Sydney  New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hien T. T.","family":"Duong","sequence":"additional","affiliation":[{"name":"The School of Pharmacy The University of Sydney  New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahnaz","family":"Maddahfar","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Materials and Devices, School of Mathematical and Physical Sciences, Faculty of Science University of Technology Sydney  New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian Peter","family":"Su","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Materials and Devices, School of Mathematical and Physical Sciences, Faculty of Science University of Technology Sydney  New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David Gallego","family":"Ortega","sequence":"additional","affiliation":[{"name":"ARC Research Hub for Integrated Device for End\u2010user Analysis at Low\u2010levels (IDEAL), Faculty of Science University of Technology Sydney  New South Wales Australia"},{"name":"School of Biomedical Engineering, Faculty of Engineering and IT University of Technology Sydney  Ultimo New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanling","family":"Lu","sequence":"additional","affiliation":[{"name":"ARC Research Hub for Integrated Device for End\u2010user Analysis at Low\u2010levels (IDEAL), Faculty of Science University of Technology Sydney  New South Wales Australia"},{"name":"Minomic International Ltd  Macquarie Park New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas H.","family":"Campbell","sequence":"additional","affiliation":[{"name":"ARC Research Hub for Integrated Device for End\u2010user Analysis at Low\u2010levels (IDEAL), Faculty of Science University of Technology Sydney  New South Wales Australia"},{"name":"Minomic International Ltd  Macquarie Park New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley J.","family":"Walsh","sequence":"additional","affiliation":[{"name":"ARC Research Hub for Integrated Device for End\u2010user Analysis at Low\u2010levels (IDEAL), Faculty of Science University of Technology Sydney  New South Wales Australia"},{"name":"Minomic International Ltd  Macquarie Park New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1046-2666","authenticated-orcid":false,"given":"Dayong","family":"Jin","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Materials and Devices, School of Mathematical and Physical Sciences, Faculty of Science University of Technology Sydney  New South Wales Australia"},{"name":"ARC Research Hub for Integrated Device for End\u2010user Analysis at Low\u2010levels (IDEAL), Faculty of Science University of Technology Sydney  New South Wales Australia"},{"name":"UTS\u2010SUStech Joint Research Centre for Biomedical Materials &amp; Devices, Department of Biomedical Engineering Southern University of Science and Technology  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,10,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-008-2379-z"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11183"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2019.06.019"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471140864.ps2701s72"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.6b04290"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-011-0098-y"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2015.03.083"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8LC00535D"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04813-5"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22283-0"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/lsa.2018.7"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05842-w"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11603-0"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03092-9"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.0c00448"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21366"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201905572"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19952-x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01141-y"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-021-00852-0"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2048-8"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.1c02404"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nphoton.2013.322"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40843-018-9341-8"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpclett.9b03838"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10254"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.6b05331"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08777"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.7b04240"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7RA13765F"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2015.06.058"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.7b05341"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.5b02523"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.1c00192"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2019.11.048"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.7b03542"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.9b02872"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.8b04330"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2020.03.010"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-47874-2"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-15-0123"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/418340"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.3233\/CBM-2010-0136"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605834"},{"key":"e_1_2_9_47_1","first-page":"610","article-title":"Osteopontin expression and distribution in human carcinomas","volume":"145","author":"Brown LF","year":"1994","journal-title":"Am J Pathol"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2012.345"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781420084474-c12"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.4103\/2229-5186.79345"}],"container-title":["Cytometry Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cyto.a.24504","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cyto.a.24504","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cyto.a.24504","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T08:19:49Z","timestamp":1692865189000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cyto.a.24504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,3]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1002\/cyto.a.24504"],"URL":"https:\/\/doi.org\/10.1002\/cyto.a.24504","archive":["Portico"],"relation":{},"ISSN":["1552-4922","1552-4930"],"issn-type":[{"value":"1552-4922","type":"print"},{"value":"1552-4930","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,3]]},"assertion":[{"value":"2021-07-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}