{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:28:57Z","timestamp":1791325737320,"version":"4.3.1"},"reference-count":99,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T00:00:00Z","timestamp":1707782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T00:00:00Z","timestamp":1707782400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFE0103500"],"award-info":[{"award-number":["2022YFE0103500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"publisher","award":["2019CXJQ03"],"award-info":[{"award-number":["2019CXJQ03"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"publisher","award":["2022JC013"],"award-info":[{"award-number":["2022JC013"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"publisher","award":["202240361"],"award-info":[{"award-number":["202240361"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003395","name":"Shanghai Municipal Education Commission","doi-asserted-by":"publisher","award":["ZXWF082101"],"award-info":[{"award-number":["ZXWF082101"]}],"id":[{"id":"10.13039\/501100003395","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["20DZ2220400"],"award-info":[{"award-number":["20DZ2220400"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["BX2021182"],"award-info":[{"award-number":["BX2021182"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Phenylketonuria (PKU) is the most common inherited metabolic disease in humans. Clinical screening of newborn heel blood samples for PKU is costly and time\u2010consuming because it requires multiple procedures, like isotope labeling and derivatization, and PKU subtype identification requires an additional urine sample. Delayed diagnosis of PKU, or subtype identification can result in mental disability. Here, plasmonic silver nanoshells are used for laser desorption\/ionization mass spectrometry (MS) detection of PKU with label\u2010free assay by recognizing metabolic profile in dried blood spot (DBS) samples. A total of 1100 subjects are recruited and each DBS sample can be processed in seconds. This platform achieves PKU screening with a sensitivity of 0.985 and specificity of 0.995, which is comparable to existing clinical liquid chromatography MS (LC\u2010MS) methods. This method can process 360 samples per hour, compared with the LC\u2010MS method which processes only 30 samples per hour. Moreover, this assay enables precise identification of PKU subtypes without the need for a urine sample. It is demonstrated that this platform enables high\u2010performance and fast, low\u2010cost PKU screening and subtype identification. This approach might be suitable for the detection of other clinically relevant biomarkers in blood or other clinical samples.<\/jats:p>","DOI":"10.1002\/advs.202305701","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T04:30:35Z","timestamp":1707798635000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Fast Label\u2010Free Metabolic Profile Recognition Identifies Phenylketonuria and Subtypes"],"prefix":"10.1002","volume":"11","author":[{"given":"Haiyang","family":"Su","sequence":"first","affiliation":[{"name":"Henan Key Laboratory of Rare Diseases Endocrinology and Metabolism Center The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology  Luoyang 471003 P. R. China"},{"name":"State Key Laboratory of Systems Medicine for Cancer School of Biomedical Engineering Institute of Medical Robotics and Shanghai Academy of Experimental Medicine Shanghai Jiao Tong University  Shanghai 200030 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xinhua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200092 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Systems Medicine for Cancer School of Biomedical Engineering Institute of Medical Robotics and Shanghai Academy of Experimental Medicine Shanghai Jiao Tong University  Shanghai 200030 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Huang","sequence":"additional","affiliation":[{"name":"Country Department of Clinical Laboratory Medicine Shanghai Chest Hospital Shanghai Jiao Tong University  Shanghai 200030 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengji","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Systems Medicine for Cancer School of Biomedical Engineering Institute of Medical Robotics and Shanghai Academy of Experimental Medicine Shanghai Jiao Tong University  Shanghai 200030 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Oncogenes and Related Genes Division of Cardiology Renji Hospital, School of Medicine, Shanghai Jiao Tong University  Shanghai 200127 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Systems Medicine for Cancer School of Biomedical Engineering Institute of Medical Robotics and Shanghai Academy of Experimental Medicine Shanghai Jiao Tong University  Shanghai 200030 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanshan","family":"Liu","sequence":"additional","affiliation":[{"name":"Xinhua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200092 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Electronics Information and Electrical Engineering Shanghai Jiao Tong University  Shanghai 200240 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Henan Key Laboratory of Rare Diseases Endocrinology and Metabolism Center The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology  Luoyang 471003 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefan","family":"Gu","sequence":"additional","affiliation":[{"name":"Xinhua Hospital School of Medicine Shanghai Jiao Tong University  Shanghai 200092 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1666-1965","authenticated-orcid":false,"given":"Kun","family":"Qian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Systems Medicine for Cancer School of Biomedical Engineering Institute of Medical Robotics and Shanghai Academy of Experimental Medicine Shanghai Jiao Tong University  Shanghai 200030 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,13]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"a)M.Roser H.Ritchie E.Ortiz\u2010Ospina Our World in Data 2019 https:\/\/ourworldindata.org\/world\u2010population\u2010growth;"},{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-017-0131-6"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mas.21463"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25515-5"},{"key":"e_1_2_9_2_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0020-9"},{"key":"e_1_2_9_2_4","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26524-0"},{"key":"e_1_2_9_2_5","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(01)00100-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00267-0"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4222"},{"key":"e_1_2_9_3_3","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2010.125"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2012.76"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2015.03.002"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.08.017"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60961-0"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(16)30320-5"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.32.3.338"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/35.10.2112"},{"key":"e_1_2_9_7_3","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(01)00736-7"},{"key":"e_1_2_9_7_4","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/39.1.66"},{"key":"e_1_2_9_7_5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa025225"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat7992"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba4991"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00897-6"},{"key":"e_1_2_9_9_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2023.05.004"},{"key":"e_1_2_9_10_1","volume":"8","author":"Remmington T.","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-023-00621-w"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2003.022178"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-015-9041-3"},{"key":"e_1_2_9_12_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2020.112346"},{"key":"e_1_2_9_12_4","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202106156"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032487"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3310\/hta8120"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2023-330045"},{"key":"e_1_2_9_15_2","volume":"35","author":"Pei C. C.","year":"2023","journal-title":"Adv. Mater."},{"key":"e_1_2_9_15_3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2122245119"},{"key":"e_1_2_9_15_4","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202201422"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.6339\/21-JDS1022"},{"key":"e_1_2_9_16_2","first-page":"43","volume":"8","author":"Zhang S. C.","year":"2017","journal-title":"ACM Trans. Intell. Syst. Technol."},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.engappai.2016.02.002"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ins.2018.02.056"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/00401706.1970.10488634"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1080\/02664763.2014.980789"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9868.2011.00771.x"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.10895"},{"key":"e_1_2_9_19_3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9868.2005.00503.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v033.i01"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1109\/TCYB.2020.2982445"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.00115"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.986556"},{"key":"e_1_2_9_22_1","first-page":"401","volume":"42","author":"Gu X.\u2010f.","year":"2004","journal-title":"Chin. J. Pediatr."},{"key":"e_1_2_9_22_2","first-page":"107","volume":"37","author":"Gu X.","year":"2008","journal-title":"Ann. Acad. Med. Singapore"},{"key":"e_1_2_9_22_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2018.02.035"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-01379-8"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9550-6"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.22665"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2021-0077"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.01.002"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2017-104875"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2017.01.019"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9300-1"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12100927"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/nxx039"},{"key":"e_1_2_9_29_2","doi-asserted-by":"publisher","DOI":"10.18388\/abp.2018_2565"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.685656"},{"key":"e_1_2_9_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-018-0245-0"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)70370-0"},{"key":"e_1_2_9_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/7.3.203"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/189926a0"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0966-5"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/47.11.1945"},{"key":"e_1_2_9_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2018.07.010"},{"key":"e_1_2_9_34_3","doi-asserted-by":"publisher","DOI":"10.1002\/VIW.20220011"},{"key":"e_1_2_9_34_4","doi-asserted-by":"publisher","DOI":"10.1002\/smtd.202301046"},{"key":"e_1_2_9_34_5","volume":"19","author":"Cao J.","year":"2023","journal-title":"Small"},{"key":"e_1_2_9_34_6","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101109"},{"key":"e_1_2_9_34_7","volume":"10","author":"Wu J.","year":"2023","journal-title":"Adv. Sci."},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/VIW.20220086"},{"key":"e_1_2_9_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/VIW.20220032"},{"key":"e_1_2_9_35_3","doi-asserted-by":"publisher","DOI":"10.1002\/VIW.20210019"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/VIW.20220048"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/VIW.20220038"},{"key":"e_1_2_9_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c03765"},{"key":"e_1_2_9_37_3","doi-asserted-by":"publisher","DOI":"10.1002\/VIW.20200063"},{"key":"e_1_2_9_37_4","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c09864"},{"key":"e_1_2_9_37_5","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202206670"},{"key":"e_1_2_9_37_6","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202007978"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2005-2633H"},{"key":"e_1_2_9_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2011_119"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2014.09.008"},{"key":"e_1_2_9_40_1","first-page":"35","volume":"145","author":"Azen C. G.","year":"1991","journal-title":"Am. J. Dis. Child."},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2008.12.039"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9797(68)90272-5"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200904885"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202101333"},{"key":"e_1_2_9_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00220-4"},{"key":"e_1_2_9_44_3","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202002021"},{"key":"e_1_2_9_44_4","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17347-6"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9550-6"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202002791"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202305701","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202305701","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202305701","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T12:11:44Z","timestamp":1770984704000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202305701"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,13]]},"references-count":99,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/advs.202305701"],"URL":"https:\/\/doi.org\/10.1002\/advs.202305701","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,13]]},"assertion":[{"value":"2023-08-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2305701"}}